False-positive Results Research Articles

Benchmark Investigation of SARS-CoV-2 Mutants’ Immune Escape with 2B04 Murine Antibody: A Step Towards Unraveling a Larger Picture

Even though COVID-19 is no longer the primary focus of the global scientific community, its high mutation rate (nearly 30 substitutions per year) poses a threat of a potential comeback. Effective vaccines have been developed and administered to the population, ending the pandemic. Nonetheless, reinfection by newly emerging subvariants, particularly the latest JN.1 strain, remains common. The rapid mutation of this virus demands a fast response from the scientific community in case of an emergency. While the immune escape of earlier variants was extensively investigated, one still needs a comprehensive understanding of how specific mutations, especially in the newest subvariants, influence the antigenic escape of the pathogen. Here, we tested comprehensive in silico approaches to identify methods for fast and accurate prediction of antibody neutralization by various mutants. As a benchmark, we modeled the complexes of the murine antibody 2B04, which neutralizes infection by preventing the SARS-CoV-2 spike glycoprotein’s association with angiotensin-converting enzyme (ACE2). Complexes with the wild-type, B.1.1.7 Alpha, and B.1.427/429 Epsilon SARS-CoV-2 variants were used as positive controls, while complexes with the B.1.351 Beta, P.1 Gamma, B.1.617.2 Delta, B.1.617.1 Kappa, BA.1 Omicron, and the newest JN.1 Omicron variants were used as decoys. Three essentially different algorithms were employed: forced placement based on a template, followed by two steps of extended molecular dynamics simulations; protein–protein docking utilizing PIPER (an FFT-based method extended for use with pairwise interaction potentials); and the AlphaFold 3.0 model for complex structure prediction. Homology modeling was used to assess the 3D structure of the newly emerged JN.1 Omicron subvariant, whose crystallographic structure is not yet available in the Protein Database. After a careful comparison of these three approaches, we were able to identify the pros and cons of each method. Protein–protein docking yielded two false-positive results, while manual placement reinforced by molecular dynamics produced one false positive and one false negative. In contrast, AlphaFold resulted in only one doubtful result and a higher overall accuracy-to-time ratio. The reasons for inaccuracies and potential pitfalls of various approaches are carefully explained. In addition to a comparative analysis of methods, some mechanisms of immune escape are elucidated herein. This provides a critical foundation for improving the predictive accuracy of vaccine efficacy against new viral subvariants, introducing accurate methodologies, and pinpointing potential challenges.

Troponin Test, Not Only a Number: An Unusual Case of False Positive

Heterophile antibodies, which can arise from infections, autoimmune disorders, or exposure to animal antigens, can interfere with immunoassays. These antibodies can cross-react with the test reagents used in troponin assays, causing a false elevation in troponin levels. The paper describes a case of a 37-year-old male drug abuser admitted to the emergency room with chest pain. A series of troponin measurements performed using different assays gave discrepant results. Only thanks to the use of Scantibodies HBT tubes, which remove heterophile antibodies, was it possible to make a correct diagnosis of troponin negativity. In conclusion, a correct laboratory/clinical approach to the identification of heterophile antibody interference is essential for accurate troponin testing in order to avoid false positive results. Implementing neutralizing tests can significantly improve the reliability of these diagnostic assays, ensuring better patient outcome.

Evaluation of the clinical utility of NIPT-plus and analysis of adverse pregnancy outcomes.

