False-positive Results Research Articles

How Much is Too Much? Evaluation of the Clinical Relevance of Routine Preoperative Investigations in American Society of Anaesthesiologist (ASA) Grades I and II Patients Undergoing Minor to Intermediate Elective Surgeries at Tertiary Care Teaching Hospital - Influence on Change in the Surgical Plan and Outcome

Abstract Background: In recent decades, experts have questioned the necessity of routine preoperative investigations due to their limited influence on perioperative management, higher expenses, postponed surgical procedures, patient anxiety resulting from false-positive results for minor operations and increased workload for laboratories. Objective: Our objective was to systematically evaluate the impact of pre-operative investigations on the treatment of patients opting for elective procedures. The study aimed to evaluate the impact of pre-operative investigations and peri-operative management on elective surgeries of the American Society of Anesthesiologists (ASA) physical status classification grades I and II, identifying common inappropriate investigations and assessing the impact of abnormal results on patient management. Materials and Methods: We conducted a prospective, cross-sectional, clinical, observational, single-centre study from February 2020 to March 2021 on 500 cases in the General Surgery Department of Tertiary Care Teaching Hospital. This study assessed the importance of pre-operative investigations in low-risk patients undergoing low-grade elective general surgical procedures. We recruited consecutive patients from the surgery wards of the institute, who fulfilled the inclusion criteria and obtained informed written consent for anaesthesia, surgery and participation in the study. Demographic data, the type of investigation conducted and test results were noted. We followed up with patients who had abnormal test results to record the consequences of the abnormality, such as the postponement of surgery and the requirement for additional investigations. Pre-operative transfusion, change in the management plan and change in the anaesthesia plan were recorded. Results: In the current study, the age of the patients ranged from 20 years to 45 years, and the mean age of the patients was 32.208 ± 9.16. The age group of 20–30 years was the commonest, being 158 (31.6%) patients. Out of 500 patients, 296 (59.2%) patients were males and the remaining 204 (40.8%) were female patients. Out of 500 tests, 44 (8.8%) had abnormal results. Most of the changes in our study were based on abnormal ECG findings. Out of a total of 500 surgical procedures performed, 497 (99.4%) were carried out without any difficulty, with two (0.4%) postponed due to abnormality in the pre-operative investigations and one (0.2%) cancelled. A total of 490 (98%) patients did not have any post-operative complications. Only ten (2%) patients developed post-operative complications, and out of those, only one (0.1%) had some abnormality in the pre-operative investigations. Conclusion: Preoperative laboratory investigations do not significantly influence the surgical outcome of the patients belonging to ASA grades I and II.

Investigation of suspected false positive norovirus results on a syndromic gastrointestinal multiplex molecular panel

BackgroundSuspected false positive norovirus results occurred after introduction of the BioFire® FilmArray® Gastrointestinal panel (BF-GIP) into 6 laboratory sites, in British Columbia, Canada. ObjectivesThe primary objective was to investigate suspected false positive results by performing additional molecular assays and whole genome sequencing (WGS). The second objective was to determine if melting curve review could predict false positive results. Study designFrom February 2023 to May 2024, the proportion of potential false positive norovirus results from the BF-GIP was calculated based on confirmatory testing using alternate molecular method. A subset of 65 norovirus BF-GIP positive specimens, including 35 negatives and 30 positives on additional molecular assays, underwent WGS. Melting curves appearances from 150 specimens were reviewed. ResultsOverall, 215/784 (27.4 %) BF-GIP norovirus results were suspected to be false positives. When using WGS, 64/65 results were in agreement with confirmatory testing. Notably, 35 specimens negative on confirmatory testing and suspected to be BF-GIP norovirus false positive results were undetectable by WGS. Melting curves did not accurately predict false positives, since 20/72 (27.8 %) had typical appearances upon review. ConclusionsBF-GIP produces false positive results for norovirus, which cannot be predicted by melting curve review.

