Search

Background Empyema thoracis is a serious infectious disease and is associated with high morbidity and mortality. The perioperative outcomes between culture-positive and culture-negative empyema after thoracoscopic decortication remained controversial, especially since there were no studies that reported the survival outcomes between culture-positive and culture-negative empyema. Methods This single-institute study involved a retrospective analysis. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. Patients were grouped into a culture-positive group and a culture-negative group according to culture results obtained no later than 2 weeks after surgery. Results A total of 1087 patients with empyema received surgery, and 824 were enrolled after exclusion. Among these, 366 patients showed positive culture results and 458 patients showed negative results. Longer intensive care unit stays (11.69 vs 5.64 days, P <.001), longer ventilator usage (24.70 vs 14.01 days, P =.002), and longer postoperative hospital stays (40.83 vs 28.37 days, P <.001) were observed in the culture-positive group. However, there was no significant difference in 30-day mortality between the 2 groups (5.2% in culture negative vs 5.0% in culture positive, P =.913). The 2-year survival was not significantly different between the 2 groups (P =.236). Conclusions Patients with culture-positive or culture-negative empyema who underwent thoracoscopic decortication showed similar short-term and long-term survival outcomes. A higher risk of death was associated with advanced age, a higher Charlson Comorbidity Index score, phase III empyema, and a cause other than pneumonia. [ABSTRACT FROM AUTHOR]

Neural-aided cryptanalysis is a challenging topic, in which the neural distinguisher (⁠|$\mathcal{ND}$|⁠) is a core module. In this paper, we propose a new |$\mathcal{ND}$| considering multiple ciphertext pairs simultaneously. Besides, multiple ciphertext pairs are constructed from different keys. The motivation is that the distinguishing accuracy can be improved by exploiting features derived from multiple ciphertext pairs. To verify this motivation, we have applied this new |$\mathcal{ND}$| to five different ciphers. Experiments show that taking multiple ciphertext pairs as input indeed brings accuracy improvement. Then, we prove that our new |$\mathcal{ND}$| applies to two different neural-aided key recovery attacks. Moreover, the accuracy improvement is helpful for reducing the data complexity of the neural-aided statistic attack. The code is available at https://github.com/AI-Lab-Y/ND_mc. [ABSTRACT FROM AUTHOR]

Continental deep subduction after the closure of large oceanic basins is commonly ascribed to the gravitational pull of the subducting oceanic slab. However, it is not clear how continental lithosphere adjacent to small oceanic basins was subducted to mantle depths. The Sesia Zone in the Western Alps provides an excellent target for exploration of subduction dynamics in such a tectonic setting. Here we report the first finding of coesite in a jadeite-bearing orthogneiss from the Sesia Zone, providing the first evidence for deep subduction of the continental crust to mantle depths for ultrahigh-pressure (UHP) metamorphism in this zone. Three coesite inclusions were identified by laser Raman spectroscopy in two garnet grains. Based on zircon U-Pb dating and trace element analysis, the UHP metamorphic age was constrained to be 76.0 ± 1.0 Ma. The phase equilibrium modeling yields peak metamorphic pressures of 2.8–3.3 GPa, demonstrating the continental deep subduction to mantle depths of >80 km. The subducted continental crust was a rifted hyperextended continental margin, which was converted to the passive continental margin during seafloor spreading and then deeply subducted during the oblique convergence between the Adria microplate and Eurasian plate in the Late Cretaceous. Because the slab pull could only play a limited role in closing small oceanic basins for continental collision, the distal push of either continental breakup or seafloor spreading is suggested as the major driving force for the deep subduction of continental crust in the Western Alps. Therefore, deep subduction of the continental crust bordering small oceanic basins would have been induced by the far-field stress of compression, whereas that bordering large oceanic basins was spontaneous due to the oceanic slab pull. This provides a new insight into the geodynamic mechanism of continental deep subduction. The ultrahigh-pressure metamorphism in the Sesia zone of Western Alps is firstly reported, demonstrating the deep subduction of continental crust to mantle depths of >80 km. The continental deep subduction is driven by the distal push of either continental breakup or seafloor spreading, rather than by the proximal pull of the subducting oceanic slab. [ABSTRACT FROM AUTHOR]

Thrips hawaiiensis (Morgan) (Thysanoptera: Thripidae) is a sap-sucking pest that seriously damages several crops and reduces their economic value. Exposure to low concentrations of insecticides may have a sublethal effect on surviving insects. In order to provide a reference for the rational application of emamectin benzoate, its sublethal effects on the development and reproduction of T. hawaiiensis were evaluated. Pupal development time was significantly shorter in T. hawaiiensis treated with sublethal concentrations of emamectin benzoate (LC10 and LC20) than in control. Female adult longevity and female total longevity were significantly longer following LC20 treatment than in the control and LC10 treatment groups. Nevertheless, male adult longevity and male total longevity were significantly shorter in the LC10 treatment group than in the control and LC20 treatment groups. The sublethal concentration of emamectin benzoate (LC20) significantly shortened the preadult stages and the mean generation. Meanwhile, it significantly increased the finite rate of increase, intrinsic rate of increase, and net reproductive rate. The fecundity was significantly higher after LC20 treatment than after LC10 and control treatments. Compared with the control group, the LC10 and LC20 groups of T. hawaiiensis adults showed a significantly higher expression of the vitellogenin (Vg) and vitellogenin receptor (VgR) genes, which played a key role in increasing their fecundity. These findings suggest that short-term exposure to sublethal concentrations of emamectin benzoate may lead to a resurgence and secondary outbreak of T. hawaiiensis infestation. The results have practical applications for the management of this important and noxious pest. [ABSTRACT FROM AUTHOR]

Background Galectin-3 is a multi-functional lectin protein and a ligand of mucin-1 (CA15-3), and has been linked to renal fibrosis in animal models and renal function in humans. However, no population study has ever explored the associations with both ligand and receptor. We therefore investigate the independent association of renal function with serum galectin-3 and mucin-1 (CA15-3) in untreated Chinese patients. METHODS The study participants were outpatients who were suspected of hypertension, but had not been treated with antihypertensive medication. Serum galectin-3 and mucin-1 (CA15-3) concentrations were both measured by the enzyme-linked immunosorbent assay (ELISA) method. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine by the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results The 1,789 participants included 848 (47.4%) men. Mean (±SD) age was 51.3 ± 10.7 years. Multiple regression analyses showed that eGFR was significantly associated with serum galectin-3 and mucin-1 (CA15-3) concentration (0.68 and 1.32 ml/min/1.73 m2 decrease per 1-SD increase in log transformed serum galectin-3 and mucin-1 (CA15-3) concentration, respectively; P ≤ 0.006). The association of eGFR with serum mucin-1 (CA15-3) concentration was significantly stronger in the overweight (BMI 24.0–27.9 kg/m2) and obese (BMI ≥ 28.0 kg/m2) than in normal weight subjects (BMI < 24.0 kg/m2, P for interaction 0.018). Path analysis showed that serum galectin-3 concentration had both a direct (P = 0.016) and a mucin-1 mediated indirect effect (P = 0.014) on eGFR. Conclusions Both circulating galectin-3 and mucin-1 (CA15-3) were significantly associated with renal function. The role of galectin-3 on renal function might be partially via mucin-1. [ABSTRACT FROM AUTHOR]

YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5 −/− mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5 −/− mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates. [ABSTRACT FROM AUTHOR]

Drug resistance is increasingly among the main issues affecting human health and threatening agriculture and food security. In particular, developing approaches to overcome target mutation-induced drug resistance has long been an essential part of biological research. During the past decade, many bioinformatics tools have been developed to explore this type of drug resistance, and they have become popular for elucidating drug resistance mechanisms in a low cost, fast and effective way. However, these resources are scattered and underutilized, and their strengths and limitations have not been systematically analyzed and compared. Here, we systematically surveyed 59 freely available bioinformatics tools for exploring target mutation-induced drug resistance. We analyzed and summarized these resources based on their functionality, data volume, data source, operating principle, performance, etc. And we concisely discussed the strengths, limitations and application examples of these tools. Specifically, we tested some predictive tools and offered some thoughts from the clinician's perspective. Hopefully, this work will provide a useful toolbox for researchers working in the biomedical, pesticide, bioinformatics and pharmaceutical engineering fields, and a good platform for non-specialists to quickly understand drug resistance prediction. [ABSTRACT FROM AUTHOR]

Aims Macrophage migration inhibitory factor (MIF), a pleiotropic inflammatory cytokine, is highly expressed in patients with atrial fibrillation (AF). Inflammation increases the risk of AF and is primarily triggered by pulmonary vein (PV) arrhythmogenesis. This study investigated whether MIF can modulate the electrical activity of the PV and examined the underlying mechanisms of MIF. Methods and results A conventional microelectrode, a whole-cell patch clamp, western blotting, and immunofluorescent confocal microscopy were used to investigate electrical activity, calcium (Ca2+) regulation, protein expression, ionic currents, and cytosolic reactive oxygen species (ROS) in rabbit PV tissue and isolated single cardiomyocytes with and without MIF incubation (100 ng/mL, treated for 6 h). The MIF (100 ng/mL)-treated PV tissue (n = 8) demonstrated a faster beating rate (1.8 ± 0.2 vs. 2.6 ± 0.1 Hz, P < 0.05), higher incidence of triggered activity (12.5 vs. 100%, P < 0.05), and premature atrial beat (0 vs. 100%, P < 0.05) than the control PV tissue (n = 8). Compared with the control PV cardiomyocytes, MIF-treated single PV cardiomyocytes had larger Ca2+ transients (0.6 ± 0.1 vs. 1.0 ± 0.1, Δ F / F 0, P < 0.05), sarcoplasmic reticulum Ca2+ content (0.9 ± 0.20 vs. 1.7 ± 0.3 mM of cytosol, P < 0.05), and cytosolic ROS (146.8 ± 5.3 vs. 163.7 ± 3.8, Δ F / F 0, P < 0.05). Moreover, MIF-treated PV cardiomyocytes exhibited larger late sodium currents (INa-Late), L-type Ca2+ currents, and Na+/Ca2+ exchanger currents than the control PV cardiomyocytes. KN93 [a selective calcium/calmodulin-dependent protein kinase II (CaMKII) blocker, 1 μM], ranolazine (an INa-Late inhibitor, 10 μM), and N -(mercaptopropionyl) glycine (ROS inhibitor, 10 mM) reduced the beating rates and the incidence of triggered activity and premature captures in the MIF-treated PV tissue. Conclusion Macrophage migration inhibitory factor increased PV arrhythmogenesis through Na+ and Ca2+ dysregulation through the ROS activation of CaMKII signalling, which may contribute to the genesis of AF during inflammation. Anti-CaMKII treatment may reverse PV arrhythmogenesis. Our results clearly reveal a key link between MIF and AF and offer a viable therapeutic target for AF treatment. [ABSTRACT FROM AUTHOR]

Background The association of pelvic radiation with pelvic fracture risk has not been examined in prospective cohort settings with comprehensive fracture risk assessment, cancer-free comparison populations, and long-term follow-up. Our objective is to better characterize pelvic fracture and overall mortality risks in postmenopausal women participating in the Women's Health Initiative. Methods A total of 135 743 Women's Health Initiative participants aged 50 to 79 years enrolled from 40 US clinical centers from 1993 to 1998 who had entry Fracture Risk Assessment Tool scores were eligible. Outcomes included pelvic cancer diagnosis, pelvic fracture occurrence, and mortality. Cox proportional hazards regression models were used to examine associations of pelvic cancer and pelvic radiation with pelvic fracture and mortality risk. Results After 17.7 years (median) follow-up, 4451 pelvic cancers, 10 139 pelvic fractures, and 33 040 deaths occurred. In multivariable analyses, women with incident pelvic cancer, compared with women who remained pelvic cancer free, had higher pelvic fracture risk (hazard ratio [HR] = 1.26, 95% confidence interval [CI] = 1.11 to 1.43) and higher overall mortality risk (HR = 2.91, 95% CI = 2.77 to 3.05). Women with pelvic cancer treated with pelvic radiation, compared with women with pelvic cancer not treated with pelvic radiation, had higher pelvic fracture risk (HR = 1.98, 95% CI = 1.41 to 2.78) and higher overall mortality after pelvic cancer (HR = 1.32, 95% CI = 1.15 to 1.52). Conclusions Postmenopausal women with pelvic cancer, especially those receiving pelvic radiation, are at higher pelvic fracture risk and higher overall mortality risk. As therapeutic advances have reduced cancer mortality, attention to and interventions for pelvic fracture prevention may be important in pelvic cancer survivors. [ABSTRACT FROM AUTHOR]

