T2Candida Assay in the Diagnosis of Intraabdominal Candidiasis: A Prospective Multicenter Study

The T2Candida magnetic resonance assay is a direct-from-blood pathogen detection assay that delivers a result within 3–5 h, targeting the most clinically relevant Candida species. Between February 2019 and March 2021, the study included consecutive patients aged >18 years admitted to an intensive care unit or surgical high-dependency unit due to gastrointestinal surgery or necrotizing pancreatitis and from whom diagnostic blood cultures were obtained. Blood samples were tested in parallel with T2Candida and 1,3-β-D-glucan. Of 134 evaluable patients, 13 (10%) were classified as having proven intraabdominal candidiasis (IAC) according to the EORTC/MSG criteria. Two of the thirteen patients (15%) had concurrent candidemia. The sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were 46%, 97%, 61%, and 94% for T2Candida and 85%, 83%, 36%, and 98% for 1,3-β-D-glucan. All positive T2Candida results were consistent with the culture results at the species level, except for one case of dual infection. The performance of T2Candida was comparable with that of 1,3-β-D-glucan for candidemic IAC but had a lower sensitivity for non-candidemic IAC (36% vs. 82%). In conclusion, T2Candida may be a valuable complement to 1,3-β-D-glucan in the clinical management of high-risk surgical patients because of its rapid results and ease of use.

Use of Circulating Tumour DNA (ctDNA) for Measurement of Therapy Predictive Biomarkers in Patients with Cancer

Biomarkers that predict likely response or resistance to specific therapies are critical in personalising treatment for cancer patients. Such biomarkers are now available for an increasing number of anti-cancer therapies, especially targeted therapy and immunotherapy. The gold-standard method for determining predictive biomarkers requires tumour tissue. Obtaining tissue, however, is not always possible and even if possible, the amount or quality of tissue obtained may be inadequate for biomarker analysis. Tumour DNA, however, can be released into the bloodstream, giving rise to what is referred to as circulating tumour DNA (ctDNA). In contrast to tissue, blood can be obtained from effectively all patients in a minimally invasive and safe manner. Other advantages of blood over tissue for biomarker testing include a shorter turn-around time and an ability to perform serial measurements. Furthermore, blood should provide a more complete profile of mutations present in heterogeneous tumours than a single-needle tissue biopsy. A limitation of blood vis-à-vis tissue, however, is lower sensitivity and, thus, the possibility of missing an actionable mutation. Despite this limitation, blood-based predictive biomarkers, such as mutant EGFR for predicting response to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer and mutant PIK3CA for predicting response to alpelisib in combination with fulvestrant in advanced breast cancer, may be used when tissue is unavailable. Although tissue remains the gold standard for detecting predictive biomarkers, it is likely that several further blood-based assays will soon be validated and used when tissue is unavailable or unsuitable for analysis.

Development and Clinical Validation of a Potential Penside Colorimetric Loop-Mediated Isothermal Amplification Assay of Porcine Circovirus Type 3

Porcine circovirus type 3 (PCV3), a novel circovirus, imposes great burdens on the global pig industry. The penside tests for detecting PCV3 are critical for assessing the epidemiological status and working out disease prevention and control programs due to the unavailability of a commercial vaccine. A one-step molecular assay based on visual loop-mediated isothermal amplification (vLAMP) was developed for simple and rapid detection of PCV3. We compared its sensitivity and specificity with TaqMan quantitative real-time polymerase chain reaction (qPCR) and applied the developed assay in the epidemiological study of (n = 407) pooled swine sera collected from almost the entire mainland China during the years 2017–2018. We also explored the feasibility of the vLAMP assay for detecting raw samples without a prior DNA isolation step to expand its application capability. Results showed that the vLAMP assay could reliably detect the PCV3 cap gene with a detection limit of 10 DNA copies equal to that of the Taqman qPCR assay. In the epidemiological study, the PCV3 positive detection rate for 407 swine pooled sera detected by the vLAMP assay was 37.35% (152/407), whereas it was 39.01% (159/407) for Taqman qPCR. For the detection method without genome extraction, the results kept satisfactory specificity (100%) but displayed lower sensitivity (100% for CT < 32), indicating the direct detection is not sensitive enough to discriminate the samples with low viral loads. The one-step vLAMP is a convenient, rapid, and cost-effective diagnostic for penside detection and will enable the epidemiological surveillance of PCV3, which has widely spread in mainland China.

