Validation Rounds Research Articles

Validation of a Photonumeric Scale for Evaluation of Telangiectasia in Rosacea.

Telangiectasia is a prominent feature of rosacea leading to a high demand for effective treatment. To ensure consistent clinical and scientific evaluations and assess treatment response accurately, standardized assessment tools are necessary for grading the severity of telangiectasia. However, no validated grading scales for this condition are currently available. To develop and validate a photonumeric scale for assessing the severity of telangiectasia in rosacea patients. The five-point photonumeric Telangiectasia in Rosacea Severity Assessment (TRoSA) scale was developed for the severity of telangiectasia in rosacea. Sixteen experts participated in the validation process, evaluating 50 images of rosacea patients in two rounds. Interrater and intrarater reliability were analyzed using the intraclass correlation coefficient (ICC) and weighted kappa, respectively. Interrater reliability was found to be "almost perfect" in both validation rounds (Round 1: ICC 0.847; Round 2: ICC 0.828). The mean weighted kappa indicated "substantial" intrarater reliability between the two rounds with a weighted kappa of 0.719. A bubble plot of the two rounds illustrated a diagonal order, confirming the consistency of the intrarater agreement. The TRoSA scale demonstrated high interrater and intrarater reliability indicating that it is a consistent and reproducible tool for grading the severity of telangiectasia in rosacea. This scale can standardize clinical assessments, assisting in diagnosis, treatment planning, and evaluation of therapeutic efficacy.

Smart variant filtering - A blueprint solution for massively parallel sequencing-based variant analysis.

Massively parallel sequencing helps create new knowledge on genes, variants and their association with disease phenotype. This important technological advancement simultaneously makes clinical decision making, using genomic information for cancer patients, more complex. Currently, identifying actionable pathogenic variants with diagnostic, prognostic, or predictive impact requires substantial manual effort. Objective: The purpose is to design a solution for clinical diagnostics of lymphoma, specifically for systematic variant filtering and interpretation. Methods: A scoping review and demonstrations from specialists serve as a basis for a blueprint of a solution for massively parallel sequencing-based genetic diagnostics. Results: The solution uses machine learning methods to facilitate decision making in the diagnostic process. A validation round of interviews with specialists consolidated the blueprint and anchored it across all relevant expert disciplines. The scoping review identified four components of variant filtering solutions: algorithms and Artificial Intelligence (AI) applications, software, bioinformatics pipelines and variant filtering strategies. The blueprint describes the input, the AI model and the interface for dynamic browsing. Conclusion: An AI-augmented system is designed for predicting pathogenic variants. While such a system can be used to classify identified variants, diagnosticians should still evaluate the classification's accuracy, make corrections when necessary, and ultimately decide which variants are truly pathogenic.

Building a performance measurement framework for telephone triage services in Finland: a consensus-making study based on nominal group technique

BackgroundThere has been a significant expansion in the measurement of healthcare system performance. However, there is a lack of a comprehensive performance measurement framework to assess the effects of telephone triage services on the urgent care system. The aim of our Delphi study was to construct and validate a performance measurement framework designed explicitly for telephone triage services.MethodsThis study was conducted in Finland with a group of eight experienced senior physicians from the country's 20 largest joint emergency departments, serving over 90% of the population for urgent care. The Nominal Group Technique (NGT) was utilised to achieve consensus on measuring telephone triage performance. Initially, performance indicators (PIs) were identified through Delphi method rounds from December 10th to December 27th, 2021, with eight experts participating, and from December 29th, 2021, to January 23rd, 2022, where five of these experts responded. NGT further deepened these themes and perspectives, aiding in the development of a comprehensive performance measurement framework. The final framework validation began with an initial round from February 13th to March 3rd, 2022, receiving five responses. Due to the limited number of responses, an additional validation round was conducted from October 29th to November 7th, 2023, resulting in two more responses, increasing the total number of respondents in the validation phase to seven.ResultsThe study identified a strong desire among professionals to implement a uniform framework for measuring telephone triage performance. The finalised framework evaluates telephone triage across five dimensions: service accessibility, patient experience, quality and safety, process outcome, and cost per case. Eight specific PIs were established, including call response metrics, service utility, follow-up care type and distribution, ICPC-2 classified encounter reasons, patient compliance with follow-up care, medical history review during assessment, and service cost per call.ConclusionsThis study validated a performance measurement framework for telephone triage services, utilising existing literature and the NGT method. The framework includes five key dimensions: patient experience, quality and safety, outcome of the telephone triage process, cost per case, and eight PIs. It offers a structured and comprehensive approach to measuring the overall performance of telephone triage services, enhancing our ability to evaluate these services effectively.

