Testing Approach Research Articles

Proposal of Testing Procedure for Resonance and Ferroresonance Inception Possibility in Instrument Transformers

This paper deals with the possibility of ferroresonance occurence in the interaction between circuit breakers and inductive instrument transformers. Existing standards lack guidance on testing for ferroresonant behaviour. The paper proposes a standardized testing procedure and presents measurements on a full-scale system. EMTP simulations complement the measurements for a broader network topology analysis, i.e. circuit breaker capacitance combinations. EMTP simulations are validated for a 170 kV voltage transformer and a combined instrument transformer, showing accuracy within 10%. The paper also extends the EMTP modelling application to a 420 kV voltage power transformer during design phase, ensuring it doesn't experience ferroresonance. This study offers a practical approach for testing and simulating ferroresonance in inductive instrument transformers, contributing to the safe operation of power networks.

Machine Translation Testing via Syntactic Tree Pruning

Machine translation systems have been widely adopted in our daily life, making life easier and more convenient. Unfortunately, erroneous translations may result in severe consequences, such as financial losses. This requires to improve the accuracy and the reliability of machine translation systems. However, it is challenging to test machine translation systems because of the complexity and intractability of the underlying neural models. To tackle these challenges, we propose a novel metamorphic testing approach by syntactic tree pruning (STP) to validate machine translation systems. Our key insight is that a pruned sentence should have similar crucial semantics compared with the original sentence. Specifically, STP (1) proposes a core semantics-preserving pruning strategy by basic sentence structures and dependency relations on the level of syntactic tree representation, (2) generates source sentence pairs based on the metamorphic relation, and (3) reports suspicious issues whose translations break the consistency property by a bag-of-words model. We further evaluate STP on two state-of-the-art machine translation systems (i.e., Google Translate and Bing Microsoft Translator) with 1,200 source sentences as inputs. The results show that STP accurately finds 5,073 unique erroneous translations in Google Translate and 5,100 unique erroneous translations in Bing Microsoft Translator (400% more than state-of-the-art techniques), with 64.5% and 65.4% precision, respectively. The reported erroneous translations vary in types and more than 90% of them are not found by state-of-the-art techniques. There are 9,393 erroneous translations unique to STP, which is 711.9% more than state-of-the-art techniques. Moreover, STP is quite effective in detecting translation errors for the original sentences with a recall reaching 74.0%, improving state-of-the-art techniques by 55.1% on average.

Does economic policy uncertainty and stock market development affect natural resources: Evidence from United States of America

AbstractThis study investigates the impact of economic policy uncertainty (EPU) and stock market development (SMD) on natural resources in the United States during the period between 1985 and 2021 by keeping the GDP and innovation as control variables. For empirical analysis, the autoregressive distributed lag model (ARDL) and Kernel Regularized Least Squares (KRLS) regression techniques were used to investigate the long‐ and short‐run relationships. To check the robustness of results, this study uses a machine learning approach, i.e., Canonical Cointegrating Regression (CCR). The results of the ARDL bounds test approach suggest the presence of long‐run relationships among the study variables, and these results were confirmed through KRLS and CCR. The long‐run results indicate that economic policy uncertainty and SMD increase natural resource rent. Moreover, GDP and innovation also increase natural resource rent. However, a weak relationship exists between innovation and natural resource rent in the short run. Policymakers need to provide stable and encouraging economic policies to promote sustainable resource management, while stock markets need to facilitate long‐term planning and responsible investment in natural resource industries.

Self‐help or self‐sabotage? A common invader's soil legacy does not impede, and may facilitate, potential competitors