Accumulating evidences demonstrate that circular RNA (circRNA) plays an important role in human diseases. Identification of circRNA-disease associations can help for the diagnosis of human diseases, while the traditional method based on biological experiments is time-consuming. In order to address the limitation, a series of computational methods have been proposed in recent years. However, few works have summarized these methods or compared the performance of them. In this paper, we divided the existing methods into three categories: information propagation, traditional machine learning and deep learning. Then, the baseline methods in each category are introduced in detail. Further, 5 different datasets are collected, and 14 representative methods of each category are selected and compared in the 5-fold, 10-fold cross-validation and the de novo experiment. In order to further evaluate the effectiveness of these methods, six common cancers are selected to compare the number of correctly identified circRNA-disease associations in the top-10, top-20, top-50, top-100 and top-200. In addition, according to the results, the observation about the robustness and the character of these methods are concluded. Finally, the future directions and challenges are discussed. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common neoplasm in the world among women. The age-specific incidences and onset ages vary widely between Asian and Western countries/regions. Invasive breast cancer cases among women from 1997 to 2011 were abstracted from the International Agency for Research on Cancer and the Taiwan Cancer Registry. Age-period-cohort analysis was performed to examine the trends. The cohort effect was prominent in South Korea, Taiwan, Japan, and Thailand, possibly related to the timing of westernization. The risk of breast cancer initially rose with the birth cohorts in Hong Kong and India (both former British colonies), peaked, and then declined in recent birth cohorts. Unlike other Asian countries/regions, virtually no birth cohort effect was identified in the Philippines (a Spanish colony in 1565 and the first Asian country to adopt Western cultural aspects). Moreover, an at-most negligible birth cohort effect was identified for all ethnic groups (including Asian immigrants) in the United States. This global study identified birth cohort effects in most Asian countries/regions but virtually no impact in Western countries/regions. The timing of westernization was associated with the birth cohort effect. [ABSTRACT FROM AUTHOR]

Background: Sodium–glucose co‐transporter 2 inhibitor (SGLT2i) treatment may exert anti‐inflammatory effects by modulating the NOD‐like receptor family pyrin domain‐containing 3 inflammasome and interleukin‐17/23 inflammatory axis, which are both involved in the pathogenesis of psoriasis. However, the relationship between SGLT2i treatment and psoriasis remains unclear. Aim: To investigate the association between SGLT2i treatment and incident psoriasis. Methods: Using the Taiwan National Health Insurance Database for the period 2007–2018, we matched 103 745 patients with Type 2 diabetes mellitus (T2DM) receiving SGLT2i with a control group of patients with T2DM who did not use SGLT2i, matching them in a 1 : 2 ratio by age, sex, diabetes duration, insulin use and comorbidities, and evaluating the psoriasis risk in both groups. Results: The incident psoriasis risk did not significantly differ between the SGLT2i and control groups [hazard ratio (HR) = 1.24, 95% CI 0.95–1.64] after adjustment for potential confounders. Insulin use (HR = 1.65, 95% CI 1.24–2.19) and chronic liver disease and cirrhosis (HR = 1.34, 95% CI 1.01–1.77) were significantly associated with increased psoriasis risk. A slightly increased psoriasis risk was also detected in certain SGLT2i user subgroups, especially those with renal disease (HR = 2.73, 95% CI 1.45–5.13). Conclusion: SGLT2i‐mediated protective effects in psoriasis could not be established. SGLT2i treatment increased psoriasis risk by 2.7‐fold in patients with T2DM exhibiting renal diseases. [ABSTRACT FROM AUTHOR]

In summary, we reported the increased incidence of AMN, a very rare retinal disease, in patients with COVID-19 after the lifting of travel restrictions in China. A total of 27 eyes of 14 patients with AMN and 56 eyes of 28 sex- and age-matched controls who recovered from COVID-19 during the same pandemic wave were recruited. Keywords: COVID-19; ocular manifestation; acute macular neuroretinopathy; retina; choroid; ocular imaging EN COVID-19 ocular manifestation acute macular neuroretinopathy retina choroid ocular imaging 1 3 3 09/13/23 20230701 NES 230701 In response to the latest status of the coronavirus disease-2019 (COVID-19) pandemic, China has adjusted public health policies and preventive strategies in a more targeted manner, notably by 10 new measures issued in December 2022. [Extracted from the article]

The evolutionary dynamics and phylogenetic utility of mitochondrial genomes (mitogenomes) have been of particular interest to systematists and evolutionary biologists. However, certain mitochondrial features, such as the molecular evolution of the control region in insects, remain poorly explored due to technological constraints. Using a combination of long- and short-read sequencing data, we assembled ten complete mitogenomes from ten Hercules beetles. We found large-sized mitogenomes (from 24 to 28 kb), which are among the largest in insects. The variation in genome size can be attributed to copy-number evolution of tandem repeats in the control region. Furthermore, one type of tandem repeat was found flanking the conserved sequence block in the control region. Importantly, such variation, which made up around 30% of the size of the mitogenome, may only become detectable should long-read sequencing technology be applied. We also found that, although different mitochondrial loci often inferred different phylogenetic histories, none of the mitochondrial loci statistically reject a concatenated mitochondrial phylogeny, supporting the hypothesis that all mitochondrial loci share a single genealogical history. We on the other hand reported statistical support for mito-nuclear phylogenetic discordance in 50% of mitochondrial loci. We argue that long-read DNA sequencing should become a standard application in the rapidly growing field of mitogenome sequencing. Furthermore, mitochondrial gene trees may differ even though they share a common genealogical history, and ND loci could be better candidates for phylogenetics than the commonly used COX1. [ABSTRACT FROM AUTHOR]

Crop multi-model ensembles (MME) have proven to be effective in increasing the accuracy of simulations in modelling experiments. However, the ability of MME to capture crop responses to changes in sowing dates and densities has not yet been investigated. These management interventions are some of the main levers for adapting cropping systems to climate change. Here, we explore the performance of a MME of 29 wheat crop models to predict the effect of changing sowing dates and rates on yield and yield components, on two sites located in a high-yielding environment in New Zealand. The experiment was conducted for 6 years and provided 50 combinations of sowing date, sowing density and growing season. We show that the MME simulates seasonal growth of wheat well under standard sowing conditions, but fails under early sowing and high sowing rates. The comparison between observed and simulated in-season fraction of intercepted photosynthetically active radiation (FIPAR) for early sown wheat shows that the MME does not capture the decrease of crop above ground biomass during winter months due to senescence. Models need to better account for tiller competition for light, nutrients, and water during vegetative growth, and early tiller senescence and tiller mortality, which are exacerbated by early sowing, high sowing densities, and warmer winter temperatures. [ABSTRACT FROM AUTHOR]

