Alternative Test Research Articles

An Alternative in Managing Duane Retraction Syndrome Type I Using Modified Nishida Procedure: A Case Report

Introduction : Various surgical approaches have been proposed to address the challenge in managing abduction deficit in Duane Retraction Syndrome (DRS) Type I, with no clear guidelines to achieve optimal result. This report aims to describe the outcome of combining medial rectus (MR) recession and modified Nishida procedure to improve abduction in DRS Type I.
 Case Illustration : Twenty six year-old female came with inability to abduct her left eye (LE) since early childhood and an abnormal left head turn. No complaints of double vision nor visual impairment. There was -5 abduction on LE with a noticeable narrowing of vertical palpebral fissure during adduction. Prism alternate prism cover test shared a 30 PD esotropia with normal anterior and posterior segment. Patient was assessed with DRS Type I of LE and managed with 5mm MR recession combined with modified Nishida procedure (vertical rectus transposition without tenotomy and muscle splitting). On postoperative day 1 and last follow-up (1 year), the alignment was ortophoric, abduction improvement of -2, and diminished anomalous head posture.
 Discussion : Although studies have only reported successful cases of modified Nishida procedure in CN VI palsy, it can be assumed that the procedure can also be implemented to treat lateral rectus muscle innervation abnormality such as in DRS type I. Surgical intervention may not normalize abduction deficit. However, the procedure successfully corrects ocular alignment, eliminates anomalous head posture, and able to improve abduction with no complications.
 Conclusion : Modified Nishida procedure can be implemented as an alternative in managing DRS type I with relatively satisfactory result.

Augmented Surgical Treatment in Patient with Partially Accomodative Esotropia

Introduction : Esotropia is a disorder of the position of the eyeball when the eye deviates inward. Surgical treatment is indicated when the eyes are not aligned with the glasses. We report a case of augmented surgical treatment in a partially accommodative esotropia patient.
 Case Illustration : A 18-year-old girl comes to the hospital with vision loss in both eyes since 1 year prior admission. Ocular alignment sinne correction was 300 (Figure 1) and cum correction was 150. Prism alternate cover test (PACT) showed deviation in sinne correction distance 60?BO dan near 50?BO, and deviation in cum correction distance 40?BO dan near 35?BO. Surgical formula with augmented surgery was (60?BO + 40?BO)/2 equal to 50?BO. Patient was diagnosed with Compositus Hypermetropia ODS + Partially Accommodative Esotropia. Patient underwent bilateral medial rectus recess surgery of 6 mm. Ophthalmology examination after 1 and 2.5 month surgery showed ocular alignment without spectacles showed microtropia and with spectacles showed orthotropia (Figure 2, 3a and 3b).
 Discussion : Various approaches can improve outcomes, including using different surgical formulas. Augmented surgery are the mean of deviation with and without surgery as the final deviation surgical formula.
 Conclusion : The amount of surgery in strabismus was based on the size of preoperative deviation. Augmented surgical treatment can be one of the choices to determine preoperative deviation in an esotropia patient.

Urinary fatty acid biomarkers for prostate cancer detection.

The lack of accuracy in the current prostate specific antigen (PSA) test for prostate cancer (PCa) screening causes around 60-75% of unnecessary prostate biopsies. Therefore, alternative diagnostic methods that have better accuracy and can prevent over-diagnosis of PCa are needed. Researchers have examined various potential biomarkers for PCa, and of those fatty acids (FAs) markers have received special attention due to their role in cancer metabolomics. It has been noted that PCa metabolism prefers FAs over glucose substrates for continued rapid proliferation. Hence, we proposed using a urinary FAs based model as a non-invasive alternative for PCa detection. Urine samples collected from 334 biopsy-designated PCa positive and 232 biopsy-designated PCa negative subjects were analyzed for FAs and lipid related compounds by stir bar sorptive extraction coupled with gas chromatography/mass spectrometry (SBSE-GC/MS). The dataset was split into the training (70%) and testing (30%) sets to develop and validate logit models and repeated for 100 runs of random data partitioning. Over the 100 runs, we confirmed the stability of the models and obtained optimal tuning parameters for developing the final FA based model. A PSA model using the values of the patients' PSA test results was constructed with the same cohort for the purpose of comparing the performances of the FA model against PSA test. The FA final model selected 20 FAs and rendered an AUC of 0.71 (95% CI = 0.67-0.75, sensitivity = 0.48, and specificity = 0.83). In comparison, the PSA model performed with an AUC of 0.51 (95% CI = 0.46-0.66, sensitivity = 0.44, and specificity = 0.71). The study supports the potential use of urinary FAs as a stable and non-invasive alternative test for PCa diagnosis.

