Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of prognosis in patients with tetralogy of Fallot based on deep learning imaging analysis

Objective To assess the utility of machine learning algorithms for automatically estimating prognosis in patients with repaired tetralogy of Fallot (ToF) using cardiac magnetic resonance (CMR). Methods We included 372 patients with ToF who had undergone CMR imaging as part of a nationwide prospective study. Cine loops were retrieved and subjected to automatic deep learning (DL)-based image analysis, trained on independent, local CMR data, to derive measures of cardiac dimensions and function. This information was combined with established clinical parameters and ECG markers of prognosis. Results Over a median follow-up period of 10 years, 23 patients experienced an endpoint of death/aborted cardiac arrest or documented ventricular tachycardia (defined as >3 documented consecutive ventricular beats). On univariate Cox analysis, various DL parameters, including right atrial median area (HR 1.11/cm², p=0.003) and right ventricular long-axis strain (HR 0.80/%, p=0.009) emerged as significant predictors of outcome. DL parameters were related to adverse outcome independently of left and right ventricular ejection fraction and peak oxygen uptake (p<0.05 for all). A composite score of enlarged right atrial area and depressed right ventricular longitudinal function identified a ToF subgroup at significantly increased risk of adverse outcome (HR 2.1/unit, p=0.007). Conclusions We present data on the utility of machine learning algorithms trained on external imaging datasets to automatically estimate prognosis in patients with ToF. Due to the automated analysis process these two-dimensional-based algorithms may serve as surrogates for labour-intensive manually attained imaging parameters in patients with ToF.
Development and validation of a multiplex UHPLC‐MS/MS assay with stable isotopic internal standards for the monitoring of the plasma concentrations of the antiretroviral drugs bictegravir, cabotegravir, doravirine, and rilpivirine in people living with HIV

Abstract The widespread use of highly active antiretroviral treatments has dramatically changed the prognosis of people living with HIV (PLWH). However, such treatments have to be taken lifelong raising issues regarding the maintenance of both therapeutic effectiveness and long‐term tolerability. Recently approved or investigational antiretroviral drugs present considerable advantages, allowing once daily oral dosage along with activity against resistant variants (eg, bictegravir and doravirine) and also parenteral intramuscular administration that facilitates treatment adherence (eg, long‐acting injectable formulations such as cabotegravir and rilpivirine). Still, there remains a risk of insufficient or exaggerated circulating exposure due to absorption issues, abnormal elimination, drug‐drug interactions, and others. In this context, a multiplex ultra‐high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC‐MS/MS) bioassay has been developed for the monitoring of plasma levels of bictegravir, cabotegravir, doravirine, and rilpivirine in PLWH. A simple and convenient protein precipitation was performed followed by direct injection of the supernatant into the UHPLC‐MS/MS system. The four analytes were eluted in less than 3 minutes using a reversed‐phase chromatography method coupled with triple quadrupole mass spectrometry detection. This bioassay was fully validated following international guidelines and achieved good performances in terms of trueness (94.7%‐107.5%), repeatability (2.6%‐11%), and intermediate precision (3.0%‐11.2%) over the clinically relevant concentration ranges (from 30 to 9000 ng/mL for bictegravir, cabotegravir, and doravirine and from 10 to 1800 ng/mL for rilpivirine). This sensitive, accurate, and rapid UHPLC‐MS/MS assay is currently applied in our laboratory for routine therapeutic drug monitoring of the oral drugs bictegravir and doravirine and is also intended to be applied for the monitoring of cabotegravir/rilpivirine levels in plasma from PLWH receiving once monthly or every 2‐month intramuscular injection of these long‐acting antiretroviral drugs.
Epigenome, Transcriptome, and Protection by Sulforaphane at Different Stages of UVB-Induced Skin Carcinogenesis