Fermentation dynamics of bile salt hydrolase production in Heyndrickxia coagulans ATCC 7050 and Lactiplantibacillus plantarum ATCC 10012: Addressing ninhydrin assay limitations with a novel HPTLC–MS method

Bile salt hydrolase (BSH), a pivotal enzyme in cholesterol management, holds significant promise in both human and animal subjects. This study investigated the effect of fermentation dynamics in Heyndrickxia coagulans ATCC 7050 and Lactiplantibacillus plantarum ATCC 10012 to enhance BSH production. Cultivation of cultures in MRS and M17 media revealed that MRS medium enhanced BSH production by 235.98 % in H. coagulans ATCC 7050 and 147.37 % in L. plantarum ATCC 10012, compared to M 17 medium. Additionally, varying oxygen concentration levels indicated that H. coagulans ATCC 7050 exhibited its minimum doubling time of 79.8 ± 0.64 min in anaerobic conditions, whereas L.plantarum ATCC 10012 demonstrated its minimum doubling time of 85.5 ± 1.2 min under microaerophilic conditions. However, their highest BSH activity was observed during the stationary phase under anaerobic conditions, yielding 17.14 ± 0.78 U/mL by H. coagulans ATCC 7050 and 19.04 ± 0.81 U/mL by L.plantarum ATCC 10012. Furthermore, it was observed that both organisms did not retain BSH within their cells. BSH activity was assessed using ninhydrin assay that detected free taurine liberated from sodium taurocholate. However, ninhydrin can yield false–positive results owing to its interaction with other free amino acids. To subjugate this limitation, the study introduced a novel and sensitive HPTLC–MS method capable of accurately detecting taurine. By comprehending fermentation dynamics and selecting appropriate conditions, BSH production increased 2.1–fold in both organisms. These findings illuminate critical insights, offering a pathway for novel strategies to enhance the BSH–producing capabilities of these LAB strains.

Atomically Fe(Ⅲ) anchored metal-organic frameworks-based fluorescent nanozyme for smartphone-adopted chemiluminescence-fluorescence dual-mode analysis of Uric acid

BackgroundChemiluminescence (CL) analysis is a promising analytical method with advantages including easy operation, high sensitivity and simple instrument. However, the single CL mode usually suffered from poor stability and reproducibility as a result of the flash-type nature of luminescent molecules, leading to false positive or negative results in practical applications. Dual-mode detection is an advanced sensing methodology that identifies analytes through independent output signals. This approach has the ability to circumvent the inherent constraints of individual sensing modes while integrating their respective strengths, thereby yielding a synergistic enhancement in the detection system. ResultsHerein, a chemiluminescence-fluorescence (FL) dual-mode analysis and imaging system is designed by constructing an atomically Fe(Ⅲ) anchored PCN-224 peroxidase-mimicking nanozyme (PCN-224/Fe(Ⅲ)) and achieve an ultrasensitive detection of Uric Acid (UA). The multifunctional PCN-224/Fe(Ⅲ) serves as a high-efficiency co-reaction promoter in the generation of reactive oxygen species (ROS) in both the CL and FL system, while also demonstrating exceptional capabilities as fluorescent nanoprobes. Ultimately, a smartphone-adopted CL imaging device was developed to achieve a visual CL detection through the design of portable paper-based chips. Besides, with the assistance of the TMB-mediated fluorescence energy resonance transfer, the fluorescent PCN-224/Fe(Ⅲ) nanoprobes exhibited good fluorescence detection performance for UA. The limit of detection was achieved as low as 2.45 × 10−10 M and 1.99 × 10−9 M in the CL and FL mode, respectively. SignificanceThis study engineered an atomically Fe(Ⅲ)- MOF-based multifunctional nanozyme and developed an innovative approach for creating CL-FL dual-mode analysis and imaging detection for UA. The proposed CL-FL dual-mode detection system not only provided a portable and sensitive method for UA detection but also offered valuable insights into the mechanism of the co-reaction promoter enhanced CL and FL analysis.

Effective Laboratory Diagnosis of Parasitic Infections of the Gastrointestinal Tract: Where, When, How, and What Should We Look For?

