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Treatment options for highly drug-resistant tuberculosis are limited. In this study in South Africa, a new agent, pretomanid, was combined with bedaquiline and linezolid for a 26-week course to treat extensively drug-resistant and complicated multidrug-resistant pulmonary TB. Although there were toxic effects, 90% of patients had favorable outcomes.

This study aimed to investigate the relationship between lipoprotein(a) [Lp(a)] levels and non-alcoholic fatty liver disease (NAFLD), and to analyze its linear association and subgroup differences. This cross-sectional analysis was based on data from 2308 participants in the National Health and Nutrition Examination Survey (NHANES) III. Multivariate logistic regression models were used to assess the association between Lp(a) and NAFLD, adjusting for demographic factors, lifestyle behaviors, comorbidities, and biomarkers. Subgroup analyses were conducted based on age, sex, body mass index (BMI), diabetes, and hypertension. Restricted cubic spline (RCS) regression model was used to explore the nonlinear relationship between Lp(a) and NAFLD. Higher Lp(a) levels were significantly associated with a lower risk of NAFLD. In the fully adjusted model, compared to the lowest quartile group (Q1), the third and fourth quartiles (Q3 and Q4) had significantly reduced risks of NAFLD [Q3: OR = 0.701, 95% CI 0.511, 0.961; P  = 0.027; Q4: OR = 0.605, 95% CI 0.438, 0.835; P  = 0.002]. Subgroup analysis showed that the association between higher Lp(a) levels and reduced NAFLD risk was significant in individuals aged 50 years and older, those with BMI ≥ 30 kg/m 2 , non-diabetics, and those with hypertension. RCS analysis further confirmed a linear negative association between Log 10 Lp(a) and NAFLD risk ( P  = 0.029, P nonlinearity = 0.888). There is a significant linear negative association between Lp(a) levels and the risk of NAFLD, suggesting that Lp(a) may serve as a potential biomarker for assessing NAFLD risk.

To investigate how N-fertilization affects the growth, carbon and nitrogen (N) physiology, and wood properties of poplars with contrasting growth characteristics, slow-growing (Populus popularis, Pp) and fast-growing (P. alba×P. glandulosa, Pg) poplar saplings were exposed to different N levels. Above-ground biomass, leaf area, photosynthetic rates (A), instantaneous photosynthetic nitrogen use efficiency (PNUE i), chlorophyll and foliar sugar concentrations were higher in Pg than in Pp. Foliar nitrate reductase (NR) activities and root glutamate synthase (GOGAT) activities were higher in Pg than in Pp as were the N amount and NUE of new shoots. Lignin contents and calorific values of Pg wood were less than that of Pp wood. N-fertilization reduced root biomass of Pg more than of Pp, but increased leaf biomass, leaf area, A, and PNUEi of Pg more than of Pp. Among 13 genes involved in the transport of ammonium or nitrate or in N assimilation, transcripts showed more pronounced changes to N-fertilization in Pg than in Pp. Increases in NR activities and N contents due to N-fertilization were larger in Pg than in Pp. In both species, N-fertilization resulted in lower calorific values as well as shorter and wider vessel elements/fibres. These results suggest that growth, carbon and N physiology, and wood properties are more sensitive to increasing N availability in fast-growing poplars than in slow-growing ones, which is probably due to prioritized resource allocation to the leaves and accelerated N physiological processes in fast-growing poplars under higher N levels.

: Subjective cognitive decline (SCD) is considered a preclinical state of Alzheimer's disease (AD) and may represent a more advanced preclinical status than amnestic mild cognitive impairment (aMCI). Our aim was to explore changes in the white matter (WM) microstructure and their correlation with cognitive function in these AD-spectrum patients. : Diffusion tensor images from 43 individuals with normal cognition (NC), 38 SCD patients, and 36 aMCI patients were compared using an atlas-based segmentation strategy. The correlation between diffusion parameters and cognitive function was further analyzed. : The anatomical pattern of WM impairment was generally similar between SCD and aMCI patients. However, aMCI patients showed significantly lower fractional anisotropy (i.e., corpus callosum forceps major and forceps minor) and increased mean diffusivity [i.e., bilateral anterior thalamic radiation (ATR), left corticospinal tract (CST), forceps minor, left cingulum (cingulate gyrus), left cingulum hippocampus, and left inferior fronto-occipital fasciculus (IFO)] in some tracts than did SCD subjects, indicating a disruption in WM microstructural integrity in the aMCI. Individuals with microstructural disruption in forceps minor, left cingulum (cingulate gyrus), and left cingulum hippocampus tracts performed worse in general cognition and memory function tests, as indicated by line regression analysis. : SCD individuals had extensive WM microstructural damage in a pattern similar to that seen in aMCI, although presenting a cognitive performance comparable with that of cognitively healthy individuals. Our results suggest that WM integrity might precede objectively measurable memory decline and may be a potential early biomarker for AD.