Sulforaphane (SFN), a potent antioxidant and antiinflammatory agent, has been shown to protect against cancers especially at early stages. However, how SFN affects UVB-mediated epigenome/DNA methylome and transcriptome changes in skin photodamage has not been fully assessed. Herein, we investigated the transcriptomic and DNA methylomic changes during tumor initiation, promotion, and progression and its impact and reversal by SFN using next-generation sequencing (NGS) technology. The results show that SFN reduced tumor incidence and tumor number. SFN's protective effects were more dramatic in the early stages than with later stages. Bioinformatic analysis of RNA sequencing (RNA-seq) data shows differential expressed genes and identifies the top canonical pathways related to SFN treatment of UVB-induced different stages of epidermal carcinogenesis. These pathways include p53 signaling, cell cycle: G2–M DNA damage checkpoint regulation, Th1, and Th2 activation pathway, and PTEN signaling pathways. The top upstream regulators related to UVB and SFN treatment as time progressed include dextran sulfate, TP53, NFE2L2 (Nrf2), IFNB1, and IL10RA. Bioinformatic analysis of Methyl-seq data shows several differential methylation regions induced by UVB were attenuated by SFN. These include Notch1, Smad6, Gnai3, and Apc2. Integrative analysis of RNA-seq and DNA-seq/CpG methylome yields a subgroup of genes associated with ultraviolet B (UVB) and SFN treatment. The changes in gene expression were inversely correlated with promoter CpG methylation status. These genes include Pik3cd, Matk, and Adm2. In conclusion, our study provides novel insights on the impact of SFN on the transcriptomic and DNA methylomic of UVB-induced different stages of skin cancer in mice.
Rb and p53-Deficient Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma Require Skp2 for Survival

Loss of both Rb and p53 renders myxofibrosarcoma and undifferentiated pleomorphic sarcoma dependent on Skp2, which could provide the basis for promising novel systemic therapies. Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are highly genetically complex soft tissue sarcomas. Up to 50% of patients develop distant metastases, but current systemic therapies have limited efficacy. MFS and UPS have recently been shown to commonly harbor copy number alterations or mutations in the tumor suppressor genes RB1 and TP53. As these alterations have been shown to engender dependence on the oncogenic protein Skp2 for survival of transformed cells in mouse models, we sought to examine its function and potential as a therapeutic target in MFS/UPS. Comparative genomic hybridization and next-generation sequencing confirmed that a significant fraction of MFS and UPS patient samples (n = 94) harbor chromosomal deletions and/or loss-of-function mutations in RB1 and TP53 (88% carry alterations in at least one gene; 60% carry alterations in both). Tissue microarray analysis identified a correlation between absent Rb and p53 expression and positive expression of Skp2. Downregulation of Skp2 or treatment with the Skp2-specific inhibitor C1 revealed that Skp2 drives proliferation of patient-derived MFS/UPS cell lines deficient in both Rb and p53 by degrading p21 and p27. Inhibition of Skp2 using the neddylation-activating enzyme inhibitor pevonedistat decreased growth of Rb/p53-negative patient-derived cell lines and mouse xenografts. These results demonstrate that loss of both Rb and p53 renders MFS and UPS dependent on Skp2, which can be therapeutically exploited and could provide the basis for promising novel systemic therapies for MFS and UPS. Significance: Loss of both Rb and p53 renders myxofibrosarcoma and undifferentiated pleomorphic sarcoma dependent on Skp2, which could provide the basis for promising novel systemic therapies. See related commentary by Lambert and Jones, p. 2437
Relative Tolerance of Three Morphotypes of the Anastrepha fraterculus Complex (Diptera: Tephritidae) to Cold Phytosanitary Treatment

