Heterozygous carriers of the survival of motor neuron 1 (SMN1) gene deletion in parents account for approximately 95% of neonatal spinal muscular atrophy cases. Given the severity of the disease, professional organizations have recommended periconceptional spinal muscular atrophy carrier screening to all couples, regardless of race or ethnicity. However, the prevalence of screening activities in mainland China remains suboptimal, mainly attributed to the limitations of the existing carrier screening methods. Herein, we aimed to develop a low-cost, accessible, and accurate carrier screening method based on duplex droplet digital PCR (ddPCR), to cover a wider population in developing countries, including China. The receiver operating characteristic curve was used to determine the cut-off value of SMN1 copy numbers. Performance validation was conducted for linearity, precision, and accuracy. In total, 482 cases were considered to validate the concordance between the developed ddPCR assay and multiplex ligation-dependent probe amplification. Linear correlations were excellent between the expected concentration of the reference gene and the observed values (R2 > 0.99). Both the intra- and inter-assay precision of our ddPCR assays were less than 6.0%. The multiplex ligation-dependent probe amplification and ddPCR results were consistent in 480 of the 482 cases (99.6%). Two cases with multiplex ligation-dependent probe amplification, suggestive of two copies of SMN1 exon 7, were classified into three copies by ddPCR analysis. The overall correct classification of the samples included in our ddPCR assay was 100%. This study demonstrates that an appropriate cut-off value is an important prerequisite for establishing a semi-quantitative method to determine the SMN1 copy numbers. Compared to conventional methods, our ddPCR assay is low-cost, highly accurate, and has full potential for application in population spinal muscular atrophy carriers screening.

BACKGROUND: Traditionally, liver biopsy has been the gold standard for fibrosis staging. However, it is an invasive, expensive and uncomfortable procedure that is associated with the risk of complications. Thus, non-invasive methods such as shear wave elastography (SWE) have been developed as potential alternatives to liver biopsy. The aim of this study is to evaluate the diagnostic performance of SWE in pediatric patients with liver fibrosis, specifically in a group of Algerian children and to determine whether this method can be a reliable alternative to liver biopsy.
METHODS: This prospective, descriptive, monocentric study evaluated the non-invasive diagnostic performance of 2D-SWE in assessing liver fibrosis in pediatric patients. The assessment was carried out using various statistical methods, including Spearman\'s correlation coefficient, Kappa concordance coefficients, regression analysis, as well as the calculation of area under the receiver operating characteristic (AUROC) values and corresponding cut-off points based on the receiver operating characteristic (ROC) curve.
RESULTS: Our study found that 2D-SWE is strongly correlated with liver biopsy in estimating liver fibrosis in children, with a correlation coefficient greater than 0.8. Furthermore, the Kappa correlation coefficients exceeded 0.8, indicating a strong agreement between 2D-SWE and liver biopsy results. The AUROC value was not less than 0.9 for significant fibrosis and above (≥ F2), indicating that it has satisfactory diagnostic performance in detecting liver fibrosis in children.
CONCLUSIONS: 2D-SWE shows promise as a non-invasive method for evaluating liver fibrosis in children, offering a potential alternative to liver biopsy. Larger studies are needed to substantiate the findings of this study and to confirm the accuracy and reliability of 2D-SWE for assessing liver fibrosis in children.

UNASSIGNED: This study evaluated whether anthropometric measurements and the five times sit-to-stand test could be used to identify dynapenia. The cut-off values of accurate screening tools for identifying dynapenia were also established.
UNASSIGNED: This was a cross-sectional study conducted on individuals ≥ 60 years old (N = 529). All participants underwent handgrip strength measurement, anthropometric measurements and the five times sit-to-stand test. The participants whose handgrip strength was < 28 kg for men and < 18 kg for women were considered to have dynapenia. The association between the recorded variables and dynapenia was determined using logistic regression, and cut-off values were established by performing the Receiver Operating Characteristic curve analysis.
UNASSIGNED: The prevalence of dynapenia was 35.42% in men and 25.61% in women. For males, both calf circumference (≤ 35.2 cm) and the five times sit-to-stand test (≥ 14.6 s) could be used as accurate tools for dynapenia. For females, only the five times sit-to-stand test (≥ 11.8 s) had sufficient accuracy to be used as a screening tool for dynapenia.
UNASSIGNED: The five times sit-to-stand test was an accurate screening tool for identifying dynapenia. The calf circumference could be only used as a screening tool in males.
Calf circumference and the five times a sit-to-stand test can be used as accurate screening tools in males with dynapenia.Only the five times sit-to-stand test had sufficient accuracy in females with dynapenia.The optimal cut-off values established for older males and females are only applicable to the Asian population.

