Multilevel Pain Assessment with Functional Near-Infrared Spectroscopy: Evaluating ΔHBO2 and ΔHHB Measures for Comprehensive Analysis.

Assessing pain in non-verbal patients is challenging, often depending on clinical judgment which can be unreliable due to fluctuations in vital signs caused by underlying medical conditions. To date, there is a notable absence of objective diagnostic tests to aid healthcare practitioners in pain assessment, especially affecting critically-ill or advanced dementia patients. Neurophysiological information, i.e., functional near-infrared spectroscopy (fNIRS) or electroencephalogram (EEG), unveils the brain's active regions and patterns, revealing the neural mechanisms behind the experience and processing of pain. This study focuses on assessing pain via the analysis of fNIRS signals combined with machine learning, utilising multiple fNIRS measures including oxygenated haemoglobin (ΔHBO2) and deoxygenated haemoglobin (ΔHHB). Initially, a channel selection process filters out highly contaminated channels with high-frequency and high-amplitude artifacts from the 24-channel fNIRS data. The remaining channels are then preprocessed by applying a low-pass filter and common average referencing to remove cardio-respiratory artifacts and common gain noise, respectively. Subsequently, the preprocessed channels are averaged to create a single time series vector for both ΔHBO2 and ΔHHB measures. From each measure, ten statistical features are extracted and fusion occurs at the feature level, resulting in a fused feature vector. The most relevant features, selected using the Minimum Redundancy Maximum Relevance method, are passed to a Support Vector Machines classifier. Using leave-one-subject-out cross validation, the system achieved an accuracy of 68.51%±9.02% in a multi-class task (No Pain, Low Pain, and High Pain) using a fusion of ΔHBO2 and ΔHHB. These two measures collectively demonstrated superior performance compared to when they were used independently. This study contributes to the pursuit of an objective pain assessment and proposes a potential biomarker for human pain using fNIRS.

Experimental Exploration of Multilevel Human Pain Assessment Using Blood Volume Pulse (BVP) Signals.

Critically ill patients often lack cognitive or communicative functions, making it challenging to assess their pain levels using self-reporting mechanisms. There is an urgent need for an accurate system that can assess pain levels without relying on patient-reported information. Blood volume pulse (BVP) is a relatively unexplored physiological measure with the potential to assess pain levels. This study aims to develop an accurate pain intensity classification system based on BVP signals through comprehensive experimental analysis. Twenty-two healthy subjects participated in the study, in which we analyzed the classification performance of BVP signals for various pain intensities using time, frequency, and morphological features through fourteen different machine learning classifiers. Three experiments were conducted using leave-one-subject-out cross-validation to better examine the hidden signatures of BVP signals for pain level classification. The results of the experiments showed that BVP signals combined with machine learning can provide an objective and quantitative evaluation of pain levels in clinical settings. Specifically, no pain and high pain BVP signals were classified with 96.6% accuracy, 100% sensitivity, and 91.6% specificity using a combination of time, frequency, and morphological features with artificial neural networks (ANNs). The classification of no pain and low pain BVP signals yielded 83.3% accuracy using a combination of time and morphological features with the AdaBoost classifier. Finally, the multi-class experiment, which classified no pain, low pain, and high pain, achieved 69% overall accuracy using a combination of time and morphological features with ANN. In conclusion, the experimental results suggest that BVP signals combined with machine learning can offer an objective and reliable assessment of pain levels in clinical settings.

Hexavalent Chromium Targets Securin to Drive Numerical Chromosome Instability in Human Lung Cells.

