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Abstract Background Lazertinib is a potent, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with significant efficacy in patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC). This is the final overall survival (OS) report from the phase 1/2 LASER201 study in patients with advanced NSCLC with disease progression on or after prior EGFR TKI therapy. Methods Eligible patients were aged ≥ 20 years, with advanced EGFR-mutated NSCLC and previous therapy with EGFR TKI. Patients in this integrated analysis received oral lazertinib 240 mg/day. Endpoints included efficacy and safety; exploratory analyses included associations between circulating EGFR-mutant tumor DNA (ctDNA) and efficacy parameters. Results This integrated analysis included 78 patients in Korea who received second- or later-line lazertinib. The median OS was 38.9 months; estimated survival rates at 12, 24, and 36 months were 89.5%, 73.9%, and 52.8%, respectively. The cumulative 12-month incidence of central nervous system progression was 9.4%. EGFR-mutant ctDNA was detected in 46 patients (62.2%) at baseline. The presence of ctDNA at baseline significantly predicted progression-free survival (PFS), disease control rate (DCR), and OS. PFS, response rate, and DCR were significantly associated with EGFR-mutant ctDNA clearance at cycle 3; PFS and OS were significantly associated with ctDNA clearance at cycle 5. The safety profile of lazertinib 240 mg/day was consistent with previous findings. Conclusions Lazertinib is a promising treatment option for patients with EGFR T790M-positive NSCLC following disease progression on prior EGFR-directed TKIs. Patients in LASER201 experienced prolonged OS, regardless of their EGFR mutation, brain metastases, or prior brain radiation status. Clearance of plasma EGFR mutations after lazertinib was associated with patient outcomes. Trial registration ClinicalTrials.gov identifier NCT03046992.

BackgroundMefunidone is a novel synthetic compound and is better when compared to pirfenidone for the anti-fibrotic treatment of renal fibrosis in end-stage renal disease. We conducted this first-in-human, phase I clinical trial to determine the safety, tolerability, and pharmacokinetic (PK) (including food effect) profiles of mefunidone administered orally as single and multiple ascending doses in healthy subjects.MethodsPart A assessed single ascending doses of mefunidone from 25 mg to 800 mg or placebo once daily in the fasting state. Part A also assessed the effect of food on tolerability and PK in the 100 mg cohort. Part B consisted of three treatment groups who received 100 mg, 200 mg, or 400 mg of mefunidone or placebo twice daily (BID, bis in die) on days 1–6 and once in the morning on day 7.ResultsSingle oral doses of mefunidone up to 800 mg and multiple doses of mefunidone up to 400 mg BID were all well-tolerated. Mefunidone behaved with ideal dose proportionality within the single-dose range of 50 mg–600 mg and the multiple-dose range of 100 mg BID to 400 mg BID by day 7. High-fat fed conditions led to a delay in Tmax by approximately 1 h and a slight reduction of approximately 20% in Cmax compared to that in fasting conditions, but it did not significantly affect systemic exposure.ConclusionMefunidone exhibited favorable pharmacokinetics and safety profiles. The present study informed and supported further developmental clinical studies of mefunidone.Clinical Trial Registrationclinicaltrials.gov, identifier CXHL1900206

Abstract Autophagosomes are double-membrane vesicles generated intracellularly to encapsulate substrates for lysosomal degradation during autophagy. Phase separated p62 body plays pivotal roles during autophagosome formation, however, the underlying mechanisms are still not fully understood. Here we describe a spatial membrane gathering mode by which p62 body functions in autophagosome formation. Mass spectrometry-based proteomics reveals significant enrichment of vesicle trafficking components within p62 body. Combining cellular experiments and biochemical reconstitution assays, we confirm the gathering of ATG9 and ATG16L1-positive vesicles around p62 body, especially in Atg2ab DKO cells with blocked lipid transfer and vesicle fusion. Interestingly, p62 body also regulates ATG9 and ATG16L vesicle trafficking flux intracellularly. We further determine the lipid contents associated with p62 body via lipidomic profiling. Moreover, with in vitro kinase assay, we uncover the functions of p62 body as a platform to assemble ULK1 complex and invigorate PI3KC3-C1 kinase cascade for PI3P generation. Collectively, our study raises a membrane-based working model for multifaceted p62 body in controlling autophagosome biogenesis, and highlights the interplay between membraneless condensates and membrane vesicles in regulating cellular functions.

Congenital chloride diarrhea (CLD) is a rare autosomal recessive disease caused by mutations in the solute carrier family 26 member 3 (SLC26A3) gene on chromosome 7q31. Affected neonates are vulnerable to dehydration, electrolyte imbalance in the form of hyponatremia, metabolic alkalosis, failure to thrive, or even death if left untreated. Genetic testing for mutations should be considered if the clinical diagnosis remains uncertain because early diagnosis and appropriate management are critical to the disease course in CLD. Several mutations have been reported in Korean patients with CLD, with the most common being the c.2063-1G>T mutation. Here, we report the case of a neonate with prenatally suspected CLD with confirmed novel mutations in the SLC26A3 gene (c.2147C>G; p.Ala716Gly).

ObjectiveIntermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis.MethodsIn this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples.ResultsOur results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced E. coli abundance across multiple timepoints while elevating the abundance of obesity-related Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis. Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes.ConclusionsThere was dynamical alteration of BGM axis (the communication of E. coli with specific brain regions) during the weight loss under the IER.

