Interpretive Criteria Research Articles

Australian Meningococcal Surveillance Programme Annual Report, 2023.

In Australia, both probable and laboratory-confirmed cases of invasive meningococcal disease (IMD) are reported to the National Notifiable Diseases Surveillance System (NNDSS). When compared to 2022, the number of IMD notifications in 2023 increased by 14% to 143. Laboratory confirmation of IMD occurred in 140/143 (98%) of these cases, with 64% (90/140) diagnosed by bacterial culture and 36% (50/140) by nucleic acid amplification testing. The serogroup was determined for 96% of laboratory-confirmed cases (134/140): serogroup B (MenB) accounted for 84% of infections (112/134); MenW for 8% (11/134); MenY for 8% (11/134). There were no infections attributed to MenC disease. Fine typing was available on 75% of the cases for which the serogroup was determined (100/134). In MenB isolates, 25 porA types were detected, the most prevalent of which were P1.7-2,4 (32%; 26/82), P1.7,16-26 (16%; 13/82) and P1.22,14 (9%; 7/82). All eight typed MenW infections identified as porA type P1.5,2, with two different multi-locus sequence types (MLST) present: ST-11 (5) and ST-1287 (3) from the clonal complex 11, the hypervirulent strain reported in outbreaks in Australia and overseas. In MenY, the predominant porA type was P1.5-1,10-1 (90%; 9/10), ST-1655 and from clonal complex 23. Peaks of IMD occurred in children aged less than 5 years and in those aged 15-24 years, accounting for 21% (30/140) and 26% (37/140) of laboratory-confirmed cases respectively. In children aged under 5 years, 93% of IMD (27/29) was MenB; in those aged 15-24 years, 97% of IMD (36/37) was MenB, with serogroup not determined for one case in each of these age groups. Of note, 14-15% of IMD occurred in each of the older age groups reported: adults 25-44 years (14%, 19/140), 45-64 years (14%, 20/140), and in those aged 65 years and older (15%, 21/140). Whilst MenB predominated in all age groups, the majority of MenY and MenW IMD cases were reported in adults aged 45 years and older. All cultured IMD isolates (n = 90) had antimicrobial susceptibility testing performed. Minimum inhibitory concentration (MIC) values were reported using Clinical Laboratory Standards Institute (CLSI) interpretative criteria: 9% (8/90) were defined as penicillin resistant (MIC value: ≥ 0.5 mg/L); 71% (64/90) had intermediate susceptibility to penicillin (MIC values: 0.125 and 0.25 mg/L) and 20% (18/90) were susceptible to penicillin (MIC values: ≤ 0.064 mg/L). All isolates tested susceptible to ceftriaxone, ciprofloxacin and rifampicin.

A new interpretable behavior prediction method based on belief rule base with rule reliability measurement

The realization of interpretable system behavior prediction is crucial for improving the credibility of prediction results and ensuring the reliability of complex systems. As an interpretable modeling approach, the application of belief rule base (BRB) in interpretable behavior prediction still faces two challenges: (1) The stochastic nature of the optimization process tends to undermine the interpretability of the model, which in turn reduces the reliability of the prediction results. (2) Different rules have different reliabilities due to the limitation of expert knowledge reliability. The parameters of different rules should be treated differently in the optimization process. Therefore, this paper proposes a new behavior prediction method based on interpretable BRB with rule reliability measurement (BRB-IR). First, interpretability criteria for the behavior prediction method are proposed to regulate the interpretability of the whole modeling process. Second, expert knowledge reliability is quantified, and on this basis, rule reliability before and after optimization are quantified to guide an interpretable optimization process and analyze the effectiveness of the optimization. Third, on the basis of quantified rule reliability, three interpretability constraint strategies are proposed to enhance the interpretability and reliability of the model. The BRB-IR validity is verified via diesel engine and lithium-ion battery experiments.

