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Identification of optimal target antigens that distinguish cancer cells from normal surrounding tissue cells remains a key challenge in chimeric antigen receptor (CAR) cell therapy for tumors with intratumoral heterogeneity. In this study, we dissected tissue complexity to the level of individual cells through the construction of a single-cell expression atlas that integrates ~1.4 million tumor, tumor-infiltrating normal and reference normal cells from 412 tumors and 12 normal organs. We used a two-step screening method using random forest and convolutional neural networks to select gene pairs that contribute most to discrimination between individual malignant and normal cells. Tumor coverage and specificity are evaluated for the AND, OR and NOT logic gates based on the combinatorial expression pattern of the pairing genes across individual single cells. Single-cell transcriptome-coupled epitope profiling validates the AND, OR and NOT switch targets identified in ovarian cancer and colorectal cancer. CAR-T targets are identified using logic gates and single-cell expression data. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the incidence and risk of pancreatic cancer (PC) in pancreatitis. We identified patients with acute pancreatitis (AP) (n = 225,811, 50.0%) and chronic pancreatitis (CP) (n = 225,685, 50.0%) from Korean population-based data and matched them with age- and sex-matched controls (n = 4,514,960). We analyzed the incidence and adjusted hazard ratios (aHRs) of PC among patients followed for more than 2 years or 5 years, and assessed risk changes over time in single episode of AP (SAP), recurrent AP (RAP), CP with AP, and CP without AP groups. We also performed subgroup analysis for both sexes. The incidences (per 104 person-years) and risks (aHR) of PC were higher in the RAP (12.69, 5.00) or CP with AP (12.12, 5.74) groups compared to the SAP (2.31, 1.32) or CP without AP (2.28, 1.57) groups. The risks of PC decreased over time, however, the risk of PC remained elevated in the RAP and CP with AP groups for more than 8 years. Females with RAP, SAP, and CP with AP had higher risks of PC than males. The risk of PC is higher and persists for longer duration in patients with RAP and CP with AP compared to those with SAP or CP without AP. [ABSTRACT FROM AUTHOR]

Treatment for hair loss is largely limited, and any beneficial effects are often transient. Based on the critical role of the FGF5 isoform, FGF5s, in the hair growth cycle, it may be a good therapeutic candidate for the prevention of hair loss, as well as the promotion of hair growth. To investigate its potential use for hair growth, a mutant form of the FGF5s protein (FGF5sC93S) was generated, expressed, and purified. The FGF5sC93S mutant was able to antagonize FGF5‐induced mitogenic activity, which normally triggers the conversion of hair follicles from the anagen phase to the catagen phase. In addition, the FGF5sC93S mutant efficiently suppressed gene expression induced by FGF5 both human outer root sheath (hORS) and human dermal papilla (hDP) cells. Administration of FGF5sC93S proteins onto the scalps of human subjects significantly increased the total number of hairs at 24 weeks. Together, our data demonstrate that a mutant form of the FGF5s protein could be used as a potential hair promoting agent. [ABSTRACT FROM AUTHOR]

• Spastic ataxia caused by various neurological conditions and different genes. • The diagnostic clues of SPG11 is MRI images such as thin corpus callosum and "ears of the lynx" sign. • We experienced the patient who showed similar features of MLD but later diagnosed as SPG11. [ABSTRACT FROM AUTHOR]

Genome-wide association studies of gastric cancer (GC) cases have revealed common gastric cancer susceptibility loci with low effect size. We investigated rare variants with high effect size via whole-exome sequencing (WES) of subjects with familial clustering of gastric cancer. WES of DNAs from the blood of 19 gastric cancer patients and 36 unaffected family members from 14 families with two or more gastric cancer patients were tested. Linkage analysis combined with association tests were performed using Pedigree Variant Annotation, Analysis, and Search Tool (pVAAST) software. Based on the logarithm of odds (LOD) and permutation-based composite likelihood ratio test (CLRT) from pVAAST, MUC4 was identified as a predisposing gene (LOD P-value = 1.9×10−5; permutation-based P-value of CLRT ≤ 9.9×10−9). In a larger cohort consisting of 597 GC patients and 9,759 healthy controls genotyped with SNP array, we discovered common variants in MUC4 regions (rs148735556, rs11717039, and rs547775645) significantly associated with GC supporting the association of MUC4 with gastric cancer. And the MUC4 variants were found in higher frequency in The Cancer Genome Atlas Study (TCGA) germline samples of patients with multiple cancer types. Immunohistochemistry indicated that MUC4 was downregulated in the noncancerous gastric mucosa of subjects with MUC4 germline missense variants, suggesting that loss of the protective function of MUC4 predisposes an individual to gastric cancer. Rare variants in MUC4 can be novel gastric cancer susceptibility loci in Koreans possessing the familial clustering of gastric cancer. [ABSTRACT FROM AUTHOR]

CHARGE syndrome has a clinically broad spectrum of phenotypes, including partial or atypical type. CHD7 mutation is related to CHARGE syndrome that shows various phenotypes according to the CHD7 variant. Developments in genetic analysis techniques, such as next-generation sequencing (NGS), are helping both diagnosis and treatment of diseases. We report the case of a preterm infant diagnosed with atypical CHARGE who has a novel and de novo CHD7 variant that was identified using whole-genome sequencing (WGS). Neonatologists tend to be reluctant to diagnose infants with multiple malformations because they have to focus on treating life-threatening complications; however, NGS is considered helpful for the early diagnosis of broad-spectrum anomalies during the neonatal period. [ABSTRACT FROM AUTHOR]

Background: Treatments for inflammatory bowel diseases (IBD) have evolved in the era of biologics. However, the real-world data on their usage patterns and sequencing are still limited. Objectives: We aimed to investigate treatment persistence and dose intensification of first- and second-line biologics in patients with IBD. Design: In this retrospective, cohort study using nationwide claims data, 13,087 patients with IBD initiating biologic therapy between 2010 and 2020 were identified. Methods: Treatment persistence and dose intensification during the first 2 years and switching patterns of biologics were analysed while identifying predictors of non-persistence. Results: As a first-line treatment of Crohn's disease (CD), ustekinumab had a lower risk for non-persistence compared to infliximab [adjusted hazard ratio (aHR), 0.69, p = 0.048]. Second-line ustekinumab and vedolizumab showed the highest and lowest persistence (79.2% and 54.9%), respectively. As a first-line treatment of ulcerative colitis (UC), golimumab had a higher risk for non-persistence compared to infliximab (aHR, 1.68, p < 0.001). Second-line golimumab also showed a significantly lower persistence rate than adalimumab and vedolizumab. The risk of non-persistence was higher in UC than in CD (first line: aHR, 1.97; second line: aHR, 1.39; p < 0.001), and in the second-line treatment than in the first-line treatment for CD (aHR, 1.55; p < 0.001). The cumulative rate of dose intensification was highest with ustekinumab for CD (first line, 43.3%, second line, 69.1%) and adalimumab for second-line UC (40.7%). It was significantly increased in second-line therapy in CD, but not in UC. Among switchers of first-line anti-tumour necrosis factor-α inhibitor therapy, after all biologics were approved, 69% of CD patients and 78.4% of UC patients switched to other classes of second-line treatment. Conclusion: Ustekinumab had higher persistence in the first-line treatment of CD, while golimumab had lower persistence for first- and second-line treatments of UC. Dose intensification rates varied, with the highest cumulative rates observed for ustekinumab in CD and adalimumab in second-line UC. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the effects of oxiracetam on cognitive impairment in the early phase of traumatic brain injury (TBI), for which no specific treatment is currently available. Methods: The in vitro study used a cell injury controller to damage SH-SY5Y cells and evaluate the effect of oxiracetam at a dosage of 100 nM. The in vivo study used a stereotaxic impactor to induce a TBI model in C57BL/6 J mice and analyzed immunohistochemical changes and cognitive function after an intraperitoneal injection of oxiracetam (30 mg/kg/day) for 5 days. The number of mice used in this study was 60. They were divided into three groups (sham, TBI, and TBI with oxiracetam treatment) (20 mice in each group). Results: The in vitro study showed that oxiracetam treatment resulted in increased superoxide dismutase (SOD)1 and SOD2 mRNA expression. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and interleukin (IL)-1 β were decreased after oxiracetam treatment, along with decreases in intracellular reactive oxygen species production and apoptotic effects. TBI mice treated with oxiracetam exhibited the loss of fewer cortical damaged lesions, less brain edema, and fewer Fluoro-Jade B (FJB)-positive and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-positive cells compared to those without oxiracetam treatment. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and IL-1β were decreased significantly after oxiracetam treatment. These inflammation-related markers, which colocalized with Iba-1-positive or GFAP-positive cells after TBI, were also decreased after oxiracetam treatment. TBI mice treated with oxiracetam had a smaller decrease in preference and more latency time than those not treated with oxiracetam, suggesting the amelioration of impaired cognitive impairment. Conclusions: Oxiracetam may be helpful in restoring cognitive impairment by ameliorating neuroinflammation in the early phase of TBI. [ABSTRACT FROM AUTHOR]

