Month: February 2025

An assessment of survival and independent prognostic factors was undertaken, employing the Kaplan-Meier method and Cox regression.
In the study, 79 patients were involved, and their five-year survival rates totaled 857% for overall survival and 717% for disease-free survival. Cervical nodal metastasis risk was affected by gender and clinical tumor stage. The pathological stage of lymph nodes (LN) and tumor size proved to be independent prognostic factors for adenoid cystic carcinoma (ACC) of the sublingual gland; on the other hand, age, the pathological stage of lymph nodes (LN), and distant metastases were significant prognostic determinants for non-ACC sublingual gland cancers. Individuals exhibiting a more advanced clinical stage demonstrated a heightened predisposition to tumor recurrence.
Malignant sublingual gland tumors, a rare entity, warrant neck dissection in male patients presenting with a higher clinical stage. A poor prognosis is associated with the presence of pN+ in MSLGT patients, including those co-diagnosed with ACC and non-ACC forms.
While uncommon, malignant sublingual gland tumors in men require neck dissection when the clinical stage is elevated. In patients exhibiting both ACC and non-ACC MSLGT, a positive pN status correlates with a less favorable prognosis.

The substantial increase in high-throughput sequencing data necessitates the creation of data-driven computational methods, optimized for both efficiency and effectiveness, to annotate protein function. Currently, most functional annotation methods primarily utilize protein information, but disregard the interactions and correlations among the various annotations.
This study presents PFresGO, a novel deep learning approach employing attention mechanisms. It integrates hierarchical structures from Gene Ontology (GO) graphs with advanced natural language processing techniques for the precise functional annotation of proteins. PFresGO employs self-attention to capture the interplay between Gene Ontology terms, dynamically updating its corresponding embedding. Thereafter, it uses cross-attention to map protein representations and GO embeddings into a common latent space, enabling the identification of global protein sequence patterns and the location of functional residues. lactoferrin bioavailability We show that PFresGO consistently delivers better results than competing 'state-of-the-art' methods when classifying across GO categories. Significantly, our findings indicate that PFresGO excels at determining functionally essential residues in protein sequences through an examination of the distribution patterns in attention weights. To accurately describe the function of proteins and their functional components, PFresGO should serve as a highly effective resource.
PFresGO's academic availability can be confirmed at this GitHub location: https://github.com/BioColLab/PFresGO.
Online, Bioinformatics provides the supplementary data.
Supplementary data can be accessed online at the Bioinformatics website.

Multiomics technologies lead to a more profound biological understanding of health status among people living with HIV who are undergoing antiretroviral therapy. A rigorous and detailed assessment of metabolic risk profiles, in cases of sustained and successful treatment, is not presently available. We identified metabolic risk profiles in individuals with HIV (PWH) through a data-driven stratification process incorporating multi-omics data from plasma lipidomics, metabolomics, and fecal 16S microbiome analysis. Network analysis combined with similarity network fusion (SNF) revealed three patient groups, characterized as SNF-1 (healthy-like), SNF-3 (mild at-risk), and SNF-2 (severe at-risk). The PWH individuals within the SNF-2 (45%) cluster displayed a severe metabolic risk, characterized by heightened visceral adipose tissue, BMI, a more frequent occurrence of metabolic syndrome (MetS), and increased di- and triglycerides, despite their superior CD4+ T-cell counts compared to the other two cluster groups. Despite displaying similar metabolic characteristics, the HC-like and severely at-risk groups differed significantly from HIV-negative controls (HNC) in their amino acid metabolism, which exhibited dysregulation. The HC-like group's microbiome profile showed lower species richness, a reduced percentage of men who have sex with men (MSM), and an abundance of the Bacteroides genus. Alternatively, in at-risk groups, there was an increase in Prevotella, especially in men who have sex with men (MSM), which could potentially result in an increase in systemic inflammation and a higher cardiometabolic risk profile. A multi-omics integrative analysis highlighted a complicated microbial interplay concerning microbiome-associated metabolites in PWH. Severely at-risk groups can experience positive outcomes from personalized medicine and lifestyle interventions aimed at addressing their dysregulated metabolic characteristics, ultimately leading to healthier aging.