BackgroundIntermittent energy restriction (IER) is an effective weight loss strategy. However, the accompanying changes in spontaneous neural activity are unclear, and the relationship among anthropometric measurements, biochemical indicators, and adipokines remains ambiguous.MethodsThirty-five obese adults were recruited and received a 2-month IER intervention. Data were collected from anthropometric measurements, blood samples, and resting-state functional magnetic resonance imaging at four time points. The regional homogeneity (ReHo) method was used to explore the effects of the IER intervention. The relationships between the ReHo values of altered brain regions and changes in anthropometric measurements, biochemical indicators, and adipokines (leptin and adiponectin) were analyzed.ResultsResults showed that IER significantly improved anthropometric measurements, biochemical indicators, and adipokine levels in the successful weight loss group. The IER intervention for weight loss was associated with a significant increase in ReHo in the bilateral lingual gyrus, left calcarine, and left postcentral gyrus and a significant decrease in the right middle temporal gyrus and right cerebellum (VIII). Follow-up analyses showed that the increase in ReHo values in the right LG had a significant positive correlation with a reduction in Three-factor Eating Questionnaire (TFEQ)-disinhibition and a significant negative correlation with an increase in TFEQ-cognitive control. Furthermore, the increase in ReHo values in the left calcarine had a significant positive correlation with the reduction in TFEQ-disinhibition. However, no significant difference in ReHo was observed in the failed weight loss group.ConclusionOur study provides objective evidence that the IER intervention reshaped the ReHo of some brain regions in obese individuals, accompanied with improved anthropometric measurements, biochemical indicators, and adipokines. These results illustrated that the IER intervention for weight loss may act by decreasing the motivational drive to eat, reducing reward responses to food cues, and repairing damaged food-related self-control processes. These findings enhance our understanding of the neurobiological basis of IER for weight loss in obesity.

This paper focuses on solving a class of equilibrium problems, namely, the fixed point problem of set-valued mappings with second-order cone double constraints. Under certain conditions, the variational inequality form of the fixed point problem of set-valued mappings with second-order cone double constraints is obtained by using the generalized saddle point theory three times. The alternating direction method is used to solve the fixed point problem of set-valued mappings with second-order cone double constraints, and the global convergence of the algorithm is proved. Finally, numerical results of solving five examples with an inexact alternating direction method are given, and the feasibility and effectiveness of the algorithm are demonstrated by comparing with other algorithms.

Objective: The glycation inhibition of 8 different non-Camellia teas was evaluated by detecting the content of non-enzymatic advanced glycation end-products (AGEs) and the inhibition mechanism of different teas with good inhibition effect on AGEs formation at various stages were investigated. Methods: Firstly, the total flavonoid content of the water extracts of 8 non-Camellia teas water extracts were detected, then all teas were tested by constructing an in vitro protein non-enzymatic glycation model experiment to evaluate the ability of inhibit the production of AGEs. Finally, the inhibitory ability of fructosamine (early glycation product), active carbonyl compound (intermediate glycation product), and the protein cross-linking were determined to explore the inhibitory mechanism of the non-enzymatic glycation reaction. Results: The inhibitory effect of Ilex latifolia tea and Rubus suavissimus tea on AGEs showed more prominent among the eight non-Camellia teas, and the inhibitory rate of AGEs reached at 76.31%±0.87% and 81.75%±0.41% at 50 µg/mL respectively. Further experimental results showed that Ilex latifolia tea and Rubus suavissimus tea mainly reduced the production of AGEs by inhibiting the formation of early and intermediate products of glycation, and 500 μg/mL Rubus suavissimus tea had the highest inhibition rate of fructosamine(59.12%) and protein cross-linking inhibition rate (81.41%), 5000 μg/mL Ilex latifolia tea had the highest inhibition rate of active carbonyl compounds (94.24%). Conclusion: Ilex latifolia tea and Rubus suavissimus tea could be used as functional foods to inhibit glycation reaction. This study could provide a theoretical basis for the comprehensive development and utilization of anti-glycation diet materials.

Prenatal diagnosis of clubfoot traditionally relied on two-dimensional ultrasonography. To enhance diagnosis and predict postnatal outcomes, we examined the parameters that differentiate pathological clubfoot using three-dimensional ultrasonography. In our retrospective study, we examined the findings of prenatal ultrasound and the postnatal outcomes of pregnancies with suspected congenital clubfoot between 2018 and 2021. Based on the three-dimensional perspective, we measured the angles of varus, equinus, calcaneopedal block, and forefoot adduction and compared the sonographic variables between the postnatal treated and non-treated groups. We evaluated 31 pregnancies (47 feet) with suspected clubfoot using three-dimensional ultrasonography. After delivery, a total of 37 feet (78.7%) underwent treatment involving serial casting only or additional Achilles tenotomy. The treated group showed significantly greater hindfoot varus deviation (60.5° vs. 46.6°, p = 0.026) and calcaneopedal block deviation (65.6° vs. 26.6°, p < 0.05) compared to the non-treated group. The calcaneopedal block had an area under the curve of 0.98 with a diagnostic threshold of 46.2 degrees (sensitivity of 97%, specificity of 90%, positive predictive value of 97%, and negative predictive value of 90%). During prenatal evaluation of clubfoot using three-dimensional ultrasonography, the calcaneopedal block deviation has the potential to predict postnatal treatment.

Partial trisomy 1q is a rare chromosomal disorder characterized by ventriculomegaly with craniofacial, renal, cardiac, and finger and toe anomalies. Most reported cases of partial trisomy1q have involved stillborn or premature deaths due to cardiac or liver failure. This case report describes an 18-month-old patient with partial duplication of the 1q32-44 segments and consequent developmental delays who exhibited improvement in developmental status with rehabilitation. Prenatal ultrasonography and magnetic resonance imaging of the mother revealed ventriculomegaly and atrophic changes in the left cerebral hemisphere of the fetus. The infant was born with micrognathia, microphthalmia, macrocephaly, low-set ears, polydactyly, and long feet at 37+5 weeks of gestation. A chromosomal study revealed an abnormal male karyotype of 46,XY,rec(1)dup(1)(q32.1q44)inv(1)(p36.3q32.1)pat. In this rare case of a patient with partial trisomy, we observed improvement in developmental delays following treatment using appropriate rehabilitation techniques. Further research is required to help validate the findings of this case study and establish a standardized rehabilitation technique that can be subsequently applied to such cases.

In cells, p62/SQSTM1 undergoes liquid–liquid phase separation (LLPS) with poly-ubiquitin chains to form p62 bodies that work as a hub for various cellular events, including selective autophagy. Cytoskeleton components such as Arp2/3-derived branched actin network and motor protein myosin 1D have been shown to actively participate in the formation of phase-separated p62 bodies. Here, we describe a detailed protocol on the purification of p62 and other proteins, the assembly of the branched actin network, and the reconstitution of p62 bodies along with cytoskeletal structures in vitro. This cell-free reconstitution of p62 bodies vividly mimics the phenomenon in which low concentrations of protein in vivo rely on cytoskeleton dynamics to increase the local concentration to reach the threshold for phase separation. This protocol provides an easily implemented and typical model system to study cytoskeleton-involved protein phase separation.

