The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.

Statistical considerations for some issues in clinical bridging studies evaluating companion diagnostic devices.

An in vitro diagnostic device (IVD) that is essential for the safe and effective use of a corresponding therapeutic product is commonly referred to as companion diagnostic device. Clinical trials using companion diagnostic devices (tests) together with therapies can yield the information necessary to address whether both products are safe and effective. A clinical trial ideally assesses safety and effectiveness of a therapy, where the clinical trial enrolls subjects based on the final market ready companion diagnostic test (CDx). However, such a requirement may be difficult to accomplish or impractical to achieve at the time of the clinical trial enrollment, due to unavailability of the CDx. Instead, clinical trial assay(s) (CTA), which are not the final marketable product, are often used in enrollment of patients in a clinical trial. When CTA is used for subject enrollment, a clinical bridging study provides a mechanism to bridge the clinical efficacy of the therapeutic product from CTA to CDx. This manuscript reviews some issues and challenges commonly associated with clinical bridging studies, including missing data, use of local tests for enrollment, prescreening before enrollment, and evaluation of CDx for low positive rate biomarkers, with particular focus on clinical trials using a binary endpoint and provide alternative statistical methodologies to assess effectiveness of CDx.

Alteration of the immune microenvironment in the axillary metastatic lymph nodes of luminal A breast cancer patients.

BACKGROUND: The alteration of the immune microenvironment in the axillary metastatic lymph nodes of luminal A breast cancer patients is still unclear. METHODS: Postsurgical tissues from the enrolled luminal A BCs were divided into five categories: primary BC lesion at stage N0 (PL1), primary BC lesion at stage N1 (PL2), negative axillary lymph node at stage N0 BC (LN1), negative axillary lymph node at stage N1 BC (LN2), and positive axillary lymph node at stage N1 BC (LN3). The frequencies of positive immune markers (CD4, CD8, PD1, PD-L1, T-cell immunoglobulin and mucin domain 3 (TIM3), and forkhead box protein 3 (Foxp3)) in the above tissues were quantified by AKOYA Opal Polaris 7 Color Manual IHC Detection Kit. RESULTS: A total of 50 female patients with luminal A BC were enrolled in this study. Among these patients, 23 had stage N1 disease, and 27 had stage N0 disease. Compared with that in the PL2 subgroup, the frequency of PD-1-positive cells was significantly greater in the PL1 subgroup, whether at the stromal or intratumoral level (P value < 0.05). Both the frequency of CD8 + T cells in LN1 and that in LN2 were significantly greater than that in LN3 (P value < 0.05). The frequency of TIM3 + T cells in LN1 was significantly greater than that in PL1 (P value < 0.05). The frequency of CD8 + TIM3 + T cells was significantly greater in both the LN2 and LN3 groups than in the PL2 group (P value < 0.05). The frequency of CD4 + Foxp3 + T cells was significantly greater in LN1 than in PL1 (P value < 0.05), which was the same for both LN3 and PL2 (P value < 0.05). CONCLUSION: Increased frequencies of CD8 + PD1+, CD8 + TIM3 + and CD4 + Foxp3 + T cells might inhibit the immune microenvironment of axillary metastatic lymph nodes in luminal A breast cancer patients and subsequently promote lymph node metastasis.

Influence of the COVID-19 Pandemic on the Prevalence Pattern of Allergens.