Development of Neurospecific Assessment Scale for Nomophobics – An Observational Study

Abstract Background: Nomophobia is a condition where people feel anxious or tense when they need to disconnect from their phone or other Internet-connected devices. Because of this elevated level of dependence on modern gadgets to offload the cognitive demands of life, anxiety develops when they are expected to be detached from it. The role of neurospecific domains such as cognitive flexibility, memory, attention, information processing, inhibitory control, and reward perception has previously been studied in nomophobics. However, there is no tool developed yet that quantifies the affection of these neurospecific domains in nomophobics. Objective: The objective of this study was to develop a scale for the assessment of “Neurospecific Domains” (in terms of memory, attention, cognitive flexibility, inhibitory control, information processing, and reward perception) among nomophobics. Methods: The neurospecific assessment scale for nomophobics (NSASN) was developed using a multistep method which included conceptualization and item generation followed by one round of expert validation of the item and of the scale. The content validity index was used to validate the various domains in the scale. Results: The computed content validity final score for Round 1 of the scale was found to be 0.79. Conclusion: The NSASN was developed to assess neurospecific domains among nomophobics and achieved a statistically satisfactory content validity.

Assessing Functional Capacity in Myalgic Encephalopathy/Chronic Fatigue Syndrome: A Patient-Informed Questionnaire.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an acquired disease with significant morbidity that affects both children and adults. Post-exertional malaise is a cardinal symptom of ME/CFS and impacts a patient's functional capacity (FC). The absence of effective tools to assess FC has significant consequences for timely diagnosis, clinical follow-up, assessments for patient disability benefits, and research studies. In interventional studies, the inability to assess FC can result in an incomplete assessment of the potential benefit of the intervention, leading to beneficial treatment outcomes being missed. Methods: Using extensive, repeated patient feedback, we have developed a new questionnaire, FUNCAP, to accurately assess FC in ME/CFS patients. The questionnaire consists of eight domains divided by activity types: A. personal hygiene/basic functions, B. walking/movement, C. being upright, D. activities in the home, E. communication, F. activities outside the home, G. reactions to light and sound, and H. concentration. Results: Through five rounds of anonymous web-based surveys and a further test-retest validation round, two versions of the questionnaire were developed: a longer version comprising 55 questions (FUNCAP55), developed for improved diagnostic and disability benefit/insurance FC assessments; and a shorter version (FUNCAP27) for clinical patient follow-up and potential use in research. Good reliability and validity and negligible floor and ceiling effects were found, with comparable findings in all aspects in both a large Norwegian (n = 1263) and a separate English-language international sample (n = 1387) demonstrating the validity and reliability of FUNCAP. Conclusions: Our findings support the utility of FUNCAP as an effective, reliable and valid tool for assessing FC in ME/CFS patients.

Preimplementation of Critical Care Early Mobility Clinical Decision Support: A Content Validation Study.

