Diagnostic Performance for Detection of Glaucomatous Structural Damage Using Pixelwise Analysis of Retinal Thickness Measurements.

Purpose: To compare the diagnostic accuracy of thickness measurements of individual and combined macular retinal layers to discriminate 188 glaucomatous and 148 glaucoma suspect eyes from 362 healthy control (HC) eyes on a pixel-by-pixel basis. Methods: For this retrospective study, we manually corrected the segmentations of posterior pole optical coherence tomography (OCT) scans to determine the thickness of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), the ganglion cell complex (GCC), and the total neural retina (TR). For each eye, the total number of pixels with thickness values less than the fifth percentile of the HC distribution was used to create a receiver operating characteristic (ROC) curve for each layer and for layer combinations. Results: Using total abnormal pixel count criteria to discriminate glaucoma from HC eyes, the individual layers with the highest area under the ROC curve (AUC) were the NFL and GCL; IPL performance was significantly lower (P < 0.05). GCC had a significant higher AUC (94.3%) than individual the AUC of the NFL (92.3%) (P = 0.0231) but not higher than AUC of the GCL (93.4%) (P = 0.3487). The highest AUC (95.4%) and sensitivity (85.1%) at 95% specificity was found for the Boolean combination of NFL or GCL. The highest AUC is not significantly higher (P = 0.0882) than the AUC of the GCC but the highest sensitivity is significantly higher than the sensitivity of the GCC. This pattern was similar for discriminating between suspect and HC eyes (P = 0.0356). Conclusions: Using pixel-based methods, the diagnostic accuracy of NFL and GCL exceeded that of IPL and TR. GCC had equivalent performance as NFL and GCL. The specific spatial locations within the posterior pole that exhibit best performance vary depending on which layer is being assessed. Recognizing this dependency highlights the importance of considering multiple layers independently, as they offer complementary information for effective and comprehensive diagnosis.

Borna disease virus 1 induces ferroptosis, contributing to lethal encephalitis.

Borna disease virus 1 (BoDV-1) is a neurotropic RNA virus that has been linked to fatal BoDV-1 encephalitis (BVE) in humans. Ferroptosis represents a newly recognized kind of programmed cell death that marked by iron overload and lipid peroxidation. Various viral infections are closely related to ferroptosis. However, the link between BoDV-1 infection and ferroptosis, as well as its role in BVE pathogenesis, remains inadequately understood. Herein, we used primary rat cortical neurons, human microglial HMC3 cells, and Sprague‒Dawley rats as models. BoDV-1 infection induced ferroptosis, as ferroptosis characteristics were detected (iron overload, reactive oxygen species buildup, decreased antioxidant capacity, lipid peroxidation, and mitochondrial damage). Analysis via qRT-PCR and Western blot demonstrated that BoDV-1-induced ferroptosis was mediated through Nrf2/HO-1/SLC7a11/GPX4 antioxidant pathway suppression. Nrf2 downregulation was due to BoDV-1 infection promoting Nrf2 ubiquitination and degradation. Following BoDV-1-induced ferroptosis, the PTGS2/PGE2 signaling pathway was activated, and various intracellular lipid peroxidation products and damage-associated molecular patterns were released, contributing to BVE occurrence and progression. More importantly, inhibiting ferroptosis or the ubiquitin‒proteasome system effectively alleviated BVE. Collectively, these findings demonstrate the interaction between BoDV-1 infection and ferroptosis and reveal BoDV-1-induced ferroptosis as an underlying pathogenic mechanism of BVE.

A Nucleophilicity-Engineered DNA Ligation Blockade Nanoradiosensitizer Induces Irreversible DNA Damage to Overcome Cancer Radioresistance.

