Miracle-dz/UniFAR-FTUs huggingface dataset:
Pediatric delirium: epidemiology and outcomes

Purpose of review Delirium is a frequent complication of serious medical illness in children. The purpose of this review is to highlight recent data on the epidemiology and outcomes related to pediatric delirium, and discuss prevention strategies. Recent findings Delirium rates in the pediatric ICU are greater than 25%. Delirium in children is associated with prolonged mechanical ventilation and hospital length of stay, increased costs, and excess mortality. Pediatric delirium may affect postdischarge cognition and quality of life. Recent initiatives targeting universal screening, early mobilization, and minimization of benzodiazepine-based sedation have shown reduction in delirium prevalence. Summary Widespread screening is needed in critically ill children to detect and mitigate delirium. The identification of modifiable risk factors has provided an opportunity for delirium prevention. Large-scale longitudinal studies are needed to investigate the long-term sequelae of delirium in children.
Characterization of Altered MicroRNA Expression in Cervical Cancer

Cervical cancer is the third most common cancer among women worldwide, and the fourth leading cause of cancer mortality. Despite significant declines in the incidence and mortality rates of cervical cancer in Canada, it remains the 4 most common cancer in women aged 20-29 years. In order to gain novel insights into cervical cancer tumourigenesis and clinical outcome, we investigated and characterized the alterations in microRNA (miRNA) expression in this disease. Firstly, we performed global miRNA expression profiling of cervical cancer cell lines (n=3), and patient specimens (n=79). From this analysis, we identified miR-196b to be significantly down-regulated in cervical cancer, and characterized its role in regulating the HOXB7~VEGF axis. The global miRNA expression data also led to the development of a candidate 9-miRNA signature that was prognostic for disease-free survival in patients with cervical cancer, although we were unable to validate this signature in an independent cohort. This report describes important considerations concerning the development and validation of microRNA signatures for cervical cancer. Our investigations also led us to a comparison of three methods for measuring miRNA abundance: the TaqMan Low Density Array, the NanoString nCounter assay, and single-well quantitative real-time PCR. Our findings demonstrated limited concordance between the TLDA and NanoString platforms, although each platform correlated well with PCR, which is considered the gold standard for nucleic acid quantification. Furthermore, we examined biases created by amplification protocols for microarray studies. Our analysis demonstrated that performing a
Automated Smart Home Assessment to Support Pain Management: Multiple Methods Analysis

Background Poorly managed pain can lead to substance use disorders, depression, suicide, worsening health, and increased use of health services. Most pain assessments occur in clinical settings away from patients’ natural environments. Advances in smart home technology may allow observation of pain in the home setting. Smart homes recognizing human behaviors may be useful for quantifying functional pain interference, thereby creating new ways of assessing pain and supporting people living with pain. Objective This study aimed to determine if a smart home can detect pain-related behaviors to perform automated assessment and support intervention for persons with chronic pain. Methods A multiple methods, secondary data analysis was conducted using historic ambient sensor data and weekly nursing assessment data from 11 independent older adults reporting pain across 1-2 years of smart home monitoring. A qualitative approach was used to interpret sensor-based data of 27 unique pain events to support clinician-guided training of a machine learning model. A periodogram was used to calculate circadian rhythm strength, and a random forest containing 100 trees was employed to train a machine learning model to recognize pain-related behaviors. The model extracted 550 behavioral markers for each sensor-based data segment. These were treated as both a binary classification problem (event, control) and a regression problem. Results We found 13 clinically relevant behaviors, revealing 6 pain-related behavioral qualitative themes. Quantitative results were classified using a clinician-guided random forest technique that yielded a classification accuracy of 0.70, sensitivity of 0.72, specificity of 0.69, area under the receiver operating characteristic curve of 0.756, and area under the precision-recall curve of 0.777 in comparison to using standard anomaly detection techniques without clinician guidance (0.16 accuracy achieved; P<.001). The regression formulation achieved moderate correlation, with r=0.42. Conclusions Findings of this secondary data analysis reveal that a pain-assessing smart home may recognize pain-related behaviors. Utilizing clinicians’ real-world knowledge when developing pain-assessing machine learning models improves the model’s performance. A larger study focusing on pain-related behaviors is warranted to improve and test model performance.
Self-compassion as a mediator of the association between autistic traits and depressive/anxious symptomatology