Early mobility is a form of critical care rehabilitation ranging from in-bed exercise to ambulation and is known to limit post-intensive-care functional decline. Multiple barriers prevent widespread early mobility implementation. Clinical decision support systems can optimize the decision-making process and overcome barriers to care. However, critical care early mobility clinical decision support does not exist. Our objective was to develop and establish the content validation of the operational definitions for a novel critical care early mobility assessment instrument. Content validation was conducted in two steps: (1) development of operational definitions by the research team and (2) content validation with 10 nurse experts. Quality assessment and suitability of the operational definitions for 30 items, across four safety domains, were assessed using a 7 point-Likert scale. Item content validity index scores ranged from 0.6 to 0.1 after the first validation round. Domains containing items with item content validity index scores less than the lower limit of 0.78 were modified for clarity of language. Item content validity index scores ranged from 0.8 to 1.0, and the scale-level content validity index was 0.93 after the second content validation round. Excellent content validity of the operational definitions was achieved. This is the first methodological step in a larger project to develop clinical decision support for critical care early mobility.

An Adaptation and Validation of Cocaine Craving Questionnaire for Malaysians Who Use Amphetamine-Type Stimulants.

Cases of amphetamine-type stimulants (ATS) use have been increasing over the past decade. Cravings are considered a causal factor for recurrent relapses in ATS use cases. The absence of questionnaires measuring cravings for ATS in the local population necessitates the creation of one, especially considering the rising number of cases. This study aimed to adapt and validate the Cocaine Cravings Questionnaire into a questionnaire suitable for measuring cravings for ATS in the local population. The original questionnaire was adapted by substituting "cocaine" with "ATS". The process involved a back-to-back translation, followed by a round of face and content validation. The participants included people who use drugs (PWUD) with a history of ATS use recruited from rehabilitation centers in Malaysia. A set of questionnaires consisting of demographic items and the adapted ATS Cravings Questionnaire (ATS-CQ) were given. This cross-sectional study recruited a total of 205 PWUD, mostly single men, with a mean age of 33.32 (s.d.=13.14). The mean age of ATS initiation was 22.89 (s.d.=9.39), with a median duration of ATS use of 60 months (IQR=24.00, 120.00). The adapted questionnaire received a good score for content validation. Unlike the original, this adapted version was found to have only three factors showing good internal consistency, ranging from 0.707 to 0.918 for all three factors. Test-retest reliability also showed good results, with an interclass correlation coefficient of 0.875 (95% CI=0.835, 0.905). The translated ATS-CQ has been finalized and deemed valid and reliable for use among Malaysian substance users to measure ATS cravings.

IL21R hypomethylation as a biomarker for distinguishing benign and malignant breast tumours

ABSTRACT Some benign and malignant breast tumours are similar in pathological morphology, which are difficult to be distinguished in clinical diagnosis. In this study, we intended to explore novel biomarkers for differential diagnosis of benign and malignant breast tumours. Methylation EPIC 850K beadchip and RNA-sequencing were used to analyse 29 tissue samples from patients with early-stage breast cancer (BC) and benign breast tumours for differently methylated and expressed genes. The altered methylation of IL21R was semi-quantitatively validated in an independent study with 566 tissue samples (279 BC vs. 287 benign breast tumours) using mass spectrometry. Binary logistic regression analysis was performed to evaluate the association between IL21R methylation and BC. BC-associated IL21R hypomethylation and overexpression were identified in the discovery round. In the validation round, BC patients presented significant IL21R hypomethylation compared to women with benign breast tumours (ORs ≥1.29 per-10% methylation, p-values ≤ 5.69E–14), and this hypomethylation was even enhanced in BC patients with ER-negative and PR-negative tumours as well as with triple-negative tumours. The methylation of IL21R showed efficient discriminatory power to distinguish benign breast tumours from BC (area under curve (AUC) = 0.88), and especially from ER-negative BC (AUC = 0.95), PR-negative BC (AUC = 0.93) and triple-negative BC (AUC = 0.96). We disclosed significant IL21R hypomethylation in patients with BC compared to women with benign breast tumours, and revealed the somatic change of DNA methylation could be a potential biomarker for molecular pathology of BC.

