Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Paclitaxel Derivative for Triple-Negative Breast Cancer Chemotherapy

Paclitaxel-triethylenetetramine hexaacetic acid conjugate (PTX-TTHA), a novel semi-synthetic taxane, is designed to improve the water solubility and cosolvent toxicity of paclitaxel in several aminopolycarboxylic acid groups. In this study, the in vitro and in vivo antitumor effects and mechanisms of PTX-TTHA against triple-negative breast cancer (TNBC) and its intravenous toxicity were evaluated. Results showed the water solubility of PTX-TTHA was greater than 5 mg/mL, which was about 7140-fold higher than that of paclitaxel (<0.7 µg/mL). PTX-TTHA (10–105 nmol/L) could significantly inhibit breast cancer proliferation and induce apoptosis by stabilizing microtubules and arresting the cell cycle in the G2/M phase in vitro, with its therapeutic effect and mechanism similar to paclitaxel. However, when the MDA-MB-231 cell-derived xenograft (CDX) tumor model received PTX-TTHA (13.73 mg/kg) treatment once every 3 days for 21 days, the tumor inhibition rate was up to 77.32%. Furthermore, PTX-TTHA could inhibit tumor proliferation by downregulating Ki-67, and induce apoptosis by increasing pro-apoptotic proteins (Bax, cleaved caspase-3) and TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and reducing anti-apoptotic protein (Bcl-2). Moreover, PTX-TTHA demonstrated no sign of acute toxicity on vital organs, hematological, and biochemical parameters at the limit dose (138.6 mg/kg, i.v.). Our study indicated that PTX-TTHA showed better water solubility than paclitaxel, as well as comparable in vitro and in vivo antitumor activity in TNBC models. In addition, the antitumor mechanism of PTX-TTHA was related to microtubule regulation and apoptosis signaling pathway activation.
Validation of CHA2DS2 VASc Score Predictability of Stroke and Systemic Embolization in a Middle Eastern Population with AF: The Jordan Atrial Fibrillation (JoFib) Study

Background and Purpose CHA2DS2-VASc score is one of the most widely used scoring systems to assess the risk of systemic embolization and stroke in patients suffering from atrial fibrillation (Afib); furthermore, it is important in guiding their treatment. This study aimed to evaluate the predictivity of this score in the Jordanian population, build a deeper understanding of patients’ demographic and risk factors, and assess the usefulness of anticoagulation as a preventive measure. Methods A total of 2020 patients with Afib registered in the Jordanian Atrial Fibrillation (JoFib) registry were enrolled in this study. All patients were followed up for 1 year to assess their susceptibility to develop cerebrovascular accident (CVA) and systemic embolism (SE). The association between CHA2DS2-VASc score and risk of development of stroke or systemic embolization was analyzed based on bivariate and adjusted multivariate analyses. The ROC curve was used to assess the predictivity of the CHA2DS2-VASc score. Results The mean age of the study population was 67.8 years; 45.8% were males, and 81.8% were on anticoagulants. And, 71.8% had a CHA2DS2-VASc score of ≥3. During the follow-up period of 1 year; 69 developed new CVA (mean age, 72.8 years), and 9 developed SE. A total of 276 patients died; 18 patients died (6.5% out of all deceased)% from CVA. A moderate predictive power of the CHA2DS2-VASc score was demonstrated through ROC curve analysis with C statistics of 0.689 CI (0.634 to 0.744) for predicting the development of SE or CVA at 1 year. Conclusion CHA2DS2-VASc showed a moderate predictivity of stroke, SE, and all-cause mortality at 1 year. The study suggested disregarding gender differences in deciding to initiate anticoagulant therapy.
Existence and stability of a two-parameter family of solitary waves for a 2-coupled nonlinear Schrödinger system