UNASSIGNED: Specific IgE (sIgE) is merely a sensitization marker that cannot be used for allergy diagnosis if there are no associated clinical symptoms. As of 2023, there is still no evidence regarding the quantity of sIgE necessary to confirm or exclude clinical disease. Therefore, this study aimed to calculate cut-offs for sIgE, allowing us to effectively diagnose olive or grass pollen allergy and select allergenic immunotherapy (AIT) candidate patients in a region under high olive and grass allergenic pressure.
UNASSIGNED: An observational retrospective study consisting of the review of electronic medical records from 1,172 patients diagnosed with seasonal rhino-conjunctivitis and suspected allergy to olive or grass pollen. Symptoms correlated with sIgE to Poaceae and Oleaceae whole extracts and sIgE to genuine allergenic components were evaluated. Optimal cut-off values were calculated using receiver operating characteristic curves. Relevant clinical symptoms and AIT indications were taken into consideration when determining the clinical allergy diagnosis.
UNASSIGNED: sIgE to Lolium showed the best area under the curve (AUC) for both diagnosis (0.957) and an indication of AIT (0.872). The optimal cut-off values for grass diagnosis and AIT indication were 1.79 kUA/L and 8.83 kUA/L, respectively. A value of 5.62 kUA/L was associated with a positive likelihood ratio (LR) of 10.08 set for grass allergy. Olea sIgE showed the best AUC for the diagnosis (0.950). The optimal cut-off for diagnosis was 2.41 kUA/L. A value of 6.49 kUA/L was associated with a positive LR of 9.98 to confirm olive pollen allergy. In regard to immunotherapy, Ole e 1 sIgE showed the best AUC (0.860). The optimal cut-off was 14.05 kUA/L. Ole e 1 sIgE value of 4.8 kUA/L was associated with a 0.09 negative LR to exclude olive AIT indication.
UNASSIGNED: The sIgE cut-offs found in this population under high olive and grass allergenic pressure reduce the gap between sensitization and clinical allergy, providing a new tool for the diagnosis of seasonal allergic rhinitis/asthma and helping to discriminate patients who will benefit from AIT.

The high preweaning mortality rate is a concerning issue for the commercial dairy industry. In this context, early identification of at-risk individuals can be instrumental. To address this, we conducted a prospective cohort study with the objective of evaluating plasma immunoglobulin G concentration (pIgG-24 h) and initial BW (IBW) measured at 1d old in 363 male dairy kids (Saanen) for predicting preweaning mortality under commercial conditions. Receiver operator characteristic (ROC) analysis was used to determine critical thresholds for pIgG-24 h and IBW. Subsequently, areas under the curve (AUC), sensitivity (Se), and specificity (Sp) were examined to assess the accuracy of these thresholds. Multivariable regressions were used to model odds ratios (OR) for mortality, controlling for confounding effects between IBW and pIgG-24 h. The mean (±SD) pIgG-24 h and IBW were 16.4 ± 9.37 g/L and 4.0 ± 0.61 kg. Overall mortality ≤ 14d and ≤42d old was 12% and 21%, respectively. Critical pIgG-24 h thresholds predicting mortality ≤ 14 d and ≤42 d old were < 10.1 g/L (AUC = 0.74, Se = 59%, and Sp = 82%) and <11.4 g/L (AUC 0.70, Se = 53%, and Sp = 77%), respectively. Kids with pIgG-24 h < 10.1 g/L were six times more likely to die ≤ 14 d old [OR; 95% CI (6; 3-12)], and kids with pIgG-24 h < 11.4 g/L were four times more likely to die ≤ 42 d old (4; 2-6). The IBW threshold most linked to mortality ≤ 14 d was <3.95 kg (AUC 0.60, Se = 59%, and Sp = 61%). However, this association became inconclusive after adjusting for pIgG-24 h differences. Conversely, an IBW of <3.0 kg was associated with notably higher mortality odds within both 14 and 42 d, irrespective of pIgG-24 h levels (10; 3-37, and 4; 1-20, respectively), suggesting that kids with an IBW < 3.0 kg face an increased likelihood of dying before 42 d, irrespectively of their IgG levels. While our findings suggest pIgG-24 h < 11.4 g/L and IBW < 3.0 kg as strong indicators of early mortality risks in male dairy kids, these results require further validation for other systems.