During fractionated radiotherapy, DNA damage repair intensifies in tumor cells, culminating in cancer radioresistance and subsequent radiotherapy failure. Despite the recent development of nanoradiosensitizers targeting specific DNA damage repair pathways, the persistence of repair mechanisms involving multiple pathways remains inevitable. To address this challenge, a nucleophilicity-engineered DNA ligation blockade nanoradiosensitizer (DLBN) comprising Au/CeO2 heteronanostructure modified with trans-acting activator of transcription peptides is reported, which targets and inhibits the DNA ligation inside cancer cell nuclei via heterointerface-mediated dephosphorylation of DNA, a crucial step in overcoming cancer radioresistance. First, the Schottky-type heteronanostructure of cancer cell nucleus-targeting DLBN effectively intensifies radiation-induced DNA damage via catalase-mimetic activity and radiation-triggered catalytic reactions. Notably, by leveraging Au/CeO2 heterointerface, DLBN spontaneously dissociates H2O to hydroxide, a nucleophile with higher nucleophilicity, thereby exhibiting remarkable dephosphorylation capability at DNA nicks through facilitated nucleophilic attack. This enables the blockade of DNA ligation, a pivotal step in all DNA damage repair pathways, effectively interrupting the repair process. Consequently, DLBN resensitizes radioresistant cells by overcoming therapy-induced radioresistance, leading to a substantial accumulation of unrepaired DNA damage. These findings offer insight into the dephosphorylation of DNA within nuclei, and underscore the potential of heteronanostructure-based nanoradiosensitizer to block DNA ligation against therapy-induced radioresistance.

Chitosan-Stabilized Selenium Nanoparticles Alleviate High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease (NAFLD) by Modulating the Gut Barrier Function and Microbiota.

Low molecular weight chitosan selenium nanoparticles (LCS-SeNPs), a biologically active compound derived from selenium polysaccharides, have demonstrated potential in addressing obesity. However, the mechanism through which LCS-SeNPs alleviate high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) remains unclear. Our results elucidated that LCS-SeNPs significantly inhibited fat accumulation and markedly improved the intestinal barrier by increasing mucus secretion from goblet cells. Moreover, LCS-SeNPs reshaped intestinal flora composition by increasing the abundance of mucus-associated microbiota (Bifidobacterium, Akkermansia, and Muribaculaceae_unclassified) and decreasing the abundance of obesity-contributed bacterium (Anaerotruncus, Lachnoclostridium, and Proteus). The modulation of intestinal microbiota by LCS-SeNPs influenced several metabolic pathways, including bile acid secretion, purine metabolites, and tryptophan derivation. Meanwhile, glycocholic acid and tauro-beta-muricholic acid were significantly reduced in the LCS-SeNP group. Our study suggests the crucial role of intestinal microbiota composition and metabolism, providing a new theoretical foundation for utilizing selenium polysaccharides in the intervention of HFD-induced NAFLD.

Comparative genomic and transcriptomic analyses provide new insight into symbiotic host specificity.

Host specificity plays important roles in expanding the host range of rhizobia, while the genetic information responsible for host specificity remains largely unexplored. In this report, the roots of four symbiotic systems with notable different symbiotic phenotypes and the control were studied at four different post-inoculation time points by RNA sequencning (RNA-seq). The differentially expressed genes (DEGs) were divided into "found only in soybean or Lotus," "only expressed in soybean or Lotus," and "expressed in both hosts" according to the comparative genomic analysis. The distributions of enriched function ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways vary significantly in different symbiotic systems. Host specific genes account for the majority of the DEGs involved in response to stimulus, associated with plant-pathogen interaction pathways, and encoding resistance (R) proteins, the symbiotic nitrogen fixation (SNF) proteins and the target proteins in the SNF-related modules. Our findings provided molecular candidates for better understanding the mechanisms of symbiotic host-specificity.

Combined application of myo-inositol and corn steep liquor enhances seedling growth and cold tolerance in cucumber and tomato.

Low temperatures pose a common challenge in the production of cucumbers and tomatoes, hindering plant growth and, in severe cases, leading to plant death. In our investigation, we observed a substantial improvement in the growth of cucumber and tomato seedlings through the application of corn steep liquor (CSL), myo-inositol (MI), and their combinations. When subjected to low-temperature stress, these treatments resulted in heightened levels of photosynthetic pigments, thereby fostering enhanced photosynthesis in both tomato and cucumber plants. Furthermore, it contributed to a decrease in malondialdehyde (MDA) levels and electrolyte leakage (REP). The effectiveness of the treatment was further validated through the analysis of key gene expressions (CBF1, COR, MIOX4, and MIPS1) in cucumber. Particularly, noteworthy positive outcomes were noted in the treatment involving 0.6 mL L-1 CSL combined with 72 mg L-1 MI. This study provides valuable technical insights into leveraging the synergistic effects of inositol and maize leachate to promote early crop growth and bolster resistance to low temperatures.

