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Diagnosing Meckel's diverticulum in emergency conditions remains challenging, especially in adult cases for acute abdominal complaints. Here, retrospective analysis of computed tomography (CT) findings in such conditions was performed. Retrospective analysis of fifteen adults (sixteen CT scans) with a final diagnosis of Meckel's diverticulum who underwent a CT scan for acute abdominal complaints was performed. Nine patients received an intravenous (IV) contrast–enhanced CT scan; four of these were CT enteroclysis with oral contrast (mannitol). The accuracy of CT diagnosis was compared with pathological results. The overall accuracy of CT for diagnosing Meckel's diverticulum is 56.2% (9/16) in our cohort. The accuracy of non-IV contrast CT and IV contrast CT is 25% (4/16) and 77.8% (7/9). All patients undergoing oral contrast (mannitol)–enhanced CT promptly received correct diagnosis. Meckel's diverticulum localized mostly to the right quadrant, presenting with spherical/oblong morphology or blind-ended tubular aspects. Meckel's diverticulum contained liquid and gas-like substances, and sometimes enteroliths. Inflammatory infiltrates were present in 9 cases, one with concomitant appendicitis. Obstruction was observed in 6 patients. CT is valuable for identifying Meckel's diverticulum, especially in conjunction with contrast imaging and with good bowel preparation. An outpouching, blind-ended digestive structure from the distal small bowel is an alarm signal for Meckel's diverticulum. [ABSTRACT FROM AUTHOR]

A chitosan plate assay was employed to screen for chitosanase-producing bacterial strains and isolate 141 was found to exhibit high activity. Characterization of this isolate revealed that it belonged to Mitsuaria (designated as Mitsuaria sp. 141). The encoded chitosanase ( choA) gene was then cloned by PCR and the deduced amino acid sequence showed 98% identity to a formerly described Mitsuaria chitosanitabida 3001 ChoA (McChoA). Surprisingly, the ChoA encoded by Mitsuaria sp. 141 (MsChoA) appeared to have a much higher optimum temperature compared to McChoA. Site-directed mutagenesis was then employed to generate five MschoA mutant genes encoding MsChoA K204Q, R216K, T222N, R216K/T222N, or K204Q/R216K/T222N. All the ChoA mutants exhibited a much lower specific activity and a lower optimum temperature. The results confirmed that the substitution of three non-conserved amino acids accounts for the major reduction of the enzyme activity in MsChoA. Furthermore, the MschoA gene was cloned for over-expression in Pichia pastoris after coding sequence optimization. One of the P. pastoris transformants with Mut phenotype was found to produce 1,480.2 ± 340.9 U ChoA mL of cell culture by high-cell-density fermentation. This represents the highest yield of recombinant ChoA production that has ever been reported thus far. The recombinant P. pastoris strain should therefore be well suited for industrial-scale production of chitosanase. [ABSTRACT FROM AUTHOR]

Also, there were no significant differences between patients with either 2-5% or 5-20% CPCs and those with >= 20% CPCs in PFS and OS ( I P i > 0.05). Compared to patients with < 2% CPCs, median PFS and OS of patients with 2-20% CPCs were 11.2 months (vs 18.8 months, I P i = 0.0001; Fig. [Extracted from the article]

Dear Editor, Leukoencephalopathy is a term given to any disorder that affects the white matter in the CNS [[1]]. On August 19, the brain MRI revealed patchy T2/fluid-attenuated inversion recovery (FLAIR) hyperintense signal in bilateral frontal and parietal white matter, centrum semiovale, and corona radiate (Fig. Whereas daratumumab-associated AEs involving CNS are relatively rare (e.g., only one case of progressive multifocal leukoencephalopathy reported thus far in the trials involving daratumumab) [[2]], DRL has been reported in at least three cases [[3]], showing DRL as a late AE after long-term use of daratumumab (Supplemental Table S1). [Extracted from the article]