Self-compassion refers to the extension of kindness to oneself when faced with inadequacies, shortcomings or failures. This study examined the mediating role of self-compassion in the relationship between autistic traits and depressive/anxious symptomatology in the general population. Participants included 164 university students (69 males and 95 females) ranging in age from 18 to 51 years (mean = 23.16, standard deviation = 7.81). Participants completed the Autism Spectrum Quotient, the Self-Compassion Scale, and the Hospital Anxiety and Depression Scale. A series of multiple mediation analyses was conducted using the bootstrapping method, and it was found that Total Self-Compassion and the two subscales of Compassionate Self-Responding and Uncompassionate Self-Responding partially mediated the relationship between autistic traits and anxious/depressive symptoms. The indirect effect of self-compassion accounted for 41.9% of the variance in the relationship between autistic traits and depressive symptoms and 50% of the variance in the relationship between autistic traits and anxiety symptoms. It was also further found that the correlation between autistic traits and self-compassion was significantly stronger in males than females. Although preliminary, the current findings suggest that self-compassion could potentially serve as a target for clinical intervention in individuals with elevated autistic traits who experience anxiety and/or depression. Lay Abstract In this study, we asked 164 undergraduate students to complete an online questionnaire. The questionnaire measured the students’ levels of autistic traits, self-compassion, and experience of anxiety and depression. We were interested in knowing if self-compassion (defined as the extension of kindness to oneself when faced with challenges) had any influence on the relationship between autistic traits and experiences of anxiety and depression. The results of the study indicated that self-compassion may be an important factor influencing the relationship between autistic traits and mental health, with higher levels of self-compassion being related to more positive mental health outcomes. Although the findings should be considered preliminary in nature, they do suggest that self-compassion could potentially be a target for clinical intervention in people with elevated autistic traits and experience anxiety and/or depression.
STAT3-Mediated Astrocyte Reactivity Associated with Brain Metastasis Contributes to Neurovascular Dysfunction

These findings demonstrate that selectively targeting STAT3-mediated astrocyte reactivity ameliorates the cerebrovascular dysfunction associated with brain metastasis, providing a potential therapeutic avenue for improved patient outcome. Astrocytes are thought to play a pivotal role in coupling neural activity and cerebral blood flow. However, it has been shown that astrocytes undergo morphologic changes in response to brain metastasis, switching to a reactive phenotype, which has the potential to significantly compromise cerebrovascular function and contribute to the neurological sequelae associated with brain metastasis. Given that STAT3 is a key regulator of astrocyte reactivity, we aimed here to determine the impact of STAT3-mediated astrocyte reactivity on neurovascular function in brain metastasis. Rat models of brain metastasis and ciliary neurotrophic factor were used to induce astrocyte reactivity. Multimodal imaging, electrophysiology, and IHC were performed to determine the relationship between reactive astrocytes and changes in the cerebrovascular response to electrical and physiological stimuli. Subsequently, the STAT3 pathway in astrocytes was inhibited with WP1066 to determine the role of STAT3-mediated astrocyte reactivity, specifically, in brain metastasis. Astrocyte reactivity associated with brain metastases impaired cerebrovascular responses to stimuli at both the cellular and functional level and disrupted astrocyte–endothelial interactions in both animal models and human brain metastasis samples. Inhibition of STAT3-mediated astrocyte reactivity in rats with brain metastases restored cerebrovascular function, as shown by in vivo imaging, and limited cerebrovascular changes associated with tumor growth. Together these findings suggest that inhibiting STAT3-mediated astrocyte reactivity may confer significant improvements in neurological outcome for patients with brain metastases and could potentially be tested in other brain tumors. Significance: These findings demonstrate that selectively targeting STAT3-mediated astrocyte reactivity ameliorates the cerebrovascular dysfunction associated with brain metastasis, providing a potential therapeutic avenue for improved patient outcome.
Associations Between Quality Measures and Outcomes for Children Hospitalized With Bronchiolitis.

