Detailed Testing Research Articles

Foot peripheral sensory neuropathy: a frequent disabling manifestation in systemic sclerosis.

Peripheral Sensory Neuropathy (PSN) is an under-recognized feature in systemic sclerosis (SSc). Moreover, SSc foot involvement is frequent but poorly investigated. We aimed to provide a detailed characterization of foot PSN in a large cohort of SSc patients, describing its associations with disease-specific features, physical disability, and Quality of Life (QoL). SSc patients and healthy controls (HC) comparable for age and gender, were enrolled in a cross-sectional observational case-control study. All subjects underwent a detailed quantitative sensory testing of feet evaluating touch, vibratory, thermal, and pain sensitivity; ultimately investigating the presence of large and small fiber neuropathy. Patient-reported outcomes (Scleroderma Health Assessment Questionnaire, Manchester Foot Pain and Disability Index, and Systemic Sclerosis Quality of Life Questionnaire) were administered to assess neuropathic symptoms, foot disability and QoL. 109 SSc patients (88.1% female, median age 59.0 years) and 51 HC were enrolled. SSc patients presented with a significant impairment in each sensory parameter assessed (p≤ 0.01 for all). Foot PSN was present in 85.3% of the patients, with 80% having small fiber and 57% large fiber neuropathy; co-existing in 51.4% of the cases. PSN was associated with age, smoking, foot ulceration, disease duration and corticosteroids use. 80.6% subjects with PSN reported at least one neuropathic symptom. Patients with neuropathic symptoms reported worse physical function, worse foot disability, and more impaired QoL. Foot PSN presents as a common and disabling manifestation in SSc patients, involving small and large fibres. Hence, foot PSN assessment should be included as a part of the SSc workup.

Tests of Solar X-ray Image Reconstruction: Study of X-ray Imaging Algorithms and Reconstruction Parameters

Abstract Abstract Imaging observations of solar X-ray bursts can reveal details of the energy release process and particle acceleration in flares. Most hard X-ray imagers make use of the modulation-based Fourier transform imaging method, an indirect imaging technique that requires algorithms to reconstruct and optimize images. During the last decade, a variety of algorithms have been developed and improved. However, it is difficult to quantitatively evaluate the image quality of different solutions without a true, reference image of observation. How to choose the values of imaging parameters for these algorithms to get the best performance is also an open question. In this study, we present a detailed test of the characteristics of these algorithms, imaging dynamic range and a crucial parameter for the CLEAN method, clean beam width factor (CBWF). We first used SDO/AIA EUV images to compute DEM maps and calculate thermal X-ray maps. Then these realistic sources and several types of simulated sources are used as the ground truth in the imaging simulations for both RHESSI and ASO-S/HXI. The different solutions are evaluated quantitatively by a number of means. The overall results suggest that EM, PIXON, and CLEAN are exceptional methods for sidelobe elimination, producing images with clear source details. Although MEM_GE, MEM_NJIT, VIS_WV and VIS_CS possess fast imaging processes and generate good images, they too possess associated imperfections unique to each method. The two forward fit algorithms, VF and FF perform differently, and VF appears to be more robust and useful. We also demonstrated the imaging capability of HXI and available HXI algorithms. Furthermore, the effect of CBWF on image quality was investigated, and optimal settings for both RHESSI and HXI were proposed.

Effectiveness and utilization of a cognitive screening program for primary geriatric care