AbstractIntroduced plants create lasting abiotic and biotic changes to soil that are increasingly implicated as major drivers of invasion success, yet models for investigating patterns in the impacts of these soil legacies are lacking. Here, we used Bohemian knotweed (Reynoutria × bohemica) to present a novel approach for testing whether accounting for diverse evolutionary drivers can clarify how an invader's soil legacy mediates its success. For most tested species, R. × bohemica's soil legacy did not influence seedling performance irrespective of its evolutionary history or the evolutionary novelty of species that share its soil. However, we found the relative importance of legacy effects versus other mechanisms of invader dominance depends on the life stage of the plants growing in soil conditioned by the invader. While the effects of R. × bohemica's soil legacy on seedling performance were context dependent, emergence was, on average, higher in R. × bohemica‐conditioned soils than in unconditioned soils. Thus, contrary to theory, R. × bohemica's soil legacy not only fails to impede potential competitors but may also facilitate them. Our results are particularly powerful: we detected novel insights in the face of biological complexity, even for R. × bohemica, which likely does not depend on heterospecific plant–soil feedbacks for its competitive dominance in its introduced range. Designing rigorous investigations that explore how plant species' evolutionary histories mediate an invader's soil legacy across diverse abiotic environments, as shown here, is key for producing insights in other systems.

Implementation of video assisted point-of-care germline genetic education and testing for patients with peri-diagnostic pancreatic cancer.

e22530 Background: Germline genetic testing is universally recommended for patients with exocrine pancreatic cancer (PC). Pretest consultation with a genetics professional is recommended to ensure patients are informed about risks, benefits, and limitations of testing. This is a resource intensive process and is associated with a suboptimal testing rate (~30%). Prior work demonstrates that video-assisted pre-test education does not increase patient anxiety compared to traditional pre-test genetic counseling in peridiagnostic ovarian cancer patients. In this report, we assess the feasibility of using a similar video assisted, streamlined genetic education and testing approach in peridiagnostic PC patients. Methods: As part of a pilot quality improvement initiative, patients with a diagnosis of exocrine PC seen in a single academic practice were offered streamlined, video-assisted genetic education followed by germline testing. Patient eligibility for this pilot included: new diagnosis or radiographic suspicion of PC; English language proficiency; and no prior germline testing. After this approach was presented by the medical oncology team, eligible patients viewed a 9-minute educational video describing the goals, pros, and cons of germline genetic testing. After watching the video, patients were given the option to proceed with testing that day. Patients with pathogenic mutations were referred for formal post-test genetic counseling, and patients with variants of uncertain significance (VUSs) were referred on a case-by-case basis. Following IRB approval, we conducted a retrospective review of the experience of all patients presenting to this pilot site from April-Dec 2023. Results: During the study period, 56 new patients with exocrine PC presented to the pilot site. 50 patients were eligible for participating in the pilot program. All patients, except one who declined on the basis of transferring care, consented to testing (49/50; 98%). Median patient age was 71, 49% were female. Race distribution was: White (30), Asian (6), Black (4), Other (2), Declined (7). Median time from patient diagnosis to testing was 11 days. One patient had a germline ATM mutation, and this patient was seen for formal posttest counseling 18 days after testing was initiated. Seven patients had VUSs. Six new patients presenting during the study period were not eligible for this pilot, all due to limited English proficiency. All 6 of these patients underwent genetic testing after translation service assisted counseling by either the primary oncology or cancer genetics team. Conclusions: Video assisted point-of-care genetics education and testing led to nearly universal uptake of genetic testing in peridiagnostic PC patients. This workflow was feasible, timely, and optimized use of genetic counseling resources.

A comparison of real-world incidence of EGFR exon 20 insertion mutations among patients with NSCLC in five Asian markets, stratified by testing methodology.

