Notes

Inbuilt lymphoid cells (ILC) in SARS-CoV-2 contamination.
Managed agricultural ecosystems are unique systems where crops and microbes are intrinsically linked. This study focuses on discerning microbiome successional patterns across all plant organs and tests for evidence of niche differentiation along temporal and spatial axes. Soybean plants were grown in an environmental chamber till seed maturation. Samples from various developmental stages (emergence, growth, flowering and maturation) and compartments (leaf, stem, root and rhizosphere) were collected. Community structure and composition were assessed with 16S rRNA gene and ITS region amplicon sequencing. Overall, the interaction between spatial and temporal dynamics modulated alpha and beta diversity patterns. Time lag analysis on measured diversity indices highlighted a strong temporal dependence of communities. Spatial and temporal interactions influenced the relative abundance of the most abundant genera, whilst random forest predictions reinforced the observed localisation patterns of abundant genera. Overall, our results show that spatial and temporal interactions tend to maintain high levels of biodiversity within the bacterial/archaeal community, whilst in fungal communities OTUs within the same genus tend to have overlapping niches.
The inability of enzyme replacement therapy (ERT) to prevent progression of Fabry nephropathy (FN) in the presence of >1 g/day proteinuria underscores the necessity of identifying effective biomarkers for early diagnosis of FN preceding proteinuria. Here we attempted to identify biomarkers for early detection of FN.

Fifty-one Fabry disease (FD) patients were enrolled. Urinary mulberry bodies (uMBs) were immunostained for globotriaosylceramide (Gb3) and renal cell markers to determine their origin. The association between semiquantitative uMB excretion and the histological severity of podocyte vacuolation was investigated in seven patients using the vacuolated podocyteglomerular average area ratio. The association between the semiquantitative estimate of uMB excretion and duration of ERT was analyzed. A longitudinal study was conducted to assess the effect of ERT on uMB excretion.

Thirty-two patients (63%) had uMBs, while only 31% showed proteinuria. The uMBs were positive for Gb3, lysosomal-associated membrane protein 1 and podocalyxin, suggesting they were derived from lysosomes with Gb3 accumulation in podocytes. We observed more severe podocyte vacuolation with increased uMB excretion (P = 0.03 for trend); however, the same was not observed with increased proteinuria. The percentage of patients with substantial uMB excretion increased with shorter ERT duration (P = 0.018). Eighteen-month-long ERT reduced uMB excretion (P = 0.03) without affecting proteinuria.

uMB excretion, implying ongoing podocyte injury, preceded proteinuria in most patients. Semiquantitative uMB estimates can serve as novel biomarkers for early FN diagnosis and for monitoring the efficacy of FD-specific therapies.
uMB excretion, implying ongoing podocyte injury, preceded proteinuria in most patients. Semiquantitative uMB estimates can serve as novel biomarkers for early FN diagnosis and for monitoring the efficacy of FD-specific therapies.
Previous studies have shown that lipid accumulation product (LAP) was associated with the risk of cardiometabolic disease, it is not clear whether LAP could be used as a marker to identify metabolic syndrome (MetS) among Chinese ethnic groups.

To assess the reliability of LAP as a maker to identify MetS among Dong adults.

Population-based cross-sectional study.

We included 6,494 Dong individuals (1,403 patients) aged 30-79 years from southwest China. MetS was established by Chinese Diabetes Society. Logistic regression model was utilized to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curve was utilized to calculate area under the ROC curve (AUC) and 95% CIs to obtain the identification ability for MetS.

The risk of MetS was increased with per 5 units increase of LAP (OR 1.37 [95% CI, 1.34-1.39]). Similar results were found in subgroup analyses and sensitivity analyses. Clustered metabolic risk associated with per 5 units increase of LAP was observed for people with 1 (OR 1.59 [95% CI, 1.53-1.65]), 2 (2.15 [2.06-2.24]), 3 (2.59 [2.48-2.71]), 4 (2.81 [2.69-2.95]), and 5 (3.03 [2.87-3.21]) MetS components. LAP presented higher AUC (0.915 [95% CI, 0.907-0.923]) than other included obesity indices (P < 0.05).