Pre-Numerical Tests for a New Conjugate Gradient Method

The performance of a new beta in conjugate gradient method is generally measured on its CPU time and the number of iterations using large scale problems without concerning the accuracy of the solution attained. The method is claimed to be the best when less CPU time is used in comparison with the other classical beta. However, the accuracy of the solution gained compared to the exact solution of the function has never been tested as part of the performance measurement. Our previous research has already proven that our new beta perform well in both speed and number of iterations used. Therefore, in this research, we will accommodate this with alternative numerical test on the new beta in assessing the accuracy of the gained solution. This is to further ensure the efficiency of the new beta. Assessment was done with four other classical conjugate gradient methods on fourteen small scale problems. Results attained were promising to be tested for more tests in real functional problems.

Artificial Intelligence Tools for Improving Manometric Diagnosis of Esophageal Dysmotility.

Artificial intelligence (AI) is a broad term that pertains to a computer's ability to mimic and sometimes surpass human intelligence in interpretation of large datasets. The adoption of AI in gastrointestinal motility has been slower compared to other areas such as polyp detection and interpretation of histopathology. Within esophageal physiologic testing, AI can automate interpretation of image-based tests, especially high resolution manometry (HRM) and functional luminal imaging probe (FLIP) studies. Basic tasks such as identification of landmarks, determining adequacy of the HRM study and identification from achalasia from non-achalasia patterns are achieved with good accuracy. However, existing AI systems compare AI interpretation to expert analysis rather than to clinical outcome from management based on AI diagnosis. The use of AI methods is much less advanced within the field of ambulatory reflux monitoring, where challenges exist in assimilation of data from multiple impedance and pH channels. There remains potential for replication of the AI successes within esophageal physiologic testing to HRM of the anorectum, and to innovative and novel methods of evaluating gastric electrical activity and motor function. The use of AI has tremendous potential to improve detection of dysmotility within the esophagus using esophageal physiologic testing, as well as in other regions of the gastrointestinal tract. Eventually, integration of patient presentation, demographics and alternate test results to individual motility test interpretation will improve diagnostic precision and prognostication using AI tools.

Application of alternative identification methods for live tularaemia and brucellosis vaccines