e20622 Background: Despite the arrival of drugs targeting EGFR exon 20 insertions mutations (ex20ins) in non-small cell lung cancer (NSCLC), testing practices for this specific mutation vary widely between hospitals. In addition, there is a lack of real world data on incidence of ex20ins in different countries in Asia. This study tracks real-world ex20ins incidence by country/region as well as by methodology across 5 different Asian markets. Methods: Ipsos’ Exon 20 Insertion Tracker is an ongoing physician-reported syndicated study. Hospitals in Asia (n = 7 in South Korea; n = 5 in Taiwan; n = 4 in India; n = 5 in Thailand; n = 1 in Hong Kong) were asked to submit data on total number of NSCLC patients tested for EGFR mutations using single marker tests vs multi-gene panel tests, and subsequently asked how many tested positive for ex20ins. Data were collected online on a regular basis from September 2022 in South Korea and Taiwan, from January 2023 in India, and from September 2023 in Thailand and Hong Kong, until December 2023 in all markets. A total of n = 7,657 EGFR-tested patients in South Korea, n = 2,260 in Taiwan, n = 3,970 in India, n = 407 in Thailand and n = 114 in Hong Kong were reported on. Results: Incidence of ex20ins was markedly higher in Hong Kong (3.5%) and Taiwan (3.7%) than in South Korea (1.6%), India (1.4%) and Thailand (1.0%), pointing to a potentially higher incidence in Greater China compared to other parts of Asia. Among this cohort, the use of panel testing for EGFR mutations was highest in India (99%) and lowest in Taiwan (1%). Across the markets, incidence of ex20ins appears to be somewhat higher among those tested with single-marker EGFR tests (2.2%) than those tested with panel-based tests (1.4%), although the opposite was observed in Thailand and Hong Kong. Conclusions: In this large study based on testing results from over 14,400 EGFR-tested patients across 5 different markets in Asia, clear differences in observed incidence of ex20ins mutations were observed, with the incidence in Taiwan being nearly 4 times as high as that in Thailand. This highlights that different testing and biomarker sequencing strategies may be necessary in markets with the highest observed incidence. A secondary finding from this study is that test methodology does appear to have an impact on observed incidence, though this is in part due to very different testing approaches (single-marker vs panel-based) between markets, with the majority of hospitals included in the study in Taiwan preferring a single-marker approach. [Table: see text]

Incidence and demographics of bile duct cystadenocarcinoma from the National Cancer Database.

e16231 Background: Bile duct cystadenocarcinoma, a rare tumor of the biliary tree, manifests itself within both multilocular and unilocular cysts composed of mucous-secreting, cytologically malignant epithelial cell populations. While similar in presentation to other biliary tree malignancies, bile duct cystadenocarcinoma has unique morphological variations between sexes. This contrast in disease manifestation based on sex could potentially impact diagnostic imaging, testing approaches, and treatment strategies for both female and male patients. The potential impact of demographics on the prognosis of bile duct cystadenocarcinoma, along with limited literature on the subject, make it a compelling subject for hypothesis generating epidemiological inquiry. The National Cancer Database will be used to illuminate the demographic intricacies. In this pursuit, we aim to provide a demographic and incidence background to prompt future research dedicated to the understanding of bile duct cystadenocarcinoma. Methods: The National Cancer Database (NCDB) was used to complete a retrospective cohort analysis of all patients diagnosed with histologically confirmed bile duct cystadenocarcinoma from the years 2004 to 2020. Demographic factors were subjected to descriptive statistical techniques, while a comprehensive regression analysis was employed to analyze the patterns in disease incidence. Results: Between 2004 and 2020, 64 patients were diagnosed with bile duct cystadenocarcinoma in the NCDB. There was a decline of incidence per year (R2 = 0.0392). The majority of those diagnosed with this disease were female (70%). Most of the patients were from Caucasian ethnicity (73%). The average age of diagnosis was 65 years old ( SD = 12.5, range = 33-88). The highest percentage of patients were on Medicare (55%). The primary site of the cancer was in the intrahepatic bile duct (63%). 70% of patients had a Charlson-Deyo Score of 0. Stage 1 was the most detected stage (42%). The average size of the tumor when detected was 65 mm (SD = 35.5, range = 9-144 mm). Most patients (72%) received surgical treatment and the remainder received radiation or chemotherapy alone. Regarding margins post-surgery, most of the patients (56%) had no residual tumor. Almost all patients (92%) received treatment designed for cure/remission. Mean survival after diagnosis was 8 years. Conclusions: Consistent with a vast majority of case reports, our results demonstrated that the majority of cases of bile duct cystadenocarcinoma were found in women (70%). Moreover, given that a significant proportion of patients affected by this disease are covered by Medicare (55%), we contend that investigating the precise influence of demographic factors and social determinants of health in this context presents a compelling avenue for future research.

