Reducing false positive rate of docking-based virtual screening by active learning.

Machine learning-based scoring functions (MLSFs) have become a very favorable alternative to classical scoring functions because of their potential superior screening performance. However, the information of negative data used to construct MLSFs was rarely reported in the literature, and meanwhile the putative inactive molecules recorded in existing databases usually have obvious bias from active molecules. Here we proposed an easy-to-use method named AMLSF that combines active learning using negative molecular selection strategies with MLSF, which can iteratively improve the quality of inactive sets and thus reduce the false positive rate of virtual screening. We chose energy auxiliary terms learning as the MLSF and validated our method on eight targets in the diverse subset of DUD-E. For each target, we screened the IterBioScreen database by AMLSF and compared the screening results with those of the four control models. The results illustrate that the number of active molecules in the top 1000 molecules identified by AMLSF was significantly higher than those identified by the control models. In addition, the free energy calculation results for the top 10 molecules screened out by the AMLSF, null model and control models based on DUD-E also proved that more active molecules can be identified, and the false positive rate can be reduced by AMLSF.

Site-Specific Identification of Protein S-Acylation by IodoTMT0 Labeling and Immobilized Anti-TMT Antibody Resin Enrichment.

Protein S-acylation is a reversible post-translational modification (PTM). It is present on diverse proteins and has important roles in regulating protein function. Aminolysis with hydroxylamine is widely used in the global identification of the PTM. However, the identification is indirect. Distinct criteria have been used for identification, and the false discovery rate has not been addressed. Here, we report a site-specific method for S-acylation identification based on tagging of S-acylation sites with iodoTMT0. Efforts to improve the performance of the method and confidence of identification are discussed, highlighting the importance of reducing contaminant peptides and keeping the recovery rate consistent between aliquots with or without hydroxylamine treatment. With very stringent criteria, presumptive S-acylation sites of 269, 684, 695, and 780 were identified from HK2 cells, HK11 cells, mouse brain, and mouse liver samples, respectively. Among them, the newly identified protein S-acylation sites are equivalent to 34% of human and 24% of mouse S-acylation sites reported previously. In addition, false-positive rates for S-acylation identification and S-acylation abundances were estimated. Significant differences in S-acylation abundance were found from different samples (from 0.08% in HK2 cells to 0.76% in mouse brain), and the false-positive rates were significantly higher for samples with a low abundance of S-acylation.

Revisiting Cytomegalovirus Serology in Allogeneic Hematopoietic Cell Transplant Recipients.

BACKGROUND: Allogeneic hematopoietic cell transplant recipients (allo-HCTRs) with positive cytomegalovirus (CMV) serology may have false-positive results due to blood product transfusion-associated passive immunity. METHODS: This single-center cohort study included allo-HCTRs with negative baseline (at malignancy diagnosis) CMV serology and indeterminate/low-positive (CMV IgG titer, ≥0.6-<50 U/mL) pretransplant CMV serology with negative pretransplant plasma CMV DNAemia. The CMV status of those patients was reclassified from R+ to R- (CMVR- reclassification group). We compared those patients to allo-HCTRs with negative (CMV IgG titer <0.6 U/mL) pretransplant CMV IgG (CMVR- group). We describe the number and type of patients whose pretransplant CMV status was reclassified from indeterminate/positive to negative. We reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups to assess the safety of this approach. RESULTS: Among 246 (84.5%) of 291 transplanted patients identified as CMVR+ pretransplant, 60 (24.4%) were reclassified from CMV serology indeterminate (N:10)/low-positive (N:50) to R-. Only 1 of 60 patients (1.67%) in the CMVR- reclassification group versus 3 of 44 (6.8%; P = .30) in the CMVR- group developed CMV DNAemia during the follow-up period. There were no significant differences in the number of CMV DNAemia tests performed, CMV DNAemia range, and time posttransplant between the 2 groups. CONCLUSIONS: One of 4 allo-HCT CMVR+ may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV serology testing at hematologic malignancy diagnosis in allo-HCT candidates and careful review of pretransplant CMV IgG titers may help correctly classify CMV serology status.