SCIENTIFIC RELEVANCE. The sanctions currently imposed on the Russian Federation requireusing Russian diagnostic products in vaccine quality assessments, as well as searching for alternative testing methods, in particular, serological ones.AIM. This study aimed to demonstrate the possibility of using alternative serological methods, including immunoenzymatic, direct agglutination, and indirect haemagglutination methods, for the identification of tularaemia and brucellosis vaccines in studies and quality assessments. MATERIALS AND METHODS. This study used the established pharmacopoeial reference standard (RS) for the bacterial suspension opacity of 10 international opacity units, the established pharmacopoeial RS for and two commercial batches of the live brucellosis vaccine (Brucella abortus 19 BA), and the established and candidate pharmacopoeial RSs for the live tularaemia vaccine (Francisella tularensis 15 NIIEG). These pharmacopoeial RSs were certified by the Scientific Centre for Expert Evaluation of Medicinal Products. Serological testing used Russian commercial diagnostic products, including dry diagnostic sera (polyvalent brucellosis and tularaemia sera for agglutination tests), a liquid erythrocytic diagnostic preparation of tularaemia immunoglobulin, and enzyme immunoassay (ELISA) diagnostic kits for detecting the causative agents for brucellosis and tularaemia. Statistical analysis involved using Microsoft Excel (P=0.95) for ELISA results and qualitative evaluation for the results of direct agglutination and indirect haemagglutination tests.RESULTS. All the tested batches demonstrated positive results. Live brucellosis vaccine batches showed positive results in the slide agglutination tests, while live tularaemia vaccine batches yielded positive results in the tube agglutination tests. All indirect haemagglutination tests showed haemagglutination in live tularaemia vaccine samples at the same concentration as positive control samples (6.25×106 cells/mL). ELISA tests showed similar optical density values (D)for the two vaccines and positive control samples. Live tularaemia and brucellosis vaccines (undiluted, 1.0×109 cells/mL) had D=2.133±0.273 and D=0.127±0.013, whereas the corresponding control samples had D=1.942±0.056 and D=0.123±0.007, respectively. The results reflected the presence of brucellosis or tularaemia microbes in the samples, confirming the identity of the vaccines.CONCLUSIONS. Serological immunoenzymatic, direct agglutination, and indirect haemagglu tination methods with Russian diagnostic products can be used to identify live brucellosis and tularaemia vaccines during quality assessment. The agglutination method with Russian diagnostic sera can be recommended as an alternative quality assessment method for the identification of live brucellosis and tularaemia vaccines, as this method offers time efficiency, simple visual evaluation of results, and low costs and relatively long shelf lives of diagnostic products. However, ELISA and indirect haemagglutination methods cannot be recommended for this purpose because of their labour-intensive and uneconomical nature. The results of this study may support the introduction of the agglutination method in the regulatory documents for live brucellosis and tularaemia vaccines (as an alternative method).

Development of Colloidal Gold-Based Immunochromatographic Strips for Rapid Detection and Surveillance of Japanese Encephalitis Virus in Dogs across Shanghai, China.

Japanese encephalitis virus (JEV) causes acute encephalitis in humans and is of major public health concern in most Asian regions. Dogs are suitable sentinels for assessing the risk of JEV infection in humans. A neutralization test (NT) or an enzyme-linked immunosorbent assay (ELISA) is used for the serological detection of JEV in dogs; however, these tests have several limitations, and, thus, a more convenient and reliable alternative test is needed. In this study, a colloidal gold immunochromatographic strip (ICS), using a purified recombinant EDIII protein, was established for the serological survey of JEV infection in dogs. The results show that the ICSs could specifically detect JEV antibodies within 10 min without cross-reactions with antibodies against other canine viruses. The test strips could detect anti-JEV in serum with dilution up to 640 times, showing high sensitivity. The coincidence rate with the NT test was higher than 96.6%. Among 586 serum samples from dogs in Shanghai examined using the ICS test, 179 (29.98%) were found to be positive for JEV antibodies, and the high seropositivity of JEV in dogs in China was significantly correlated with the season and living environment. In summary, we developed an accurate and economical ICS for the rapid detection of anti-JEV in dog serum samples with great potential for the surveillance of JEV in dogs.

Heterophoria, fusional vergence, and near point of convergence in Sudanese hospital-based population