To evaluate the performance of NIPT-plus in detecting fetal aneuploidies and CNVs and analyze the factors influencing adverse pregnancy outcomes. The retrospectively analyzed 8726 pregnant women who underwent NIPT-plus for fetal screening were classified into low- (who tested voluntarily) and high-risk (women with advanced age, abnormal ultrasound, abnormal serological screening, or a combination of indications) groups. Basic maternal information, prenatal findings, and pregnancy outcomes were recorded. NIPT-plus performance was assessed for various chromosomal abnormalities and the association between the fetal fraction and adverse pregnancy outcomes. Thirty-six (0.4%) patients had failed tests; 144 (1.65%) positive cases were detected, of which, 107 (74.31%) opted for invasive testing, and 51 were verified as true positives. The total positive predictive value was 45.45% and 48.65% in the low- and high-risk groups, respectively, and the difference was not significant. Among the subsequent cases with abnormal ultrasound monitoring, two false-negative cases were identified, and pathogenic CNV diagnosis was confirmed through amniocentesis, resulting in pregnancy termination. Fetal fraction was not associated with an increased adverse pregnancy outcome risk; however, ethnic differences may affect pregnancy outcomes. NIPT-plus technology use is no longer restricted to high-risk pregnant women, and it may produce false-positive results. The stakeholders should be aware of this limitation. The uncertainties and potential risks of the test results should be explained to the test takers to enable informed decision making and to minimize unnecessary anxiety and concerns. Ethnicity may influence adverse pregnancy outcomes in local multiracial settings.

Poor correlation between diaphragm ultrasound and invasive gold standard technique derived respiratory muscle strength assessment in patients after hospitalization for COVID-19.

Individuals who survive acute coronavirus disease 2019 (COVID-19) might experience diaphragm muscle weakness. Diaphragm ultrasound may be an easy-to-obtain bedside tool for determining diaphragm function. However, twitch transdiaphragmatic pressure (twPdi) following magnetic stimulation (MS) of the phrenic nerves is the gold standard for non-volitional assessment of diaphragm strength. This study investigated whether diaphragm thickening ratio (DTR) measured on diaphragm ultrasound reflects diaphragm strength as measured by twPdi following MS of the phrenic nerves or other (volitional) invasively obtained pressure values and could therefore be used to accurately diagnose diaphragm weakness. One year after discharge, 50 individuals (14 female, age 58±12 years) who had been hospitalised and treated for moderate-severe COVID-19 underwent standard spirometry and diaphragm ultrasound. TwPdi following cervical MS of the phrenic nerve and volitional inspiratory manoeuvres (Sniff and Mueller manoeuvre) were measured using oesophageal and gastric balloon catheters after transnasal placement. At follow-up, no clinically meaningful restrictive lung function impairment was evident on spirometry. On diaphragm ultrasound, diaphragm dysfunction, i. e. an impaired diaphragm thickening ratio was detected in 24% (12/50) of participants. An objective diagnosis of diaphragm dysfunction, defined as twPdi <16 cmH2O, was made in 60% (30/50) of participants. The measurement results of the two methods did not agree, given that there were many false negative, but also false positive results, so diaphragm ultrasound diagnosed in parts other patients with diaphragm dysfunction than TwPdi. Diaphragm ultrasound had a sensitivity of 26.67% and a specificity of 80.0% in the detection of diaphragm dysfunction (Positive predictive value 66.67%, negative predictive value 42.10%). Diagnosis of diaphragm weakness in individuals who have recovered from COVID-19 cannot be made accurately on diaphragm ultrasound (via DTR), but requires twPdi as the gold standard for assessment of diaphragm strength.

American Society for Microbiology evidence-based laboratory medicine practice guidelines to reduce blood culture contamination rates: a systematic review and meta-analysis.