BackgroundEffective detection of cognitive impairment in the primary care setting is limited by lack of time and specialized expertise to conduct detailed objective cognitive testing and few well-validated cognitive screening instruments that can be administered and evaluated quickly without expert supervision. We therefore developed a model cognitive screening program to provide relatively brief, objective assessment of a geriatric patient’s memory and other cognitive abilities in cases where the primary care physician suspects but is unsure of the presence of a deficit.MethodsReferred patients were tested during a 40-min session by a psychometrist or trained nurse in the clinic on a brief battery of neuropsychological tests that assessed multiple cognitive domains. Short questionnaires covering subjective cognitive complaints, symptoms of depression, and medical history were also administered. Results were conveyed to a dementia specialist who reviewed them and returned their judgement of the validity of the cognitive complaint to the primary care provider. Retrospective medical records review was carried out for a random (stratified) half of the sample to determine how screening results were utilized. Screening tests were repeated after two years in a subset of 69 patients.ResultsThe 638 patients screened (mean age = 75.9 years; mean education = 14.9 years; 58% women) were classified by screening as having normal cognition (n = 177), depression (with possible cognitive changes; n = 115), mild cognitive impairment (MCI; n = 107), or dementia (n = 239). Classification accuracy was shown by high agreement with the eventual clinical diagnosis in the medical record (69%; Cohen’s Kappa = .38; p < .001; 77% if MCI and dementia were collapsed; Cohen’s Kappa = .58; p < .001) and longitudinal decline in cognitive test scores only in those initially classified as having MCI or dementia. Medical records documented discussion of screening results with the patient in 69% of cases (80% if MCI or dementia was detected) and often referral to a specialist (62%), new brain imaging (54%), or change in medication (58%) when screening indicated potential cognitive impairment.ConclusionThe cognitive screening program was well accepted by primary care providers as an efficient and effective way to evaluate concerns about cognitive decline in older adults.

The clinical presentation and genetic diagnosis of Tangier disease in the pediatric age group.

Tangier disease (TD) is a rare autosomal recessive condition characterized by high-density lipoprotein (HDL) deficiency; involving symptoms of polyneuropathy, hyperplastic orange-yellow tonsils, vision disorder, and sudden cardiac death. The major clinical symptoms of TD may not all be co-present. This study evaluates patients diagnosed with TD in childhood to improve the possibility of early diagnosis ofasymptomatic cases by reporting our patients' clinical characteristics in order to minimize delayed diagnosis and emphasize the importance of TD, easily detected by HDL measurement. This retrospective and cross-sectional study investigated seven patients from three different families diagnosed with TD. Four of seven patients were girls. Median age was 5.7 years at symptom onset and 6.5 years at diagnosis. The index case presented with neuropathy findings, and TD was diagnosed based on genetic analysis. Low lipid levels were determined in a sibling and cousins with cardiac death and gait disturbance in the family. TD was confirmed by genetic investigation. Our other patients were evaluated due to anemia, thrombocytopenia, yellow-orange hypertrophy in the tonsils, and organomegaly. Diagnosis was established with genetic analysis and low HDL. No coronary artery disease or ocular involvement was observed in any case. All patients presenting with neuropathy and gait disorders should undergo detailed tonsil examinations and HDL tests. Genetic analysis should be carried out if necessary. Family screening should be recommended to patients with consanguineous marriages after diagnosis of TD.

A System Control and Waveform Acquisition Framework for the Kicker System at SHINE

A lumped kicker magnet system is being developed as part of the electron beam switchyard of the Shanghai High Repetition Rate X-Ray Free-Electron Laser (XFEL) and Extreme Light (SHINE) facility at Shanghai Advanced Research Institute (SARI), Chinese Academy of Sciences (CAS). SHINE is a linac-based facility with an energy of 8 GeV and a repetition rate of 1 MHz for multiple users. The kicker system is a critical element of the deflection system and determines the stability performance of the beamlines. To ensure autonomous and reliable operation in a harsh environment, a dedicated control system—consisting of a custom-designed programmable logic controller (PLC) and waveform acquisition system—has been developed based on the Experimental Physics and Industrial Control System (EPICS). The PLCsystem enables status acquisition, control implantations, and alarm handling, allowing for automated operation. The waveform acquisition system provides an intuitive demonstration and enables the real-time diagnosis of kicker waveforms. The results demonstrate a half quasi-sinuous waveform with a peak current of 11.5 A and a full width at half maximum of 218 ns at a repetition rate of 10 kHz. The detailed design, overall concept, achieved performance, and initial test results of two modular controls are provided for further demonstration.