Background Lamb-Shaffer syndrome (LAMSHF, OMIM: 616803) is a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, which is attributed to haploinsufficiency by heterozygous variants of SOX5 gene (SRY-Box Transcription Factor 5, HGNC: 11201) on chromosome 12p12. A total of 113 cases have been reported in the world, however, only 3 cases have been reported.in China. Here, we aimed to report novel variants of SOX5 gene and provide examples for clinical diagnosis by reporting the clinical phenotype of a series of Chinese patients with LAMSHF. Methods This study retrospectively collected the information of families of LAMSHF patients in China. Whole Exome Sequencing (WES) were performed to confirm the diagnosis of 4 children with unexplained developmental delay or epilepsy. A minigene splicing assay was used to verify whether the splice variant affected splicing. Meanwhile, a literature review was conducted to analyze the clinical and genetic characteristics of patients with LAMSHF. Results Three of the LAMSHF patients had a de novo heterozygous mutation in the SOX5 gene respectively, c.290delC (p.Pro97fs*30), chr12:23686019_24048958del, c.1772-1C > A, and the remaining one had a mutation inherited from his father, c.1411C > T (p.Arg471*). The main clinical manifestations of these children were presented with global developmental delays, and one of them also had seizures. And the results of the minigene experiment indicated that the splice variant, c.1772-1C > A, transcribed a novel mRNA product which leaded to the formation of a truncated protein. Conclusions Through a comprehensive review and analysis of existing literature and this study showed intellectual disability, speech delay and facial dysmorphisms were common clinical manifestation, while the seizures and EEG abnormalities were rare (21/95, 22.16%). Notably, we represent the largest sample size of LAMSHF in Asia that encompasses previously unreported SOX5 gene mutation, and a minigene testing have been conducted to validate the pathogenicity of the c.1772-1C > A splice variant. The research further expands the phenotype and genotype of LAMSHF while offers novel insights for potential pathogenicity of genes locus.

Acute respiratory distress syndrome (ARDS) is a major disease that threatens the life and health of neonates. Vitamin A (VA) can participate in early fetal lung development and affect lung immune function. Researches revealed that the serum VA level in premature infants with ARDS was lower than that in premature infants without ARDS of the same gestational age, and premature infants with VA deficiency (VAD) were more likely to develop ARDS. Moreover, the VA levels can be used as a predictor of the development and severity of neonatal ARDS. However, the critical question here is; Does ARDS develop due to VAD in these systemic diseases? Or does ARDS develop because these diseases cause VAD? We hypothesize that VAD may aggravate neonatal ARDS by affecting immunity, metabolism, barriers and other pathways. In this article, we used multiomics analysis to find that VAD may aggravate ARDS mainly through the Fc epsilon RI signaling pathway, the HIF-1 signaling pathway, glutathione metabolism, and valine, leucine and isoleucine degradation signaling pathways, which may provide the molecular pathogenic mechanism behind the pathology of VAD-aggravated ARDS and can also provide potential molecular targets for subsequent research on ARDS.

Scholars have shown significant interest in the design and investigation of mechanical metamaterials with a negative Poisson’s ratio as a result of the rapid progress in additive manufacturing technology, giving rise to the concept of metamaterials. The mechanical properties of structures with a negative Poisson’s ratio, including Poisson’s ratio, elastic modulus, and impact performance, have received growing scrutiny. This paper introduces the design of a novel concave beetle-shaped structure with a negative Poisson’s ratio. The structure is developed using the variable density topology optimization method, with the design parameters adjusted to achieve optimal results from six datasets. The mechanical properties of the concave beetle-shaped structure are comprehensively assessed with the integration of mathematical models derived from mechanics theory, quasi-static compression tests, and finite element analyses. This study’s findings indicate that the intrinsic parameters of the structure significantly influence its properties. The structure’s Poisson’s ratio ranges from −0.267 to −0.751, the elastic modulus varies between 1.078 and 5.481 MPa, and the specific energy absorption ranges from 1.873 to 2.634 kJ/kg, demonstrating an improvement of up to 40%.