Enhancing the quality of banking technology platforms through a hybrid AI testing approach

In the dynamic landscape of the banking sector, marked by increased operational complexity and regulatory scrutiny, the pursuit of innovation demands a strategic orientation. While offering advantages in cost, quality and speed, this strategic approach to innovation should mandate a cautious consideration of the risks inherent in the integration of emerging technologies. With the continuous advancement of artificial intelligence (AI), particularly generative AI (GenAI), as a method for emerging banking technologies, its wider adoption in the financial industry demands careful consideration of associated risk implications. This paper advocates for a software testing approach that delves into the complexities of banking technology platforms by leveraging generative algorithms to attain extensive test coverage and simultaneously employs rule-based analytics to refine the generated datasets, optimising coverage for faster execution and efficient resource utilisation. Such an approach is in line with a risk-averse innovation strategy, as it balances out the smart creativity of novel GenAI methods with a rule-based discriminative potential of more established symbolic AI methods. This paper serves as a position paper, contributing to the discourse on the integration of innovative testing methodologies in the banking domain.

Advancements in Nanoparticle Biosensors: Applications, Properties, and Considerations for Improving Performance and Detection Capabilities

Nanoparticle biosensors have emerged as a powerful diagnostic tool, offering highly sensitive and specific detection of biomarkers and pathogenic agents. This article discusses various applications of nanoparticle biosensors in disease diagnosis and public health monitoring. Magnetic nanoparticles have unique magnetic properties that enable their application in novel separation techniques. This review aims to evaluate the use of magnetic separation across various fields including mineral processing, environmental remediation, and biomedical research. In mineral processing, magnetic separation techniques are commonly employed to separate magnetite from iron ore or other naturally magnetic minerals from gangue material. This allows for an efficient concentration of valuable ore. Similarly, in environmental applications, magnetic nanoparticles can selectively bind to pollutants such as heavy metals in soil and water, permitting separation using an external magnetic field and removal of contaminants. Within biomedical research, magnetic separation has proved a versatile technique for isolating target cells, proteins, and pathogens. Functionalization of magnetic nanoparticles allows specific binding followed by magnetic retrieval. This provides a simple, rapid approach for diagnostic tests, biomarker analysis, and other medical applications. Magnetic separation offers an effective means of differentiating between magnetic and non-magnetic components across many industries and research disciplines.

Basis path coverage testing of MPI programs based on multi-task evolutionary optimization

A Message-Passing Interface (MPI) program usually consists of several processes, and a target path of this program is composed of a target sub-path selected in each process. However, there may be coverage conflict between different target sub-paths in the target path, and there is currently no effective approach to avoid this problem. Therefore, this paper proposes an approach of basis path coverage testing of MPI programs based on multi-task evolutionary optimization, which is used to generate a test case set that meets the criteria of branch and sentence coverage. Firstly, the proposed approach samples a certain number of representative test inputs, and calculates the coverage level of each test input for each target sub-path in the target path, which is used to group the target sub-paths with coverage conflict. Then, we construct an optimization model for each group of the target sub-paths, which can guide test case generation with high effectiveness. Finally, each optimization model is solved by an evolutionary algorithm, and the efficiency of solving these optimization models is improved based on a multi-task framework. The proposed approach is applied to basis path coverage testing of seven benchmark MPI programs under test, and compared with several state-of-the-art approaches. Experimental results indicate that the proposed approach has significant advantages in test case generation, as well as performs good scalability.

A novel, noninvasive, multimodal screening test for the early detection of precancerous lesions and colorectal cancers using an artificial intelligence–based algorithm.