A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay

IntroductionInternational guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high sensitivities and specificities, they differ regarding subjective or objective interpretation, throughput and workload. Chemiluminescence immunoassays (CLIAs) are cost- and time-effective automated methods for detecting treponemal antibodies. The Treponema pallidum particle agglutination assay (TPPA) has been considered the “gold standard” treponemal assay, however, this includes a highly manual procedure, low throughput and subjective interpretation. The present multi-country study evaluated the ADVIA Centaur® Syphilis CLIA (Siemens Healthcare) assay compared to the reference SERODIA-TP·PA® (Fujirebio Diagnostics) for the serodiagnosis of syphilis amongst men who have sex with men (MSM).Method1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a larger WHO multi-country and multi-site ProSPeRo study. Ethical approval was obtained. Serum was tested with the ADVIA Centaur® Syphilis CLIA assay and SERODIA-TP·PA®, in accordance with the manufacturers’ instructions, for a first round of validation. A second round of validation was carried out for discrepant results that were additionally tested with both Western Blot (Westernblot EUROIMMUN®) and an Immunoblot (INNO-LIA, Fujirebio Diagnostics).Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-test probability (Fagan's nomogram) were calculated.ResultsOut of 1,485 eligible samples analysed in the first phase, the SERODIA-TP·PA® identified 360 positive and 1,125 negative cases. The ADVIA Centaur® Syphilis CLIA assay (Siemens) identified 366 positives, missclassifying one TPPA-positive sample. In the second phase, the ADVIA Centaur® Syphilis CLIA resulted in 1 false negative and 4 false positive results. Considering the syphilis study prevalence of 24% (95% CI: 22–26.7), The sensitivity of the ADVIA Centaur® Syphilis CLIA assay was 99.7% (95% CI: 98.5–100), and the specificity was 99.4% (95% CI: 98.7–99.7). The ROC area values were 0.996 (95% CI: 0.992–0.999), and both the PPV and NPV values were above 98% (PPV 98.1%, 95% CI: 96.1–99.2; NPV 99.9%, 95% CI: 99.5–100).ConclusionsThe ADVIA Centaur® Syphilis CLIA assay showed similar performance compared to the SERODIA-TP·PA®. Considering the study is based on QUADAS principles and with a homogeneous population, results are also likely to be generalisable to MSM population but potentially not applicable to lower prevalence populations routinely screened for syphilis. The automated CLIA treponemal assay confirmed to be accurate and appropriate for routine initial syphilis screening, i.e. when the reverse testing algorithm is applied.

Adapting a self-efficacy scale to the task of teaching scientific reasoning: collecting evidence for its psychometric quality using Rasch measurement.

Besides teachers' professional knowledge, their self-efficacy is a crucial aspect in promoting students' scientific reasoning (SR). However, because no measurement instrument has yet been published that specifically refers to self-efficacy beliefs regarding the task of teaching SR, we adapted the Science Teaching Efficacy Belief Instrument (STEBI) accordingly, resulting in the Teaching Scientific Reasoning Efficacy Beliefs Instrument (TSR-EBI). While the conceptual framework of the TSR-EBI is comparable to that of the STEBI in general terms, it goes beyond it in terms of specificity, acknowledging the fact that teaching SR requires very specific knowledge and skills that are not necessarily needed to the same extent for promoting other competencies in science education. To evaluate the TSR-EBI's psychometric quality, we conducted two rounds of validation. Both samples (N1 = 114; N2 = 74) consisted of pre-service teachers enrolled in university master's programs in Germany. The collected data were analyzed by applying Rasch analysis and known-group comparisons. In the course of an analysis of the TSR-EBI's internal structure, we found a 3-category scale to be superior to a 5-category structure. The person and item reliability of the scale proved to be satisfactory. Furthermore, during the second round of validation, it became clear that the results previously found for the 3-category scale were generally replicable across a new (but comparable) sample, which clearly supports the TSR-EBI's psychometric quality. Moreover, in terms of test-criterion relationships, the scale was also able to discriminate between groups that are assumed to have different levels of self-efficacy regarding teaching SR. Nonetheless, some findings also suggest that the scale might benefit from having the selection of individual items reconsidered (despite acceptable item fit statistics). On balance, however, we believe that the TSR-EBI has the potential to provide valuable insights in future studies regarding factors that influence teachers' self-efficacy, such as their professional experiences, prior training, or perceived barriers to effective teaching.