Heterogeneity of Prevalence of Social Media Addiction Across Multiple Classification Schemes: Latent Profile Analysis

Background As social media is a major channel of interpersonal communication in the digital age, social media addiction has emerged as a novel mental health issue that has raised considerable concerns among researchers, health professionals, policy makers, mass media, and the general public. Objective The aim of this study is to examine the prevalence of social media addiction derived from 4 major classification schemes (strict monothetic, strict polythetic, monothetic, and polythetic), with latent profiles embedded in the empirical data adopted as the benchmark for comparison. The extent of matching between the classification of each scheme and the actual data pattern was evaluated using sensitivity and specificity analyses. The associations between social media addiction and 2 comorbid mental health conditions—depression and anxiety—were investigated. Methods A cross-sectional web-based survey was conducted, and the replicability of findings was assessed in 2 independent samples comprising 573 adults from the United Kingdom (261/573, 45.6% men; mean age 43.62 years, SD 12.24 years) and 474 adults from the United States (224/474, 47.4% men; mean age 44.67 years, SD 12.99 years). The demographic characteristics of both samples were similar to those of their respective populations. Results The prevalence estimates of social media addiction varied across the classification schemes, ranging from 1% to 15% for the UK sample and 0% to 11% for the US sample. The latent profile analysis identified 3 latent groups for both samples: low-risk, at-risk, and high-risk. The sensitivity, specificity, and negative predictive values were high (83%-100%) for all classification schemes, except for the relatively lower sensitivity (73%-74%) for the polythetic scheme. However, the polythetic scheme had high positive predictive values (88%-94%), whereas such values were low (2%-43%) for the other 3 classification schemes. The group membership yielded by the polythetic scheme was largely consistent (95%-96%) with that of the benchmark. Conclusions Among the classification schemes, the polythetic scheme is more well-balanced across all 4 indices.

Global prevalence and epidemiology of Strongyloides stercoralis in dogs: a systematic review and meta-analysis

Background Strongyloides stercoralis, a soil-transmitted helminth, occurs in humans, non-human primates, dogs, cats and wild canids. The zoonotic potential between these hosts is not well understood with data available on prevalence primarily focused on humans. To increase knowledge on prevalence, this review and meta-analysis was performed to estimate the global status of S. stercoralis infections in dogs. Methods Following the PRISMA guidelines, online literature published prior to November 2020 was obtained from multiple databases (Science Direct, Web of Science, PubMed, Scopus and Google Scholar). Prevalence was calculated on a global and country level, by country income and climate, and in stray/animal shelter dogs versus owned dogs. Statistical analyses were conducted using R-software (version 3.6.1). Results From 9428 articles, 61 met the inclusion criteria. The estimated pooled global prevalence of S. stercoralis in dogs was 6% (95% CI 3–9%). Infection was found to be the most prevalent in low-income countries with pooled prevalence of 22% (95% CI 10–36%). The highest pooled prevalence of S. stercoralis in dogs was related to regions with average temperature of 10–20 °C (6%; 95% CI 3–11%), an annual rainfall of 1001–1500 mm (9%; 95% CI 4–15%) and humidity of 40–75% (8%; 95% CI 4–13%). Prevalence was higher in stray and shelter dogs (11%; 95% CI 1–26%) than in owned dogs (3%; 95% CI 1–7%). Conclusions As with S. stercoralis in humans, higher prevalence in dogs is found in subtropical and tropical regions and lower-income countries, locations which also can have high dog populations. While this study presents the first estimated global prevalence of S. stercoralis in dogs, it is potentially an underestimation with 15 of 61 studies relying on diagnostic methods of lower sensitivity and a paucity of data from most locations. Standardized protocols (e.g. quantity of feces and number of samples for a Baermann) in future studies could improve reliability of results. More prevalence studies and raising veterinary awareness of S. stercoralis are needed for a One Health approach to protect humans and dogs from the impact of the infection. Graphical Abstract