3627 Background: Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality worldwide, and its incidence is increasing in younger populations. Detection of early-stage CRC and its precursor lesions, such as advanced adenomas (AA), is crucial for successful treatment and reduces CRC-related mortality. Although non-invasive methods for early detection are available and increase screening compliance, their performance with respect to detection of advanced adenomas and early-stage cancers is limited. Here, we describe a novel and non-invasive stool-based approach combining diagnostic biomarkers with an algorithm generated by machine learning/artificial intelligence (ML/AI) resulting in significantly improved diagnostic performance for the detection of not only CRC, but especially precancerous lesions like AA. Methods: Data were generated from a combined cohort of stool samples collected at 10 clinical sites in Europe (COLOFUTURE study) and 21 clinical sites in the US (eAArly DETECT study). The evaluable study cohort consists of 690 subjects, including 78 CRC, 146 AA, 147 with non-advanced adenoma (AD) and 319 normal colonoscopy negative control (NC) subjects (49% female, 51% male, average age 61.8 years). Results were compared with colonoscopy and pathology findings to determine sensitivity and specificity for detection of early-stage CRC and AA vs. AD and NC. Nucleic acids were extracted from stabilized stool samples using a silica bead-based extraction method. Expression of mRNA biomarkers was analyzed utilizing Real-Time PCR. Human hemoglobin was quantified using FIT. The Emerge Quantitative Evolution ML/AI platform was leveraged to develop classifiers capable of distinguishing CRC and AA from AD and NC. Results: Applying the combined approach of non-invasive diagnostic testing with an AI/ML generated algorithm, the sensitivity for detection of CRC overall was 92.3%. In addition, this method enabled AA detection with a sensitivity of 82.2%. Specificity turned out to be 90.1 % (AD+NC). Conclusions: This innovative, non-invasive, multimodal screening strategy based on self-collected stool samples which combines mRNA expression patterns and FIT analysis with an AI/ML-generated algorithm represents a substantial improvement in the effectiveness of non-invasive CRC screening. Such improvements in usability and performance leading to reliable detection of early-stage CRC and precursor lesions, such as advanced adenomas, are required for wide-spread availability and adaption of non-invasive screening tests to accepted clinically relevant usage and to prevent the development of CRC effectively.

Wind and rainfall erosion energy in large sediment generating and coarse sediment class areas of the middle Yellow river

Joint action by strong winds and high-intensive rainfall leads to serious soil erosion problems in large sediment generating and coarse sediment class areas of the middle Yellow River. Investigating the variation of trend and alternating wind and rainfall energy is an important prerequisite for controlling regional sediment transport problems. We calculated the wind and rainfall erosion energies by using the aerodynamic energy and rainfall kinetic energy formulas. The Mann-Kendall (MK) trend test and Theil-Sen approach were used to analyze the spatial-temporal variation and alternation of joint erosion energy during the last 40 years (1979–2018). The results show the following. 1) Wind erosion energy increased and rainfall erosion energy decreased. However, the former is larger than the latter. 2) The dominant erosive energy varies for different seasons. Wind erosive energy dominates in spring, and rainfall erosive energy dominates in summer. 3) There is a regular wind-rainfall-wind alternation of erosive energy. The wind-rainfall energies were alternately distributed in May–July and the rainfall-wind energies were alternately distributed in September–December. Furthermore, the dominant time of rainfall erosive energy decreased when wind erosive energy increased. The results can help decision makers to develop soil erosion control strategies to reduce soil erosion when it occurs in wind and water staggered areas.

SENEM: A software engineering-enabled educational metaverse

Context:The term metaverse refers to a persistent, virtual, three-dimensional environment where individuals may communicate, engage, and collaborate. One of the most multifaceted and challenging use cases of the metaverse is education, where educators and learners may require multiple technical, social, psychological, and interaction instruments to accomplish their learning objectives. While the characteristics of the metaverse might nicely fit the problem’s needs, our research points out a noticeable lack of knowledge into (1) the specific requirements that an educational metaverse should actually fulfill to let educators and learners successfully interact towards their objectives and (2) how to design an appropriate educational metaverse for both educators and learners. Objective:In this paper, we aim to bridge this knowledge gap by proposing SENEM, a novel software engineering-enabled educational metaverse. We first elicit a set of functional requirements that an educational metaverse should fulfill. Method:In this respect, we conduct a literature survey to extract the currently available knowledge on the matter discussed by the research community, and afterward, we assess and complement such knowledge through semi-structured interviews with educators and learners. Upon completing the requirements elicitation stage, we then build our prototype implementation of SENEM, a metaverse that makes available to educators and learners the features identified in the previous stage. Finally, we evaluate the tool in terms of learnability, efficiency, and satisfaction through a Rapid Iterative Testing and Evaluation research approach, leading us to the iterative refinement of our prototype. Results:Through our survey strategy, we extracted nine requirements that guided the tool development that the study participants positively evaluated. Conclusion:Our study reveals that the target audience appreciates the elicited design strategy. Our work has the potential to form a solid contribution that other researchers can use as a basis for further improvements.