(1) Introduction: Gastrointestinal parasites (GIPs) are one of the most common causes of disease in the world. Clinical diagnosis of most parasitic diseases is difficult because they do not produce characteristic symptoms. (2) Methods: The PubMed, Science Direct, and Wiley Online Library medical databases were reviewed using the following phrases: "parasitic infections and diagnostics", "intestinal parasites", "gastrointestinal parasites", "parasitic infections and diagnostics", and their combinations. (3) Results and Conclusions: Correct diagnosis of GIP involves determining the presence of a parasite and establishing a relationship between parasite invasion and disease symptoms. The diagnostic process should consider the possibility of the coexistence of infection with several parasites at the same time. In such a situation, diagnostics should be planned with consideration of their frequency in each population and the local epidemiological situation. The importance of the proper interpretation of laboratory test results, based on good knowledge of the biology of the parasite, should be emphasized. The presence of the parasite may not be causally related to the disease symptoms. Due to wide access to laboratories, patients often decide to perform tests themselves without clinical justification. Research is carried out using various methods which are often unreliable. This review briefly covers current laboratory methods for diagnosing the most common gastrointestinal parasitic diseases in Europe. In particular, we provide useful information on the following aspects: (i) what to look for and where to look for it (suitability of feces, blood, duodenal contents, material taken from endoscopy or biopsy, tissue samples, and locations for searching for eggs, cysts, parasites, parasite genetic material, and characteristics of immune responses indicating parasitic infections); (ii) when material should be collected for diagnosis and/or to check the effectiveness of treatment; (iii) how-that is, by what methods-laboratory diagnostics should be carried out. Here, the advantages and disadvantages of direct and indirect methods of detecting parasites will be discussed. False-positive or false-negative results are a problem facing many tests. Available tests have different sensitivities and specificities. Therefore, especially in doubtful situations, tests for the presence of the pathogen should be performed using various available methods. It is important that the methods used make it possible to distinguish an active infection from a past infection. Finally, we present laboratory "case reports", in which we will discuss the diagnostic procedure that allows for the successful identification of parasites. Additionally, we briefly present the possibilities of using artificial intelligence to improve the effectiveness of diagnosing parasitic diseases.

ASPYRE-Lung: validation of a simple, fast, robust and novel method for multi-variant genomic analysis of actionable NSCLC variants in FFPE tissue.

Genomic variant testing of tumors is a critical gateway for patients to access the full potential of personalized oncology therapeutics. Current methods such as next-generation sequencing are costly and challenging to interpret, while PCR assays are limited in the number of variants they can cover. We developed ASPYRE® (Allele-Specific PYrophosphorolysis REaction) technology to address the urgent need for rapid, accessible and affordable diagnostics informing actionable genomic target variants of a given cancer. The targeted ASPYRE-Lung panel for non-small cell carcinoma covers 114 variants in 11 genes (ALK, BRAF, EGFR, ERBB2, KRAS, RET, ROS1, MET & NTRK1/2/3) to robustly inform clinical management. The assay detects single nucleotide variants, insertions, deletions, and gene fusions from tissue-derived DNA and RNA simultaneously. We tested the limit of detection, specificity, analytical accuracy and analytical precision of ASPYRE-Lung using FFPE lung tissue samples from patients with non-small cell lung carcinoma, variant-negative FFPE tissue from healthy donors, and FFPE-based contrived samples with controllable variant allele fractions. The sensitivity of ASPYRE-Lung was determined to be ≤ 3% variant allele fraction for single nucleotide variants and insertions or deletions, 100 copies for fusions, and 200 copies for MET exon 14 skipping. The specificity was 100% with no false positive results. The analytical accuracy test yielded no discordant calls between ASPYRE-Lung and expected results for clinical samples (via orthogonal testing) or contrived samples, and results were replicable across operators, reagent lots, runs, and real-time PCR instruments with a high degree of precision. The technology is simple and fast, requiring only four reagent transfer steps using standard laboratory equipment (PCR and qPCR instruments) with analysis via a cloud-based algorithm. The ASPYRE-Lung assay has the potential to be transformative in facilitating access to rapid, actionable molecular profiling of tissue for patients with non-small cell carcinoma.