In this paper, the existence and stability results for a two-parameter family of vector solitary-wave solutions (i.e both components are nonzero) of the nonlinear Schrodinger system \begin{equation*} \left\{ \begin{matrix} iu_t+ u_{xx} + (a |u|^2 + b |v|^2) u=0,\\ iv_t+ v_{xx} + (b |u|^2 + c |v|^2) v=0,\\ \end{matrix} \right. \end{equation*} where $u,v$ are complex-valued functions of $(x,t)\in \mathbb R^2$, and $a,b,c \in \mathbb R$ are established. The results extend our earlier ones as well as those of Ohta, Cipolatti and Zumpichiatti and de Figueiredo and Lopes. As opposed to other methods used before to establish existence and stability where the two constraints of the minimization problems are related to each other, our approach here characterizes solitary-wave solutions as minimizers of an energy functional subject to two independent constraints. The set of minimizers is shown to be stable; and depending on the interplay between the parameters $a,b$ and $c$, further information about the structures of this set are given.
N-Acetylaspartate and Choline Metabolites in Cortical and Subcortical Regions in Clinical High Risk Relative to Healthy Control Subjects: An Exploratory 7T MRSI Study

N-acetylaspartate (NAA) and choline (Cho) are two brain metabolites implicated in several key neuronal functions. Abnormalities in these metabolites have been reported in both early course and chronic patients with schizophrenia (SCZ). It is, however, unclear whether NAA and Cho’s alterations occur even before the onset of the disorder. Clinical high risk (CHR) individuals are a population uniquely enriched for psychosis and SCZ. In this exploratory study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to examine differences in total NAA (tNAA; NAA + N-acetylaspartylglutamate [NAAG]) and major choline-containing compounds, including glycerophosphorylcholine and phosphorylcholine [tCho], over the creatine (Cre) levels between 26 CHR and 32 healthy control (HC) subjects in the subcortical and cortical regions. While no tCho/Cre differences were found between groups in any of the regions of interest (ROIs), we found that CHR had significantly reduced tNAA/Cre in the right dorsal lateral prefrontal cortex (DLPFC) compared to HC, and that the right DLPFC tNAA/Cre reduction in CHR was negatively associated with their positive symptoms scores. No tNAA/Cre differences were found between CHR and HC in other ROIs. In conclusion, reduced tNAA/Cre in CHR vs. HC may represent a putative molecular biomarker for risk of psychosis and SCZ that is associated with symptom severity.
Stress-strain behaviour of unsaturated compacted coal rejects and tailings

The paper presents the results of an experimental study aimed at evaluating the stress-strain response of unsaturated tailings (Mixed Plant Reject and Dewatered Tailings) from a mine in Queensland, Australia, which can be applied to further optimise current tailings disposal strategies of the mine. Triaxialtests at constant gravimetric water content were performed on specimens prepared at different compaction states using dynamic and static methods, to determine their shear strength. The dynamically compactedspecimens display a higher strength than that statically compacted ones, which highlights the significance of stress history for tailings strength. As-compacted and post-testing suction measurements, performed using a high-capacity tensiometer, showed a reduction in matric suction irrespective of the material type, which is caused by mechanical wetting. The strength envelope was found to be non-linear, partly because of suction changes during testing. Post-testing suction measurement showed spatial variability within each specimen, with the central part of the samples experiencing the maximum suction reduction. The paper concludes with a discussion on the interpretation of such results.
Engineering a Phosphoketolase Pathway to Supplement Cytosolic Acetyl-CoA in Aspergillus niger Enables a Significant Increase in Citric Acid Production

Citric acid is widely used in the food, chemical and pharmaceutical industries. Aspergillus niger is the workhorse used for citric acid production in industry. A canonical citrate biosynthesis that occurred in mitochondria was well established; however, some research suggested that the cytosolic citrate biosynthesis pathway may play a role in this chemical production. Here, the roles of cytosolic phosphoketolase (PK), acetate kinase (ACK) and acetyl-CoA synthetase (ACS) in citrate biosynthesis were investigated by gene deletion and complementation in A. niger. The results indicated that PK, ACK and ACS were important for cytosolic acetyl-CoA accumulation and had significant effects on citric acid biosynthesis. Subsequently, the functions of variant PKs and phosphotransacetylase (PTA) were evaluated, and their efficiencies were determined. Finally, an efficient PK-PTA pathway was reconstructed in A. niger S469 with Ca-PK from Clostridium acetobutylicum and Ts-PTA from Thermoanaerobacterium saccharolyticum. The resultant strain showed an increase of 96.4% and 88% in the citrate titer and yield, respectively, compared with the parent strain in the bioreactor fermentation. These findings indicate that the cytosolic citrate biosynthesis pathway is important for citric acid biosynthesis, and increasing the cytosolic acetyl-CoA level can significantly enhance citric acid production.
What would other emergency stroke teams do? Using explainable machine learning to understand variation in thrombolysis practice