OBJECTIVES To use adherence to the Pediatric Respiratory Illness Measurement System (PRIMES) indicators to evaluate the strength of associations for individual indicators with length of stay (LOS) and cost for bronchiolitis. METHODS We prospectively enrolled children with bronchiolitis at 5 children's hospitals between July 1, 2014, and June 30, 2016. We examined associations between adherence to each individual PRIMES indicator for bronchiolitis and LOS and cost. Sixteen indicators were included, 9 "overuse" indicators for care that should not occur and 7 "underuse" indicators for care that should occur. We performed mixed effects linear regression to examine the association between adherence to each individual indicator and LOS (hours) and cost (dollars). All models controlled for patient demographics, patient complexity, and hospital. RESULTS We enrolled 699 participants. The mean age was 8 months; 56% were male, 38% were white, and 63% had public insurance. Three indicators were significantly associated with shorter LOS and lower cost. All 3 indicators were overuse indicators and related to laboratory testing: no blood cultures (adjusted mean difference in LOS: -24.3 hours; adjusted mean cost difference: -$731, P < .001), no complete blood cell counts (LOS: -17.8 hours; cost: -$399, P < .05), and no respiratory syncytial virus testing (LOS: -16.6 hours; cost: -$272, P < .05). Two underuse indicators were associated with higher cost: documentation of oral intake at discharge ($671, P < .01) and documentation of hospital follow-up ($538, P < .05). CONCLUSIONS A subset of PRIMES quality indicators for bronchiolitis are strongly associated with improved outcomes and can serve as important measures for future quality improvement efforts.
Recombinant Fowlpox Virus Expressing gB Gene from Predominantly Epidemic Infectious Larygnotracheitis Virus Strain Demonstrates Better Immune Protection in SPF Chickens

Background: Infectious laryngotracheitis (ILT) is a highly contagious acute respiratory disease of chickens. Antigenic mutation of infectious laryngotracheitis virus (ILTV) may result in a vaccination failure in the poultry industry and thus a protective vaccine against predominant ILTV strains is highly desirable. Methods: The full-length glycoprotein B (gB) gene of ILTV with the two mutated synonymous sites of fowlpox virus (FPV) transcription termination signal sequence was cloned into the insertion vector p12LS, which was co-transfected with wild-type (wt) FPV into chicken embryo fibroblast (CEF) to develop a recombinant fowlpox virus-gB (rFPV-gB) candidate vaccine strain. Furthermore, its biological and immunological characteristics were evaluated. Results: The results indicated that gB gene was expressed correctly in the rFPV by indirect immunofluorescent assay and Western blot, and the rFPV-gB provided a 100% protection in immunized chickens against the challenge of predominant ILTV strains that were screened by pathogenicity assay when compared with the commercialized rFPV vaccine, which only provided 83.3%. Conclusion: rFPV-gB can be used as a potential vaccine against predominant ILTV strains.
Structural insights into long-distance signal transduction pathways mediated by plant glutamate receptor-like channels.

In recent years, studies have shed light on the physiological role of plant glutamate receptor-like channels (GLRs). However, the mechanism by which these channels are activated, and in particular, what is the physiological role of their binding to amino acids, remains elusive. The first direct biochemical demonstration that the Arabidopsis thaliana GLR3.3 isoform binds glutamate and other amino acids in a low micromolar range of concentrations was only recently reported. The first crystal structures of the ligand-binding domains of AtGLR3.3 and AtGLR3.2 isoforms have also been released. We foresee that these new experimental pieces of evidence provide the basis for a better understanding of how GLRs are activated and modulated in different physiological responses.
Short-Term Efficacy of Presurgical Vacuum Formed Nasoalveolar Molding Aligners on Nose, Lip, and Maxillary Arch Morphology in Infants With Unilateral Cleft Lip and Palate: A Prospective Clinical Trial