Development and testing of an additively manufactured lattice for DEMO limiters

In the conceptual design of EU-DEMO, damage to plasma-facing components under disruption events is planned to be mitigated by specific sacrificial limiter components. A new limiter concept has been proposed using lattice structures fabricated with tungsten powder by additive manufacturing techniques. The major potential benefits of using a lattice structure for limiters are the possibility to customise the thermal conductivity and structural compliance of the structure to manage temperatures and stress within material limits and lower sensitivity to crack propagation. This paper presents the results of the first investigations into the production, characterisation, and high heat flux testing of the lattices to assess their suitability for DEMO limiters. First stage prototypes have been manufactured from tungsten and tungsten tantalum mixed powder with two distinct laser power bed fusion processes, namely pulsed laser and continuous laser with heated bed. The samples are characterised in terms of mass, volume, density, extent of microcracks and voids, level of un-melted or partially melted particulates, texture and grain size, as well as tantalum segregation when applicable. High transient (0.25ms) heat load testing, with hydrogen plasma of energy density up to ~3 MJm-2 was carried out at KIPT on the QSPA Kh-50. These tests have shown that the energy absorbed by latticed targets preheated at 500°C is close to that absorbed by solid tungsten, suggesting that they may be used for limiter applications with the added advantage of adjustment of the heat transfer and stiffness performance by geometry design or material properties.

Bacteroides Microbial Source Tracking Markers Perform Poorly in Predicting Enterobacteriaceae and Enteric Pathogen Contamination of Cow Milk Products and Milk-Containing Infant Food

Consumption of microbiologically contaminated food is one of the leading causes of diarrheal diseases. Understanding the source of enteric pathogens in food is important to guide effective interventions. Enterobacteriaceae bacterial assays typically used to assess food safety do not shed light on the source. Source-specific Bacteroides microbial source tracking (MST) markers have been proposed as alternative indicators for water fecal contamination assessment but have not been evaluated as an alternative fecal indicator in animal-derived foods. This study tested various milk products collected from vendors in urban Kenyan communities and infant foods made with the milk (n = 394 pairs) using conventional culture methods and TaqMan qPCR for enteric pathogens and human and bovine-sourced MST markers. Detection profiles of various enteric pathogens and Bacteroides MST markers in milk products differed from that of milk-containing infant foods. MST markers were more frequently detected in infant food prepared by caregivers, indicating recent contamination events were more likely to occur during food preparation at home. However, Bacteroides MST markers had lower sensitivity in detecting enteric pathogens in food than traditional Enterobacteriaceae indicators. Bacteroides MST markers tested in this study were not associated with the detection of culturable Salmonella enterica and Shigella sonnei in milk products or milk-containing infant food. The findings show that while Bacteroides MST markers could provide valuable information about how foods become contaminated, they may not be suitable for predicting the origin of the enteric pathogen contamination sources.

Meta-analysis of the diagnostic performance of serum carbohydrate antigen 19-9 for the detection of gallbladder cancer

Introduction Carbohydrate antigen 19-9 (CA19-9) is a well-studied tumor marker, yet its diagnostic value for gallbladder cancer remains unclear. The present meta-analysis was conducted to validate the role of serum CA19-9 for the detection of gallbladder cancer. Methods A systematic search of digital databases was conducted, complemented by additional hand-searching. Studies that reported serum CA19-9 for the differentiation of gallbladder cancer cases from non-gallbladder cancer controls were considered eligible. Results A total of 27 studies involving 4300 subjects were included. The pooled sensitivity, specificity, and area under the curve in diagnosing gallbladder cancer were 0.70 (95% confidence interval (CI): 0.63–0.76), 0.92 (95% CI: 0.88–0.94), and 0.89 (95% CI: 0.86–0.92), respectively. The pooled positive likelihood rate, negative likelihood rate, and diagnostic odds rate were 8.30 (95% CI: 5.84–11.69), 0.33 (95% CI: 0.27–0.41), and 25.13 (95% CI: 5.83–39.89), respectively. Meta-regression analysis revealed that there was significantly lower sensitivity (0.69, 95% CI: 0.61–0.77) and specificity (0.91, 95% CI: 0.87–0.95) when CA19-9 was used for the differentiation of gallbladder cancer cases from benign biliary diseases. A better specificity of 0.93 (95% CI: 0.90–0.96) was reached in the setting of a sample size ≥100. Conclusions Serum CA19-9 can be a potential candidate marker for the detection of gallbladder cancer, which maintains moderate sensitivity and good specificity. Attention should be paid to the control type and sample size, which may affect its diagnostic accuracy. Also, results should be interpreted with caution due to significant heterogeneity primarily caused by different thresholds between included studies.