Assessment of Surface Sterilisation Approaches for the Removal of Pollen DNA from Philaenus spumarius.

Dietary analysis of herbivorous insects relies on successfully eliminating surface contamination. If this cannot be performed reliably, then it will not be possible to differentiate between plants that the insect is feeding on and plants the insect has been in contact with, either directly or via pollen. Methods in the literature often use bleach and alcohol washes to remove contamination. We perform a controlled metabarcoding baseline study on a herbivorous, xylem-feeding insect, the Meadow Spittlebug (Philaenus spumarius), using Oxford Nanopore Technologies (ONT) sequencing, and identify possible contamination that persists after washes. Despite the reported success of methods in the literature, we find that contamination is still present, leading to possible false-positive results. We hypothesise that pollen is the main source of contamination, its robust nature making it difficult to remove, and conduct a further three experiments with the goal of removing pollen from the surface of Philaenus spumarius. This study investigates the effectiveness of robust bleach/Tween/alcohol washes, sterile gut excision (including combined with Distel application), and ultraviolet light as alternative sterilisation approaches. Overall, our findings indicate that we are unable to remove surface contamination and still detect signals that may originate in the gut. In no experiment did we unequivocally detect plant DNA that originated in the P. spumarius gut.

Unveiling the correlation between in vivo endodontic reciprocate instrumentation and crack formation

IntroductionDentinal microcracks have been supposedly associated with unrestorable vertical root fractures and consequently long-term treatment failure. This study aimed to investigate whether in vivo root canal instrumentation in mandibular incisors with vital pulps causes dentinal microcracks using two different irrigating solutions. MethodsFive patients with four vital mandibular incisors indicated for extraction were included. In vivo root canal preparation was performed using Reciproc R40 (tip #40 and taper 0.06). From these, two teeth were randomly assigned for root canal instrumentation irrigated with 5.25 % sodium hypochlorite irrigation (n = 10) or 2 % chlorhexidine gel with saline solution irrigation (n = 10). In sequence, all teeth were carefully extracted, stored in saline solution until microtomography (µCT) scan. Images were reconstructed and assessed for the presence or absence of dentinal microcracks where microcracks originating from the root canal lumen would be considered. All reconstructed samples were analysed dynamically and rendered in videos through the entire extension of the teeth, evaluating the axial cuts considering each third separately from the apex to the enamel-dentinal junction. Teeth were analysed using the DataViewer software at 100 % magnification without filters by three examiners blinded to the condition allocation. ResultsNo complete dentinal microcracks were observed after root canal instrumentation of mandibular incisors with vital pulps using Reciproc R40 regardless the irrigating solutions, 5.25 % sodium hypochlorite or 2 % chlorhexidine gel. ConclusionsIn vivo root canal instrumentation of mandibular incisors with vital pulps and bone/periodontal insertion does not cause dentinal microcracks and the irrigating solutions tested did not influence this occurrence. Microcrack evaluation must be performed in vivo conditions of dental tissue moist and periodontal support to avoid dryness dentinal alterations after extraction provoking false positive results. Clinical relevanceReciprocating instrumentation performed in vivo is safe and do not induce dentinal microcracks in mandibular incisors.

HAPLN3 p.T34A contributes to incomplete penetrance of moyamoya disease in Chinese carrying RNF213 p.R4810K.