IntroductionDry matter accumulation (DMA) and dry matter partitioning (DMP) are important physiological processes determining crop yield formation. Deep understanding of the DMA and DMP processes and their responses to drought are limited by difficulty in acquiring total root biomass.MethodsPot experiments with treatments quitting and ceasing ear growth (QC) and controlling soil water (WC) during vegetative (VP) and reproductive (RP) growth stages of maize (Zea mays) were conducted in Jinzhou in 2019 and 2020 to investigate the effects of drought and rewatering on DMW and DMP of different organs.ResultsThe response of DMW of reproductive organ to drought was more sensitive than those of vegetative organs, and was maintained after rehydration. Drought during VP (VPWC) reduced more sharply DMW of stalk than of leaves, and that during RP (RPWC) decreased more substantially leaves DMW. The effect of drought on DMPR was inconsistent with that on DMW for each organ. The DMP patterns of maize in different growth stages have adaptability to some level of water stress, and their responses increased with drought severity. Drought increased significantly DMP rates (DMPRs) of vegetative organs and reduced the ear DMPR and harvest index (HI), attributing to the suppressed photosynthates partitioning into ear and dry matter redistribution (DMRD) of vegetative organs, especially for stalk DMRD decreasing 26%. The persistence of drought impact was related to its occurrence stage and degree as well as the duration during rewatering to maturity. The aftereffect of drought during different growth periods on DMP were various, and that of VPWC enlarged and drastically induced the reduction of HI, also was larger than that of RPWC which demonstrated obvious alleviation in the previous responses of DMP and HI. Root-shoot ratio (RSR) increased under VPWC and RPWC and subsequent rehydration.DiscussionThe DMWs of stalk, roots and leaves were affected by VPWC in order from large to small, and were close to or larger than the controls after rehydration, indicating the compensation effect of rewatering after drought. The DMPRs, RSR AND HI are the important parameters in agricultural production, and are often used as the constants, but in fact they vary with plant growth. In addition, the interannual differences in ear and stalk DMPRs in response to drought were probably caused by the difference in degree and occurrence stage of drought, further reflecting the variation in response of allometry growth among organs to the environment. Besides, the persistence of drought impact was related to the occurrence stage and degree of drought, which is also associated with the duration during rewatering to maturity. Notably, the effect of drought on DMW was inconsistent with that on DMPR for each organ meaning that the two variables should be discussed separately. The QC did not affect total DMW but increased RSR, changed and intensified the effect and aftereffect of RPWC on DMP, respectively, indicating that the DMP pattern and its response to drought occur change under the condition of QC.

A method was put forward to identify the combined heat and drought (CHD) events that occurred in summer and affected spring maize in Liaoning province. The spatial and temporal characteristics of CHD and its effects on maize were evaluated based on daily meteorological data at 52 meteorological stations in Liaoning from 1961 to 2020, as well as agricultural data including details of the maize development periods. The effects of CHD on the photosynthetic capacity of maize were evaluated using SIF remote sensing data from 2001 to 2020. The differences in maize photosynthetic capacity in the summers of 2009 and 2018 were compared in detail. The results show that from 1961 to 2020, the occurrence range, frequency, and severity of summer CHD events increased in Liaoning. CHD events were more frequent in June/July, and higher-intensity CHD events were more frequent in July/August. From 1961 to 2020, CHD events occurred in 69% of the years of reduced meteorological yield, and reduced meteorological yield occurred in 41% of the years with CHD events. Maize solar-induced chlorophyll fluorescence (SIF), an index of photosynthesis, was sensitive to temperature (negatively correlated) and precipitation (positively correlated). The CHD events slowed the increasing SIF from the three-leaf stage to the jointing stage, and they stopped the increasing SIF or decreased it at the tasseling–flowering to silking stages. Therefore, maize photosynthesis may be most sensitive to CHD during the flowering to silking stages, and CHD during the silking to milk stages may have the greatest impact on maize yield. Understanding the effects of CHD on maize growth/yield provides a scientific basis for reducing its negative impacts on maize production.

Double-stranded RNA-binding proteins are small molecules in the RNA interference (RNAi) pathway that form the RNAi machinery together with the Dicer-like protein (DCL) as a cofactor. This machinery cuts double-stranded RNA (dsRNA) to form multiple small interfering RNAs (siRNAs). Our goal was to clarify the function of DRB in tomato resistant to TYLCV. In this experiment, the expression of the SlDRB1 and SlDRB4 genes was analyzed in tomato leaves by qPCR, and the function of SlDRB1 and SlDRB4 in resistance to TYLCV was investigated by virus-induced gene silencing (VIGS). Then, peroxidase activity was determined. The results showed that the expression of SlDRB1 gradually increased after inoculation of ‘dwarf tomato’ plants with tomato yellow leaf curl virus (TYLCV), but this gene was suppressed after 28 days. Resistance to TYLCV was significantly weakened after silencing of the SlDRB1 gene. However, there were no significant expression differences in SlDRB4 after TYLCV inoculation. Our study showed that silencing SlDRB1 attenuated the ability of tomato plants to resist virus infection; therefore, SlDRB1 may play a key role in the defense against TYLCV in tomato plants, whereas SlDRB4 is likely not involved in this defense response. Taken together, These results suggest that the DRB gene is involved in the mechanism of antiviral activity.

