Cellular plasticity and immune microenvironment of malignant pleural effusion are associated with EGFR-TKI resistance in non-small-cell lung carcinoma.

Malignant pleural effusion (MPE) is a complication of lung cancer that can be used as an alternative method for tissue sampling because it is generally simple and minimally invasive. Our study evaluated the diagnostic potential of non-small-cell lung carcinoma (NSCLC)-associated MPE in terms of understanding tumor heterogeneity and identifying response factors for EGFR tyrosine kinase inhibitor (TKI) therapy. We performed a single-cell RNA sequencing analysis of 31,743 cells isolated from the MPEs of 9 patients with NSCLC (5 resistant and 4 sensitive to EGFR TKI) with EGFR mutations. Interestingly, lung epithelial precursor-like cells with upregulated GNB2L1 and CAV1 expression were enriched in the EGFR TKI-resistant group. Moreover, GZMK upregulated transitional effector T cells, and plasmacytoid dendritic cells were significantly enriched in the EGFR TKI-resistant patients. Our results suggest that cellular plasticity and immunosuppressive microenvironment in MPEs are potentially associated with the TKI response of patients with EGFR-mutated NSCLC.

Changes to Gut Microbiota Following Systemic Antibiotic Administration in Infants.

Long-term antibiotic use can have consequences on systemic diseases, such as obesity, allergy, and depression, implicating the causal role of gut microbiome imbalance. However, the evaluation of the effect of antibiotics in early infancy on alterations to the gut microbiome remains poorly understood. This study aimed to evaluate the gut microbiome state in infancy following systemic antibiotic treatment. Twenty infants under 3 months of age who had received antibiotics for at least 3 days were enrolled, and their fecal samples were collected 4 weeks after antibiotic administration finished. Thirty-four age-matched healthy controls without prior exposure to antibiotics were also assessed. The relative bacterial abundance in feces was obtained via sequencing of 16 S rRNA genes, and alpha and beta diversities were evaluated. At the genus level, the relative abundance of Escherichia/Shigella and Bifidobacterium increased (p = 0.03 and p = 0.017, respectively) but that of Bacteroides decreased (p = 0.02) in the antibiotic treatment group. The microbiome of the antibiotic treatment group exhibited an alpha diversity lower than that of the control group. Thus, systemic antibiotic administration in early infancy affects the gut microbiome composition even after a month has passed; long-term studies are needed to further evaluate this.

Delivery and feeding mode affects fecal calprotectin levels in infants <7months old.

BACKGROUND: Elevated fecal calprotectin (FC) is a non-invasive marker of inflammation indicating bowel disease. However, healthy infants have displayed high FC levels, with large variation. We sought to determine what factors might affect FC levels in children <6months old. METHODS: We recruited 133 healthy infants aged 0-6months from four Korean day care centers. Stool samples were analyzed by immunosorbent assay. All infants completed a questionnaire related to clinical characteristics including birth and feeding history. RESULTS: The mean FC concentration of all of participants was 237.40µg/g (range 11.5-1330.6µg/g). FC levels between 0 and 6months reduced with increasing age and the differences were statistically significant. The mean FC value according to feeding mode was 354.67µg/g for those fed breast milk and 149.44µg/g for those fed formula milk (p<0.001). Mean FC values were 319.69µg/g vs. 130.97µg/g for normal spontaneous vaginal delivery (NSVD) vs. caesarean section births, respectively (p<0.001). In addition, delivery mode affected the FC level at 0-6months regardless of feeding mode. CONCLUSION: The FC levels of infants aged 0-6months reduced with age and were higher than the normal levels observed in healthy older infants. The FC value at <7months was higher in infants who were fed breast milk and born by NSVD.

Prenatal diagnosis of aberrant right subclavian artery in an unselected population.

PURPOSE: The purpose of this study was to determine the frequency of aberrant right subclavian artery (ARSA) among unselected fetuses and to evaluate its association with chromosomal abnormalities and other congenital anomalies. METHODS: In all, 7,547 fetuses (gestational age, 20 to 34 weeks) were examined using routine antenatal sonography at our institution between April 2014 and September 2015. The right subclavian artery was assessed using grayscale and color Doppler ultrasonography in the transverse 3-vessel and tracheal view, and confirmed in the coronal plane. RESULTS: ARSA was found in 28 fetuses (0.4%). Further, 27 of these 28 fetuses were euploid (96.4%). Trisomy 18 was the only chromosomal anomaly (3.6%) found in the study sample. ARSA was an isolated finding in 23 of the 28 cases (82.1%). In the remaining three cases (10.7%), ARSA was accompanied with extracardiac anomalies. Other cardiac defects were present in three cases (10.7%). CONCLUSION: Isolated ARSA does not seem to be associated with a significantly increased risk of aneuploidy. However, the possibility of fetal karyotyping, which is a more invasive procedure, should be discussed in the light of the overall risk of the fetus.

Fecal calprotectin level in healthy children aged less than 4 years in South Korea.