Breast thermography: a systematic review and meta-analysis

BackgroundBreast thermography originated in the 1950s but was later abandoned due to the contradictory results obtained in the following decades. However, advances in infrared technology and image processing algorithms in the twenty-first century led to a renewed interest in thermography. This work aims to provide an updated and objective picture of the recent scientific evidence on its effectiveness, both as a screening and as a diagnostic tool.MethodsWe searched for clinical studies published between 2001 and May 31, 2023, in the databases PubMed and Scopus, that aimed to evaluate the effectiveness of digital, long-wave infrared imaging for detecting breast cancer. Additional documents were retrieved from the studies included in the systematic reviews that resulted from the search and by searching for the names of commercial systems. We limited our selection to studies that reported the sensitivity and specificity of breast thermography (or the data needed to calculate them) using images collected by themselves, with at least five breast cancer cases. Studies that considered breast diseases other than cancer to be positive or that did not use standard tests to set the ground truth diagnosis were excluded, as well as articles written in a language other than English and documents we could not access. We also conducted meta-analyses of proportions of the sensitivity and specificity values reported in the selected studies and a bivariate meta-analysis to account for the correlation between these metrics.ResultsOur systematic search resulted in 22 studies, with an average pooled sensitivity and specificity of 88.5% and 71.8%, respectively. However, the differences in patient recruitment, sample size, imaging protocol, equipment, and interpretation criteria yielded a high heterogeneity measure (79.3% and 99.1% I2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${I}^{2}$$\\end{document} value, respectively).ConclusionsOverall, thermography showed a high sensitivity in the selected studies, whereas specificity started off lower and increased over time. The most recent studies reported a combination of sensitivity and specificity comparable to standard diagnostic tests. Most of the selected studies were small and tend to include only patients with a suspicious mass that requires biopsy. However, larger studies with a wider variety of patient types (asymptomatic, women with dense breasts, etc.) have been published in the latest years.

Shuntogram technique for diagnosing shunt failure in patients with programmable valves: A literature review and a case scenario

Diagnosing shunt patency is crucial in the neurosurgical care of patients with shunted hydrocephalus. The shuntogram is a commonly used method to assess patency, yet its utility in accurately diagnosing shunt failure remains inconsistent. In this article, we examined studies on shuntograms performed in patients with fixed-pressure valves to clarify the techniques used and establish criteria for interpretation. We further reviewed conflicting evidence in the literature regarding the utility of shuntograms and outlined our institution’s protocol in the context of programmable valves. Studies included in this review detailed the following elements of shuntogram techniques: patient age, indication for shunt failure assessment, positioning, skin preparation, imaging protocol, contrast agents, patency testing, criteria for negative and positive results, troubleshooting shunt, and sensitivity and specificity of findings. Selection criteria included vague symptoms of shunt malfunction in the presence of non-diagnostic imaging. Patients were typically positioned supine or recumbent, with skin prepared using iodine-based products. Shunts were accessed using a 23 – 25-gauge needle, observing cerebrospinal fluid pressure and aspirate. The contrast agent most frequently used was 99mTc-diethylene-triamine-pentaacetate, although the exact volume injected was inconsistently reported. Imaging protocols were not standardized, with delayed imaging intervals usually ranging from 9 to 20 min. Failure criteria for shuntograms varied significantly, with limited guidance on follow-up interventions or troubleshooting. Notably, there was no mention of shunt reprogramming during these studies. This review highlights the significant variability in shuntogram techniques and outcomes. We present our institution’s protocol and a case scenario demonstrating successful implementation. With proper techniques and protocolization, shuntograms hold the potential as a valuable resource for accurately diagnosing shunt patency.