Ferrous sulfide (FeS) nanoparticles constitute an effective hexavalent chromium (Cr(VI)) treatment reagent. However, FeS nanoparticles aggregate easily, significantly limiting their engineering applicability. To overcome this shortcoming and further improve Cr(VI) removal efficiency, this study used tannic acid (TA) to modify FeS nanoparticles. The results demonstrated that TA-modified FeS nanoparticles, TA-nano-FeS, had a significantly reduced tendency to agglomerate, and maintained particle diameters of 10–100 nm, which were much shorter than diameters of FeS nanoparticles. In addition, TA-nano-FeS could combine the surface-active functional groups of TA. The maximum removal capacity of TA-nano-FeS was 381.04 mg/g, which was 2.92 and 1.83 times higher than those of TA and nano-FeS, respectively. Furthermore, the acidic condition was more beneficial for Cr(VI) removal, and the coexisting cations (Ca2+ and Mg2+) slightly decreased the removal efficiency of Cr(VI). Adsorption, reduction, and co-precipitation were the removal mechanisms, and the reaction products included FeCr2O4, Cr2O3, Fe2O3, Cr(OH)3, and S8. The results provided valuable information for the practical application of TA-nano-FeS in Cr(VI) removal.

Abstract We aimed to compare accelerated post-contrast magnetization-prepared rapid gradient-echo (MPRAGE) using wave-controlled aliasing in parallel imaging (wave-CAIPI) with conventional MPRAGE as a reliable method to diagnose intracranial lesions in pediatric patients. A total of 23 consecutive pediatric patients who underwent post-contrast wave-CAIPI and conventional MPRAGE (scan time: 2 min 39 s vs. 5 min 46 s) were retrospectively evaluated. Two radiologists independently assessed each image for the presence of intracranial lesions. Quantitative [contrast-to-noise ratio (CNR), contrast rate (CR), and signal-to-noise ratio (SNR)] and qualitative parameters (overall image quality, gray-white matter differentiation, demarcation of basal ganglia and sulci, and motion artifacts) were also surveyed. Wave-CAIPI MPRAGE and conventional MPRAGE detected enhancing and non-enhancing intracranial lesions with 100% agreement. Although wave-CAIPI MPRAGE had a lower SNR (all p 0.05). Wave-CAIPI MPRAGE was a reliable method for diagnosing intracranial lesions in pediatric patients as conventional MPRAGE at half the scan time.

Oseltamivir is a widely used influenza virus neuraminidase (NA) inhibitor that prevents the release of new virus particles from host cells. However, oseltamivir-resistant strains have emerged, but effective drugs against them have not yet been developed. Elucidating the binding mechanisms between NA and oseltamivir may provide valuable information for the design of new drugs against NA mutants resistant to oseltamivir. Here, we conducted large-scale (353.4 μs) free-binding molecular dynamics simulations, together with a Markov State Model and an importance-sampling algorithm, to reveal the binding process of oseltamivir and NA. Ten metastable states and five major binding pathways were identified that validated and complemented previously discovered binding pathways, including the hypothesis that oseltamivir can be transferred from the secondary sialic acid binding site to the catalytic site. The discovery of multiple new metastable states, especially the stable bound state containing a water-mediated hydrogen bond between Arg118 and oseltamivir, may provide new insights into the improvement of NA inhibitors. We anticipated the findings presented here will facilitate the development of drugs capable of combating NA mutations.

The Northeast China maize belt is one of the three major golden maize belts in the world and has been severely affected by climate change, however, the evapotranspiration (ET) partitioning is not clear. It is important to study ET and its components under climate change. In this paper, the water balance model SOILWAT2 was used to estimate ET partitioning in drought and humid years, seasons, and maize growth stages from 1989 to 2018 over rainfed maize farmland. The results indicated that the SOILWAT2 model performed well for the prediction of ET and its partitioning compared with eddy covariance measurements. The mean yearly ET, transpiration (T), soil evaporation (Es), and canopy interception evaporation (Int) were 432.3 mm, 197.6 mm, 204.7 mm and 19.2 mm, respectively, over 30 years. Es/ET was 6.3% lower in drought years than in humid years, T/ET was conversely higher (6.2% higher in drought years). There was no clear difference of Int/ET between humid and drought years. In the growing season, T/ET, Es/ET, and Int/ET varied from 40.0% to 75.0%, 22.8% to 55.7%, and 0.7% to 7.0%, respectively. T/ET decreased along with the growth of maize and was greatest at the greening–jointing stage. Es/ET was smallest at the greening–jointing stage. We found a power function relationship between T/ET, Es/ET, and leaf area index (LAI) and above-ground biomass. Our results indicated that for the rainfed farmland, drought may limit maize yield by increasing water loss of maize through increasing T under climate change conditions. Therefore, securing food yield will depend on increases in water-use efficiency and other adaptive strategies, such as drought-resistant varieties, and irrigation.

Purpose Previous estimates of the cause- and age-specific frequency of pediatric meningitis in Korea were mainly derived from single- and multi-center studies. Herein, we used data on the number of cases of bacterial and viral meningitis from the Health Insurance Review and Assessment Service database to examine time- and sex-related trends. Methods We extracted data on meningitis diagnoses registered in the Health Insurance Review and Assessment Service from 2009 to 2017, using Korean Standard Classification of Disease and Cause of Death codes. Information on 202,254 children aged 0 to 18 years was extracted. Detailed demographic and disease information was available for 84,543 children who underwent hospitalization. Results Among all hospitalized patients, 2166, 36,155, and 46,192 children were diagnosed with bacterial, viral, or other types of meningitis, respectively. There were 30 cases of fungal meningitis and another 30 cases of meningitis attributable to other pathogens. The number of cases of bacterial and viral meningitis was highest among infants (1,087 [50.2%]) and patients in their early childhood (12,949 [35.9%]), respectively. Meningitis outbreaks were most likely to occur during the summer, and boys were more susceptible to meningitis than girls. The following pathogens most commonly caused infant meningitis: group B Streptococcus, Escherichia coli, and type B Haemophilus influenzae. Conclusion This study reports the number of pediatric meningitis cases, stratified by age, disease type, and month/year. The present findings contribute to a better understanding of pediatric meningitis in Korea and provide a foundation for future research to identify the risk factors for this disease.