INTRODUCTION: The effect of the COVID-19 pandemic on allergic diseases is not certain, as people's living habits and the environment have been affected by the pandemic. The present study described the influence of the COVID-19 pandemic on the allergen sensitization rate in patients with allergic diseases in central China. The results provide reliable epidemiological data for the prevention and control of allergic diseases during the COVID-19 epidemic. METHODS: Data were collected from a total of 6,915 patients with symptoms of allergic diseases who visited the Third Xiangya Hospital of Central South University in China for allergen testing from January 1, 2018, to December 31, 2021. Patients were divided into a children group (<14 years old), youth group (15∼44 years old), middle-aged group (45∼59 years old), and elderly group (>60 years old). Immunoblotting was used to detect 20 serum allergen-specific IgE (sIgE) antibodies in patient serum samples. We compared the positive rates of various allergens in different age and sex groups before and during the COVID-19 epidemic, and the prevalence data of sIgE sensitization were analysed. RESULTS: Among the 6,915 patients with symptoms of allergic diseases, 2,838 (41.04%) patients were positive for at least one of the allergens. The top three positive rates of inhaled allergens were Dermatophagoides farinae (1,764 cases, 25.51%), Dermatophagoides pteronyssinus (1,616 cases, 23.37%), and house dust (645 cases, 9.33%). The top three positive rates of food allergens were eggs (686 cases, 9.92%), milk (509 cases, 7.36%), and crabs (192 cases, 2.78%). The total positive rate of allergens was higher in men (46.99%) than in women (37.30%). Compared to 2 years before the COVID-19 epidemic, the rate of sensitization to indoor inhalant allergens increased, but outdoor inhalant allergens showed no significant change. The positive rates of milk and eggs peaked during the outbreak of COVID-19 (2020) then declined in 2021. The total positive rate of allergens was higher in males than females before and during the COVID-19 epidemic, but more allergens were different between males and females during the pandemic. Compared to middle-aged and older adults, the children and youth groups were more susceptible to allergic diseases, and they exhibited an increasing positive rate for most common allergens, especially indoor inhalant allergens, during the COVID-19 epidemic than before the pandemic. CONCLUSION: D. pteronyssinus and D. farinae are the most common allergens in South China. Under the background of normalization of epidemic prevention, indoor inhaled allergens should be first in the prevention and control of allergic diseases, and a combination of various indoor cleaning measures should be used to improve the efficiency of interventions.

Accuracy of placental growth factor alone or in combination with soluble fms-like tyrosine kinase-1 or maternal factors in detecting preeclampsia in asymptomatic women in the second and third trimesters: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with soluble fms-like tyrosine kinase-1), and of placental growth factor-based models (placental growth factor combined with maternal factors±other biomarkers) in the second or third trimester to predict subsequent development of preeclampsia in asymptomatic women; (2) estimate a hierarchical summary receiver-operating characteristic curve for studies reporting on the same test but different thresholds, gestational ages, and populations; and (3) select the best method to screen for preeclampsia in asymptomatic women during the second and third trimester of pregnancy by comparing the diagnostic accuracy of each method. DATA SOURCES: A systematic search was performed through MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform databases from January 1, 1985 to April 15, 2021. STUDY ELIGIBILITY CRITERIA: Studies including asymptomatic singleton pregnant women at >18 weeks' gestation with risk of developing preeclampsia were evaluated. We included only cohort or cross-sectional test accuracy studies reporting on preeclampsia outcome, allowing tabulation of 2×2 tables, with follow-up available for >85%, and evaluating performance of placental growth factor alone, soluble fms-like tyrosine kinase-1- placental growth factor ratio, or placental growth factor-based models. The study protocol was registered on the International Prospective Register Of Systematic Reviews (CRD 42020162460). METHODS: Because of considerable intra- and interstudy heterogeneity, we computed the hierarchical summary receiver-operating characteristic plots and derived diagnostic odds ratios, ß, θi, and Λ for each method to compare performances. The quality of the included studies was evaluated by the QUADAS-2 tool. RESULTS: The search identified 2028 citations, from which we selected 474 studies for detailed assessment of the full texts. Finally, 100 published studies met the eligibility criteria for qualitative and 32 for quantitative syntheses. Twenty-three studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the second trimester, including 16 (with 27 entries) that reported on placental growth factor test alone, 9 (with 19 entries) that reported on the soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 6 (16 entries) that reported on placental growth factor-based models. Fourteen studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the third trimester, including 10 (with 18 entries) that reported on placental growth factor test alone, 8 (with 12 entries) that reported on soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 7 (with 12 entries) that reported on placental growth factor-based models. For the second trimester, Placental growth factor-based models achieved the highest diagnostic odds ratio for the prediction of early preeclampsia in the total population compared with placental growth factor alone and soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 63.20; 95% confidence interval, 37.62-106.16 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 6.96; 95% confidence interval, 1.76-27.61 vs placental growth factor alone, 5.62; 95% confidence interval, 3.04-10.38); placental growth factor-based models had higher diagnostic odds ratio than placental growth factor alone for the identification of any-onset preeclampsia in the unselected population (28.45; 95% confidence interval, 13.52-59.85 vs 7.09; 95% confidence interval, 3.74-13.41). For the third trimester, Placental growth factor-based models achieved prediction for any-onset preeclampsia that was significantly better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 27.12; 95% confidence interval, 21.67-33.94 vs placental growth factor alone, 10.31; 95% confidence interval, 7.41-14.35 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 14.94; 95% confidence interval, 9.42-23.70). CONCLUSION: Placental growth factor with maternal factors ± other biomarkers determined in the second trimester achieved the best predictive performance for early preeclampsia in the total population. However, in the third trimester, placental growth factor-based models had predictive performance for any-onset preeclampsia that was better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio. Through this meta-analysis, we have identified a large number of very heterogeneous studies. Therefore, there is an urgent need to develop standardized research using the same models that combine serum placental growth factor with maternal factors ± other biomarkers to accurately predict preeclampsia. Identification of patients at risk might be beneficial for intensive monitoring and timing delivery.