Background: Fusional vergence amplitude is the amount of convergence and divergence that can be induced before fusion is lost and fusional vergence amplitude controls heterophoria.Aim: This study aimed to investigate the relationship between near heterophoria, near fusional vergence (NFV), and near point of convergence (NPC).Setting: Al-Neelain Eye Hospital Khartoum, Sudan.Methods: A hospital-based prospective study from February to October 2019, included 230 patients with age range of 15–30 years and mean age and standard deviation of 19.46 ± 3.33 years. The alternate cover test with prism was used to measure near heterophoria and a prism bar was used to measure quantity of fusional vergence. All measurements were taken at near heterophoria (0.33 m). Then the associations between near heterophoria, NFV and NPC were assessed.Results: The most common heterophoria at near among the participants was exophoria: 200 (87.0%). Reported complaints of asthenopia were commonly found among these exophoric patients: 106 (86.9%) (P = 0.735). Positive fusional vergence (PFV) to the break point varied according to the forms of heterophoria (P = 0.003). Esophoria had a higher PFV to break point than exophoria (30.83 ± 8.79Δ compared to 25.59 ± 10.07Δ). Negative fusional vergence at the break and recovery points were higher among those with exophoria and lower in esophoria (P ˃ 0.05). The NPC differed by the type of heterophoria (P = 0.01), with exophoria and slightly receded NPC (8.38 cm ± 3.33 cm) than for participants with esophoria (6.77 cm ± 1.52 cm).Conclusions: Exophoria was the most common type of near heterophoria, with asthenopia being the most reported complaint. Esophoria was found to be strongly associated with high PFV. Exophoria, on the contrary, is related to significant high NFV at the blur, beak, and recovery point. The NPC differed significantly by the type of near heterophoria, with exophoria having more receded NPC compared to those with esophoria.Contribution: This study provides information on the commonest type of near heterophorias among a sample of Sudanese adolescents and young adults, namely exophoria. Near point of convergence and NFV at break and recovery points were significantly different according to forms of near heterophoria.

High life satisfaction reported among small-scale societies with low incomes

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.

Laboratory and field validation of the recombinase polymerase amplification assay targeting the Schistosoma mansoni mitochondrial minisatellite region (SmMIT-RPA) for snail xenomonitoring for schistosomiasis

Improvements in diagnostics for schistosomiasis in both humans and snail hosts are priorities to be able to reach the World Health Organization (WHO) goal of eliminating the disease as a public health problem by 2030. In this context, molecular isothermal amplification tests, such as Recombinase Polymerase Amplification (RPA), are promising for use in endemic areas at the point-of-need for their accuracy, robustness, simplicity, and time-effectiveness. The developed recombinase polymerase amplification assay targeting the Schistosoma mansoni mitochondrial minisatellite region (SmMIT-RPA) was used to detect S. mansoni DNA from both laboratory and field Biomphalaria snails. Laboratory snails were experimentally infected and used at one, seven, and 28 days post-exposure (dpe) to 10 S. mansoni miracidia to provide samples in the early pre-patent infection stage. Field samples of Biomphalaria spp. were collected from the Mucuri Valley and Jequitinhonha Valley regions in the state of Minas Gerais, Brazil, which are endemic for S. mansoni. The sensitivity and specificity of the SmMIT-RPA assay were analysed and compared with existing loop-mediated isothermal amplification (LAMP), PCR-based methods, parasitological examination of the snails, and nucleotide sequencing. The SmMIT-RPA assay was able to detect S. mansoni DNA in the experimentally infected Biomphalaria glabrata as early as one dpe to 10 miracidia. It also detected S. mansoni infections (55.5% prevalence) in the field samples with the highest accuracy (100% sensitivity and specificity) compared with the other molecular tests used as the reference. Results from this study indicate that the SmMIT-RPA assay is a good alternative test to be used for snail xenomonitoring of S. mansoni due to its high sensitivity, accuracy, and the possibility of detecting early pre-patent infection. Its simplicity and portability also make it a suitable methodology in low-resource settings.

Adverse effects in traditional and alternative toxicity tests

Chemical safety assessment begins with defining the lowest level of chemical that alters one or more measured endpoints. This critical effect level, along with factors to account for uncertainty, is used to derive limits for human exposure. In the absence of data regarding the specific mechanisms or biological pathways affected, non-specific endpoints such as body weight and non-target organ weight changes are used to set critical effect levels. Specific apical endpoints such as impaired reproductive function or altered neurodevelopment have also been used to set chemical safety limits; however, in test guidelines designed for specific apical effect(s), concurrently measured non-specific endpoints may be equally or more sensitive than specific endpoints. This means that rather than predicting a specific toxicological response, animal data are often used to develop protective critical effect levels, without assuming the same change would be observed in humans. This manuscript is intended to encourage a rethinking of how adverse chemical effects are interpreted: non-specific endpoints from in vivo toxicological studies data are often used to derive points of departure for use with safety assessment factors to create recommended exposure levels that are broadly protective but not necessarily target-specific.