Abstract Background To confirm the accuracy of transcutaneous bilirubin (TcB) in the neonatal intensive care unit both with and without phototherapy, and compare forehead and sternum as the TcB assessment site. Methods We simultaneously assessed the total serum bilirubin (TSB) and TcB at the forehead and sternum, using a JM-103 bilirubinometer. We analyzed the correlation between the TSB and TcB assessed at the forehead and sternum, with measurements classified as ‘without phototherapy’ (before phototherapy and > 24 hours after phototherapy discontinuation) and ‘with phototherapy’ (after 24 hours of phototherapy). Results There were 1,084 paired forehead and sternum TcB measurements, with the corresponding TSB measurement, from 384 infants. Their mean gestational age of 35.4 ± 3.2 weeks (62% were preterm) and a mean birth weight of 2434 ± 768 grams, and TSB was 6.61 ± 3.56 mg/dL. Without phototherapy, TcB values at the forehead and sternum were correlated well to the TSB value (r = 0.925 and 0.915, respectively). With phototherapy, TcB values at the forehead and sternum were significantly correlated with the TSB value, but TcB at the forehead (r = 0.751) was a better match to the TSB than was TcB at the sternum (r = 0.668). Additionally, Bland-Altman plots showed a greater degree of underestimation of the TSB by TcB at the sternum with phototherapy. Conclusions TcB was more accurate in infants not receiving phototherapy. During phototherapy, it is better to assess TcB at the forehead rather than at the sternum.

ObjectivesWe investigated the clinical efficacy of a modified nasobiliary fixation and drainage technique which was designed in an attempt to reduce unplanned extubation and tube blockage and improve bile drainage and the comfort of catheterized patients.MethodsFrom January 2019 to December 2020, 230 patients receiving Endoscopic nasobiliary drainage (ENBD) during hospitalization were recruited to this study. Participants were randomly allocated to 2 groups by using the block randomization method: in the control group: the conventional method of nasobiliary fixation was adopted after surgery; in the test group: intraoperative annular cutting of nasobiliary tubes was performed and the exposed catheter length was standardized. The modified “tube-nose-ear” three-step technique was performed after surgery. The clinical efficacy of a modified nasobiliary fixation and drainage technique was evaluated and compared between the test group and the control group.ResultsThe rate of unplanned extubation and incidence of complications were significantly lower in the test group than the control group. In addition, the rate of bilirubin decrease after drainage was higher in the test group. Patient discomfort during catheterization was also significantly reduced using the modified technique (P < 0.05).ConclusionsThe modified technique of nasobiliary fixation and drainage technique can significantly reduce unplanned extubation and nasobiliary tube blockage after ENBD, facilitate biliary drainage, and improve patient comfort. This technique warrants wider application in clinical practice.

To understand the drought response mechanisms of dry matter partitioning of maize, pot experiments under drought conditions were conducted during the vegetative and reproductive growth periods of maize. The aim was to calculate allometric relationships between the dry matter weight of different organs and their responses to drought. Results showed that allometric relationships between the roots, above-ground plant, and total biomass gradually increased with maize growth approaching maturity under a normal water supply. Drought during the vegetative period reinforced allometric relationships during the growth process and after rewatering and increased the size-dependence of the root shoot ratio. However, drought during the reproductive period weakened them. The ear–shoot allometric relationship was more significant during growth than at later growth under normal conditions but strengthened during later growth in those plants suffering droughts during the vegetative and reproductive stages. The ear–shoot allometric relationship and the size-dependence of harvest index at later growth were significantly enhanced by drought during the reproductive period compared to the vegetative period.

Bacterial infections (BIs) need to be differentiated from non-BIs (NBIs) to enable prompt administration of antibiotics. Therefore, inflammatory biomarkers are needed as they can accurately identify BIs. This study evaluated the usefulness of procalcitonin (PCT) in the diagnosis of BI in immunocompetent children. We retrospectively reviewed the medical records of patients p = 0.008) and ESR (39.1 ± 32.4 vs. 54.8 ± 28.2 mm/h; p < 0.001) were significantly different. Between the IBI and other groups, WBC (14,797 ± 7148 vs. 12,622 ± 5770 × 106/L; p = 0.007), ESR (35.3 ± 30.3 vs. 51.5 ± 30.3 mm/h; p < 0.001), and PCT (8.1 ± 23.8 vs. 1.0 ± 3.4 ng/mL; p = 0.005) were significantly different. However, none of the biomarkers were useful in differentiating BI from NBI. While WBC (area under curve (AUC) = 0.615, p = 0.003) and PCT (AUC = 0.640, p < 0.001) were useful, they fared poorly in differentiating IBI from other groups. Thus, additional studies are needed to identify more accurate biomarkers capable of differentiating BIs, especially IBIs.

Background An increase in the numbers of patients with gastrointestinal symptoms has recently been observed. Purpose To investigate the effects of proton pump inhibitor (PPI) therapy on intestinal inflammation in children and adolescents as confirmed by clinical manifestations and objectively assessed by fecal calprotectin (FC) level measurement. Methods Consecutive children (aged 3–18 years) who presented with gastrointestinal symptoms and were treated with or without PPI for at least 1 month were enrolled. Patients were divided into PPI and non-PPI groups. The PPI group was further subdivided by treatment duration and type of PPI used. Stool samples were collected for FC evaluation at baseline and after treatment and clinical data and FC levels were compared between the groups. Results Fifty-one patients (15 boys, 36 girls) were enrolled in the study. The PPI group included 37 patients, while the non-PPI group included 14 patients. Clinical symptoms were not significantly different. FC levels and laboratory results, including C-reactive protein levels, white blood cell count, and absolute neutrophil count, were not statistically different before versus after PPI treatment. After treatment, FC levels decreased to 8.1 mg/kg (-575.4 to 340.3 mg/kg) in the PPI group and increased to 5.6 mg/kg (-460.0 to 186.9 mg/kg) in the non-PPI group compared to those before treatment (P=0.841). The number of patients with increased FC levels was not significantly different between the 2 groups (48.6% vs. 64.3%, P=0.363), similar to that observed in patients with an FC level > 50 mg/kg (24.3% and 7.1%, P=0.250). PPI therapy type and duration did not affect the FC levels (P=0.811 and P=0.502, respectively). Conclusion Although we aimed to confirm the evidence of intestinal inflammation due to PPI use in children and adolescents through clinical symptoms and FC measurement, no significant changes were observed.