Pulmonary arterial endothelial cells (PAEC) are mechanistically linked to origins of pulmonary arterial hypertension (PAH). Here, global proteomics and phosphoproteomics of PAEC from PAH (n = 4) and healthy lungs (n = 5) were performed using LC-MS/MS to confirm known pathways and identify new areas of investigation in PAH. Among PAH and control cells, 170 proteins and 240 phosphopeptides were differentially expressed; of these, 45 proteins and 18 phosphopeptides were located in the mitochondria. Pathologic pathways were identified with integrative bioinformatics and human protein-protein interactome network analyses, then confirmed with targeted proteomics in PAH PAEC and non-targeted metabolomics and targeted high-performance liquid chromatography of metabolites in plasma from PAH patients (n = 30) and healthy controls (n = 12). Dysregulated pathways in PAH include accelerated one carbon metabolism, abnormal tricarboxylic acid (TCA) cycle flux and glutamate metabolism, dysfunctional arginine and nitric oxide pathways, and increased oxidative stress. Functional studies in cells confirmed abnormalities in glucose metabolism, mitochondrial oxygen consumption, and production of reactive oxygen species in PAH. Altogether, the findings indicate that PAH is typified by changes in metabolic pathways that are primarily found in mitochondria. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is an insidious disease characterized by severe remodeling of the pulmonary vasculature caused in part by pathologic changes of endothelial cell functions. Although heterogeneity of endothelial cells across various vascular beds is well known, the diversity among endothelial cells in the healthy pulmonary vascular bed and the pathologic diversity among pulmonary arterial endothelial cells (PAEC) in PAH is unknown and previously unexplored. Here single-cell RNA sequencing technology was used to decipher the cellular heterogeneity among PAEC in the human pulmonary arteries isolated from explanted lungs from three patients with PAH undergoing lung transplantation and three healthy donor lungs not utilized for transplantation. Datasets of 36,368 PAH individual endothelial cells and 36,086 healthy cells were analyzed using the SeqGeq bioinformatics program. Total population differential gene expression analyses identified 629 differentially expressed genes between PAH and controls. Gene Ontology and Canonical Ingenuity analysis revealed pathways that are known to be involved in pathogenesis, as well as unique new pathways. At the individual cell level, dimensionality reduction followed by density based clustering revealed the presence of eight unique PAEC clusters that were typified by proliferative, angiogenic or quiescent phenotypes. While control and PAH harbored many similar subgroups of endothelial cells, PAH had greater proportions of angiogenic and proliferative subsets. These findings identify that only specific subgroups of PAH PAEC have gene expression different than healthy PAEC, and suggest these subpopulations lead to the pathologic functions leading to remodeling. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is an insidious disease characterized by severe remodeling of the pulmonary vasculature caused in part by pathologic changes of endothelial cell functions. Although heterogeneity of endothelial cells across various vascular beds is well known, the diversity among endothelial cells in the healthy pulmonary vascular bed and the pathologic diversity among pulmonary arterial endothelial cells (PAEC) in PAH is unknown and previously unexplored. Here single-cell RNA sequencing technology was used to decipher the cellular heterogeneity among PAEC in the human pulmonary arteries isolated from explanted lungs from three patients with PAH undergoing lung transplantation and three healthy donor lungs not utilized for transplantation. Datasets of 36,368 PAH individual endothelial cells and 36,086 healthy cells were analyzed using the SeqGeq bioinformatics program. Total population differential gene expression analyses identified 629 differentially expressed genes between PAH and controls. Gene Ontology and Canonical Ingenuity analysis revealed pathways that are known to be involved in pathogenesis, as well as unique new pathways. At the individual cell level, dimensionality reduction followed by density based clustering revealed the presence of eight unique PAEC clusters that were typified by proliferative, angiogenic or quiescent phenotypes. While control and PAH harbored many similar subgroups of endothelial cells, PAH had greater proportions of angiogenic and proliferative subsets. These findings identify that only specific subgroups of PAH PAEC have gene expression different than healthy PAEC, and suggest these subpopulations lead to the pathologic functions leading to remodeling. [ABSTRACT FROM AUTHOR]

The sex discordance in COVID-19 outcomes has been widely recognized, with males generally faring worse than females and a potential link to sex steroids. A plausible mechanism is androgen-induced expression of TMPRSS2 and/or ACE2 in pulmonary tissues that may increase susceptibility or severity in males. This hypothesis is the subject of several clinical trials of anti-androgen therapies around the world. Here, we investigated the sex-associated TMPRSS2 and ACE2 expression in human and mouse lungs and interrogated the possibility of pharmacologic modification of their expression with anti-androgens. We found no evidence for increased TMPRSS2 expression in the lungs of males compared to females in humans or mice. Furthermore, in male mice, treatment with the androgen receptor antagonist enzalutamide did not decrease pulmonary TMPRSS2. On the other hand, ACE2 and AR expression was sexually dimorphic and higher in males than females. ACE2 was moderately suppressible with enzalutamide administration. Our work suggests that sex differences in COVID-19 outcomes attributable to viral entry are independent of TMPRSS2. Modest changes in ACE2 could account for some of the sex discordance. [ABSTRACT FROM AUTHOR]

"All data associated with this study are available in the main text or the Supplementary materials." now reads: "All raw mRNA-seq data files are available on NCBI's Gene Expression Omnibus (GEO), accessible using the following link https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185479." Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-94163-y, published online 19 July 2021 The original version of this Article omitted an URL to all of the raw single-cell omics data in Data availability section. [Extracted from the article]