Refining a Framework to Enhance Communication in the Emergency Department During the Diagnostic Process: An eDelphi Approach

Emergency departments (EDs) are susceptible to diagnostic error. Suboptimal communication between the patient and the interdisciplinary care team increases risk to diagnostic safety. The role of communication remains underrepresented in existing diagnostic decision-making conceptual models. The authors used eDelphi methodology, whereby data are collected electronically, to achieve consensus among an expert panel of 18 clinicians, patients, family members, and other participants on a refined ED-based diagnostic decision-making framework that integrates several potential opportunities for communication to enhance diagnostic quality. This study examined the entire diagnostic process in the ED, from prehospital to discharge or transfer to inpatient care, and identified where communication breakdowns could occur. After four iterative rounds of the eDelphi process, including a final validation round by all participants, the project's a priori consensus threshold of 80% agreement was reached. The authors developed a final framework that positions communication more prominently in the diagnostic process in the ED and enhances the original National Academies of Sciences, Engineering, and Medicine (NASEM) and ED-adapted NASEM frameworks. Specific points in the ED journey were identified where more attention to communication might be helpful. Two specific types of communication-information exchange and shared understanding-were identified as high priority for optimal outcomes. Ideas for communication-focused interventions to prevent diagnostic error in the ED fell into three categories: patient-facing, clinician-facing, and system-facing interventions. This project's refinement of the NASEM framework adapted to the ED can be used to develop communications-focused interventions to reduce diagnostic error in this highly complex and error-prone setting.

Board game on sexually transmitted infections for imprisoned women

IntroductionThe board games is an educational technology that represents an appealing, active and playful pedagogical strategy and may be capable of motivating imprisoned women to learn about Sexually Transmitted Infections.MethodsA methodological study to develop and evaluate a board game, following these stages: 1. Integrative literature review to identify educational technologies on Sexually Transmitted Infections used by imprisoned women; 2. Development of the board game; and 3. Content validation performed by 23 evaluators and semantic evaluation carried out with 10 imprisoned women who were enrolled in a school located within a female prison unit in the city of Recife, state of Pernambuco, Brazil.ResultsThe board game consisted of the following: 01 board; 01 instructions manual; 05 pawns; 52 cards; and 01 dice. A global Content Validity Index of 0.966 was reached in the content validation process performed by health and education professionals. In the validation of the board game content regarding appearance, performed by designers/developers, most of the items obtained a Content Validity Coefficient below 0.85, which resulted in the need for adjustments and a new validation round with these professionals, in which Content Validity Coefficient = 0.917 was obtained. In the semantic evaluation, all the women stated that they improved their knowledge, increased their motivation to attend the class and would like to play the board game again.ConclusionsThe “Previna” board game has been validated and can be considered an important pedagogical tool in the construction of knowledge in relation to the prevention, treatment and control of Sexually Transmitted Infections in the female prison context. The quality of this educational technology is directly related to its development based on an appropriate theoretical and methodological framework, in addition to satisfactory feedback from the target audience.Trial registrationNot applicable.

Three-phase generalized raking and multiple imputation estimators to address error-prone data.

Validation studies are often used to obtain more reliable information in settings with error-prone data. Validated data on a subsample of subjects can be used together with error-prone data on all subjects to improve estimation. In practice, more than one round of data validation may be required, and direct application of standard approaches for combining validation data into analyses may lead to inefficient estimators since the information available from intermediate validation steps is only partially considered or even completely ignored. In this paper, we present two novel extensions of multiple imputation and generalized raking estimators that make full use of all available data. We show through simulations that incorporating information from intermediate steps can lead to substantial gains in efficiency. This work is motivated by and illustrated in a study of contraceptive effectiveness among 83 671 women living with HIV, whose data were originally extracted from electronic medical records, of whom 4732 had their charts reviewed, and a subsequent 1210 also had a telephone interview to validate key study variables.