SUMMARYBlood cultures (BCs) are one of the critical tests used to detect bloodstream infections. BC results are not 100% specific. Interpretation of BC results is often complicated by detecting microbial contamination rather than true infection. False positives due to blood culture contamination (BCC) vary from 1% to as high as >10% of all BC results. False-positive BC results may result in patients undergoing unnecessary antimicrobial treatments, increased healthcare costs, and delay in detecting the true cause of infection or other non-infectious illness. Previous guidelines from the Clinical and Laboratory Standards Institute, College of American Pathologists, and others, based on expert opinion and surveys, promoted a limit of ≤3% as acceptable for BCC rates. However, the data supporting such recommendations are controversial. A previous systematic review of BCC examined three practices for reducing BCC rates (venipuncture, phlebotomy teams, and pre-packaged kits). Subsequently, numerous studies on different practices including using diversion devices, disinfectants, and education/training to lower BCC have been published. The goal of the current guideline is to identify beneficial intervention strategies to reduce BCC rates, including devices, practices, and education/training by providers in collaboration with the laboratory. We performed a systematic review of the literature between 2017 and 2022 using numerous databases. Of the 11,319 unique records identified, 311 articles were sought for full-text review, of which 177 were reviewed; 126 of the full-text articles were excluded based on pre-defined inclusion and exclusion criteria. Data were extracted from a total of 49 articles included in the final analysis. An evidenced-based committee's expert panel reviewed all the references as mentioned in Data Collection and determined if the articles met the inclusion criteria. Data from extractions were captured within an extraction template in the US Agency for Healthcare Research and Quality's Systematic Review Data Repository (https://srdr.ahrq.gov/). BCC rates were captured as the number of events (contaminated samples) per arm (standard practice versus improvement practice). Modified versions of the National Heart, Lung, and Blood Institute Study Quality Assessment Tools were used for risk of bias assessment (https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools). We used Grading of Recommendations, Assessment, Development and Evaluations to assess strength of evidence. There are several interventions that resulted in significant reduction in BCC rates: chlorhexidine as a disinfectant for skin preparation, using a diversion device prior to drawing BCs, using sterile technique practices, using a phlebotomy team to obtain BCs, and education/training programs. While there were no substantial differences between methods of decreasing BCC, our results indicate that the method of implementation can determine the success or failure of the intervention. Our evidence-based systematic review and meta-analysis support several interventions to effectively reduce BCC by approximately 40%-60%. However, devices alone without an education/training component and buy-in from key stakeholders to implement various interventions would not be as effective in reducing BCC rates.

Strategies to Overcome Erroneous Outcomes in Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Testing: Insights From the COVID-19 Pandemic.

The reverse transcription-polymerase chain reaction (RT-PCR) test to detect SARS-CoV-2, the virus causing COVID-19, has been regarded as the diagnostic gold standard. However, the excessive sensitivity of RT-PCR may cause false-positive outcomes from contamination. Again, its technical complexity increases the chances of false-negatives due to pre-analytical and analytical errors. This narrative review explores the elements contributing to inaccurate results during the COVID-19 pandemic and offers strategies to minimize these errors. False-positive results may occur due to specimen contamination, non-specific primer binding, residual viral RNA, and false-negatives, which may arise from improper sampling, timing, labeling, storage, low viral loads, mutations, and faulty test kits. Proposed mitigation strategies to enhance the accuracy of RT-PCR testing include comprehensive staff training in specimen collection, optimizing the timing of tests, analyzing multiple gene targets, incorporating clinical findings, workflow automation, and implementing stringent contamination control measures. Identifying and rectifying sources of error in RT-PCR diagnosis through quality control and standardized protocols is imperative for ensuring quality patient care and effective epidemic control.

A brief harvesting-freezing delay significantly alters the kidney metabolome and leads to false positive and negative results.