Differences in Systemic Pulse Waveform Between Individuals With Glaucoma, Glaucoma Suspects, and Healthy Controls.

Purpose: It has been hypothesized that compromised ocular circulation in glaucoma may be concomitant of systemic changes. The purpose of this study is to test whether systemic blood flow pulse waveform patterns differ between individuals with glaucoma (GL), glaucoma suspects (GLS), and normal healthy controls (HC). Methods: The study included 35 bilateral GL, 67 bilateral GLS, 29 individuals with unilateral GL who were considered GLS in the other eye, and 44 healthy controls. Systemic pulsatile blood pressure waveforms were recorded using a finger cuff. A continuous 200 Hz plethysmography recording is made to obtain a pulse waveform. Waveform parameters were extracted using custom software from an average of eight pulse cycles. These were compared between GL, GLS, and HC groups on a per-eye basis, using generalized estimating equation models to account for intereye correlations; and plotted against disease severity by visual field linearized mean deviation (MDlin) and retinal nerve fiber layer thickness (RNFLT). Results: Averaged blood pressure was significantly lower in the HC group (mean ± standard deviation 91.7 ±11.7 mm Hg) than the GLS (102.4 ± 13.9) or GL (102.8 ± 13.7) groups, with P < 0.0001 (generalized estimating equation regression). Waveform parameters representing vascular resistance were higher in both GLS and GL groups than the HC group; and were correlated with RNFLT and MDlin (P ≤ 0.05). Conclusions: The shape of the systemic pulsatile waveform differs in individuals with GL/GLS suspects, compared to HC eyes. Blood pressure changes more rapidly in individuals with GL, which suggests higher arterial stiffness.

Gelatinous quality and quantitative proteomic analyses of snakehead (Channa argus) surimi treated by atmospheric cold plasma.

In this study, the comprehensive quality characteristics and proteome changes of snakehead (Channa argus) surimi gel under different atmospheric cold plasma (ACP) treatment times were systematically analyzed and compared. The results showed that the ubiquitin-associated proteins and heat shock proteins were activated after ACP treatment for 90 s (ACP90), thus inducing rearrangement of surimi structural proteins. Meanwhile, the increased hydrophobic interactions and disulfide bonds might strengthen the interactions among the myofibrillar protein, keratin, and type-I collagen, which led to the formation of a dense gel network. Moreover, the high nodality between actin and myosin promoted the regulation of muscle contraction by changing the spatial obstruction of their binding sites. These beneficial effects obviously contributed to the superior water-holding capacity (76.13%), gel strength (285.6 g·cm) and viscoelasticity of snakehead surimi in the ACP90 group. These results would provide some useful information for the in-depth and efficient processing of surimi products.

The role of Interleukin-22 in severe acute pancreatitis.

Severe acute pancreatitis (SAP) begins with premature activation of enzymes, promoted by the immune system, triggering a potential systemic inflammatory response that leads to organ failure with increased mortality and a bleak prognosis. Interleukin-22 (IL-22) is a cytokine that may have a significant role in SAP. IL-22, a member of the IL-10 cytokine family, has garnered growing interest owing to its potential tissue-protective properties. Recently, emerging research has revealed its specific effects on pancreatic diseases, particularly SAP. This paper provides a review of the latest knowledge on the role of IL-22 and its viability as a therapeutic target in SAP.

Exploring Stigma Experience and Coping Strategies Among Women Living with HIV/AIDS in China: A Phenomenological Study.