Introduction: The aim of this work was to understand between-hospital variation in thrombolysis use among emergency stroke admissions in England and Wales. Patients: A total of 88,928 patients who arrived at all 132 emergency stroke hospitals in England Wales within 4 h of stroke onset, from 2016 to 2018. Methods: Machine learning was applied to the Sentinel Stroke National Audit Programme (SSNAP) data set, to learn which patients in each hospital would likely receive thrombolysis. We used XGBoost machine learning models, coupled with a SHAP model for explainability; Shapley (SHAP) values, providing estimates of how patient features, and hospital identity, influence the odds of receiving thrombolysis. Results: Thrombolysis use in patients arriving within 4 h of known or estimated stroke onset ranged 7% -49% between hospitals. The odds of receiving thrombolysis reduced 9-fold over the first 120 min of arrival-to-scan time, varied 30-fold with stroke severity, reduced 3-fold with estimated rather than precise stroke onset time, fell 6-fold with increasing pre-stroke disability, fell 4-fold with onset during sleep, fell 5-fold with use of anticoagulants, fell 2-fold between 80 and 110 years of age, reduced 3-fold between 120 and 240 min of onset-to-arrival time and varied 13-fold between hospitals. The majority of between-hospital variance was explained by the hospital, rather than the differences in local patient populations. Conclusions: Using explainable machine learning, we identified that the majority of the between-hospital variation in thrombolysis use in England and Wales may be explained by differences in in-hospital processes and differences in attitudes to judging suitability for thrombolysis.
Trauma‐informed co‐production: Collaborating and combining expertise to improve access to primary care with women with complex needs

Health, social care, charitable and justice sectors are increasingly recognising the need for trauma‐informed services that seek to recognise signs of trauma, provide appropriate paths to recovery and ensure that services enable people rather than retraumatise. Foundational to the development of trauma‐informed services is collaboration with people with lived experience of trauma. Co‐production principles may provide a useful framework for this collaboration, due to their emphasis on lived experience, and intent to address power imbalances and promote equity. This article aims to examine trauma‐informed and co‐production principles to consider the extent to which they overlap and explore how to tailor co‐production approaches to support people who have experienced trauma.
To Be or Not to Be: Alicante-8, a Cluster or Not?

Recent surveys have uncovered new young massive clusters that host dozens of red supergiants (RSGs) near the inner Galaxy. However, many of them have still not been fully studied. Using Very Large Telescope/X-shooter near-infrared spectra, we present the first radial velocity analysis for the putative members of the candidate RSG cluster Alicante-8. Our results show a large dispersion of radial velocities among the candidate member stars, indicating that Alicante-8 does not seem to be a real cluster, unlike Alicante-7 and Alicante-10, which are confirmed by the distribution of the radial velocities of their RSG members. Measuring the spectral indices reveals that the assumption that the candidate stars are RSGs was incorrect, leading to the misclassification of Alicante-8 as a candidate RSG cluster. Our results imply that spectral classification based on the widely used CO band at 2.3 μm alone is not a sufficient criterion, because both red giants and RSGs can attain similar CO equivalent widths, and that spectroscopic radial velocities are needed in order to confirm unambiguously the cluster membership.
Helium abundance enhancements in the solar wind