The performance of interferon gamma release assays in patients with nontuberculous mycobacterial infection: a systematic review and meta-analysis.

BACKGROUND: The actual positive rate of interferon gamma release assays (IGRAs) in patients with nontuberculous mycobacteria (NTM) infections remains unclear. This review and meta-analysis present the prevalence of positive IGRAs (T-SPOT.TB and QuantiFERON [QFT] tests) among patients infected with NTM isolates (with or without ESAT-6/CFP-10). METHODS: Several databases, including PubMed, Scopus, Embase, and Web of Science were searched (until June 18th, 2022). Studies that had the following data were included: (1) results of T-SPOT.TB, QuantiFERON (QFT) test, or both, (2) NTM species, and (3) NTM diseases, or NTM colonization. The metaprop command that incorporates a Freeman-Tukey double arcsine transformation is used for pooling proportions. RESULTS: A total of 11 articles (n = 929) were deemed eligible for inclusion. Meta-analysis identified that the overall pooled positive and indeterminate rates of IGRA results in patients with NTM infections was 16% and 5%, respectively. Subgroup analysis showed that the positive rate of IGRAs in patients infected with NTM (without ESAT-6/CFP-10) was 7% (95% CI, 1%-18%), and 44% (95%CI, 22%-68%) in patients infected with NTM (with ESAT-6/CFP-10). In addition, the indeterminate rate of QFT (7%, 95% CI: 4%-12%) was higher than that of T-SPOT.TB (0%; 95% CI, 0%-2%) among the overall population with NTM infections. CONCLUSIONS: The IGRAs have a moderate positive rate for the diagnosis of NTM (expressing ESAT-6/CFP-10) infections, and a significant indeterminate rate is observed among the overall population infected with NTM. However, these findings should be interpreted with caution because of the high heterogeneity among studies.

Comparing the diagnostic performance of QuantiFERON-TB Gold Plus with QFT-GIT, T-SPOT.TB and TST: a systematic review and meta-analysis.