The BioPlex project's work has yielded two proteome-scale, cell-type-specific protein-protein interaction networks. The first, in 293T cells, reveals 120,000 interactions among 15,000 proteins. The second, in HCT116 cells, documents 70,000 interactions between 10,000 proteins. Importazole We illustrate programmatic access to BioPlex PPI networks and their integration with pertinent resources using the R and Python programming languages. Liquid Handling This resource, containing PPI networks for 293T and HCT116 cells, also provides access to CORUM protein complex data, PFAM protein domain data, PDB protein structures, and the transcriptome and proteome data for the two cell lines. The functionality implemented provides a foundation for integrative downstream analysis of BioPlex PPI data, leveraging domain-specific R and Python packages, enabling efficient maximum scoring sub-network analysis, protein domain-domain association analysis, mapping of PPIs onto 3D protein structures, and analysis of BioPlex PPIs within the context of transcriptomic and proteomic data.
From the Bioconductor (bioconductor.org/packages/BioPlex) repository, the BioPlex R package is accessible. A corresponding Python package, BioPlex, can be obtained from PyPI (pypi.org/project/bioplexpy). GitHub (github.com/ccb-hms/BioPlexAnalysis) provides the necessary applications and subsequent analyses.
The BioPlex R package is found on Bioconductor (bioconductor.org/packages/BioPlex). The BioPlex Python package is accessible through PyPI (pypi.org/project/bioplexpy). Applications and downstream analysis tools are available from the GitHub repository github.com/ccb-hms/BioPlexAnalysis.

Documented evidence highlights significant differences in ovarian cancer survival outcomes across racial and ethnic groups. Nonetheless, there has been a restricted investigation into the contribution of healthcare access (HCA) to these disparities.
To determine the correlation between HCA and ovarian cancer mortality, we analyzed the 2008-2015 Surveillance, Epidemiology, and End Results-Medicare data. Cox proportional hazards regression models, multivariable in nature, were employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the correlation between HCA dimensions (affordability, availability, and accessibility) and mortality—specifically, mortality attributable to OCs and all-cause mortality—while accounting for patient characteristics and the receipt of treatment.
A study cohort of 7590 patients with OC included 454 (60%) Hispanic individuals, 501 (66%) non-Hispanic Black individuals, and 6635 (874%) non-Hispanic White individuals. Higher affordability, availability, and accessibility scores demonstrated a connection with lower ovarian cancer mortality risk, adjusting for pre-existing demographic and clinical factors (HR = 0.90, 95% CI = 0.87 to 0.94; HR = 0.95, 95% CI = 0.92 to 0.99; HR = 0.93, 95% CI = 0.87 to 0.99). Accounting for healthcare access characteristics, non-Hispanic Black ovarian cancer patients experienced a 26% greater risk of mortality than non-Hispanic White patients (hazard ratio [HR] = 1.26, 95% confidence interval [CI] = 1.11 to 1.43). Among survivors beyond 12 months, the risk was 45% higher (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.16 to 1.81).
There is a statistically important link between HCA dimensions and mortality after ovarian cancer (OC), partially, but not entirely, elucidating the observed racial disparities in patient survival. Although attaining equal access to quality healthcare is imperative, additional research concerning other healthcare dimensions is needed to determine the additional elements contributing to health disparities based on race and ethnicity and advance health equity.
Post-operative mortality following OC procedures is demonstrably linked to HCA dimensions, and these associations are statistically significant, while only partially explaining the noted racial disparities in patient survival. Equitable access to quality healthcare, while essential, requires an accompanying exploration into other factors related to healthcare access to uncover further contributors to disparate health outcomes among racial and ethnic groups and advance the pursuit of health equity.

Urine samples now offer improved detection capabilities for endogenous anabolic androgenic steroids (EAAS), including testosterone (T), as doping agents, thanks to the introduction of the Steroidal Module of the Athlete Biological Passport (ABP).
Doping practices, especially those using EAAS, will be targeted, particularly in individuals who show low urinary biomarker levels, by integrating the measurement of new target compounds in blood.
Anti-doping data spanning four years yielded T and T/Androstenedione (T/A4) distributions, used as prior information for analyzing individual profiles from two T administration studies in male and female subjects.
At the anti-doping laboratory, athletes' samples are examined for banned substances. Within the study, 823 elite athletes were examined alongside 19 males and 14 females participating in clinical trials.
Two open-label administration experiments were performed. Male volunteers experienced a control phase, followed by patch application, and concluded with oral T administration in one study. In another, female volunteers were monitored across three 28-day menstrual cycles, marked by a continuous daily transdermal T application during the second month.

