Associations between OGTT results during pregnancy and offspring TSH levels: a birth cohort study.

BACKGROUND: Limited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT). METHODS: A population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio [RR]) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values. RESULTS: Out of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 [95% CI: 0.04-0.36]. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 [95% CI 1.64-13.96]). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L). CONCLUSIONS: For newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.

Association between prenatal exposure to rare earth elements and the neurodevelopment of children at 24-months of age: A prospective cohort study.

The increasing consumption of rare earth elements (REEs) has resulted in a considerable risk of environmental exposure. However, the adverse effects of prenatal REEs exposure on children's neurodevelopment are not yet fully recognized. Therefore, we investigated the individual and joint effects of prenatal exposure to 13 REEs on children's neurocognitive development based on 809 mother-child pairs from a large birth cohort in Wuhan, China. Maternal urinary concentrations of 13 REEs were repeatedly measured by inductively coupled plasma mass spectrometry. Children's neurodevelopment [e.g., mental and psychomotor development index (MDI/PDI)] at 24-months was assessed using Bayley Scales of Infant Development of Chinese Revision. GEE and BKMR models were applied to estimate the individual and joint effects of prenatal REE exposure on child neurodevelopment level. After controlling for typical confounders, we observed that exposure to 9 REEs during the first trimester were significantly associated with decreased MDI scores [ßs and 95% confidence intervals (CIs) ranging from -2.24 (-3.86 âˆ¼ -0.63) to -1.44 (-2.26∼ -0.26)], and 7 REEs during third trimester were significantly associated decreased PDI scores [ß and 95% CIs ranging from -1.95 (-3.19 âˆ¼ -0.71) to -1.25 (-2.34 âˆ¼ -0.16)]. Higher quantiles of REE mixture in first and third trimester were associated with decreased MDI and PDI score. Thulium, erbium in the first trimester and cerium, lanthanum in the third trimester accounted most importance to joint effects on MDI and PDI, respectively. In conclusion, prenatal exposure to higher concentrations of REEs during the first and third trimester were negative associated with children's neurodevelopment.

DKI can distinguish high-grade gliomas from IDH1-mutant low-grade gliomas and correlate with their different nuclear-to-cytoplasm ratio: a localized biopsy-based study.

OBJECTIVES: To explore whether differences in diffusional kurtosis imaging (DKI) between therapy-naïve high-grade gliomas (HGGs) and low-grade gliomas (LGGs) are related to the cellularity and/or the nuclear-to-cytoplasmic (N/C) ratio. METHODS: We analyzed 44 and 40 diffuse glioma samples that were pathologically confirmed as HGGs and IDH1-mutant LGGs, respectively. The DKI parameters included kurtosis metrics (mean kurtosis [MK], axial kurtosis [K//], and radial kurtosis [K⊥]), and the diffusional metrics (fractional anisotropy [FA], mean diffusion [MD], axial diffusion [λ//], and radial diffusion [λ⊥]). The cellularity and the N/C ratio were compared within LGGs and HGGs using the Mann-Whitney U test (significant level, p < 0.007 [0.05/7]); Bonferroni correction). Spearman's correlation analysis was used to calculate the correlation coefficients among DKI metrics, cellularity, and the N/C ratio at a significant level of p = 0.05. RESULTS: Excluding FA, all DKI metrics showed significant differences between HGGs and LGGs (all p ≤ 0.001). The N/C ratio of HGGs was significantly higher than that of LGGs; however, differences in cellularity were not significant between the two glioma groups (p = 0.525). Similarly, excluding FA, all DKI metrics were significantly correlated with the N/C ratio in LGGs, with correlation coefficients of - 0.365 (MD), - 0.313 (λ//), - 0.376 (λ⊥), 0.859 (MK), 0.772 (K//), and 0.842 (K//). There was a non-significant correlation between any DKI parameters and the cellularity in LGGs. Additionally, the cellularity and N/C ratios in HGGs did not correlate with any DKI metrics. CONCLUSIONS: DKI differentiate LGGs from HGGs associated with their different N/C ratios. CLINICAL RELEVANCE STATEMENT: This study shows that DKI differentiates LGGs from HGGs may correlated with their different N/C ratios, this could provide a possible histopathological mechanism about why DKI can DKI differentiate LGGs from HGGs. KEY POINTS: • Excluding FA, all DKI metrics showed a significant difference between high-grade gliomas and IDH1-mutant low-grade gliomas. • The nuclear-to-cytoplasm ratios in high-grade gliomas were significantly more extensive than that in IDH1-mutant low-grade gliomas, but not the cellularity. • Significant associations were seen between DKI measures and the N/C ratio; a non-significant correlation was noted between any DKI metric and cellularity in glioma specimens.