Hexavalent chromium [Cr(VI)] is a known human lung carcinogen with widespread exposure in environmental and occupational settings. Despite well-known cancer risks, the molecular mechanisms of Cr(VI)-induced carcinogenesis are not well understood, but a major driver of Cr(VI) carcinogenesis is chromosome instability. Previously, we reported Cr(VI) induced numerical chromosome instability, premature centriole disengagement, centrosome amplification, premature centromere division, and spindle assembly checkpoint bypass. A key regulator of these events is securin, which acts by regulating the cleavage ability of separase. Thus, in this study we investigated securin disruption by Cr(VI) exposure. We exposed human lung cells to a particulate Cr(VI) compound, zinc chromate, for acute (24 h) and prolonged (120 h) time points. We found prolonged Cr(VI) exposure caused marked decrease in securin levels and function. After prolonged exposure at the highest concentration, securin protein levels were decreased to 15.3% of control cells, while securin mRNA quantification was 7.9% relative to control cells. Additionally, loss of securin function led to increased separase activity manifested as enhanced cleavage of separase substrates; separase, kendrin, and SCC1. These data show securin is targeted by prolonged Cr(VI) exposure in human lung cells. Thus, a new mechanistic model for Cr(VI)-induced carcinogenesis emerges with centrosome and centromere disruption as key components of numerical chromosome instability, a key driver in Cr(VI) carcinogenesis.

Empirical comparison of deep learning models for fNIRS pain decoding.

Introduction: Pain assessment is extremely important in patients unable to communicate and it is often done by clinical judgement. However, assessing pain using observable indicators can be challenging for clinicians due to the subjective perceptions, individual differences in pain expression, and potential confounding factors. Therefore, the need for an objective pain assessment method that can assist medical practitioners. Functional near-infrared spectroscopy (fNIRS) has shown promising results to assess the neural function in response of nociception and pain. Previous studies have explored the use of machine learning with hand-crafted features in the assessment of pain. Methods: In this study, we aim to expand previous studies by exploring the use of deep learning models Convolutional Neural Network (CNN), Long Short-Term Memory (LSTM), and (CNN-LSTM) to automatically extract features from fNIRS data and by comparing these with classical machine learning models using hand-crafted features. Results: The results showed that the deep learning models exhibited favourable results in the identification of different types of pain in our experiment using only fNIRS input data. The combination of CNN and LSTM in a hybrid model (CNN-LSTM) exhibited the highest performance (accuracy = 91.2%) in our problem setting. Statistical analysis using one-way ANOVA with Tukey's (post-hoc) test performed on accuracies showed that the deep learning models significantly improved accuracy performance as compared to the baseline models. Discussion: Overall, deep learning models showed their potential to learn features automatically without relying on manually-extracted features and the CNN-LSTM model could be used as a possible method of assessment of pain in non-verbal patients. Future research is needed to evaluate the generalisation of this method of pain assessment on independent populations and in real-life scenarios.

Exploring Indonesian actinomycete extracts for anti-tubercular compounds: Integrating inhibition assessment, genomic analysis, and prediction of its target by molecular docking.

Tuberculosis (TB) is the foremost cause of infectious fatality globally. The primary global challenge in combatting TB lies in addressing the emergence of drug-resistant variants of the disease. However, the number of newly approved agents for treating TB has remained remarkably low over recent decades. Hence, research endeavors for discovering novel anti-TB agents are always needed. In the present study, we screened over 1,500 culture extracts from actinomycetes isolated in Indonesia for their inhibitory activity against Mycobacterium smegmatis used as a surrogate in the primary screening. The initial screening yielded approximately 6.2 % hit extracts, with a selection criterion of >80 % growth inhibition. The confirmed hit extracts were subsequently subjected to growth inhibition assay against Mycobacterium bovis and Mycobacterium tuberculosis. Approximately 20 % of the hit extracts that showed growth inhibition also exhibited efficacy against M. bovis BCG and M. tuberculosis H37Rv pathogenic strain. An active compound was successfully purified from a large-scale culture of the most potent representative extract by high-performance liquid chromatography and thin-layer chromatography. The structure of the active compound was elucidated by mass spectrometry and nuclear magnetic resonance. This compound displayed structural similarities to actinomycin group and exhibited robust inhibition, with IC50 values of 0.74, 0.02, and 0.07 µg/mL against M. smegmatis, M. bovis, and M. tuberculosis, respectively. The Actinomycetes strain A612, which produced the active compound, was taxonomically classified by phylogenetic analysis of 16s rRNA gene and whole genome sequencing data as Streptomyces parvus. Computational genome analysis utilizing anti-SMASH 7.0 unveiled that S. parvus A612 strain harbors 40 biosynthetic gene clusters with the potential to produce 16 known (with >70 % similarity) and 24 unknown compounds. A non-ribosomal peptide synthesis (NRPS) gene cluster associated with actinomycin D biosynthesis was also identified, boasting an 85 % similarity. Molecular docking analysis of actinomycin D and 21 potential M. tuberculosis targets revealed possible interactions with multiple targets. The purified active compound inhibited recombinant M. tuberculosis shikimate kinase (MtSK), which validated the results obtained from the docking analysis.