The penetrance of the RNF213 p.R4810K, a founder mutation of moyamoya disease (MMD), is estimated to be only 1/150-1/300. However, the factors affecting its penetrance remain unclear. Therefore, our study aims to identify modifier genes associated with the incomplete penetrance of this founder mutation. Whole-exome sequencing (WES) was performed on 36 participants, including 22 MMD patients and 14 non-MMD controls with RNF213 p.R4810K mutation. Fisher's exact test was used to assess the presence of genetic variants that differed significantly between MMD patients and non-MMD controls. In order to exclude false-positive results, another 55 carriers were included to perform Fisher's exact test for the selected sites in the WES discovery stage. Subsequently, human brain microvascular endothelial cells were transfected with wild-type and mutant HAPLN3 for tube formation assays and western blotting to explore the impact of candidate genes on angiogenesis. Analysis of variants from WES data revealed a total of 12 non-synonymous variants. Through bioinformatics analysis, the focus was on the HAPLN3 p.T34A variant with a significant p value of 0.00731 in Fisher's exact test. Validation through Sanger sequencing confirmed the presence of this variant in the WES data. Invitro experiments revealed that silencing HAPLN3 and transfecting HAPLN3 p.T34A significantly enhanced tube formation and increased the relative protein expression of vascular endothelial growth factor in endothelial cells. These results suggest that HAPLN3 may function as a modifier gene of RNF213 p.R4810K, promoting the development of MMD and contributing to the incomplete penetrance of MMD founder mutations.

Diagnostic Accuracy of Five Molecular Assays for the Detection of Dengue Virus.

Background and Objectives: The steady spread of dengue virus (DENV) poses a profound public health threat worldwide. Reverse transcription real-time polymerase chain reaction (RT2-PCR) has been increasingly recognized as a reference method for the diagnosis of acute dengue infection. The goal of this study was to assess the diagnostic accuracy of five different RT2-PCR kits for the detection of DENV in a historically processed set of sera samples. Materials and Methods: In this retrospective study, 25 sera samples from routinely processed unique adult patients with a known DENV status (previously tested in both molecular and serological assays) were tested in parallel using four conventional (RealStar Dengue PCR Kit 3.0, Clonit'ngo Zika, Dengue & Chikungunya, BioPerfectus Zika Virus/Dengue Virus/Chikungunya Virus Real Time PCR Kit and Novaplex Tropical fever virus) and one sample-to-result (STANDARD M10 Arbovirus Panel) RT2-PCR assays. Additionally, an end-point dilution analysis was conducted in quintuplicate on six serial dilutions of an RNA preparation obtained from a culture-grown DENV serotype 1 strain for a total of 150 tests. Results: The overall accuracy of the evaluated tests ranged from 84% to 100%. In particular, the sensitivity of three conventional RT2-PCR assays (RealStar, Clonit'ngo and Novaplex) was 100% (95% CI: 79.6-100%), while it was lower (73.3%; 95% CI: 48.1-89.1%) for the BioPerfectus kit. The sample-to-result STANDARD M10 panel performed comparatively well, showing a sensitivity of 92.9% (95% CI: 68.5-98.7%). No false positive results were registered in any assay. The end-point dilution analysis suggested that the RealStar kit had the lowest limit of detection. Conclusions: Available RT2-PCR kits for the detection of DENV are highly specific and generally sensitive and, therefore, their implementation in diagnostic pathways is advisable.

In-Depth Analysis of Molecular Network Based on Liquid Chromatography Coupled with Tandem Mass Spectrometry in Natural Products: Importance of Redundant Nodes Discovery.

The identification of molecules within complex mixtures is a major bottleneck in natural products (NPs) research. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as the main tool for the high-throughput characterization of NPs. The large amount of data sets by LC-MS/MS presents a challenge for data processing and interpretation, and the LC-MS/MS molecular network (MN) is one of the most prominent tools for analyzing large MS/MS data sets, widely used for rapid classification, identification, and structural speculation of unknown compounds. However, the existence of a large number of redundant nodes leads to false-positive results. To solve this problem, we proposed the in-depth analysis of MN. In this study, in-depth analysis of MN of five NPs representing the common structures of saponin, steroid, flavonoid, alkaloid, and phenolic acid revealed the presence of redundant nodes (including other adducts, isotope, and in-source fragmentation) in addition to the normal nodes, which can lead to false-positive identification results. Additionally, the reasons for different redundant nodes are discussed and experimentally verified, and it was found that the impact of redundant nodes can be mitigated by optimizing the experimental conditions and employing Feature-Based Molecular Networking. Furthermore, Ion Identity Molecular Networking can rapidly discover and screen redundant nodes, simplifying the in-depth analysis of MN and improving the network connectivity of structurally related molecules. Finally, a combination formulation of 7 NPs is used as an example to provide a guide for in-depth analysis of MN for comprehensive characterization of complex systems. This study highlights the importance of an in-depth analysis of MN for better understanding and utilization of MS/MS data in complex systems to reduce the false-positive rate of identification by screening and filtering redundant nodes.