Background: Although adequate management of postoperative pain with oral analgesics is an important aspect of surgical procedures, inadvertent overprescribing can lead to excess availability of opioids in the community for potential diversion. The purpose of our study was to prospectively evaluate opioid consumption following outpatient upper-extremity surgical procedures to determine opioid utilization patterns and to develop prescribing guidelines.Methods: All patients undergoing outpatient upper-extremity surgical procedures over a consecutive 6-month period had the following prospective data collected: patient demographic characteristics, surgical details, anesthesia type, and opioid prescription and consumption patterns. Analysis of variance and post hoc comparisons were performed using t tests, with the p value for multiple pairwise tests adjusted by the Bonferroni correction.Results: A total of 1,416 patients with a mean age of 56 years (range, 18 to 93 years) were included in the study. Surgeons prescribed a mean total of 24 pills, and patients reported consuming a mean total of 8.1 pills, resulting in a utilization rate of 34%. Patients undergoing soft-tissue procedures reported requiring fewer opioids (5.1 pills for 2.2 days) compared with fracture surgical procedures (13.0 pills for 4.5 days) or joint procedures (14.5 pills for 5.0 days) (p < 0.001). Patients who underwent wrist surgical procedures required a mean number of 7.5 pills for 3.1 days and those who underwent hand surgical procedures required a mean number of 7.7 pills for 2.9 days, compared with patients who underwent forearm or elbow surgical procedures (11.1 pills) and those who underwent upper arm or shoulder surgical procedures (22.0 pills) (p < 0.01). Procedure type, anatomic location, anesthesia type, age, and type of insurance were also all significantly associated with reported opioid consumption (p < 0.001).Conclusions: In this large, prospective evaluation of postoperative opioid consumption, we found that patients are being prescribed approximately 3 times greater opioid medications than needed following upper-extremity surgical procedures. We have provided general prescribing guidelines, and we recommend that surgeons carefully examine their patients' opioid utilization and consider customizing their opioid prescriptions on the basis of anatomic location and procedure type to prescribe the optimal amount of opioids while avoiding dissemination of excess opioids. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the effect of DA-9701, a novel prokinetic drug, on gastric motility evaluated by magnetic resonance imaging in patients with Parkinson's disease (PD).Methods: Forty PD patients were randomly allocated to receive either domperidone or DA-9701. Their gastric functions were evaluated using magnetic resonance imaging before and after 4-week treatment period. Information on levodopa daily dose, disease duration, and Unified PD Rating Scale scores was collected. In 18 patients (domperidone: 9, DA-9701: 9), plasma levodopa concentrations were determined. Primary outcome was assessed by a one-sided 95% confidence interval to show non-inferiority of DA-9701 vs. domperidone with a pre-determined non-inferiority margin of -10%.Results: Thirty-eight participants (19 men and 19 women; mean age, 67.1 years) completed the study protocol (domperidone: DA-9701 = 19:19). Gastric emptying rate at 120 min (2-hr GER) was comparable between the 2 groups; it was not correlated with levodopa daily dose or disease duration or Unified PD Rating Scale scores (all p > 0.05). DA-9701 was not inferior to domperidone in changes of 2-hr GERs before and after the treatment (absolute difference, 4.0 %; one-sided 95% confidence interval, - 3.7 to infinity). However, a significant increase in 2-hr GER was observed only in DA-9701 group (54.5% and 61.8%, before and after treatment, respectively, p < 0.05). Plasma levodopa concentration showed an insignificant but increasing trend in DA-9701 group. There were neither adverse reactions nor deteriorations of parkinsonian symptoms observed in the study participants.Conclusion: DA-9701 can be used for the patients with PD to enhance gastric motility without aggravating PD symptoms (ClinicalTrials.gov number: NCT03022201). [ABSTRACT FROM AUTHOR]

Background: In Alzheimer's disease (AD) brain, neuronal polarity and synaptic connectivity are compromised. A key structure for regulating polarity and functions of neurons is the axon initial segment (AIS), which segregates somatodendritic from axonal proteins and initiates action potentials. Toxic tau species, including extracellular oligomers (xcTauOs), spread tau pathology from neuron to neuron by a prion-like process, but few other cell biological effects of xcTauOs have been described. Objective: Test the hypothesis that AIS structure is sensitive to xcTauOs. Methods: Cultured wild type (WT) and tau knockout (KO) mouse cortical neurons were exposed to xcTauOs, and quantitative western blotting and immunofluorescence microscopy with anti-TRIM46 monitored effects on the AIS. The same methods were used to compare TRIM46 and two other resident AIS proteins in human hippocampal tissue obtained from AD and age-matched non-AD donors. Results: Without affecting total TRIM46 levels, xcTauOs reduce the concentration of TRIM46 within the AIS and cause AIS shortening in cultured WT, but not TKO neurons. Lentiviral-driven tau expression in tau KO neurons rescues AIS length sensitivity to xcTauOs. In human AD hippocampus, the overall protein levels of multiple resident AIS proteins are unchanged compared to non-AD brain, but TRIM46 concentration within the AIS and AIS length are reduced in neurons containing neurofibrillary tangles. Conclusion: xcTauOs cause partial AIS damage in cultured neurons by a mechanism dependent on intracellular tau, thereby raising the possibility that the observed AIS reduction in AD neurons in vivo is caused by xcTauOs working in concert with endogenous neuronal tau. [ABSTRACT FROM AUTHOR]

Background Amoxicillin (Amx) is one of the most important antibiotics for eradication of Helicobacter pylori ( H. pylori). Main determinants of genetically stable Amx resistance are mutations in the C-terminus of penicillin-binding protein 1A ( pbp1A). However, contribution of individual mutation remains unclear. Methods 77 Amx-resistant (AmxR) and 77 Amx-susceptible (AmxS) H. pylori strains were isolated from gastric tissues, and DNA sequencing was performed to compare C-terminus sequences of pbp1A gene between AmxR and AmxS strains. Natural transformation of these mutated genes into amoxicillin-susceptible strains was performed. Results Among many mutations in pbp1A, D479E ( OR: 37.4, 95% CI: 5.53-252.49, P < .001), and T593 mutation ( OR: 32.0, 95% CI: 4.04-252.86, P < .001) independently contributed to Amx resistance in H. pylori strains. In the transformation experiment, T593 mutations were identified in their transformants showing Amx resistance. However, PCR product of D479E was not inserted into recipient ( ATCC 43504) resulting in transformation failure. Conclusion Amx resistance is associated with various substitutions in pbp1A and T593 mutation contributes to Amx resistance of H. pylori. [ABSTRACT FROM AUTHOR]