A summary of how to use the model for age prediction is given here.

This study, a registry-based, retrospective cohort study in young adults, focused on identifying the variables that contribute to the onset of periodontitis.
The Swedish Quality Registry for Caries and Periodontal diseases (SKaPa) facilitated a 31-year follow-up of 345 Swedish subjects, clinically examined at age 19 as part of an epidemiological survey. The period between 2010 and 2018 (23-31 years) yielded registry data including crucial periodontal parameters. Periodontitis risk factors (PPD 6 mm at 2 teeth) were determined using logistic regression and survival models.
A striking 98% incidence of periodontitis was observed over the 12-year observation period. Cigarette smoking (modified pack-years, hazard ratio 235, 95% confidence interval 134-413) and increased probing pocket depths (number of sites with probing pocket depth 4-5 mm, hazard ratio 104, 95% confidence interval 101-107) at 19 years were identified as risk factors for periodontitis during subsequent young adulthood. For the factors of gender, snuff use, plaque, and marginal bleeding, no statistically significant association was detected.
Increased probing pocket depth (4 mm) and cigarette smoking, prevalent in late adolescence (19 years), emerged as factors relevant to the development of periodontitis in young adulthood.
In late adolescence, cigarette smoking and increased probing depths were, as our study determined, significant risk factors for periodontitis later in young adulthood. Japanese medaka A comprehensive risk assessment for preventive programs should factor in both cigarette smoking and probing pocket depth.
Our study established a connection between cigarette smoking and increased probing depth in late adolescence and the risk of periodontitis in young adulthood. Risk assessments for preventive programs ought to factor in both cigarette smoking and probing pocket depths.

Targeted expression of bgl23-D, a dominant-negative variant of ATCSLD5, constitutes a valuable genetic method for functionally characterizing ATCSLDs within specific plant cells and tissues. In plants, stomata are cellular components essential for the exchange of gases and water, and their development is dictated by the intricate orchestration of several genes. In the A. thaliana bagel23-D (bgl23-D) mutant, we detected an anomaly: irregular bagel-shaped single guard cells. A dominant mutation, bgl23-D, in the A. thaliana cellulose synthase-like D5 (ATCSLD5) gene, a gene reported to be involved in the division of guard mother cells, was a novel finding. The prevailing feature of bgl23-D was used to impede the function of ATCSLD5 within designated cells and tissues. In transgenic A. thaliana plants, the expression of bgl23-D cDNA under the control of stomatal lineage genes' promoters (SDD1, MUTE, and FAMA) resulted in stomata with a bagel shape, replicating the phenotype observed in the bgl23-D mutant. The FAMA promoter displayed a notable prevalence of bagel-shaped stomata, marked by profound cytokinesis disruptions. Tamoxifen in vivo Expression of bgl23-D cDNA under the SP11 promoter in the tapetum or the ATSP146 promoter in the anther resulted in abnormal exine patterns and pollen shapes, distinct from those observed in the bgl23-D mutant. bgl23-D's observed results highlighted a suppression of unknown ATCSLD(s), which are known to orchestrate exine formation within the tapetum. A. thaliana plants that were genetically modified to express bgl23-D cDNA, governed by the SDD1, MUTE, and FAMA promoters, showcased increased rosette diameters and improved leaf expansion. These observations, in their entirety, suggest the possibility that the bgl23-D mutation could function as a useful genetic tool for understanding ATCSLD function and influencing plant growth.