These data support evidence that LAP was related to the risk of MetS, had a high AUC, and could be a reliable index for identifying MetS patients among Dong adults in Chinese.
These data support evidence that LAP was related to the risk of MetS, had a high AUC, and could be a reliable index for identifying MetS patients among Dong adults in Chinese.
Patients with metastatic breast cancer (MBC) are living longer, but development of brain metastases often limits their survival. selleck compound We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population.

Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with HER2+, triple negative, and hormone receptor (HR)+/HER2- MBC; pooled overall estimates for incidence were calculated using random effects models.

937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up 30.7 months, IQR 24.0 - 34.0), 32% for the triple negative subgroup (median follow-up 32.8 months, IQR 18.5 - 40.6), and 15% among patients with HR+/HER2- MBC (median follow-up 33.0 months, IQR 31.9 - 36.2). The corresponding incidences per patient-year were 0.13 (95% CI 0.10 - 0.16) for the HER2+ subgroup, 0.13 (95%CI 0.09 - 0.20) for the triple negative subgroup, and only 0.05 (95%CI 0.03 - 0.08) for patients with HR+/HER2- MBC.

There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.
There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and non-neuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.
Bright IDEAS (BI) is a problem-solving skills training (PSST) program that has been demonstrated in earlier randomized controlled trials (RCTs) to be an effective and specific intervention for improving problem-solving skills and reducing negative affect in caregivers of children with cancer. The objectives of this study were to (a) offer an approach to defining meaningful treatment response and to determine the rates of responsivity to PSST; and (b) identify characteristics of PSST responders and nonresponders.

Data from 154 mothers receiving the BI intervention were analyzed. Drawing on the literature on minimal clinically important differences, two criteria for determining responsivity were calculated for the primary outcome of problem-solving skills (a) The reliable change index (RCI) based on group data, and; (b) The effect size (ES) of each participant's pre/postintervention change score as a function of the group's baseline SD.

Thirty-three percent of the sample met both responsivity criteria immediately posttreatment (39% at follow-up) and 38% (39% at follow-up) met neither. An additional 29% demonstrated a small or greater ES (≥ 0.2) but did not meet the RCI criteria, suggesting possible benefit. The single consistent predictor of responsivity was participants' pretreatment problem-solving skills, with lower skills at baseline predicting greater improvement (p < .001).

These findings highlight the need to go beyond group data in interpreting RCTs and to incorporate measures of meaningful treatment response. Our ability to predict and screen for meaningful treatment response is critical to more precise targeting, enhanced outcomes, and better resource allocation.
These findings highlight the need to go beyond group data in interpreting RCTs and to incorporate measures of meaningful treatment response. Our ability to predict and screen for meaningful treatment response is critical to more precise targeting, enhanced outcomes, and better resource allocation.
Glioblastoma is the most common and aggressive type of primary brain tumor, as most patients succumb to the disease less than two years after diagnosis. Critically, studies demonstrate that glioma recruits surrounding blood vessels, while some work suggests that tumor stem cells themselves directly differentiate into endothelial cells, yet the molecular and cellular dynamics of the endothelium in glioma are poorly characterized. The goal of this study was to establish molecular and morphological benchmarks for tumor associated vessels (TAVs) and tumor derived endothelial cells (TDECs) during GBM progression.

Using In-Utero Electroporation and CRISPR/Cas9 genome engineering to generate a native, immunocompetent mouse model of glioma, we characterized vascular-tumor dynamics in three dimensions during tumor progression. We employed bulk and single-cell RNA-Sequencing to elucidate the relationship between TAV and TDECs. We confirmed our findings in a patient derived orthotopic xenograft (PDOX) model.

Using a mouse model of glioma, we identified progressive alteration of vessel function and morphogenesis over time. We also showed in our mouse model that TDECs are a rare subpopulation that contributes to vessels within the tumor, albeit to a limited degree. Furthermore, transcriptional profiling demonstrates that both TAVs and TDECs are molecularly distinct, and both populations feature extensive molecular heterogeneity. Finally, the distinct molecular signatures of these heterogenous populations are also present in human glioma.

Our findings show extensive endothelial heterogeneity within the tumor and tumor microenvironment, and provide insights into the diverse cellular and molecular mechanisms that drive glioma vascularization and angiogenesis during tumorigenesis.
Our findings show extensive endothelial heterogeneity within the tumor and tumor microenvironment, and provide insights into the diverse cellular and molecular mechanisms that drive glioma vascularization and angiogenesis during tumorigenesis.
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