Abnormalities in distinct metabolic pathways have been associated with the pathogenesis and progression of many forms of kidney disease. Metabolomics analyses can be used to determine organ-specific metabolic fingerprints and, ideally, should represent the metabolic state of the organ at the exact moment the sample is harvested. However, conventional harvesting methods depend on posteuthanasia tissue harvest, which results in ischemia conditions and metabolome changes that could potentially introduce artifacts into the final studies. We recently optimized a modified clamp-freezing technique for rodent kidney harvesting and freezing, significantly reducing ischemia and freezing times and granting a closer snapshot of in vivo metabolism. In this study, we characterized and compared the metabolome of kidneys harvested using our modified approach versus traditional techniques to determine which metabolites are preferentially affected by a brief lapse of ischemia and freezing delay and which are more stable. We used Sprague-Dawley rats as a model of wild-type (WT) kidneys and PCK [polycystic kidney disease (PKD)] rats as a model of chronic kidney disease kidneys. Finally, we compared the metabolic profile of clamp-frozen and delayed WT and PKD kidneys to determine which metabolic changes are most likely observed in vivo in PKD and which could be subjected to false positive or negative results. Our data indicate that a short harvesting-freezing delay is sufficient to impart profound metabolic changes in WT and PKD kidneys, leading to false positive and negative differences when comparing these genotypes. In addition, we identified a group of metabolites that were more stable. Interestingly, while the delay had a similar effect between WT and PKD, there were notable differences. The data obtained indicate that the quick clamp-freezing technique for kidney metabolomics provides a more accurate interpretation of the in vivo metabolic changes associated with the disease state. NEW & NOTEWORTHY Our study shows that a brief harvesting-freezing delay associated with organ collection and freezing can significantly alter the kidney metabolic profile of both male and female wild-type and a genetic model of chronic kidney disease. Importantly, given that the effect of this delay differs among genotypes, it is not safe to assume that equally delaying harvesting-freezing in wild-type and polycystic kidney disease kidneys adequately controls this effect, ultimately leading to false positive and negative results among different renal diseases.

Dual "Turn-On" Fluorescent and Colorimetric Sensing of Permanganate Based on Yellow Carbon Dots.

Existing permanganates (MnO4 -) sensing methods suffered from the poor selectivity, restricted solubility, and/or less desirable signaling mechanisms (e.g., "turn-off" processes), resulting in the false positive result. In this work, an effective "turn-on" fluorescence method for MnO4 - detection in aqueous media was proposed via yellow fluorescence carbon dots (Y-CDs) with the maximum emission peak of 553 nm. Upon the introduction of MnO4 -, the fluorescence of Y-CDs increased significantly due to the enhanced surface passivation degree and intramolecular charge transfer. In the range of 0.1-10 μM, the fluorescence ratio (F/F0) is proportional to the MnO4 - ions concentration, realizing the "turn-on" fluorescence sensing of MnO4 -. On the other hand, utilizing the significant color change of Y-CDs by MnO4 - ions, the colorimetric analysis can also be established for MnO4 - assay. Compared with other probes, the analysis results obtained by bimodal sensing tactics of fluorescent and colorimetric can be mutually verified to improve the reliability and meet the sensing needs of targets in complex environments.

A Review of Drug Abuse, Misuse, and Related Laboratory Challenges.

Various definitions can be considered for drugs and substance abuse. According to the National Institute on Abuse, the use of an over-the-counter drug in a different way than that prescribed to experience or arouse emotion is a simple form of drug abuse. The World Health Organization (WHO) also defines drug abuse as the persistent or sporadic use of drugs that are incompatible or unrelated to acceptable medical practice. With the increasing non-therapeutic use of prescription drugs, serious related consequences have also increased. Therefore, there is a need to know more precisely about the types of substances and drug abuse, which is the most important part of diagnosis and recognizing the tests that cause false positive and negative results. The purpose of this review article is to collect and summarize the most important and more common types of drugs of abuse and review the drugs that cause false results in screening tests. In addition, the most common detection methods of the drug will be reviewed and the advantages and drawbacks of each method will be discussed. In this article, we aimed to point out all the facts about the emerging problems in drug abuse, the methods of screening, and the possible false results in addition to troubleshooting strategies.

Beyond Eyeball Tests: A Methodical Rebuttal to Fillon et al.'s Commentary.