BACKGROUND: QuantiFERON-TB Gold Plus (QFT-Plus) is an important test that has emerged in recent years for detecting TB infection. We conducted a review to compare the sensitivity, specificity and positive rate of QFT-Plus with that of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-cell spot of tuberculosis assay (T-SPOT.TB) and Tuberculin test (TST). METHODS: PubMed and Embase were searched, without language restrictions, from 1 January 2015 to 31 March 2022 using "Mycobacterium tuberculosis Infections" and "QuantiFERON-TB-Plus" as search phrases. We estimated the sensitivity from studies of patients with active tuberculosis, specificity from studies of populations with very low risk of TB exposure, and positive rate from studies of high-risk populations. The methodological quality of the eligible studies was assessed, and a random-effects model meta-analysis was used to determine the risk difference (RD). We assessed the pooled rate by using a random-effects model. This study was registered in PROSPERO (CRD 42021267432). RESULTS: Of 3996 studies, 83 were eligible for full-text screening and 41 were included in the meta-analysis. In patients with active TB, the sensitivity of QFT-Plus was compared to that of QFT-GIT and T-SPOT.TB, respectively, and no statistically differences were found. In populations with a very low risk of TB exposure, the specificity of QFT-Plus was compared with that of QFT-GTI and T-SPOT.TB, respectively, and no statistically differences were found. Two studies were eligible to compare the specificity of the QFT-Plus test with that of the TST test, and the pooled RD was 0.12 (95% CI 0.02 to 0.22). In high-risk populations, 18 studies were eligible to compare the positive rate of the QFT-Plus test with that of the QFT-GIT test, and the pooled RD was 0.02 (95% CI 0.01 to 0.03). The positive rate of QFT-Plus was compared with that of T-SPOT.TB and TST groups, and no statistically differences were found. CONCLUSIONS: The diagnostic performance of QFT-Plus was similar to that of QFT-GIT and T-SPOT.TB, but was slightly more specific than TST.

Analysis of retest reliability for pregnant women undergoing cfDNA testing with a no-call result.

BACKGROUND: Determining the reasons for unreportable or no-call cell-free DNA (cfDNA) test results has been an ongoing issue, and a consensus on subsequent management is still lacking. This study aimed to explore potential factors related to no-call cfDNA test results and to discuss whether retest results are reliable. METHODS AND RESULTS: This was a retrospective study of women with singleton pregnancies undergoing cfDNA testing in 2021. Of the 9871 pregnant patients undergoing cfDNA testing, 111 had a no-call result, and their results were compared to those of 170 control patients. The no-call rate was 1.12% (111/9871), and the primary cause for no-call results was data fluctuation (88.29%, 98/111). Medical conditions were significantly more frequent in the no-call group than in the reportable results group (P < 0.001). After retesting, 107 (107/111, 96.40%) patients had a result, and the false-positive rate (FPR) of retesting was 10.09% (10.09%, 11/109). In addition, placental lesions were more frequent in the no-call group than in the reportable results group (P = 0.037), and 4 patients, all in the no-call group, experienced pregnancy loss. CONCLUSIONS: Pregnant women with medical conditions are more likely to have a no-call result. A retest is suggested for patients with a no-call result, but retests have a high FPR. In addition, pregnant women with a no-call result are at increased risk of adverse pregnancy outcomes. In conclusion, more attention should be given to pregnant women for whom a no-call cfDNA result is obtained.

Transrectal versus transperineal prostate biopsy in detection of prostate cancer: a retrospective study based on 452 patients.

BACKGROUND: Transrectal (TR) ultrasound guided prostate biopsy and transperineal (TP) ultrasound guided prostate biopsy are the two most commonly used methods to detect prostate cancer, the detection rate of the two biopsy approaches may differ in patients with different clinical characteristics. Here we aimed to compare the prostate cancer detection rate and positive rate of biopsy cores between TR and TP prostate biopsy in patients with different clinical characteristics. METHODS: We retrospectively analyzed and compared the clinical data of 452 patients underwent TR or TP prostate biopsy in our hospital from June 2017 to September 2021. And patients were stratified according to several clinical characteristic (serum PSA level, prostate volume, PSA density, T stage and ISUP grade), cancer detection rate and positive rate of biopsy cores were compared in different stratified groups. RESULTS: There was no significant difference in age, PSA level, prostate volume, and PSA density between the TR and TP groups. TR group had a higher overall cancer detection rate and positive rate of biopsy cores than TP group. Further subgroup analysis showed that TR group had a higher cancer detection rate in patients with prostate volumes 30-80 mL, and that the TR group had a higher positive rate of biopsy cores among the patients with T3-T4 stages, while TP group had a higher positive rates of biopsy cores among the patients with T1-T2 stages. There were no significant differences between the TR and TP groups for each subgroup when stratified by PSA level, PSA density and ISUP grade. CONCLUSIONS: TR approach may have advantage in patients with prostate volumes 30-80 mL and T3-T4 stages, while TP approach may have advantage in patients with T1-T2 stages.