The prognosis of acute lymphoblastic leukemia (ALL) in adults is inferior to that in children. Hence, ALL remains challenging to cure in the adult population. Aberrant genetic alterations have been observed in ALL, although the patterns of differential gene alterations in adult and pediatric ALL have not been comprehensively determined on a genome‐wide scale. We investigated the biologic differences in genomic profiles between adults (n = 64) and children (n = 54) with ALL and relationship between genomic heterogeneity and prognosis. The 2 populations showed similar common mutation types but an increased prevalence of genetic alterations in adult ALL. The median numbers of gene mutations were 17 (range: 1–53) and 4.5 (range: 1–19) per sample in adult and pediatric ALL, respectively (p < 0.001). An increased number of gene mutations and age were significantly correlated (R2 = 0.5853, p < 0.001). We identified 122 and 53 driver genes in adult and pediatric ALL samples, respectively. IKZF1, IDH1, and TTN mutations were significantly enriched in adult patients with ALL. KRAS, ARID1A, and CREBBP mutations were significantly enriched in pediatric patients with ALL (p < 0.05). The incidence of relapse was 40.0% and 9.6% in adult and pediatric patients with ALL, respectively (p = 0.003). The overall survival and relapse‐free survival of adult patients with ALL were poorer than those of pediatric patients with ALL (p = 0.002 and p < 0.001, respectively). This genomic landscape enhances the understanding of the biologic differences in ALL between the 2 populations and provides insight for developing therapeutic approaches. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic cell transplantation (HCT) and is associated with significant morbidity and mortality. For many years, there have been few effective treatment options for patients with GVHD. First-line systemic treatment remains corticosteroids, but up to 50% of patients will develop steroid-refractory GVHD and the prognosis for these patients is poor. Elucidation of the pathophysiological mechanisms of acute and chronic GVHD has laid a foundation for novel therapeutic approaches. Since 2017, there have now been 4 approvals by the US Food and Drug Administration (FDA) for GVHD. Ruxolitinib, an oral selective JAK1/2 inhibitor, received FDA approval for the treatment of steroid-refractory acute GVHD in 2019 and remains the only agent approved for acute GVHD. There are currently 3 FDA approvals for the treatment of chronic GVHD: (1) ibrutinib, a BTK inhibitor traditionally used for B-cell malignancies, was the first agent approved for chronic GVHD after failure of one or more lines of systemic therapy, (2) belumosudil, an oral selective inhibitor of ROCK2, for patients with chronic GVHD who received at least 2 prior lines of treatment, and (3) ruxolitinib for chronic GVHD after failure of one or two lines of systemic therapy. In this review, we highlight the clinical data which support these FDA approvals in acute and chronic GVHD with a focus on mechanism of actions, clinical efficacy, and toxicities associated with these agents. [ABSTRACT FROM AUTHOR]

Aims: Ventricular arrhythmia (VA) frequently occurs in fatty infiltrative cardiomyopathy or epicardial adipose tissue (EAT) abundant hearts. Right ventricular outflow tract (RVOT), commonly covered with EAT, is vital for VA genesis. This study explored whether EAT contributes to RVOT arrhythmogenesis.Methods and Results: Conventional microelectrodes and whole-cell patch clamp were used to record electrical activity and ionic currents in rabbit RVOT tissue preparation or isolated single cardiomyocytes with or without (control) connected EAT. Epicardial adipose tissue-connected (N = 6) RVOT had more portions of fibrosis than did control (N = 5) RVOT (160.3 ± 23.2 vs. 91.9 ± 13.4 μm2/mm2, P < 0.05). Epicardial adipose tissue-connected RVOT cardiomyocytes (n = 18) had lower negative resting membrane potential (-68 ± 1 vs. -73 ± 2 mV, P < 0.05); smaller action potential (AP) amplitude (108 ± 4 vs. 135 ± 6 mV, P < 0.005); and longer 90%, 50%, and 20% of AP duration repolarization (361 ± 18 vs. 309 ± 9 ms, P < 0.05; 310 ± 17 vs. 256 ± 13 ms, P < 0.05; and 182 ± 19 vs. 114 ± 24 ms, P < 0.05, respectively) than did control (n = 13) RVOT cardiomyocytes. Moreover, compared with control RVOT cardiomyocytes, EAT-connected RVOT cardiomyocytes had larger transient outward potassium currents, similar delayed rectifier potassium currents, smaller L-type calcium currents, and inward rectifier potassium currents. After ajmaline (10 μM, a sodium channel blocker) superfusion, high VA inducibility was observed through rapid pacing in EAT-connected RVOT but not in control RVOT.Conclusions: Epicardial adipose tissue exerts distinctive electrophysiological effects on RVOT with a propensity towards VA induction, which might play a role in lipotoxicity pathogenesis-related ventricular arrhythmogenesis. [ABSTRACT FROM AUTHOR]

A study published in the American Journal of Hypertension explores the relationship between blood pressure variability and left ventricular diastolic dysfunction. The study found that long-term systolic blood pressure variability is associated with cardiovascular disease through an increase in arterial stiffness, independent of average blood pressure levels. The researchers also discovered a significant association between blood pressure variability and left ventricular diastolic function. However, the study's cross-sectional design and exclusion of certain factors in diastolic function evaluation warrant further investigation. The study was funded by various organizations and the authors declare no conflicts of interest. [Extracted from the article]

Objectives Despite of strenuous research in the past decades, the etiology of schizophrenia (SCZ) still remains incredibly controversial. Previous genetic analysis has uncovered a close association of Unc-51 like kinase 4 (ULK4), a family member of Unc-51-like serine/threonine kinase, with SCZ. However, animal behavior data which may connect Ulk4 deficiency with psychiatric disorders, particularly SCZ are still missing. Methods We generated Emx1-Cre:Ulk4flox/flox conditional knockout (CKO) mice, in which Ulk4 was deleted in the excitatory neurons of cerebral cortex and hippocampus. Results The cerebral cellular architecture was maintained but the spine density of pyramidal neurons was reduced in Ulk4 CKO mice. CKO mice showed deficits in the spatial and working memories and sensorimotor gating. Levels of p-Akt and p-GSK-3α/β were markedly reduced in the CKO mice indicating an elevation of GSK-3 signaling. Mechanistically, Ulk4 may regulate the GSK-3 signaling via putative protein complex comprising of two phosphatases, protein phosphatase 2A (PP2A) and 1α (PP1α). Indeed, the reduction of p-Akt and p-GSK-3α/β was rescued by administration of inhibitor acting on PP2A and PP1α in CKO mice. Conclusions Our data identified potential downstream signaling pathway of Ulk4, which plays important roles in the cognitive functions and when defective, may promote SCZ-like pathogenesis and behavioral phenotypes in mice. [ABSTRACT FROM AUTHOR]

Background Bipolar disorder (BD) is associated with cognitive impairment and mitochondrial dysfunction. However, the associations among mitochondrial DNA copy number (MCN), treatment response, and cognitive function remain elusive in BD patients. Methods Sixty euthymic BD patients receiving valproate (VPA) and 66 healthy controls from the community were recruited. The indices of metabolic syndrome (MetS) were measured. Quantitative polymerase chain reaction analysis of blood leukocytes was used to measure the MCN. Cognitive function was measured by calculating perseverative errors and completed categories on the Wisconsin Card Sorting Test (WCST). The VPA treatment response was measured using the Alda scale. Results BD patients had significantly higher MCN, triglyceride, and C-reactive protein (CRP) levels, waist circumference, and worse performance on the WCST than the controls. Regression models showed that BD itself and the VPA concentration exerted significant effects on increased MCN levels. Moreover, the receiver operating characteristic curve analysis showed that an MCN of 2.05 distinguished VPA responders from nonresponders, with an area under the curve of 0.705 and a sensitivity and specificity of 0.529 and 0.816, respectively. An MCN level ≥2.05 was associated with 5.39 higher odds of being a VPA responder (P  = .006). BD patients who were stratified into the high-MCN group had a higher VPA response rate, better WCST performance, lower CRP level, and less MetS. Conclusions The study suggests a link between the peripheral MCN and cognitive function in BD patients. As an inflammatory status, MetS might modulate this association. [ABSTRACT FROM AUTHOR]