Motivating students and facilitating their learning is facilitated by the feedback provided through formative assessments. There is an imperative to upgrade clinical pharmacotherapy (CPT) training for junior doctors, given their frequent prescribing errors. The present study sought to ascertain if the integration of personalized narrative feedback into formative assessment could result in an improvement in medical students' prescribing skills.
Master's medical students at Erasmus Medical Centre, The Netherlands, were the subjects of a retrospective cohort study. Students' clerkship curriculum incorporated both formative and summative skill-based assessment modules. The two assessments' errors, classified by type and their projected consequences, were compared, revealing comparable issues.
A collective student body of 388 students presented 1964 errors in their formative assessment and 1016 errors in the summative assessment. Following the formative assessment, a substantial increase in prescriptions including the weight of a child was observed (n=242, 19%). Usage instructions were missing from a considerable portion of errors on the summative assessment, both new (82, 16%) and repeated (121, 41%).
Students have witnessed a rise in the technical correctness of their prescriptions, thanks to the personalized and individual narrative feedback inherent in this formative assessment. Errors that persisted following feedback were predominantly attributed to a single formative assessment's failure to sufficiently enhance the competency in clinical prescribing.
This formative assessment, using personalized and individual narrative feedback, has been instrumental in improving students' technical precision in prescribing. Repeated errors, despite feedback, largely indicated the lack of sufficient clinical prescribing improvement stemming from a single formative assessment.

This research investigated the correlation between the quantity of metoprolol administered and the long-term success of fat grafts.
The research team used ten Sprague-Dawley rats in their study. The dorsal regions of the rats were mapped into four quadrants: right and left cranial, and also right and left caudal. The quadrants were each independently grouped. Fat grafts, extracted from the groin, were placed into 5mL solutions composed of 0.9% sodium chloride (control), 1mg/mL metoprolol (Group 1), 2mg/mL metoprolol (Group 2), and 3mg/mL metoprolol (Group 3), to be incubated. Fat grafts were carefully inserted into pockets prepared by dissecting each of the four dorsal quadrants. The three-month study concluded with the euthanasia of all the rats. Fat grafts and the surrounding tissue they had permeated were jointly extracted from the area. A histopathological examination was conducted using hematoxylin and eosin (H&E) and Masson Trichrome staining protocols, in conjunction with immunohistochemical analysis of fibroblast growth factor-2 and perilipin expression.
The scores of Group 2 and Group 3 were statistically higher than those of the control group, as determined by HE and Masson Trichrome staining (p<0.005). Group 3 scores showed a substantial and statistically significant (p<0.005) advantage over Group 1 scores. Group 2 and Group 3 exhibited significantly higher fibroblast growth factor-2 staining scores in comparison to the control group (p<0.05), as determined by the examination. Statistically significant differences (p<0.005) were observed, with Group 3 demonstrating markedly higher scores compared to Group 1 and Group 2. The perilipin staining examinations showed that Groups 1, 2, and 3 achieved significantly greater scores than the control group, as indicated by a p-value less than 0.05.
While prior studies suggested metoprolol extended the lifespan of fat grafts, this research immunohistochemically revealed an increase in fat graft quality and viability as metoprolol dosage escalated.
In accordance with Evidence-Based Medicine rankings, this journal mandates that authors assign a level of evidence to each relevant submission. This selection does not incorporate Review Articles, Book Reviews, nor any manuscripts concerning Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. To fully understand these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors provided on www.springer.com/00266.
Submissions to this journal, where an Evidence-Based Medicine ranking is pertinent, mandate that authors assign a level of evidence to each. Review Articles, Book Reviews, and manuscripts concerning Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies are excluded from this. Within the Table of Contents or the online Instructions to Authors, found on the internet address www.springer.com/00266, you will find a complete explanation of these Evidence-Based Medicine ratings.

Elemental RE, specifically Sc, Y, La, Yb, and Lu, were combined to create the cubic Laves-phase aluminides REAl2, the synthesis of which was facilitated using arc-melting techniques or induction heating methods within ampoules made from refractory metals. Within the cubic crystal system, the Fd3m space group dictates their crystallization, which follows the MgCu2 structural pattern. Spectroscopic analysis, including powder X-ray diffraction, Raman and 27Al spectroscopy, and, in the case of ScAl2, 45Sc solid-state MAS NMR, was performed on the title compounds. Aluminides' Raman and NMR spectral signatures are unified by a single peak, attributable to their crystal structure. medical treatment Charge transfer in these compounds was illustrated by Bader charges calculated from DFT, along with NMR parameters and densities of states. Lastly, the bonding scenario was examined utilizing ELF calculations, resulting in the identification of these compounds as aluminides with positively charged RE+ cations embedded within a polyanionic [Al2] structure.