BACKGROUND: Fecal calprotectin (FC) is non-invasive inflammatory marker indicating various bowel diseases. However, the median-specific cut-off values and the standard deviations (SD) of the FC levels in each age group <4 years were not elucidated. METHODS: Healthy volunteers were enrolled from four kindergartens. A questionnaire was used to confirm that the children met the inclusion criteria, and several demographics and history of bowel symptoms were collected. The FC level was measured. RESULTS: A total of 234 healthy children aged between 6 months and 4 years were recruited. The median FC concentration of all participants was 245 µg/g (range 12-1033 µg/g, mean 68.5 µg/g, SD 123.12 µg/g). The children were divided into six age groups. The upper limit of 95% CI of median FC values was 135 µg/g in 7-12 months group, 65 µg/g in 13-18 months group, 55 µg/g in 19-24 months group, 40 µg/g in 25-30 months group, 21 µg/g in 31-36 months group, and 12 µg/g in 37-48 months group. A negative correlation trend was found between the age and the FC concentration. CONCLUSION: This is the first study to present the FC median levels in the specific age groups <4 years in Korea. We found a FC level reduction with age, indicating a bowel maturation process and decreased intestinal permeability of the intestinal mucosa. In our study, FC levels reached the values of 50 µg/g around the age of 2 years.

Xerogel Interfaced Nanofibers Stimulate Bone Regeneration Through the Activation of Integrin and Bone Morphogenetic Protein Pathways.

A xerogel was interfaced onto biopolymer nanofibers though a core­shell electrospinning design for bone regeneration. The xerogel-interfaced biopolymer nanofibrous matrix was bioactive and highly hydrophilic, with a significant decrease in the water contact angle. The matrix showed excellent in vitro responses of primary osteoblasts in terms of adhesion, proliferation, and migration. Furthermore, the osteoblastic differentiation of cells, including alkaline phosphatase activity, mineralization, and gene expression, was significantly upregulated by the xerogel interface. In vivo animal tests in a critical-sized calvarial defect confirmed the new bone formation ability of the xerogel-surfaced nanofiber matrices. The underlying signaling mechanisms of the stimulation were implied to be integrin and bone morphogenetic protein (BMP) pathways, as demonstrated by the activation of integrin (α2ß1) and downstream signaling molecules (FAK, paxillin, RhoA, MAPK, and NF-κB), as well as the BMPs and the downstream transcription factor Smad1/5/8. Taking these findings together, the xerogel-surfaced biopolymer nanofibers are proposed to be a promising scaffold candidate for bone regeneration.

Delivery of dexamethasone from bioactive nanofiber matrices stimulates odontogenesis of human dental pulp cells through integrin/BMP/mTOR signaling pathways.

Therapeutically relevant design of scaffolds is of special importance in the repair and regeneration of tissues including dentin and pulp. Here we exploit nanofiber matrices that incorporate bioactive glass nanoparticles (BGNs) and deliver the odontogenic drug dexamethasone (DEX) to stimulate the odontogenic differentiation of human dental pulp cells (HDPCs). DEX molecules were first loaded onto the BGN, and then the DEX-BGN complex was incorporated within the biopolymer nanofiber matrix through electrospinning. The release of DEX continued over a month, showing a slow releasing profile. HDPCs cultured on the DEX-releasing BGN matrices were viable, proliferating well up to 14 days. The odontogenic differentiation, as assessed by alkaline phosphatase activity, mRNA expression of genes, and mineralization, was significantly stimulated on the matrices incorporating BGN and further on those releasing DEX. The DEX-releasing BGN matrices highly upregulated the expression of the integrin subsets α1, α5, and ß3 as well as integrin downstream signaling molecules, including focal adhesion kinase (FAK), Paxillin, and RhoA, and activated bone morphogenetic protein mRNA and phosphorylation of Smad1/5/8. Furthermore, the DEX-releasing BGN-matrices stimulated Akt and mammalian target of rapamycin (mTOR), which was proven by the inhibition study. Collectively, the designed therapeutic nanofiber matrices that incorporate BGN and deliver DEX were demonstrated to promote odontogenesis of HDPCs, and the integrins, bone morphogenetic protein, and mTOR signaling pathways are proposed to be the possible molecular mechanisms. While further in vivo studies are still needed, the DEX-releasing bioactive scaffolds are considered as a potential therapeutic nanomatrix for regenerative endodontics and tissue engineering.

Recent viral pathogen in acute gastroenteritis: a retrospective study at a tertiary hospital for 1 year.

PURPOSE: Viral gastroenteritis among children is mainly caused by rotavirus, norovirus, astrovirus, or adenovirus strains. However, changing socioeconomic conditions and a rotavirus vaccination program may be affecting the prevalence of these viral infections. Therefore, we aimed to elucidate the season-specific trends in viral infections for facilitating prophylaxis and surveillance in our region. METHODS: We evaluated 345 pediatric patients (203 males, 142 females; age, 1 month to 16 years) who visited the CHA Bundang Medical Center because of gastroenteric symptoms between June 2014 and May 2015. The specimens were simultaneously tested for norovirus, rotavirus, astrovirus, and adenovirus via multiplex reverse transcription polymerase chain reaction. Clinical characteristics of patients were analyzed retrospectively. RESULTS: The most common virus was norovirus, followed by rotavirus, adenovirus, and astrovirus. Of all viral infections, 45.2% occurred mainly between 6 and 24 months of age; in particular, norovirus infection mostly occurred in all age groups except those below 6 months of age, when rotavirus was most prevalent. In addition, seasonal variation was observed, such as norovirus infection from December to February, rotavirus infection from February to April, and adenovirus infection from July to October. CONCLUSION: Our results showed that the most common cause of acute pediatric viral gastroenteritis had changed from rotavirus to norovirus in our patients, because of effective rotaviral vaccination. We recommend the management of food and personal hygiene in accordance with age or seasons as well as active vaccination for preventing viral gastroenteritis.