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We aimed to evaluate the indeterminate rate of interferon gamma release assays (IGRAs) in the detection of latent tuberculosis infection (LTBI). On 15 November 2022, we searched the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators independently extracted the study data and assessed their quality using a modified quality assessment of diagnostic accuracy studies (i.e., QUADAS-2) tool. A random-effects model was used to calculate pooled results. We included 403 studies involving 486,886 individuals and found that the pooled indeterminate rate was 3.9% (95% CI 3.5%-4.2%). The pooled indeterminate rate for QuantiFERON®-TB (QFT) was similar to that for T-SPOT®.TB (T-SPOT) [odds ratio (OR) = 0.88, 95% CI 0.59-1.32]; however, the indeterminate rate for a new generation of QFT (QFT-plus) was lower than that of T-SPOT (OR = 0.24, 95% CI 0.16-0.35). The indeterminate rate in the immunocompromised population was significantly higher than that in healthy controls (OR = 3.51, 95% CI 2.11-5.82), and it increased with the reduction of CD4+ cell count in HIV-positive patients. Children's pooled indeterminate rates (OR = 2.56, 95% CI 1.79-3.57) were significantly higher than those of adults, and the rates increased as the children's age decreased. On average, 1 in 26 tests yields indeterminate IGRA results in LTBI screening. The use of advanced versions of the QuantiFERON-TB assay (QFT-plus), may potentially reduce the occurrence of an indeterminate result. Our study emphasizes the high risk of immunosuppression and young age in relation to indeterminate IGRA, which should receive more attention in the management of LTBI. PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211363, CRD42020211363.

Lyme disease (LD), a multifaceted condition caused by Borrelia burgdorferi (Bb), remains poorly understood, particularly regarding metabolic pathways. This study aimed to evaluate the role of glycolysis-related genes (GRGs) in LD pathogenesis and identify key genes and mechanisms relevant to diagnosis and therapy. Differentially expressed GRGs were identified and further analyzed by correlation analysis and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Key genes were screened using least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination, followed by gene set enrichment analysis, gene set variation analysis and immune infiltration analysis using CIBERSORT. Diagnostic value was assessed by receiver operating characteristic and nomogram analyses, and a competing endogenous RNA network and protein-drug interaction predictions were constructed. The expression of key genes was further validated by reverse transcription-quantitative PCR (RT-qPCR) in Bb-infected THP-1 cells, and glucose and lactate concentrations in the culture supernatants were measured using commercial colorimetric assay kits. A total of 63 differentially expressed GRGs were identified. Of note, two key genes [lactate dehydrogenase A (LDHA) and thioredoxin (TXN)] exhibited a strong diagnostic performance. Immune infiltration analysis revealed that these genes were associated with regulatory T cells (r=0.33, P=0.05), gamma delta T cells (r=-0.34, P=0.042), CD4 memory resting T cells (r=-0.4, P=0.016) and monocytes (r=-0.36, P=0.03). The potential glycolysis-targeting drugs were predicted. RT-qPCR analysis revealed increased LDHA and TXN expression in Bb-infected THP-1 cells. In addition, Bb stimulation reduced extracellular glucose levels and increased lactate accumulation in culture supernatants. Overall, this integrative analysis revealed notable alterations in glycolytic genes during Bb infection, suggesting that dysregulation of glycolysis contributes to LD immunopathology. The identified key genes (LDHA and TXN) may serve as infection-related transcriptional response markers, offering insights into LD mechanisms and potential precision-based strategies.