Low-Temperature Cleanup Followed by Dispersive Solid-Phase Extraction for Determination of Nine Polar Plant Growth Regulators in Herbal Matrices Using Liquid Chromatography-Tandem Mass Spectrometry.

Polar plant growth regulators, used alone or doped in fertilizers, are most effective and widely utilized plant growth regulators (PGRs) in agriculture, which play important roles in mediating the yield and quality of crops and foodstuffs. The application scope has been extended to herbal medicines in the past 2 decades and relevant study is inadequate. The aim of this study is to establish a QuPPe-based extraction method containing low-temperature and d-SPE cleanup procedure followed by the detection on a selective multiresidue ultrahigh-performance liquid chromatography - triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) in three herbal matrices. This simple, accurate, versatile and robust method was verified according to the validation criteria of the SANTE/12682/2019 guideline document. The analytical range was from 2.5 to 200 µg/L, and the average recoveries were in the range of 64.6-117.8% (n = 6). The optimized method was applied to 135 herbal medicines thereof. Result showed that the detection frequency of chlormequat was the highest in the investigated PGRs, with the positive rate of 15.6%. Improvement of the detection method for polar PGRs will enrich the coverage of PGRs, which is conducive to safeguard public health and ensure drug safety. Supplementary Information: The online version contains supplementary material available at 10.1007/s10337-023-04254-3.

Positive rate and quality assessment of CT pulmonary angiography in sickle cell disease: a case‒control study.

BACKGROUND: Pulmonary complications are common in sickle cell disease (SCD) and can mimic pulmonary embolisms (PEs), leading to potential overuse of computed tomography pulmonary angiography (CTPA). Maximizing the quality of CTPA is essential for its diagnostic accuracy. However, little is known about the positive rate and quality of CTPA in SCD. METHODS: This retrospective case‒control study aimed to determine the positive rate and quality of CTPA studies performed to rule out PE in SCD (HbSS genotype) patients compared to a control group. Logistic regression analysis was used to identify independent factors associated with suboptimal CTPA studies, defined as a mean enhancement of < 210 HU in the pulmonary artery. RESULTS: The study included 480 patients, consisting of 240 SCD patients and 240 controls. The positive rate of PE was 4.0%, with a similar rate in both SCD patients and the control group (4.2% vs. 3.8%, p = 0.08). However, SCD patients had significantly lower contrast enhancement of the pulmonary artery than the control group (266.1 ± 90.5 HU vs. 342.2 ± 116.1 HU, p < 0.01). Notably, 25.4% of SCD patients had suboptimal scans. The logistic regression model demonstrated that SCD was significantly associated with suboptimal pulmonary arterial contrast enhancement compared to the control group (OR = 4.4; 95% CI: 2.4-8.3). CONCLUSIONS: This study revealed a relatively low positive rate of CTPA in both SCD patients and the control group. However, SCD was significantly associated with suboptimal image quality due to inadequate contrast enhancement of the pulmonary artery. Further research is needed to identify measures that can enhance the quality of CTPA studies in SCD patients and to establish a specific imaging protocol for this patient population.

Credit Card Fraud Detection: An Improved Strategy for High Recall Using KNN, LDA, and Linear Regression.

Efficiently and accurately identifying fraudulent credit card transactions has emerged as a significant global concern along with the growth of electronic commerce and the proliferation of Internet of Things (IoT) devices. In this regard, this paper proposes an improved algorithm for highly sensitive credit card fraud detection. Our approach leverages three machine learning models: K-nearest neighbor, linear discriminant analysis, and linear regression. Subsequently, we apply additional conditional statements, such as "IF" and "THEN", and operators, such as ">" and "<", to the results. The features extracted using this proposed strategy achieved a recall of 1.0000, 0.9701, 1.0000, and 0.9362 across the four tested fraud datasets. Consequently, this methodology outperforms other approaches employing single machine learning models in terms of recall.

Allergen-specific IgE in the tear fluid of Chinese patients with common allergic conjunctivitis in autumn and winter.