A step‐by‐step progressive strategy exploring whole metabolic profiles in vivo for Polygalae Radix with/without licorice

AbstractIntroductionPolygalae Radix (PR) is known to relieve toxicity and increase efficiency in various diseases after processing. However, there were few studies for aromatic carboxylic acids (ACAs) due to the limited detection, especially for the metabolites within m/z 100–2000.ObjectivesThis study aims to elucidate the whole metabolism of PR with/without licorice (LP), focusing on metabolites within m/z 100–2000 and pharmacodynamics in vivo.Material and methodsThis study was established by the combination of multidimensional ultra‐high performance liquid chromatography coupled with a mass spectrometer (UPLC–MS) technology with protein sedimentation method to analyze metabolites in plasma, brain, colon, and stomach contents. Quantitative monitoring ACAs was enhanced with our novel stable isotope derivatization (SILD) technique. And then the pharmacokinetics (PK) study of relatively large metabolites was carried out. A targeted network pharmacology approach was established to avoid false positive results, mapping interactions relevant to Alzheimer's disease (AD), and other conditions.ResultsThe 85 polygala metabolites were qualitatively analyzed in plasma, brain, colon, and stomach contents. The 11 types of relatively large metabolites and 8 types of ACAs were quantitatively monitored. Among them, nine types of relatively large metabolites were assessed through PK studies. In targeted network pharmacology, it highlighted the significance of small molecular metabolites, including ACAs et al, which were frequently overlooked. LP may play a more key role mainly through neural active ligand‐receptor interaction, AD, and pertussis pathways. These findings have outlined a step‐by‐step strategy for in‐depth research in vivo, laying a foundation for further verification of biological function.

Immunity to Non-Dengue Flaviviruses Impacts Dengue Virus Immunoglobulin G Enzyme-Linked Immunosorbent Assay Specificity in Cambodia.

Seroprevalence studies are the standard for disease surveillance, and serology determined eligibility for the first dengue vaccine. Expanding flavivirus co-circulation and vaccination complicate testing. We evaluate the accuracy of a common dengue virus serological assay, examine immunity to non-dengue flaviviruses as a contributor to decreased performance, and assess whether alternative cut points may improve assay performance. Children (n = 770) aged 2-9 years in Kampong Speu, Cambodia were enrolled in a prospective longitudinal study, and PanBio indirect dengue virus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) was performed. Plaque reduction neutralization tests (PRNTs) using dengue viruses were performed on a subset to assess the accuracy of the IgG ELISA, and PRNTs with Zika, Japanese encephalitis, and West Nile viruses evaluated immunity to non-dengue flaviviruses. Receiver operating curve analysis identified an alternative cut point to improve IgG ELISA accuracy. The dengue IgG ELISA had a lower specificity than previously reported (58% vs 93%-100%). Of those with false-positive IgG results, 46% had detectable neutralizing antibodies against other flaviviruses including 14% against West Nile virus. A higher IgG cut point improved the test accuracy in this population. Physicians and public health authorities should be alert for West Nile in Cambodia. Immunity to non-dengue flaviviruses can impact dengue surveillance. NCT03534245.

Benefits and Harms of Hepatocellular Carcinoma Screening Outreach in Patients with Cirrhosis: A Multi-Center Randomized Clinical Trial.