In our original study, "Consumed by Creed" (Adam-Troian & Bélanger, 2024), we established significant and consistent associations between obsessive-compulsive disorder symptom severity and radical intentions across four distinct U.S. population samples-Environmentalists, Republicans, Democrats, and Muslims-partially or fully mediated by obsessive passion. Fillon et al. (2024) challenged our findings, alleging methodological errors and an excessive degree of researcher flexibility, which they claim could lead to false-positive results. In this response, we critically examine Fillon et al.'s commentary, arguing that it exemplifies flawed meta-scientific critique. We demonstrate that their approach relies on a series of unsupported and misleading claims, including a misinterpretation of the literature, unjustified reliance on visual data inspection, speculative assumptions about religious influences on our findings, and a shifting of the burden of proof. Through rigorous re-analyses, we reaffirm the robustness of our original results and address the unfounded allegations regarding our methodological practices. We also critique Fillon et al.'s approach, highlighting the necessity of domain-specific expertize in meta-scientific evaluations and cautioning against the risks of speculative and defamatory criticism in academic discourse. This exchange underscores the importance of maintaining rigorous standards in both original research and its critique, ensuring that scientific debate remains grounded in evidence rather than conjecture.

A phenomap of TTR amyloidosis to aid diagnostic screening.

Cardiac amyloidosis due to transthyretin (ATTR) remains an underdiagnosed cause of cardiomyopathy. As awareness of the disease grows and referrals for ATTR increase, clinicians are likely to encounter more atypical forms of the condition in clinical practice. Therefore, physicians and treating cardiologists should be aware of the full phenotypic spectrum of ATTR. The phenotypic manifestation of ATTR varies depending on the stage of the disease, the presence and type of TTR mutation and the patient's comorbidities. ATTR findings can be grouped into four major categories: clinical profile and cardiac phenotype, extra-cardiac findings, electrocardiogram and imaging findings, which cumulatively form the full phenomap of ATTR. Results from any diagnostic test for ATTR should be interpreted in light of the pre-test probability for the disease. Findings that suggest negative markers for ATTR can point towards other forms of amyloidosis (such as AL amyloidosis) or alternate causes of left ventricular hypertrophy, including hypertrophic cardiomyopathy or Fabry disease. The rising number of referrals for ATTR cardiomyopathy presents a challenge in daily clinical practice. To prevent an increase in false-positive diagnostic test results, an ATTR phenomap can serve as a valuable tool for guiding diagnostic assessments, interpreting test outcomes and prioritizing appropriate referrals for ATTR screening.

Can Ki-67 serve as a suitable marker to indicate the necessity of staging diagnostics in cases of low-risk breast cancer?

For many years, staging tests have not been routinely employed for low-risk early breast cancer (EBC). However, the role of Ki-67 in determining the need for staging tests in low-risk EBC remains unclear. Our study aimed to assess the number and types of staging diagnostics, additional imaging, false-positive results, and rate of distant metastases in low-risk EBC with low and high Ki-67 (< / ≥ 25%). This is a retrospective, single institution cohort study. All patients with newly diagnosed low-risk breast cancer at the University Medical Center in Freiburg in 2017 and 2021 were included. Low-risk was defined as clinical tumor stage T1/2, node negative (N0), hormone receptor positive, HER2 negative, asymptomatic EBC. Information on demographics, clinical and pathological characteristics, as well as number and type of performed staging diagnostics was obtained. Rate and type of additional imaging or follow-up diagnostics due to suspicious findings was analyzed. The patients were divided into two groups (Ki-67 < and ≥ 25%) and rates of distant metastases, performed staging diagnostics and false positive rates were compared. A total of 189 patients with low-risk EBC were identified, with 54% (n = 102) having Ki-67 < 25% and 46% (n = 87) having Ki-67 ≥ 25%. Risk for distant metastases was 0% in Ki-67 < 25% and 1.1% in patients with Ki-67 ≥ 25% (p = 0.46). Due to suspicious findings in the initial staging diagnostic, additional imaging was required for 11.8% (n = 12) of patients with Ki-67 < 25% compared to 19.5% (n = 17) of patients with Ki-67 ≥ 25% (p = 0.16). False positive rates did not differ significantly between the two groups (7.6% in Ki-67 < 25% vs. 9.8% in Ki-67 ≥ 25%; p = 0.55). Distant metastases are rare in low-risk EBC. All in all, staging diagnostics should not be routinely employed in this patient population. Only patients with high Ki-67 developed distant metastases. In these cases, staging diagnostics may be discussed with the patient.