Genomics of Yoonia sp. Isolates (Family Roseobacteraceae) from Lake Zhangnai on the Tibetan Plateau.

Understanding the genomic differentiation between marine and non-marine aquatic microbes remains a compelling question in ecology. While previous research has identified several lacustrine lineages within the predominantly marine Roseobacteraceae family, limited genomic data have constrained our understanding of their ecological adaptation mechanisms. In this study, we isolated four novel Yoonia strains from a brackish lake on the Tibetan Plateau. These strains have diverged from their marine counterparts within the same genus, indicating a recent habitat transition event from marine to non-marine environments. Metabolic comparisons and ancestral genomic reconstructions in a phylogenetic framework reveal metabolic shifts in salinity adaptation, compound transport, aromatics degradation, DNA repair, and restriction systems. These findings not only corroborate the metabolic changes commonly observed in other non-marine Roseobacters but also unveil unique adaptations, likely reflecting the localized metabolic changes in responses to Tibetan Plateau environments. Collectively, our study expands the known genomic diversity of non-marine Roseobacteraceae lineages and enhances our understanding of microbial adaptations to lacustrine ecosystems.

Ecological divergence of syntopic marine bacterial species is shaped by gene content and expression.

Identifying mechanisms by which bacterial species evolve and maintain genomic diversity is particularly challenging for the uncultured lineages that dominate the surface ocean. A longitudinal analysis of bacterial genes, genomes, and transcripts during a coastal phytoplankton bloom revealed two co-occurring, highly related Rhodobacteraceae species from the deeply branching and uncultured NAC11-7 lineage. These have identical 16S rRNA gene amplicon sequences, yet their genome contents assembled from metagenomes and single cells indicate species-level divergence. Moreover, shifts in relative dominance of the species during dynamic bloom conditions over 7 weeks confirmed the syntopic species' divergent responses to the same microenvironment at the same time. Genes unique to each species and genes shared but divergent in per-cell inventories of mRNAs accounted for 5% of the species' pangenome content. These analyses uncover physiological and ecological features that differentiate the species, including capacities for organic carbon utilization, attributes of the cell surface, metal requirements, and vitamin biosynthesis. Such insights into the coexistence of highly related and ecologically similar bacterial species in their shared natural habitat are rare.

The cross-sectional area ratio of a specific part of the flexor pollicis longus tendon- a stable sonographic measurement for trigger thumb: a cross-sectional trial.

BACKGROUND: Trigger thumb is a pathologic condition of the digital pulleys and flexor tendons. To find a cutoff value of the cross-sectional area ratio of specific parts of the flexor pollicis longus tendon to diagnosis trigger thumb in the high-frequency ultrasound examination. METHODS: We evaluated 271 healthy volunteers and 57 patients with clinical diagnosis of trigger thumb. The cross-sectional area of the metacarpophalangeal joint of flexor pollicis longus tendon (C1) and the cross-sectional area of the midpoint of the first metacarpal of flexor pollicis longus tendon (C2) were analyzed. RESULTS: There is no difference between gender, age and left and right hands in the ratio of C1 to C2 (C1/ C2). The mean of C1/ C2 in the healthy thumb was 0.983 ± 0.103, which was significantly smaller in comparison to the diseased thumb (P < 0.05). Based on the receiver operating characteristic curve, we chose the diagnostic cut-off value for the C1/ C2 to be 1.362 and 1.153 in order to differ a trigger thumb from children and adults. CONCLUSIONS: The C1/ C2 of the healthy thumb was relatively stable, with a mean value of 0.983 ± 0.103. The cutoff value of C1/C2 to distinguish healthy thumb from diseased thumb in children and adults were 1.362 and 1.153, respectively.