A NON-MOTORIZED TREADMILL VALIDATED FOR THE TRADITIONAL OVERGROUND 6-MIN WALK TEST

https://youtu.be/Md1_zvpPsTc BACKGROUND The six-minute walk test (6MWT) is a commonly used clinical and research test to assess aerobic capacity. However, in many settings, the 30-m corridor required to conduct the test may not be available. Evaluation of the use of a non-motorized treadmill as an alternative method has not been well studied. PURPOSE: This study compared the distances walked during the traditional (TRAD) 6MWT on a flat indoor surface to a non-motorized treadmill (NMT) to validate the use of the NMT as an alternative testing method. METHODS A total of 55 healthy adults (28 females) completed the TRAD 6MWT and NMT 6MWT during the same testing session (randomized order). The levels of agreement between the two methods were quantified using Lin’s concordance correlation coefficients. Additionally, a multiple linear regression was developed to predict TRAD 6MWT distance with covariates age, sex, and body mass index (BMI) from NMT distance walked. RESULTS The average TRAD distance walked was 630 m and the average NMT distance walked was 607 m. The mean difference of 23 m between the two methods was nonsignificant. There was good agreement between methods (rc = 0.84) showing no differences. A multiple linear regression was developed and revealed that NMT distance significantly predicted TRAD distance when controlling for age, sex, height, and weight (Standardized Beta = 0.791, p < 0.001). CONCLUSION The use of the NMT for 6MWT was deemed a valid and feasible replacement for the TRAD 6MWT based on the results of this study.

Should non-invasive prenatal testing be recommended for patients who achieve pregnancy with PGT?

ObjectiveTo determine whether non-invasive prenatal testing is an alternative testing option to preimplantation genetic testing (PGT) in pregnant patients.MethodsThis was a retrospective study of the clinical outcomes of patients who underwent PGT and invasive or non-invasive pregnancy testing after euploid blastocyst transfer at our IVF centre between January 2017 and December 2022.ResultsIn total, 321 patients were enrolled in this study, 138 (43.0%) received invasive pregnancy testing, and 183 (57.0%) patients underwent non-invasive testing. The mean age of the patients in Group 2 was higher than that of the patients in Group 1 (35.64 ± 4.74 vs. 31.04 ± 4.15 years, P < 0.001). The basal LH and AMH levels were higher in Group 1 than in Group 2 (4.30 ± 2.68 vs. 3.40 ± 1.88, P = 0.003; 5.55 ± 11.22 vs. 4.09 ± 3.55, P = 0.012), but the clinical outcomes were not significantly different. Furthermore, the clinical outcomes of patients undergoing invasive testing were similar to those of patients undergoing non-invasive testing with the same PGT indication.ConclusionOur results suggest that non-invasive pregnancy testing is a suitable alternative option for detecting the foetal chromosomal status in a PGT cycle. However, the usefulness of non-invasive testing in PGT-M patients is still limited.

Spiritual Well-Being to the Quality of Life of Heart Failure Patients

Heart failure is caused by the heart being unable to maintain normal blood flow. Some patients with heart failure expressed that they needed nurses' help with their physical, psychological, and spiritual problems. Spiritual Well-Being and its components play an important role in a person's declining quality of life and have been linked to various other health factors. This research aims to determine the relationship between spiritual well-being and the quality of life of heart failure patients. The sample for this research was 100 respondents taken using the accidental sampling technique. Data analysis uses the chi-square correlation test if the test conditions are met. If the test requirements are not met, use the alternative Fisher exact test. The instruments used in this research were the Spiritual Needs Questionnaire (SpNQ) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The results of this study illustrate that there is no relationship between quality of life scores and all aspects of the spiritual needs of heart failure patients (p&gt; 0.05). The results of the analysis carried out showed that NYHA functional status (p= 0.044) and ejection fraction (r= -0.205, p= 0.041) influenced the spiritual needs of heart failure patients. The results of this study indicate that the patient's spiritual needs are not related to the general quality of life score, but have a significant relationship with the physiological dimensions of quality of life, ejection fraction, and NYHA functional status.