Development of the Ready to Care Survey for VA Women's Health Primary Care Provider.

Women Veterans are at increased risk for poor pregnancy outcomes and are increasingly using Veteran Affairs (VA) for maternity benefits. VA Women's Health Primary Care Providers (WH-PCPs) are well positioned to improve maternal outcomes for women Veterans, yet little is understood about their experience and comfort with perinatal care. The objective of this study was to develop and validate a survey that could be utilized to assess WH-PCPs' experience, comfort, and attitudes towards perinatal care. After a review of the literature, we adapted a previously published survey to address four content areas including clinical experience, comfort level, and attitudes towards perinatal care and knowledge of VA specific maternity services. This survey was piloted with five WH-PCPs before undergoing two rounds of content validation with content experts. Content validity indexes (CVI) were calculated based on the content experts' ratings. Qualitative feedback from the content experts were summarized and reviewed by the research team. The CVI and qualitative responses were utilized to guide the decision to revise, refine, or delete survey questions. After the first round of content validation, we deleted three questions, revised three questions, and add three questions to the content areas of clinical experience and comfort. In the domain of attitudes towards perinatal care, we deleted one question and revised two questions and three questions were added to the knowledge of VA specific maternity services domain. After the second round of content validation, only one question was deleted from the attitudes domain. We developed and validated the Ready to Care Survey for VA WH-PCP using two rounds of content validation. The final survey had face and content validity. This survey tool can be used to assess VA WH-PCP's knowledge and readiness in caring for Veterans of child-bearing age for operational and research needs.

Development and Validation of the Outpatient Nurses Communication Behavior Inventory

Outpatient clinics in medical centers are the most common location where people seek medical treatment. Because they must provide patients with treatment information in a timely manner, good communication skills are a key competency for outpatient nurses. However, the tools available for communication behavior assessment are general and rarely tailored for outpatient settings. The purpose was to develop a communication behavior inventory for outpatient nurses and to examine its reliability and validity. During phase one, the authors conducted a literature search and synthesis, using the findings to develop the Outpatient Nurses Communication Behavior Inventory. During phase two, two expert validation rounds were conducted to confirm content validity. During phase three, 220 licensed outpatient nurses were recruited from a medical center in northern Taiwan to complete the instrument (December 2018 - January 2019.) The construct validity and internal consistency of the inventory were evaluated. The literature search and synthesis identified six domains of communication, including connect, introduce, communicate, ask, respond, and exit. A total of 25 items were generated. Following the two expert panel validation rounds, the six domains remained but the inventory items were reduced to 21. Both item-content validity index and scale-level content validity index were 1.0. In phase three, the results of the confirmatory factor analysis retained six factors with a total of 16 items. Model three showed that the inventory demonstrated goodness of fit (Χ ² = 155.75, p < .001, RMSEA = .06, GFI = .92, AGFI = .87, NNFI = .97, NFI = .95, Model AIC = 253.75). Internal consistency was demonstrated with a Cronbach's α of .89. The Outpatient Nurses Communication Behavior Inventory exhibits good reliability and validity and may be used to assess outpatient nurses' communication behaviors and as a basis for education. The six CICARE (connect, introduce, communicate, ask, respond and exit) domains may be utilized to remind outpatient nurses to demonstrate effective communication consistently, promote outpatient nurses' communication with patients, and improve quality of care.

Otilonium Bromide acts as a selective USP28 inhibitor and exhibits cytotoxic activity against multiple human cancer cell lines

