Browse Articles

A rare PRIMER cell state in plant immunity

Abstract Plants lack specialized and mobile immune cells. Consequently, any cell type that encounters pathogens must mount immune responses and communicate with surrounding cells for successful defence. However, the diversity, spatial organization and function of cellular immune states in pathogen-infected plants are poorly understood1. Here we infect Arabidopsis thaliana leaves with bacterial pathogens that trigger or supress immune responses and integrate time-resolved single-cell transcriptomic, epigenomic and spatial transcriptomic data to identify cell states. We describe cell-state-specific gene-regulatory logic that involves transcription factors, putative cis-regulatory elements and target genes associated with disease and immunity. We show that a rare cell population emerges at the nexus of immune-active hotspots, which we designate as primary immune responder (PRIMER) cells. PRIMER cells have non-canonical immune signatures, exemplified by the expression and genome accessibility of a previously uncharacterized transcription factor, GT-3A, which contributes to plant immunity against bacterial pathogens. PRIMER cells are surrounded by another cell state (bystander) that activates genes for long-distance cell-to-cell immune signalling. Together, our findings suggest that interactions between these cell states propagate immune responses across the leaf. Our molecularly defined single-cell spatiotemporal atlas provides functional and regulatory insights into immune cell states in plants.

Emergency care utilization by refugee children compared to controls: A statewide database analysis

Background Refugees face barriers to accessing healthcare despite provision of short-term services after arrival. Limited access to sustained primary care may lead to increased emergency department (ED) utilization and little is known regarding how refugee children access emergency care. Objective To compare the proportion of ED claims and median level of service (LOS) between refugee children and general population controls in a statewide claims database. Methods We conducted a retrospective cohort study of medical claims for patients aged 0 to 18 years old in a statewide claims database from 2014–2019. Refugee claims were identified using deterministic linkage of children with known refugee status. Procedure and diagnosis ICD9/10, Healthcare Common Procedure Coding System, and Current Procedural Terminology codes were obtained from the statewide database to indicate type of claim (ED vs outpatient) and LOS. Demographics were extracted from a data warehouse. Primary outcome was the number of ED claims per 1000 combined ED and outpatient claims. LOS was measured as a proxy for ED visit complexity. We compared demographics, frequency of claims, and median LOS using chi-square. Results There were 5,590,808 total claims with 1,235,476 ED claims. Median number of ED claims per individual patient was the same between groups, however the proportion of claims related to an ED visit was significantly higher in the refugee population than the general population controls (244 vs 221, p = 0.001). Median LOS for ED claims was Level 3 (99283) and there was no difference between groups. Conclusion Proportion of ED claims was higher in a refugee population compared to controls with no differences in LOS, indicating higher ED utilization among refugees for all acuity levels. Further study is needed to determine if healthcare disparities account for this difference and if population specific services may support the care of the refugee children.

Traveling Companions

Public health implications of multidrug-resistant and methicillin-resistant Staphylococcus aureus in retail oysters

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is a major challenge for food safety and public health. This study aimed to investigate the potential role of oysters sold in Egypt as a source for Staphylococcus aureus (S. aureus), MRSA, and multidrug-resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA). It also examined the occurrence of tsst-1 virulence gene and assessed the associated zoonotic risks. Thirty-three pooled fresh oyster samples were acquired from different retail fish markets in Egypt. S. aureus was identified by conventional culture-based and molecular methods. Antimicrobial resistance was performed by the disk-diffusion method, and the multiple antibiotic resistance index (MARI) was calculated. Antimicrobial resistance (mecA and mecC) and virulence (tsst-1) genes were screened using polymerase chain reaction. The clustering of virulent MDR-MRSA isolates was performed using R with the pheatmap package. The prevalence of S. aureus was 39.4% (13 /33), and 77% of them (10/13) were classified as MDR with MARI values greater than 0.2. Notably, 46.2% (6 /13) of isolates were identified as MRSA and all MRSA isolates displayed MDR. Of the MDR-MRSA isolates, 66.7% (4 /6) possessed the mecA gene, while 16.7% (1 /6) tested positive for the mecC gene. Additionally, the tsst-1 gene was identified in one isolate (16.7%). Interestingly, two MDR-MRSA isolates exhibited a clustered pattern. The study sheds light on the emergence of virulent MDR-MRSA isolates in Egyptian oysters. It highlights oysters as a potential source for spreading these isolates within aquatic ecosystems, posing a threat to food safety and public health.

Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway

The nutraceutical COMP-4 –consisting of L-citrulline, ginger extract, and herbal components Paullinia cupana and muira puama–has been shown previously to stimulate the production of nitric oxide (NO) in a variety of tissue types. We hypothesized that COMP-4 may have a protective, stimulatory effect on the vascular endothelial cell. Human umbilical arterial endothelial cells were incubated for 24 hours with or without COMP-4 and, to replicate impairment of endothelial function, co-incubated with or without H2O2. NO intracellular content, nitrite formation and cGMP content in culture media, nitric oxide synthase (NOS) isoforms and mRNA content, pro-inflammatory cytokines, and PAI-1 expression and activity were measured. COMP-4 increased endothelial cell production of NO and cGMP and the expression of both endothelial NOS (eNOS) and inducible NOS (iNOS), in tandem with a reduction in cytokine expression and activity of PAI-1. Co-incubation of COMP-4 with H2O2 reversed detrimental effects of H2O2 on endothelial function, evidenced by improvement in NO availability and abrogation of the pro-inflammatory milieu. These results suggest that COMP-4 exerts a stimulatory effect on endothelial cell eNOS and iNOS to increase NO bioavailability, leading to a reduction in pro-inflammatory cytokines, particularly the prothrombotic PAI-1.

Cell and Gene Therapies — Improving Access and Outcomes for Medicare and Medicaid Beneficiaries

The fault systems that control the occurrences of iron ore deposits in northeastern Aswan, Egypt

Abstract The present study combines remote sensing data (Landsat-8 and ASTER) with structural analysis to identify the fault systems affecting the distribution of the ironstone beds in northeastern Aswan, Egypt. Sedimentary rocks, such as the Abu Aggag, Timsah, and Umm Brammily formations, characterize northeastern Aswan. The Abu Aggag Formation consists of kaolinitic conglomerate, conglomeratic sandstone, and mudstone. The upper Timsah Formation consists of ferruginous sandstones, oolitic ironstone, and mudstone. Fluvial sandstone forms the Umm Brammily Formation. The oolitic sandy ironstone (2–2.5 m thick) is rich in dark red oolitic hematite and goethite. The ironstone deposit ranges in composition from oolitic sandy ironstone to oolitic ironstone. The distribution of iron minerals is extremely consistent with the iron concentration grade indicated by the Landsat-8 and ASTER Brand Ratios. Five main fault sets to control the extension of the ironstone beds: NNE-SSW left-lateral strike-slip faults (set 1); ENE-WSW normal faults (set 2); NNW-SSE normal faults (set 3); NW–SE normal faults (set 4); and NE-SW normal faults (set 5). The subsequent displacement of Set 3 faults increased the depth of the ironstone bed, which raised the sedimentary overburden load and increased the cost of ironstone exploitation, as well as the absence of iron ore exploitation zones bordering the Nile River.

PGC-1α activation to enhance macrophage immune function in mycobacterial infections

Nontuberculous Mycobacteria (NTM) are a heterogeneous group of environmental microorganisms with distinct human pathogenesis. Their incidence and prevalence are rising worldwide, due in part to elevated antimicrobial resistance which complicates treatment and potential successful outcomes. Although information exists on the clinical significance of NTMs, little is known about host immune response to infection. NTM infections alter macrophage mitochondrial capacity and decrease ATP production, efficient immune response, and bacterial clearance. Transcription factor peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis, influencing metabolism, mitochondrial pathways, and antioxidant response. Mitochondrial transcription factor A (TFAM) is a protein essential for mitochondrial DNA (mtDNA) genome stability, integrity, and metabolism. Both PGC-1α and TFAM regulate mitochondrial biogenesis and activity, and their disruption is linked to inflammatory signaling and altered macrophage function. We show that NTM causes macrophage mitochondrial damage and disrupted bioenergetics. Mechanistically we show that this is related to attenuation of expression of PGC-1α and TFAM in infected macrophages. Importantly, rescuing expression of PGC-1α and TFAM using pharmacologic approaches restored macrophage immune function. Our results suggest that pharmacologic approaches to enhance mitochondrial function provide a novel approach to target macrophage immune function and means to combat NTM infections.