Purpose: As of the end of 2022, over 20 million women worldwide, aged 15 and above, are living with HIV. Stigma remains a formidable barrier for women living with HIV/AIDS, hindering their access to healthcare and exacerbating health disparities. Indeed, some women living with HIV/AIDS can successfully confront and overcome stigma. There remains a paucity of qualitative research exploring the stigma coping strategies of women living with HIV/AIDS in China. This study was aimed to gain the deeper understanding of stigma experienced by women living with HIV/AIDS and coping strategies. Patients and Methods: We recruited diverse participants using snowball sampling and purposive sampling. Semi-structured personal in-depth interviews were conducted with 30 women living with HIV/AIDS from December 2022 to June 2023. The samples were from four HIV/AIDS designated hospitals. The data were analyzed using the Colaizzi seven-step model. Results: The experiences of stigma among women living with HIV/AIDS included family role (wife/mother/grandmother) collapse and disgusted by family, resignation in being shunned by others, helplessness due to social exclusion, grief at being devaluated, and resentment for experiencing injustice. The coping strategies used to deal with stigma included concealing their conditions, avoiding socialization, and attempting to retaliate against society. Conclusion: Healthcare professionals are recommended to offer women living with HIV/AIDS effective emotional support and guidance to cope with stigma. The study highlights the stigma they face, providing valuable evidence for policymakers. Recommendations emphasize the importance of developing services addressing both physical and psychological needs of women living with HIV/AIDS.

Exploring the pathogenesis of chronic atrophic gastritis with atherosclerosis via microarray data analysis.

Although several studies have reported a link between chronic atrophic gastritis (CAG) and atherosclerosis, the underlying mechanisms have not been elucidated. The present study aimed to investigate the molecular mechanisms common to both diseases from a bioinformatics perspective. Gene expression profiles were obtained from the Gene Expression Omnibus database. Data on atherosclerosis and CAG were downloaded from the GSE28829 and GSE60662 datasets, respectively. We identified the differentially expressed genes co-expressed in CAG and atherosclerosis before subsequent analyses. We constructed and identified the hub genes and performed functional annotation. Finally, the transcription factor (TF)-target genes regulatory network was constructed. In addition, we validated core genes and certain TFs. We identified 116 common differentially expressed genes after analyzing the 2 datasets (GSE60662 and GSE28829). Functional analysis highlighted the significant contribution of immune responses and the positive regulation of tumor necrosis factor production and T cells. In addition, phagosomes, leukocyte transendothelial migration, and cell adhesion molecules strongly correlated with both diseases. Furthermore, 16 essential hub genes were selected with cytoHubba, including PTPRC, TYROBP, ITGB2, LCP2, ITGAM, FCGR3A, CSF1R, IRF8, C1QB, TLR2, IL10RA, ITGAX, CYBB, LAPTM5, CD53, CCL4, and LY86. Finally, we searched for key gene-related TFs, especially SPI1. Our findings reveal a shared pathogenesis between CAG and atherosclerosis. Such joint pathways and hub genes provide new insights for further studies.

The Temporal Relation Between Rates of Retinal Nerve Fiber Layer and Minimum Rim Width Changes in Glaucoma.

Purpose: This study aims to determine whether OCT-derived rates of change in minimum rim width (MRW) are associated with and can potentially predict corresponding alterations in retinal nerve fiber layer thickness (RNFLT) in people with glaucoma. Methods: The rates of change between six-monthly visits were taken from 568 eyes of 278 participants in the P3 Study. Structural equation models (SEM) assessed whether one parameter was predicted by the concurrent or previous rate of the other parameter, after adjusting for its own rate in the previous time interval. Root mean square error of approximation (RMSEA, with 90% confidence intervals [CI]), Tucker Lewis index (TLI) and the comparative fit index (CFI) assessed goodness of fit. Results: Models without a time lag provided a better fit for the data (RMSEA = 0.101 [CI, 0.089, 0.113]), compared to a model featuring a time lag in RNFLT (RMSEA = 0.114 [CI, 0.102, 0.126]) or MRW (RMSEA = 0.114 [CI, 0.102, 0.127]). The SEMs indicated that rates for both MRW and RNFLT were predicted by their own rate in the previous time interval and by the other measure's change in the concurrent time interval (P > 0.001 for all). No evidence of a clinically significant time lag for either parameter was determined. Conclusions: MRW and RNFLT exhibit concurrent changes over time in patients with glaucoma, with no clinically significant time lag determined. Translational Relevance: RNFLT may be more useful than MRW in early glaucoma assessment because of its previously reported lower variability and reduced sensitivity to intraocular pressure changes.

CRISPR/Cas9-mediated editing of GmDWF1 brassinosteroid biosynthetic gene induces dwarfism in soybean.