High-altitude heart disease (HAHD) is characterized by pulmonary hypertension and progressive right ventricular dysfunction. Tricuspid annular plane systolic excursion (TAPSE) may have limited ability to characterize right ventricular impairment at higher pulmonary pressures. We aimed to determine whether three-dimensional speckle-tracking-derived right ventricular free-wall longitudinal strain, reported as an absolute magnitude (absolute RVFWLS), better identifies an operationally defined higher Doppler-estimated pulmonary artery systolic pressure (PASP) subgroup within HAHD than TAPSE, and to explore the relationships of PASP with right ventricular volumetric remodeling and strain. This retrospective study included 100 participants who underwent standardized two-dimensional and three-dimensional echocardiography: 40 high-altitude controls and 60 patients with HAHD. Patients with HAHD were categorized using an operational analytical threshold into higher-PASP (PASP ≥60 mmHg) and lower-PASP (PASP <60 mmHg) subgroups. Single-index receiver operating characteristic (ROC) curves were compared using paired DeLong tests. A logistic model evaluated absolute RVFWLS beyond TAPSE, age, and sex. Exploratory regression-based mediation-model frameworks with 5,000 bootstrap iterations examined whether right ventricular end-systolic volume (RV-ESV) statistically accounted for the associations of PASP with three-dimensional right ventricular ejection fraction (3D-EF) and absolute RVFWLS. Of the 60 patients with HAHD, 26 met the operational higher-PASP threshold. Absolute RVFWLS showed better discrimination than TAPSE, with areas under the ROC curve of 0.886 and 0.647, respectively (difference, 0.238;  = 0.002). Adding absolute RVFWLS to TAPSE, age, and sex improved model fit (likelihood-ratio  < 0.001); the odds ratio per 1-percentage-point decrement in absolute RVFWLS was 1.81 (95% confidence interval, 1.29-2.54). RV-ESV statistically accounted for 45.0% (95% confidence interval, 34.8%-67.2%) of the PASP-3D-EF association, whereas it did not materially account for the PASP-absolute RVFWLS association (-1.6%; 95% confidence interval, -8.4% to 5.7%). Septal longitudinal strain was also reduced in HAHD. Three-dimensional absolute RVFWLS showed better discrimination than TAPSE for identifying an operationally defined higher-PASP subgroup within HAHD. The association between PASP and absolute RVFWLS was less closely related to RV-ESV than the PASP-3D-EF association. These exploratory cross-sectional findings require prospective validation against invasive hemodynamic measurements and clinical outcomes.

Spatial biodiversity is a key issue in biogeography for the explorations of biological origin and diversification. However, seldom studies have addressed the temporal changes in spatial patterns of biodiversity. We explored the taxonomic and functional diversities of riverine macroinvertebrates in central China, with the elevational gradient, in different seasons in a normal climate year (i.e., no extreme anomalies in the annual precipitation or average annual temperature). The air temperature and streamflow discharge were decreased monotonically with the increase of elevation both in the dry and wet seasons. In addition, the total nitrogen had no significant change with the increase of elevational gradient in the dry season but showed a monotonically decreasing pattern in the wet season. The total phosphorus showed a monotonically decreasing pattern with the elevational gradient in the dry season but had no significant change in the wet season. The spatial pattern of taxonomic diversity of macroinvertebrates along the elevational gradient showed complex patterns, but the functional diversity had either the unimodal or monotonically decreasing pattern. In addition, the functional diversity with the elevational gradient had similar patterns between the dry and wet seasons. Further analysis of the elevational pattern in different seasons is an important basis for understanding the status quo of functional diversity and formulating countermeasures for biodiversity conservation.

The rock-breaking efficiency of a drilling tool directly affects the production costs and progress of foundation construction. It is essential to understand the mechanism of mechanical rock-breaking to improve rock-breaking efficiency. In this study, dynamic rock-breaking simulation research was carried out on a drill bit and was based on the LS-DYNA simulation platform. Additionally, the influence of the rotational speed of the spindle and the feed rate on the force of the drill bit in the rock-breaking process was obtained. The influence of the rotational speed of the spindle and the feed rate on drill vibration was also analyzed. The content of the presented theoretical and simulation research was verified through experiments. The following conclusions were drawn: first, the reaction force that rock has on the drill bit presents a law according to different rock types and drilling process parameters. With the increase in rotational speed, the axial reaction force decreases. With the increase in the feed rate, the axial reaction force increases. The effect of rock type on axial reaction force is nonlinear. Second, the influence of the spindle rotational speed and feed rate on the vibration of the drill bit also presents a law during rock-breaking. When the feed amount is constant, the transverse vibration slows down, and the axial vibration intensifies as the rotational speed increases. When the rotational speed is constant, as the feed increases, the transverse vibration slows down and the axial vibration intensifies. The research results provide a theoretical basis for selecting drilling process parameters and for improving rock-breaking efficiency.