Hypothyroid Myopathy with Muscle Pseudohypertrophy

Sorghum yield prediction based on remote sensing and machine learning in conflict affected South Sudan

Cuproptosis-related lncRNAs and genes: Potential markers for glioblastoma prognosis and treatment

Despite the availability of various treatment options, glioblastoma (GBM) remains an extremely aggressive form of glioma with a poor prognosis. In recent studies, regulatory cell death (RCD) has been identified as an effective mechanism to suppress glioma. Cuproptosis, caused by intracellular copper, is a novel RCD process that affects chemotherapy efficacy and glioma progression; however, the precise function of cuproptosis-related lncRNAs (CRLs) and cuproptosis-related genes (CRGs) in GBM remains uncertain. To determine whether CRLs and CRGs have prognostic significance, a GBM cohort in TCGA to build a novel cuproptosis-related risk model. Two high-risk CRLs (AC091182.2, AC005229.4) and their co-expression CRGs (LIPT2, GLS) were identified and verified to constitute an independent prognostic indicator of GBM. RT-qPCR analysis confirmed that the high-risk CRLs and CRGs were highly expressed in GBM cells compared to normal astrocytes. By constructing a mouse GBM model, high-risk CRLs and CRGs were found to be expressed at higher levels in tumor tissues. Furthermore, to verify whether these CRLs and CRGs are associated with GBM cuproptosis, cuproptosis cell models were constucted in GBM cell lines and astrocyte by using Elesclomol and CuCl2. It was found that the expression of high-risk CRLs and CRGs was decreased upon cuproptosis-induced in GBM cells. Interestingly, normal astrocytes were less sensitive than GBM cells to cuproptosis-inducing drugs, and the effects of the drugs on the expression of the CRLs and CRGs in normal astrocytes were opposite to that of in GBM cells. In conclusion, by constructing a novel cuproptosis-related risk model, two high-risk CRLs and CRGs were identified. Their specific pointing to GBM has been demonstrated through a variety of experiments. These CRLs and CRGs might serve as prognostic markers and indicators for GBM and provide theoretical support for future GBM treatment.

CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in <i>TP53</i>

Psychometric validation and cultural adaptation of the Persian Galveston orientation and amnesia test and orientation-log for assessing traumatic brain injury

Prevalence of prolonged transitional neonatal hypoglycemia and associated factors in Ethiopia: A systematic review and meta-analysis

Introduction Most neonates experience transient hypoglycemia, which typically responds well to treatment and is associated with a favorable prognosis. However, hypoglycemia persisting beyond 48 hours, termed prolonged transitional Neonatal hypoglycemia (PTNHG), can result in abrupt neuronal injury and long-term neurodevelopmental impairments. Identifying its prevalence and associated risk factors is critical to inform clinical practices and improve neonatal outcomes. Methods A weighted inverse-variance random-effects model was employed for the analysis. Heterogeneity among the studies was assessed using a forest plot, I2 statistics, and Egger’s test. Data extraction was conducted from May 20 to May 27, 2023, for studies published since 2020. A random blood sugar (RBS) concentration of &lt;47 mg/dL measured 48–72 hours after birth was used to define PTNHG. Eight studies comprising a total of 3686 neonates were included in the analysis. Results The pooled prevalence of PTNHG was 19.71% (95% CI: 16.85–22.56) with substantial heterogeneity (I2 = 79.20%, P &lt; 0.001). Subgroup analysis revealed that PTNHG prevalence was similar for studies with sample sizes &gt;400 and ≤400, at 18% (95% CI: 15–22) and 21% (95% CI: 17–26), respectively. Similarly, prevalence estimates were comparable when using RBS thresholds of &lt;47 mg/dL (21%; 95% CI: 16–27) and &lt;40 mg/dL (18%; 95% CI: 15–22). Significant factors associated with PTNHG included preterm birth (AOR = 3.31; 95% CI: 2.57–4.04), hypothermia (AOR = 3.41; 95% CI: 2.19–4.62), being an infant of a diabetic mother (IDM) (AOR = 4.71; 95% CI: 2.15–7.26), delayed breastfeeding initiation beyond one hour (AOR = 3.26; 95% CI: 2.03–4.49), and pathological jaundice (AOR = 2.37; 95% CI: 1.91–2.84). Conclusions Nearly one-fifth of hospitalized neonates experienced PTNHG. Fortunately, most of the associated risk factors were modifiable. Prioritizing early breastfeeding initiation, particularly in cesarean section deliveries and IDM cases, and integrating PTNHG management into national NICU guidelines could significantly reduce the burden of neonatal hypoglycemia. Trial registration Prospero ID: CRD42023424953. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023424953.