Glioma grade discrimination with dynamic contrast-enhanced MRI: An accurate analysis based on MRI guided stereotactic biopsy.

PURPOSE: To evaluate the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) metrics for glioma grading on a point-to-point basis. METHODS: Forty patients with treatment-naïve glioma underwent DCE-MR examination and stereotactic biopsy. DCE-derived parameters including endothelial transfer constant (Ktrans), volume of extravascular-extracellular space (ve), fractional plasma volume (fpv), and reflux transfer rate (kep) were measured within ROIs on DCE maps accurately matched with biopsies used for histologic grades diagnosis. Differences in parameters between grades were evaluated by Kruskal-Wallis tests. Diagnostic accuracy of each parameter and their combination was assessed using receiver operating characteristic curve. RESULTS: Eighty-four independent biopsy samples from 40 patients were analyzed in our study. Significant statistical differences in Ktrans and ve were observed between grades except ve between grade 2 and 3. Ktrans showed good to excellent accuracy in discriminating grade 2 from 3, 3 from 4, and 2 from 4 (area under the curve = 0.802, 0.801 and 0.971, respectively). Ve indicated good accuracy in discriminating grade 3 from 4 and 2 from 4 (AUC = 0.874 and 0.899, respectively). The combined parameter demonstrated fair to excellent accuracy in discriminating grade 2 from 3, 3 from 4, and 2 from 4 (AUC = 0.794, 0.899 and 0.982, respectively). CONCLUSION: Our study had identified Ktrans, ve and the combination of parameters to be an accurate predictor for grading glioma.

Intravoxel incoherent motion MRI for rectal cancer: correlation of diffusion and perfusion characteristics with clinical-pathologic factors.

BACKGROUND: Colorectal cancer is the most common cause of cancer-related death worldwide. Magnetic resonance imaging (MRI) has become a promising alternative method for staging the cancer. PURPOSE: To evaluate parameters of intravoxel incoherent motion (IVIM) and their relationships with clinical-pathologic factors in rectal cancers. MATERIAL AND METHODS: A total of 51 patients with histopathologically proven rectal cancer who underwent preoperative pelvic MRI were prospectively enrolled. Parameters (ADC, D, D*, and f) derived from IVIM-diffusion-weighted imaging (DWI) were independently measured by two radiologists. Student's t-test, receiver operating characteristic curves, and Spearman correlation were used for statistical analysis. RESULTS: ADC, D, and D* were significantly higher in pT1-2 tumors than in pT3-4 tumors (1.108 ± 0.233 vs. 0.950 ± 0.176, 0.796 ± 0.199 vs. 0.684 ± 0.114, 0.013 ± 0.005 vs. 0.008 ± 0.003, respectively; P < 0.05). D* exhibited a strong correlation with the tumor stage (r = -0.675, P < 0.001). In poorly differentiated cluster (PDC) grading, ADC, D*, and f were significantly lower in high-grade tumors than in low-grade tumors (0.905 ± 0.148 vs. 1.064 ± 0.200, 0.008 ± 0.002 vs. 0.011 ± 0.005, and 0.252 ± 0.032 vs. 0.348 ± 0.058, respectively; P < 0.05). The f value exhibited a significantly strong correlation with the PDC grades (r = -0.842, P < 0.001), and higher sensitivity and specificity (95.2% and 75.9%) than those shown by the ADC, D, and D* values. CONCLUSION: IVIM parameters, especially f, demonstrated a strong correlation with histologic grades and showed a better performance in differentiating between high- and low-grade rectal cancers. These parameters would be helpful in predicting tumor aggressiveness and prognosis.

Challenges in estimating effective population sizes from metagenome-assembled genomes.

