Human T cells efficiently control RSV infection.

Respiratory syncytial virus (RSV) infection causes significant morbidity and mortality in infants, immunocompromised individuals, and older individuals. There is an urgent need for effective antivirals and vaccines for high-risk individuals. We used 2 complementary in vivo models to analyze RSV-associated human lung pathology and human immune correlates of protection. RSV infection resulted in widespread human lung epithelial damage, a proinflammatory innate immune response, and elicited a natural adaptive human immune response that conferred protective immunity. We demonstrated a key role for human T cells in controlling RSV infection. Specifically, primed human CD8+ T cells or CD4+ T cells effectively and independently control RSV replication in human lung tissue in the absence of an RSV-specific antibody response. These preclinical data support the development of RSV vaccines, which also elicit effective T cell responses to improve RSV vaccine efficacy.

On modeling and utilizing chemical compound information with deep learning technologies: A task-oriented approach.

A large number of chemical compounds are available in databases such as PubChem and ZINC. However, currently known compounds, though large, represent only a fraction of possible compounds, which is known as chemical space. Many of these compounds in the databases are annotated with properties and assay data that can be used for drug discovery efforts. For this goal, a number of machine learning algorithms have been developed and recent deep learning technologies can be effectively used to navigate chemical space, especially for unknown chemical compounds, in terms of drug-related tasks. In this article, we survey how deep learning technologies can model and utilize chemical compound information in a task-oriented way by exploiting annotated properties and assay data in the chemical compounds databases. We first compile what kind of tasks are trying to be accomplished by machine learning methods. Then, we survey deep learning technologies to show their modeling power and current applications for accomplishing drug related tasks. Next, we survey deep learning techniques to address the insufficiency issue of annotated data for more effective navigation of chemical space. Chemical compound information alone may not be powerful enough for drug related tasks, thus we survey what kind of information, such as assay and gene expression data, can be used to improve the prediction power of deep learning models. Finally, we conclude this survey with four important newly developed technologies that are yet to be fully incorporated into computational analysis of chemical information.

Usefulness of Allogenic Acellular Dermal Matrix for Prevention of Scalp Depression after Burr Hole Trephination.

OBJECTIVE: Burr hole trephination is a common treatment for chronic subdural hematoma, intracranial hematoma, and intraventricular hematoma due to its effective drainage of hematoma, minimal invasiveness and short operation time. However, cosmetic complications such as scalp depression can occur. The aim of this study was to evaluate the usefulness of an allogenic acellular dermal matrix (ADM) to prevent scalp depression at the burr hole site. METHODS: A retrospective analysis was performed with 75 cases in 66 patients who were treated with burr hole trephination from January 2018 to December 2019. These cases divided into 2 groups; based on the method used to cover the burr hole site: Gelfoam packing only (GPO) and ADM. The degree of the scalp depression was measured from the more recent follow-up brain computed tomography scan. RESULTS: There was a significant difference in the degree of scalp depression between GPO and ADM groups (p=0.003). No significant correlation between patient's age and the degree of scalp depression (GPO: p=0.419, ADM: p=0.790). There were no wound infection complication in either group. CONCLUSION: ADM is a suitable material to prevent scalp depression after burr hole trephination.

Genome Mining Reveals High Topological Diversity of ω-Ester-Containing Peptides and Divergent Evolution of ATP-Grasp Macrocyclases.