KEY MESSAGE: The study on the GmDWF1-deficient mutant dwf1 showed that GmDWF1 plays a crucial role in determining soybean plant height and yield by influencing the biosynthesis of brassinosteroids. Soybean has not adopted the Green Revolution, such as reduced height for increased planting density, which have proven beneficial for cereal crops. Our research identified the soybean genes GmDWF1a and GmDWF1b, homologous to Arabidopsis AtDWF1, and found that they are widely expressed, especially in leaves, and linked to the cellular transport system, predominantly within the endoplasmic reticulum and intracellular vesicles. These genes are essential for the synthesis of brassinosteroids (BR). Single mutants of GmDWF1a and GmDWF1b, as well as double mutants of both genes generated through CRISPR/Cas9 genome editing, exhibit a dwarf phenotype. The single-gene mutant exhibits moderate dwarfism, while the double mutant shows more pronounced dwarfism. Despite the reduced stature, all types of mutants preserve their node count. Notably, field tests have shown that the single GmDWF1a mutant produced significantly more pods than wild-type plants. Spraying exogenous brassinolide (BL) can compensate for the loss in plant height induced by the decrease in endogenous BRs. Comparing transcriptome analyses of the GmDWF1a mutant and wild-type plants revealed a significant impact on the expression of many genes that influence soybean growth. Identifying the GmDWF1a and GmDWF1b genes could aid in the development of compact, densely planted soybean varieties, potentially boosting productivity.

An pair of an atypical NLR encoding genes confer Asian soybean rust resistance in soybean.

Asian soybean rust (ASR), caused by Phakopsora pachyrhizi, is a devastating disease that is present in all major soybean-producing regions. The limited availability of resistant germplasm has resulted in a scarcity of commercial soybean cultivars that are resistant to the disease. To date, only the Chinese soybean landrace SX6907 has demonstrated an immune response to ASR. In this study, we present the isolation and characterization of Rpp6907-7 and Rpp6907-4, a gene pair that confer broad-spectrum resistance to ASR. Rpp6907-7 and Rpp6907-4 encode atypic nucleotide-binding leucine-rich repeat (NLR) proteins that are found to be required for NLR-mediated immunity. Genetic analysis shows that only Rpp6907-7 confers resistance, while Rpp6907-4 regulates Rpp6907-7 signaling activity by acting as a repressor in the absence of recognized effectors. Our work highlights the potential value of using Rpp6907 in developing resistant soybean cultivars.

An artificial protein modulator reprogramming neuronal protein functions.

Reversible protein phosphorylation, regulated by protein phosphatases, fine-tunes target protein function and plays a vital role in biological processes. Dysregulation of this process leads to aberrant post-translational modifications (PTMs) and contributes to disease development. Despite the widespread use of artificial catalysts as enzyme mimetics, their direct modulation of proteins remains largely unexplored. To address this gap and enable the reversal of aberrant PTMs for disease therapy, we present the development of artificial protein modulators (APROMs). Through atomic-level engineering of heterogeneous catalysts with asymmetric catalytic centers, these modulators bear structural similarities to protein phosphatases and exhibit remarkable ability to destabilize the bridging µ3-hydroxide. This activation of catalytic centers enables spontaneous hydrolysis of phospho-substrates, providing precise control over PTMs. Notably, APROMs, with protein phosphatase-like characteristics, catalytically reprogram the biological function of α-synuclein by directly hydrolyzing hyperphosphorylated α-synuclein. Consequently, synaptic function is reinforced in Parkinson's disease. Our findings offer a promising avenue for reprogramming protein function through de novo PTMs strategy.

Changes in the Physicochemical Properties and Microbial Communities of Air-Fried Hairtail Fillets during Storage.

This study assessed the physicochemical properties of air-fried hairtail fillets (190 °C, 24 min) under different storage temperatures (4, 25, and 35 °C). The findings revealed a gradual decline in sensory scores across all samples during storage, accompanied by a corresponding decrease in thiobarbituric acid reactive substances (TBARS) and total viable count over time. Lower storage temperatures exhibited an effective capacity to delay lipid oxidation and microbiological growth in air-fried hairtail fillets. Subsequently, alterations in the microbiota composition of air-fried hairtail fillets during cold storage were examined. Throughout the storage duration, Achromobacter, Escherichia-Shigella, and Pseudomonas emerged as the three dominant genera in the air-fried hairtail samples. Additionally, Pearson correlation analysis demonstrated that among the most prevalent microbial genera in air-fried hairtail samples, Achromobacter and Psychrobacter exhibited positive correlations with the L* value, a* value, and sensory scores. Conversely, they displayed negative correlations with pH, b* value, and TBARS. Notably, air-fried samples stored at 4 °C exhibited prolonged freshness compared with those stored at 25 °C and 35 °C, suggesting that 4 °C is an optimal storage temperature. This study offers valuable insights into alterations in the physicochemical properties and microbial distribution in air-fried hairtail fillets during storage, facilitating the improvement of meat quality by adjusting microbial communities in air-fried hairtail fillets.