Effective population size (Ne) plays a critical role in shaping the relative efficiency between natural selection and genetic drift, thereby serving as a cornerstone for understanding microbial ecological dynamics. Direct Ne estimation relies on neutral genetic diversity within closely related genomes, which is, however, often constrained by the culturing difficulties for the vast majority of prokaryotic lineages. Metagenome-assembled genomes (MAGs) offer a high-throughput alternative for genomic data acquisition, yet their accuracy in Ne estimation has not been fully verified. This study examines the Thermococcus genus, comprising 66 isolated strains and 29 MAGs, to evaluate the reliability of MAGs in Ne estimation. Despite the even distribution across the Thermococcus phylogeny and the comparable internal average nucleotide identity (ANI) between isolate populations and MAG populations, our results reveal consistently lower Ne estimates from MAG populations. This trend of underestimation is also observed in various MAG populations across three other bacterial genera. The underrepresentation of genetic variation in MAGs, including loss of allele frequency data and variable genomic segments, likely contributes to the underestimation of Ne. Our findings underscore the necessity for caution when employing MAGs for evolutionary studies, which often depend on high-quality genome assemblies and nucleotide-level diversity.

Case report: Efficacy analysis of radiofrequency catheter ablation combined with atrial appendage resection for atrial tachycardia originating from the atrial appendage in children.

Objective: The aim of this study was to investigate the efficacy of radiofrequency catheter ablation (RFCA) combined with atrial appendage (AA) resection to treat atrial tachycardia (AT) originating from the AA in children. Materials and methods: Using the Ensite three-dimensional electroanatomic mapping system, three children with AT originating from the AA were diagnosed. Clinical features and electrocardiographic (ECG) manifestations were analyzed. Ablations were performed using a cold saline-infused catheter at appendages targeting loci of AT origin under the guidance of the Ensite system. Atrial appendage resection was performed in combination with cardiac surgery, and the curative effect was evaluated. Results: The ages of the three patients were 3.5, 5.75, and 12.9 years. Two cases originated from the right atrial appendage (RAA) and one originated from the left atrial appendage (LAA). The ECG characteristics of AT from the RAA were as follows: (1) negative P waves in lead V1; (2) positive P waves in leads II, III, and aVF; (3) positive P wave in lead I with varying shapes in lead aVL; and (4) prolonged PR interval with no QRS wave after some P waves. The ECG of the LAA was characterized by (1) positive P waves in lead V1 with a bimodal pattern; (2) positive P waves in leads II, III, and aVF; and (3) negative P waves in leads I and aVL. Preoperative echocardiography showed cardiac enlargement and a decreased left ventricular ejection fraction (LVEF) in all three cases. One case was cured after RFCA, and the remaining two cases required AA resection after RFCA. No recurrence was detected at 1-18 months of follow-up, and the left ventricular end-diastolic diameter and LVEF returned to normal. Conclusion: Atrial tachycardia originating from the AA in children showed a characteristic P-wave presentation on ECG, and sustained episodes of AT resulted in tachycardia-induced cardiomyopathy. Children who are not successfully controlled by RFCA or who have a recurrence after RFCA could benefit from AA resection.

Incorporating multiple magnetic resonance diffusion models to differentiate low- and high-grade adult gliomas: a machine learning approach.