The value of hepatocellular carcinoma (HCC) screening is defined by the balance of benefits from early tumor detection vs harms due to false positive results. We evaluated the value of a mailed outreach strategy for HCC screening in patients with cirrhosis. We conducted a multi-center pragmatic randomized clinical trial comparing mailed outreach for HCC screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at three health systems from March 2018 to September 2021. Outcomes of interest were early-stage HCC detection (ie, screening benefit) and diagnostic evaluation for false positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses. Of 125 patients diagnosed with HCC (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan Criteria. Early tumor detection did not significantly differ between the outreach and usual care arms (64.2% vs 79.3%, p = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%, p = .95) with 5.9% in both arms having mild harms, 4.0% and 3.8% respectively with moderate harms, and 0.9% and 1.0% respectively with severe harms. Most patients enrolled in HCC screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not significantly increase early HCC detection or physical harms compared to usual care. NCT02582918 and NCT03756051.

MIDF-DMAP: Multimodal information dynamic fusion for drug molecule activity prediction

BackgroundComputer-aided drug development can alleviate limitations in drug research and development processes, such as long cycles, high costs, and limited targeting. Deep learning models can be used to predict the activity of drug compound molecules. However, existing models still need to adequately address semantic redundancy, conflicts, and noise between different data modalities. It results in low accuracy in predicting molecular activity and many false positive results that need further resolution. ObjectiveThis study aims to design a parallel deep learning model for processing multimodal molecular information fusion, dynamically adjusting the weights of different modal features during the fusion process. This approach ensures that high-quality modal information is more significant in molecular activity prediction, improving the model’s predictive accuracy. MethodsFirst, three modal features of drug molecules are extracted: one-dimensional fingerprints, two-dimensional topological structures, and three-dimensional geometric structures. Then, a dynamic weighting mechanism is proposed to fuse these three modal features organically. Finally, the fused features are input into the model classifier to obtain molecular activity prediction results. ResultsExperimental results show that the proposed model improved the Receiver Operating Characteristic-Area Under the Curve (ROC-AUC) value by 29.96% compared to the Weave model and 26.38% compared to the GC model on the BBBP dataset. Compared to the GraphMVP model and the multi-channel substructure graph model MSGG, the ROC-AUC value increased by 20.44% and 15.80%, respectively. This method also achieved good results on imbalanced samples and small molecule datasets. ConclusionThis study provides an effective multimodal dynamic fusion method for virtual drug screening, enriching computer-aided drug development theory and improving drug research and development efficiency.

Development and validation of highly sensitive multiplex real-time RT-PCR assay for detection of classical swine fever virus genome

Classical swine fever (CSF) remains a challenge for pig farming industrial lover the world despite the measures taken. The last CS case in the Russian Federation was reported in 2020, however, the threat of the disease emerging still persists. A set of anti-epidemic measures including mainly preventive vaccination and annual diagnostic monitoring using molecular-genetic and serological methods is required for CSF virus introduction prevention and rapid eradication of potential disease out breaks. Therefore, areal-time reverse transcription-polymerase chain reaction using an internal control sample has been developed. Therefore, areal time reverse transcription-polymerase chain reaction using an internal control sample has been developed. Modified primers (locked nucleic acids containing conformationally blocked nucleosides) providing a higher affinity to the DNA matrix and physico-chemical stability and a FAM-labeled TaqMan probe were selected for 5’-untranslatedregion of the genome. The following validation parameters were defined: accuracy, repeatability, reproducibility, specificity and sensitivity. For comparative analysis of the developed as say sensitivity, swabs, samples of organs and tissues collected from pigs experimentally infected with an epizootic strain of the classical swine fever virus (spleen, kidney, liver, blood, lymph nodes, rectal and oral smears), animal-contaminated feed and virus-containing material with known virus titres were also tested in parallel with coded test systems No. x1 andx2. The developed assay was shown to have 100% diagnostic sensitivity and detection limit of 0,23 lgCCID50/cm3. Therewith, there sults of analysis of test systems No. x1, x2 based on above parameters were lower that could give rise to false positive real-time RT-PCR results and incorrect diagnosis. Thus, described assay can be used for extensive monitoring of classical swine fever in the Russian Federation

False-Positive Human Immunodeficiency Virus-1 Test Results With Rapid Seroreversion After Third-Trimester Tdap Booster Vaccination.

