Which sample type is better for Xpert MTB/RIF to diagnose adult and pediatric pulmonary tuberculosis?

OBJECTIVE: This review aimed to identify proper respiratory-related sample types for adult and pediatric pulmonary tuberculosis (PTB), respectively, by comparing performance of Xpert MTB/RIF when using bronchoalveolar lavage (BAL), induced sputum (IS), expectorated sputum (ES), nasopharyngeal aspirates (NPAs), and gastric aspiration (GA) as sample. METHODS: Articles were searched in Web of Science, PubMed, and Ovid from inception up to 29 June 2020. Pooled sensitivity and specificity were calculated, each with a 95% confidence interval (CI). Quality assessment and heterogeneity evaluation across included studies were performed. RESULTS: A total of 50 articles were included. The respective sensitivity and specificity were 87% (95% CI: 0.84-0.89), 91% (95% CI: 0.90-0.92) and 95% (95% CI: 0.93-0.97) in the adult BAL group; 90% (95% CI: 0.88-0.91), 98% (95% CI: 0.97-0.98) and 97% (95% CI: 0.95-0.99) in the adult ES group; 86% (95% CI: 0.84-0.89) and 97% (95% CI: 0.96-0.98) in the adult IS group. Xpert MTB/RIF showed the sensitivity and specificity of 14% (95% CI: 0.10-0.19) and 99% (95% CI: 0.97-1.00) in the pediatric ES group; 80% (95% CI: 0.72-0.87) and 94% (95% CI: 0.92-0.95) in the pediatric GA group; 67% (95% CI: 0.62-0.72) and 99% (95% CI: 0.98-0.99) in the pediatric IS group; and 54% (95% CI: 0.43-0.64) and 99% (95% CI: 0.97-0.99) in the pediatric NPA group. The heterogeneity across included studies was deemed acceptable. CONCLUSION: Considering diagnostic accuracy, cost and sampling process, ES was a better choice than other sample types for diagnosing adult PTB, especially HIV-associated PTB. GA might be more suitable than other sample types for diagnosing pediatric PTB. The actual choice of sample types should also consider the needs of specific situations

Security boundaries of an optical power limiter for protecting quantum key distribution systems

Unauthorized light injection has always been a vital threat to the practical security of a quantum key distribution (QKD) system. An optical power limiter (OPL) based on the thermo-optical defocusing effect has been proposed and implemented, limiting the injected hacking light. As a hardware countermeasure, the performance of the OPL under various light-injection attacks shall be tested to clarify the security boundary before being widely deployed. To investigate the OPL's security boundary in quantum cryptography, we comprehensively test and analyse the behavior of OPL under continuous-wave (c.w.) light-injection attacks and pulse illumination attacks with pulses' repetition rate at 0.5-Hz,40-MHz, and 1-GHz. The testing results illuminate the security boundary of the OPL, which allows one to properly employ the OPL in the use cases. The methodology of testing and analysis proposed here is applicable to other power-limitation components in a QKD system.Comment: 14 pages, 13 figure

From Tuberculosis Bedside to Bench: UBE2B Splicing as a Potential Biomarker and Its Regulatory Mechanism

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB

Precore Mutation of Hepatitis B Virus May Contribute to Hepatocellular Carcinoma Risk: Evidence from an Updated Meta-Analysis