ІНСТРУМЕНТАРІЙ ВИЯВЛЕННЯ ПЛАГІАТУ В НАУКОВИХ РОБОТАХ: АНАЛІЗ ПРОГРАМНИХ РІШЕНЬ

The article deals with the concept of plagiarism, self-plagiarism and their basic types. It is described a classification of plagiarism automatic detection tools for text documents and the basic methods that underlie their functioning. It is considered a number of popular software and online resources to check text similarity, carried out their detailed analysis, testing and evaluation according to defined software specifications, productivity of functioning and obtained results during the checking. There are presented recommendations of the best tools that can be used by the research institutions and scientific journals’ editors.

Neurological post-COVID syndrome is associated with substantial impairment of verbal short-term and working memory

A substantial proportion of patients suffer from Post-COVID Syndrome (PCS) with fatigue and impairment of memory and concentration being the most important symptoms. We here set out to perform in-depth neuropsychological assessment of PCS patients referred to the Neurologic PCS clinic compared to patients without sequelae after COVID-19 (non-PCS) and healthy controls (HC) to decipher the most prevalent cognitive deficits. We included n = 60 PCS patients with neurologic symptoms, n = 15 non-PCS patients and n = 15 healthy controls. Basic socioeconomic data and subjective complaints were recorded. This was followed by a detailed neuropsychological test battery, including assessments of general orientation, motor and cognitive fatigue, screening of depressive and anxiety symptoms, information processing speed, concentration, visuomotor processing speed, attention, verbal short-term and working memory, cognitive flexibility, semantic and phonematic word fluency, as well as verbal and visual memory functions. Neurologic PCS patients had more complaints with significantly higher fatigue scores as well as higher levels of depressive and anxiety symptoms compared to Non-PCS and HC. Deep neuropsychological assessment showed that neurologic PCS patients performed worse in a general screening of cognitive deficits compared to HC. Neurologic PCS patients showed impaired mental flexibility as an executive subfunction, verbal short-term memory, working memory and general reactivity (prolonged reaction time). Multiple regression showed fatigue affected processing speed; depression did not. Self-reported cognitive deficits of patients with neurologic PCS including fatigue, concentration, and memory deficits, are well mirrored in impaired performance of cognitive domains of concentration and working memory. The present results should be considered to optimize treatment algorithms for therapy and rehabilitation programs of PCS patients with neurologic symptoms.

Structure factor line shape model gives approximate nanoscale size of polar aggregates in pyrrolidinium-based ionic liquids.

Room temperature ionic liquids (RTILs) are interesting due to their myriad uses in fields such as catalysis and electrochemistry. Their properties are intimately related to their structures, yet structural understanding is difficult to achieve. This work presents a derivation of an approximate expression for the radial distribution function, g(r). The derivation assumes a Lorentzian line shape for total structure factors, S(Q). The derived form for g(r) is used to present new equations for maxima and minima in g(r) and to define a half-length, the value of r where g(r) decays to one-half its maximum value. A detailed test of the model is presented using experimentally measured and calculated S(Q) for N-methyl-N-propylpyrrolidinium bis(trifluoromethylsulfonyl)imide (C1C3pyrrTFSI). Then, the model is extended to the series of RTILs with anions of increasing size, C1C3pyrrX (X- = Cl-, Br-, BF4-, PF6-, OTf-, TFSI-). The model predicts maxima and minima in the entire series within 4.2% of those calculated directly from molecular dynamics simulations. This reinforces our previous conclusion that distances within "polar scattering domains" responsible for the charge alternation peak in S(Q) are quantitatively related to inter-ionic distances within polar aggregates in these RTILs. The half-length is found to increase approximately linearly as anion size increases. We argue that the half-length is a measure of polar aggregate size in these RTILs.