ω-Ester-containing peptides (OEPs) are a family of ribosomally synthesized and post-translationally modified peptides (RiPPs) containing intramolecular ω-ester or ω-amide bonds. Although their distinct side-to-side connections may create considerable topological diversity of multicyclic peptides, it is largely unknown how diverse ring patterns have been developed in nature. Here, using genome mining of biosynthetic enzymes of OEPs, we identified genes encoding nine new groups of putative OEPs with novel core consensus sequences, disclosing a total of ∼1500 candidate OEPs in 12 groups. Connectivity analysis revealed that OEPs from three different groups contain novel tricyclic structures, one of which has a distinct biosynthetic pathway where a single ATP-grasp enzyme produces both ω-ester and ω-amide linkages. Analysis of the enzyme cross-reactivity showed that, while enzymes are promiscuous to nonconserved regions of the core peptide, they have high specificity to the cognate core consensus sequence, suggesting that the enzyme-core pair has coevolved to create a unique ring topology within the same group and has sufficiently diversified across different groups. Collectively, our results demonstrate that the diverse ring topologies, in addition to diverse sequences, have been developed in nature with multiple ω-ester or ω-amide linkages in the OEP family of RiPPs.

Assessment of cerebral autoregulation using continuous-wave near-infrared spectroscopy during squat-stand maneuvers in subjects with symptoms of orthostatic intolerance.

Orthostatic lightheadedness in healthy young adults often leads to syncope in severe cases. One suggested underlying mechanism of orthostatic lightheadedness is a drop in transient blood pressure (BP); however, a decrease in BP does not always lead to a drop in cerebral blood flow (CBF) due to cerebral autoregulation (CA). We present a direct assessment method of CA using a multichannel continuous-wave near-infrared spectroscopy (CW-NIRS) device that measures the temporal changes in oxy- and deoxy-hemoglobin concentrations in the prefrontal cortex. Twenty healthy young adults were recruited. During the experiment, continuous beat-to-beat BP and heart rate were simultaneously measured during repetitive squat-stand maneuvers. We introduce a new metric termed 'time-derivative hemodynamic model (DHbT)', which is the time-derivative of total-hemoglobin concentration change that reflects the changes of cerebral blood volume and CBF. Although the absolute levels and the variations of systolic and diastolic BPs and mean arterial pressure showed no significant difference between the two groups, the proposed model showed a distinct difference in slope variation and response time of DHbT between the subjects with frequent symptom of orthostatic intolerance and the healthy control subjects. Thus, these results clearly demonstrate the feasibility of using CW-NIRS devices as a CA performance assessment tool.

Reference values of lead in blood and related factors among Korean adolescents: the Korean National Health and Nutrition Examination Survey 2010-2013.

PURPOSE: This study aimed to assess the reference values and factors influencing blood lead levels among Korean adolescents. METHODS: The study population consisted of 1,585 adolescents (801 males, 784 females; aged 10-19 years) who participated in the Korea National Health and Nutrition Examination Survey 2010-2013. We analyzed blood lead concentrations in relation to demographic/lifestyle characteristics for all participants. "Reference values" of blood lead levels were calculated as the upper limit of the 95% confidence interval of the 95th percentile. RESULTS: The average "reference value" for blood lead concentrations among Korean adolescents was 2.25 µg/dL (2.49 µg/dL for males, 2.07 µg/dL for females), and the geometric mean of the blood lead concentrations was 1.34 µg/dL. Males had higher blood lead concentrations than females (male, 1.48 µg/dL; female, 1.19 µg/dL; P<0.001). Elementary school students had higher blood lead concentrations than junior and senior high school students (1.44 µg/dL vs. 1.31 µg/dL, P<0.001). Participants living in detached houses had higher blood lead concentrations than those living in apartments (P<0.001) and current smokers had higher concentrations than nonsmokers or participants with secondhand smoke exposure (P<0.05). Additionally, participants with excessive alcohol consumption had higher levels than non-drinkers (P<0.001). CONCLUSION: This study provides national reference data on blood lead concentrations stratified by demographic and lifestyle factors among Korean adolescents. Further studies are needed to elucidate the relationship between increased lead exposure and demographic factors including type of housing.

Obesity Alters the Microbial Community Profile in Korean Adolescents.