Comparative study of immunoassays, a microelectromechanical systems-based biosensor, and RT-QuIC for the diagnosis of chronic wasting disease in white-tailed deer

BackgroundChronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy in cervids. The disease is caused by a pathogenic prion, namely PrPSc. Currently, diagnosis of CWD relies on IHC detection of PrPSc in the obex or retropharyngeal lymph nodes (RPLN) or ELISA screening of obex and RPLN followed by IHC confirmation of positive results. In this study, we assessed the performance characteristics of two immunoassays: CWD Ag-ELISA and TeSeE ELISA, RT-QuIC, and MEMS biosensor via testing 30 CWD + and 30 CWD- white-tailed deer RPLN samples.ResultsBoth CWD Ag-ELISA and TeSeE ELISA correctly identified all CWD + and CWD- samples. A greater intra-assay coefficient of variation (CV) in S/P ratios was observed for the TeSeE ELISA (16.52%), compared to CWD Ag-ELISA (9.49%). However, the high CV did not affect the qualitative results of triplicate assays when the corresponding manufacturer’s cutoff was used. The MEMS biosensor not only correctly identified all CWD + and CWD- RPLN samples, but also demonstrated a 100% detection rate for all CWD + samples at dilutions from 10− 0 to 10− 3. Evaluation of RT-QuIC indicated that the rate of false negative reactions decreased from 21.98% at 10− 2 dilution to 0% at 10− 4 and 10− 5 dilutions; and the rate of false positive reactions reduced from 56.42% at 10− 2 dilution to 8.89% and 2.22% at 10− 4 and 10− 5 dilutions, respectively. Based on a stringent threshold of 2 x the first 10 fluorescent readings of each well and a final cutoff of 2/3 positive reactions for each sample, RT-QuIC correctly identified all positive and negative samples at 10− 4 and 10− 5 dilutions. Both MEMS biosensor and RT-QuIC achieved 100% sensitivity and 100% specificity under the experimental conditions described in this study.ConclusionsThe two immunoassays (CWD Ag-ELISA and TeSeE ELISA) performed comparably on white-tailed deer RPLN samples. MEMS biosensor is a reliable portable tool for CWD diagnosis and RT-QuIC can be used for routine testing of CWD if appropriate testing parameters and interpretive criteria are applied.

Evaluation of serum protein electrophoresis and immunofixation in dogs seropositive for various vector-borne pathogens.

Canine vector-borne diseases (VBDs) induce non-specific dysproteinemias, detectable by serum protein electrophoresis (SPE). VBDs have been reported to induce a monoclonal gammopathy pattern. Monoclonal gammopathies are commonly the result of paraprotein (M-protein) produced by an immunoglobulin-secreting neoplasm. The aims of this study were to characterize and compare SPE and immunofixation (IF) changes, evaluate the performance of previously identified SPE and IF interpretative criteria, and identify M-proteins in a cohort of dogs seropositive for a VBD and with an unknown history for an immunoglobulin-secreting neoplasm. A total of 143 serum samples from dogs that tested seropositive for different vector-borne pathogens were assessed by SPE. Cases with abnormal globulin fractions were further characterized by IF. Protein fraction and IF labeling results were evaluated using Kruskal-Wallis with Dunn's multiple comparisons and principal component analysis (PCA). IF was performed in 112 VBD-seropositive samples with dysproteinemia evaluated by SPE. Most (84/112, 75%) had a polyclonal expansion. Only two dogs had findings suggestive of an M-protein when considering both SPE and immunofixation. PCA clustered E.canis/A.phagocytophilum and B.gibsoni/CM.haematoparvum groups with relatively more γ-globulins than albumin and α-globulins, and the B.gibsoni/CM.haematoparvum group with more prominent IgA and IgM labeling than IgG labeling. Additionally, D.immitis clustered with more prominent β-globulins than γ-globulins and more IgG4 than IgG-FC. The previously derived interpretative criteria suggested an M-protein in very few VBD-seropositive dogs. PCA identified SPE and immunofixation pattern differences between dogs seropositive for different infectious agents.

Natural Cover suppression patterns used in PRODES Caatinga mapping

Abstract. Since 2022, we have mapped native vegetation removal for all Brazilian biomes within the scope of the PRODES Project. In this study, our main objective was to present interpretation criteria for feature detection used to identify natural vegetation removal throughout the Caatinga. To this end, we created a catalog of typical patterns that can be used for supervised and unsupervised deforestation mapping. We used PRODES data from 2023 year's PRODES Caatinga based on the composition of top of atmosphere (TOA) reflectance images from MSI/Sentinel-2 satellite. The original reflectance data was used to generate false color images in the following combination: band 8 (Red), band 11 (Green) and band 4 (Blue). This image was then visually classified into different natural vegetation removal classes. These are good examples of what PRODES interpreters have encountered throughout this diverse region and can help any future mapping efforts of the Caatinga.