Pseudoxanthoma elasticum: A case study of three family members

Aims/Purpose: To evaluate the evolution and various clinical presentations of pseudoxanthoma elasticum in three family members.Methods: Continuous follow‐up was conducted in the outpatient ophthalmology clinics at our hospital. Clinical characteristics, including the presence of exudation, neovascular membranes, angioid streaks, and posterior pole atrophy, were documented and analyzed through detailed ophthalmological examinations and imaging tests. Visual acuity was assessed, and autofluorescence imaging was performed. Additionally, optical coherence tomography (OCT) and OCT angiography (OCT‐A) were utilized to obtain high‐resolution images of the retina and its blood flow.Results: One daughter presented with exudation accompanied by a neovascular membrane, which was treated with intravitreal anti‐VEGF injections. The other daughter maintains good vision and shows angioid streaks in the fundus without macular involvement. The mother is in an advanced stage of the disease, with significant retinoschisis and posterior pole atrophy.Conclusions: This case study highlights the variability in the presentation and progression of pseudoxanthoma elasticum within the same family. Continuous and personalized follow‐ up is crucial for the appropriate management and early detection of complications in PXE patients.

Exercise-induced bronchoconstriction in children: Delphi study and consensus document about definition and epidemiology, diagnostic work-up, treatment, and follow-up

BackgroundExercise-induced bronchoconstriction (EIB) is common in children with asthma but can be present also in children without asthma, especially athletes. Differential diagnosis includes several conditions such as exercise-induced laryngeal obstruction (EILO), cardiac disease, or physical deconditioning. Detailed medical history, clinical examination and specific tests are mandatory to exclude alternative diagnoses. Given the high prevalence of EIB in children and its potential impact on health, sport performance, and daily levels of physical activity, health care professionals should be aware of this condition and able to provide a specific work-up for its identification. The aims of the present study were: (a) to assess the agreement among hospital pediatricians and primary care pediatricians of Emilia-Romagna Region (Italy) about the management of EIB in children and (b) formulate statements in a consensus document to help clinicians in daily clinical practice.MethodsAccording to Delphi method, a panel of specialists scored 40 statements that were then revised and discussed during online meetings to reach full consensus. Statements were then formulated.ResultsTo obtain full consensus, the questionnaire was administered in two rounds after full discussion of the uncertain topics on the basis of the latest evidence on EIB published over the last 10 years. Despite an overall agreement on EIB management, some gaps emerged in the sections dedicated to diagnosis and treatment. Nine summary statements on definition, pathogenesis, diagnostic work-up, treatment, and follow-up were eventually formulated.ConclusionsThis study describes the knowledge of EIB in a group of pediatricians and highlights gaps and uncertainties in diagnosis and treatment. The creation of statements shared by the specialists of the same area may improve the management of EIB in children. However, more research and evidence are needed to better clarify the best treatment and to standardize the best diagnostic protocol limiting useless examinations but at the same time assuring the best management.

Laser Welding of Micro-Wire Stent Electrode as a Minimally Invasive Endovascular Neural Interface.

Minimally invasive endovascular stent electrodes are an emerging technology in neural engineering, designed to minimize the damage to neural tissue. However, conventional stent electrodes often rely on resistive welding and are relatively bulky, restricting their use primarily to large animals or thick blood vessels. In this study, the feasibility is explored of fabricating a laser welding stent electrode as small as 300 μm. A high-precision laser welding technique was developed to join micro-wire electrodes without compromising structural integrity or performance. To ensure consistent results, a novel micro-wire welding with platinum pad method was introduced during the welding process. The fabricated electrodes were integrated with stent structures and subjected to detailed electrochemical performance testing to evaluate their potential as neural interface components. The laser-welded endovascular stent electrodes exhibited excellent electrochemical properties, including low impedance and stable charge transfer capabilities. At the same time, in this study, a simulation is conducted of the electrode distribution and arrangement on the stent structure, optimizing the utilization of the available surface area for enhanced functionality. These results demonstrate the potential of the fabricated electrodes for high-performance neural interfacing in endovascular applications. The approach provided a promising solution for advancing endovascular neural engineering technologies, particularly in applications requiring compact electrode designs.