PURPOSE: In this study, we determined the positive rates of allergen-specific immunoglobulin E (IgE) in the tear fluid of Chinese patients with common allergic conjunctivitis (AC) in autumn and winter, compared systemic and ocular allergen tests, and explored the correlation between the numbers and categories of allergens and clinical AC features. METHODS: This cross-sectional study recruited 44 patients with AC (86 eyes). Specific IgEs for allergens common in China (house dust mite, cat/dog dander, mugwort/ragweed pollen, cottonwood/willow/elm pollen, milk, egg whites, soybeans) were measured in collected tears using kits for allergen-specific IgE antibodies. AC signs and symptoms were graded according to severity. RESULTS: Specific IgE in tears was positive in 87.2% of eyes. House dust mite was the most common allergen (86.0%), followed by cat (24.4%) and dog (7.0%) dander; tree and grass pollen accounted for only 4.7% and 2.3%, respectively. Food allergens were not detected. The positive rates of the systemic allergen tests were lower than in tear fluid tests in both eyes, especially for house dust mites (P = 0.000). In patients with more allergens, itching was more severe (P = 0.035), while conjunctival hyperemia was milder (P = 0.002). CONCLUSION: In autumn and winter, the most common AC allergen in Chinese patients was house dust mites. Compared with systemic allergen tests, measuring specific IgE in tears may be a non-invasive method to diagnose and evaluate AC severity, which may be more suitable to reflect the local conditions of ocular surface inflammation due to its high positive rate and convenience.

Positive rates of interferon-γ release assay and tuberculin skin test in detection of latent tuberculosis infection: A systematic review and meta-analysis of 200,000 head-to-head comparative tests.

OBJECTIVE: To compare the positive rates of IGRA and TST in detection of LTBI. METHODS: We searched PubMed, Embase, and the Cochrane Library on March 12, 2022. A random-effects model was used to calculate pooled results. RESULTS: We included 458 head-to-head studies. Compared with immunocompetent controls, TST positive rate in immunosuppressed population decreased more than IGRA positive rate (OR 0.36 [95% CI: 0.31 to 0.41] versus 0.53 [0.46 to 0.61]). In immunocompetent BCG-vaccinated individuals, IGRA positive rate in low-TB burden areas was significantly lower than TST positive rate, but the difference was decreased in high-TB burden areas (OR 0.75 [0.60 to 0.94]). Additionally, IGRA positive rate was equal to that of TST in the elderly (OR 0.98 [0.66 to 1.46]). CONCLUSION: TST is more susceptible to immunosuppression than IGRA. The effect of BCG on TST might be weakened in high-TB burden areas, and TST response waned in the elderly. REVIEW REGISTRATION: PROSPERO CRD42020180163.

Reverse Bayesian Implications of p-Values Reported in Critical Care Randomized Trials.

BACKGROUND: Misinterpretations of the p-value in null-hypothesis statistical testing are common. We aimed to determine the implications of observed p-values in critical care randomized controlled trials (RCTs). METHODS: We included three cohorts of published RCTs: Adult-RCTs reporting a mortality outcome, Pediatric-RCTs reporting a mortality outcome, and recent Consecutive-RCTs reporting p-value ≤.10 in six higher-impact journals. We recorded descriptive information from RCTs. Reverse Bayesian implications of obtained p-values were calculated, reported as percentages with inter-quartile ranges. RESULTS: Obtained p-value was ≤.005 in 11/216 (5.1%) Adult-RCTs, 2/120 (1.7%) Pediatric-RCTs, and 37/90 (41.1%) Consecutive-RCTs. An obtained p-value .05-.0051 had high False Positive Rates; in Adult-RCTs, minimum (assuming prior probability of the alternative hypothesis was 50%) and realistic (assuming prior probability of the alternative hypothesis was 10%) False Positive Rates were 16.7% [11.2, 21.8] and 64.3% [53.2, 71.4]. An obtained p-value ≤.005 had lower False Positive Rates; in Adult-RCTs the realistic False Positive Rate was 7.7% [7.7, 16.0]. The realistic probability of the alternative hypothesis for obtained p-value .05-.0051 (ie, Positive Predictive Value) was 28.0% [24.1, 34.8], 30.6% [27.7, 48.5], 29.3% [24.3, 41.0], and 32.7% [24.1, 43.5] for Adult-RCTs, Pediatric-RCTs, Consecutive-RCTs primary and secondary outcome, respectively. The maximum Positive Predictive Value for p-value category .05-.0051 was median 77.8%, 79.8%, 78.8%, and 81.4% respectively. To have maximum or realistic Positive Predictive Value >90% or >80%, RCTs needed to have obtained p-value ≤.005. The credibility of p-value .05-.0051 findings were easy to challenge, and the credibility to rule-out an effect with p-value >.05 to .10 was low. The probability that a replication study would obtain p-value ≤.05 did not approach 90% unless the obtained p-value was ≤.005. CONCLUSIONS: Unless the obtained p-value was ≤.005, the False Positive Rate was high, and the Positive Predictive Value and probability of replication of "statistically significant" findings were low.