Measuring Investor Attention Using Google Search

Although investor attention is fundamental to the efficient functioning of capital markets, it is also an elusive construct that researchers struggle to measure. In recent years, the search volume index (SVI) of ticker searches on Google has become a ubiquitous measure of investor attention, but the amount and effects of measurement error in ticker SVI are unknown. We investigate measurement error in ticker SVI using a data set of 2.7 billion website visits following Standard and Poor’s 500 firms’ ticker searches. We find that 69% of searches are unrelated to investing, that this measurement error is highly correlated with firm characteristics, and that this measurement error can easily generate false-positive or false-negative results in common settings. We go on to show that a modified version of SVI using both a firm’s ticker and the word “stock” (e.g., searches for “CAT stock,” which we label “ticker-stock SVI”) not only better captures the search terms that investors typically use, but also has considerably less measurement error that is largely uncorrelated with observable firm characteristics. Ticker-stock SVI produces better specified tests, and although researchers must still carefully consider the effects of measurement error, we recommend that ticker-stock SVI is used in place of ticker SVI in most settings. We provide a data set of ticker-stock SVI to facilitate future work. This paper was accepted by Suraj Srinivisan, accounting. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.02174 . TS-SVI for the Russell 3000 is available for download at: github.com/robinlitjens/GoogleTickerStock-SVI and will be updated annually.

Strategy to develop and validate digital droplet PCR methods for global antimicrobial resistance wastewater surveillance.

According to World Health Organization (WHO), antimicrobial resistance (AMR) is currently one of the world's top 10 health threats, causing infections to become difficult or impossible to treat, increasing the risk of disease spread, severe illness, disability, and death. Accurate surveillance is a key component in the fight against AMR. Wastewater is progressively becoming a new player in AMR surveillance, with the promise of a cost-effective real-time tracking of global AMR profiles in specific regions. One of the most useful analytical methods for wastewater surveillance is currently based on real-time PCR (qPCR) and digital droplet PCR (ddPCR) technologies. As stated in the EU Wastewater Treatment Directive proposal, methodological standardization, including a workflow for method development and validation, will play a crucial role in global monitoring of AMR in wastewater. However, according to our knowledge, there are currently no qPCR and ddPCR methods for AMR surveillance available that have been validated according to international standard performance criteria. Therefore, this study proposes a workflow for the development and validation of PCR-based methods for a harmonized and global AMR surveillance, including the construction of specific sequence databases and microbial collections for an efficient method development and method specificity evaluation. Following this strategy, we have developed and validated four duplex ddPCR methods responding to international standard performance criteria, focusing on seven AMR genes (ARG's), including extended spectrum beta-lactam (blaCTX-M), carbapenem (blaKPC-2/3), tetracycline (tet(M)), erythromycin (erm(B)), vancomycin (vanA), sulfonamide (sul2), and aminoglycoside (aac(3)-IV), as well as one indicator of antibiotic (multi-) resistance and horizontal gene transfer, named the class I integron (intl1). The performance of these ddPCR methods was successfully assessed for their specificity, as no false-positive and false-negative results were observed. These ddPCR methods were also considered to be highly sensitive as showing a limit of detection below 25 copies of the targets. In addition, their applicability was confirmed using 14 wastewater samples collected from two Belgian water resource recovery facilities. The proposed study represents therefore a step forward to reinforce method harmonization in the context of the global AMR surveillance in wastewater. PRACTITIONER POINTS: In the context of wastewater surveillance, no PCR-based methods for global AMR monitoring are currently validated according to international standards. Consequently, we propose a workflow to develop and validate PCR-based methods for a harmonized and global AMR surveillance. This workflow resulted here in four duplex ddPCR methods targeting seven ARGs and one general indicator for mobilizable resistance genes. The applicability of these validated ddPCR methods was confirmed on 14 wastewater samples from two Belgian water resource recovery facilities.