Obesity is an increasing public health concern worldwide. According to the latest Organization for Economic Co-operation and Development (OECD) report (2014), the incidence of child obesity in Korea has exceeded the OECD average. To better understand and control this condition, the present study examined the composition of the gut microbial community in normal and obese adolescents. Fecal samples were collected from 67 obese (body mass index [BMI] ≥ 30 kg/m2, or ≥ 99th BMI percentile) and 67 normal (BMI < 25 kg/m2 or < 85th BMI percentile) Korean adolescents aged 13-16 years and subjected to 16S rRNA gene sequencing. Analysis of bacterial composition according to taxonomic rank (genus, family, and phylum) revealed marked differences in the Bacteroides and Prevotella populations in normal and obese samples (p < 0.005) at the genus and family levels; however, there was no difference in the Firmicutes-to-Bacteroidetes (F/B) ratio between normal and obese adolescents samples at the phylum level (F/B normal = 0.50 ± 0.53; F/B obese = 0.56 ± 0.86; p = 0.384). Statistical analysis revealed a significant association between the compositions of several bacterial taxa and child obesity. Among these, Bacteroides and Prevotella showed the most significant association with BMI (p < 0.0001 and 0.0001, respectively). We also found that the composition of Bacteroides was negatively associated with triglycerides (TG), total cholesterol, and high-sensitive C-reactive protein (hs-crp) (p = 0.0049, 0.0023, and 0.0038, respectively) levels, whereas that of Prevotella was positively associated with TG and hs-crp levels (p = 0.0394 and 0.0150, respectively). We then applied the association rule mining algorithm to generate "rules" to identify the association between the populations of multiple bacterial taxa and obesity; these rules were able to discriminate obese from normal states. Therefore, the present study describes a systemic approach to identify the association between bacterial populations in the gut and childhood obesity.

The relationship between primary headache and constipation in children and adolescents.

PURPOSE: Many patients presenting with headache also complain of constipation; the relationship between these two symptoms has not been explored in detail. The aim of this study was to investigate the association between primary headache and constipation. METHODS: This retrospective study included all children who attended the Inje University Sanggye Paik Hospital complaining of headache, and who had been followed up for at least 100 days. Patients were divided into 2 groups: group A, in whom the headache improved after treatment for constipation, and group B, in whom headache was not associated with constipation. RESULTS: Of the 96 patients with primary headache, 24 (25.0%) also had constipation (group A). All 24 received treatment for constipation. Follow-up revealed an improvement in both headache and constipation in all patients. Group B contained the remaining 72 children. Comparison of groups A and B indicated a significant difference in sex ratio (P=0.009, chi-square test). Patients with probable tension-type headache were more likely to be in Group A (P=0.006, chi-square test). CONCLUSION: Resolution of constipation improves headache in many patients diagnosed with primary headache, especially those with probable tension-type headache. We suggest that either constipation plays a key role in triggering headache, or that both constipation and headache share a common pathophysiology.

Genome-wide association study of liver enzymes in korean children.

Liver enzyme elevations, as an indicator of liver function, are widely associated with metabolic diseases. Genome-wide population-based association studies have identified a genetic susceptibility to liver enzyme elevations and their related traits; however, the genetic architecture in childhood remains largely unknown. We performed a genome-wide association study to identify new genetic loci for liver enzyme levels in a Korean childhood cohort (n = 484). We observed three novel loci (rs4949718, rs80311637, and rs596406) that were multiply associated with elevated levels of alanine transaminase and aspartate transaminase. Although there are some limitations, including genetic power, additional replication and functional characterization will support the clarity on the genetic contribution that the ST6GALNAC3, ADAMTS9, and CELF2 genes have in childhood liver function.

Efficient data extraction method for near-infrared spectroscopy (NIRS) systems with high spatial and temporal resolution.

An hardware-efficient method for the extraction of hemodynamic responses in near-infrared spectroscopy systems is proposed to increase the spatial and temporal resolution. The performance improvement is attributed to high signal-to-noise ratio receivers, a modulation scheme, and a multi-input-multi-output based data extraction algorithm. The proposed system shows more than twofold improvement in the figure of merit compared to conventional designs. Experimental results support the validity of the proposed system.