<i>Plaques en Prairie Fauchée</i> Tongue Lesions in Secondary Syphilis

Non-lethal sonodynamic therapy mitigates hypertensive renal fibrosis through the PI3K/AKT/mTORC1-autophagy pathway

Calculating age-specific prevalence rates of female genital mutilation / cutting (FGM/C) for use as an input variable in extrapolation calculations and as predictors of future prevalence in countries of origin

This paper proposes a refined method for calculating age-specific prevalence rates of Female Genital Mutilation/Cutting (FGM/C) to enhance the accuracy of estimates calculated using Yoder and Van Baelen’s Extrapolation-of-FGM/C-Countries-Prevalence-Data method. Previous studies, particularly in the United States, have faced limitations, including the failure to disaggregate prevalence data by age and overlooking historical trends. To address these limitations, this study outlines a comprehensive seven-step approach. Using Ethiopia as a case study, prevalence rates were calculated and aligned with target migrant population data. This involved adjusting age cohorts, extrapolating prevalence to younger age groups, and considering historical trends. Results demonstrate significant differences compared to previous estimates, indicating overestimation of girls at risk of FGM/C in some studies. The proposed method offers a standardized approach applicable beyond the United States, potentially improving estimates globally. By providing nuanced prevalence data, this method contributes to better understanding the true prevalence of FGM/C in migrant populations. This same method can also be used to predict future trends in FGM/C and other practices.

Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy

Machine learning optimized design of THz piezoelectric perovskite-based biosensor for the detection of formalin in aqueous environments

Abstract This investigation presents the development and characterization of an advanced piezoelectric perovskite-based biosensing platform optimized for formalin detection in aqueous media through the implementation of Locally Weighted Linear Regression (LWLR) machine learning algorithms. The sensor architecture operates within the terahertz spectral region and incorporates an advanced nanomaterial composite system comprising black phosphorus, gold nanostructures, graphene, and barium titanate to maximize detection sensitivity and operational performance metrics. The engineered platform integrates a circular graphene metasurfaces configuration with a gold-based H-resonator assembly and concentrically arranged circular ring resonators. Computational simulations demonstrate vigorous sensing capabilities across three discrete frequency bands, achieving remarkable sensitivity parameters of 444 GHzRIU⁻¹, accompanied by a quality factor of 5.970 and detection accuracy of 7.576. The integration of LWLR-based optimization protocols substantially enhances prediction accuracy while reducing computational time by ≥ 85% as well as cutting down the required resources. The proposed sensor architecture presents significant potential for environmental monitoring and clinical applications, offering a highly sensitive and efficient methodology for quantitative formalin detection in aqueous environments.

Comparisons of performances of structural variants detection algorithms in solitary or combination strategy

Structural variants (SVs) have been associated with changes in gene expression, which may contribute to alterations in phenotypes and disease development. However, the precise identification and characterization of SVs remain challenging. While long-read sequencing offers superior accuracy for SV detection, short-read sequencing remains essential due to practical and cost considerations, as well as the need to analyze existing short-read datasets. Numerous algorithms for short-read SV detection exist, but none are universally optimal, each having limitations for specific SV sizes and types. In this study, we evaluated the efficacy of six advanced SV detection algorithms, including the commercial software DRAGEN, using the GIAB v0.6 Tier 1 benchmark and HGSVC2 cell lines. We employed both individual and combination strategies, with systematic assessments of recall, precision, and F1 scores. Our results demonstrate that the union combination approach enhanced detection capabilities, surpassing single algorithms in identifying deletions and insertions, and delivered comparable recall and F1 scores to the commercial software DRAGEN. Interestingly, expanding the number of algorithms from three to five in the combination did not enhance performance, highlighting the efficiency of a well-chosen ensemble over a larger algorithmic pool.