Alkalic basalts from continental regions have been widely used to fingerprint chemically and lithologically distinct components in the mantle. However, superimposed on mantle source effects are the effects of intra-crustal magma differentiation, which may be underestimated when exclusively considering fractional crystallization (FC) in melt-rich magma chambers. Here we present extensive mineralogical and geochemical data for mafic cumulates and dolerite dikes from central Tibet to demonstrate that tholeiitic magma differentiation occurred in crystal-rich mushes and melt-filled fractures. The mafic cumulates provide a snapshot of the percolation of water-poor (<0.9 wt% H2O), oxide-undersaturated, tholeiitic melts through slightly hotter mushes (50–60% crystals) with a framework of primitive olivine ± plagioclase crystals. The highly corroded olivines indicate that thermo-chemical disequilibrium between the later percolating melts and pre-existing crystal framework triggered melt–mush reactions in an open system. High-temperature (>1060°C) reactions were accompanied by a decreasing melt mass, causing the initial tholeiitic melts to evolve into alkalic mafic melts during slow cooling. This process involved the dissolution and reprecipitation of olivine, plagioclase, and clinopyroxene as well as the late crystallization of high-TiO2 (up to 3.4 wt%) clinopyroxene and kaersutite. In contrast, the same tholeiitic magmas (i.e. dolerite dikes) that intruded the cold country rocks along fractures produced silica-rich residual melts saturated in Fe–Ti oxides and sodic plagioclase by FC during rapid cooling. The residual melt was always in equilibrium with the instantaneous crystal during closed-system FC, so there was no reaction between the interstitial melt and adjacent crystal even after a high degree of crystallization. Alkalic mafic melts that can be formed by melt–mush reactions exhibit strong enrichment of incompatible element contents (e.g. Ti and alkali and rare earth elements) and ratios (e.g. Ce/Y), but little Si enrichment and Mg depletion, compared with the parental tholeiitic magma, which cannot be reproduced by simple FC. We argue that tholeiitic melt–mush reactions at mid- to lower-crustal pressures (≥0.5 GPa) are a new mechanism for the generation of interstitial alkalic mafic melts in continental mush reservoirs. Continental alkalic basalts could be produced by this mechanism if such interstitial melts were concentrated into melt lenses by compaction and then transported rapidly upward to the surface by focused flow. [ABSTRACT FROM AUTHOR]

Objectives: There is an urgent need for novel drugs that target unique cellular pathways to combat infections caused by Mycobacterium tuberculosis. CRISPR interference (CRISPRi)-mediated transcriptional repression has recently been developed for use in mycobacteria as a genetic tool for identifying and validating essential genes as novel drug targets. Whilst CRISPRi has been applied to extracellular bacteria, no studies to date have determined whether CRISPRi can be used in M. tuberculosis infection models.Methods: Using the human monocytic macrophage-like THP-1 cell line as a model for M. tuberculosis infection we investigated if CRISPRi can be activated within intracellular M. tuberculosis.Results: The transcriptional repression of two candidate M. tuberculosis genes, i.e. mmpL3 and qcrB, leads to a reduction in viable M. tuberculosis within infected THP-1 cells. The reduction in viable colonies is dependent on both the level of CRISPRi-mediated repression and the duration of repression.Conclusions: These results highlight the utility of CRISPRi in exploring mycobacterial gene function and essentiality under a variety of conditions pertinent to host infection. [ABSTRACT FROM AUTHOR]

Aims The secreted and membrane-anchored signal peptide-CUB-EGF domain-containing proteins (SCUBE) gene family composed of three members was originally identified from endothelial cells (ECs). We recently showed that membrane SCUBE2 binds vascular endothelial growth factor (VEGF) and acts as a co-receptor for VEGF receptor 2 to modulate EC migration, proliferation, and tube formation during postnatal and tumour angiogenesis. However, whether these SCUBE genes cooperate in modulating VEGF signalling during embryonic vascular development remains unknown. Methods and results To further dissect the genetic interactions of these scube genes, transcription activator-like effector nuclease-mediated genome editing was used to generate knockout (KO) alleles of each scube gene. No overt vascular phenotypes were seen in any single scube KO mutants because of compensation by other scube genes during zebrafish development. However, scube1 and scube2 double KO (DKO) severely impaired EC filopodia extensions, migration, and proliferation, thus disrupting proper vascular lumen formation during vasculogenesis and angiogenesis as well as development of the organ-specific intestinal vasculature. Further genetic, biochemical, and molecular analyses revealed that Scube1 and Scube2 might act cooperatively at the cell-surface receptor level to facilitate Vegfa signalling during zebrafish embryonic vascularization. Conclusions We showed for the first time that cooperation between scube1 and scube2 is critical for proper regulation of angiogenic cell behaviours and formation of functional vessels during zebrafish embryonic development. [ABSTRACT FROM AUTHOR]

The authors comment on the study "Association Between Clostridium innocuum and Antibiotic-Associated Diarrhea in Adults and Children: A Cross-Sectional Study and Comparative Genomics Analysis," by K. E. Cherny, E. B. Muscat and A. Balaji which appeared in the 2022 issue. Topics covered include the issue with the colonization rate in gastrointestinal tract of healthy populations, the carriage rate of Clostridium innocuum in children and adults and the pathogenicity of Clostridium innocuum.