Next Generation Sequencing, and Development of a Pipeline as a Tool for the Detection and Discovery of Citrus Pathogens to Facilitate Safer Germplasm Exchange

Citrus is affected by many diseases, and hence, the movement of citrus propagative materials is highly regulated in the USA. Currently used regulatory pathogen detection methods include biological and laboratory-based technologies, which are time-consuming, expensive, and have many limitations. There is an urgent need to develop alternate, rapid, economical, and reliable testing methods for safe germplasm exchange. Citrus huanglongbing (HLB) has devastated citrus industries leading to an increased need for germplasm exchanges between citrus growing regions for evaluating many potentially valuable hybrids for both HLB resistance and multilocational performance. In the present study, Next-Generation Sequencing (NGS) methods were used to sequence the transcriptomes of 21 test samples, including 15 well-characterized pathogen-positive plants. A workflow was designed in the CLC Genomics Workbench software, v 21.0.5 for bioinformatics analysis of the sequence data for the detection of pathogens. NGS was rapid and found to be a valuable technique for the detection of viral and bacterial pathogens, and for the discovery of new citrus viruses, complementary to the existing array of biological and laboratory assays. Using NGS methods, we detected beet western yellows virus, a newly reported citrus virus, and a variant of the citrus yellow vein-associated virus associated with the “fatal yellows” disease.

Multi-omics analysis identifies potential microbial and metabolite diagnostic biomarkers of bacterial vaginosis.

Bacterial vaginosis (BV) is a common clinical manifestation of a perturbed vaginal ecology associated with adverse sexual and reproductive health outcomes if left untreated. The existing diagnostic modalities are either cumbersome or require skilled expertise, warranting alternate tests. Application of machine-learning tools to heterogeneous and high-dimensional multi-omics datasets finds promising potential in data integration and may aid biomarker discovery. The present study aimed to evaluate the potential of the microbiome and metabolome-derived biomarkers in BV diagnosis. Interpretable machine-learning algorithms were used to evaluate the utility of an integrated-omics-derived classification model. Vaginal samples obtained from reproductive-age group women with (n = 40) and without BV (n = 40) were subjected to 16S rRNA amplicon sequencing and LC-MS-based metabolomics. The vaginal microbiome and metabolome were characterized, and machine-learning analysis was performed to build a classification model using biomarkers with the highest diagnostic accuracy. Microbiome-based diagnostic model exhibited a ROC-AUC (10-fold CV) of 0.84 ± 0.21 and accuracy of 0.79 ± 0.18, and important features were Aerococcus spp., Mycoplasma hominis, Sneathia spp., Lactobacillus spp., Prevotella spp., Gardnerella spp. and Fannyhessea vaginae. The metabolome-derived model displayed superior performance with a ROC-AUC of 0.97 ± 0.07 and an accuracy of 0.92 ± 0.08. Beta-leucine, methylimidazole acetaldehyde, dimethylethanolamine, L-arginine and beta cortol were among key predictive metabolites for BV. A predictive model combining both microbial and metabolite features exhibited a high ROC-AUC of 0.97 ± 0.07 and accuracy of 0.94 ± 0.08 with diagnostic performance only slightly superior to the metabolite-based model. Application of machine-learning tools to multi-omics datasets aid biomarker discovery with high predictive performance. Metabolome-derived classification models were observed to have superior diagnostic performance in predicting BV than microbiome-based biomarkers.