This analysis aimed to provide an updated overview of the evidence for convalescent plasma transfusion (CPT) in patients with coronavirus disease 2019 (COVID-19), exploring its benefits. A review of databases was performed to discover randomized controlled trials (RCTs) examining CPT plus standard care versus only standard care in adult individuals with COVID-19. The primary outcomes of interest were mortality and the necessity for employing invasive mechanical ventilation (IMV).

Adverse outcomes for mothers and their children are significantly influenced by the occurrence of maternal mental illness. Minimal research has tackled the simultaneous occurrence of maternal depression and anxiety, or the influence of maternal mental health conditions on the mother-infant relationship. We sought to explore the correlation between early postnatal bonding and the development of mental illness, measured at 4 and 18 months post-partum.
In a secondary analysis, the 168 mothers who were part of the BabySmart Study were re-evaluated. Healthy infants, born at full term, were delivered by all women. Depressive and anxious symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) at 4 months and the Beck's Depression and Anxiety Inventory at 18 months. Participants completed the Maternal Postnatal Attachment Scale (MPAS) assessment at the four-month postpartum period. The investigation of associated risk factors, utilizing negative binomial regression analysis, covered both time points.
Postpartum depression, prevalent at 125% in the fourth month, exhibited a decrease to 107% within eighteen months. During simultaneous time frames, anxiety prevalence escalated from 131% to 179%. Sixteen months after the initial observation, both symptoms were newly observed in approximately two-thirds of the female participants, exhibiting a significant 611% and 733% increase, respectively. Microbiota functional profile prediction The anxiety component of the EPDS and the total EPDS p-score were significantly correlated (R = 0.887, p < 0.0001). Independent of other factors, early postpartum anxiety was associated with an elevated risk of later anxiety and depressive episodes. Strong attachment scores acted as an independent protective factor against depression at both four months (RR = 0.943; 95% CI = 0.924-0.962; p < 0.0001) and 18 months (RR = 0.971; 95% CI = 0.949-0.997; p = 0.0026), and also provided protection against early postpartum anxiety (RR = 0.952; 95% CI = 0.933-0.970; p < 0.0001).
Similar to national and international patterns, the incidence of postnatal depression at four months was comparable. However, clinical anxiety increased significantly over time, with roughly one in five women exhibiting clinical anxiety by 18 months. Maternal attachment strength corresponded with a reduction in self-reported symptoms of depression and anxiety. The determination of persistent maternal anxiety's impact on maternal and infant well-being is crucial.
Similar postnatal depression rates were observed at four months when compared to national and international norms, yet clinical anxiety showed a rise over time, with almost one-fifth of women reaching a clinical threshold for anxiety by 18 months. Reported symptoms of depression and anxiety were lessened in individuals with strong maternal attachments. Determining the influence of sustained maternal anxiety on the health outcomes of both mother and infant is essential.

Currently, a count exceeding sixteen million Irish people call rural Ireland home. In Ireland, the rural areas boast a significant senior population, with ensuing health needs that surpass those of the urban areas' younger residents. Rural areas have seen a 10% drop in general practices since 1982, a noticeable trend. see more This research employs a novel survey to understand the requirements and difficulties faced by rural general practice in Ireland.
Survey responses from the 2021 Irish College of General Practitioners (ICGP) membership survey will be the source of information for this study's methodology. An online survey, sent anonymously via email to ICGP members in late 2021, probed practice locations and past rural living/working experiences, specifically for this research project. HIV unexposed infected A series of statistical analyses, tailored to the characteristics of the dataset, will be performed.
We are currently conducting a study to gather data on the demographics of rural general practitioners and the associated contributing factors.
Past research suggests a higher probability of those who were educated or trained in rural environments continuing their professional lives in those same rural areas following qualification. A further investigation into this survey's data will be important to see if this established pattern is discernible in this setting as well.
Past research indicates a correlation between rural upbringing or training and subsequent rural employment post-qualification. Subsequent analysis of this survey data will be vital in evaluating whether this pattern holds true here as well.