Motivation Transcriptomics is a common approach to identify changes in gene expression induced by a disease state. Standard transcriptomic analyses consider differentially expressed genes (DEGs) as indicative of disease states so only a few genes would be treated as signals when the effect size is small, such as in brain tissue. For tissue with small effect sizes, if the DEGs do not belong to a pathway known to be involved in the disease, there would be little left in the transcriptome for researchers to follow up with. Results We developed RNA Solutions: Synthesizing Information to Support Transcriptomics (RNASSIST), a new approach to identify hidden signals in transcriptomic data by linking differential expression and co-expression networks using machine learning. We applied our approach to RNA-seq data of post-mortem brains that compared the Alcohol Use Disorder (AUD) group with the control group. Many of the candidate genes are not differentially expressed so would likely be ignored by standard transcriptomic analysis pipelines. Through multiple validation strategies, we concluded that these RNASSIST-identified genes likely play a significant role in AUD. Availability and implementation The RNASSIST algorithm is available at https://github.com/netrias/rnassist and both the software and the data used in RNASSIST are available at https://figshare.com/articles/software/RNAssist%5fSoftware%5fand%5fData/16617250. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Bacterial membrane vesicles (MVs) have been reported to kill other bacteria. In the case of Pseudomonas aeruginosa the bactericidal activity has been attributed to an unidentified 26 kDa peptidoglycan (PG) hydrolase that is associated with MVs and gives rise to a lytic band on zymograms using murein sacculi as substrate. In this study, we employed a proteomics approach to show that this PG hydrolase is the AmphD3 amidase. The analysis of an amphD3 mutant as well as of an AmphD3 overexpression derivative revealed that this enzyme is not required for the bactericidal activity of P. aeruginosa MVs but is involved in cell wall recycling and thus protects the cell against PG damage. Another 23 kDa PG hydrolase, which we observed on zymograms of SOS-induced MVs, was identified as the endolysin Lys, which triggers explosive cell lysis but is shown to be dispensable for MV-mediated killing. We conclude that the lytic activities observed on zymograms do not correlate with the bactericidal potential of MVs. We demonstrate that P. aeruginosa MVs are enriched for several autolysins, suggesting that the predatory activity of MVs depends on the combined action of different murein hydrolases. Peptidoglycan hydrolytic activities on zymograms do not correlate with the bacteriocidal potential of membrane vesicles. [ABSTRACT FROM AUTHOR]

Sequencing technologies, in particular RNASeq, have become critical tools in the design, build, test and learn cycle of synthetic biology. They provide a better understanding of synthetic designs, and they help identify ways to improve and select designs. While these data are beneficial to design, their collection and analysis is a complex, multistep process that has implications on both discovery and reproducibility of experiments. Additionally, tool parameters, experimental metadata, normalization of data and standardization of file formats present challenges that are computationally intensive. This calls for high-throughput pipelines expressly designed to handle the combinatorial and longitudinal nature of synthetic biology. In this paper, we present a pipeline to maximize the analytical reproducibility of RNASeq for synthetic biologists. We also explore the impact of reproducibility on the validation of machine learning models. We present the design of a pipeline that combines traditional RNASeq data processing tools with structured metadata tracking to allow for the exploration of the combinatorial design in a high-throughput and reproducible manner. We then demonstrate utility via two different experiments: a control comparison experiment and a machine learning model experiment. The first experiment compares datasets collected from identical biological controls across multiple days for two different organisms. It shows that a reproducible experimental protocol for one organism does not guarantee reproducibility in another. The second experiment quantifies the differences in experimental runs from multiple perspectives. It shows that the lack of reproducibility from these different perspectives can place an upper bound on the validation of machine learning models trained on RNASeq data. Graphical Abstract [ABSTRACT FROM AUTHOR]

The tobacco thrips, Frankliniella fusca Hinds, is a phytophagous pest and vector of orthotospoviruses in many crops around the world. F. fusca causes direct feeding injury to peanut plants, resulting in leaf chlorosis and curling, and yield loss. Adults and larvae also transmit the economically important tomato spotted wilt orthotospovirus (TSWV) in all peanut market types grown in the U.S. TSWV infection causes spotted wilt disease, a plant disease characterized by chlorosis, stunting, and death. From 1996 to 2006, spotted wilt disease resulted in an estimated U.S.$140 million in annual peanut production losses in the U.S. At present, a thorough documentation of F. fusca 's impacts on the U.S. peanut production system is not available. Here, we describe the morphology, life cycle, and biology of F. fusca and provide images of immature life stages. Feeding injury characteristics and TSWV transmission in peanuts are also discussed. Currently, F. fusca and TSWV are managed in peanut with a combination of tactics, including prophylactic insecticide applications and TSWV-resistant cultivars. However, standardized scouting protocols and economic thresholds for F. fusca are not yet available. Very few biological control agents have been evaluated for use against F. fusca , and few studies have quantified the contributions of native natural enemies. More research into natural enemies' contributions to F. fusca management and the mechanisms underlying TSWV-resistance in peanut could help inform and diversify integrated pest management programs. [ABSTRACT FROM AUTHOR]

Background: Integrase strand transfer inhibitor (InSTI)-based regimens have become the major first-line treatment for HIV-1-infected patients in Taiwan. Transmitted drug resistance (TDR) and several clinical characteristics are associated with time to virological failure or viral suppression; however, these have not been investigated in Taiwan.Objectives: To determine the impact of several factors on treatment outcomes in HIV-1-infected patients in Taiwan.Methods: The cohort included 164 HIV-1 treatment-naive patients in Taiwan from 2018 to 2020. Blood specimens were collected to determine the genotypic drug resistance using the Stanford University HIV drug resistance database. Cox proportional hazards models were used to identify factors associated with time to virological failure or viral suppression.Results: The prevalence of TDR in Taiwan was 27.4% and an increasing trend was seen from 2018 to 2020. TDR mutations related to NNRTIs were the most prevalent (21%) while TDR to InSTIs remained at a relatively low level (1.3%). A baseline HIV-1 viral load of ≥100 000 copies/mL was associated with a shorter time to virological failure [multivariate hazard ratio (mHR) 7.84; P = 0.018] and longer time to viral suppression (mHR 0.46; P < 0.001). Time to viral suppression was shorter in patients receiving InSTI-based regimens (mHR 2.18; P = 0.006). Different InSTI-based regimens as initial treatment did not affect the treatment outcomes.Conclusions: This study found an increasing trend of HIV-1 TDR prevalence from 2018 to 2020 in Taiwan. Baseline HIV-1 viral load and receiving InSTI-based regimens are important factors associated with time to virological failure or viral suppression. [ABSTRACT FROM AUTHOR]

In this research, we explored various state-of-the-art biomedical-specific pre-trained Bidirectional Encoder Representations from Transformers (BERT) models for the National Library of Medicine - Chemistry (NLM CHEM) and LitCovid tracks in the BioCreative VII Challenge, and propose a BERT-based ensemble learning approach to integrate the advantages of various models to improve the system's performance. The experimental results of the NLM-CHEM track demonstrate that our method can achieve remarkable performance, with F1-scores of 85% and 91.8% in strict and approximate evaluations, respectively. Moreover, the proposed Medical Subject Headings identifier (MeSH ID) normalization algorithm is effective in entity normalization, which achieved a F1-score of about 80% in both strict and approximate evaluations. For the LitCovid track, the proposed method is also effective in detecting topics in the Coronavirus disease 2019 (COVID-19) literature, which outperformed the compared methods and achieve state-of-the-art performance in the LitCovid corpus. Database URL : https://www.ncbi.nlm.nih.gov/research/coronavirus/. [ABSTRACT FROM AUTHOR]