Obesity is known to be one of the most significant risk factors for essential hypertension in childhood. However, whether obesity cut-offs may predict hypertension screening in adolescents remains controversial. This study investigated the performance of obesity cut-off values for the screening of hypertension in a South African adolescent population. In this cross-sectional study, 1144 adolescents aged between 11 and 17 years were recruited from the Eastern Cape Province of South Africa. Anthropometric and blood pressure (BP) parameters including diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) were measured. Assessment of the sensitivity and specific of obesity cut-off values in predicting hypertension was performed using receiver operating characteristic (ROC) analysis. Obesity was positively associated (p < 0.01) with hypertension. Obese individuals, based on the predicted obesity using BMI percentile cut-off (pBMI85.2%), were more likely to develop hypertension (odds ratio: 2.070; p < 0.001) than their counterparts based on the observed obesity cut-off (pBMI95%) (Odd ratio: 1.748 p = 0.004). The area under the curve (AUC) of BMI percentile and WHtR for screening SBP percentile, and DBP percentile and HR as per ROC analysis, was low (<0.65). Equally, the sensitivity and specificity were low (<0.6) for all BP measures (SBP, DBP, and HR). Furthermore, the cut-off values for blood pressure measures, as established by ROC analysis using anthropometric measures, were far below the recommended cut-off values for hypertension screening. The obesity cut-offs for BMI percentile and WHtR established in this populations showed poor performance in diagnosing hypertension even though they were strong predictors of hypertension.

BACKGROUND: Total knee arthroplasty (TKA) reduces pain and improves physical function; however, not all patients have successful outcomes after surgery. To identify these patients would be critical information for improving rehabilitation programs. The purpose of this study was to clarify the cut-off values of lower extremity muscle strength for predicting postoperative good walking ability.
METHODS: Timed Up and Go test of 105 patients was measured at 6 months postoperatively, and participants were divided into good (< 9.1 s) and poor (≥ 9.1 s) walking ability. Both sides of knee extensor strength (KES) and hip abductor strength (HAS) were measured using hand-held dynamometer preoperatively. Receiver operating characteristic (ROC) curve analysis was used to identify cut-off values for classifying the participants into the two groups.
RESULTS: Of the 105 patients, 54 were allocated in the poor walking ability group, whereas 51 were allocated in the good walking ability group. KES and HAS were significantly greater in the good walking ability group than in the poor walking ability group. ROC curve analysis revealed that the cut-off value for KES was 0.79 Nm/kg (area under the curve (AUC) 0.68; sensitivity 64.7%; specificity 68.5%) on the involved side and 0.86 Nm/kg (AUC 0.73; sensitivity 84.6%; specificity 55.6%) on the uninvolved side, and for HAS was 0.57 Nm/kg (AUC 0.71; sensitivity 60.8%; specificity 71.7%) on the involved side and 0.61 Nm/kg (AUC 0.76; sensitivity 66.7%; specificity 77.4%) on the uninvolved side.
CONCLUSIONS: The cut-off values of preoperative KES and HAS for predicting good walking ability after TKA are 0.79 Nm/kg on the involved side and 0.86 Nm/kg on the uninvolved side, and 0.57 Nm/kg on the involved side and 0.61 Nm/kg on the uninvolved side, respectively. We should provide enhanced pre- and post-operative rehabilitation programs for patients with muscle strength lower than these values.