When to Trust Epigenetic Clocks: Avoiding False Positives in Aging Interventions.

Recent human studies have suggested that aging interventions can reduce aging biomarkers related to morbidity and mortality risk. Such biomarkers may potentially serve as early, rapid indicators of effects on healthspan. An increasing number of studies are measuring intervention effects on epigenetic clocks, commonly used aging biomarkers based on DNA methylation profiles. However, with dozens of clocks to choose from, different clocks may not agree on the effect of an intervention. Furthermore, changes in some clocks may simply be the result of technical noise causing a false positive result. To address these issues, we measured the variability between 6 popular epigenetic clocks across a range of longitudinal datasets containing either an aging intervention or an age-accelerating event. We further compared them to the same clocks re-trained to have high test-retest reliability. We find the newer generation of clocks, trained on mortality or rate-of-aging, capture aging events more reliably than those clocks trained on chronological age, as these show consistent effects (or lack thereof) across multiple clocks including high-reliability versions, and including after multiple testing correction. In contrast, clocks trained on chronological age frequently show sporadic changes that are not replicable when using high-reliability versions of those same clocks, or when using newer generations of clocks and these results do not survive multiple-testing correction. These are likely false positive results, and we note that some of these clock changes were previously published, suggesting the literature should be re-examined. This work lays the foundation for future clinical trials that aim to measure aging interventions with epigenetic clocks, by establishing when to attribute a given change in biological age to a bona fide change in the aging process.

Т-РЕЦЕПТОРНЫЕ И КАППА-ДЕЛЕЦИОННЫЕ РЕКОМБИНАЦИОННЫЕ ЭКСЦИЗИОННЫЕ КОЛЬЦА КАК ИНСТРУМЕНТ ОЦЕНКИ ФУНКЦИИ Т- И В-КЛЕТОЧНОГО ЗВЕНА ИММУНИТЕТА У НОВОРОЖДЕННЫХ С ЭКСТРЕМАЛЬНО НИЗКОЙ МАССОЙ ТЕЛА ПРИ РОЖДЕНИИ: ФАКТОРЫ РИСКА

Early detection of newborns with congenital immune errors has become possible as yet thanks to the recent nationwide introduction of expanded neonatal screening into routine practice. The stake of false-positive results is higher in premature infants than in other age groups. This therefore requires further and more thorough investigation of both TREC and KREC dynamics in preterm infants. The purpose of this research was to identify significant factors affecting the levels of TREC and KREC in infants born with extremely low birth weight and to evaluate the dynamics of these parameters depending on the gestational age. Materials and methods used: the study that involved 43 (51,2% (22) girls/48,8% (21) boys) extremely low birth weight newborns with gestational age of 26 [25; 27] weeks who were born at the Perinatal Center with the Voronezh Oblast Regional Clinical Hospital No. 1 (Voronezh, Russia) in 2022-2024 had been carried out. The dynamics of TREC and KREC indicators from the gestational age was evaluated. The influence of significant prenatal and postnatal factors on TREC and KREC indicators was considered. The material for the study was dried blood spots drawn on Guthrie cards and taken as part of neonatal screening. Results: it was revealed that TREC levels increased, KREC values remained relatively stable with increasing gestation period. A decrease in TREC levels is observed in newborns who were born to mothers whose pregnancy was complicated by fetoplacental insufficiency (p=0,012) as well as in those who had required the extended cardiotonic support aiming to stabilize the main hemodynamic parameters (p=0.042). A decrease in KREC levels was observed in newborns from mothers with a history of two and more frozen pregnancies (p&lt;0,001). Conclusion: statistically significant prenatal and postnatal factors affecting TREC and KREC levels in children born with extremely low birth weight have been revealed. The dynamics of TREC/KREC indices depending on the gestational age was noted.

Interlaboratory comparison of endotoxin contamination assessment of nanomaterials.