False-positive and false-negative results in human immunodeficiency virus (HIV) testing are expected at some frequency. False-positive results have been reported in association with various conditions, including pregnancy, autoimmune disease, and infection. We present an atypical case of a pregnant patient receiving false-positive HIV results for both screening and antibody confirmatory tests after a recent routine vaccination. A 34-year-old woman, G4P1021, with a negative first-trimester HIV test result received a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) booster at 35 2/7 weeks of gestation. Test results at 36 2/7 weeks of gestation were positive in both HIV-1/2 antigen-antibody screening and a confirmatory HIV-1 antibody differentiation immunoassay, but follow-up test results at 36 5/7 weeks and later were negative. Repeat testing and erythrocyte typing confirmed that this was not a result of laboratory error or specimen mishandling. HIV antiretroviral therapy was started and was later discontinued. A scheduled primary cesarean delivery performed at 39 1/7 weeks of gestation due to breech presentation was uncomplicated. False-positive results in HIV screen and confirmation testing were associated with receipt of a Tdap vaccine booster 7 days prior. This test result pattern is similar to that seen very rarely in previous cases, and the rapid seroreversion to negative suggests an acute immunologic trigger leading to a falsely reactive antibody. Clinicians should be aware of the potential for false-positive HIV test results in patients who recently received vaccination or with other immune triggers and retest at a short interval if suspected.

Thymoglobulin therapy leads to false positive antibody and crossmatch results

Thymoglobulin therapy leads to false positive antibody and crossmatch results

Performance and value of 18F‑FDG PET/CT in patients with fever of unknown origin.

Fever of unknown origin (FUO) is a common clinical and diagnostic challenge. The main aim of the present study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT in patients who present with FUO. Overall, 105 consecutive patients (61 men and 44 women) with a mean age of 51±35 years with FUO underwent 18FDG PET/CT scans. The performance of 18FDG PET/CT in determining the etiology of FUO was assessed. According to the PET/CT results, patients were classified into four groups: Group 1, patients with true-positive results (n=51; 49%), in whom abnormal 18FDG uptake identified the final diagnosis; group 2, patients with false-positive results (n=24; 23%), in whom 18FDG uptake was not consistent with the final diagnosis; group 3, patients with true-negative results (n=10; 9.5%), in whom the 18FDG uptake was normal and no final disease was established; and group 4, patients with false-negative results (n=20; 19%), in whom 18FDG uptake was normal and disease was finally established. Of the 51 patients with true-positive PET/CT results, 51% had infections, 35% had malignancies and 14% had inflammatory processes. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 72, 29, 68, 33 and 58%, respectively. In conclusion, the present results demonstrated that 18FDG PET/CT established the final diagnosis of FUO in the majority of patients (72%). These results support the use of 18FDG PET/CT in the initial evaluation and management of patients with FUO.

Quantitative Compliance Based Classification of Submental Sign or Javid Sign

Prediction of difficult intubation is still a dilemma. Despite various predictors of difficult airway reported and discussed in the literature, no definite test exists to prevent mortality and morbidity related to difficult airway. Using a combination of different predictors of difficult intubation is logical to help minimizing this difficulty and establishing a safe anesthesia. Detection and presentation of any novel predictor can be helpful in achieving this goal. “Submental Sign” or “Javid Sign” a new predictor of difficult intubation, was reported by MJ Javid in 2011, but qualitative characteristic of this predictor was the most considerable drawback for using Submental Sign as an accurate predictor. The goal of this study is quantitative classification of Submental Sign or Javid classification to overcome false positive and false negative results of Submental Sign. In this article a novel scale is introduced for evaluating submental compressibility quantitatively.