Repeat testing of mpox specimens with late CTs improves detection of potential false positive cases.

The mpox pandemic necessitated the rapid development of clinical assays for monkeypox virus detection. While the majority of mpox specimens have high viral loads with corresponding early cycle threshold (CT) values, reports have indicated some specimens with late CT values can represent false positive results. To mitigate this risk, the Centers for Disease Control and Prevention (CDC) published an advisory recommending repeat testing of all specimens with CT values ≥34. However, limited experimental data were available to support this specific cutoff. In this study, we examine whether a more conservative approach in which all specimens with CT values ≥29 are repeated would improve the detection of potential false positive results. Compared to the CDC algorithm, our approach identified an additional 20% (5/25) of potential false positive results. To assess the impact of this cutoff on laboratory workload, we modeled the expected increase in test volume and turnaround time (TAT) relative to the CDC method. Using a lower repeat threshold, test volume increased by 0.7% while mean TAT increased by less than 15 minutes. Overall, a lower threshold than recommended by the CDC for repeating late CT mpox specimens may reduce the number of false positives reported while minimally impacting testing volume and TAT.

A public, cross-reactive glycoprotein epitope confounds Ebola virus serology.

Ebola disease (EBOD) in humans is a severe disease caused by at least four related viruses in the genus Orthoebolavirus, most often by the eponymous Ebola virus. Due to human-to-human transmission and incomplete success in treating cases despite promising therapeutic development, EBOD is a high priority in public health research. Yet despite almost 50 years since EBOD was first described, the sources of these viruses remain undefined and much remains to be understood about the disease epidemiology and virus emergence and spread. One important approach to improve our understanding is detection of antibodies that can reveal past human infections. However, serosurveys routinely describe seroprevalences that imply infection rates much higher than those clinically observed. Proposed hypotheses to explain this difference include existence of common but less pathogenic strains or relatives of these viruses, misidentification of EBOD as something else, and a higher proportion of subclinical infections than currently appreciated. The work presented here maps B-cell epitopes in the spike protein of Ebola virus and describes a single epitope that is cross-reactive with an antigen seemingly unrelated to orthoebolaviruses. Antibodies against this epitope appear to explain most of the unexpected reactivity towards the spike, arguing against common but unidentified infections in the population. Importantly, antibodies of cross-reactive donors from within and outside the known EBOD geographic range bound the same epitope. In light of this finding, it is plausible that epitope mapping enables broadly applicable specificity improvements in the field of serology.

A single-center, multi-factor, retrospective study to improve the diagnostic accuracy of primary prostate cancer using [68Ga]Ga-PSMA-11 total-body PET/CT imaging.

PURPOSE: To improve the diagnostic accuracy of initial detection in patients with suspected primary prostate cancer (PCa). METHODS: Eighty-four patients who underwent Gallium-68-labeled prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) total-body positron emission tomography/computed tomography (PET/CT) imaging before treatment in our department were enrolled. The maximum standard uptake value (SUVmax) of the prostate (SUVmax-PSMA), liver (SUVmax-PSMA-L), and mediastinal blood pool (SUVmax-PSMA-M) was measured using [68Ga]Ga-PSMA-11 total-body PET/CT imaging. The [68Ga]Ga-PSMA-11 derived metabolic tumor volume (MTV), the total lesion (TLP), and the cross-sectional areas of focal concentration in the prostate (CAP) were also determined. Besides, the prostate-specific antigen (PSA) levels and the above imaging characteristics were analyzed using receiver operating characteristic curves to identify the cutoff value to improve the diagnostic accuracy of suspected PCa. Finally, a multivariate regression analysis was conducted to discover the independent predictor to improve the diagnostic accuracy on [68Ga]Ga-PSMA-11 total-body imaging. RESULTS: There was no significant difference between the PCa and Non-PCa groups in age, height, weight, injected dose, except for the PSA levels, the SUVmax-PSMA, TLP, MTV, and CAP. Besides, the SUVmax-PSMA-T/L and SUVmax-PSMA-T/M derived from SUVmax-PSMA were both significantly different. In addition, the areas under the curve of PSA levels, SUVmax-PSMA, SUVmax-PSMA-T/L, SUVmax-PSMA-T/M, TLP, MTV, and CAP to predict PCa on [68Ga]Ga-PSMA-11 imaging were 0.620 (95% confidence interval (CI) 0.485-0.755), 0.864 (95% CI 0.757-0.972), 0.819 (95% CI 0.704-0.935), 0.876 (95% CI 0.771-0.980), 0.845 (95% CI 0.741-0.949), 0.820 (95% CI 0.702-0.938), 0.627 (95% CI 0.499-0.754), respectively. However, a multivariate regression analysis showed that SUVmax-PSMA was an independent predictor, with a cutoff value of 11.5 and an odds ratio of 1.221. CONCLUSION: The SUVmax-PSMA with a cutoff value of 11.5 was an independent predictor to improve the diagnostic accuracy of PCa on [68Ga]Ga-PSMA-11 total-body imaging.