Fosfomycin-Overcoming Problematic In Vitro Susceptibility Testing and Tricky Result Interpretation: Comparison of Three Fosfomycin Susceptibility Testing Methods.

Background: Fosfomycin (FOS) is an older antimicrobial agent newly rediscovered as a possible treatment for infections with limited therapeutic options (e.g., Gram-negative bacteria with difficult-to-treat resistance, DTR), especially in intravenous form. However, for correct usage of FOS, it is necessary to have a reliable susceptibility testing method suitable for routine practice and robust interpretation criteria. Results: The results were interpreted according to 2023 interpretation criteria provided by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). DTR Gram-negatives were more likely to be resistant to FOS (45% in Enterobacterales and 20% in P. aeruginosa) than non-DTR (10% and 6.7%, resp.). All isolates of S. aureus were susceptible to FOS. In Gram-negatives, all agreement values were unacceptable. Etest® performed better in the DTR cohort (categorical agreement, CA, 80%) than in the non-DTR cohort (CA 45.7%). There were no very major errors (VREs) observed in P. aeruginosa. S. aureus had surprisingly low essential agreement (EA) rates (53% for MRSA and 47% for MSSA) for Etest®, but categorical agreement was 100%. Methods: A total of 130 bacterial isolates were tested and compared using the disc diffusion method (DD) and gradient strip method (Etest®) with the reference method (agar dilution, AD). The spectrum of isolates tested was as follows: 40 Enterobacterales (20 DTR vs. 20 non-DTR), 30 Pseudomonas aeruginosa (15 DTR vs. 15 non-DTR), and 60 Staphylococcus aureus (30 methicillin-susceptible, MSSA, vs. 30 methicillin-resistant, MRSA). Conclusions: Neither one of the tested methods was identified as a suitable alternative to AD. It would be beneficial to define more interpretation criteria, at least in some instances.

Being and Becoming of Music: Limits of Thought and Practice

According to musicologist Christopher Small, the treatment of music in musicology carries fundamentally flawed historical premises. Instead of focusing on music through art „objects“, anything understood as „music“ should be examined on the grounds of its spatiotemporal appearance, as a social activity of musicking and the unfolding event. The emphasis of the verb „musicking“ instead of the substantive „music“ signifies a reinterpretation of a static into a processual concept. According to Small, musical meaning is formed with regards to the time and space of the immersive situation and the bodily encounter of participating individuals. This processual intervention over existing musical concepts through reinterpretation as „musicking“ opens the door to a broader philosophical scope. In order to approach two seemingly opposed interpretations of the subject matter mentioned above, I will attempt a reinterpretation of Small with reference to Arthur Schopenhauer’s concept of the „Will“, but with a more detailed emphasis on the expanded principle of the „Dyonisian“ and „Apollonian“ as suggested by Friedrich Nietzsche. I will further suggest some criteria for interpretation of any potential „musicking“ through several points of contention between Small’s musicology and Nietzsche’s philosophy. For this, I will utilize Nietzsche’s philosophical opposition between Being and Becoming serving as foundations of knowledge and art. The suggestion is that, while the entanglement of the Apollonian „image“ and the Dyonisian „rush“ enables the emergence of music as art, the foundation of Small’s „musicking“ lies in the non-ethical character of the Dyonisian—in what lies „behind“ the phenomenon and conceptualization of it. This ultimately questions the implication of music „as“ art, as it suggests that any justification thereof can not be considered outside of the subjective disposition encountering the event, nor beyond the individual disposition emerging within it. „Musicking“ doesn’t emerge with any cultural, social, symbolic or teleological purpose, but attains any one of these as soon as it’s designated „as-such“ by those principles that enable the concept to emerge in the first place. This, despite its broadly influential treatise, ultimately reveals the limits of Small’s „musicking“.