We performed targeted re-sequencing to identify the genetic etiology of early-onset postlingual deafness and encountered a frequent TMPRSS3 allele harboring two variants in a cis configuration. We aimed to evaluate the pathogenicity of the allele. Among 88 cochlear implantees with autosomal recessive non-syndromic hearing loss, subjects with GJB2 and SLC26A4 mutations were excluded. Thirty-one probands manifesting early-onset postlingual deafness were sorted. Through targeted re-sequencing, we detected two families with a TMPRSS3 mutant allele containing p.V116M and p.V291L in a cis configuration, p.[p.V116M; p.V291L]. A minor allele frequency was calculated and proteolytic activity was measured. A p.[p.V116M; p.V291L] allele demonstrated a significantly higher frequency compared to normal controls and merited attention due to its high frequency (4.84%, 3/62). The first family showed a novel deleterious splice site variant--c.783-1G>A--in a trans allele, while the other showed homozygosity. The progression to deafness was noted within the first decade, suggesting DFNB10. The proteolytic activity was significantly reduced, confirming the severe pathogenicity. This frequent mutant allele significantly contributes to early-onset postlingual deafness in Koreans. For clinical implication and proper auditory rehabilitation, it is important to pay attention to this allele with a severe pathogenic potential. [ABSTRACT FROM AUTHOR]

Thermally excited ferromagnetic resonance (TEFMR) in a spin valve head gives rise to mag-noise while its power spectral density directly reflects the magnetic field distribution in the sensing layer as well as the corresponding micromagnetic states. In this article, we report an experimental study on utilization of TEFMR spectral characteristics for spin valve head diagnosis and characterization. The study suggests that the variation of the micromagnetic states in the PM layer at the junctions is one of the most important factors causing the head-to-head variations of the recording performance, especially the heads from the same wafer. [ABSTRACT FROM AUTHOR]

Background: Severe to profound sensorineural hearing loss (SNHL) requires cochlear implantation (CI) for auditory rehabilitation. Etiologic diagnoses can contribute to candidacy selection and decision-making regarding the timing of successful CI. However, few studies have been performed to address the etiologic spectrum of severe SNHL in the population where there is no consanguineous marriage and the majority of SNHL cases are sporadic in small sized families. The authors sought to comprehensively understand the etiologies of Korean cochlear implantees by incorporating the targeted resequencing of 204 candidate deafness genes (TRS-204) and a phenotype-driven candidate gene approach.Methods: Ninety-three that consented to molecular genetic testing and underwent at least one molecular genetic test were included. Patients with a characteristic Phenotypic marker were subject to Sanger sequencing to detect variants in corresponding candidate genes. The rest of patients without any prominent phenotype were tested on GJB2. Next, TRS-204 was applied in GJB2-negative cases without any phenotypic marker. In addition, the sibling recurrence-risk of SNHL among families with non-diagnostic genotypes after TRS-204 was performed to gain insight of etiologies in non-diagnostic cases.Results: Overall, we could find causative variants in 51 (54.8%) of the 93 cochlear implantees. Thirty (32.3%) probands could be diagnosed by direct Sanger sequencing of candidate genes selected by their phenotypes. GJB2 sequencing added 10 subjects to the group with a diagnostic genotype. TRS-204 could detect a causative variant from additional 11 cases (11.8%). We could not detect any pathogenic deletion or duplication on 204 target genes. The sibling recurrence-risk of SNHL among 42 genetically undiagnosed families with 0.03 (1/38) was significantly lower than among genetically diagnosed recessive families with 0.19 (7/37).Conclusion: Despite that the majority of severe or more degree of SNHL occurs sporadically in Koreans, at least 54.8% of such cases that were willing to join the genetic study in the Korean population are monogenic Mendelian disorders with convincing causative variants. This study also indicates that a substantial portion of unsolved cases after applying our current protocol are predicted to have non-genetic or complex etiology rather than a Mendelian genetic disorder involving new genes beyond the 204 target genes. [ABSTRACT FROM AUTHOR]

One-step fabrication method for thin films and shells is developed with nature-derived eggshell membrane hydrolysates (ESMHs) and coffee melanoidins (CMs) that have been discarded as food waste. The nature-derived polymeric materials, ESMHs and CMs, prove highly biocompatible with living cells, and the one-step method enables cytocompatible construction of cell-in-shell nanobiohybrid structures. Nanometric ESMH-CM shells are formed on individual probiotic Lactobacillus acidophilus, without any noticeable decrease in viability, and the ESMH-CM shells effectively protected L. acidophilus in the simulated gastric fluid (SGF). The cytoprotection power is further enhanced by Fe3+-mediated shell augmentation. For example, after 2 h of incubation in SGF, the viability of native L. acidophilus is 30%, whereas nanoencapsulated L. acidophilus, armed with the Fe3+-fortified ESMH-CM shells, show 79% in viability. The simple, time-efficient, and easy-to-process method developed in this work would contribute to many technological developments, including microbial biotherapeutics, as well as waste upcycling. [ABSTRACT FROM AUTHOR]

Background: The increasing trend of antibiotic resistance requires effective second-line Helicobacter pylori (H. pylori) treatment in high prevalence area of H. pylori. The aim of our study was to evaluate the reinfection rate of H. pylori after second-line treatment that would determine the long-term follow up effect of the rescue therapy.Methods: A total of 648 patients who had failed previous H. pylori eradication on standard triple therapy were randomized into two regimens: 1, esomeprazole (20 mg b.i.d), tripotassium dicitrate bismuthate (300 mg q.i.d), metronidazole (500 mg t.i.d), and tetracycline (500 mg q.i.d) (EBMT) or 2, moxifloxacin (400 mg q.d.), esomeprazole (20 mg b.i.d), and amoxicillin (1000 mg b.i.d.) (MEA). At four weeks after completion of eradication therapy, H. pylori tests were performed with 13C urea breath test or invasive tests. In patients who maintained continuous H. pylori negativity for the first year after eradication therapy, H. pylori status was assessed every year. For the evaluation of risk factors of reinfection, gender, age, clinical diagnosis, histological atrophic gastritis or intestinal metaplasia were analyzed.Results: The recrudescence rate of the EBMT was 1.7% and of the MEA group 3.3% (p = 0.67). The annual reinfection rate of H. pylori of EBMT was found to be 4.45% and the MEA group 6.46%. Univariate analysis (Log-rank test) showed no association with any clinical risk factor for reinfection.Conclusions: The long-term reinfection rate of H. pylori stayed low in both of bismuth-containing quadruple therapy and moxifloxacin-based triple therapy; thus reinfection cannot affect the choice of second-line treatment.Trial Registration: Clinical Trial Registration Number NCT01792700. [ABSTRACT FROM AUTHOR]

As the economical and environmental damages due to the accidental oil-spills in marine environment increase gradually, more active countermeasure needs to be developed. In this respect, in the present study, we propose a new design of oil-water separation system and investigate the effects of several geometrical features on the oil-recovery rate, based on a two-dimensional numerical simulation. The working mechanism of current separator is to utilize the density difference between the oil and water, which is strengthened by adding momentum to the oil-water mixture flow through a 'U-shaped' passage. Along the flow passage, we locate additional parts such as baffle plate, weir plate, and water outlet. While optimizing the conditions of these to maximize the oil recovery, it is found that the formation and stable retention of water layer between the water outlet and weir plate is critical to separate and store the above-layered oil. Finally, these findings are further confirmed with a basic experimental test with a three-dimensional oil-water separator model. [ABSTRACT FROM AUTHOR]