Increasing evidences have proved that circRNA plays a significant role in the development of many diseases. In addition, many researches have shown that circRNA can be considered as the potential biomarker for clinical diagnosis and treatment of disease. Some computational methods have been proposed to predict circRNA-disease associations. However, the performance of these methods is limited as the sparsity of low-order interaction information. In this paper, we propose a new computational method (KGANCDA) to predict circRNA-disease associations based on knowledge graph attention network. The circRNA-disease knowledge graphs are constructed by collecting multiple relationship data among circRNA, disease, miRNA and lncRNA. Then, the knowledge graph attention network is designed to obtain embeddings of each entity by distinguishing the importance of information from neighbors. Besides the low-order neighbor information, it can also capture high-order neighbor information from multisource associations, which alleviates the problem of data sparsity. Finally, the multilayer perceptron is applied to predict the affinity score of circRNA-disease associations based on the embeddings of circRNA and disease. The experiment results show that KGANCDA outperforms than other state-of-the-art methods in 5-fold cross validation. Furthermore, the case study demonstrates that KGANCDA is an effective tool to predict potential circRNA-disease associations. [ABSTRACT FROM AUTHOR]

Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation. The circadian rhythm controls cell proliferation and energy metabolism. However, the role of circadian genes in inflammatory bowel disease is largely unknown. The purpose of this study was to investigate whether disrupting the circadian rhythm in mice can worsen colitis by altering mitochondrial energy metabolism. Mice in the experimental groups were under physiologic stress with an 8-h light shift jet-lag schedule every 3 days, whereas those in the control group were not. Subsequently, half of the mice in the control and jet-lagged groups were given dextran sodium sulfate (DSS) to induce colitis. Mice in each group were euthanized at zeitgeber time (ZT)0, ZT4, ZT8, ZT12, ZT16, and ZT20. To investigate the effects of jet lag on the mice, colon specimens were subjected to hematoxylin and eosin staining to analyse mRNA and protein expression of core circadian clock genes (Bmal1 , Clock , Per1 , Per2 , Cry1 , Cry2 , and Nr1d1). We analysed the mitochondrial morphology, adenosine triphosphate (ATP) levels, and the expression of dynamin-related protein 1 (Drp1) and ser637-phosphorylated (p)-Drp1, which are closely related to ATP production. We further investigated the effect of PER2 knock-down in the colon epithelial cells (CCD 841 CoN) by measuring ATP and cell proliferation levels. Disrupting the circadian rhythm changed the oscillation of clock genes in the colon of mice, altered the mitochondrial morphology of the colon specimens, decreased the expression of p-Drp1, reduced ATP production, and exacerbated inflammatory responses in mice with DSS-induced colitis. Additionally, silencing of PER2 in the colon epithelial cells reduced ATP production and cell proliferation. Disrupting the circadian rhythm in mice decreases mitochondrial energy metabolism in the colon and exacerbates symptoms of colitis. [ABSTRACT FROM AUTHOR]

In higher plants, whole-genome duplication (WGD) is thought to facilitate the evolution of C4 photosynthesis from C3 photosynthesis. To understand this issue, we used new and existing leaf-development transcriptomes to construct two coding sequence databases for C4 Gynandropsis gynandra and C3 Tarenaya hassleriana , which shared a WGD before their divergence. We compared duplicated genes in the two species and found that the WGD contributed to four aspects of the evolution of C4 photosynthesis in G. gynandra. First, G. gynandra has retained the duplicates of ALAAT (alanine aminotransferase) and GOGAT (glutamine oxoglutarate aminotransferase) for nitrogen recycling to establish a photorespiratory CO2 pump in bundle sheath (BS) cells for increasing photosynthesis efficiency, suggesting that G. gynandra experienced a C3–C4 intermediate stage during the C4 evolution. Second, G. gynandra has retained almost all known vein-development-related paralogous genes derived from the WGD event, likely contributing to the high vein complexity of G. gynandra. Third, the WGD facilitated the evolution of C4 enzyme genes and their recruitment into the C4 pathway. Fourth, several genes encoding photosystem I proteins were derived from the WGD and are upregulated in G. gynandra , likely enabling the NADH dehydrogenase-like complex to produce extra ATPs for the C4 CO2 concentration mechanism. Thus, the WGD apparently played an enabler role in the evolution of C4 photosynthesis in G. gynandra. Importantly, an ALAAT duplicate became highly expressed in BS cells in G. gynandra , facilitating nitrogen recycling and transition to the C4 cycle. This study revealed how WDG may facilitate C4 photosynthesis evolution. [ABSTRACT FROM AUTHOR]

Objective The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort. Methods Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count <0.8 × 109/l) and neutropenia (neutrophil count <1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses. Results Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia. Conclusion Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE. [ABSTRACT FROM AUTHOR]

Background: The genomic and transcriptomic landscape of widely invasive follicular thyroid carcinomas (wiFTCs) and Hürthle cell carcinoma (HCC) are poorly characterized, and subsets of these tumors lack information on genetic driver events.Objective: The aim of this study was to bridge this gap.Methods: We performed whole-genome and RNA sequencing and subsequent bioinformatic analyses of 11 wiFTCs and 2 HCCs with a particularly poor prognosis, and matched normal tissue.Results: All wiFTCs exhibited one or several mutations in established thyroid cancer genes, including TERT (n = 4), NRAS (n = 3), HRAS, KRAS, AKT, PTEN, PIK3CA, MUTYH, TSHR, and MEN1 (n = 1 each). MutSig2CV analysis revealed recurrent somatic mutations in FAM72D (n = 3, in 2 wiFTCs and in a single HCC), TP53 (n = 3, in 2 wiFTCs and a single HCC), and EIF1AX (n = 3), with DGCR8 (n = 2) as borderline significant. The DGCR8 mutations were recurrent p.E518K missense alterations, known to cause familial multinodular goiter via disruption of microRNA (miRNA) processing. Expression analyses showed reduced DGCR8 messenger RNA expression in FTCs in general, and the 2 DGCR8 mutants displayed a distinct miRNA profile compared to DGCR8 wild-types. Copy number analyses revealed recurrent gains on chromosomes 4, 6, and 10, and fusion gene analyses revealed 27 high-quality events. Both HCCs displayed hyperploidy, which was fairly unusual in the FTC cohort. Based on the transcriptome data, tumors amassed in 2 principal clusters.Conclusion: We describe the genomic and transcriptomic landscape in wiFTCs and HCCs and identify novel recurrent mutations and copy number alterations with possible driver properties and lay the foundation for future studies. [ABSTRACT FROM AUTHOR]