The InVitro Activity of Rezafungin Against Uncommon Species of Candida.

Invasive candidiasis (IC) is increasing due to the rising numbers of immunocompromised patients. Increasing azole resistance rates and daily dosing required for most echinocandins have complicated its treatment. The approval of rezafungin has provided an option for weekly echinocandin treatment. The susceptibility of less common Candida spp. to rezafungin is unclear. We looked at the minimum inhibitory concentrations (MICs) of rezafungin and comparator agents against Candida spp. collected as part of a global surveillance program. The CLSI reference broth microdilution method was performed to test 590 clinical isolates of 28 different Candida species, including Candida auris. Species-specific interpretative criteria by breakpoints or epidemiological cutoff values were applied where available. Rezafungin was within ±2-fold MIC50/90 values of other echinocandins against all Candida spp. The lowest rezafungin MIC50/90 values were noted against C. kefyr (0.03/0.06 mg/L) and C. pelliculosa (0.015/0.03 mg/L). Higher rezafungin MIC50/90 values were noted for C. guilliermondii (1/1 mg/L) and for isolates in the C. parapsilosis complex (C. orthopsilosis, 0.5/1 mg/L, C. metapsilosis, 0.12/0.5 mg/L). Rezafungin was active against 97.7% of C. dubliniensis and 95.4% of C. auris by CLSI breakpoints. For fluconazole, 69.7% of C. guilliermondii, 85.7% of C. orthopsilosis, and 100% of C. metapsilosis were wildtype by ECV, and 10.8% of C. auris were susceptible by CDC breakpoint. Rezafungin was highly active by invitro testing against less common Candida spp. Rezafungin MICs were comparable to other echinocandins. Rezafungin is a desirable therapeutic alternative due to its reduced dosing frequency.

Standardization of criteria for interpreting the results of mutagenicity assessment in the Ames test

Introduction. Currently, various combinations of criteria for interpreting the results are used to make a conclusion about the mutagenic activity in the Ames test. In some cases where weak effects are present, especially when evaluating the mutagenicity of generic pesticides that may contain mutagenic impurities, different conclusions are possible, depending on the criteria chosen. Material and methods. To standardize the criteria for interpreting the results in the Ames test, data obtained earlier in the assessment of the mutagenic activity of technical pesticide products were used. The studies were carried out in accordance with the OECD Standard Protocol No. 471 and State Standard (Russian: ГОСТ) 32376–2013 by direct application to the plate and under pre-incubation conditions. Results. The applicability of three combinations of criteria for interpretation of Ames test results was evaluated using our own previously obtained experimental data. It was established that as criteria of biological significance of the results of mutagenicity evaluation in the Ames test it is reasonable to use not only the conservative approach based on the fold increase rule, but also to compare them with the data of the ranges of historical negative laboratory control. Limitations. The study is limited to evaluating the results of experiments obtained using the standard plate test, but not the fluctuation format. Conclusion. A conclusion about the presence of mutagenic activity of the test item in the Ames test can be made if the following criteria are fulfilled: the presence of a statistically significant increase in the number of revertants on the plates with the test item compared to the concomitant negative control; the presence of a concentration-effect relationship; the mean number of revertants for at least one of the concentrations tested, with or without metabolic activation, must exceed the upper limit of the distribution of the historical negative laboratory control; the number of revertants on the plates with the test item must be 2 or more times compared to that one in the negative control for TA97, TA98, TA100, TA102 and 3 or more for TA1535; the reproducible effects.

Issues with Cefiderocol Testing: Comparing Commercial Methods to Broth Microdilution in Iron-Depleted Medium-Analyses of the Performances, ATU, and Trailing Effect According to EUCAST Initial and Revised Interpretation Criteria.