Ethyl carbamate (EC) is formed through a reaction between ethanol and either cyanate or N-carbamyl compounds. This study aimed to develop and validate analytical methods for EC determination in nine food matrices: apple juice, soju , milk, corn oil, rice porridge, peanut butter, beef, flat fish, and sea mustard. Differences from AOAC procedure were use of d 5 -EC as internal standard, dilution of alcohol content, removal of lipophilic compounds by hexane, and removal of hydrophilic polysaccharides by gel-forming. Standard curves had a good linearity ( R 2 > 0.997) in all matrices tested. LOD and LOQ were in the range of 0.69–6.08 μg/kg and 2.10–18.43 μg/kg, respectively. Recovery rates ranged from 80.75 to 121.82% for intra-day and ranged from 78.84 to 116.98% for inter-day. The relative standard deviations (RSDs) were below 14%. These results indicate that the established methods can be applied to determine EC in a variety of foods. [ABSTRACT FROM AUTHOR]

Background Little is known about the role of gastric microbiota except for Helicobacter pylori (HP) in human health and disease. We compared the differences of human gastric microbiota according to gastric cancer or control and HP infection status and assessed the role of bacteria other than HP. Methods Gastric microbiota of 63 antral mucosal and 18 corpus mucosal samples were analyzed by bar-coded 454 pyrosequencing of the 16S rRNA gene. Antral samples were divided into four subgroups based on HP positivity in pyrosequencing and the presence of cancer. The analysis was focused on bacteria other than HP, especially nitrosating or nitrate-reducing bacteria (NB). The changes of NB in antral mucosa of 16 subjects were followed up. Results The number of NB other than HP (non-HP-NB) was two times higher in the cancer groups than in the control groups, but it did not reach statistical significance. The number of non-HP-NB tends to increase over time, but this phenomenon was prevented by HP eradication in the HP-positive control group, but not in the HP-positive cancer group. Conclusion We could not find the significant role of bacteria other than HP in the gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Although increased plasma growth differentiation factor-15 (GDF15) levels have been reported in patients with various cancers, the predictive role of PD-1/PD-L1 inhibitors in advanced cancers remains unknown. This study aimed to investigate GDF15 levels as a predictive marker in advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors and analyze their association with immune cell populations. Methods: This study included 87 patients with advanced NSCLC receiving anti-PD-1/PD-L1 inhibitors between March 2018 and May 2020. Blood samples were obtained immediately before and months after PD-1/PD-L1 inhibitor administration. Results: The objective response rate (ORR) was significantly higher in the low GDF15 than in the high GDF15 group (39.2% vs. 15.3%, P = 0.013). The median progression-free survival (PFS) was significantly longer in the low GDF15 than in the high GDF15 group (13.2 [95% CI 7.6–18.9] vs. 7.2 [95% CI 4.8–9.6] months, P = 0.048). Moreover, plasma GDF15 levels negatively correlated with PD-1+/CD8+ T cells (r = − 0.399, P = 0.003) and positively with PD-1+/Treg cells (r = 0.507, P < 0.001) and PD-1+Treg/CD4+ T cells (r = 0.439, P < 0.001). The ORR was significantly higher in the group with decreased GDF15 from baseline than in the increased GDF15 group (37.2% vs. 10.0%, P = 0.026). The median PFS was significantly longer in the decreased GDF15 group (14.8 [95% CI 10.4–19.2] vs. 5.9 [95% CI 2.8–9.0] months, P = 0.002). Plasma GDF15 levels were associated with PD-1+CD8+ T cells and PD-1+ Treg cells. Conclusion: Plasma GDF15 could be a potential biomarker for predicting the efficacy and survival benefit of immunotherapy in advanced NSCLC. [ABSTRACT FROM AUTHOR]

A response by Nayoung Kim and Hyuk Yoon to the letter to the editor on their article in the 2011 issue regarding Helicobacter (H.) pylori-negative gastric cancer incidence rate in South Korean patients is presented.

Over the past two decades, state policy pertaining to school counselors has grown to the point that most states now require the delivery of counseling services. Some states mandate the presence of a school counselor in each school, and several specify required student-to-school counselor ratios. In 2019, New York State instituted regulations requiring the delivery of a comprehensive school counseling program. The purpose of this study was to measure the impact of this mandate on the perceptions of principals, assistant principals, school counselors, and counseling supervisors. This study includes a comparison of these professionals' understanding of the school counselor's role and responsibilities, and school building and district expectations and priorities. Results suggest that a mandate requiring comprehensive school counseling programs fostered more agreement between school counselors and principals than found in previous studies. Implications for practice include state policy as a tool to increase collaboration and opportunities for social capital between school counselors and principals. [ABSTRACT FROM AUTHOR]

Purpose: The effects of anesthetic technique on intermediate-term postoperative adrenocorticotropic hormone (ACTH) functional outcomes have not been fully determined in non-functioning pituitary adenoma (NFPA) patients. Postoperative hypocortisolism is potentially life-threatening and requires steroid replacement after pituitary surgery. The present study determined whether sevoflurane anesthesia was predictive of 3-month postoperative hypocortisolism in NFPA patients with preoperative normal hypothalamic–pituitary–adrenal (HPA) axis. Methods: Demographics, preoperative pituitary hormone status, intraoperative data, and tumor characteristics were retrospectively collected from 429 NFPA patients, who had preoperative normal HPA axis and underwent endoscopic transsphenoidal surgery. Patients were divided into two groups based on intraoperative anesthetic technique: sevoflurane-based inhalation anesthesia group (n = 74) and propofol-based intravenous anesthesia group (n = 355). After propensity score matching, 73 patients were selected in each group and the incidence of 3-month postoperative hypocortisolism (primary outcome measure) was compared between the two groups. Results: The incidence of 3-month postoperative hypocortisolism was higher in the sevoflurane anesthesia group than the propofol anesthesia group before (n = 20[27.0%] vs. n = 49[13.8%], P = 0.008) and after (n = 20 [27.4%] vs. n = 5 [6.8%], P = 0.002) propensity score matching, respectively. Sevoflurane anesthetic use (odds ratio [95% CI] 5.37[1.80–15.98], P = 0.003) and postoperative steroid administration (2.89 [1.06–7.92], P = 0.039) were predictors of 3-month postoperative hypocortisolism. Conclusion: In patients with preoperative normal HPA axis undergoing endoscopic transsphenoidal surgery for NFPA, sevoflurane anesthesia and postoperative steroid administration were associated with the development of 3-month postoperative hypocortisolism. A large-scale prospective study is needed to confirm the negative association between sevoflurane anesthesia and postoperative ACTH functional outcome. [ABSTRACT FROM AUTHOR]

Intratumor heterogeneity within individual cancer tissues underlies the numerous phenotypes of cancer. Tumor subclones ultimately affect therapeutic outcomes due to their distinct molecular features. Drug-resistant subclones are present at a low frequency in tissues at the time of biopsy, but can also arise as a result of acquired somatic mutations. A number of different approaches have been utilized to understand the nature of intratumor heterogeneity. Clonal analysis using whole exome or genome sequencing data can help monitor subclones in the context of tumor progression. Multiregional biopsies permit the molecular characterization of subclones within tumors. Deep sequencing has also provided researchers with the ability to measure the low allele fraction variant within a small number of cells. Ultimately, single-cell sequencing will enable the identification of every minor population within a tumor microenvironment. In the clinical context, the ability to identify and monitor the subclonal architecture of a tumor is valuable for the development of precise cancer therapeutic methods. [ABSTRACT FROM AUTHOR]

Spondyloepimetaphyseal dysplasias (SEMDs) comprise a heterogeneous group of autosomal-dominant and autosomal-recessive disorders. An apparent X-linked recessive (XLR) form of SEMD in a single Italian family was previously reported. We have been able to restudy this family together with a second family from Korea by segregating a severe SEMD in an X-linked pattern. Exome sequencing showed missense mutations in BGN c.439A>G (p.Lys147Glu) in the Korean family and c.776G>T (p.Gly259Val) in the Italian family; the c.439A>G (p.Lys147Glu) mutation was also identified in a further simplex SEMD case from India. Biglycan is an extracellular matrix proteoglycan that can bind transforming growth factor beta (TGF-β) and thus regulate its free concentration. In 3-dimensional simulation, both altered residues localized to the concave arc of leucine-rich repeat domains of biglycan that interact with TGF-β. The observation of recurrent BGN mutations in XLR SEMD individuals from different ethnic backgrounds allows us to define “XLR SEMD, BGN type” as a nosologic entity. [ABSTRACT FROM AUTHOR]