BACKGROUND: Studies focused on the correlation of mutations in the genome of Hepatitis B Virus (HBV) like Pre-S mutation, Basal Core promoter (BCP), Enhancer II (EnhII), especially Precore mutation, with the risk of hepatocellular carcinoma (HCC) have triggered stiff controversies. With an increasing number of studies in this field recently, we conducted this meta-analysis to appraise the correlations. METHODS: We searched the commonly used databases both in English and Chinese till February 1(st), 2012. Meta-analysis was performed in fixed/random-effects models using STATA 10.0. Publication bias was examined through Egger's test and Begg's funnel plot. RESULTS: In total, 85 case-control studies were included involving 16745 HBV-infected patients, of whom 5781 had HCC. Statistically significant correlations were observed in Precore mutation G1896A (OR = 1.46, 95% confidence interval [CI] = 1.15-1.85, P(OR) = 0.002), G1899A (OR = 3.13, 95%CI = 2.38-4.13, P(OR)<0.001) and Pre-S mutation especially Pre-S1 deletion (OR = 2.94, 95%CI = 2.22 to 3.89) and Pre-S2 deletion (OR = 3.02, 95%CI = 2.03 to 4.50). Similar correlation existed between BCP double mutation A1762T/G1764A, T1753V, C1653T and HCC. In subgroup analysis, the Asians, genotype C or HBeAg positive patients with certain above mutations may be more susceptible to HCC. Besides, the mutations like G1896A and BCP double mutation may be associated with the progression of the liver diseases. CONCLUSIONS: Precore mutation G1896A, G1899A, deletions in Pre-S region as well as the other commonly seen mutations correlated with the increased risk of HCC, especially in Asians and may predict the progression of the liver disease

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (D500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-beta levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-beta responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.Peer reviewe

Editorial: Disease biomarker analysis based on optical biosensing

Disease biomarker analysis has become a crucial tool for diagnosing and evaluating disease prognosis, especially with the increasing understanding of diseases at the molecular level. Abnormalities in various biomarkers can indicate diseased states, and can be used to rapidly and specifically detect and quantify diseases using optical biosensing techniques (Gao et al., 2023). Optical biosensing techniques have several advantages over traditional methods including higher sensitivity, specificity, and faster analysis times (Plikusiene and Ramanaviciene, 2023). It also allows for non-invasive sample collection. With advancements in optical biosensing technology, many medical conditions including cancers, infectious diseases, and autoimmune disorders can be accurately diagnosed and efficiently treated (Singh et al., 2023; Tang et al., 2023). The combination of optical biosensing with emerging technologies such as material science, optics, and electronics has further accelerated its development in biomarker analysis (Qureshi et al., 2022). Interdisciplinary collaboration between experts in fields such as physics, chemistry, bioengineering, and medicine has helped pave the way for novel optical biosensing technologies as well as improving existing ones. Continued interdisciplinary collaboration is essential in advancing the field of disease biomarker analysis based on optical biosensing. This exciting area of research holds great potential for the future of personalized and precision medicine, and will likely lead to more effective disease diagnoses and treatments (Duo et al., 2023)

Genetic Profile of Two Tibetan Populations from China by Analysis of 15 STR Loci

Allele frequency data for the STR systems D3S1358, TH01, D21S11, D18S51, PENTAE, D5S818, D13S317, D7S820, D16S539, CSF1PO, PENTAD, VWA, D8S1179, TPOX, and FGA were determined in two population samples of unrelated, healthy Tibetan individuals. All loci met Hardy-Weinberg expectations, and there was no evidence of association of alleles among the 15 loci. These findings suggest that these STR loci could be particularly powerful tools in forensic medicine and could provide the necessary fundamental population genetic data for the reconstruction of recent human evolutionary history

Diagnostic Accuracy of the Artificial Intelligence Methods in Medical Imaging for Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

Tuberculosis (TB) remains one of the leading causes of death among infectious diseases worldwide. Early screening and diagnosis of pulmonary tuberculosis (PTB) is crucial in TB control, and tend to benefit from artificial intelligence. Here, we aimed to evaluate the diagnostic efficacy of a variety of artificial intelligence methods in medical imaging for PTB. We searched MEDLINE and Embase with the OVID platform to identify trials published update to November 2022 that evaluated the effectiveness of artificial-intelligence-based software in medical imaging of patients with PTB. After data extraction, the quality of studies was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using a bivariate random-effects model. In total, 3987 references were initially identified and 61 studies were finally included, covering a wide range of 124,959 individuals. The pooled sensitivity and the specificity were 91% (95% confidence interval (CI), 89–93%) and 65% (54–75%), respectively, in clinical trials, and 94% (89–96%) and 95% (91–97%), respectively, in model-development studies. These findings have demonstrated that artificial-intelligence-based software could serve as an accurate tool to diagnose PTB in medical imaging. However, standardized reporting guidance regarding AI-specific trials and multicenter clinical trials is urgently needed to truly transform this cutting-edge technology into clinical practice