Abstract Background Intussusception is a gastrointestinal condition in which early treatment is critical. Although its epidemiology and comorbidities have been studied, few studies have included the entire pediatric population of a country. Therefore, we aimed to analyze the epidemiologic features of pediatric intussusception patients and identify comorbidities associated with intussusception in South Korea, using the public health database. Methods We analyzed the data of children below 18 years of age, from the national database of South Korea, who were diagnosed with intussusception and managed such as air reduction or surgical methods from 2008 to 2016. Patients were categorized into six groups based on the comorbid diseases. Patients with structural lesion in gastrointestinal tract were divided diagnosis or diagnosis code. Results The number of patients diagnosed with intussusception were 25,023 (16,024 males, 64.0%). Of them, the highest percentage was patients aged between 2 and 36 months (20,703; 82.7%). The incidence per 100,000 individuals aged up to 2 years was 196.7. The number of males were 16,024 (64.0%) and were almost twice the number of 8999 (36.0%) female patients. The maximum number of cases (n = 2517; 10.1%) were seen in September, followed by July (n = 2469; 9.9%). In February, the number of cases was lowest at 1448 (5.8%) patients (P

Previous studies showed that the COpper Metabolism gene MURR1 Domain (COMMD) family of proteins was abnormally expressed in hepatocellular carcinoma (HCC). This study aimed to explore the roles of COMMD1 and COMMD7 in regulating nuclear factor κB (NF-κB) signaling in HCC stem cells (HCSCs). In vivo, the expression of COMMD7 and COMMD1 was determined in 35 pairs of HCC cancer tissues and adjacent tissues, and the effect of COMMD7 silencing on xenograft tumor growth was evaluated. In vitro, the effects of COMMD7 silencing and COMMD1 overexpression on HCSC function were assessed. Results found that the expression levels of COMMD7 were higher, whereas COMMD1 levels were lower in HCC tissues and HCSCs. COMMD7 silencing or COMMD1 overexpression inhibited cell proliferation, migration, and invasion through suppression of NF-κB p65. Furthermore, COMMD7 positively regulated NF-κB by upregulating protein inhibitor for activated stat 4 (PIAS4). This study demonstrates that COMMD7 has a dual regulatory role in the NF-κB signaling pathway in Nanog+ HCSCs. Keywords: hepatocellular carcinoma, cancer stem cells, tumorigenicity

Observational data on dry matter accumulation (DMA) and dry matter partitioning (DMP) from the experiment of maize sown on four different dates in a normal year (2012) and three drought years (2014, 2015, 2018) were analyzed to assess the impact of drought and the sowing date on DMA and DMP in different above-ground organs. The phenology of maize was more closely related to the sowing date than to drought. In the normal year, the amount of dry matter in different organs differed slightly among sowing dates, except for those at maturity, and increased linearly after jointing: the dry matter of leaves and stalks increased rapidly before tasselling and the milk stage, respectively, and both increased slowly thereafter, whereas the dry matter of the ears increased linearly. In the drought years, DMA was more sensitive to precipitation relative to the normal year and was affected by the sowing date and drought. Specifically, drought lowered the dry matter of the above-ground organs to varying degrees and accentuated that variation in crops sown on different dates. From the view of DMP, a mild drought lowers the stalk DMP rate but increases the rate in ears. The more severe the drought, the smaller the DMP rate in ears and the stronger the inhibition of the transfer of dry matter from stalk to ears, as well as the more significant difference in the DMP pattern among the sowing dates. High temperatures and drought had a significant synergistic effect on DMAs in all the organs relative to that of drought alone, reversely having an inappreciable impact on the DMP pattern. During the three growth periods, namely jointing to tasselling, tasselling to the milk stage, and the milk stage to maturity, DMA during any two adjacent periods had a clear complementary effect, especially before and after tasselling. Dry matters of the above-ground parts in aggregate, of the stalk and of the ears, at the milk and maturity stages were negatively correlated to the degree of drought, and the maximum correlation was for the ears.

Determining the effects of progressive drought (PD) on dry matter production, partitioning, and grain yield of maize will help in designing a suitable strategy for water management. Though influences of drought on maize growth and development have been investigated extensively, few of them focused on the effects of different duration and occurrence stage of PD on yield formation of maize. Six variations of PD, in the form of withholding irrigation for varying lengths of time from jointing or tasselling, were tested in the field, using a mobile rain shelter, in terms of their effects on aboveground biomass accumulation, partitioning, and grain yield in 2015-2016. The results showed that grain yield was significantly reduced by PD during either vegetative or reproductive stage, and the reduction in grain yield from reproductive PD (41.6-46.6%) was greater than that from vegetative PD (18.6-26.2%). The decrease in grain yield was largely caused by the decrease in kernels per ear (r2 = 0.88, P < 0.001). This research implied that guaranteeing water supply for maize during reproductive stage is crucially important to avoid the reduction in kernels per ear and grain yield.

Objectives: Computed tomography should be performed after careful consideration due to radiation hazard, which is why interest in low dose CT has increased recently in acute appendicitis. Previous studies have been performed in adult and adolescents populations, but no studies have reported on the efficacy of using low‐dose CT in children younger than 10 years. Methods: Patients (n = 475) younger than 10 years who were examined for acute appendicitis were recruited. Subjects were divided into three groups according to the examinations performed: low‐dose CT, ultrasonography, and standard‐dose CT. Subjects were categorized according to age and body mass index (BMI). Results: Low‐dose CT was a contributive tool in diagnosing appendicitis, and it was an adequate method, when compared with ultrasonography and standard‐dose CT in terms of sensitivity (95.5% vs. 95.0% and 94.5%, p = 0.794), specificity (94.9% vs. 80.0% and 98.8%, p = 0.024), positive‐predictive value (96.4% vs. 92.7% and 97.2%, p = 0.019), and negative‐predictive value (93.7% vs. 85.7% and 91.3%, p = 0.890). Low‐dose CT accurately diagnosed patients with a perforated appendix. Acute appendicitis was effectively diagnosed using low‐dose CT in both early and middle childhood. BMI did not influence the accuracy of detecting acute appendicitis on low‐dose CT. Conclusion: Low‐dose CT is effective and accurate for diagnosing acute appendicitis in childhood, as well as in adolescents and young adults. Additionally, low‐dose CT was relatively accurate, irrespective of age or BMI, for detecting acute appendicitis. Therefore, low‐dose CT is recommended for assessing children with suspected acute appendicitis.