USP28 contributes to tumorigenesis through modulating the lifespan of oncogenic factors such as c-Myc and ΔNp63, and it has been identified as a potential target for anti-cancer drug development. Currently, although quite a number of USP28 inhibitors have been developed, they all are still in preclinical research stage. Besides, none of them exhibits satisfying inhibition selectivity against USP28 over its closest homologue USP25. Here in this manuscript, a high-throughput screening aiming to discover USP28 inhibitors with novel scaffold and enhanced inhibition selectivity were conducted. After the primary screening and the second round of validation, Otilonium Bromide, an approved drug for treating irritable bowel syndrome, was identified to inhibit USP28′s activity with the IC50 value at 6.90 ± 0.90 μM. Besides, the drug exhibits a 3–4 folds inhibition selectivity against USP28 over USP25. According to the enzymatic kinetics analysis data and the hydrogen–deuterium exchange mass spectrometry results, Otilonium Bromide could bind to the allosteric pocket of USP28 and inhibit its activity in a reversible and non-competitive mode. The following performed cell-based assays revealed that the drug could cause cytotoxicity against human colorectal cancer cells and lung squamous carcinoma cells potentially through down-regulating USP28′s oncogenic substrates c-Myc and/or ΔNp63. Meanwhile, since Otilonium Bromide has been found to preferentially distribute to gastrointestinal tissues, we then evaluated its potential in the combination treatment of colorectal cancer cells with Regorafenib, which is an approved drug for colorectal cancer therapy. As expected, Otilonium Bromide could significantly enhance the sensitivity of colorectal cancer cells to Regorafenib.

Image Perceptual Similarity Metrics for the Assessment of Basal Cell Carcinoma.

Efficient management of basal cell carcinomas (BCC) requires reliable assessments of both tumors and post-treatment scars. We aimed to estimate image similarity metrics that account for BCC's perceptual color and texture deviation from perilesional skin. In total, 176 clinical photographs of BCC were assessed by six physicians using a visual deviation scale. Internal consistency and inter-rater agreement were estimated using Cronbach's α, weighted Gwet's AC2, and quadratic Cohen's kappa. The mean visual scores were used to validate a range of similarity metrics employing different color spaces, distances, and image embeddings from a pre-trained VGG16 neural network. The calculated similarities were transformed into discrete values using ordinal logistic regression models. The Bray-Curtis distance in the YIQ color model and rectified embeddings from the 'fc6' layer minimized the mean squared error and demonstrated strong performance in representing perceptual similarities. Box plot analysis and the Wilcoxon rank-sum test were used to visualize and compare the levels of agreement, conducted on a random validation round between the two groups: 'Human-System' and 'Human-Human.' The proposed metrics were comparable in terms of internal consistency and agreement with human raters. The findings suggest that the proposed metrics offer a robust and cost-effective approach to monitoring BCC treatment outcomes in clinical settings.

Localized Validation Accelerates Distributed Transactions on Disaggregated Persistent Memory

Persistent memory (PM) disaggregation significantly improves the resource utilization and failure isolation to build a scalable and cost-effective remote memory pool in modern data centers. However, due to offering limited computing power and overlooking the bandwidth and persistence properties of real PMs, existing distributed transaction schemes, which are designed for legacy DRAM-based monolithic servers, fail to efficiently work on the disaggregated PM. In this article, we propose FORD, a F ast O ne-sided R DMA-based D istributed transaction system for the new disaggregated PM architecture. FORD thoroughly leverages one-sided remote direct memory access to handle transactions for bypassing the remote CPU in the PM pool. To reduce the round trips, FORD batches the read and lock operations into one request to eliminate extra locking and validations for the read-write data. To accelerate the transaction commit, FORD updates all remote replicas in a single round trip with parallel undo logging and data visibility control. Moreover, considering the limited PM bandwidth, FORD enables the backup replicas to be read to alleviate the load on the primary replicas, thus improving the throughput. To efficiently guarantee the remote data persistency in the PM pool, FORD selectively flushes data to the backup replicas to mitigate the network overheads. Nevertheless, the original FORD wastes some validation round trips if the read-only data are not modified by other transactions. Hence, we further propose a localized validation scheme to transfer the validation operations for the read-only data from remote to local as much as possible to reduce the round trips. Experimental results demonstrate that FORD significantly improves the transaction throughput by up to 3× and decreases the latency by up to 87.4% compared with state-of-the-art systems.

