An adaptive data-driven architecture for mental health care applications.

Background: In the current era of rapid technological innovation, our lives are becoming more closely intertwined with digital systems. Consequently, every human action generates a valuable repository of digital data. In this context, data-driven architectures are pivotal for organizing, manipulating, and presenting data to facilitate positive computing through ensemble machine learning models. Moreover, the COVID-19 pandemic underscored a substantial need for a flexible mental health care architecture. This architecture, inclusive of machine learning predictive models, has the potential to benefit a larger population by identifying individuals at a heightened risk of developing various mental disorders. Objective: Therefore, this research aims to create a flexible mental health care architecture that leverages data-driven methodologies and ensemble machine learning models. The objective is to proficiently structure, process, and present data for positive computing. The adaptive data-driven architecture facilitates customized interventions for diverse mental disorders, fostering positive computing. Consequently, improved mental health care outcomes and enhanced accessibility for individuals with varied mental health conditions are anticipated. Method: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the researchers conducted a systematic literature review in databases indexed in Web of Science to identify the existing strengths and limitations of software architecture relevant to our adaptive design. The systematic review was registered in PROSPERO (CRD42023444661). Additionally, a mapping process was employed to derive essential paradigms serving as the foundation for the research architectural design. To validate the architecture based on its features, professional experts utilized a Likert scale. Results: Through the review, the authors identified six fundamental paradigms crucial for designing architecture. Leveraging these paradigms, the authors crafted an adaptive data-driven architecture, subsequently validated by professional experts. The validation resulted in a mean score exceeding four for each evaluated feature, confirming the architecture's effectiveness. To further assess the architecture's practical application, a prototype architecture for predicting pandemic anxiety was developed.

Response of Pediatric Choroidal Neovascularization to Anti-Vascular Endothelial Growth Factor.

Choroidal neovascularization (CNV) is a rare condition in children but poses a substantial threat to vision. Anti-vascular endothelial growth factor (anti-VEGF) therapy is commonly used in the pediatric population to treat retinopathy of prematurity. However, the use of anti-VEGF is less common for childhood CNV due to the rarity of CNV in the pediatric population. We report the case of a 10-year-old male presenting with an idiopathic choroidal neovascular membrane. Following a relapse of subretinal fluid after photodynamic therapy, anti-VEGF (bevacizumab) was injected and resulted in remission of the neovascular membrane and improved visual outcome. Further studies are required to elucidate the long-term outcomes associated with the use of anti-VEGF in pediatric patients.

Review of economic evaluations of teleophthalmology as a screening strategy for chronic eye disease in adults.

BACKGROUND/AIMS: Teleophthalmology is well positioned to play a key role in screening of major chronic eye diseases. Economic evaluation of cost-effectiveness of teleophthalmology, however, is lacking. This study provides a systematic review of economic studies of teleophthalmology screening for diabetic retinopathy (DR), glaucoma and macular degeneration. METHODS: Structured search of electronic databases and full article review yielded 20 cost-related articles. Sixteen articles fulfilled the inclusion criteria and were retained for a narrative review: 12 on DR, 2 on glaucoma and 2 on chronic eye disease. RESULTS: Teleophthalmology for DR yielded the most cost savings when compared with traditional clinic examination. The study settings varied among urban, rural and remote settings, community, hospital and health mobile units. The most important determinant of cost-effectiveness of teleophthalmology was the prevalence of DR among patients screened, indicating an increase of cost savings with the increase of screening rates. The required patient pool size to be screened varied from 110 to 3500 patients. Other factors potentially influencing cost-effectiveness of teleophthalmology were older patient age, regular screening and full utilisation of the equipment. Teleophthalmology for glaucoma was more cost-effective compared with in-person examination. Similarly, increasing number of glaucoma patients targeted for screening yielded more cost savings. CONCLUSIONS: This economic review provides supportive evidence of cost-effectiveness of teleophthalmology for DR and glaucoma screening potentially increasing screening accessibility especially for rural and remote populations. Special selection of the targeted screening population will optimise the cost-effectiveness of teleophthalmology.

Tele-Ophthalmology for Age-Related Macular Degeneration and Diabetic Retinopathy Screening: A Systematic Review and Meta-Analysis.

BACKGROUND: To synthesize high-quality evidence to compare traditional in-person screening and tele-ophthalmology screening. METHODS: Only randomized controlled trials (RCTs) were included in this systematic review and meta-analysis. The intervention of interest was any type of tele-ophthalmology, including screening of diseases using remote devices. Studies involved patients receiving care from any trained provider via tele-ophthalmology, compared with those receiving equivalent face-to-face care. A search was executed on the following databases: Medline, EMBASE, EBM Reviews, Global Health, EBSCO-CINAHL, SCOPUS, ProQuest Dissertations and Theses Global, OCLC Papers First, and Web of Science Core Collection. Six outcomes of care for age-related macular degeneration (AMD), diabetic retinopathy (DR), or glaucoma were measured and analyzed. RESULTS: Two hundred thirty-seven records were assessed at the full-text level; six RCTs fulfilled inclusion criteria and were included in this review. Four studies involved participants with diabetes mellitus, and two studies examined choroidal neovascularization in AMD. Only data of detection of disease and participation in the screening program were used for the meta-analysis. Tele-ophthalmology had a 14% higher odds to detect disease than traditional examination; however, the result was not statistically significant (n = 2,012, odds ratio: 1.14, 95% confidence interval (CI): 0.52-2.53, p = 0.74). Meta-analysis results show that odds of having DR screening in the tele-ophthalmology group was 13.15 (95% CI: 8.01-21.61; p < 0.001) compared to the traditional screening program. CONCLUSIONS: The current evidence suggests that tele-ophthalmology for DR and age-related macular degeneration is as effective as in-person examination and potentially increases patient participation in screening.

Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here, we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and invasiveness, correlating with diminished glucose uptake, glycolytic flux, and oncogenic PI3 kinase signaling which in turn could rescue TBL1 deficiency-dependent phenotypes. TBL1 deficiency both prevented and reversed pancreatic tumor growth, mediated transcriptional PI3 kinase inhibition, and increased chemosensitivity of PDAC cells in vivo. As TBL1 mRNA levels were also found to correlate with PI3 kinase levels and overall survival in a cohort of human PDAC patients, TBL1 was identified as a checkpoint in the malignant behavior of pancreatic cancer and its expression may serve as a novel molecular target in the treatment of human PDAC.

Development, validation and quantitative assessment of an enzymatic assay suitable for small molecule screening and profiling: A case-study.

The successful discovery and subsequent development of small molecule inhibitors of drug targets relies on the establishment of robust, cost-effective, quantitative, and physiologically relevant in vitro assays that can support prolonged screening and optimization campaigns. The current study illustrates the process of developing and validating an enzymatic assay for the discovery of small molecule inhibitors using alkaline phosphatase from bovine intestine as model target. The assay development workflow includes an initial phase of optimization of assay materials, reagents, and conditions, continues with a process of miniaturization and automation, and concludes with validation by quantitative measurement of assay performance and signal variability. The assay is further evaluated for dose-response and mechanism-of-action studies required to support structure-activity-relationship studies. Emphasis is placed on the most critical aspects of assay optimization and other relevant considerations, including the technology, assay materials, buffer constituents, reaction conditions, liquid handling equipment, analytical instrumentation, and quantitative assessments. Examples of bottlenecks encountered during assay development and strategies to address them are provided.

Assays, surrogates, and alternative technologies for a TB lead identification program targeting DNA gyrase ATPase.

Mycobacterium tuberculosis (Mtb) DNA gyrase ATPase was the target of a tuberculosis drug discovery program. The low specific activity of the Mtb ATPase prompted the use of Mycobacterium smegmatis (Msm) enzyme as a surrogate for lead generation, since it had 20-fold higher activity. Addition of GyrA or DNA did not significantly increase the activity of the Msm GyrB ATPase, and an assay was developed using GyrB alone. Inhibition of the Msm ATPase correlated well with inhibition of Mtb DNA gyrase supercoiling across three chemical scaffolds, justifying its use. As the IC50 of compounds approached the enzyme concentration, surrogate assays were used to estimate potencies (e.g., the shift in thermal melt of Mtb GyrB, which correlated well with IC(50)s >10 nM). Analysis using the Morrison equation enabled determination of K(i)(app)s in the sub-nanomolar range. Surface plasmon resonance was used to confirm these IC(50)s and measure the K ds of binding, but a fragment of Mtb GyrB had to be used. Across three scaffolds, the dissociation half life, t1/2, of the inhibitor-target complex was ≤ 8 min. This toolkit of assays was developed to track the potency of enzyme inhibition and guide the chemistry for progression of compounds in a lead identification program.

Assessment of Mycobacterium tuberculosis pantothenate kinase vulnerability through target knockdown and mechanistically diverse inhibitors.

Pantothenate kinase (PanK) catalyzes the phosphorylation of pantothenate, the first committed and rate-limiting step toward coenzyme A (CoA) biosynthesis. In our earlier reports, we had established that the type I isoform encoded by the coaA gene is an essential pantothenate kinase in Mycobacterium tuberculosis, and this vital information was then exploited to screen large libraries for identification of mechanistically different classes of PanK inhibitors. The present report summarizes the synthesis and expansion efforts to understand the structure-activity relationships leading to the optimization of enzyme inhibition along with antimycobacterial activity. Additionally, we report the progression of two distinct classes of inhibitors, the triazoles, which are ATP competitors, and the biaryl acetic acids, with a mixed mode of inhibition. Cocrystallization studies provided evidence of these inhibitors binding to the enzyme. This was further substantiated with the biaryl acids having MIC against the wild-type M. tuberculosis strain and the subsequent establishment of a target link with an upshift in MIC in a strain overexpressing PanK. On the other hand, the ATP competitors had cellular activity only in a M. tuberculosis knockdown strain with reduced PanK expression levels. Additionally, in vitro and in vivo survival kinetic studies performed with a M. tuberculosis PanK (MtPanK) knockdown strain indicated that the target levels have to be significantly reduced to bring in growth inhibition. The dual approaches employed here thus established the poor vulnerability of PanK in M. tuberculosis.