Due to their superior structural and mechanical properties, materials with negative Poisson’s ratio are of increasing interest to research scholars, especially in fuel-efficient vehicles. In this work, a new concave I-shaped honeycomb structure is established by integrating the re-entrant hexagon and the I-shaped beam structure, and its negative Poisson’s ratio characteristics and energy absorption properties are investigated. The effect of structural parameters on the energy absorption characteristics is analyzed using the finite element model. The results show that both the specific energy absorption and peak impact force decrease with the increase in cellular length and vertical short cellular height, and increase with the increase in horizontal short cellular length and cellular thickness. To obtain a smaller peak impact force and larger specific energy absorption with smaller mass, the four cell sizes were optimized by using Latin hypercube sampling, Gaussian radial basis function, and non-dominated sorting genetic algorithm II (NSGA-II). Compared with the original design, the SEA increased by 44.175%, and the PCF increased by 25.857%. Meanwhile, the mass decreased by 31.140%. Hence, the optimal structure has better crashworthiness.

Objective: To characterize earlier damage pattern of white matter (WM) microstructure in cerebral small vessel disease (CSVD) and its relationship with cognitive domain dysfunction. Methods: A total of 144 CSVD patients and 100 healthy controls who underwent neuropsychological measurements and diffusion tensor imaging (DTI) examination were recruited. Cognitive function, emotion, and gait were assessed in each participant. The automated fiber quantification (AFQ) technique was used to extract different fiber properties between groups, and partial correlation and general linear regression analyses were performed to assess the relationship between position-specific WM microstructure and cognitive function. Results: Specific segments in the association fibers, commissural WM regions of interest (ROIs), and projection fibers were damaged in the CSVD group [ P < 0.05, family-wise error (FWE) correction], and these damaged segments showed interhemispheric symmetry. In addition, the damage to specific tract profiles [including the posteromedial component of the right cingulum cingulate (CC), the occipital lobe portion of the callosum forceps major, the posterior portion of the left superior longitudinal fasciculus (SLF), and the bilateral anterior thalamic radiation (ATR)] was related to the dysfunction in specific cognitive domains. Among these tracts, we found the ATR to be the key set of tracts whose profiles were most associated with cognitive dysfunction. The left ATR was a specific fiber bundle associated with episode memory and language function, whereas the fractional anisotropy (FA) values of the intermediate component of the right ATR were negatively correlated with executive function and gait evaluation. It should be noted that the abovementioned relationships could not survive the Bonferroni correction ( p < 0.05/27), so we chose more liberal uncorrected statistical thresholds. Conclusions: Damage to the WM fiber bundles showed extensive interhemispheric symmetry and was limited to particular segments in CSVD patients. Disruption of strategically located fibers was associated with different cognitive deficits, especially the bilateral ATR.

Neuroimaging evidence has suggested white matter microstructure are heavily affected in Alzheimer's disease (AD). However, whether white matter dysfunction is localized at the specific regions of fiber tracts and whether they would be a potential biomarker for AD remain unclear. By automated fiber quantification (AFQ), we applied diffusion tensor images from 25 healthy controls (HC), 24 amnestic mild cognitive impairment (aMCI) patients and 18 AD patients to create tract profiles along 16 major white matter fibers. We compared diffusion metrics [Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR)] between groups. To assess the diagnostic value, we applied a random forest (RF) classifier, a type of machine learning method. In the global tract level, we found that aMCI and AD patients showed higher MD, DA, and DR values in some fiber tracts mostly in the left hemisphere compared to HC. In the point-wise level, widespread disruption were distributed on specific locations of different tracts. The point-wise MD measurements presented the best classification performance with respect to differentiating AD from HC. The two most important variables were localized in the prefrontal potion of left uncinate fasciculus and anterior thalamic radiation. In addition, the point-wise DA in the posterior component of the left cingulum cingulate displayed the most robust discriminative ability to identify AD from aMCI. Our findings provide evidence that white matter abnormalities based on the AFQ method could be as a diagnostic biomarker in AD.