Background: Despite the prevalence of CDH23 mutations in East Asians, its large size hinders investigation. The pathologic mutation p.P240L in CDH23 is common in East Asians. However, whether this mutation represents a common founder or a mutational hot spot is unclear. The prevalence of CDH23 mutations with prelingual severe-to-profound sporadic or autosomal recessive sensorineural hearing loss (arSNHL) is unknown in Koreans. Methods: From September 2010 to October 2014, children with severe-to-profound sporadic or arSNHL without phenotypic markers, and their families, were tested for mutations in connexins GJB2, GJB6 and GJB3. Sanger sequencing of CDH23 p.P240L was performed on connexin-negative samples without enlarged vestibular aqueducts (EVA), followed by targeted resequencing of 129 deafness genes, including CDH23, unless p.P240L homozygotes were detected in the first screening. Four p.P240L-allele-linked STR markers were genotyped in 40 normal-hearing control subjects, and the p.P240L carriers in the hearing-impaired cohort, to identify the haplotypes. Results: Four (3.1 %) of 128 children carried two CDH23 mutant alleles, and SLC26A4 and GJB2 accounted for 18.0 and 17.2 %, respectively. All four children showed profound nonsyndromic SNHL with minimal residual hearing. Interestingly, all had at least one p.P240L mutant allele. Analysis of p.P240L-linked STR markers in these children and other postlingual hearing-impaired adults carrying p.P240L revealed that p.P240L was mainly carried on a single haplotype. Conclusions: p.P240L contributed significantly to Korean pediatric severe arSNHL with a strong founder effect, with implications for future phylogenetic studies. Screening for p.P240L as a first step in GJB2-negative arSNHL Koreans without EVA is recommended. [ABSTRACT FROM AUTHOR]

A new photo-crosslinkable donor polymer, PM6-Br50 facilitates the fabrication of p- PHJ OPDs through LbL deposition of D and A materials overcoming solvent-imposed constraints. The integration of a p- PHJ architecture with a conjugated polyelectrolyte as a hole-transport layer resulted in a significantly reduced dark current, leading to a remarkably high specific detectivity. [Display omitted] • A new polymer donor is synthesized by introduction of photo-crosslinkable side chains. • Layer-by-layer OPDs are fabricated utilizing a photo-crosslinkable polymer donor. • A conjugated polyelectrolyte-based HTL is employed to inhibit electron injection. • A significantly high detectivity is achieved with a suppressed dark current. The effective reduction of dark (or noise) current presents a significant hurdle in enhancing the detectivity of organic photodetectors (OPDs). To address this challenge, a photo-crosslinkable donor polymer, PM6-Br50, is synthesized by introducing bromoalkyl side-chains onto the PM6 structure. This modification enables the formation of a pseudo planar heterojunction (p- PHJ) structure of crosslinked donor/acceptor through a layer-by-layer (LbL) sequential process without the necessity for an semi-orthogonal solvent. This innovation effectively overcomes solvent-related limitations in the LbL process. Additionally, we replace the semi-metallic hole-transport layer (HTL), PEDOT:PSS, with a semiconducting conjugated polyelectrolyte (TPAFS-TMA) with a high conduction band. The p- PHJ configuration, featuring pure donor/anode and pure acceptor/cathode contacts, enhances the charge injection barrier for electrons (holes) from the anode (cathode) in the dark under reverse bias, effectively minimizing dark current. Furthermore, the TPAFS-TMA HTL serves to impede electron injection from the anode. Through the synergistic combination of these two strategies, a significantly reduced dark current density (4.03 × 10−10 A cm−2) is measured by four orders of magnitude, compared to the bulk heterojunction OPDs with PEDOT:PSS. Furthermore, we measure remarkably high shot noise-based and total noise current-based specific detectivities of 4.27 × 1013 and 6.97 × 1012 cm Hz1/2 W−1 (with linear dynamic range of 73.7 dB), respectively. [ABSTRACT FROM AUTHOR]

Background: Gastric adenomas can be successfully treated with endoscopic resection, including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The aim of this study was to evaluate and compare the efficacy of ESD and EMR with circumferential precutting (EMR-P) in the treatment of small gastric adenomas. Methods: This study included 1014 gastric adenomas ≤ 15 mm in diameter treated with ESD or EMR-P from 2012 to 2019, retrospectively. Propensity score matching between the ESD and EMR-P groups (1:1 to 3:1) was performed according to age, sex, tumor size, tumor location (upper, middle, and lower thirds), morphology, and preprocedural histology. The procedure time and the rates of en bloc resection, complete resection, adverse events, and local recurrence were compared between the two groups. Results: After propensity score matching, 478 lesions (ESD: 295, EMR-P: 183) were analyzed. The rates of en bloc resection (94.9% vs. 93.4%, p = 0.498), complete resection (93.6% vs. 90.2%, p = 0.177), bleeding (8.1% vs. 3.8%, p = 0.063), and local recurrence (0.0% vs. 1.4%, p = 0.185) did not significantly differ between the two groups. The procedure time was significantly longer for ESD than for EMR-P (p < 0.001). In the EMR-P group, the complete resection rate was significantly lower in the upper third than in the middle and lower thirds (p < 0.001). Conclusion: EMR-P is as effective as ESD for the treatment of small gastric adenomas. However, the efficacy of EMR-P is lower for gastric adenomas in the proximal stomach. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical resection plus intraoperative radiofrequency ablation showed better survival outcomes than transarterial chemoembolization in selected patients with intermediate-stage hepatocellular carcinoma and Child–Pugh class A liver function. These findings suggest that surgical resection plus intraoperative radiofrequency ablation may provide an opportunity for curative treatment to selected patients deemed eligible only for palliative treatment. The purpose of this study was to compare the efficacy and safety of surgical resection (SR) plus intraoperative radiofrequency ablation (IORFA) with transarterial chemoembolization (TACE) in patients with intermediate-stage HCC and Child–Pugh class A liver function. Treatment-naïve patients who received SR plus IORFA (n = 104) or TACE (n = 513) were retrospectively evaluated. Patients were subjected to a maximum 1:3 propensity score matching (PSM), yielding 95 patients who underwent SR plus IORFA and 252 who underwent TACE. Evaluation of the entire study population showed that progression-free survival (PFS) and overall survival (OS) were significantly better in the SR plus IORFA than in the TACE group. After PSM, the median PFS (18.4 vs. 15.3 months) and OS (88.6 vs. 56.2 months) were significantly longer, and OS rate significantly higher (HR: 0.65, p = 0.026), in the SR plus IORFA group than in the TACE group. Stratified Cox regression analysis and doubly robust estimation revealed that treatment type was significantly associated with both OS and PFS. Rates of major complications were similar in the SR plus IORFA and TACE groups. In conclusion, SR plus IORFA showed better survival outcomes than TACE. SR plus IORFA may provide curative treatment to patients with intermediate-stage HCC with ≤4 tumors and Child–Pugh class A. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the relevance between the pH parameters and baseline impedance level or esophageal hypomotility in patients with suspected gastroesophageal reflux. Method: The recordings of 51 patients with heartburn, acid regurgitation, globus or noncardiac chest pain were analyzed. Evaluation included a 24-h multichannel intraluminal impedance-pH test while on off-proton pump inhibitor therapy over 1 week, high-resolution manometry and Bernstein test. Mean baseline impedance level at the most distal portion of the impedance channel was assessed manually. Esophageal hypomotility was evaluated using transitional zone defect (TZD) and distal break (DB) length measurement. Result: In the study subjects ( n = 51), 6 had a DeMeester score of more than 14.7 and 14 had a positive symptom index. The Bernstein test was positive in ten patients. The baseline impedance level was inversely correlated with the acid exposure time % ( r = −0.660, P < 0.001). Also, all reflux and weakly acid reflux time % measured by impedance monitoring showed a weak correlation with TZD + DB length ( r = 0.327 and 0.324, P = 0.019 and 0.020, respectively). Although a positive Bernstein test has no relevance for the acid exposure time or acid-related symptoms as represented by the DeMeester score or symptom index, the baseline impedance level was significantly lower in patients with a positive Bernstein test than in those with a negative one (2,628.4 ± 862.7 vs. 1,752.2 ± 611.1 Ω, P = 0.004). Conclusion: A lower baseline impedance level is closely related to increased esophageal acid exposure. Hypersensitivity induced by esophageal acid infusion might be attributed to acid-induced mucosal changes of the esophagus. [ABSTRACT FROM AUTHOR]