Use of an interferon-γ (IFN-γ) release assay or tuberculin skin test for detection and management of latent tuberculosis infection is controversial. For both types of test, we assessed their predictive value for the progression of latent infection to active tuberculosis disease, the targeting value of preventive treatment, and the necessity of dual testing. In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and the Cochrane Library, with no start date or language restrictions, on Oct 18, 2019, using the keywords (“latent tuberculosis” OR “latent tuberculosis infection” OR “LTBI”) AND (“interferon gamma release assays” OR “Interferon-gamma Release Test” OR “IGRA” OR “QuantiFERON®-TB in tube” OR “QFT” OR “T-SPOT.TB”) AND (“tuberculin skin test” OR “tuberculin test” OR “Mantoux test” OR “TST”). We included articles that used a cohort study design; included information that individuals with latent tuberculosis infection detected by IFN-γ release assay, tuberculin skin test, or both, progressed to active tuberculosis; reported information about treatment; and were limited to high-risk populations. We excluded studies that included patients with active or suspected tuberculosis at baseline, evaluated a non-commercial IFN-γ release assay, and had follow-up of less than 1 year. We extracted study details (study design, population investigated, tests used, follow-up period) and the number of individuals observed at baseline, who progressed to active tuberculosis, and who were treated. We then calculated the pooled risk ratio (RR) for disease progression, positive predictive value (PPV), and negative predictive value (NPV) of IFN-γ release assay versus tuberculin skin test. We identified 1823 potentially eligible studies after exclusion of duplicates, of which 256 were eligible for full-text screening. From this screening, 40 studies (50 592 individuals in 41 cohorts) were identified as eligible and included in our meta-analysis. Pooled RR for the rate of disease progression in untreated individuals who were positive by IFN-γ release assay versus those were negative was 9·35 (95% CI 6·48–13·49) compared with 4·24 (3·30–5·46) for tuberculin skin test. Pooled PPV for IFN-γ release assay was 4·5% (95% CI 3·3–5·8) compared with 2·3% (1·5–3·1) for tuberculin skin test. Pooled NPV for IFN-γ release assay was 99·7% (99·5–99·8) compared with 99·3% (99·0–99·5) for tuberculin skin test. Pooled RR for rates of disease progression in individuals positive by IFN-γ release assay who were untreated versus those who were treated was 3·09 (95% CI 2·08–4·60) compared with 1·11 (0·69–1·79) for the same populations who were positive by tuberculin skin test. Pooled proportion of disease progression for individuals who were positive by IFN-γ release assay and tuberculin skin test was 6·1 (95% CI 2·3–11·5). Pooled RR for rates of disease progression in individuals who were positive by IFN-γ release assay and tuberculin skin test who were untreated versus those who were treated was 7·84 (95% CI 4·44–13·83). IFN-γ release assays have a better predictive ability than tuberculin skin tests. Individuals who are positive by IFN-γ release assay might benefit from preventive treatment, but those who are positive by tuberculin skin test probably will not. Dual testing might improve detection, but further confirmation is needed. National Natural Science Foundation of China and Natural Foundation of Yunnan Province.