Effect of screening with a pan-TRK immunohistochemistry-based algorithm on NTRK fusion detection rates.

e15135 Background: Rearrangements in the NTRK1, NTRK2, and NTRK3 genes are clinical actionable and predictive of response to TRK kinase inhibitors in solid tumors. Their detection in clinical practice is a priority, but their low prevalence (0.25-1%) poses a diagnostic challenge. In this study, we describe our immunohistochemical-based and cost-effective approach for NTRK rearrangements detection. Methods: We implemented a comprehensive NTRK testing approach at a reference center that combined clinical criteria (e.g., iodine therapy-resistant thyroid cancer); molecular biomarkers (e.g., non-small-cell lung carcinoma negative for driver alterations, colorectal carcinoma with deficient MMR and/or microsatellite instability); and histopathological criteria (identifying tumor subtypes associated with NTRK fusions, such as breast secretory carcinoma). Automated immunohistochemistry (Ventana BenchMark ULTRA IHC/ISH System) using the antibody pan-TRK (Ventana, EPR17341) was used as a screening tool. Positive results were confirmed through molecular techniques, including Next Generation Sequencing, NGS (Oncomine Focus Assay, Thermo Fisher, based on DNA and RNA) and/or FISH (NTRK3 break-apart probe, Zytovision). Results: We evaluated 172 patients (99 female/73 male), with a mean age of 52 years (SD 23.8). Eighteen (18) patients with neoplasms expressing TRK proteins were identified. Confirmatory studies using NGS identified fusions in 7 cases. In instances of poor RNA quality, FISH techniques (NTRK3) were employed, confirming the findings in an additional 3 patients. Overall prevalence of NTRK fusions was 5.8%. Histological types included the following tumor types: Thyroid carcinoma, 4 patients (one medullary and 3 papillary carcinomas, two of them in the pediatric population); soft tissue sarcomas, 3 patients (2 corresponding to infantile fibrosarcoma and a soft tissue provisional entity, "NTRK-rearranged spindle cell neoplasm”); secretory carcinoma of the breast, one patient; secretory carcinoma of the salivary gland, one patient; colorectal carcinoma, one patient, with a deficient MMR phenotype. NTRK3 gene fusions were found in 10 patients, (6 fusions with ETV6 detected by NGS and 3 detected by FISH), and NTRK1 fusion in 1 case (fusion with LMNA detected by NGS). The positive predictive value of pan-TRK immunohistochemistry as a screening tool was 0.55. Conclusions: In our experience, the comprehensive screening approach based on morphological and clinical/ molecular inclusion criteria, along with the use of immunohistochemical techniques (pan-TRK antibody), significantly enhances the detection rate of NTRK fusions (5.8% vs. 0.25-1%). Additionally, FISH provides a valuable tool in samples with poor RNA quality. This approach allows for a reduction in the impact of costly testing, such as NGS, on the healthcare system.

The Impact of Financial Development, Net Foreign Assets and Domestic Businesses on Export Performance: A case of Singapore Economy

The effects of financial sector liberalization; foreign assets, domestic businesses in the form of listed companies and domestic manufacturing, and real interest rate on export performance of Singapore economy are tested by using ARDL bounds testing approach by covering period from 1978-2023. The empirical results suggest that liberalizing financial sector and foreign assets significantly accelerate export performance. This study considers two proxies for domestic businesses – listed companies and manufacturing. The results uncover the significantly expansionary effects of both indicators of domestic businesses on export performance. Lastly, real interest rate is adversely affecting export performance in Singapore. This study suggests that by expanding domestic businesses; increasing investments in foreign assets, liberalizing financial sector and reducing real interest rate can give boost to exports in Singapore.

Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics.