Abstract The Anastrepha fraterculus (Wiedemann) complex is currently comprised of at least eight morphotypes, including several that are likely to be described as new species. It is critical to evaluate whether the morphotypes differ in tolerance to phytosanitary treatments. Temperatures from 0 to 3°C are used as a phytosanitary treatment for some commodities exported from the region and at risk of infestation by the A. fraterculus complex. Description of A. fraterculus morphotypes as new species could result in the annulation of phytosanitary treatment schedules for the new species. This study compared the relative cold tolerance of five populations from three morphotypes of the A. fraterculus complex: Andean, Peruvian, and Brazilian-1. Both a laboratory and wild strain of the Brazilian-1 morphotype were studied. Differences in mortality of third instars of the five A. fraterculus populations reared on nectarines were observed only with short treatment durations at temperatures ranging from 1.38 ± 0.04°C to 1.51 ± 0.08°C (mean ± SEM). Estimated times to achieve the LT99.99682 (probit 9) showed that Brazilian-1 wild, Brazilian-1 laboratory, and Cusco population were the most cold tolerant, followed by Andean and Peruvian, the least cold tolerant morphotype (i.e., Brazilian-1 wild = Brazilian-1 laboratory = Cusco population > Andean > Peruvian). These findings suggest that the current cold treatment schedules of 15 d at ≤ 1.11°C and 17 d at ≤ 1.67°C can be applied as cold treatments to any potential new species that may arise from the A. fraterculus complex.
Anomalous hydrogen dynamics of the ice VII–VIII transition revealed by high-pressure neutron diffraction

Significance We report high-pressure neutron data which reveal a highly unusual behavior of the hydrogen dynamics in ice under high pressure: The transition rate from hydrogen-disordered ice VII to ordered ice VIII slows down dramatically up to 10 GPa but becomes more rapid again above. This finding is quantitatively explainable by a competition between the rotational and translational dynamics of water molecules. Our findings reply to a long-standing problem of unexplained anomalies of ice VII in the 10–15 GPa range reported by Raman spectroscopy, X-ray diffraction, and proton conductivity. Since ice VII and ice VIII are prototypical hydrogen-bonded materials with order–disorder transition, the pressure-induced cross-over in the hydrogen dynamics found in this study might be commonly observable in other materials. Above 2 GPa the phase diagram of water simplifies considerably and exhibits only two solid phases up to 60 GPa, ice VII and ice VIII. The two phases are related to each other by hydrogen ordering, with the oxygen sublattice being essentially the same. Here we present neutron diffraction data to 15 GPa which reveal that the rate of hydrogen ordering at the ice VII–VIII transition decreases strongly with pressure to reach timescales of minutes at 10 GPa. Surprisingly, the ordering process becomes more rapid again upon further compression. We show that such an unusual change in transition rate can be explained by a slowing down of the rotational dynamics of water molecules with a simultaneous increase of translational motion of hydrogen under pressure, as previously suspected. The observed cross-over in the hydrogen dynamics in ice is likely the origin of various hitherto unexplained anomalies of ice VII in the 10–15 GPa range reported by Raman spectroscopy, X-ray diffraction, and proton conductivity.
Activation of a nerve injury transcriptional signature in airway-innervating sensory neurons after LPS induced lung inflammation

The lungs, the immune and nervous systems functionally interact to respond to respiratory environmental exposures and infections. The lungs are innervated by vagal sensory neurons of the jugular and nodose ganglia, fused together in smaller mammals as the jugular-nodose complex (JNC). While the JNC shares properties with the other sensory ganglia, the trigeminal (TG) and dorsal root ganglia (DRG), these sensory structures express differential sets of genes that reflect their unique functionalities. Here, we used RNAseq in mice to identify the differential transcriptomes of the three sensory ganglia types. Using a fluorescent retrograde tracer and fluorescence-activated cell sorting we isolated a defined population of airway-innervating JNC neurons and determined their differential transcriptional map after pulmonary exposure to lipopolysaccharide (LPS), a major mediator of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) after infection with Gram-negative bacteria or inhalation of organic dust. JNC neurons activated an injury response program leading to increased expression of gene products such as the G-protein coupled receptors, Cckbr, inducing functional changes in neuronal sensitivity to peptides, and Gpr151, also rapidly induced upon neuropathic nerve injury in pain models. Unique JNC-specific transcripts, present at only minimal levels in TG, DRG and other organs, were identified. These included TMC3, encoding for a putative mechanosensor, and Urotensin 2B, a hypertensive peptide. These findings highlight the unique properties of the JNC and reveal that ALI/ARDS rapidly induce a nerve-injury related state changing vagal excitability. SIGNIFICANCE STATEMENT The lungs are innervated by sensory neurons of the jugular-nodose ganglia complex (JNC) that detect toxic exposures and interact with lung-resident cells and the immune system to respond to pathogens and inflammation. Here we report the expression of specific genes that differentiate these neurons from neurons in the other sensory ganglia, the trigeminal (TG) and dorsal root ganglia (DRG). Through nerve tracing we identified and isolated airway innervating JNC neurons and determined their differential transcriptional map after lung inflammation induced by a bacterial product, lipopolysaccharide (LPS). We observed the rapid activation of a nerve injury transcriptional program that increased nerve sensitivity to inflammation. This mechanism may result in more permanent nerve injury associated with chronic cough and other respiratory complications.
Wingless counteracts epithelial folding by increasing mechanical tension at basal cell edges in Drosophila