Tunable Mechanically Interlocked Semi‐Crystalline Networks

High‐performance polymers based on dynamic chemistry have been widely explored for multi‐field advanced applications. However, noncovalent sacrifice bond mediated energy dissipation mechanism causes a trade‐off between mechanical toughness and resilience. Herein, we achieved the synchronous boost of seemingly conflicting material properties including mechanical robustness, toughness and elasticity via the incorporation of mechanical chemistry into traditional semi‐crystalline networks. Detailed rheological tests and all‐atom molecular dynamics simulation reveal that the excellent mechanical robustness and toughness are attributed to the dissociation of crystalline domains threading through the sieve‐shape macrocycles. Reversible nano‐crystalline domains and ring‐sliding effect accelerated segment motion efficiently reduce energy dissipation to achieve instantaneous resilience. Moreover, the model polymers demonstrate that the multiple dynamic components endow the resulting polymer with excellent reprocessability under mild conditions. This mechanically interlocked semi‐crystalline polymer exhibits potential application as thermal/photo actuator. This work deeply reveals the synergic effects of mechanically interlocked sites and tunable crystalline domains, thus providing a reliable guide for comprehensive improvement of material performance.

Pharmacists' practice in providing pharmaceutical services of treating paediatric diarrhoea in pharmacies: A qualitative study

Background: Diarrhoea is a significant cause of morbidity and mortality in developing countries. Pharmacists in pharmacies are essential in managing the treatment of diarrhoea in children and its prevention, particularly in preventing dehydration in children with diarrhoea. Objective: This study aims to explore the practice of pharmacists in providing pharmaceutical services related to treating diarrhoea in children in pharmacies. Method: The research was conducted using a qualitative, non-experimental method through in-depth interviews. Interviews were conducted face-to-face. Informants were recruited until data saturation, and ten pharmacist informants were obtained. Data validity was assessed through credibility testing with member checking, transferability testing with a detailed description, dependability testing, and confirmability testing through peer debriefing. Interview results were analysed descriptively using an inductive reasoning process. Result: In practice, not all pharmacists obtain complete drug information, make recommendations for appropriate treatment of paediatric diarrhoea, and provide complete drug information. The inhibiting factors for the implementation of pharmaceutical services related to paediatric diarrhoea therapy in the pharmacy is the lack of up-to-date knowledge among pharmacists and the limited human resources in the pharmacy. Conclusion: Pharmacists have a role in preventing and treating diarrhoea in children because they are health professionals who can be found in pharmacies and whom the public can consult about treating diarrhoea in their children.

Tunable Mechanically Interlocked Semi-Crystalline Networks.

High-performance polymers based on dynamic chemistry have been widely explored for multi-field advanced applications. However, noncovalent sacrificial bond-mediated energy dissipation mechanism causes a trade-off between mechanical toughness and resilience. Herein, we achieved the synchronous boost of seemingly conflicting material properties including mechanical robustness, toughness and elasticity via the incorporation of mechanical chemistry into traditional semi-crystalline networks. Detailed rheological tests and all-atom molecular dynamics simulation reveal that the excellent mechanical robustness and toughness are attributed to the dissociation of crystalline domains threading through the sieve-shape macrocycles. Reversible nano-crystalline domains and ring-sliding-effect accelerated segment motion efficiently reduce energy dissipation to achieve instantaneous resilience. Moreover, the model polymers demonstrate that the multiple dynamic components endow the resulting polymer with excellent reprocessability under mild conditions. This mechanically interlocked semi-crystalline polymer exhibits potential applications as a thermal/photo actuator. This work reveals the synergic effects of mechanically interlocked sites and tunable crystalline domains, thus providing a reliable guide for the comprehensive improvement of material performance.