Objectives: The purpose of this study was to evaluate the short-term effect of series of preadjusted vacuum formed nasoalveolar molding VF NAM aligners on the morphology of nose, lip, and maxillary arch in infants with unilateral cleft lip and palate (UCLP). Design: Prospective clinical trial. Setting: Unilateral cleft lip and palate patients referred to outpatients’ clinic. Patients: Sixteen nonsyndromic infants with UCLP, less than 2 months of age were included from April 2017 to April 2018. Interventions: All infants received VF NAM therapy. Standardized digital frontal and basilar photographs and 3D digital models were taken before initiation of VF NAM therapy (T1) and after completion of VF NAM therapy (T2). Main Outcome Measure(s): Changes in morphology of the nose, lip, and maxillary arch. Results: Statistical analysis comparing T1 and T2 measurements was performed. Frontal and basilar photographic analysis showed a statistically significant reduction of columella displacement, interlabial gap distance, and nostril width at cleft side (CS), while the nasal height, nostril height at CS, nostril width at noncleft side (NCS), columella deviation angle, nasal tip protrusion, and nostril area at both CS and NCS increased significantly with VF NAM therapy. The nasal width, nostril height at NCS showed no significant change after presurgical VF NAM aligners therapy. The analysis of digital models demonstrated a statistically significant reduction of alveolar cleft width, anterior arch width, arch length, midline deviation, and palatal cleft width, while the posterior arch width and arch perimeter increased significantly with VF NAM therapy. Conclusion: Vacuum formed NAM therapy was effective in reducing the nasoalveolar deformities associated with infants with UCLP and improved the alveolar morphology and nasal symmetry.
Effects of oxidative stress and apoptosis on vascularity and viability of perforator flaps

ABSTRACT We investigated lateral thoracic and posterior thigh perforator flaps for viability, vascularization, perfusion and apoptosis in a rat model. Wistar albino rats were divided into six groups: lateral thoracic artery perforator flap (LTPF) sham, 3 × 2 cm2 LTPF, 3 × 6 cm2 LTPF, posterior thigh perforator flap (PTPF) sham, 3 × 2 cm2 PTPF, and 3 × 6 cm2 PTPF. Flap viability was determined on postoperative days 1 and 7. On day 7, flaps were photographed and their viability was measured using two-dimensional planimeter paper. Tissue samples were harvested for examination by histology and immunohistochemistry. Viability differences were statistically significant. Epithelial thickness, vascularity and number of fibroblasts were reduced in the 3 × 6 cm2 groups. Neovascularization and apoptosis based on molecular tests were not significantly different among groups. Flap size and location are important factors for closure of surgical or traumatic defects. We suggest that for clinical application, wound complications will occur less frequently with perforators that nourish large areas of flaps.
The mouse Gene Expression Database (GXD): 2021 update

Abstract The Gene Expression Database (GXD; www.informatics.jax.org/expression.shtml) is an extensive and well-curated community resource of mouse developmental gene expression information. For many years, GXD has collected and integrated data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot, and western blot experiments through curation of the scientific literature and by collaborations with large-scale expression projects. Since our last report in 2019, we have continued to acquire these classical types of expression data; developed a searchable index of RNA-Seq and microarray experiments that allows users to quickly and reliably find specific mouse expression studies in ArrayExpress (https://www.ebi.ac.uk/arrayexpress/) and GEO (https://www.ncbi.nlm.nih.gov/geo/); and expanded GXD to include RNA-Seq data. Uniformly processed RNA-Seq data are imported from the EBI Expression Atlas and then integrated with the other types of expression data in GXD, and with the genetic, functional, phenotypic and disease-related information in Mouse Genome Informatics (MGI). This integration has made the RNA-Seq data accessible via GXD’s enhanced searching and filtering capabilities. Further, we have embedded the Morpheus heat map utility into the GXD user interface to provide additional tools for display and analysis of RNA-Seq data, including heat map visualization, sorting, filtering, hierarchical clustering, nearest neighbors analysis and visual enrichment.
Real‐world, population‐based cohort study of toxicity and resource utilization of second‐line ipilimumab for metastatic melanoma in Ontario, Canada

