Deep Learning-Guided Fiberoptic Raman Spectroscopy Enables Real-Time In Vivo Diagnosis and Assessment of Nasopharyngeal Carcinoma and Post-treatment Efficacy during Endoscopy.

In this work, we develop a deep learning-guided fiberoptic Raman diagnostic platform to assess its ability of real-time in vivo nasopharyngeal carcinoma (NPC) diagnosis and post-treatment follow-up of NPC patients. The robust Raman diagnostic platform is established using innovative multi-layer Raman-specified convolutional neural networks (RS-CNN) together with simultaneous fingerprint and high-wavenumber spectra acquired within sub-seconds using a fiberoptic Raman endoscopy system. We have acquired a total of 15,354 FP/HW in vivo Raman spectra (control: 1761; NPC: 4147; and post-treatment (PT): 9446) from 888 tissue sites of 418 subjects (healthy control: 85; NPC: 82; and PT: 251) during endoscopic examination. The optimized RS-CNN model provides an overall diagnostic accuracy of 82.09% (sensitivity of 92.18% and specificity of 73.99%) for identifying NPC from control and post-treatment patients, which is superior to the best diagnosis performance (accuracy of 73.57%; sensitivity of 89.74%; and specificity of 58.10%) using partial-least-squares linear-discriminate-analysis, proving the robustness and high spectral information sensitiveness of the RS-CNN model developed. We further investigate the saliency map of the best RS-CNN models using the correctly predicted Raman spectra. The specific Raman signatures that are related to the cancer-associated biomolecular variations (e.g., collagens, lipids, and nucleic acids) are uncovered in the map, validating the diagnostic capability of RS-CNN models to correlate with biomolecular signatures. Deep learning-based Raman spectroscopy is a powerful diagnostic tool for rapid screening and surveillance of NPC patients and can also be deployed for longitudinal follow-up monitoring of post-treatment NPC patients to detect early cancer recurrences in the head and neck.

Examining Intraprofessional Competencies for Occupational Therapist and Occupational Therapy Assistant Collaboration.

This study examined competencies perceived by occupational therapists and occupational therapy assistants as important for intraprofessional collaboration. While interprofessional practice is well defined, less is known about collaboration within professions with varied levels of practice credentials. Occupational therapy practitioners (N = 351) rated 20 competencies in four domains (Intraprofessional Teamwork, Roles/Responsibilities, Communication, and Values/Ethics) through an online survey. A high percentage of respondents perceived all competencies as important or very important. There were significant differences between occupational therapists and occupational therapy assistants in ratings of five competencies, including: seeking information/support from the team partner, flexibility for effective partnership, engagement in professional development for collaboration, communicating ideas, and providing feedback about performance. Outcomes contribute to understanding intraprofessional collaboration for occupational therapy practice. Competencies can serve as guidelines for education and professional development.

Dampened Inflammation and Improved Survival After CXCL5 Administration in Murine Lupus via Myeloid and Neutrophil Pathways.

OBJECTIVE: To determine the efficacy of CXCL5 administration in lupus-prone MRL/lpr (Faslpr ) mice and elucidate its working mechanisms. METHODS: CXCL5 expression in blood (obtained from SLE patients and Faslpr mice) and major internal organs (obtained from Faslpr mice) was examined by Luminex, real-time polymerase chain reaction, and immunofluorescent staining analyses. Pharmacokinetic studies were performed in Faslpr mice and healthy Institute of Cancer Research mice. Efficacy of CXCL5 administration was demonstrated in Faslpr mice, and the working mechanism of CXCL5 treatment was elucidated by flow cytometry, Luminex, and RNA sequencing. RESULTS: In SLE patients, serum CXCL5 levels were significantly lower than in healthy individuals (P < 0.0001) and negatively correlated with disease activity (P = 0.004). In Faslpr mice, disease severity progressed with age and was negatively associated with plasma CXCL5 levels. Intravenous administration of CXCL5 to Faslpr mice restored endogenous circulatory CXCL5, improved mice survival, and reduced anti-double-stranded DNA antibodies, proteinuria, lupus nephritis activity and chronicity indices, renal complements, and neutrophil extracellular traps over short-term (10 weeks) and long-term (2 years) time periods. In vitro and in vivo assays demonstrated that CXCL5 dictated neutrophil trafficking and suppressed neutrophil activation, degranulation, proliferation, and renal infiltration. Renal and splenic RNA sequencing further showed that CXCL5-mediated immunomodulation occurred by promoting energy production in renal-infiltrated immune cells, activating certain T cells, and reducing tissue fibrosis, granulocyte extravasation, complement components, and interferons. Further factorial design results indicated that CXCL5 appears to enhance host tolerability to cyclophosphamide in vulnerable individuals. CONCLUSION: We found that serum CXCL5 levels were significantly lower in SLE patients than in healthy individuals and were negatively correlated with disease activity. By administering CXCL5 intravenously in a mouse model of lupus, mouse survival improved, and indices of disease activity reduced significantly. Taken together, these findings indicate CXCL5 administration may represent a novel myeloid/neutrophil-targeting therapy for SLE.