Background and Aim Dendritic cells ( DCs) are observed on the Helicobacter pylori-infected gastric mucosa. DCs generally play an important role in the regulation of inflammation. Although stimulation of gastric epithelial cells with H. pylori vacuolating cytotoxin ( VacA) has been reported to induce apoptosis and endoplasmic reticulum ( ER) stress, the effects of VacA on the DC apoptotic response have not been well elucidated. This study was conducted to investigate the role of H. pylori VacA on the apoptotic process and ER stress in DCs. Methods Murine and human DCs were generated from specific pathogen-free C57 BL/6 mice and human peripheral blood mononuclear cells, respectively. DCs were incubated with purified VacA, after which Bax activation, cytochrome c release, and DNA fragmentation for apoptosis were measured by fluorescent microscopy, immunoblot, and ELISA. ER stress-related molecules such as GRP78 and CHOP were analyzed by immunoblot. Results Treatment of DCs with purified H. pylori VacA resulted in the induction of apoptosis. DC stimulation with VacA led to the translocation of cytoplasmic Bax to mitochondria and cytochrome c release from mitochondria. H. pylori VacA induced signals for ER stress early during the stimulation process in DCs. Furthermore, suppression of ER stress resulted in a significant inhibition of the VacA-induced apoptosis in DCs. Conclusion These results suggest that ER stress is critical for regulation of DC apoptotic process in response to VacA stimulation. [ABSTRACT FROM AUTHOR]

Background: To evaluate whether the risk of metachronous high-risk colorectal neoplasm (HR-CRN) differs according to the indication for surveillance colonoscopy.Methods: Patients who underwent polypectomy or endoscopic resection of colorectal neoplasms were enrolled and classified into three groups according to the indication for surveillance colonoscopy: advanced colorectal neoplasm (ACRN: adenoma ≥ 10 mm, adenoma with high-degree dysplasia and/or villous component), advanced serrated polyps (ASP: hyperplastic polyp or sessile serrated lesion ≥ 10 mm, traditional serrated polyp), and high-risk polyps (HRP: 3 or more adenomas or serrated polyps). The primary outcome was the development of metachronous HR-CRN, defined as ACRN, ASP, or HRP at the first follow-up colonoscopy.Results: In total, 367 patients were enrolled (ACRN group: N = 264; ASP group: N = 33; HRP group: N = 70). Among the 160 patients who underwent follow-up colonoscopy, 28 (18%) had HR-CRN. In univariable analysis, indication for surveillance colonoscopy was not found to be associated with the development of metachronous HR-CRN. Instead, the total polyp number at index colonoscopy showed a positive association with the risk of metachronous HR-CRN in trend analysis (p = 0.001). In multivariable analysis, the presence of 5 or more polyps at index colonoscopy was found to be associated with the risk of metachronous HR-CRN (OR, 2.575, p = 0.049) after adjusting for risk factors, such as obesity, diabetes, and smoking.Conclusions: The risk of metachronous HR-CRN did not differ according to the main indications for surveillance colonoscopy. The presence of 5 or more polyps at index colonoscopy was the only risk factor for metachronous HR-CRN. [ABSTRACT FROM AUTHOR]

Summary: Faecalibacterium prausnitzii (F. prausnitzii) is one of the most abundant bacteria in the human intestine, with its anti‐inflammatory effects establishing it as a major effector in human intestinal health. However, its extreme sensitivity to oxygen makes its cultivation and physiological study difficult. F. prausnitzii produces butyric acid, which is beneficial to human gut health. Butyric acid is a short‐chain fatty acid (SCFA) produced by the fermentation of carbohydrates, such as dietary fibre in the large bowel. The genes encoding butyryl‐CoA dehydrogenase (BCD) and butyryl‐CoA:acetate CoA transferase (BUT) in F. prausnitzii were cloned and expressed in E. coli to determine the effect of butyric acid production on intestinal health using DSS‐induced colitis model mice. The results from the E. coli Nissle 1917 strain, expressing BCD, BUT, or both, showed that BCD was essential, while BUT was dispensable for producing butyric acid. The effects of different carbon sources, such as glucose, N‐acetylglucosamine (NAG), N‐acetylgalactosamine (NAGA), and inulin, were compared with results showing that the optimal carbon sources for butyric acid production were NAG, a major component of mucin in the human intestine, and glucose. Furthermore, the anti‐inflammatory effects of butyric acid production were tested by administering these strains to DSS‐induced colitis model mice. The oral administration of the E. coli Nissle 1917 strain, carrying the expression vector for BCD and BUT (EcN‐BCD‐BUT), was found to prevent DSS‐induced damage. Introduction of the BCD expression vector into E. coli Nissle 1917 led to increased butyric acid production, which improved the strain's health‐beneficial effects. [ABSTRACT FROM AUTHOR]

Background/Aims Despite numerous studies on the relation of genetic polymorphisms with irritable bowel syndrome (IBS), the results still remain inconclusive. The aim of this study was to assess the possible association between SLC6A4 serotonin transporter gene linked polymorphic region (5-HTTLPR), ADRA2A -1291C>G, GNB3 825C>T, CCK1R intron 779T>C and TRPV1 945G>C polymorphisms and IBS based on Rome III criteria in Korea. Methods Study subjects were prospectively recruited from visitors to Seoul National University Bundang Hospital between July 2009 and January 2014. Ninety-nine IBS patients and 171 healthy controls were enrolled. Polymorphisms of above-mentioned 5 genes were genotyped. Serum serotonin from 101 participants was measured by ELISA and compared according to SLC6A4 5-HTTLPR polymorphisms and IBS subtypes. Results Regarding SLC6A4 5-HTTLPR polymorphism, L/L genotype was significantly associated with the total IBS, constipation predom - inant IBS (IBS-C) and mixture of diarrhea and constipation IBS (IBS-M) (adjusted OR: 4.35, 95% CI: 1.04-16.67; adjusted OR: 11.11, 95% CI: 1.69-50.00 and adjusted OR: 5.56, 95% CI: 1.05-33.33, respectively). Carrying ADRA2A -1291G allele was significantly associated with total IBS and diarrhea predominant IBS (adjusted OR: 3.37, 95% CI: 1.16-9.77 and adjusted OR: 5.64, 95% CI: 1.18-27.01, respectively). IBS-C patients showed reduced level of serum serotonin compared to controls and patients with diarrhea predominant IBS (50.2 ng/mL vs. 69.0 ng/mL and 92.9 ng/mL, P = 0.017 and P = 0.001, respectively). Conclusions Genetic polymorphisms of SLC6A4 5-HTTLPR and ADRA2A -1291C>G could be one of the pathophysiological factors of IBS in Korea. Reduced serum serotonin shown in the IBS-C group suggested a role of serotonin in IBS, but large study is needed for confirming genotypic difference in serum serotonin level. [ABSTRACT FROM AUTHOR]