The rise of multi-drug-resistant Gram-negative bacteria necessitates the development of new antimicrobial agents. Cefiderocol shows promising activity by exploiting bacterial iron transport systems to penetrate the outer membranes of resistant pathogens. This study evaluates the efficacy of cefiderocol testing methods and trailing effect impact using a ComASP® Cefiderocol panel, disk diffusion (DD), and MIC test strips (MTS) compared to iron-depleted broth microdilution (ID-BMD). A total of 131 Gram-negative strains from clinical samples was tested by commercial methods and the gold standard. Results were interpreted as per 2024 and 2023 EUCAST guidelines. ID-BMD revealed high cefiderocol susceptibility among Enterobacterales and Pseudomonas aeruginosa, with one Klebsiella pneumoniae isolate being resistant. Acinetobacter baumannii exhibited higher MIC values, particularly considering trailing effects that complicated MIC readings. ComASP® showed 97% categorical agreement (CA) and 66% essential agreement (EA) with ID-BMD for Enterobacterales but failed to detect the resistant K. pneumoniae. DD tests demonstrated variable CA (72% or 93%), and 38% or 34% of strains within the ATU according to EUCAST Breakpoint Tables v13.0 and 14.0, respectively, with major errors only. MTS for P. aeruginosa had 100% CA but 44% EA, and often underestimated MIC values. The study emphasizes the need for standardized criteria to address trailing effects and ATU and highlights the discrepancies between testing methods. While cefiderocol resistance remains rare, accurate susceptibility testing is crucial for its effective clinical use. The findings suggest that current commercial tests have limitations, necessitating careful interpretation and potential supplementary testing to guide appropriate antibiotic therapy.

EANM/SNMMI guideline/procedure standard for [18F]FDG hybrid PET use in infection and inflammation in adults v2.0.

Hybrid [18F]FDG PET imaging is currently the method of choice for a wide variety of infectious and inflammatory disorders and was recently adopted in several clinical guidelines. A large amount of evidence-based articles, guidelines and appropriate use criteria have been published since the first version of this guideline in 2013. To provide updated evidence-based information to assist physicians in recommending, performing and interpreting hybrid [18F]FDG PET examinations for infectious and inflammatory disorders in the adult population. A systematic literature search of evidence-based articles using whole-body [18F]FDG hybrid imaging on the indications covered within this guideline was performed. All systematic reviews and meta-analyses published within the last 10 years until January 2023 were identified in PubMed/Medline or Cochrane. For each indication covered in this manuscript, diagnostic performance was provided based on meta-analyses or systematic reviews. If not available, results from prospective or retrospective studies were considered based on predefined selection criteria. RESULTSAND CONCLUSIONS: Hybrid [18F]FDG PET is extremely useful in the work-up and management of adults with infectious and inflammatory diseases, as supported by extensive and rapidly growing evidence-based literature and adoption in clinical guidelines. Practical recommendations are provided describing evidence-based indications as well as interpretation criteria and pitfalls.Monitoring treatment response is the most challenging but insufficiently studied potential application in infection and inflammation imaging.

Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance.

SUMMARYAntibiotic treatment failures in the absence of resistance are not uncommon. Recently, attention has grown around the phenomenon of antibiotic tolerance, an underappreciated contributor to recalcitrant infections first detected in the 1970s. Tolerance describes the ability of a bacterial population to survive transient exposure to an otherwise lethal concentration of antibiotic without exhibiting resistance. With advances in genomics, we are gaining a better understanding of the molecular mechanisms behind tolerance, and several studies have sought to examine the clinical prevalence of tolerance. Attempts have also been made to assess the clinical significance of tolerance through in vivo infection models and prospective/retrospective clinical studies. Here, we review the data available on the molecular mechanisms, detection, prevalence, and clinical significance of genotypic tolerance that span ~50 years. We discuss the need for standardized methodology and interpretation criteria for tolerance detection and the impact that methodological inconsistencies have on our ability to accurately assess the scale of the problem. In terms of the clinical significance of tolerance, studies suggest that tolerance contributes to worse outcomes for patients (e.g., higher mortality, prolonged hospitalization), but historical data from animal models are varied. Furthermore, we lack the necessary information to effectively treat tolerant infections. Overall, while the tolerance field is gaining much-needed traction, the underlying clinical significance of tolerance that underpins all tolerance research is still far from clear and requires attention.