Second‐line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real‐world toxicity of second‐line ipilimumab compared to standard second‐line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included. Patients receiving second‐line ipilimumab after September 2012 were considered as cases, and those who received second‐line treatment prior to the funding date were included as historical controls. Outcomes assessed include treatment‐related mortality, any‐cause hospital visits, ipilimumab‐related hospital visits and specialist visits (eg, endocrinologists, ophthalmologists, gastroenterologists, rheumatologists and respirologists), which were captured from up to 30 and/or 90 days after end of second‐line treatment. Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Odds ratios (ORs) from logistic regressions and rate ratios (RRs) from rate regressions were used to assess differences between groups. We identified 329 MM patients who received second‐line treatments (ipilimumab: 189; controls: 140). Ipilimumab was associated greater any‐cause (60.1% vs 45.7%; OR = 1.81; P value = .019) and ipilimumab‐related (47.2% vs 31.9%; OR = 1.91; P value = .011) hospital visits. Adjusting for different follow‐up days, ipilimumab was associated with higher rates of all‐cause (RR = 1.56 [95%CI: 1.12‐2.16]), and ipilimumab‐related (RR = 2.18 [95% CI: 1.45‐3.27]) hospital visits. Patients receiving ipilimumab were more likely to visit specialist involved in immunotherapy toxicity management (23.5% vs 13.7%; P value = .04). Compared to historical second‐line treatments, second‐line ipilimumab was associated with more health service utilization (specifically hospital visits and specialist visits), suggestive of potentially increased toxicity in the real world.
Quantification of Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Protein Expression in Bone Biopsies by Targeted Mass Spectrometry without Acid Decalcification.

Bone is a common site of metastasis in breast cancer. Due to discordance between biomarker expression in primary and metastatic tumors, biopsies of bone metastases are performed prior to treatment to reassess estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) to guide treatment (1). Decalcifying agents used to enable sectioning of bone biopsies affect the accuracy and feasibility of ER, PR, and HER2 determinations using immunohistochemistry (IHC) and fluorescence in situ hybridization by negatively impacting antigenicity and DNA quality (2). A more robust technique for evaluating expression of key receptors could help to ensure optimal treatment. We assessed the feasibility of extracting protein from non-decalcified bone biopsies and quantifying ER, PR, and HER2 via proteotypic peptides using peptide immunoenrichment-multiple reaction monitoring-mass spectrometry (immuno-MRM-MS). We previously described an immuno-MRM-MS assay for quantifying ER and HER2 from cell lysates and tissues (3).
Writhing Movement Detection in Newborns on the Second and Third Day of Life Using Pose-Based Feature Machine Learning Classification

Observation of neuromotor development at an early stage of an infant’s life allows for early diagnosis of deficits and the beginning of the therapeutic process. General movement assessment is a method of spontaneous movement observation, which is the foundation for contemporary attempts at objectification and computer-aided diagnosis based on video recordings’ analysis. The present study attempts to automatically detect writhing movements, one of the normal general movement categories presented by newborns in the first weeks of life. A set of 31 recordings of newborns on the second and third day of life was divided by five experts into videos containing writhing movements (with occurrence time) and poor repertoire, characterized by a lower quality of movement in relation to the norm. Novel, objective pose-based features describing the scope, nature, and location of each limb’s movement are proposed. Three machine learning algorithms are evaluated in writhing movements’ detection in leave-one-out cross-validation for different feature extraction time windows and overlapping time. The experimental results make it possible to indicate the optimal parameters for which 80% accuracy was achieved. Based on automatically detected writhing movement percent in the video, infant movements are classified as writhing movements or poor repertoire with an area under the ROC (receiver operating characteristics) curve of 0.83.