• The results of two large-scale eye-tracking studies are reported. • A novel variable trailing mask paradigm was used to determine whether amount or location of rereading of NP/Z garden-path sentences was related to offline comprehension. • E1 presented comprehension questions after each sentence, and E2 presented the comprehension questions both before and after each sentence. • Results provide strong evidence (of multiple types) against selective reanalysis of NP/Z garden-paths. When people read temporarily ambiguous ("garden-path") sentences, the forward movement of their eyes is often interrupted by regressions. These regressions are usually followed by rereading some portion of the previously read text. Frazier and Rayner (1982) proposed the Selective Reanalysis Hypothesis (SRH), which proposed that readers regress to critical choice points in the syntactic phrase marker of garden-paths where misparses had occurred, and furthermore, then reanalyzed the syntactic structure to arrive at a correct parse in most cases. A considerable amount of more recent work, however, suggests that readers often do not derive a correct parse or interpretation from such sentences. If these more recent observations are accurate, perhaps rereading is not necessarily strategic, controlled, or predictable. The current study consists of two large-scale eye-tracking experiments designed specifically to examine where and how much people reread garden-path sentences, and whether rereading influences comprehension accuracy. A variable text-masking paradigm was employed to restrict access to portions of garden-paths and non-garden-paths during rereading. Scanpath analyses were used to determine whether some or all participants targeted syntactically critical parts of previously read text. Comprehension questions probed final interpretations. In short, readers often misinterpreted the garden-paths, and no rereading measures predicted better comprehension. Furthermore, scanpath analyses revealed considerable variation across and within readers; only small percentages of trials conformed to structurally-based predictions. Taken together, we fail to find support for structurally strategic rereading. We therefore propose that rereading of these sentences is more often "confirmatory" than "revisionary" in nature. [ABSTRACT FROM AUTHOR]

Background and Aim Although several meta-analyses suggested that sequential therapy ( SQT) is superior to standard triple therapy ( STT) for the eradication of Helicobacter pylori, these results were mainly based on the studies from Italy. The aim of this study was to assess the efficacy of 10-day SQT for H. pylori infection compared with STT in Asian adults. Methods We performed an electronic search of the Cochrane Library, Medline, and Embase up to April 21, 2013, with no language restrictions. Randomized controlled trials comparing 10-day SQT with STT for H. pylori eradication in Asian adults were included in this analysis. The primary outcome measures were the risk ratios ( RRs) for successful eradication of H. pylori based on intention to treat comparing SQT with STT. The secondary outcome measures were the RRs for side effects. Results Seventeen randomized controlled trials with a total of 3419 participants (1591 for SQT and 1828 for STT) met the inclusion criteria. The eradication rate was 81.8% (95% CI: 78.9−84.6) for SQT and 74.3% (95% CI: 69.6−78.8) for SST, respectively. The pooled RR was 1.10 (95% CI: 1.04−1.16, P = 0.0005), which demonstrated significant superiority of SQT over STT, and the number needed to treat was 14 (95% CI: 9-29). There were no significant differences between SQT and STT in the risk of side effects (the pooled RR: 0.98, 95% CI: 0.87−1.10, P = 0.73). Conclusion Ten-day SQT appears to be superior to STT for H. pylori eradication in Asian adults. However, the pooled efficacy is lower than results from earlier European studies. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate if the HEROES Initiative, a school-based childhood obesity prevention program based on the U. S. Centers for Disease Control and Prevention (CDC)'s coordinated school health approach was able to effectively increase physical activity among elementary and middle school students who were exposed to the program for 18months and to determine student and school-level predictors of success. Method: Students who participated in physiological data collection were invited to participate in a survey at baseline, 6months, and 18months (N=1091, 8 schools). The dropout rate at 18months was 39.1% when graduates were counted. Data was analyzed using generalized estimating equations. Results: A significant increase (p =.0067) was observed in vigorous-intensity physical activity (VPA) but a non-significant increase (p =.1753) was observed in moderate-intensity physical activity (MPA). Each school's implementation fidelity score was also only associated with VPA increases. Students' screen time and vegetable/fruit intake were independently associated with both VPA and MPA increases. Body mass index of students was not predictive of VPA or MPA changes. Conclusion: An 18-month school-based intervention that employs the CDC's coordinated school health approach appears to be effective in increasing physical activity among elementary and middle school children. [Copyright &y& Elsevier]

Addition of excipients is a common strategy to slow protein aggregation during storage. Excipient effects on the mechanism(s) and temperature ( T) dependence of aggregation for a monoclonal antibody solution were tested using size-exclusion chromatography, differential scanning calorimetry ( DSC), temperature scanning monomer loss ( TSML), and laser light scattering; previous work in buffer-only conditions had shown non- Arrhenius behavior and implicated Fab and/or C H3 unfolding as a key step in aggregation. Excipients included citrate, amino acid salts (histidine- HCl, arginine- HCl), and polyols (mannitol and glycerol). DSC and TSML showed that Fab, rather than CH3, unfolding corresponded with the onset of aggregation for each condition. Isothermal incubation at 56.5° C, 40° C, and 2° C-8° C resulted in aggregation, while fragmentation occurred readily at only 40° C. The primary effect of the different excipients appeared to be preferential accumulation/exclusion, affecting the concentrations of partially unfolded monomer key intermediates. In addition, aggregation rates were clearly non- Arrhenius, causing aggregation to dominate over fragmentation at high and low T, and making long-term stability predictions problematic based on commonly employed 40° C conditions. Possible reasons for non- Arrhenius behavior include a strong T-dependence of the Fab unfolding enthalpy and/or a switch from Fab-mediated to Fc-mediated aggregation as one moves from high to low T. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3556-3566, 2013 [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 variants belong to S, V, L, G, GH, and GR clades. • Genome mutations form new variants which are spreading globally. • K18-hACE2 heterozygous mice were used to compare the lethality of viral clades. • GH and GR clades had significantly lower LD50 values compared to other clades. • This is the first study that compares the pathogenicity of SARS-CoV-2 clades. This study compared the lethality of severe acute respiratory syndrome coronavirus 2 variants belonging to the S, V, L, G, GH, and GR clades using K18-human angiotensin-converting enzyme 2 heterozygous mice. To estimate the 50% lethal dose (LD 50) of each variant, increasing viral loads (100–104 plaque-forming units [PFU]) were administered intranasally. Mouse weight and survival were monitored for 14 days. The LD 50 of the GH and GR clades was significantly lower than that of other clades at 50 PFU. These findings suggest that the GH and GR clades, which are prevalent worldwide, are more virulent than the other clades. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A).The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS).The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group.RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function.This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas.• The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear.• Overall survival rate was significantly higher in the RFA group.• The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.Materials and methods: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A).The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS).The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group.RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function.This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas.• The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear.• Overall survival rate was significantly higher in the RFA group.• The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.Results: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A).The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS).The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group.RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function.This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas.• The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear.• Overall survival rate was significantly higher in the RFA group.• The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.Conclusion: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A).The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS).The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group.RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function.This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas.• The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear.• Overall survival rate was significantly higher in the RFA group.• The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.Clinical relevance statement: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A).The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS).The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group.RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function.This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas.• The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear.• Overall survival rate was significantly higher in the RFA group.• The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.Key Points: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A).The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS).The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group.RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function.This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas.• The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear.• Overall survival rate was significantly higher in the RFA group.• The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups. [ABSTRACT FROM AUTHOR]