Critical CHD screening programme: a 3-year multicentre experience in Mexico.

INTRODUCTION: CHDs are the most common type of birth defect. One in four newborns with a heart defect has a critical CHD. In Mexico, there is a lack of data available to determine its prevalence. Pulse oximetry screening programmes have been implemented worldwide, reporting opportunity areas in algorithm interpretation and data management. Our study aims to share preliminary results of a 3-year experience of a multicentre pulse oximetry screening programme that addresses critical challenges. MATERIALS AND METHODS: This retrospective study examined the reports of newborns screened from February 2016 to July 2019 from five hospitals. Two algorithms -the New Jersey and the American Academy of Pediatrics- were implemented over consecutive periods. The algorithms' impact was assessed through the calculation of the false-positive rate in an eligible population. RESULTS: A total of 8960 newborns were eligible for the study; from it, 32.27% were screened under the New Jersey and 67.72% under the American Academy of Pediatrics algorithm - false-positive rate: 1% (CI 95: ± 0.36%) and 0.71% (CI 95: ± 0.21%), respectively. Seventy-nine newborns were referred, six were diagnosed with critical CHD, and six with CHD. The critical CHD estimated prevalence was 6.69:10,000 newborns (CI 95: ± 5.36). Our results showed that the algorithm was not related to the observable false-positive rate reduction. DISCUSSION: Other factors may play a role in decreasing the false-positive rate. Our experience implementing this programme was that a systematic screening process led to more confident results, newborn's report interpretation, and follow-up.

Anomaly Detection with Feature Extraction Based on Machine Learning Using Hydraulic System IoT Sensor Data.

Hydraulic systems are advanced in function and level as they are used in various industrial fields. Furthermore, condition monitoring using internet of things (IoT) sensors is applied for system maintenance and management. In this study, meaningful features were identified through extraction and selection of various features, and classification evaluation metrics were presented through machine learning and deep learning to expand the diagnosis of abnormalities and defects in each component of the hydraulic system. Data collected from IoT sensor data in the time domain were divided into clusters in predefined sections. The shape and density characteristics were extracted by cluster. Among 2335 newly extracted features, related features were selected using correlation coefficients and the Boruta algorithm for each hydraulic component and used for model learning. Linear discriminant analysis (LDA), logistic regression, support vector classifier (SVC), decision tree, random forest, XGBoost, LightGBM, and multi-layer perceptron were used to calculate the true positive rate (TPR) and true negative rate (TNR) for each hydraulic component to detect normal and abnormal conditions. Valve condition, internal pump leakage, and hydraulic accumulator data showed TPR performance of 0.94 or more and a TNR performance of 0.84 or more. This study's findings can help to determine the stable and unstable states of each component of the hydraulic system and form the basis for engineers' judgment.

Adjusting Coronavirus Prevalence Estimates for Laboratory Test Kit Error.