Problem Solving MRI to Reduce False-Positive Biopsy Related to Breast US: Conductivity vs. DWI vs. Abbreviated Contrast-Enhanced MRI.

BACKGROUND: While breast ultrasound (US) is a useful tool for diagnosing breast masses, it can entail false-positive biopsy results because of some overlapping features between benign and malignant breast masses and subjective interpretation. PURPOSE: To evaluate the performance of conductivity imaging for reducing false-positive biopsy results related to breast US, as compared to diffusion-weighted imaging (DWI) and abbreviated MRI consisting of one pre- and one post-contrast T1-weighted imaging. STUDY TYPE: Prospective. SUBJECTS: Seventy-nine women (median age, 44 years) with 86 Breast Imaging Reporting and Data System (BI-RADS) category 4 masses as detected by breast US. FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted turbo spin echo sequence, DWI, and abbreviated contrast-enhanced MRI (T1-weighted gradient echo sequence). ASSESSMENT: US-guided biopsy (reference standard) was obtained on the same day as MRI. The maximum and mean conductivity parameters from whole and single regions of interest (ROIs) were measured. Apparent diffusion coefficient (ADC) values were obtained from an area with the lowest signal within a lesion on the ADC map. The performance of conductivity, ADC, and abbreviated MRI for reducing false-positive biopsies was evaluated using the following criteria: lowest conductivity and highest ADC values among malignant breast lesions and BI-RADS categories 2 or 3 on abbreviated MRI. STATISTICAL TESTS: One conductivity parameter with the maximum area under the curve (AUC) from receiver operating characteristics was selected. A P-value <0.05 was considered statistically significant. RESULTS: US-guided biopsy revealed 65 benign lesions and 21 malignant lesions. The mean conductivity parameter of the single ROI method was selected (AUC = 0.74). Considering conductivity (≤0.10 S/m), ADC (≥1.60 × 10-3 mm2 /sec), and BI-RADS categories 2 or 3 reduced false-positive biopsies by 23% (15 of 65), 38% (25 of 65), and 43% (28 of 65), respectively, without missing malignant lesions. DATA CONCLUSION: Conductivity imaging may show lower performance than DWI and abbreviated MRI in reducing unnecessary biopsies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Characterization of the alcohol biomarker phosphatidylethanol in donor whole blood and apheresis red blood cells: Implications for transfusion recipients.

INTRODUCTION: Phosphatidylethanol (PEth) is a long-term marker of alcohol consumption used frequently in clinical scenarios such as liver transplant evaluation. Recent cases have demonstrated that packed red blood cell (pRBC) transfusion creates the potential for artificial elevation or decrease of observed PEth concentrations in recipients. Very little is known about the prevalence or stability of PEth in pRBCs. METHODS: Apheresis and whole-blood (WB) donations were tested for PEth using liquid chromatography - tandem mass spectrometry with limit of quantitation 10 ng/mL. Units were stored under routine blood bank conditions to evaluate the stability of PEth and the impact of irradiation. RESULTS: Over 40% of apheresis and WB donors had PEth ≥10 ng/mL (maximum observed 587 ng/mL). As WB units were processed into component pRBCs, PEth concentrations increased and were higher than donor WB levels (EDTA sample) prior to collection (maximum observed 711 ng/mL). Storage for up to 5 weeks post donation resulted in mean 17.3% decrease in PEth-positive units; in contrast to a prior report, we observed no PEth formation in units with negative (<10 ng/mL) baseline concentrations. Irradiation of pRBCs did not substantially affect PEth concentrations in either PEth-positive or PEth-negative units. DISCUSSION: PEth concentrations in healthy blood donors may potentially confound alcohol use or abstinence assessment in pRBC recipients. Transfusion medicine services and clinical practices such as transplantation and behavioral medicine should recognize this phenomenon and collaborate on testing protocols to appropriately interpret PEth in pRBC recipients.