Machine Learning to Predict Three Types of Outcomes After Traumatic Brain Injury Using Data at Admission: A Multicenter Study for Development and Validation.

The difficulty of accurately identifying patients who would benefit from promising treatments makes it challenging to prove the efficacy of novel treatments for traumatic brain injury (TBI). Although machine learning is being increasingly applied to this task, existing binary outcome prediction models are insufficient for the effective stratification of TBI patients. The aim of this study was to develop an accurate 3-class outcome prediction model to enable appropriate patient stratification. To this end, retrospective balanced data of 1200 blunt TBI patients admitted to six Japanese hospitals from January 2018 onwards (200 consecutive cases at each institution) were used for model training and validation. We incorporated 21 predictors obtained in the emergency department, including age, sex, six clinical findings, four laboratory parameters, eight CT findings, and an emergency craniotomy. We developed two machine learning models (XGBoost and dense neural network) and logistic regression models to predict 3-class outcomes based on the Glasgow Outcome Scale-Extended (GOSE) at discharge. The prediction models were developed using a training dataset with n = 1000, and their prediction performances were evaluated over two validation rounds on a validation dataset (n = 80) and a test dataset (n = 120) using the bootstrap method. Of the 1200 patients in aggregate, the median patient age was 71 years, 199 (16.7%) exhibited severe TBI, and emergency craniotomy was performed on 104 patients (8.7%). The median length of stay was 13.0 days. The 3-class outcomes were good recovery/moderate disability for 709 patients (59.1%), severe disability/vegetative state in 416 patients (34.7%), and death in 75 patients (6.2%). XGBoost model performed well with 69.5% sensitivity, 82.5% accuracy, and an area under the receiver operating characteristic curve of 0.901 in the final validation. In terms of the receiver operating characteristic curve analysis, the XGBoost outperformed the neural network-based and logistic regression models slightly. In particular, XGBoost outperformed the logistic regression model significantly in predicting severe disability/vegetative state. Although each model predicted favorable outcomes accurately, they tended to miss the mortality prediction. The proposed machine learning model was demonstrated to be capable of accurate prediction of in-hospital outcomes following TBI, even with the three GOSE-based categories. As a result, it is expected to be more impactful in the development of appropriate patient stratification methods in future TBI studies than conventional binary prognostic models. Furthermore, outcomes were predicted based on only clinical data obtained from the emergency department. However, developing a robust model with consistent performance in diverse scenarios remains challenging, and further efforts are needed to improve generalization performance.

Targeting Toxoplasma gondii ME49 TgAPN2: A Bioinformatics Approach for Antiparasitic Drug Discovery.

As fewer therapeutic options are available for treating toxoplasmosis, newer antiparasitic drugs that can block TgAPN2 M1 aminopeptidase are of significant value. Herein, we employed several computer-aided drug-design approaches with the objective of identifying drug molecules from the Asinex library with stable conformation and binding energy scores. By a structure-based virtual screening process, three molecules-LAS_52160953, LAS_51177972, and LAS_52506311-were identified as promising candidates, with binding affinity scores of -8.6 kcal/mol, -8.5 kcal/mol, and -8.3 kcal/mol, respectively. The compounds produced balanced interacting networks of hydrophilic and hydrophobic interactions, vital for holding the compounds at the docked cavity and stable binding conformation. The docked compound complexes with TgAPN2 were further subjected to molecular dynamic simulations that revealed mean RMSD for the LAS_52160953 complex of 1.45 Å), LAS_51177972 complex 1.02 Å, and LAS_52506311 complex 1.087 Å. Another round of binding free energy validation by MM-GBSA/MM-PBSA was done to confirm docking and simulation findings. The analysis predicted average MM-GBSA value of <-36 kcal/mol and <-35 kcal/mol by MM-PBSA. The compounds were further classified as appropriate candidates to be used as drug-like molecules and showed favorable pharmacokinetics. The shortlisted compounds showed promising biological potency against the TgAPN2 enzyme and may be used in experimental validation. They may also serve as parent structures to design novel derivatives with enhanced biological potency.