The imperative of high-quality education in juvenile corrections: An introduction to the special section.

The publication of "Guiding Principles for Providing High-Quality Education in Juvenile Justice Secure Care Setting" in 2014 by the U.S. Department of Education and the Department of Justice was a seminal event for those concerned about education opportunities for all young people. The articles in this special section examine the research literature since the publication of the guiding principles. In Article 1, Gagnon, Ross Benedick, and Mason-William (2021) focus on Principle I and research related to, "The provision of a safe, healthy facility-wide climate that... encourages the necessary behavioral and social support services." In the second article of this Special Section, Gagnon, Ruiz, et al. (2022) also address Principle I in their literature review of behavioral interventions for incarcerated youth. Hunter et al. (2022) focus their literature review on curriculum, instruction, and promoting college and career readiness for incarcerated youth. In the final article, Gagnon, Ross Benedick, and Mason-William (2021) detail the overarching search procedures from which all of the literature reviews emanated. They also summarize data on quality indicators for studies across all of the principles and articles in the Special Section and provide implications for research, policy, and practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Mental health interventions for youth who are incarcerated: A systematic review of literature.

To promote the safety and well-being of youth who are incarcerated, the U.S. Departments of Justice and Education identified the importance of evidence-based mental health interventions. The purpose of this systematic review is to summarize and synthesize intervention research focusing on the mental health of youth who are incarcerated since the publication of Guiding Principles for Providing High-Quality Education in Juvenile Justice Secure Care Settings. ProQuest and Ebsco databases were searched to identify relevant published studies from 2015 to 2020. Eleven studies met the inclusion criteria. Studies mainly focused on cognitive-behavior interventions and included the following outcome domains: symptoms, functioning, personal growth, and multiple domains. To evaluate study quality, modified versions of Gersten et al.'s (2005) group design and Mulcahy et al.'s (2016) single-case design quality indicators were used. Of concern are the small number of studies, methodological limitations within studies, and lack of a common intervention and outcomes of focus that limit individual study conclusions and evaluation across studies. In particular, studies rarely included necessary information, such as participant mental health characteristics, interventionist training or qualifications, intervention details, and/or measures/reports of treatment integrity. For the Guiding Principles to be realized, one key issue is for government funding to target high-quality mental health interventions in juvenile correctional facilities within identified target areas. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Interventions addressing incarcerated youth behavior: A review of literature.

Many youth who are incarcerated have serious behavioral problems that negatively affect their ability to benefit from educational services. In the Guiding Principles for Providing High-Quality Education in Juvenile Justice Secure Care Settings published at the end of 2014, the U.S. Departments of Justice and Education address this issue in Principle 1, which asserts the importance of ensuring the safety and well-being of youth who are incarcerated. To address the research progress since publication of the Guiding Principles, ProQuest and Ebsco were systematically searched and a hand search was conducted. Ten intervention studies were identified that addressed youth behavior. The studies primarily employed a single subject research design and focused on increasing youth compliance and/or decreasing disruptive behaviors. Reviewed studies provide support for providing clear behavioral expectations and reminders, praise, and reinforcement, as well as cognitive-behavioral interventions. However, methodological limitations, including the lack of treatment integrity in nine of the studies, limit conclusions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Curriculum, instruction, and promoting college and career readiness for incarcerated youth: A literature review.