Background: Accurate grading of gliomas is a challenge in imaging diagnosis. This study aimed to evaluate the performance of a machine learning (ML) approach based on multiparametric diffusion-weighted imaging (DWI) in differentiating low- and high-grade adult gliomas. Methods: A model was developed from an initial cohort containing 74 patients with pathology-confirmed gliomas, who underwent 3 tesla (3T) diffusion magnetic resonance imaging (MRI) with 21 b values. In all, 112 histogram features were extracted from 16 parameters derived from seven diffusion models [monoexponential, intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), fractional order calculus (FROC), continuous-time random walk (CTRW), stretched-exponential, and statistical]. Feature selection and model training were performed using five randomly permuted five-fold cross-validations. An internal test set (15 cases of the primary dataset) and an external cohort (n=55) imaged on a different scanner were used to validate the model. The diagnostic performance of the model was compared with that of a single DWI model and DWI radiomics using accuracy, sensitivity, specificity, and the area under the curve (AUC). Results: Seven significant multiparametric DWI features (two from the stretched-exponential and FROC models, and three from the CTRW model) were selected to construct the model. The multiparametric DWI model achieved the highest AUC (0.84, versus 0.71 for the single DWI model, P<0.05), an accuracy of 0.80 in the internal test, and both AUC and accuracy of 0.76 in the external test. Conclusions: Our multiparametric DWI model differentiated low- (LGG) from high-grade glioma (HGG) with better generalization performance than the established single DWI model. This result suggests that the application of an ML approach with multiple DWI models is feasible for the preoperative grading of gliomas.

Glymphatic system in the thalamus, secondary degeneration area was severely impaired at 2nd week after transient occlusion of the middle cerebral artery in rats.

Background and objectives: The glymphatic system is a recently discovered cerebrospinal fluid transport system and little is known about its dynamic changes after stroke. This study aimed to dynamically observe the structural and functional changes of the impaired glymphatic system in the thalamus after ischemic stroke by pathology and MRI. Materials and methods: Ischemic stroke was induced by the middle cerebral artery occlusion (MCAO) model. A total of 20 Sprague-Dawley rats were randomly assigned into four groups: sham, MCAO 1 week, MCAO 2 week, and MCAO 2 month. All rats successively underwent neurological examination, dynamic contrast-enhanced MRI (DCE-MRI), and immunofluorescence staining. Immunofluorescence staining of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), ionized calcium-binding adaptor molecule 1 (Iba1), and beta-amyloid precursor protein (APP) were done in thalamus ventroposterior nucleus. Results: The astrocyte and microglial activation and the APP deposition in the MCAO 2 week group were the highest (P < 0.05 for all). The AQP4 polarization rates of the MCAO 2 week and 2 month groups were the lowest (P < 0.05 for all). Although there was no correlation between histological changes and MRI metrics in all four groups (P > 0.05 for all), the tendency of the APP deposition was nearly consistent with the one of the contrast agent retention in DCE-MRI. Conclusion: The glymphatic system in the thalamus was severely impaired at 2nd week after MCAO, and may be revealed by DCE-MRI. This study may provide a relevant theoretical basis for making a thorough inquiry of the mechanism of brain injury after stroke and clinical treatment of ischemic stroke and help readers appreciate the importance of DCE-MRI.

Assessing a Role of Genetic Drift for Deep-Time Evolutionary Events.

Effective population size (Ne) determines the amount of genetic diversity and the fate of genetic variants in a species and thus is an essential parameter in evolutionary genetics. There are standard approaches to determine the Ne of evolving species. For example, the long-term Ne of an extant species is calculated based on its unbiased global mutation rate and the neutral genetic diversity of the species. However, approaches for inferring Ne of ancestral lineages are less known. Here, we introduce an evolutionary genetic statistic and an analytical procedure to assess the efficiency of natural selection for deep nodes by calculating rates of nonsynonymous nucleotide substitutions leading to radical (dR) and conservative (dC) amino acid replacements, respectively. Given that radical variants are more likely to be deleterious than conservative ones, an elevated dR/dC ratio in gene families across the genome means an accelerated genome-wide accumulation of the more deleterious type of mutations (i.e., radical variants), which indicates that natural selection is less efficient and genetic drift becomes more powerful. Earlier approaches that calculate dR/dC do not consider the impact of nucleotide composition (G+C content) on the dR/dC result, which is partially accounted for in more recent methods. Here, we use these methods to demonstrate that genetic drift may have driven the early evolution of Prochlorococcus, the most abundant carbon-fixing photosynthetic bacteria in the ocean.

Case Report: Tetralogy of Fallot in a Chinese Family Caused by a Novel Missense Variant of MYOM2.