This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV). Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. The data set comprised abstracted clinical data with germline and tumor genomic data, and comparative analyses were conducted. Clinically actionable germline PVs in cancer predisposition genes were identified in 16 (4.5%) of 354 patients. A higher proportion of patients with the urethra and the upper tract as the primary sites of disease had PVs with a prevalence of 11% (5/45), compared with only 3.6% (11/308) in those with the bladder as the primary site of disease (P = .04). There were no significant differences in markers of genomic instability (such as tumor mutational burden, microsatellite instability [MSI], and loss of heterozygosity, copy number, and chromosomal instability) between those with PVs and those without (P > .05). Of the PVs identified, 10 (62%) were in homologous recombination repair (HRR) genes, three (19%) in mismatch repair (MMR) genes, and three (19%) in genes associated with other pathways. Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV. A comprehensive clinical germline testing approach that includes HRR genes in addition to MMR genes is likely to yield PVs in approximately one of 10 patients with nonbladder primary disease sites such as the upper tract and the urethra.

Immunogenicity, safety and dual DIVA-like character of a recombinant candidate vaccine against neosporosis in cattle

Neosporosis is the major infectious cause of abortion and reproductive losses in cattle worldwide; however, there are no available vaccines or drugs to control this disease. Recently, a dual (positive and negative) DIVA-like (Differentiation of Infected from Vaccinated Animals) vaccine was evaluated in a pregnant mouse model of neosporosis, showing promising immunogenic and protective results. The current report aimed to study the safety, the dose-dependent immunogenicity and the dual DIVA-like character of a recombinant subunit vaccine composed of the major surface antigen from Neospora caninum (rNcSAG1) and the carrier/adjuvant Heat shock protein 81.2 from Arabidopsis thaliana (rAtHsp81.2) in cattle. Healthy heifers were separated and assigned to experimental groups A-F and subcutaneously immunized with 2 doses of vaccine formulations 30 days apart as follows: A (n = 4): 50 μg rNcSAG1 + 150 μg rAtHsp81.2; B (n = 4): 200 μg rNcSAG1 + 600 μg rAtHsp81.2; C (n = 4): 500 μg rNcSAG1 + 1,500 μg rAtHsp81.2; D (n = 3): 150 μg rAtHsp81.2; E (n = 3):1,500 μg rAtHsp81.2, and F (n = 3) 2 ml of sterile PBS. The immunization of heifers with the different vaccine or adjuvant doses (groups A-E) was demonstrated to be safe and did not modify the mean value of the evaluated serum biomarkers of metabolic function (GOT/ASP, GPT/ALT, UREA, Glucose and total proteins). The kinetics and magnitude of the immune responses were dose-dependent. The higher dose of the vaccine formulation (group C) stimulated a broad and potent humoral and cellular immune response, characterized by an IgG1/IgG2 isotype profile and IFN-γ secretion. In addition, this was the first time that dual DIVA-like character of a vaccine against neosporosis was demonstrated, allowing us to differentiate vaccinated from infected heifers by two different DIVA compliant test approaches. These results encourage us to evaluate its protective efficacy in infected pregnant cattle in the future.

Magnesium‐based nanocomposites developed through multi‐pass friction stir processing and strengthening mechanisms exploration

AbstractIn the current experimental work, using secondary phase hard nano titanium carbide (TiC) particles as reinforcement, two different magnesium metal matrices i. e., AZ31B/TiC and AZ61 A/TiC composite materials were synthesized by friction stir processing. Using the traditional testing approach for the developed materials, the simultaneous gain in metallurgical, mechanical, electrical, and tribological characteristics compared to the base substrate was examined. The microstructure study results for AZ31B/TiC and AZ61 A/TiC composites showed a uniform distribution of reinforced particles as well as an evolution in grain size, from 82 μm to 4.2 μm and from 74 μm to 3.7 μm, respectively, which consequently contribute in a significant gain in the microhardness of both composites i. e., around 2.2 times and 2.67 times respectively, greater than the base metal. When compared to monolithic alloys, the synthesized AZ31B/TiC and AZ61 A/TiC composites showed improvements in the areas of tensile strength, compressive strength, and coefficient of friction up to 1.81 times, and 1.64 times, 1.74 times and 1.58 times, and 57.92 % and 58.47 %, respectively. Furthermore, these improvements in characteristics also increase the final strengthening of the nanocomposite and reduce electrical conductivity.