Northeast China (NEC) is a region sensitive to climate change. However, the adoption of long-season maize cultivars in NEC has caused a substantial yield increase under climate change conditions. It is important to determine whether such cultivar adoptions are effective throughout the whole NEC to sustainably increase grain yield. In this study, phenological observations and meteorological data at six sites from 1981 to 2018 were used to detect thermal time (TT) trends during the maize growing period. TT, as a parameter for measuring changes in maize cultivars, was used in the crop simulation model CERES-Maize to examine the variations in maize yield produced with different cultivar × climate combinations in different decades. In NEC, both TTs from emergence to anthesis and from anthesis to physiological maturity showed significant increasing trends from 1981 to 2018. Simulation results for humid areas revealed that adopting longer-season cultivars during 2000–2018 caused yield increases, ranging from 6.3% to 13.3%, compared with the 1980s. However, for stations in semi-humid areas, maize grain yield showed a decrease or a small increase (from −12.7% to 8.0%) when longer-season cultivars were adopted during 2000–2018. For semi-humid areas, decreasing trends in the ratios of rainfed yield to no water-stress yield (Yrainfed/Yno water-stress) and lower Yrainfed/Yno water-stress values during 2000–2018 indicated a growing sensitivity of maize production to water, which was attributed to changes in TT and precipitation. Our results indicate that, for the semi-humid area, maize yield was limited by water after introducing cultivars with higher TT requirement under climate change conditions. Therefore, securing food supplies will depend on increases in water-use efficiency levels and other adaptive strategies, such as varietal diversification, drought-resistant varieties, conservation tillage and irrigation.

Background: Patent ductus arteriosus (PDA) ligation is usually performed by congenital cardiac surgeons. However, due to the uneven distribution of congenital cardiac surgeons in South Korea, many institutions depend solely on adult cardiac surgeons for congenital cardiac diseases. We report the outcomes of PDA ligations performed by adult cardiac surgeons at our institution. Methods: The electronic medical records of 852 neonates at Chung-Ang University Hospital, Seoul, South Korea from November 2010 to May 2014 were reviewed to identify patients with PDA. Results: Of the 111 neonates with a diagnosis of PDA, 26 (23%) underwent PDA ligation. PDAs were ligated within 28 days of birth (mean, 14.5±7.8 days), and the mean gestational age of these patients was 30.3±4.6 weeks (range, 26 to 40 weeks) with a mean birth weight of 1,292.5±703.5 g (range, 480 to 3,020 g). No residual shunts through the PDA were found on postoperative echocardiography. There was 1 case of 30-day mortality (3.8%) due to pneumonia, and 6 cases of in-hospital mortality (23.1%) after 30 days, which is comparable to results from other centers with congenital cardiac surgery programs. Conclusion: Although our outcomes may not be generalizable to all hospital settings without a congenital cardiac surgery program, in select centers, PDA ligations can be performed safely by adult cardiac surgeons if no congenital cardiac surgery program is available.

Abstract Background Hepatitis B virus (HBV) infection is the most common cause of liver disease in endemic areas such as South Korea. After HBV vaccination, hepatitis B surface antibody (HBsAb) titers gradually decrease. Trends in HBsAb titers have not been evaluated among children in South Korea over the past decade. Methods We screened 6155 patients (aged 7 months to 17 years) who underwent HBV antigen/antibody testing at Chung-Ang University Hospital from May 2012 to April 2015. Titer criteria were defined as follows: positive, titer ≥100 IU/L; weakly positive, titer 10–99 IU/L; and negative, titer

The aim of present study was to check the possible association of potential parental environmental exposures and maternal supplementation intake with the risk of nonsyndromic orofacial clefting (NSOC). A retrospective study comprised 499 cases and 480 controls was conducted in Heilongjiang Province. Chi-square analysis and unconditional multiple logistic regression were used in the study. The results showed that maternal history of fever and the common cold without fever (ORCL/P = 3.11 and 5.56, 95%CI: 1.67–5.82 and 2.96–10.47, ORCPO = 3.31 and 8.23, 95%CI: 1.58–6.94 and 4.08–16.95), paternal smoking and alcohol consumption (ORCL/P = 2.15 and 5.04, 95%CI: 1.37–3.38 and 3.00–8.46, ORCPO = 1.82 and 4.40, 95%CI: 1.06–3.13 and 2.50–7.74), maternal exposure to organic solvents, heavy metals, or pesticides (ORCL/P = 6.07, 5.67 and 5.97, 95%CI: 1.49–24.76, 1.34–24.09 and 2.10–16.98, ORCPO = 10.65, 7.28 and 3.48, 95%CI: 2.54–44.67, 1.41–37.63 and 1.06–11.46) and multivitamin use during the preconception period (ORCL/P = 0.06, 95%CI: 0.02–0.23, ORCPO = 0.06, 95%CI: 0.01–0.30) were associated with cleft lip or without cleft palate (CL/P) and cleft palate only (CPO). Maternal history of skin disease and negative life events (ORCL/P = 12.07 and 1.67, 95%CI: 1.81–80.05 and 1.95–2.67) were associated with CL/P. Some potential parental hazardous exposures during the periconception period and maternal use of multivitamins during the preconception period were associated with risk of NSOC.