Background: Rare genetic variants have been identified to be important contributors to the risk of Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease (CHD). But relatively limited familial studies with small numbers of TOF cases have been reported to date. In this study, we aimed to identify novel pathogenic genes and variants that caused TOF in a Chinese family using whole exome sequencing (WES). Methods: A Chinese family whose twins were affected by TOF were recruited for this study. A WES was performed for the affected twins, their healthy brother, and parents to identify the potential pathogenic mutated gene(s). Heterozygous variants carried by the twins, but not the unaffected brother, were retained. Public databases were used to assess the frequencies of the selected variants, and online prediction tools were accessed to predict the influences of these variants on protein function. The final candidate variant was further confirmed by Sanger sequencing in other members of the family. Results: After several filtering processes, a heterozygous missense variant in the MYOM2 gene (NM_003970.4:c.3097C>T:p.R1033C) was identified and confirmed by Sanger sequencing in the affected twins and their unaffected father, suggesting an inheritance pattern with incomplete penetrance. The variant was found to be extremely rare in the public databases. Furthermore, the mutated site was highly conserved among mammals, and as shown using multiple online prediction tools, this variant was predicted to be a detrimental variant. Conclusion: We assessed a family with TOF caused by a rare heterozygous missense variant of MYOM2. Our findings not only further confirm the significant role of genetics in the incidence of TOF but also expand the spectrum of the gene variants that lead to TOF.

Exploring Influential Factors Affecting the Severity of Urban Expressway Collisions: A Study Based on Collision Data.

When traffic collisions occur on urban expressways, the consequences, including injuries, the loss of lives, and damage to properties, are more serious. However, the existing research on the severity of expressway traffic collisions has not been deeply explored. The purpose of this research was to investigate how various factors affect the severity of urban expressway collisions. The severity of urban expressway collisions was set as the dependent variable, which could be divided into three categories: slight collisions, severe collisions, and fatal collisions. Ten variables, including individual characteristics, collision characteristics, and road environment conditions, were selected as independent factors. Based on 975 valid urban expressway collisions, an ordered logistic regression model was established to evaluate the impacts of influence factors on the severity of these crashes. The results show that gender, collision modality, road pavement conditions, road surface conditions, and visibility are significant factors that affect the severity of urban expressway collisions. Females were more likely to be involved in more severe urban expressway collisions than males. For collisions involving pedestrians and non-motorized vehicles, the risk of more severe injury was 7.508 times higher than that associated with vehicle-vehicle collisions. The probability of more severe collisions on urban expressways with poor pavement conditions and wet surface conditions is greater than that on urban expressways with good pavement conditions and dry surface conditions. In addition, as visibility increases, the probability of more severe collisions on urban expressways gradually decreases. These results provide more effective strategies to reduce casualties as a result of urban expressway collisions.

Coastal Transient Niches Shape the Microdiversity Pattern of a Bacterioplankton Population with Reduced Genomes.