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.

Emotion constructs and outcome measures following false positive breast screening test results: A systematic review of reporting clarity and selection rationale.

OBJECTIVE: (i) To systematically identify constructs and outcome measures used to assess the emotional and mood impact of false positive breast screening test results; (ii) to appraise the reporting clarity and rationale for selecting constructs and outcome measures. METHODS: Databases (MEDLINE, CINAHL, PsycINFO) were systematically searched from 1970. Studies using standardised and non-standardised outcome measures to evaluate the emotion or mood impact of false positive breast screening test results were eligible. A 15-item coding scheme was devised to appraise articles on clarity and rationale for selected constructs and measures. RESULTS: Forty-seven articles were identified. The most investigated constructs were general anxiety and depression and disease-specific anxiety and worry. Twenty-two standardised general outcome questionnaire measures and three standardised disease-specific outcome questionnaire measures were identified. Twenty articles used non-standardised scales/items. Reporting of constructs and outcome measures was generally clear, but rationales for their selection were lacking. Anxiety was typically justified, but justification for depression was almost always absent. Practical and psychometric justification for selecting outcome measures was lacking, and theoretical rationale was absent. CONCLUSIONS: Heterogeneity in constructs and measures, coupled with unclear rationale for these, impedes a thorough understanding of why there are emotional effects of false positive screening test results. This may explain the repeated practice of investigating less relevant outcomes such as depression. There is need to develop a consensual conceptual model of and standardised approach to measuring emotional impact from cancer screening test results, to address heterogeneity and other known issues of interpreting an inconsistent evidence base.

Towards automated animal density estimation with acoustic spatial capture-recapture.

Passive acoustic monitoring can be an effective way of monitoring wildlife populations that are acoustically active but difficult to survey visually, but identifying target species calls in recordings is non-trivial. Machine learning (ML) techniques can do detection quickly but may miss calls and produce false positives, i.e., misidentify calls from other sources as being from the target species. While abundance estimation methods can address the former issue effectively, methods to deal with false positives are under-investigated. We propose an acoustic spatial capture-recapture (ASCR) method that deals with false positives by treating species identity as a latent variable. Individual-level outputs from ML techniques are treated as random variables whose distributions depend on the latent identity. This gives rise to a mixture model likelihood that we maximize to estimate call density. We compare our method to existing methods by applying it to an ASCR survey of frogs and simulated acoustic surveys of gibbons based on real gibbon acoustic data. Estimates from our method are closer to ASCR applied to the dataset without false positives than those from a widely used false positive "correction factor" method. Simulations show our method to have bias close to zero and accurate coverage probabilities and to perform substantially better than ASCR without accounting for false positives.

The significance of low titer serum cryptococcal antigen testing from 2017 to 2023 performed in a tertiary care center.

Several false positive low serum cryptococcal antigen (SCrAg) reports by lateral flow assay (LFA) were identified in late 2016 at our tertiary care hospital. After the recall and correction of the problem in the reagent, we studied the significance of SCrAg LFA ≤ 1:10 from January 2017 to October 2023. Of 20 patients with 31 samples of SCrAg LFA ≤ 1:10, 14 patients (70%) were classified as true positives, four (20%) were indeterminate, and only two (10%) patients were false positives. If a new SCrAg LFA ≤ 1:10 is detected, it should be repeated, and additional workup should be pursued.