ABSTRACT The modulation of mechanical tension is important for sculpturing tissues during animal development, yet how mechanical tension is controlled remains poorly understood. In Drosophila wing discs, the local reduction of mechanical tension at basal cell edges results in basal relaxation and the formation of an epithelial fold. Here, we show that Wingless, which is expressed next to this fold, promotes basal cell edge tension to suppress the formation of this fold. Ectopic expression of Wingless blocks fold formation, whereas the depletion of Wingless increases fold depth. Moreover, local depletion of Wingless in a region where Wingless signal transduction is normally high results in ectopic fold formation. The depletion of Wingless also results in decreased basal cell edge tension and basal cell area relaxation. Conversely, the activation of Wingless signal transduction leads to increased basal cell edge tension and basal cell area constriction. Our results identify the Wingless signal transduction pathway as a crucial modulator of mechanical tension that is important for proper wing disc morphogenesis. Highlighted Article: Wingless signaling activity controls cell shape and mechanical tension to guide the morphogenesis of Drosophila wing discs.
A Sporolactobacillus-, Clostridium-, and Paenibacillus- Dominant Microbial Consortium Improved Anaerobic RDX Detoxification by Starch Addition

In the present study, an anaerobic microbial consortium for the degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) was selectively enriched with the co-addition of RDX and starch under nitrogen-deficient conditions. Microbial growth and anaerobic RDX biodegradation were effectively enhanced by the co-addition of RDX and starch, which resulted in increased RDX biotransformation to nitroso-derivatives at a greater specific degradation rate than those for previously reported anaerobic RDX-degrading bacteria (isolates). The accumulation of the most toxic RDX degradation intermediate (MNX [hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine]) was significantly reduced by starch addition, suggesting improved RDX detoxification by the co-addition of RDX and starch. The subsequent MiSeq sequencing that targeted the bacterial 16S rRNA gene revealed that the Sporolactobacillus, Clostridium, and Paenibacillus populations were involved in the enhanced anaerobic RDX degradation. These results suggest that these three bacterial populations are important for anaerobic RDX degradation and detoxification. The findings from this work imply that the Sporolactobacillus, Clostridium, and Paenibacillus dominant microbial consortium may be valuable for the development of bioremediation resources for RDX-contaminated environments.
Effect of an Educational Program on Student's Practices regarding Prevention and Control of Pandemic Influenza Transmission = تأثير برنامج تعليمي على ممارسات الطلاب تجاه التحكم و منع انتشار جائحة الإنفلونزا

Azza Ismail Ismail, (1) Wafaa El-Sayed Ouda, (2) Amina Mohammed Abd El-Whab, & Inas Mohammed Abd-Allah (1) Assistant Lecturer of Pediatric Nursing Department, Faculty of Nursing, Suez Canal University, Professor of Pediatric NursingFaculty of NursingAin Shams University, (3) Professor of Pediatric MedicineFaculty of MedicineSuez Canal University, (4) Assistant Professor of Maternity and Gynecologic NursingFaculty of NursingSuez Canal University Abstract: Background: Influenza is a highly contagious disease that can cause high mortality and morbidity even between pandemics. Many cases and deaths of influenza not only due to the disease, but also due to its associated cardiac and pulmonary complications. So educating hygienic practices for prevention and control of pandemic influenza transmission in schools is very important especially when there is a major public health threat like influenza pandemic. Aim of the study: was to assess student’s practice regarding prevention and control of pandemic influenza transmission. It also aims to design, implement and evaluate an educational program for students about practices for prevention and control of pandemic influenza transmission. Subjects &methods: Research design: A quasi experimental design was used. Setting: The study was conducted in four governmental schools in Ismailia. Subject: The study involved 204 students from 12-18 years. Tools of data collection: Data were collected using interview questionnaire sheet and observational checklists. Results: Total score of practices regarding prevention and control of pandemic influenza transmission were improved after implementation of the educational program and after one month later. As satisfactory practices represented by 100% post educational program and 99.5% after one month. Conclusion: Implementation of educational program for students improved significantly the student’s practices about prevention and control of pandemic influenza transmission. Recommendation: The study recommended periodic assessment of student’s practices regarding prevention of influenza transmission and accordingly apply relevant nursing intervention.
Modeling the suicidal behavior cycle: Understanding repeated suicide attempts among individuals with borderline personality disorder and a history of attempting suicide.