Cancer Spheroids Embedded in Tissue-Engineered Skin Substitutes: A New Method to Study Tumorigenicity In Vivo.

Tumorigenic assays are used during a clinical translation to detect the transformation potential of cell-based therapies. One of these in vivo assays is based on the separate injection of each cell type to be used in the clinical trial. However, the injection method requires many animals and several months to obtain useful results. In previous studies, we showed the potential of tissue-engineered skin substitutes (TESs) as a model for normal skin in which cancer cells can be included in vitro. Herein, we showed a new method to study tumorigenicity, using cancer spheroids that were embedded in TESs (cTES) and grafted onto athymic mice, and compared it with the commonly used cell injection assay. Tumors developed in both models, cancer cell injection and cTES grafting, but metastases were not detected at the time of sacrifice. Interestingly, the rate of tumor development was faster in cTESs than with the injection method. In conclusion, grafting TESs is a sensitive method to detect tumor cell growth with and could be developed as an alternative test for tumorigenicity.

Knowledge transfer based many-objective approach for finding bugs in multi-path loops

AbstractGenerating test cases is essential for discovering software bugs. However, finding bugs in multi-path loops is challenging, especially when bugs can only be exposed after a specific interleaving execution order. Furthermore, the number of paths increases exponentially when the iteration count increases. It results in running out of resources (e.g., allocated search budget) in existing algorithms for test case generation before finding program bugs. To overcome these challenges and improve the effectiveness of existing algorithms in finding bugs among multi-path loops, we propose a path-oriented test case generation framework to explore loop paths of bounded depth. To fulfill this task, we first present a method that groups loop paths based on their latent similarities. Then, we formulate the problem of generating test cases to cover loop paths as a many-objective optimization one. The many-objective optimization problem is designed to optimize one group of loop paths at a time. Finally, a many-objective test case generation framework is used to generate test cases for covering loop paths. In this framework, a knowledge transfer scheme is incorporated to reuse suitable archived test cases at the start of the search process for a similar group of paths. We have implemented the proposed knowledge transfer scheme with generalized differential evolution 3 (KT-GDE3) and evaluated it with benchmarks from the competition on software verification (SV-COMP16 and SV-COMP21). The experimental results show that KT-GDE3 outperforms alternative search-based test case generation algorithms in bug finding capability for multi-path loops. To evaluate the effectiveness of the proposed knowledge transfer scheme, our approach is compared with the variant without this scheme (called KT-GDE3-unarchived) in the benchmarks. The corresponding experimental results verify our assumption that the knowledge transfer scheme can significantly enhance the optimization process of multi-objective algorithms such as generalized differential evolution when finding bugs in multi-path loops.

P722 The steep ramp test is a valid practical test to assess cardiorespiratory fitness in patients with inflammatory bowel disease