We studied the significance of low serum cryptococcal antigen (SCrAg) titer lateral flow assay (LFA) ≤ 1:10 from January 2017 to October 2023. Of 20 patients with SCrAg LFA ≤ 1:10, only two patients (10%) were false positives. If a new SCrAg ≤ 1:10 is detected, it should be repeated, and additional workup should be done.

Assessment of the role of false-positive alerts in computer-aided polyp detection for assistance capabilities.

BACKGROUND AND AIM: False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. METHODS: The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. RESULTS: Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403). CONCLUSION: The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

Statistically significant differences versus convincing evidence of real treatment effects: an analysis of the false positive risk for single-centre trials in anaesthesia.

BACKGROUND: The American Statistical Association has highlighted problems with null hypothesis significance testing and outlined alternative approaches that may 'supplement or even replace P-values'. One alternative is to report the false positive risk (FPR), which quantifies the chance the null hypothesis is true when the result is statistically significant. METHODS: We reviewed single-centre, randomised trials in 10 anaesthesia journals over 6 yr where differences in a primary binary outcome were statistically significant. We calculated a Bayes factor by two methods (Gunel, Kass). From the Bayes factor we calculated the FPR for different prior beliefs for a real treatment effect. Prior beliefs were quantified by assigning pretest probabilities to the null and alternative hypotheses. RESULTS: For equal pretest probabilities of 0.5, the median (inter-quartile range [IQR]) FPR was 6% (1-22%) by the Gunel method and 6% (1-19%) by the Kass method. One in five trials had an FPR ≥20%. For trials reporting P-values 0.01-0.05, the median (IQR) FPR was 25% (16-30%) by the Gunel method and 20% (16-25%) by the Kass method. More than 90% of trials reporting P-values 0.01-0.05 required a pretest probability >0.5 to achieve an FPR of 5%. The median (IQR) difference in the FPR calculated by the two methods was 0% (0-2%). CONCLUSIONS: Our findings suggest that a substantial proportion of single-centre trials in anaesthesia reporting statistically significant differences provide limited evidence of real treatment effects, or, alternatively, required an implausibly high prior belief in a real treatment effect. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42023350783).

Continuous cardiac monitoring in epilepsy: an implantable loop manual activation algorithm for improving ECG signal acquisition accuracy.

BACKGROUND: The muscle artifacts, caused by prominent muscle contractions, mimicking cardiac arrhythmias, might compromise the ECG signal quality and the implantable loop recorder memory capacity in patients with epilepsy. We developed an epileptic seizures clinical pattern-based implantable loop recorder manual activation algorithm, presenting its real-world efficacy here. METHODS: One hundred ninety-three patients (18-60 years) with drug-resistant focal epilepsy were consecutively enrolled and underwent a subcutaneous loop recorder implantation. Patients with focal onset-aware seizures and patients with focal impaired awareness seizures /bilateral tonic-clonic seizures without aura were recommended to use the activator once - just after the episode. Patients with focal impaired awareness seizures/bilateral tonic-clonic seizures with aura, the caregivers of patients experiencing status epilepticus, were advised to use the activator twice - during the aura and after the episode/ regaining consciousness. RESULTS: Six thousand four hundred ninety-four ECG traces (4826 - auto-triggered events, 1668 - person-activated events) were recorded and analyzed. The rate of true positive events in the person-activated group was statistically higher than in the autoactivation group (72.5% vs.19.4%, p < 0.0001). Person-activated false-positive events were observed in 30.5% of patients with focal impaired awareness seizures and 27.7% in patients with bilateral tonic-clonic seizures. The highest rate of false-positive events (61.5%) was detected in patients undergoing epileptic status, and the lowest rate (3.8%) - was in patients with focal onset aware seizures. The rate of false-positive events was significantly higher in patients with impaired awareness seizures without aura both in focal impaired awareness (45.5% vs. 19.3%, p < 0.0001) and bilateral tonic-clonic seizure groups (38.8% vs. 5.9%, p < 0.0001). CONCLUSIONS: Arrhythmias with varying clinical outcomes are expected in epilepsy patients and have been monitored continuously. The specified loop recorder external activation algorithm can improve the clinically relevant cardiac arrhythmia detection accuracy in epilepsy patients and the value of future studies.

False-positive alarms in patients with implantable loop recorder followed by remote monitoring: A systematic review.

Remote Monitoring (RM) has been shown to provide useful information about arrhythmic events in patients with implantable loop recorders (ILRs), however there is few and conflicting data about the false positive (FP) alarms burden and characteristics among ILR recipients. The aim of the present systematic review was to evaluate incidence and characteristics of FP alarms among ILR patients followed by RM. We developed a systematic research in Embase, MEDLINE and PubMed databases and selected all papers focused on false positive ILR transmissions published from June 1, 2013 to June 1, 2023. Case reports, meeting summaries, posters and simple reviews were excluded. Twelve reports were finally selected, including five prospective and seven retrospective studies. Information about population characteristics, device type and setting, overall transmissions and FP alarms and any adopted strategies to reduce them were extracted from an overall population of 3.305 patients. FP alarms were 59.7% of the overall remote transmissions and were found in 1/5 of the analyzed population. FP alarms for atrial fibrillation were the most common cause of false transmissions and were mainly due to premature atrial and ventricular complexes. No clinical predictors of FP alarms were identified, except for nonparasternal ILR implantation site. Since the overload work due to FP alarms might reduce the benefit of remote monitoring of ILR patients, the device optimization is an important step until an help from machine-learning algorithms is available.

Aortic isthmus flow reversal in fetal coarctation of the aorta and the associated factors.

INTRODUCTION: The aim of this study was to investigate the presence of aortic isthmus flow reversal and its associated factors in fetuses with positive and false-positive coarctation of the aorta (CoA) compared with normal controls. MATERIAL AND METHODS: Pregnant women with fetuses suspected of CoA and normal control were enrolled, and these women experienced prenatal ultrasound scan and followed up for 6 months after birth to confirm the presence of CoA. All the ultrasound parameters were analyzed. RESULTS: A total of 134 pregnant women were enrolled, with 43 CoA-positive fetuses and 91 CoA false-positive fetuses, and 334 matched pregnant women were enrolled in the control group. Aortic isthmus flow reversal occurred in 28 (65.1%) fetuses in the CoA-positive group, significantly (p < 0.05) more than in the false-positive (37 or 40.7%) or control group (64 or 19.2%). Aortic isthmus flow reversal was mostly in the full systole (n = 17 or 60.7%) or late systole and early-middle diastole (n = 10 or 35.7%) in the CoA-positive fetuses (n = 27 or 96.4%), significantly (p < 0.001) different from that in the false-positive or control group. The aortic isthmus flow reversal peak systolic velocity (PSV), flow volume, and ratio of reversed flow/forward flow were significantly (p < 0.05) increased in the CoA-positive and false-positive groups than in the control group. The aortic isthmus flow reversal incidence was significantly (p < 0.05) correlated with the middle cerebral artery (MCA) PSV in the total three groups or in the false-positive group but was significantly (p < 0001) negatively correlated with the MCA resistance index (RI) in the CoA-positive group. The incidence of the aortic isthmus flow reversal was significantly (p < 0.05) positively correlated with the umbilical artery (UA) RI in the false-positive group and with the UA RI in the total three groups. Independently associated factors for aortic isthmus flow reversal were isthmic flow volume/CCO (combined cardiac output) in the CoA-positive group. CONCLUSIONS: Reversal of flow in the aortic isthmus is much more common in true-positive cases of CoA as compared to controls, and isthmic flow reversal in the full systolic phase only suggests presence of CoA. The aortic isthmic reversed flow volume accounts for over half of the isthmic forward flow volume in the CoA-positive fetuses than in the normal controls.

Development of a new staining protocol for the Kleihauer-Betke test to facilitate the reading of difficult cases.

BACKGROUND: The Kleihauer-Betke (KB) test allows the detection of fetal red blood cells (containing fetal hemoglobin, HbF) in the maternal blood to identify and quantify potential fetal-maternal hemorrhages. In certain cases, detecting fetal red blood cells with conventional staining is difficult. False-positive results or overestimation of the quantity of fetal red blood cells may occur in cases of maternal hemoglobinopathy. In this study, we developed a new staining protocol to facilitate the reading of difficult smears and improve the precision of the quantification of fetal red blood cells; we also analyzed the performance of this new method. This study assessed blood samples with and without hemoglobin abnormalities, which present difficulties when interpreting the KB test. METHODS: The new staining formula is based on an improved elution technique and the use of a different stain instead of hematoxylin. To test this staining method, 16 samples from patients with abnormal hemoglobin electrophoresis and 14 samples from patients with normal hemoglobin electrophoresis were analyzed using the KB test with the classical staining method and the new staining method. In addition, a second series was prepared using the same samples spiked with fetal red blood cells from newborn blood, to compare the accuracy of the two methods in identifying fetal red blood cells. RESULTS: In the 60 slides analyzed with both staining methods, we found that the new technique improved the accuracy from 78 to 85%; lowered the coefficient of variation between the operators, which decreased from 20.7% to 12.7%; increased the specificity in our population from 56 to 70%; and decreased the number of false-positive cases by 30%. CONCLUSIONS: We successfully developed a new staining technique that facilitates the reading of difficult slides and improves the specificity of the detection of fetal red blood cells. This technique is recommended as a secondary method to use before sending the sample for additional exploration.

Three cases of infectious mononucleosis with concurrent false-positive non-treponemal and treponemal tests: Serological findings masquerading as syphilis.

Biological false-positive reactions to non-treponemal syphilis tests occur under various conditions, including in patients with infectious mononucleosis. However, false-positive treponemal test results are rarely reported. We present three cases of Epstein-Barr virus-associated infectious mononucleosis that exhibited concurrent false-positive results in both treponemal and non-treponemal tests, effectively imitating syphilis serology. Notably, the false-positive treponemal test results were transient and persisted for more than 6 months before reverting to negative. This is atypical for true Treponema pallidum infection (syphilis), in which treponemal tests usually remain positive for life. This case series highlights the potential for misdiagnosis and emphasizes the importance of careful interpretation of syphilis serology results in the context of infectious mononucleosis. This is particularly important when typical syphilis symptoms are absent, as in our patients. The similarity in the clinical manifestations between infectious mononucleosis and syphilis, including sore throat, lymphadenopathy, rash, and hepatitis, further complicates the diagnostic process. Clinicians should consider recent Epstein-Barr virus-associated infectious mononucleosis when interpreting positive syphilis serology, especially in young adults presenting with mononucleosis-like symptoms. Follow-up serological testing is useful to avoid unnecessary treatment and potential patient mismanagement.

Healthcare professionals' experiences of caring for women with false-positive screening test results in the National Health Service Breast Screening Programme.

BACKGROUND: Understanding healthcare professionals' (HCPs) experiences of caring for women with false-positive screening test results in the National Health Service Breast Screening Programme (NHSBSP) is important for reducing the impact of such results. METHODS: Interviews were undertaken with 12 HCPs from a single NHSBSP unit, including advanced radiographer practitioners, breast radiographers, breast radiologists, clinical nurse specialists (CNSs), and a radiology healthcare assistant. Data were analysed thematically using Template Analysis. RESULTS: Two themes were produced: (1) Gauging and navigating women's anxiety during screening assessment was an inevitable and necessary task for all participants. CNSs were perceived as particularly adept at this, while breast radiographers reported a lack of adequate formal training. (2) Controlling the delivery of information to women (including amount, type and timing of information). HCPs reported various communication strategies to facilitate women's information processing and retention during a distressing time. CONCLUSIONS: Women's anxiety could be reduced through dedicated CNS support, but this should not replace support from other HCPs. Breast radiographers may benefit from more training to emotionally support recalled women. While HCPs emphasised taking a patient-centred communication approach, the use of other strategies (e.g., standardised scripts) and the constraints of the 'one-stop shop' model pose challenges to such an approach. PATIENT AND PUBLIC CONTRIBUTION: During the study design, two Patient and Public Involvement members (women with false-positive-breast screening test results) were consulted to gain an understanding of patient perspectives and experiences of being recalled specifically in the NHSBSP. Their feedback informed the formulations of the research aim, objectives and the direction of the interview guide.