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Neonates who are born preterm (PT) are usually characterized by immature physiological development, and preterm birth (PTB) is the leading cause of neonatal morbidity and mortality if intensive medical care is not available to PTB neonates. Early prediction of a PTB enables medical personnel to make preparations in advance, protecting the neonate from the subsequent health risks. Therefore, many studies have worked on identifying invasive or noninvasive PT biomarkers. In this study, we collected amniocentesis-derived (at the second trimester of gestation) amniotic fluid (AF) samples. At delivery, AF samples were classified into PTB or full-term birth (FTB). We first applied protein mass spectrometry technology to globally screen AF proteins, followed by specific protein validation with ELISA. We identified four protein biomarkers of PTB, including lactotransferrin (LTF), glutathione-disulfide reductase (GSR), myeloperoxidase (MPO) and superoxide dismutase 2 (SOD2). Further analyses demonstrated that their abundances were negatively correlated with neonatal weight and gestational age. In addition, by mimicking survival rate analysis widely used in tumor biology, we found that LTF and SOD2 were prognostic factors of gestational age, with higher levels denoting shorter gestational age. Finally, using the abundances of the four protein biomarkers, we developed a prediction model of PTB with an auROC value of 0.935 (sensitivity = 0.94, specificity = 0.89, p value = 0.0001). This study demonstrated that the abundances of specific proteins in amniotic fluid were not only the prognostic factors of gestational age but also the predictive biomarkers of PTB. These four AF proteins enable identification of PTB early in the second trimester of gestation, facilitating medical intervention to be applied in advance. [ABSTRACT FROM AUTHOR]

Systemic juvenile idiopathic arthritis (sJIA) and cryopyrin-associated periodic syndrome (CAPS) share many common manifestations. We aim to identify an applicable method to assist disease discrimination. Inflammatory cytokines were measured in the plasma of patients with CAPS, sJIA with persistent disease course and healthy controls. Supernatants collected from non-stimulated peripheral blood mononuclear cells (PBMCs) and those undergone inflammasome stimulation tests utilizing lipopolysaccharide (LPS) with and without adenosine triphosphate (ATP) were investigated. Inflammatory cytokines in patient plasma fail to differentiate sJIA from CAPS. PBMCs from sJIA secrets higher amount of IL-1β and IL-18 while CAPS PBMCs produces more caspase-1 without stimulation. IL-1β, IL-18, and caspase-1 were significantly elevated among CAPS PBMCs (all p < 0.05) upon LPS stimulation, but not when additional ATPs were provided. Levels of cytokines and PBMC responses to the stimulation assays were similar among all sJIA patients regardless of their history of macrophage activation syndrome. Unstimulated PBMC activities and the LPS inflammasome stimulation assay without exogenic ATPs can assist the differentiation of CAPS from sJIA with persistent disease course. [ABSTRACT FROM AUTHOR]

Objective: Clinical outcomes of patients with resected oral cavity squamous cell carcinoma (OCSCC) chiefly depend on the presence of specific clinicopathological risk factors (RFs). Here, we performed a combined analysis of FDG-PET, genetic markers, and clinicopathological RFs in an effort to improve prognostic stratification. Methods: We retrospectively reviewed the clinical records of 2036 consecutive patients with first primary OCSCC who underwent surgery between 1996 and 2016. Of them, 345 underwent ultra-deep targeted sequencing (UDTS, between 1996 and 2011) and 168 whole exome sequencing (WES, between 2007 and 2016). Preoperative FDG-PET imaging was performed in 1135 patients from 2001 to 2016. Complete data on FDG-PET, genetic markers, and clinicopathological RFs were available for 327 patients. Results: Using log-ranked tests based on 5-year disease-free survival (DFS), the optimal cutoff points for maximum standardized uptake values (SUV-max) of the primary tumor and neck metastatic nodes were 22.8 and 9.7, respectively. The 5-year DFS rates were as follows: SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7 (n = 77) versus SUVtumor-max < 22.8 and SUVnodal-max < 9.7 (n = 250), 32%/62%, P < 0.001; positive UDTS or WES gene panel (n = 64) versus negative (n = 263), 25%/62%, P < 0.001; pN3b (n = 165) versus pN1-2 (n = 162), 42%/68%, P < 0.001. On multivariate analyses, SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7, a positive UDTS/WES gene panel, and pN3b disease were identified as independent prognosticators for 5-year outcomes. Based on these variables, we devised a scoring system that identified four distinct prognostic groups. The 5-year rates for patients with a score from 0 to 3 were as follows: loco-regional control, 80%/67%/47%/24% (P < 0.001); distant metastases, 13%/23%/55%/92% (P < 0.001); DFS, 74%/58%/28%/7% (P < 0.001); and disease-specific survival, 80%/64%/35%/7% (P < 0.001) respectively. Conclusions: The combined assessment of tumor and nodal SUV-max, genetic markers, and pathological node status may refine the prognostic stratification of OCSCC patients. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-023-31486-y, published online 25 March 2023 The Funding section in the original version of this Article was incomplete. "This study was supported by Chang Gung Memorial Hospital (CMRPG8A0501)." now reads: "This study was supported by Chang Gung Memorial Hospital (CMRPG8A0501 and CMRPG8L0101).". [Extracted from the article]

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease in which the abnormalities in alveolar surfactant accumulation are caused by impairments of GM-CSF pathway attributing to defects in a variety of genes. However, hereditary PAP is extremely uncommon and a detailed understanding in the genetic inheritance of PAP in a family may provide timely diagnosis, treatment and proper intervention including genetic consultation. Here, we described a comprehensive analysis of genome and gene expression for a family containing one affected child with a diagnosis of PAP and two other healthy siblings. Family-based whole-genome analysis revealed a homozygous deletion that disrupts CSF2RA, CRLF2, and IL3RA gene in the pseudoautosomal region of the X chromosome in the affected child and one of asymptomatic siblings. Further functional pathway analysis of differentially expressed genes in IL-1β-treated peripheral blood mononuclear cells highlighted the insufficiency of immune response in the child with PAP, especially the protection against bacterial infection. Collectively, our results reveal a novel allele as the genetic determinant of a family with PAP and provide insights into variable expressivity and incomplete penetrance of this rare disease, which will be helpful for proper genetic consultation and prompt treatment to avoid mortality and morbidity. [ABSTRACT FROM AUTHOR]