Human Sputum Proteomics: Advancing Non-Invasive Diagnosis of Respiratory Diseases with Enhanced Biomarker Analysis Methods

Many ailments can be diagnosed while they are asymptomatic, meaning that the patient has no signs or symptoms of a progressing disease. If caught in their initial stage of formation, these disorders can be effectively treated, leading to successful outcomes; curative therapies can halt illnesses from advancing, thus improving the quality of life and long-term survival of the patient. Still, cutting-edge upgrades in precision technologies are necessary for early, reliable, affordable, and rapid disease detection, but also vital for the well-being of people and the future of global public health. The emerging role and utility of non-invasive and repeatable diagnostic test approaches for the detection of health conditions have been exemplified by liquid biopsies based on genomic biomarkers. As such, biological fluids permit any measurable molecular indicator or signature (e.g., proteins) to provide valuable information on an individual’s wellness and/or disease. Among the bodily secretions used for non-invasive diagnostics is sputum, a complex viscous gel-like biopolymeric network that has gained growing recognition as a rich source of biomarkers of airway infections and pulmonary diseases, and serves as a determinant to reveal other illnesses. As per the World Health Organization, the burden of respiratory conditions is exacerbated by factors ranging from considerable subjection to air pollution and occupational contaminants to tobacco smoking and second-hand smoke, in addition to poor socio-economic status. Due to the likely increase in these determinants, respiratory tract ailments are on the rise, affecting the health of many individuals, in addition to putting stress on healthcare facilities and services worldwide. The aim of this study was to perform a narrative review of sputum constituents with an emphasis on proteins and glycoproteins assessed as possible biomarkers of lung and other organ diseases. A search was conducted using mucus, sputum proteomics, sputum biomarkers, and point-of-care testing as keywords employing Google, PubMed (MEDLINE), and Web of Science, selecting the most referenced and related papers of the last decade. We, therefore, highlight the need to use expectorated or induced sputum specimens as a routine sample source for testing valuable protein biomarkers to diagnose these chronic disorders, predict inflammation and disease progression, as well as monitor the effectiveness of treatments. Further, we discuss the urgent need for fast and reliable point-of-care methods to detect and quantify crucial protein biomarkers in sputum specimens, and the limitations faced when dealing with their complex matrices.

Guidance on farmer participation in the design, testing and scaling of agricultural innovations

CONTEXTDespite accelerated developments in agricultural innovations, there has been a limited progress in their adoption by smallholder farmers, especially in the Global South. Innovations are not adequately reaching farmers, and new technologies are often unsuitable for farmers, or the overall innovation landscape is discouraging the deployment of innovations at scale. The methodological approaches to designing, testing and scaling of innovations play an important role. Involving farmers in the innovation process from the start increases the likelihood of them being more relevant and having a higher chance of adoption. Whereas there is much literature on participatory approaches, there is a limited guidance on choosing an appropriate level of farmer participation across the innovation process. OBJECTIVEThis study aims to develop practical guidance for researchers, development agents and project managers on how to choose an appropriate methodological approach with a suitable level of farmer participation for designing, testing and scaling of agricultural innovations, according to levels of innovation readiness and innovation use. METHODSRelevant scientific literature on participatory design, research and scaling of agricultural innovations was reviewed, followed by compiling lessons learned from selected vegetable innovation projects implemented by the World Vegetable Center (WorldVeg) in Asia and Africa. A list of methodological approaches for participatory design, testing and scaling of innovations was generated, with various levels of farmer participation. A simple guiding framework was then developed for choosing an appropriate approach with a suitable level of farmer participation, according to the readiness and use of the innovations. Examples of selected approaches and application of the proposed guidance are given in project case studies. RESULTS AND CONCLUSIONSBased on the literature review and experience at WorldVeg, we believe it is critical to choose the right level of participation based on how ready are the innovations for application in the local setting. This dimension of how ready the innovations are has been largely overlooked in earlier frameworks on farmer participation. The developed guidance generally recommends increasing participation with higher levels of technology readiness and use. In addition, farmer consultation in early research design should also be strengthened, to co-design locally relevant innovations. The overall innovation systems' landscape must be considered when researching and scaling new innovations. SIGNIFICANCEThe guidance, experiences and lessons provided in this paper will be useful to various scholars, researchers, development agents, funders and project managers who aim to design, test and scale agricultural innovations in a more inclusive and responsible way.