Évaluation de la réponse thérapeutique par TEP-FDG des cancers solides (critères PERCIST 1.0)

18F-Fluoro-Deoxyglucose (FDG) Positron Emission Tomography (PET) is an imaging technique used to study glucose metabolism in cells. It is particularly useful in oncology, especially for initial diagnosis and the detection of recurrence. Thanks to its functional approach to tissues, its use has evolved towards the evaluation of anticancer treatments, both in a personalized approach to patients and as part of clinical trials of new biotherapies. This technique provides additional information compared to conventional imaging, which is not always able to assess tumor viability of potentially necrotic or fibrotic residual masses after treatment. However, the use of FDG-PET requires a rigorous methodology, both for the performance of the studies and for their interpretation. Based on a large body of literature, interpretation criteria for solid tumors have been published and updated. PERCIST 1.0 (Positron Emission Tomography Response Criteria In Solid Tumors), proposed by an American task force in 2009, aims to clarify and standardize practice. These criteria will evolve according to the specificities of new biotherapies such as immunotherapy.

PENGEMBANGAN MEDIA PEMBELAJARAN MENTARI TERHADAP KEMAMPUAN PEMECAHAN MASALAH MATEMATIS KELAS IV SEKOLAH DASAR

This study aims to develop MENTARI learning media (E-Module in the Form of Flipbook Maker Flat Buildings Based on Ethno-Mathematics) for the Mathematical problem-solving abilities of grade IV SD 1 Mejobo. Flipbook maker media can present learning materials in the form of words, sentences, pictures, and animations which can be equipped with colors. This study applied a research and development approach. The data collection instruments were interview, observation, documentation, and test methods, with quantitative data analysis techniques. Quantitative data analysis through validation data analysis, normality tests, and N Gain Tests. The normality test of pretest and posttest data is normally distributed, because the pretest significance is 0.209>0.05 and the posttest significance is 0.917>0.05. In this test, the N-Gain results obtained were an average increase of 0.69 with the "moderate" category. The conclusions of this study are: (1) the average score of the material validity test is 93% also with the "very feasible" feasibility category; (2) Based on the questionnaire responses from 15 fourth grade students, the average score was 92% with the category "very appropriate"; (3) the average N-Gain percentage was 69.20% with the effectiveness interpretation criteria of "quite effective".

Development of Problem-Based Learning E-LKPD for Digital-Based Document

This research was conducted to determine the level of feasibility, student response, and the impact of students' critical thinking on the developed E-LKPD. The research was carried out using R&D (Research and Development) with the 4D development model from Thiagarajan. However, the researchers only conducted preliminary research in the define, design, and develop stages due to time constraints and the scope of the learning outcomes discussed. The average overall score obtained from the validation assessment by experts was 82%, using the interpretation criterion "Very Feasible". The student response questionnaire resulted in an overall score of 87% for the aspects of content, media, and the benefits of developing E-LKPD. Therefore, it can be concluded that the development of E-LKPD based on problem-based learning is highly feasible for use as a supporting teaching material in teaching and learning activities.

ENOVAT: the European Network for Optimization of Veterinary Antimicrobial Treatment

The global antimicrobial resistance crisis has been the driver of several international strategies on antimicrobial stewardship. For their implementation at the field level, the veterinary sector encounters several specific challenges and in particular: (i) a shortage of experts in key disciplines related to antimicrobial stewardship, (ii) a lack of evidence-based antimicrobial treatment guidelines, and (iii) inferior diagnostic tests available compared to human medicine. The present white paper describes how the COST Action ENOVAT (the European Network for Optimization of Veterinary Antimicrobial Treatment, CA18217), comprising 332 persons from 51 countries, worked towards solutions to these challenges. Initially, surveys were conducted to explore the present state in Europe in terms of existing antimicrobial use guidelines and microbiology practices performed. Concurrently, various research activities were launched to optimize diagnostics, including development of epidemiological cut-offs, clinical breakpoints and matrix-assisted laser desorption ionization time of flight mass spectrometry interpretive criteria. Also, guidelines drafting groups working towards evidence-based antimicrobial treatment guidelines for six conditions in food-producing and companion animals were established. The processes and outcomes, also in terms of capacity building, are summarized in this white paper where emphasis is placed on sustainability of the activities. Although several ENOVAT initiatives and spin-off projects will continue beyond the Action, we recommend that a new European veterinary research agenda is launched focusing on research and funding leading to long-term impacts on veterinary antimicrobial use.