Clinical profiles in autism spectrum disorder: Enhancing diagnosis, treatment, and overall health outcomes

AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant challenges in communication, behavior, and social interaction. The prevalence of ASD is rising, with current estimates indicating that it affects 1 in 36 children in the United States. Traditional diagnostic methods often fail to capture the full complexity of ASD, leading to incomplete treatment approaches. This study aimed to enhance diagnostic and therapeutic approaches to ASD by identifying and categorizing 10 clinical profiles using precision medicine.MethodsThis study presents a new stratification model for ASD that classifies individuals based on prevalent comorbidities and underlying biological mechanisms. The model is based on a synthesis of existing literature, clinical observations, and expert insights. Data were collected from detailed clinical evaluations, patient histories, and laboratory tests, and the model was refined through iterative analysis. It integrates findings from genetic, neurological, and psychiatric research to develop a comprehensive approach for diagnosing and treating ASD‐related comorbidities.ResultsThe study proposes 10 clinical profiles of ASD: syndromic, gastrointestinal, metabolic, mitochondrial, endocrine, bioaccumulative, infectious, immunological, inflammatory, and Neurological. Each profile is associated with specific symptoms and comorbidities influenced by genetic, environmental, and biological factors.ConclusionsThe stratification model proposed in this study enhances the diagnosis and treatment of ASD by recognizing its heterogeneity. By identifying specific clinical profiles, healthcare providers can develop personalized and integrated therapeutic strategies to improve the overall health outcomes of individuals with ASD.

Recommendations for the management of latex allergy in pediatrics

Latex allergy, or natural rubber latex allergy (NRLA), is a global health concern, even among the pediatric population, with symptoms varying in severity from mild to potentially life-threatening. Latex is derived from the Hevea Brasiliensis tree, producing twelve million tons annually for use in various everyday and medical products. Despite efforts to mitigate NRLA, its prevalence remains high, especially in at- risk groups such as children with spina bifida. Clinical manifestations include immediate and delayed symptoms, even anaphylactic reactions. Diagnosis involves a detailed medical history and specific tests. Prevention focuses on avoiding exposure, especially in medical and educational settings. Treatment, including immunotherapy, exhibits variable efficacy. NRLA has a strong negative impact on children's quality of life. The objective of this publication is to provide updated information and practical tools for the pediatrician's and allergist's practice.

Geotechnical Aspects of Salo Lawo Waterfall in Salopuru Pattappa, Pujananting District, Barru Regency, South Sulawesi

Abstract The Salo Lawo waterfall represents a significant geotourism destination for the community in Pujananting, Barru district. It is of critical importance to identify the geotechnical aspects of this site in order to ensure the safety of visitors and to prevent potential rock mass movements. This research identifies fundamental geotechnical aspects through measuring and observing joints or discontinuities using the scanline method in the field. This is complemented by a kinematic analysis of stereographic projections, which enables the determination of failure modes potential and the classification of rock masses. The Salo Lawo waterfall is formed by sandstone in the Balang Baru formation, which exhibits a medium rock compressive strength. The kinematic analysis indicated that two types of failure could potentially occur on the rock slope wall: wedge sliding (26.29%) and oblique toppling, which is part of direct toppling (23.67%). The potential for planar sliding and flexural toppling was not identified, as indicated by the absence of critical intersections and the presence of only very small critical intersections obtained from stereographic projections. The kinematic analysis conducted in this research project predicts the potential for failure modes to occur at this location. This is considered to be a basic or initial stage in the assessment of the geotechnical aspects of the area. Consequently, further research is required to employ more detailed methods and laboratory testing to estimate the stability of the rock slopes at Salo Lawo waterfall. This will enable the information on geotechnical aspects to become more complete and valuable.