Background. Oxidative stress-induced neurotoxicity plays a key role in Alzheimer’s disease (AD). 11,12-Diacetyl-carnosol (NO.20), an acetylated derivative of carnosol extracted from rosemary, displays a high antioxidative effect in vitro. Purpose. We investigated the neuroprotective effect of NO.20 on H2O2-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and its possible mechanism. Results. We found that NO.20 pretreatment (1 μM for 1 h) had cytoprotective effects and weakened H2O2-induced damage in SH-SY5Y cells by reducing viability loss, apoptotic rate, and reactive oxygen species production. In addition, NO.20 inhibited H2O2-induced mitochondrial dysfunctions: it alleviated mitochondrial membrane potential loss and cytochrome c release, decreased the Bax/Bcl-2 ratio, and reduced caspase-3 expression. NO.20 also downregulated malondialdehyde and upregulated glutathione. Furthermore, NO.20 pretreatment caused the nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2), increasing heme oxygenase-1 (HO-1) expression in SH-SY5Y cells. Notably, we found that silencing Nrf2 using small interfering RNA (siRNA) suppressed the NO.20-induced HO-1 expression and abolished the neuroprotective effect of NO.20. Conclusion. These results demonstrate that NO.20 protects SH-SY5Y cells from H2O2-induced neurotoxicity by activating the Nrf2/HO-1 pathway. Thus, the neuroprotective and antioxidative stress effects of NO.20 may make it a promising neuroprotective compound for AD treatment.

Purpose Although layer-specific strains are effective for assessing cardiac function, their application in rat models at different stages of myocardial hypertrophy (MH) is immature, and their relationship with MH and myocardial fibrosis (MF) is unclear. This study aimed to investigate changes in layer-specific strains across different disease stages and analyze their association with pathological changes. Methods A progressive MH rat model was established using isoproterenol injection and categorized into baseline, 1-week, 2-week, 3-week, and 4-week groups. Echocardiographic indices and pathological differences between the five groups were assessed. The correlation between layer-specific strain parameters and cardiomyocyte hypertrophy and MF was analyzed. Results As the disease progressed, the left ventricular (LV) dilated, with the LV wall thickening and then thinning. The left ventricular ejection fraction declined significantly in the fourth week. The endo-myocardial, mid-myocardium and epi-myocardial global longitudinal strain, along with endo-myocardial global circumferential strain (GCS) and the transmural gradient, significantly decreased in the first week, the mid-myocardium GCS in the second week, and continued to decrease as the disease progressed. The epi-myocardial GCS increased in the first week, but then decreased, becoming significantly lower than the baseline group in the third week. The degrees of MH and MF were correlated with the layer-specific strain parameters. Conclusion Layer-specific strains maybe are valuable for early and effective monitoring of LV systolic function and pathological changes in rats with MH. Longitudinal strain is more sensitive to functional changes; endomyocardial strain reflects early LV remodeling and circumferential strain perhaps indicates disease progression and severity.

Patients with ischemia with non-obstructive coronary arteries (INOCA) have an increased risk of adverse cardiovascular events in the future, which is widespread but underdiagnosed. The purpose of this study is to explore the application value of adenosine stress myocardial contrast echocardiography (ASMCE) in INOCA disease, so that clinicians can early identify and intervene patients with left ventricular function subclinical impairment in INOCA. We enrolled 118 patients with INOCA by ASMCE and invasive coronary angiography (ICA), 97 of whom had complete data. The study population was divided into two subgroups depending on coronary flow velocity reserve (CFVR): impaired CFVR group (n = 34) and normal CFVR group (n = 63). Global longitudinal strain endocardial myocardial (GLSendo), mid-myocardial (GLSmid) and epicardial myocardial (GLSepi) increased after stress in both groups; transmural strain, wall motion scored index (WMSI) and myocardial perfusion scored index (MPSI) increased and FORCE decreased in impaired CFVR group after stress, but there was no difference in normal group before and after stress. There was no significant difference in left ventricular myocardial mechanical parameters, including ΔGLSendo, ΔGLSmid, ΔGLSepi, GLSendo-epi Reserve, Δpeak strain dispersion (PSD), PSD Reserve between the two groups, but ΔEF, strain reserve and left ventricular contractile reserve (LVCR) in the impaired CFVR group were lower than those in the normal CFVR group, while ΔWMSI and ΔMPSI were increased. CFVR can be a clinically valuable indicator in the ASMCE diagnosis of patients with microvascular angina pectoris in INOCA. In the evaluation of left ventricular function in INOCA patients, attention should be paid not only to myocardial deformation, but also to the dynamic changes of LVCR and myocardial perfusion during peak hyperemia.