Health disparities, particularly in 'medical deserts', have motivated multiple countries to implement a comprehensive array of programs designed to enhance health workforce distribution. This investigation systematically analyzes the body of research, providing a comprehensive overview of the various definitions and characteristics defining medical deserts. It also points out the causes of medical deserts and ways to reduce their prevalence.
Searches of Embase, MEDLINE, CINAHL, Web of Science Core Collection, Google Scholar, and The Cochrane Library extended from their respective inceptions up to May 2021. Primary research studies that highlighted the nuances of medical deserts—their definitions, characteristics, causative factors, and mitigation approaches—were incorporated. By performing a double-blind review, two independent reviewers screened studies for eligibility, painstakingly extracted data, and finally clustered similar studies, resulting in comprehensive analysis.
The analysis encompassed two hundred and forty studies, with a breakdown of 49% from Australia/New Zealand, 43% from North America, and 8% from Europe. The employment of all observational designs, save for five quasi-experimental studies, was undertaken. Academic papers elucidated the definitions (n=160), characteristics (n=71), contributing and associated factors (n=113), and techniques for managing medical deserts (n=94). Areas experiencing a low population density often signified the existence of medical deserts. Sociodemographic characteristics of HWF (n=70), work-related factors (n=43), and lifestyle conditions (n=34) were the contributing and associated factors. Strategies focusing on rural practice encompassed adapted training programs (n=79), HWF distributions (n=3), and the development of enhanced support infrastructure (n=6), in addition to the implementation of innovative care models (n=7).
Our initial scoping review investigates definitions, characteristics, associated factors, and approaches for addressing medical deserts. Our findings pointed to a critical need for longitudinal studies into factors influencing medical deserts, and interventional studies to evaluate the effectiveness of interventions addressing medical deserts.
This scoping review, the first of its kind, examines definitions, characteristics, contributing factors, associated elements, and mitigation strategies for medical deserts. Identifying the causes of medical deserts requires more longitudinal studies, and determining the success of interventions requires more interventional studies, both of which are currently lacking.

It is estimated that knee pain afflicts at least 25% of people aged 50 or older. In Ireland's public healthcare system, orthopaedic clinics see knee pain as the primary reason for new consultations, with meniscal pathology being the most frequent subsequent diagnosis behind osteoarthritis. Clinical practice suggests avoiding surgery for degenerative meniscal tears (DMT), favoring exercise therapy as the initial treatment. However, arthroscopic meniscus surgeries, particularly for middle-aged and senior meniscus patients, remain frequent internationally. While data on Irish knee arthroscopy procedures is lacking, the considerable number of referrals to orthopaedic specialists suggests that some primary care doctors consider surgery a feasible treatment option for patients with degenerative musculoskeletal conditions. Further investigation into GPs' perspectives on DMT management and clinical decision-making is warranted, thus motivating this qualitative study to explore those views.
Ethical approval for this project was bestowed by the Irish College of General Practitioners. Online semi-structured interviews were conducted with 17 general practitioners. Understanding knee pain management required examining assessment and management approaches, the role of imaging in diagnosis, factors affecting referrals to orthopaedic specialists, and potential future support structures. Employing an inductive approach to thematic analysis, guided by the research aim and Braun and Clarke's six-step methodology, transcribed interviews are currently being examined.
At present, data analysis is being conducted. The WONCA study, completed in June 2022, yielded results that will be instrumental in creating a knowledge translation and exercise-based intervention for the management of diabetic mellitus type 2 in primary care.
Data analysis is proceeding at this time. WONCA's June 2022 results provide the necessary data for crafting a knowledge translation and exercise program aimed at managing diabetic macular edema (DME) within primary care.

Categorized as a deubiquitinating enzyme (DUB), USP21 is also a part of the ubiquitin-specific protease (USP) subfamily. Due to its crucial involvement in the progression and development of tumors, USP21 has been identified as a prospective therapeutic target for cancer treatment. We announce the discovery of the first highly potent and selective inhibitor targeting USP21. From high-throughput screening, followed by refined structure-based optimization, BAY-805 was identified as a non-covalent inhibitor of USP21, characterized by a low nanomolar binding affinity and high selectivity against other DUB targets, along with kinases, proteases, and other common off-targets. The combination of SPR and CETSA assays showed that BAY-805 engages its target with high affinity, significantly activating NF-κB as measured by a cell-based reporter assay.