EVALUATION OF INTERPOLATION METHODS FOR GNSS VELOCITIES IN CRUSTAL DEFORMATION: A CASE STUDY ON STRAIN RATE CALCULATION IN THE SOUTHERN SUMATRA

This study evaluates three interpolation methods—Inverse Distance Weighting (IDW), Kriging, and Sandwell—for analyzing crustal deformation in southern Sumatra, focusing on the on-site velocity consistency test. This test is crucial for assessing interpolation accuracy by comparing interpolated velocities to actual GNSS velocities at specific sites. Given the region's sparse GNSS network, accurate interpolation is vital for reliable deformation analysis. GNSS data from continuous and campaign sites, collected between 2017 and 2022 with a 30-second sampling interval, were processed to generate velocity. The Sandwell method, particularly with a Poisson’s ratio of 0, demonstrated superior performance, achieving the lowest mean residuals in the on-site velocity consistency test. This method consistently provided accurate interpolated velocities that closely matched original site data. IDW and Kriging methods also showed effectiveness but had different convergence behaviors: IDW required higher interpolation degrees for accuracy, while Kriging excelled in the east-west residuals. The Sandwell method’s velocities were used to calculate strain rates, revealing significant spatial variability. The findings underscore the importance of detailed on-site velocity consistency testing and highlight the need for expanding GNSS networks to improve accuracy and better assess seismic hazards in southern Sumatra.

Kanban method in digital data processing

AbstractCurrent digital education operates as a push-system, despite the content and subject characteristics suggesting a need for a pull-system. One of the features of the push-system is a tool-centered approach, where the focus on tools, including both hardware and software, is the belief that it is possible to build knowledge inventory. The consequences of the push digital education approaches are that (1) the fundamental concepts of Computer Science are not being transferred, (2) the lack of the development of supporting methods, (3) and education does not seem to be interested in revealing the root causes and to be open for fundamental changes. This paper proposes the extension of the theory of the industrial pull systems to present as a potential solution to increase the effectiveness and efficiency of digital education and reduce or eliminate data processing inefficiencies generated by undereducated but misled end-users. In addition to theoretical discussions, it also delves into the detailed analysis, design, implementation, and testing of a real-world data processing problem. The presented problem, its analysis, solution, and accompanying discussion reveal how one of the tools (kanban) of lean production can be adapted to support the Just-in-Time philosophy in digital education, focusing on end-user programming.

Local QSAR based on quantum chemistry calculations for the stability of nitrenium ions to reduce false positive outcomes from standard QSAR systems for the mutagenicity of primary aromatic amines

BackgroundPrimary aromatic amines (PAAs) present significant challenges in the prediction of mutagenicity using current standard quantitative structure activity relationship (QSAR) systems, which are knowledge-based and statistics-based, because of their low positive prediction values (PPVs). Previous studies have suggested that PAAs are metabolized into genotoxic nitrenium ions. Moreover, ddE, a relative-energy based index derived from quantum chemistry calculations that measures the stability nitrenium ions, has been correlated with mutagenicity. This study aims to further examine the ability of the ddE-based approach in improving QSAR mutagenicity predictions for PAAs and to develop a refined method to decrease false positive predictions.ResultsInformation on 1,177 PAAs was collected, of which 420 were from public databases and 757 were from in-house databases across 16 laboratories. The total dataset included 465 Ames test-positive and 712 test-negative chemicals. For internal PAAs, detailed Ames test data were scrutinized and final decisions were made using common evaluation criteria. In this study, ddE calculations were performed using a convenient and consistent protocol. An optimal ddE cutoff value of -5 kcal/mol, combined with a molecular weight ≤ 500 and ortho substitution groups yielded well-balanced prediction scores: sensitivity of 72.0%, specificity of 75.9%, PPV of 65.6%, negative predictive value of 80.9% and a balanced accuracy of 74.0%. The PPV of the ddE-based approach was greatly reduced by the presence of two ortho substituent groups of ethyl or larger, as because almost all of them were negative in the Ames test regardless of their ddE values, probably due to steric hindrance affecting interactions between the PAA and metabolic enzymes. The great majority of the PAAs whose molecular weights were greater than 500 were also negative in Ames test, despite ddE predictions indicating positive mutagenicity.ConclusionsThis study proposes a refined approach to enhance the accuracy of QSAR mutagenicity predictions for PAAs by minimizing false positives. This integrative approach incorporating molecular weight, ortho substitution patterns, and ddE values, substantially can provide a more reliable basis for evaluating the genotoxic potential of PAAs.