Testing representative populations to determine the prevalence or the percentage of the population with active severe acute respiratory syndrome coronavirus 2 infection and/or antibodies to infection is being recommended as essential for making public policy decisions to ease restrictions or to continue enforcing national, state, and local government rules to shelter in place. However, all laboratory tests are imperfect and have estimates of sensitivity and specificity less than 100%-in some cases, considerably less than 100%. That error will lead to biased prevalence estimates. If the true prevalence is low, possibly in the range of 1%-5%, then testing error will lead to a constant background of bias that most likely will be larger, and possibly much larger, than the true prevalence itself. As a result, what is needed is a method for adjusting prevalence estimates for testing error. Methods are outlined in this article for adjusting prevalence estimates for testing error both prospectively in studies being planned and retrospectively in studies that have been conducted. If used, these methods also would help harmonize study results within countries and worldwide. Adjustment can lead to more accurate prevalence estimates and to better policy decisions. However, adjustment will not improve the accuracy of an individual test.

Analysis of the positive rate of 4254 cases of COVID-19 nucleic acid tests in different aites in Wuhan, China.

There's an outbreak of coronavirus diesase 2019 (COVID-19) since December 2019, first in Wuhan. It has caused huge medical challenges to Hubei Province with currently more than 67 thousand confirmed cases till 8th March 2020. Identification, there is no clinically effective drug. Isolation and masks are essential to limit human-to-human transmission initially. The nucleic acid test (NAT) of COVID-19 currently was the most reliable established laboratory diagnosis method in clinical. From 8th February to 7th March 2020, 4254 cases were collected for analysis at six nucleic acid collection sites in the community medical team of Hubei Provincial Hospital of Traditional Chinese Medicine, which cover almost all groups who need NAT in Wuhan. Distribution of positive rates in different sites by genders, ages, or occupations were compared. The positive rates of different sites from high to low were: hospital wards (24.71%) > fever clinics (16.57%) > nursing homes (5.51%) > isolation hotels (5.30%) > rehabilitation stations (1.36%) >close contact sites (0.17%). The confirmed patients in isolation hotels, hospital ward, and fever clinical were mainly middle-aged and elderly, and most of them were women. The positive rate in isolation hotels and fever clinics gradually decreased over time. There were no significant differences between genders among those six nucleic acid collection sites (P < .05). The hospital wards have the highest positive rate; however, close contact sites have lowest one. Patients who are discharged from hospitals may still have potential risks. Middle-aged and older people remain the focus of epidemic prevention and control.

Investigation of viral pathogens in cattle with bovine respiratory disease complex in Inner Mongolia, China.

As a multifactor disease, the bovine respiratory disease complex (BRDC) causes high morbidity and mortality that is devastating to the cattle industry. To assess viral infections in beef cattle suffering from respiratory diseases in Inner Mongolia, 302 nasal swabs and serum samples were randomly collected from cattle with mild respiratory symptoms between March 2018 and May 2019. Our results showed that the rate of RT-PCR results positive for nucleic acids of viral pathogens in 6 cities was between 54 and 80%.The rates of bovine viral diarrhea virus (BVDV), bovine herpesvirus 1 (BHV-1), bovine parainfluenza virus type 3(BPIV3), and bovine respiratory syncytial virus(BRSV)infections were 44.70% (135/302), 24.83% (75/302), 5.63% (17/302), and 6.95% (21/302),respectively. There are also 8.94% (27/302) of samples were positive for BVDV and BHV-1, and 3.97% (12/302) of samples were positive for BPIV3 and BRSV. In addition, the RT-PCR products were sequenced, and phylogenetic analysis based on these sequences was performed. The results indicated that: a) all of the BVDV isolates were BVDV-1 and were classified as BVDV-1a (66.67%) and BVDV-1b (33.33%); b) all of the BHV-1 isolates were classified as subtype 1.1; 44.44% of the isolates were closely related to modified live viral vaccine strains, and 55.56% of the isolates were closer to epidemic strains; c) all of the BPIV3 isolates belonged to BPIV3c; d) all of the BRSV isolates were classified into subgroup III. It is suggested that an important cause of respiratory diseases for beef cattle is viral infection, and phylogenetic analysis can help us choose the proper strain to develop a vaccine.