Globally dominant marine bacterioplankton lineages are often limited in metabolic versatility, owing to their extensive genome reductions, and thus cannot take advantage of transient nutrient patches. It is therefore perplexing how the nutrient-poor bulk seawater sustains the pelagic streamlined lineages, each containing numerous populations. Here, we sequenced the genomes of 33 isolates of the recently discovered CHUG lineage (~2.6 Mbp), which have some of the smallest genomes in the globally abundant Roseobacter group (commonly over 4 Mbp). These genome-reduced bacteria were isolated from a transient habitat: seawater surrounding the brown alga, Sargassum hemiphyllum. Population genomic analyses showed that: (i) these isolates, despite sharing identical 16S rRNA genes, were differentiated into several genetically isolated populations through successive speciation events; (ii) only the first speciation event led to the genetic separation of both core and accessory genomes; and (iii) populations resulting from this event are differentiated at many loci involved in carbon utilization and oxygen respiration, corroborated by BiOLOG phenotype microarray assays and oxygen uptake kinetics experiments, respectively. These differentiated traits match well with the dynamic nature of the macroalgal seawater, in which the quantity and quality of carbon sources and the concentration of oxygen likely vary spatially and temporally, though other habitats, like fresh organic aggregates, cannot be ruled out. Our study implies that transient habitats in the overall nutrient-poor ocean can shape the microdiversity and population structure of genome-reduced bacterioplankton lineages. IMPORTANCE Prokaryotic species, defined with operational thresholds, such as 95% of the whole-genome average nucleotide identity (ANI) or 98.7% similarity of the 16S rRNA gene sequences, commonly contain extensive fine-grained diversity in both the core genome and the accessory genome. However, the ways in which this genomic microdiversity and its associated phenotypic microdiversity are organized and structured is poorly understood, which disconnects microbial diversity and ecosystem functioning. Population genomic approaches that allow this question to be addressed are commonly applied to cultured species because linkages between different loci are necessary but are missing from metagenome-assembled genomes. In the past, these approaches were only applied to easily cultivable bacteria and archaea, which, nevertheless, are often not representative of natural communities. Here, we focus on the recently discovered cluster, CHUG, which are representative in marine bacterioplankton communities and possess some of the smallest genomes in the globally dominant marine Roseobacter group. Despite being over 95% ANI and identical in the 16S rRNA gene, the 33 CHUG genomes we analyzed have undergone multiple speciation events, with the first split event predominantly structuring the genomic diversity. The observed pattern of genomic microdiversity correlates with CHUG members' differential utilization of carbon sources and differential ability to explore low-oxygen niches. The available data are consistent with the idea that brown algae may be home to CHUG, though other habitats, such as fresh organic aggregates, are also possible.

Impact of smoking on the incidence and post-operative complications of total knee arthroplasty: A systematic review and meta-analysis of cohort studies.

Osteoarthritis and rheumatoid arthritis are the most ubiquitous joint disorders which cause tremendous loss of life quality and impose an economic burden on society. At present, the treatment options for these two diseases comprise non-operative and surgical treatments, amongst those total knee arthroplasties (TKA). Various studies have recognized smoking as a significant risk factor for postoperative complications. Therefore, the purpose of this study was to examine the impact of smoking on the incidence and postoperative complications after a total knee arthroplasty by a systematic review and meta-analysis. The research was performed using PUBMED, Cochrane Library and EMBASE, extracting data from thirteen suitable studies and incorporating 2,109,482 patients. Cohort studies evaluating the impact of smoking on TKA with sufficient data were included for the study, and cohort studies without a proper control group and complete data were excluded. A fixed-effects or random-effects model was used to measure the pooled risk ratio (RR) or hazard ratio (HR) with 95% confidence interval (CI). Compared to non-smokers, smokers had a significantly lower incidence of TKA (p<0.01). However, smokers had a higher incidence of total complications (p=0.01), surgical complications (p<0.01), pneumonia (p<0.01) and revision surgery (p=0.01). No significant difference in the risk of blood transfusion (p=0.42), deep vein thrombosis (p=0.31), pulmonary embolism (p=0.34), urinary tract infection (p=0.46) or mortality (p=0.39) was found between smokers and non-smokers. In conclusion, the study indicated that tobacco has two diametrically opposite effects on TKA patients: 1. Tobacco increases the incidence of surgical complications, pneumonia and revision after TKA; 2. It decreases the overall risk of being a candidate for TKA.

The origin and impeded dissemination of the DNA phosphorothioation system in prokaryotes.

Phosphorothioate (PT) modification by the dnd gene cluster is the first identified DNA backbone modification and constitute an epigenetic system with multiple functions, including antioxidant ability, restriction modification, and virus resistance. Despite these advantages for hosting dnd systems, they are surprisingly distributed sporadically among contemporary prokaryotic genomes. To address this ecological paradox, we systematically investigate the occurrence and phylogeny of dnd systems, and they are suggested to have originated in ancient Cyanobacteria after the Great Oxygenation Event. Interestingly, the occurrence of dnd systems and prophages is significantly negatively correlated. Further, we experimentally confirm that PT modification activates the filamentous phage SW1 by altering the binding affinity of repressor and the transcription level of its encoding gene. Competition assays, concurrent epigenomic and transcriptomic sequencing subsequently show that PT modification affects the expression of a variety of metabolic genes, which reduces the competitive fitness of the marine bacterium Shewanella piezotolerans WP3. Our findings strongly suggest that a series of negative effects on microorganisms caused by dnd systems limit horizontal gene transfer, thus leading to their sporadic distribution. Overall, our study reveals putative evolutionary scenario of the dnd system and provides novel insights into the physiological and ecological influences of PT modification.