Obtaining spatially resolved tumor purity maps using deep multiple instance learning in a pan-cancer study.

Tumor purity is the percentage of cancer cells within a tissue section. Pathologists estimate tumor purity to select samples for genomic analysis by manually reading hematoxylin-eosin (H&E)-stained slides, which is tedious, time consuming, and prone to inter-observer variability. Besides, pathologists' estimates do not correlate well with genomic tumor purity values, which are inferred from genomic data and accepted as accurate for downstream analysis. We developed a deep multiple instance learning model predicting tumor purity from H&E-stained digital histopathology slides. Our model successfully predicted tumor purity in eight The Cancer Genome Atlas (TCGA) cohorts and a local Singapore cohort. The predictions were highly consistent with genomic tumor purity values. Thus, our model can be utilized to select samples for genomic analysis, which will help reduce pathologists' workload and decrease inter-observer variability. Furthermore, our model provided tumor purity maps showing the spatial variation within sections. They can help better understand the tumor microenvironment.

Thyroid Hormone Decreases Hepatic Steatosis, Inflammation, and Fibrosis in a Dietary Mouse Model of Nonalcoholic Steatohepatitis.

Background: Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, lobular inflammation, and fibrosis. Thyroid hormone (TH) reduces steatosis; however, the therapeutic effect of TH on NASH-associated inflammation and fibrosis is not known. This study examined the therapeutic effect of TH on hepatic inflammation and fibrosis during NASH and investigated THs molecular actions on autophagy and mitochondrial biogenesis. Methods: HepG2-TRß cells were treated with bovine serum albumin-conjugated palmitic acid (PA) to mimic lipotoxic conditions in vitro. Mice with NASH were established by feeding C57BL/6J mice Western diet with 15% fructose in drinking water for 16 weeks. These mice were administered triiodothyronine (T3)/thyroxine (T4) supplemented in drinking water for the next eight weeks. Results: In cultured HepG2-TRß cells, TH treatment increased mitochondrial respiration and fatty acid oxidation under basal and PA-treated conditions, as well as decreased lipopolysaccharides and PA-stimulated inflammatory and fibrotic responses. In a dietary mouse model of NASH, TH administration decreased hepatic triglyceride content (3.19 ± 0.68 vs. 8.04 ± 0.42 mM/g liver) and hydroxyproline (1.44 ± 0.07 vs. 2.58 ± 0.30 mg/g liver) when compared with mice with untreated NASH. Metabolomics profiling of lipid metabolites showed that mice with NASH had increased triacylglycerol, diacylglycerol, monoacylglycerol, and hepatic cholesterol esters species, and these lipid species were decreased by TH treatment. Mice with NASH also showed decreased autophagic degradation as evidenced by decreased transcription Factor EB and lysosomal protease expression, and accumulation of LC3B-II and p62. TH treatment restored the level of lysosomal proteins and resolved the accumulation of LC3B-II and p62. Impaired mitochondrial biogenesis was also restored by TH. The simultaneous restoration of autophagy and mitochondrial biogenesis by TH increased ß-oxidation of fatty acids. Additionally, the elevated oxidative stress and inflammasome activation in NASH liver were also decreased by TH. Conclusions: In a mouse model of NASH, TH restored autophagy and mitochondrial biogenesis to increase ß-oxidation of fatty acids and to reduce lipotoxicity, oxidative stress, hepatic inflammation, and fibrosis. Activating thyroid hormone receptor in the liver may represent an effective strategy for NASH treatment.

Retrospective national cohort study of pregnancy outcomes for women with type 1 and type 2 diabetes mellitus in Republic of Ireland.

AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.

Increasing compliance with stretch breaks in computer users through reminder software.

In order for a repetitive strain injury (RSI) prevention program to be effective, it is important to implement strategies to maintain a client's compliance with the program. This quantitative study explored the effectiveness of computer reminder software in increasing compliance with a stretching program designed to prevent RSI associated with prolonged computer use. Data were collected from a convenience sample of 26 participants who were instructed in a preventative stretching program and assigned to either a treatment group with the computer reminder software, or a control group without the software. To measure compliance, all participants recorded the number of times per day they stretched. Although a statistically significant difference was not found in the mean number of stretch breaks taken by the two groups (p = 0.09), further analysis suggested a type II error may have occurred. The effect size, d, revealed a large effect suggesting that the computer software had an impact on the frequency of stretch breaks, with the mean number of breaks per hour of work greater for the treatment group. Results strongly suggest that further research is warranted in this area.