OBJECTIVE Suicide remains a leading cause of death in the United States, and recent reports have suggested the suicide rate is increasing. One of the most robust predictors of future suicidal behavior is a history of attempting suicide. Despite this, little is known about the factors that reduce the likelihood of reattempting suicide. This study compares theoretically derived suicide risk indicators to determine which factors are most predictive of future suicide attempts. METHOD We used data from a randomized, controlled trial comparing 3 forms of dialectical behavior therapy (DBT; Linehan et al., 2015). Participants (N = 97, mean age = 30.3 years, 100% female, 71% White) met criteria for borderline personality disorder and had repeated and recent self-injurious behavior. Assessments occurred at 4-month intervals throughout 1 year of treatment and 1 year of follow-up. Time-lagged generalized linear mixed models (GLMMs) were used to evaluate relationship satisfaction, emotion dysregulation, and coping styles as predictors of suicide attempts. RESULTS Both univariate and multivariate models suggested that higher between-person variance in problem-focused coping and lack of access to emotion regulation strategies were weakly associated with additional suicide attempts over the 2-year study. Within-person variance in the time-lagged predictors was not associated with subsequent suicide attempts. CONCLUSIONS Among individuals with a recent suicide attempt, problem-focused coping and specific deficits in emotion regulation may differentiate those likely to reattempt from those who stop suicidal behavior during and after psychotherapy. These results suggest that treatments for recent suicide attempters should target increasing problem-focused coping and decreasing maladaptive emotion regulation skills. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Diagnosis and Treatment of Trauma-Induced Coagulopathy by Viscoelastography

Abstract This article explores the application of viscoelastic tests (VETs) in trauma-induced coagulopathy and trauma resuscitation. We describe the advantages of VETs over conventional coagulation tests in the trauma setting and refer to previous disciplines in which VET use has reduced blood product utilization, guided prohemostatic agents, and improved clinical outcomes such as the mortality of critically bleeding patients. We describe different VETs and provide guidance for blood component therapy and prohemostatic therapy based on specific VET parameters. Because the two most commonly used VET systems, rotational thromboelastometry and thromboelastography, use different activators and have different terminologies, this practical narrative review will directly compare and contrast these two VETs to help the clinician easily interpret either and use the interpretation to determine hemostatic integrity in the bleeding trauma patient. Finally, we anticipate the future of new viscoelastic technologies that can be used in this setting.
Answering the Call: Educating Future Nurses on LGBTQ HealthCare

ABSTRACT The purpose of this population-focused educational strategy was to improve knowledge and attitudes of senior-level baccalaureate nursing students regarding LGBTQ health. Surveys were conducted to assess achievement in learning objectives: (a) understanding the prevalence and impact of health disparities among individuals who identify as LGBTQ, (b) understanding the ways to provide effective support for individuals who identify as LGBTQ, (c) identification of ways to engage with individuals who identify as LGBTQ in an active partnership for health promotion. The majority of students responded to survey questions acknowledging that communication skills and style changed as a result of the innovation, new or advanced knowledge was obtained and a better awareness upon which to base decisions/actions in the practice setting was gained. All health-care professionals are encouraged to practice open-mindedness and should welcome opportunities to be educated on best practice related to care of LGBTQ individuals.