Access to high-quality curriculum and instruction is essential for all youth incarcerated in juvenile corrections facilities. In a landmark 2014 collaboration between the U.S. Departments of Education and Justice Guiding Principles for Providing High-Quality Education in Juvenile Justice Secure Care Settings were established. Principle independent variable (IV) identified the importance of access to rigorous and relevant curricula and evidence-based instruction that promotes college- and career-readiness. To explore research progress since publication of the Guiding Principles, a systematic review of research was conducted. The review identified eight peer-reviewed studies relevant to curriculum and instruction published since 2014. Employing a variety of research designs, the studies focused on literacy (n = 5) and instruction (n = 3). Quality indicators, based on modified forms of Mulcahy et al. (2016) single case design, Gersten et al. (2005) group design, and Miles et al. (2019) qualitative standards, were used to evaluate the studies. Results revealed a lack of replicable information pertinent to participants and intervention, as well as a lack of fidelity. Of grave concern is that only four of the participants included across all studies were female. Research that adheres to quality indicators, is described with replicable precision, and is representative of females is needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Providing high-quality education in juvenile corrections: Next steps.

In 2014, the U.S. Departments of Education and Justice (U.S. DOE/DOJ) jointly released the Guiding Principles for Providing High-Quality Education in Juvenile Justice Secure Care Settings to provide recommendations within five principles that affect education, including safety (i.e., behavioral and mental health interventions), funding, staffing, curriculum and instruction, and reentry. However, no systematic review has evaluated the research within and across the Guiding Principles since their publication. The purpose of the current article is to (a) describe the literature review process that resulted in 36 studies across all of the principles, (b) briefly summarize information from the separate literature reviews focusing on behavior, mental health, and curriculum and instruction for which no separate literature reviews have been conducted, (c) provide detail concerning studies focusing on staffing and reentry, and (d) identify patterns across studies in all of the reviews, particularly related to study quality. In addition, we provide implications for research, policy, and practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses.

Griffithsin (GRFT), a lectin from Griffithsia species, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assessed GRFT's effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC) viability, mitogenicity, and activation using flow-cytometry, as well as cytokine secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of microbicide development, toxicity of GRFT at 2 mg/kg was determined after subcutaneous, intravaginal, and intraperitoneal administrations, respectively. Interestingly, GRFT caused no significant cell death, mitogenicity, activation, or cytokine release in mPBMCs, validating the usefulness of a mouse model. An excellent safety profile for GRFT was obtained in vivo: no overt changes were observed in animal fitness, blood chemistry or CBC parameters. Following GRFT treatment, reversible splenomegaly was observed with activation of certain spleen B and T cells. However, spleen tissues were not pathologically altered by GRFT (either with a single high dose or chronic doses). Finally, no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which should be further developed as a microbicide for HIV prevention.

Feasibility of School-Based ADHD Interventions: A Mixed-Methods Study of Perceptions of Adolescents and Adults.

OBJECTIVE: Little is known about perceptions surrounding academic interventions for ADHD that determine intervention feasibility. METHOD: As part of a longitudinal mixed-methods research project, representative school district samples of 148 adolescents (54.8%), 161 parents (59.4%), 122 teachers (50.0%), 46 health care providers (53.5%), and 92 school health professionals (65.7%) completed a cross-sectional survey. They also answered open-ended questions addressing undesirable intervention effects, which were analyzed using grounded theory methods. RESULTS: Adolescents expressed significantly lower receptivity toward academic interventions than adult respondents. Stigma emerged as a significant threat to ADHD intervention feasibility, as did perceptions that individualized interventions foster inequality. CONCLUSION: Findings suggest that adolescents' viewpoints must be included in intervention development to enhance feasibility and avoid interventions acceptable to adults, but resisted by adolescents.

Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate.

Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin.