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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.
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Proteínas , Proteínas/metabolismo , Bases de Dados Factuais , Ligantes , Simulação de Acoplamento Molecular , Ligação ProteicaRESUMO
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.
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Processamento de Proteína Pós-Traducional , Proteínas , Animais , Camundongos , Humanos , Acilação , Lipoilação , Hidroxilamina , HidroxilaminasRESUMO
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.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplantados , Estudos de Coortes , Transplante Homólogo/efeitos adversos , Anticorpos Antivirais/uso terapêutico , Imunoglobulina G , Estudos RetrospectivosRESUMO
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.
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Mpox , Estados Unidos , Humanos , Algoritmos , Bioensaio , Centers for Disease Control and Prevention, U.S. , LaboratóriosRESUMO
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.
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Isótopos de Gálio , Radioisótopos de Gálio , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
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.
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Neoplasias da Mama , Meios de Contraste , Feminino , Humanos , Adulto , Estudos Prospectivos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Biópsia , Biópsia Guiada por Imagem , Diagnóstico Diferencial , Neoplasias da Mama/diagnóstico por imagem , Sensibilidade e EspecificidadeRESUMO
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.
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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.
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Ansiedade , Neoplasias da Mama , Depressão , Emoções , Humanos , Neoplasias da Mama/psicologia , Neoplasias da Mama/diagnóstico , Feminino , Ansiedade/psicologia , Ansiedade/diagnóstico , Reações Falso-Positivas , Depressão/psicologia , Depressão/diagnóstico , Detecção Precoce de Câncer/psicologia , Avaliação de Resultados em Cuidados de Saúde , Inquéritos e Questionários , Programas de Rastreamento/métodosRESUMO
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.
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Pólipos do Colo , Colonoscopia , Diagnóstico por Computador , Humanos , Colonoscopia/métodos , Pólipos do Colo/diagnóstico , Pólipos do Colo/diagnóstico por imagem , Diagnóstico por Computador/métodos , Reações Falso-Positivas , Masculino , Estudos Prospectivos , Inteligência Artificial , Feminino , Pessoa de Meia-Idade , Estudos Cross-Over , Adenoma/diagnóstico , Adenoma/diagnóstico por imagemRESUMO
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).
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Anestesia , Anestesiologia , Humanos , Teorema de Bayes , Interpretação Estatística de Dados , Projetos de PesquisaRESUMO
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.
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Epilepsia Tônico-Clônica , Epilepsia , Humanos , Epilepsia Tônico-Clônica/diagnóstico , Convulsões/diagnóstico , Arritmias Cardíacas , Algoritmos , EletrocardiografiaRESUMO
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.
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Alarmes Clínicos , Eletrocardiografia Ambulatorial , Humanos , Eletrocardiografia Ambulatorial/instrumentação , Reações Falso-Positivas , Arritmias CardíacasRESUMO
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.
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Transfusão Feto-Materna , Leitura , Gravidez , Feminino , Recém-Nascido , Humanos , Sangue Fetal/química , Hemoglobina Fetal/análise , Contagem de Eritrócitos , Coloração e Rotulagem , Transfusão Feto-Materna/diagnósticoRESUMO
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.
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Neoplasias da Mama , Medicina Estatal , Feminino , Humanos , Mamografia/psicologia , Pessoal de Saúde , Pessoal Técnico de Saúde , Atenção à Saúde , Neoplasias da Mama/diagnóstico , Pesquisa QualitativaRESUMO
Mysids are small crustaceans that are closely related to shrimp/prawns and crabs but not subject to food allergen labeling requirements for raw materials. In the past, a processed food that contained Japanese smelt (wakasagi) was suspected of producing a false-positive result in shrimp/prawn and crab allergen test because of the presence of consumed mysids. However, there was no reported methods to confirm mysid presence. Therefore, we developed a PCR method to detect mysids. The developed PCR method had high specificity for a mysid species, with no amplification observed from samples of shrimp, crab, krill, mantis shrimp, or the meat of Japanese smelt. In addition, DNA extracted from the internal organs of Japanese smelt was amplified by this PCR method, and sequencing revealed mysid DNA. This confirmed that mysids remained in the internal organs of Japanese smelt following consumption. This PCR method for mysid detection even amplified Japanese smelt-containing processed food samples that were suspected to have produced a false-positive result in shrimp/prawn and crab ELISA. Thus, this PCR method would enable to detect such false positives are caused by mysid contamination.
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Alérgenos , Crustáceos , Reação em Cadeia da Polimerase , Animais , Reação em Cadeia da Polimerase/métodos , Alérgenos/análise , Reações Falso-Positivas , Contaminação de Alimentos/análise , Hipersensibilidade Alimentar , Anomuros/genética , DNA/análise , Ensaio de Imunoadsorção Enzimática/métodos , Análise de Alimentos/métodosRESUMO
Background and Objectives: Breast cancer is one of the most widespread cancers among the female population around the world and is curable if diagnosed in an early stage. Consequently, breast cancer screening imaging techniques have greatly evolved and adjusted over the last decades. Alongside mammography, sonoelastography became an important tool for breast cancer detection. However, sonoelastography still has its limitations, namely, there is still a high occurrence of false positive results in the BIRADS 4 category. The aim of our study is to identify potential false positive predictors and to ascertain the factors influencing the quality of strain ultrasound elastography for the evaluation of suspicious solid breast lesions categorized as BIRADS 4B, 4C, and 5. Materials and Methods: We conducted a retrospective study in a single private medical center in Timisoara between January 2017 and January 2022 analyzing 1625 solid breast lesions by the sonoelastography strain using a standardized BIRADS-US lexicon. Results: Our study showed that most sonoelastography factors linked to incorrect and overdiagnosis were due to a nodule dimension (OR = 1.02 per unit increase), posterior acoustic shadowing (OR = 12.26), reactive adenopathy (OR = 6.35), and an increased TES score (TES3 OR = 6.60; TES4 OR = 23.02; TES5 OR = 108.24). Regarding patient characteristics, age (OR = 1.09 per unit increase), BMI, (OR = 1.09 per unit increase), and breastfeeding history (OR = 3.00) were observed to increase the likelihood of false positive results. On the other hand, the nodules less likely to be part of the false positive group exhibited the following characteristics: a regular shape (OR = 0.27), homogenous consistency (OR = 0.42), and avascularity (OR = 0.22). Conclusions: Older age, high BMI, patients with a breastfeeding history, and those who exhibit the following specific nodule characteristics were most often linked to false positive results: large tumors with posterior acoustic shadowing and high elasticity scores, accompanied by reactive adenopathy. On the other hand, homogenous, avascular nodules with regular shapes were less likely to be misdiagnosed.
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Neoplasias da Mama , Técnicas de Imagem por Elasticidade , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Reações Falso-Positivas , Adulto , Idoso , Detecção Precoce de Câncer/métodosRESUMO
OBJECTIVE: To develop the method of biological fluids' sample processing and mebeverine detection to exclude false results' receiving when diagnosing drug intoxication. MATERIAL AND METHODS: The study was carried out using «Mebeverine¼ (NJCO «North star¼, Russia) medicine and hydrolysis by enzymes, namely papain, chymotrypsin, trypsin, chymopsin and hyaluronidase, was applied for sample processing. The extractions were analyzed by methods of HPLC-MS/MS on Nexera XR modular liquid chromatograph with LCMS-8050 (Shimadzu) tandem mass spectrometer and GC-MS on gas chromatograph connected with QP-2020 (Shimadzu, Japanese) mono quadrupole mass spectrometer. RESULTS AND CONCLUSION: It has been revealed that using selective method of sample processing, which consists of aqueous phase extraction at pH=2-4 and enzymatic hydrolysis by papain and hyaluronidase during isolation from blood, is required to detect mebeverine in biological liquids. It has been proven that the native mebeverine is hydrolyzed to veratric (3.4-dimethoxybenzoic) acid and mebeverine alcohol at alkalotic pH value of medium. It has been shown that mebeverine extraction is necessary to study using HPLC-MS/MS, which will allow to avoid the native mebeverine degradation in chromatograph injector as with GC-MS method analysis.
Assuntos
Papaína , Fenetilaminas , Espectrometria de Massas em Tandem , Hialuronoglucosaminidase , Cromatografia Gasosa-Espectrometria de Massas , Cromatografia Líquida de Alta Pressão/métodosRESUMO
The steep rise in protein sequences and structures has paved the way for bioinformatics approaches to predict residue-residue interactions in protein complexes. Multiple sequence alignments are commonly used in contact predictions to identify co-evolving residues. These contacts, however, often include false positives (FPs), which may impair their use to predict three dimensional structures of biomolecular complexes and affect the accuracy of the generated models. Previously, we have developed DisVis to identify FP in mass spectrometry cross-linking data. DisVis allows to assess the accessible interaction space between two proteins consistent with a set of distance restraints. Here, we investigate if a similar approach could be applied to co-evolution predicted contacts in order to improve their precision prior to using them for modeling. We analyze co-evolution contact predictions with DisVis for a set of 26 protein-protein complexes. The DisVis-reranked and the original co-evolution contacts are then used to model the complexes with our integrative docking software HADDOCK using different filtering scenarios. Our results show that HADDOCK is robust with respect to the precision of the predicted contacts due to the 50% random contact removal during docking and can enhance the quality of docking predictions when combined with DisVis filtering for low precision contact data. DisVis can thus have a beneficial effect on low quality data, but overall HADDOCK can accommodate FP restraints without negatively impacting the quality of the resulting models. Other more precision-sensitive docking protocols might, however, benefit from the increased precision of the predicted contacts after DisVis filtering.
Assuntos
Biologia Computacional , Software , Biologia Computacional/métodosRESUMO
Women tend to make a decision about participation in breast cancer screening and adhere to this for future invitations. Therefore, our study aimed to provide high-quality information on cumulative risks of false-positive (FP) recall and screen-detected breast cancer over multiple screening examinations. Individual Dutch screening registry data (2005-2018) were gathered on subsequent screening examinations of 92 902 women age 49 to 51 years in 2005. Survival analyses were used to calculate cumulative risks of a FP and a true-positive (TP) result after seven examinations. Data from 66 472 women age 58 to 59 years were used to extrapolate to 11 examinations. Participation, detection and additional FP rates were calculated for women who previously received FP results compared to women with true negative (TN) results. After 7 examinations, the cumulative risk of a TP result was 3.7% and the cumulative risk of a FP result was 9.1%. After 11 examinations, this increased to 7.1% and 13.5%, respectively. Following a FP result, participation was lower (71%-81%) than following a TN result (>90%). In women with a FP result, more TP results (factor 1.59 [95% CI: 1.44-1.72]), more interval cancers (factor 1.66 [95% CI: 1.41-1.91]) and more FP results (factor 1.96 [95% CI: 1.87-2.05]) were found than in women with TN results. In conclusion, due to a low recall rate in the Netherlands, the cumulative risk of a FP recall is relatively low, while the cumulative risk of a TP result is comparable. Breast cancer diagnoses and FP results were more common in women with FP results than in women with TN results, while participation was lower.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Mamografia/métodos , Reações Falso-Positivas , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodosRESUMO
PURPOSE: To identify demographic and imaging features of MRI-detected enhancing lesions without clinical, ultrasound, and mammographic correlation associated with false-positive outcomes, impacting patient care. MATERIALS AND METHODS: A retrospective multi-institutional study of imaging studies and patient's chart review of consecutive women with MRI-detected enhancing lesions without clinical, mammogram, or ultrasound correlation between January and December 2018, who underwent MRI-guided biopsy. According to the BI-RADS lexicon, lesions' frequency and imaging features were recorded. The demographic and imaging characteristics variables were correlated with histopathology as the gold standard and an uneventful follow-up of at least one year. Univariate logistic regression analysis was used to explore the correlation between the baseline variables such as age, genetic mutation, family history of breast cancer, personal history of breast cancer, MRI indication, background parenchymal enhancement, and MRI characteristic of the lesion with the false-positive results in main data and subgroup analysis. RESULTS: Two hundred nineteen women (median age 49 years; range 26-85 years) with 219 MRI-detected enhancing lesions that underwent MRI-guided vacuum-assisted biopsy during the study period fulfilled the study criteria and formed the study cohort. Out of 219, 180 lesions (82.2%) yielded benign pathology results, including 137 benign outcomes (76%) and 43 high-risk lesions (24%). Most demographic and imaging characteristics variables did not help to differentiate malignant from benign lesions. The variables that showed statistically significant association with true-positive results in univariate analyses were age (OR 1.05; 95% CI 1.02-1.08; p = 0.0015), irregular mass-lesion shape when compared with oval/round mass lesion (OR 11.2; 95% CI 1.6-78.4; p = 0.015), and clumped and clustered ring of enhancement when compared with homogeneous (OR 3.22, 95% CI 1.40-7.40; p = 0.0058). For participants with mass breast lesion, the hyperintense signal on the T2-weighted sequence (compared to the normal fibroglandular signal) was significantly related to the false-positive result (OR 0.13; 95% CI 0.02-0.76; p = 0.024). CONCLUSION: Young patients, oval/round mass-lesion shape, and homogeneous pattern of non-mass enhancement showed the strongest association with false-positive results of enhancing lesions depicted by MRI. For participants with mass breast lesion, T2-bright mass lesion showed significant association with false-positive result. It may impact the patient's management with a suggestion of follow-up rather than interventional procedure when these demographic and imaging parameters are present, consequently decreasing the patient's anxiety and health care costs.