Helium abundance (A(He)) enhancements observed with Los Alamos instruments on IMP 6, 7, and 8 during the 1972–1978 interval have been investigated. Statistical analysis of 73 large events with A(He) ≥ 10% (HAEs) provides evidence for a close link between helium enhancements at 1 A.U. and transient coronal mass ejections. HAE events are sporadic, sometimes clustered in time, and their frequency of occurrence is approximately in phase with the solar cycle. Nearly 50% of HAEs are associated with interplanetary shocks and/or geomagnetic activity sudden commencements, but the plasma pattern associated with A(He) enhancements is independent of shock occurrence. This pattern features high magnetic field strength, low alpha-proton velocity difference, and low proton temperature. These plasma properties suggest that the enhancement is embedded in a ‘closed,’ magnetically dominated structure that expands adiabatically. In fact, HAEs are likely to be still evolving dynamically at 1 A.U. Evidence of a significant association between helium enhancements at 1 A.U. and type II and IV radio bursts in the corona is presented. We interpret these results to mean that most HAE events originate in transient coronal disturbances in which the magnetic field strength is enhanced.
An unbiased de novo network analysis uncovering causal genes and the developmental intersection between autism and co-occurring traits

Autism is a complex neurodevelopmental condition that manifests in various ways. Autism is often accompanied by other neurological disorders, such as ADHD, anxiety, and schizophrenia, which can complicate diagnosis and management. While research has investigated the role of specific genes in autism, their relationship with co-occurring traits is not fully understood. To address this gap, we conducted a two-sample Mendelian Randomisation analysis and identified four genes located at the 17q21.31 locus that are causally linked to autism in fetal cortical tissue (i.e. LINC02210, LRRC37A4P, RP11-259G18.1, RP11-798G7.6). LINC02210 was also identified as being causally related to autism in adult cortical tissue. By integrating data from expression quantitative trait loci [eQTLs], genes, and protein interactions we identified that the 17q21.31 locus contributes to the intersection between autism and other neurological traits and conditions in fetal cortical tissue. We also identified an additional distinct cluster of co-occurring traits, including cognition and worry, linked to genetic loci at 3p21.1. Our results support the hypothesis that an individual's autism phenotype is partially determined by their genetic risk for co-occurring conditions. Overall, our findings provide insights into the complex relationship between autism and co-occurring conditions, which could be used to develop predictive models for more accurate diagnosis and better clinical management.
A Systematic Review of the Prevalence of Persistent Gastrointestinal Symptoms and Incidence of New Gastrointestinal Illness after Acute SARS-CoV-2 Infection

It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as post-COVID syndrome. We conducted a systematic review to examine the prevalence of persistent gastrointestinal symptoms and the incidence of new gastrointestinal illness following acute SARS-CoV-2 infection. We searched scientific literature using MedLine, SCOPUS, Embase, Europe PubMed Central, medRxiv and Google Scholar from December 2019 to October 2022. Two reviewers independently identified 28 eligible articles which followed participants for various gastrointestinal outcomes after acute SARS-CoV-2 infection. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. The weighted pooled prevalence for persistent gastrointestinal symptom of any nature and duration was 10.7%, compared to 4.9% in healthy controls. For six studies at a low risk of methodological bias, the symptom prevalence ranged from 0.2% to 24.1% with a median follow-up time of 13 weeks. We also identified the presence of functional gastrointestinal disorders in historically SARS-CoV-2 exposed individuals. Our review has shown that, from a limited pool of mostly low-quality studies, previous SARS-CoV-2 exposure may be associated with ongoing gastrointestinal symptoms and the development of functional gastrointestinal illness. Furthermore, we show the need for high-quality research to better understand the SARS-CoV-2 association with gastrointestinal symptoms, particularly as population exposure to enteric infections returns to pre-COVID-19-restriction levels.
Daily allergy burden and heart rate characteristics in adults with allergic rhinitis based on a wearable telemonitoring system