This study investigated a novel kinetic model of the adsorption and photocatalytic degradation of methyl orange, an anionic dye, using a commercial ZnO and reduced commercial ZnO photocatalysts. The results were compared and discussed with our previous study on methylene blue, a cationic dye, providing new insights into the interaction of the catalyst with molecules with different charges. The kinetic model was applied to describe adsorption in the dark, followed by photocatalytic degradation under simulated sunlight. In addition, the predicted pK a values of methyl orange were estimated using the kinetic model, which were found to be 4.40 and 9.34. The effect of ZnO oxygen vacancies (created through hydrogen reduction at 500 °C) on the adsorption and photocatalytic degradation of methyl orange was investigated. The existence and effects of oxygen vacancies on ZnO were analyzed using TPR, PL, XPS, XRD, FE-SEM, EDS, BET, Tauc plot, Mott-Schottky, and cyclic Voltammetry. The appearance of oxygen vacancies was clearly observed by the characterization results, while the morphology of the nanoparticles was found to be unchanged. Additionally, the band gap of ZnO was decreased from 3.22 to 3.07 eV, and the maximum valence band of the catalyst was increased from 2.43 to 2.67 eV due to the reduction pretreatment. The findings suggest that the photocatalytic degradation rate of the reduced ZnO substantially increased. However, the adsorption removal of the anionic dye declined, which could be attributed to the more negative zeta potential of ZnO after hydrogen reduction. Finally, the quantum yield of photocatalytic process was calculated and compared with the results of methylene blue. [Display omitted] • The impact of oxygen vacancies on adsorption and photocatalytic degradation of methyl orange by ZnO. • A new approach to modeling the kinetics of continuous adsorption and photocatalytic degradation. • The influence of pH on the speciation of anionic dye and its adsorption and degradation mechanism. • Determination of pK a values by utilizing experimental data on adsorption. [ABSTRACT FROM AUTHOR]

Backgrounds and aims: Inflammatory bowel disease (IBD) patients often experience disease flare-ups during international air travel. We aimed to identify risk factors associated with IBD flare-up during international air travel. Methods: Patients with scheduled international air travel were enrolled in the study from the Seoul National University Bundang Hospital IBD clinic. Flight information and clinical data were collected via questionnaires and personal interviews, and risk factors associated with IBD flares were determined. Results: Between May 2018 and February 2020, 94 patients were prospectively enrolled in the study (mean age, 33.0 years; males, 53.2%; mean disease duration, 56.7 months), including 56 (59.6%) with ulcerative colitis and 38 (40.4%) with Crohn's disease. Of the 94 patients enrolled, 15 (16.0%) experienced an IBD flare-up and 79 (84.0%) remained in remission throughout travel. Logistic regression analysis revealed that high fecal calprotectin levels before travel (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000–1.001, p = 0.016), the presence of a comorbidity (OR: 6.334, 95% CI: 1.129–35.526, p = 0.036), and history of emergency room visit (OR: 5.283, 95% CI: 1.085–25.724, p = 0.039) were positively associated with disease flare-up. The previous and current use of immunomodulators and biologics, time of flight, altitude, number countries visited, travel duration, objective of visit, and previous medical consultations were not associated with disease flare-up. Conclusions: Elevated fecal calprotectin levels, history of emergency room visits, and the presence of a comorbidity predicted IBD flare-up during international air travel. [ABSTRACT FROM AUTHOR]

Highlights: [•] We analyzed selective response of compounds on diverse subset of cancer cell lines. [•] We used GI50 profile of >40,000 compounds on 60 cancer cell lines. [•] 3D shape-based similarity predicts the GI50 profile better than 2D chemical similarity. [•] Lineage- and genotype-specific compound response was identified. [Copyright &y& Elsevier]

Objectives: To compare the prevalence and correlates of cigarette smoking among East Asian college students. Methods: Data were collected from college students (N=16,558) in China, Hong Kong, Malay­sia, Singapore, South Korea, and Taiwan (response rate: 78%). Results: Religion was independently associated with college students' smoking in China (adjusted odds ratio [AOR] = 1.82) and South Korea (AOR = 0.80). Being a heavy drinker and having a higher exposure to secondhand smoke were associated with higher smoking rates (Ps < .001). Conclusions: The East Asian economies show a varied prevalence of college smoking but a similar pattern of relationship with its correlates. [ABSTRACT FROM AUTHOR]

Background and Aim: Western reports have suggested that the prevalence of gastric cardia cancer (GCC) has been increasing, and indicated some differences between GCC and gastric noncardia cancer (GNCC). However, few studies have been conducted in Asia. The aims of this study were to estimate the prevalence of GCC and to evaluate differences of clinicopathologic characteristics between GCC and GNCC in South Korea. Methods: This study was single-center case-control study. A total of 829 patients with gastric cancer and 270 controls were enrolled between 2003 and 2011. Baseline characteristics, Helicobacter pylori ( H. pylori) infection status, and histologic characteristics were compared among three groups (GCC, GNCC, and control). Results: Sixty cases (7.2%) of gastric cancer were located in cardia. Multivariate analysis showed that male odds ratio (OR, 5.72; 95% CI, 1.72-19.07; p = .005) and cigarette smoking (OR, 5.38; 95% CI, 1.39-20.90; p = .015) were risk factors of GCC in comparison with control group, but H. pylori infection rate was not significant. In the case of GNCC, cigarette smoking (OR, 3.87; 95% CI, 1.81-8.29; p < .001), past alcohol intake (OR, 2.82; 95% CI, 1.28-6.20; p = .010), intestinal metaplasia (OR, 3.22; 95% CI, 2.00-5.17; p < .001), and H. pylori infection (OR, 3.06; 95% CI, 1.90-4.93; p < .001) were risk factors of GNCC. Gastroesophageal reflux disease symptoms were higher in the GNCC (21.2%) than control group (13.5%) ( p = .008). However, in the case of GCC, they were similar between the GCC (12.7%) and control group ( p = .872). According to multivariate analysis, history of H. pylori eradication (OR, 0.34; 95% CI, 0.19-0.61; p < .001) was associated with a protective effect on GNCC. GCC showed higher depth of invasion ( p = .038) and frequent distant metastasis ( p = .012) than GNCC. Conclusion: In this referral center based study, the prevalence of GCC was 7.2% in South Korea. Risk factors and clinicopathologic characteristics for GCC and GNCC were different, supporting that the pathophysiology is different in the development of GCC and GNCC. [ABSTRACT FROM AUTHOR]

Abstract: The main applications of virtual chemical screening include the selection of a minimal receptor-relevant subset of a chemical library with a maximal chemical diversity. We have previously reported that the combination of ligand-centric and receptor-centric virtual screening methods may provide a compromise between computational time and accuracy during the hit enrichment process. In the present work, we propose a “progressive distributed docking” method that improves the virtual screening process using an iterative combination of shape-matching and docking steps. Known ligands with low docking scores were used as initial 3D templates for the shape comparisons with the chemical library. Next, new compounds with good template shape matches and low receptor docking scores were selected for the next round of shape searching and docking. The present iterative virtual screening process was tested for enriching Peroxisome proliferator-activated receptor and Phosphoinositide 3-kinase relevant compounds from a selected subset of the chemical libraries. It was demonstrated that the iterative combination improved the lead-hopping practice by improving the chemical diversity in the selected list of virtual hits. [Copyright &y& Elsevier]

Objectives. There have been no reported data on the medical care cost of idiopathic peptic ulcer disease (PUD) compared with H. pylori (++) and/or NSAID (++) cases although H. pylori-negative idiopathic ulcers are increasing. The aim of this study was to investigate the direct medical care costs of PUD based on whether it was H. pylori infection/from NSAIDs or idiopathic. Material and methods. One hundred and seventy three patients with PUD comprising H. pylori and/or NSAID use-associated PUD ( n == 145) and idiopathic PUD ( n == 28) were prospectively enrolled in this study. The direct medical care costs were analyzed retrospectively for the patients with PUD during a one-year follow-up period. Results. The recurrence rate within one year was significantly higher in idiopathic PUD than H. pylori and/or NSAID-associated PUD ( p == 0.002). Direct medical care costs of idiopathic PUD ($$2483.8) were higher than in patients with H. pylori and/or NSAID-associated PUD ($$1751.8) resulting from longer duration of medication and higher proportion of endoscopic hemostasis and hospitalization. Conclusions. More clinical research is needed to improve outcome and reduce recurrence rate and medical care costs of idiopathic PUD. [ABSTRACT FROM AUTHOR]