Therapeutic effect and study of human umbilical cord blood mononuclear cells in patients with ischaemic bowel disease.

Ischaemic bowel disease (ICBD) is a group of intestinal ischaemia syndromes caused by various aetiologies of reduced intestinal blood flow or vascular occlusion. ICBD can present as abdominal pain, bloody stool, and diarrhoea. This disease often occurs in middle-aged and elderly individuals with cardiovascular and cerebrovascular diseases. The incidence of ischaemic bowel disease has been increasing for decades, and it is difficult to diagnose, resulting in rapid disease progression and a high mortality rate. Therefore, fully understanding this disease, improving the diagnosis rate of this disease, and finding appropriate treatment methods are urgently needed to improve the condition and prognosis of patients. Umbilical cord blood stem cells are accessible, have weak immunogenicity, and have various biological functions, such as angiogenesis, inflammation and immune regulation. Many studies have confirmed that cord blood stem cells can relieve ischaemia, and these cells have attracted tremendous amounts of attention in regenerative medicine in recent years. In this paper, we discuss the clinical characteristics of ICBD, analyse the characteristics of human umbilical cord blood mononuclear cells (HUCB-MNCs), and use its to treat ischaemic bowel disease. Additionally, we compare the clinical manifestations and related indicators before and after treatment to evaluate the efficacy and safety of these methods.

Study on the Rectification of Ionic Diode Based on Cross-Linked Nanocellulose Bipolar Membranes.

Nanocellulose-based membranes have attracted intense attention in bioelectronic devices due to their low cost, flexibility, biocompatibility, degradability, and sustainability. Herein, we demonstrate a flexible ionic diode using a cross-linked bipolar membrane fabricated from positively and negatively charged cellulose nanofibrils (CNFs). The rectified current originates from the asymmetric charge distribution, which can selectively determine the direction of ion transport inside the bipolar membrane. The mechanism of rectification was demonstrated by electrochemical impedance spectroscopy with voltage biases. The rectifying behavior of this kind of ionic diode was studied by using linear sweep voltammetry to obtain current-voltage characteristics and the time dependence of the current. In addition, the performance of cross-linked CNF diodes was investigated while changing parameters such as the thickness of the bipolar membranes, the scanning voltage range, and the scanning rate. A good long-term stability due to the high density cross-linking of the diode was shown in both current-voltage characteristics and the time dependence of current.

Navigating the future of retinitis pigmentosa treatments: A comprehensive analysis of therapeutic approaches in rd10 mice.

Retinitis pigmentosa (RP) is a degenerative disease, caused by genetic mutations that lead to a loss in photoreceptors. For research on RP, rd10 mice, which carry mutations in the phosphodiesterase (PDE) gene, exhibit degenerative patterns comparable to those of patients with RP, making them an ideal model for investigating potential treatments. Although numerous studies have reported the potential of biochemical drugs, gene correction, and stem cell transplantation in decelerating rd10 retinal degeneration, a comprehensive review of these studies has yet to be conducted. Therefore, here, a comparative analysis of rd10 mouse treatment research over the past decade was performed. Our findings suggest that biochemical drugs capable of inhibiting the inflammatory response may be promising therapeutics. Additionally, significant progress has been made in the field of gene therapy; nevertheless, challenges such as strict delivery requirements, bystander editing, and off-target effects still need to be resolved. Nevertheless, secretory function is the only unequivocal protective effect of stem cell transplantation. In summary, this review presents a comprehensive analysis and synthesis of the treatment approaches employing rd10 mice as experimental subjects, describing a clear pathway for future RP treatment research and identifies potential clinical interventions.