Development of 18F-Fluoromisonidazole Hypoxia PET/CT Diagnostic Interpretation Criteria and Validation of Interreader Reliability, Reproducibility, and Performance.

Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with 18F-fluoromisonidazole (18F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret 18F-FMISO hypoxia PET. Methods: We randomly selected 123 patients with human papillomavirus-positive oropharyngeal cancer enrolled in a phase II trial who underwent 123 18F-FDG PET/CT and 134 18F-FMISO PET/CT scans. Four independent nuclear medicine physicians with no 18F-FMISO experience read the scans. Interpretation by a fifth nuclear medicine physician with over 2 decades of 18F-FMISO experience was the reference standard. Performance was evaluated after initial instruction and subsequent dedicated training. Scans were considered positive for hypoxia by visual assessment if 18F-FMISO uptake was greater than floor-of-mouth uptake. Additionally, SUVmax was determined to evaluate whether quantitative assessment using tumor-to-background ratios could be helpful to define hypoxia positivity. Results: Visual assessment produced a mean sensitivity and specificity of 77.3% and 80.9%, with fair interreader agreement (κ = 0.34), after initial instruction. After dedicated training, mean sensitivity and specificity improved to 97.6% and 86.9%, with almost perfect agreement (κ = 0.86). Quantitative assessment with an estimated best SUVmax ratio threshold of more than 1.2 to define hypoxia positivity produced a mean sensitivity and specificity of 56.8% and 95.9%, respectively, with substantial interreader agreement (κ = 0.66), after initial instruction. After dedicated training, mean sensitivity improved to 89.6% whereas mean specificity remained high at 95.3%, with near-perfect interreader agreement (κ = 0.86). Conclusion: Nuclear medicine physicians without 18F-FMISO hypoxia PET reading experience demonstrate much improved interreader agreement with dedicated training using specific interpretation criteria.

Additional reporting of diffuse and homogeneous ROS-1 SP384 immunoreactivity enhances prediction of ROS1 fusion-positive non-small cell lung cancer.

ROS-1 immunohistochemistry (IHC) is a common method for screening ROS1 fusion in the clinical management of non-small cell lung cancer. The interpretation criteria for ROS-1 SP384 IHC, however, remain unestablished. Sixty-five non-small cell lung cancer cases underwent AmoyDx ROS1 fusion real-time polymerase chain reaction (PCR) study and ROS-1 SP384 IHC tests, which were retrieved for analysis. ROS-1 IHC tests were interpreted based on the established classifiers as well as the presence of diffuse homogeneous immunoreactivity. The diagnostic accuracies of these ROS-1 IHC interpretation methods were evaluated by comparing them with the ROS1 real-time PCR results. Previous ROS-1 IHC classifiers demonstrated high sensitivity for positive ROS1 real-time PCR results (100%), but they showed low specificities (25%-50%) and overall accuracies (58%-72%). In contrast, the diffuse homogeneous ROS-1 immunoreactivity predicted positive ROS1 real-time PCR results with much higher specificity (94%) and overall accuracy (95%), albeit with a slightly lower sensitivity (97%). Some cases that showed discrepancy between diffuse homogeneous ROS-1 immunoreactivity and real-time PCR results involved rare ROS1::LDLR fusion and suboptimal IHC staining. A 3-tier reporting system for ROS-1 SP384 IHC testing combining previous interpretation criteria and diffuse and homogeneous immunoreactivity may better predict ROS1 fusion status without decreasing specificity.