Abstract Background Comprehensive disease management of inflammatory bowel disease (IBD) requires a holistic approach that extends beyond achieving endoscopic healing. Monitoring health-related physical fitness (HRPF) parameters (i.e. body composition, cardiorespiratory fitness, muscular strength, muscular endurance, and flexibility) may lead to a more proactive approach to managing IBD, as IBD may affect HRPF due to e.g. chronic inflammation, malnutrition, corticosteroid use, and reduced physical activity. Yet, knowledge regarding HRPF in patients with IBD is limited. Assessment of cardiorespiratory fitness (CRF), a key component of HRPF in other chronic diseases, could offer valuable insights into physical capacity and overall health. However, the gold standard, measuring oxygen uptake at peak exercise (VO2peak) achieved during cardiopulmonary exercise testing (CPET) is impractical for widespread implementation in clinical practice. The steep ramp test (SRT), a short-term maximal exercise test on a cycle ergometer, might serve as a less demanding assessment method to facilitate routine assessment of CRF in clinical practice and deliver more practical endpoints for intervention studies. This study aimed to examine the criterion validity of the SRT as compared with CPET in evaluating CRF in patients with IBD. Methods From August 2022 to October 2023, adult patients with IBD in remission or with mild-to-moderate clinical disease activity were consecutively enrolled. Each participant performed a SRT and a CPET within 14 days to examine CRF. The main outcome measures were the achieved work rate at peak exercise (WRpeak) for the SRT (SRT-WRpeak) and VO2peak as well as WRpeak for CPET (CPET-VO2peak and CPET-WRpeak). Validity of the SRT was evaluated with Pearson’s correlation coefficients between SRT-WRpeak and CPET-VO2peak and SRT-WRpeak and CPET-WRpeak. Results A total of 50 participants, with a mean age of 42.9 years and 56% diagnosed with CD, were included (Table 1). One participant was excluded from the analysis due to the inability to achieve a maximal effort during CPET. Mean (±SD) WRpeak attained at the SRT was 4.32 (±1.06) W·kg-1, and mean (±SD) VO2peak and WRpeak achieved during CPET were 33.47 (±9.85) mL·kg-1·min-1 and 2.90 (±0.95) W·kg-1, respectively. Figure 1 illustrates robust linear relationships with very strong correlations between SRT-WRpeak and CPET- VO2peak (r=0.945, p&amp;lt;0.001) and SRT-WRpeak and CPET-WRpeak (r=0.960, p&amp;lt;0.001). Conclusion Results of this study suggest that the SRT is a valid alternative test for examining CRF in patients with IBD, indicating its potential application in both clinical practice and intervention studies. Further research should explore the criterion validity of practical tests for other components of HRPF.

Adaptable test bench for ASTM-compliant permeability measurement of porous scaffolds for tissue engineering

Intrinsic permeability describes the ability of a porous medium to be penetrated by a fluid. Considering porous scaffolds for tissue engineering (TE) applications, this macroscopic variable can strongly influence the transport of oxygen and nutrients, the cell seeding process, and the transmission of fluid forces to the cells, playing a crucial role in determining scaffold efficacy. Thus, accurately measuring the permeability of porous scaffolds could represent an essential step in their optimization process. In literature, several methods have been proposed to characterize scaffold permeability. Most of the currently adopted approaches to assess permeability limit their applicability to specific scaffold structures, hampering protocols standardization, and ultimately leading to incomparable results among different laboratories. The content of novelty of this study is in the proposal of an adaptable test bench and in defining a specific testing protocol, compliant with the ASTM International F2952-22 guidelines, for reliable and repeatable measurements of the intrinsic permeability of TE porous scaffolds. The developed permeability test bench (PTB) exploits the pump-based method, and it is composed of a modular permeability chamber integrated within a closed-loop hydraulic circuit, which includes a peristaltic pump and pressure sensors, recirculating demineralized water. A specific testing protocol was defined for characterizing the pressure drop associated with the scaffold under test, while minimizing the effects of uncertainty sources. To assess the operational capabilities and performance of the proposed test bench, permeability measurements were conducted on PLA scaffolds with regular (PS) and random (RS) micro-architecture and on commercial bovine bone matrix-derived scaffolds (CS) for bone TE. To validate the proposed approach, the scaffolds were as well characterized using an alternative test bench (ATB) based on acoustic measurements, implementing a blind randomized testing procedure. The consistency of the permeability values measured using both the test benches demonstrated the reliability of the proposed approach. A further validation of the PTB’s measurement reliability was provided by the agreement between the measured permeability values of the PS scaffolds and the theory-based predicted permeability value. Once validated the proposed PTB, the performed measurements allowed the investigation of the scaffolds’ transport properties. Samples with the same structure (guaranteed by the fused-deposition modeling technique) were characterized by similar permeability values, and CS and RS scaffolds showed permeability values in agreement with the values reported in the literature for bovine trabecular bone. In conclusion, the developed PTB and the proposed testing protocol allow the characterization of the intrinsic permeability of porous scaffolds of different types and dimensions under controlled flow regimes, representing a powerful tool in view of providing a reliable and repeatable framework for characterizing and optimizing scaffolds for TE applications.