Prognostic Value of a New Integrated Parameter-Both Collateral Circulation and Permeability Surface-in Hemorrhagic Transformation of Middle Cerebral Artery Occlusion Acute Ischemic Stroke: Retrospective Cohort Study.

BACKGROUND: Multimodal CT, including CT angiography (CTA) and CT perfusion (CTP), was increasingly used in stroke triage. This study was to determine the relationship between a new integrated parameter-both collateral circulation and relative permeability surface (PS)-and the hemorrhagic transformation (HT) in acute ischemic stroke (AIS) with middle cerebral artery occlusion (MCAO). METHODS: We retrospectively reviewed consecutive AIS patients with MCAO who underwent baseline CTA/CTP within 4 h of symptom onset and follow-up susceptibility-weighted imaging (SWI) within 3 weeks. Collateral circulation was assessed on the baseline CTA. Baseline CTP data were postprocessed to generate PS parameter. The patients with poor collateral circulation and at the same time with high relative PS were classified as the group of both poor collateral circulation and high relative PS. HT was defined according to European Cooperative Acute Stroke Study II criteria on follow-up SWI imaging. Multivariate logistic regression analysis was performed using HT as an outcome variable. RESULTS: The group of patients with both poor collateral circulation and high relative PS was thirteen and thirty-three (52%) developed HT of the final cohort sixty-three AIS patients with MCAO. Multivariate logistic analysis revealed the new integrated parameter-both collateral circulation and relative PS (odds ratio, 16.59; 95% confidence interval, 13.09-19.10; P < 0.001) was independent predictor of HT. The area under the curve was 0.85 (95% confidence interval, 0.81-0.89). The sensitivity was 57%, specificity 97% and positive predictive value 92%, negative predictive value 58%. CONCLUSIONS: For AIS patients with MCAO, these with poor collateral circulation on CTA and at the same time with high relative PS on CTP were at high risk for HT.

Mechanisms driving genome reduction of a novel Roseobacter lineage.

Members of the marine Roseobacter group are key players in the global carbon and sulfur cycles. While over 300 species have been described, only 2% possess reduced genomes (mostly 3-3.5 Mbp) compared to an average roseobacter (>4 Mbp). These taxonomic minorities are phylogenetically diverse but form a Pelagic Roseobacter Cluster (PRC) at the genome content level. Here, we cultivated eight isolates constituting a novel Roseobacter lineage which we named 'CHUG'. Metagenomic and metatranscriptomic read recruitment analyses showed that CHUG members are globally distributed and active in marine pelagic environments. CHUG members possess some of the smallest genomes (~2.6 Mb) among all known roseobacters, but they do not exhibit canonical features of typical bacterioplankton lineages theorized to have undergone genome streamlining processes, like higher coding density, fewer paralogues and rarer pseudogenes. While CHUG members form a genome content cluster with traditional PRC members, they show important differences. Unlike other PRC members, neither the relative abundances of CHUG members nor their relative gene expression levels are correlated with chlorophyll a concentration across the global samples. CHUG members cannot utilize most phytoplankton-derived metabolites or synthesize vitamin B12, a key metabolite mediating the roseobacter-phytoplankton interactions. This combination of features is evidence for the hypothesis that CHUG members may have evolved a free-living lifestyle decoupled from phytoplankton. This ecological transition was accompanied by the loss of signature genes involved in roseobacter-phytoplankton symbiosis, suggesting that relaxation of purifying selection owing to lifestyle shift is likely an important driver of genome reduction in CHUG.