Endotoxin contamination is a significant hurdle to the translation of nanomaterials for biomedical applications. Multiple reports now describe that more than one-third of nanomaterials fail early pre-clinical assessment due to levels of endotoxin above regulatory requirements. Additionally, most immunological studies or in vivo studies testing nanomaterials in the literature lack inclusion of this assessment, which may lead to false-positive or false-negative results if high levels of the contaminant are present. The currently approved methods for endotoxin contamination assessment rely on enzymatic activity and wavelength absorbance as their endpoint, and many nanomaterials can interfere with such assays. For this reason, we devised an interlaboratory comparison of endotoxin contamination assessment for a range of nanomaterials to challenge the current international organization for standardization and pharmacopeia standards. Herein, we show that detected endotoxin levels could vary considerably between groups, and, in some instances, nanomaterials could both pass and fail regulatory endotoxin limits for medical devices depending on the group undertaking the assessment, all while passing all quality criteria standards. This work emphasises the requirement for multiple assays to fully assess the endotoxin levels in a nanomaterial and highlights the need for additional assays to be developed in this space.

Prostate Specific Antigen (PSA) testing in a general practice 2009-2019.

Prostate-specific antigen (PSA) testing is not recommended as a population screening measure for prostate cancer. PSA testing is nevertheless widespread and is associated with harm due to false-positive test results, overdiagnosis and economic costs. This study sought to document the exposure of patients to PSA testing over a decade in a general medical practice setting. Laboratory results for each year were extracted from the clinical record. A chart review was undertaken for cases of prostate cancer. We report 13,743 PSA results in 3313 men. In any year, 18% of all men and 33% of men aged over 50years had at least one PSA test. Between 4.8 and 21% of first tests exceeded age normal values depending on age. There were 113 incident cancers in the study interval of which 84 (74%) were screen detected. Mortality was lower in screen-detected than symptomatic cancers. Men at our practice are significantly exposed to PSA testing. We found evidence of possible overdiagnosis.

Recurrent Xp22.31-Yq11 Unbalanced Translocations: Molecular Diagnosis and Clinical Implications in Three Families.

Unbalanced translocation between chromosomes X and Y is a recurring chromosomal rearrangement. The presence of a derivative chromosome X (derX), where a Yq11-qter segment is attached to the short arm of chromosome X, replacing a terminal Xpter-p22.31, poses challenges for interpretation of findings by prenatal cell-free DNA (cfDNA) screening, establishing genotype-phenotype correlation in male and female individuals, and for genetic counseling. In this report, we provide clinical outcomes, inheritance, and clinical implications of derX in three families referred to diagnostic testing due to discrepant results for sex chromosomes reported by cfDNA, abnormal prenatal ultrasound findings, recurrent pregnancy losses, or affected family members with derX transmitted through multiple generations. Reports of discrepant sex and risk for sex chromosome aneuploidy such as 45,X, 47,XXY and 47,XYY are common false positive outcomes of a prenatal cfDNA screening if either a mother or a fetus has unbalanced Xp-Yq translocation. In addition, mothers who carry der(X) facing a recurrent risk of ambiguity in prenatal testing. Pregnancy loss and neonatal death/stillbirth of male offspring are common in affected families, but this risk does not directly correlate with the size of deleted Xp region. This study emphasizes the importance of CMA and familial testing for accurate diagnosis and genetic counseling.

Rapid urease test according to the rules and without

The article discusses the problems of diagnosing Helicobacter pylori (H.pylori) using a rapid urease test (RUT). Features of H.pylori colonization and persistence are highlighted, which affect the results of RUT and determine the preferential use of biopsy specimens for the study, rather than gastric mucus aspirate, the localization of biopsy collection and their optimal number and the factors influencing the urease activity of H.pylori are indicated. Based on the described properties, the main causes of erroneous results and methods for preventing false negative and false positive results are given, the basic rules for working with RUT are formulated to obtain optimal results.