OBJECTIVE: Among an unselected cohort of men and women from general population (n = 1.668), the prognostic effects of being over the cut-off of all-source dietary caffeine intake were studied.
RESULTS: Prognostic cut-off values for coronary events, incident heart failure (HF), cerebrovascular events (CBV) and arrhythmic events (ARR) were found by means of the receiver-operating-characteristic curves method. Those for HF (>230 mg/day), for CBV (>280 mg/day) and for ARR (>280 mg/day) were confirmed in multivariate Cox analysis adjusted for age, body mass index, circulating thyroid hormone, diabetes mellitus, arterial hypertension, smoking, dietary intake of ethanol, basal heart rate, low-density-lipoprotein cholesterol, forced expiratory volume in 1 s and β-blocking therapy. Being over these cut-off values was associated to a reduced hazard ratio during the follow-up in the whole cohort (HR 0.678, 95%CI 0.567-0.908, p = 0.009 for HF; 0.651, 95%CI 0.428-0.994, p = 0.018 for CBV; 0.395, 95%CI 0.395-0.933, p = 0.022 for ARR) and in men (0.652, 0.442-0.961, p = 0.029; 0.432, 0.201-0.927, p = 0.03; 0.553, 0.302-1.000, p = 0.05, respectively) but not in women. The caffeine-induced risk decrease observed in the whole cohort is therefore entirely attributable to men. In the case of HF, heart rate entered the risk equation in a positive manner without rejecting caffeine. The -163C>A polymorphism of the CYP1A2 gene, codifying for ability to metabolize caffeine, introduced in sensitivity analysis, did not alter the prognostic models.
CONCLUSIONS: Men introducing >230 mg/day caffeine show a reduced risk of HF, and those introducing >280 mg/day a reduced risk of CBV and ARR independent of genetic pattern.

Tandem mass spectrometry (TMS) has emerged an important screening tool for various metabolic disorders in newborns. However, there is inherent risk of false positive outcomes. Objective To establish analyte-specific cutoffs in TMS by integrating metabolomics and genomics data to avoid false positivity and false negativity and improve its clinical utility.
TMS was performed on 572 healthy and 3000 referred newborns. Urine organic acid analysis identified 23 types of inborn errors in 99 referred newborns. Whole exome sequencing was performed in 30 positive cases. The impact of physiological changes such as age, gender, and birthweight on various analytes was explored in healthy newborns. Machine learning tools were used to integrate demographic data with metabolomics and genomics data to establish disease-specific cut-offs; identify primary and secondary markers; build classification and regression trees (CART) for better differential diagnosis; for pathway modeling.
This integration helped in differentiating B12 deficiency from methylmalonic acidemia (MMA) and propionic acidemia (Phi coefficient=0.93); differentiating transient tyrosinemia from tyrosinemia type 1 (Phi coefficient=1.00); getting clues about the possible molecular defect in MMA to initiate appropriate intervention (Phi coefficient=1.00); to link pathogenicity scores with metabolomics profile in tyrosinemia (r2=0.92). CART model helped in establishing differential diagnosis of urea cycle disorders (Phi coefficient=1.00).
Calibrated cut-offs of different analytes in TMS and machine learning-based establishment of disease-specific thresholds of these markers through integrated OMICS have helped in improved differential diagnosis with significant reduction of the false positivity and false negativity rates.

The ISTH-SSC guidelines for lupus anticoagulant (LA) testing recommend using in-house determined cut-off values, pooled normal plasma (PNP) for ratio normalization, and a ratio for the mixing test interpretation. They strongly support the mixing step role in the diagnostic process.
To investigate and compare the LA testing results and interpretations obtained following the ISTH-SSC guidelines or the available alternatives.
Blood samples for LA testing from 462 consecutive patients were evaluated for screening, mixing and confirmatory tests. The analysis focused on the interpretation differences between using (1) the in-house cut-off values versus the manufacturer\'s cut-off values, (2) a normalized ratio calculated using PNP at each run versus the mean of the reference interval, (3) a normalized ratio versus the index of circulating anticoagulant to interpret the mixing step, and (4) a two-step versus three-step procedure.
LA testing outcomes were comparable when using the in-house and manufacturer\'s cut-off values. More positive dilute Russell\'s viper venom (DRVV) time results were obtained with the normalized ratio based on PNP than with the mean of the reference interval. Overall, the mixing test results obtained with the normalized ratio and the index of circulating anticoagulant showed a good agreement. Among the 97 DRVV Screen test-positive samples, 33 and 89 were classified as LA-positive with the 3-step and the 2-step procedure, respectively.
The cut-off value used and the way to normalize ratios had a limited impact. Conversely, it is important to understand the mixing test characteristics to maximize its diagnostic potential.