Abstract Background Allergic rhinitis includes a certain degree of autonomic imbalance. However, no information is available on how daily changes in allergy burden affect autonomic imbalance. We aimed to estimate associations between daily allergy burden (allergy symptoms and mood) and daily heart rate characteristics (resting heart rate and sample entropy, both biomarkers of autonomic balance) of adults with allergic rhinitis, based on real‐world measurements with a wearable telemonitoring system. Methods Adults with a tree pollen allergy used a smartphone application to self‐report daily allergy symptoms (score 0–44) and mood (score 0–4), and a Mio Alpha 2 wristwatch to collect heart rate characteristics during two pollen seasons of hazel, alder and birch in Belgium. Associations between daily allergy burden and heart rate characteristics were estimated using linear mixed effects distributed lag models with a random intercept for individuals and adjusted for potential confounders. Results Analyses included 2497 participant‐days of 72 participants. A one‐point increase in allergy symptom score was associated with an increase in next‐day resting heart rate of 0.08 (95% CI: 0.02–0.15) beats per minute. A one‐point increase in mood score was associated with an increase in same‐day sample entropy of 0.80 (95% CI: 0.34–1.26) × 10−2. No associations were found between allergy symptoms and heart rate sample entropy, nor between mood and resting heart rate. Conclusion Daily repeated measurements with a wearable telemonitoring system revealed that the daily allergy burden of adults with allergic rhinitis has systemic effects beyond merely the respiratory system.
Relationships between spiritual health and perceived stress with breastfeeding adequacy in mothers with infants aged 1–6 months

BACKGROUND: Previous studies have shown that psycho-spiritual state of mothers may have significant effects on their breastfeeding. The most common cause of nonexclusive breastfeeding is inadequate breastfeeding; therefore, this study examined the relationship between spiritual health and perceived stress with breastfeeding adequacy in mothers with infants aged 1–6 months. MATERIALS AND METHODS: This cross-sectional, descriptive, correlational study was performed on 186 mothers with infants aged 1–6 months, who referred to the health centers in Dorud city of Lorestan province, Iran, in 2021, which were selected based on cluster sampling. Data were collected through four questionnaires including demographic–fertility, spiritual health, perceived stress, and breastfeeding adequacy. Data was analyzed by Statistical Package for the Social Sciences (SPSS) software version 22 using descriptive and analytical statistics. RESULTS: The mean ± standard deviation (SD) values of spiritual health, perceived stress, and breastfeeding adequacy were 99.59 ± 12.96, 23.8 ± 72.19, and 55.67 ± 7.67, respectively. There was a significant positive relationship between spiritual health and breastfeeding adequacy (P < 0.001, r = 0.268). In addition, there was a significant negative relationship between perceived stress and breastfeeding adequacy (P = 0.002, r = −0.231). CONCLUSION: Breastfeeding adequacy has a significant positive relationship with spiritual health and a significant negative relationship with perceived stress. Since infants are one of the most vulnerable groups and breastfeeding is the best way to support their health and reduce infant mortality rates, breastfeeding adequacy can be improved by reducing stress and promoting spiritual health.
Health sciences educator's simulation debriefing practice needs: A mixed methods study

BACKGROUND: Simulation debriefing influences learning from healthcare simulation activities. Health sciences educators must be competent in conducting simulation debriefing for healthcare students. A structured faculty development intervention for health sciences educators must be informed by educator needs to enhance its utility. This paper describes the needs of health sciences educators regarding simulation debriefing at a faculty of health sciences. MATERIALS AND METHODS: A parallel convergent mixed methods study design was applied on a selected population of 30 health sciences educators at the University (x) who integrate immersive simulation for first- to final-year students in their undergraduate programs. The Objective Structured Assessment of Debriefing tool underpinned observations which informed the quantitative strand of the study, while semi-structured interviews were conducted as part of the qualitative strand. Descriptive statistics and thematic analysis were used to analyze the data. RESULTS: Health sciences educators struggled to establish the learning environment for simulation (median 1), facilitate learning (median 3), and evaluate their debriefing activities. However, they were able to apply an appropriate approach toward simulation (median 4). They identified the need to be educated on the fundamentals of simulation-based education. CONCLUSION: A continuing professional development program must be developed aimed at transforming approaches toward facilitating learning, explaining the fundamentals of simulation-based education, modeling of best-practices related to debriefing, and applying appropriate strategies for evaluating debriefing activities.