The Application of Artificial Intelligence-Assisted Colposcopy in a Tertiary Care Hospital within a Cervical Pathology Diagnostic Unit

The rising global incidence of cervical cancer is estimated to have affected more than 600,000 women, and nearly 350,000 women are predicted to have died from the disease in 2020 alone. Novel advances in cancer prevention, screening, diagnosis and treatment have all but reduced the burden of cervical cancer in developed nations. Unfortunately, cervical cancer is still the number one gynecological cancer globally. A limiting factor in managing cervical cancer globally is access to healthcare systems and trained medical personnel. Any methodology or procedure that may simplify or assist cervical cancer screening is desirable. Herein, we assess the use of artificial intelligence (AI)-assisted colposcopy in a tertiary hospital cervical diagnostic pathology unit. The study group consisted of 48 women (mean age 34) who were referred to the clinic for a routine colposcopy by their gynecologist. Cervical images were taken by an EVA-Visualcheck TM colposcope and run through an AI algorithm that gave real-time binary results of the cervical images as being either normal or abnormal. The primary endpoint of the study assessed the AI algorithm’s ability to correctly identify histopathology results of CIN2+ as being abnormal. A secondary endpoint was a comparison between the AI algorithm and the clinical assessment results. Overall, we saw lower sensitivity of AI (66.7%; 12/18) compared with the clinical assessment (100%; 18/18), and histopathology results as the gold standard. The positive predictive value (PPV) was comparable between AI (42.9%; 12/28) and the clinical assessment (41.8%; 18/43). The specificity, however, was higher in the AI algorithm (46.7%; 14/30) compared to the clinical assessment (16.7%; 5/30). Comparing the congruence between the AI algorithm and histopathology results showed agreement 54.2% of the time and disagreement 45.8% of the time. A trained colposcopist was in agreement 47.9% and disagreement 52.1% of the time. Assessing these results, there is currently no added benefit of using the AI algorithm as a tool of speeding up diagnosis. However, given the steady improvements in the AI field, we believe that AI-assisted colposcopy may be of use in the future.

A Novel Real Time PCR Method for the Detection and Quantification of Didymella pinodella in Symptomatic and Asymptomatic Plant Hosts

Didymella pinodella is the major pathogen of the pea root rot complex in Europe. This wide host range pathogen often asymptomatically colonizes its hosts, making the control strategies challenging. We developed a real-time PCR assay for the detection and quantification of D. pinodella based on the TEF-1 alpha gene sequence alignments. The assay was tested for specificity on a 54-isolate panel representing 35 fungal species and further validated in symptomatic and asymptomatic pea and wheat roots from greenhouse tests. The assay was highly consistent across separate qPCR reactions and had a quantification/detection limit of 3.1 pg of target DNA per reaction in plant tissue. Cross-reactions were observed with DNA extracts of five Didymella species. The risk of cross contamination, however, is low as the non-targets have not been associated with pea previously and they were amplified with at least 1000-fold lower sensitivity. Greenhouse inoculation tests revealed a high correlation between the pathogen DNA quantities in pea roots and pea root rot severity and biomass reduction. The assay also detected D. pinodella in asymptomatic wheat roots, which, despite the absence of visible root rot symptoms, caused wheat biomass reduction. This study provides new insights into the complex life style of D. pinodella and can assist in better understanding the pathogen survival and spread in the environment.