PurposeThe aim of this study was to investigate the potential effects of mild hypoxia in the mature and immature brain.MethodsWe prepared organotypic slice cultures of the hippocampus and used hippocampal tissue cultures at 7 and 14 days in vitro (DIV) to represent the immature and mature brain, respectively. Tissue cultures were exposed to 10% oxygen for 60 minutes. Twenty-four hours after this hypoxic insult, propidium iodide fluorescence images were obtained, and the damaged areas in the cornu ammonis 1 (CA1), CA3, and dentate gyrus (DG) were measured using image analysis.ResultsIn the 7-DIV group compared to control tissue, hypoxia-exposed tissue showed decreased damage in two regions (CA1: 5.59%±2.99% vs. 4.80%±1.37%, P=0.900; DG: 33.88%±12.53% vs. 15.98%±2.37%, P=0.166), but this decrease was not statistically significant. In the 14-DIV group, hypoxia-exposed tissue showed decreased damage compared to control tissues; this decrease was not significant in the CA3 (24.51%±6.05% vs. 18.31%±3.28%, P=0.373) or DG (15.72%±3.47% vs. 9.91%±2.11%, P=0.134), but was significant in the CA1 (50.91%±5.90% vs. 32.30%±3.34%, P=0.004).ConclusionAlthough only CA1 tissues cultured for 14 DIV showed significantly less damage after exposure to hypoxia, the other tissues examined in this study showed a tendency towards less damage after hypoxic exposure. Therefore, mild hypoxia might play a protective role in the brain.

PurposeThis study evaluated the extent of damage due to hypothermia in the mature and immature brain.MethodsHippocampal tissue cultures at 7 and 14 days in vitro (DIV) were used to represent the immature and mature brain, respectively. The cultures were exposed at 25℃ for 0, 10, 30, and 60 minutes (n=30 in each subgroup). Propidium iodide fluorescent images were captured 24 and 48 hours after hypothermic injury. Damaged areas of the cornu ammonis 1 (CA1), CA3, and dentate gyrus (DG) were measured using image analysis.ResultsAt 7 DIV, the tissues exposed to cold injury for 60 minutes showed increased damage in CA1 (P

Abstract Tailgut cysts are congenital lesions found in the presacral space. These have been mainly identified in adults and are rare in children, especially neonates. Here, we present the case of a neonate with a presacral cystic mass detected by prenatal ultrasonography that was diagnosed as a tailgut cyst after postnatal surgical removal. When a presacral cyst is encountered, tailgut cyst should be considered in the differential diagnosis.

Roots are an important water transport pathway between soil and plant. Root water uptake (RWU) plays a key role in water and heat exchange between plants and the atmosphere. Inaccurate RWU schemes in land surface models are one crucial reason for decreased model performance. Despite some types of RWU functions being adopted in land surface models, none have been certified as suitable for maize farmland ecosystems. Based on 2007–2009 data observed at the maize agroecosystem field station in Jinzhou, China, the RWU function and root distribution (RD) in the Common Land Model (CoLM) were optimized and the effects of the optimizations on model performance were compared. Results showed that RD parameters calculated with root length density were more practical relative to root biomass in reflecting soil water availability, and they improved the simulation accuracy for water and heat fluxes. The modified RWU function also played a significant role in optimizing the simulation of water and heat fluxes. Similarly, the respective and integrated roles of two optimization schemes in improving CoLM performance were significant during continuous non-precipitation days, especially during the key water requirement period of maize. Notably, the improvements were restrained within a threshold of soil water content, and the optimizations were inoperative outside this threshold. Thus, the optimized RWU function and the revised RD introduced into the CoLM model are applicable for simulation of water and heat fluxes for maize farmland ecosystems in arid areas.

An education equity mindset is fundamental to assuring all students are supported to achieve to their highest capacity. We have identified six attributes of an educational equity mindset critical to assuring teachers' practices and professional choices are aligned with meeting the needs of all students. In an effort to promote education equity mindset among teachers we determined there was a need to first empirically document the construct. We surveyed 452 teachers in the southern region of the United States. Our results indicate that we effectively measured our definition of education equity mindset. We found multiple differences in the mindset attributes based on personal and professional variables. Our data indicate that teachers may hold competing or fragmented mindsets. Our research uncovered multiple needed lines of research and implications for teacher preparation and professional development.

In this meta-analysis, we examined the effect of distance clinical supervision in comparison with traditional face-to-face supervision in conformity with the guidelines offered by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We analyzed empirical studies (i.e., three journal articles and one dissertation) on clinical supervision published between 2000 and 2018. Analyses determined the overall effect sizes of supervision by format (i.e., distance vs. face-to-face) and compared the effect sizes of distance vs. face-to-face supervision, specifically, by supervisee satisfaction, supervisory alliance, and supervisee competency. Results indicated that the overall effect sizes of supervision, as well as the effect sizes for the three variables, did not significantly differ by format. Implications of non-significant difference in the effect sizes by different formats of clinical supervision (distance vs. face-to-face) are discussed.

Purpose: Human breast milk (HBM) contains immune components that produced and delivered from the mother along with nutrients necessary for the baby. MicroRNA (miRNA) is a small noncoding RNA molecule, that is used as an ideal biomarker for diagnosis and prognosis of various diseases and are more abundant in HBM. We analyzed and compared the immune components and miRNAs of HBM. Methods: HBM were collected from 20 healthy breastfeeding mothers. We measured the amount of lactoferrin, lysozyme, and immunoglobulin A (IgA) and extracted the miRNAs from each breast milk samples. Next, the top 5 and bottom 5 expressed miRNAs were compared and analyzed based on the amounts of the 3 immune components. Results: The mean levels and ranges of lactoferrin, lysozyme, and IgA were 6.33 (2.24-14.77)x106 ng/mL, 9.90 (1.42-17.59)x107 pg/mL, and 6.64 (0.48-20.01)x105 ng/mL, respectively. The miRNAs concentration per 1 mL of skim milk was 40.54 (14.95-110.01) ng/μL. Comparing the bottom 5 and top 5 groups of each immune component, 19 miRNAs were significantly upregulated (6, 9, and 4 targeting lactoferrin, lysozyme, and IgA, respectively) and 21 were significantly downregulated (4, 9, and 8 targeting lactoferrin, lysozyme, and IgA, respectively). There were no miRNAs that were expressed significantly higher or lower in common to all 3 components. However, 2 and 3 miRNAs were commonly overexpressed and underexpressed, in the top 5 groups of lysozyme and IgA concentrations. Conclusion: We identified the immune components and miRNAs in breast milk and found that each individual has different ingredients. [ABSTRACT FROM AUTHOR]