Aims: Inflammation plays a role in the pathogenesis of atrial fibrillation (AF). Pericarditis enhanced atrial arrhythmogenesis, but the role of the pericardium remains unclear in AF. Activation of the toll-like receptor 4 (TLR4) by binding to lipopolysaccharide (LPS) promotes cardiac electrical remodelling. In this study, we hypothesized that pericarditis may induce atrial arrhythmogenesis via pericardium-myocardium interactions by TLR4 signalling.Methods and Results: Pericarditis was induced in rabbits by injecting LPS (1-2 mg/kg) into the pericardium. Conventional microelectrodes were used to record the action potentials of left atrial (LA) posterior walls (LAPWs) and LA appendages (LAAs) with and without attached pericardium in the control or pericarditis-induced rabbits. Cytokine array was used to measure the expression levels of proinflammatory cytokines in control and LPS-treated pericardium. Compared with the controls, the LPS-treated pericardium had higher expressions of IL-1α, IL-8, and MIP-1β. Rapid atrial pacing-induced burst firing in LPS-treated LAPWs and LAAs, and in control LAPWs (but not in LAAs). The incidence of pacing-induced spontaneous activity and burst firing was increased by LPS-treated pericardium but was attenuated by the control pericardium. Moreover, burst firing induced by LPS-treated pericardium was blocked upon administration of the TLR4 inhibitor, TAK-242 (100 ng/mL), ryanodine receptor inhibitor (ryanodine, 3 μM), or calmodulin kinase II inhibitor (KN-93, 1 μM).Conclusions: Healthy and inflamed pericardium differently modulate LPS-induced atrial arrhythmogenesis. Targeting pericardium via TLR4 signalling may be a novel therapeutic strategy for AF. [ABSTRACT FROM AUTHOR]

Reconstructed whole-rock (RWR) and mineral major- and trace-element compositions, as well as new oxygen isotope data, for 22 mantle eclogite xenoliths from the Catoca pipe (Kasai Craton) were used to constrain their genesis and evolution. On the basis of mineralogical and major-element compositions, the Catoca eclogites can be divided into three groups: high-alumina (high-Al) (kyanite-bearing), low-magnesian (low-Mg#), and high-magnesian (high-Mg#) eclogites. The high-Al Catoca eclogites contain kyanite and corundum; high Al2O3 contents in rock-forming minerals; rare earth element (REE) patterns in garnets showing depleted LREEs, positive Eu anomalies (1.03–1.66), and near-flat HREEs; and high Sr contents in garnets and whole-rock REE compositions. All of these features point to a plagioclase-rich protolith (probably gabbro). RWR compositions (major elements, MREEs, HREEs, Li, V, Hf, Y, Zr, and Pb) and δ18O of 5.5–7.4‰ of the low-Mg# Catoca eclogites are in good agreement with the compositions of picrite basalts and average mid-ocean ridge basalt (MORB). The depleted LREEs and NMORB-normalised Nd/Yb values of 0.07–0.41 indicate that the degree of partial melting for the majority of the low-Mg# eclogites protolith was ≥30%. The narrow δ18O range of 5.5–7.4‰ near the 'gabbro–basalt' boundary (6‰) obtained for the high-Al and low-Mg# Catoca eclogites reflects the influence of subduction-related processes. This case shows that mantle eclogites represented by two different lithologies and originating from different protoliths—plagioclase-rich precursor, presumably gabbro (for high-Al eclogites), and basalt (low-Mg# eclogites)—can provide similar and overlapping δ18O signatures on account of the influence of subduction-related processes. Chemical compositions of the high-Mg# eclogites indicate a complicated petrogenesis, and textural signatures reveal recrystallisation. The presence of Nb-rich rutile (8–12 wt% of Nb2O5) enriched with high field strength elements (HFSE) (Zr/Hf of 72.6–75.6) and multiple trace-element signatures (including RWR, NMORB-normalised Ce/Yb of 3.9–10.6 and Sr/Y of 5.8–9.6, MgO contents of 15.7–17.9 wt%, and high Ba and Sr) provide strong evidence for deep metasomatic alteration. High Cr contents in clinopyroxene (800–3740 ppm), garnet (430–1400 ppm), and accessory rutile (700–2530 ppm), together with extremely low Li contents of 1.0–2.4 ppm in clinopyroxene, may indicate hybridisation of the eclogites with peridotite. Comparison of the chemical compositions (major and trace elements) of (1) unaltered fresh cores of coarse-grained garnets from the low-Mg# eclogites, (2) secondary garnet rims (ubiquitous in the low-Mg# eclogites), (3) proto-cores in the coarse-grained garnet (high-Mg# eclogites), and (4) homogeneous recrystallised fine-grained garnets (high-Mg# eclogites) suggests that the high-Mg# eclogites formed through recrystallisation of low-Mg# eclogite in the presence of an external fluid in the mantle. Four of the five high-Mg# samples show that mantle metasomatism inside the Kasai craton mantle beneath the Catoca pipe occurred at a depth range of 145–160 km (4.5–4.8 GPa). [ABSTRACT FROM AUTHOR]

Ruxolitinib, a selective inhibitor of Janus kinases 1 and 2, is increasingly being used in allogeneic hematopoietic cell transplantation (HCT) recipients following its approval by the U.S. Food and Drug Administration for the treatment of steroid‐refractory acute graft‐versus‐host disease. Although there is extensive experience using ruxolitinib for patients with myeloproliferative neoplasms, the biologic effects and clinical implications of its dosing, tapering, and discontinuation for allogeneic HCT recipients are incompletely characterized. We describe three allogeneic HCT recipients who developed acute hypoxemic respiratory failure within 3 months of ruxolitinib discontinuation. Radiographic findings included marked bilateral ground‐glass opacities. Systemic corticosteroids and reinitiation of ruxolitinib resulted in rapid clinical improvement in all three patients. All three patients achieved a significant clinical response, with decrease in oxygen requirement and improvement in radiographic changes. Given the increasing use of ruxolitinib in allogeneic HCT recipients, there is significant impetus to characterize the biologic and clinical effects resulting from discontinuation of ruxolitinib, to better tailor treatment plans and prevent potential adverse effects. Considering the increasing use of ruxolitinib in allogeneic hematopoietic cell transplantation recipients, this brief communication emphasizes the ongoing need to better characterize the biologic and clinical effects resulting from the discontinuation of ruxolitinib and to better tailor treatment plans and prevent potential adverse effects. [ABSTRACT FROM AUTHOR]

This article discusses a case of disseminated amoebic infection with orbital compartment syndrome in an 81-year-old female patient. The patient presented with poor appetite, generalized weakness, and swelling and redness of the right eyelid. A physical examination revealed increased intraocular pressure and complete ophthalmoplegia, indicating orbital compartment syndrome. The patient underwent diagnostic laparoscopy and emergent lateral canthotomy, and treatment with intravenous metronidazole resulted in improvement. This case is the first reported instance of orbital compartment syndrome related to free-living amoebae infection. The article emphasizes the importance of early diagnosis and the potential use of a simple swab as a diagnostic tool for periorbital or cutaneous free-living amoebae infection. [Extracted from the article]