Kidney Cancer and Potential Use of Urinary Extracellular Vesicles.

Kidney cancer is the 14th most common cancer globally. The 5-year relative survival rate of kidney cancer at a localized stage is 92.9% and it declines to 17.4% in metastatic stage. Currently, the most accurate method of its diagnosis is tissue biopsy. However, the invasive and costly nature of biopsies makes it undesirable in many patients. Therefore, novel biomarkers for diagnosis and prognosis should be explored. Urinary extracellular vesicles (uEVs) are small vesicles (50-200 nm) in urine carrying nucleic acids, proteins and lipids as their cargos. These uEVs' cargos can provide non-invasive alternative to monitor kidney health. In this review, we have summarized recent studies investigating potential use of uEVs' cargos as biomarkers in kidney cancer for diagnosis, prognosis and therapeutic intervention.

Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis.

The 5-year survival rate of kidney cancer drops dramatically from 93% to 15% when it is metastatic. Metastasis constitutes for 30% of kidney cancer cases, in which clear cell renal cell carcinoma (ccRCC) is the most prominent subtype. By sequencing mRNA of ccRCC patient samples, we found that apolipoprotein L1 (APOL1) was highly expressed in tumors compared to their adjacent normal tissues. This gene has been previously identified in a large body of kidney disease research and was reported as a potential prognosis marker in many types of cancers. However, the molecular function of APOL1 in ccRCC, especially in metastasis, remained unknown. In this study, we modulated the expression of APOL1 in various renal cancer cell lines and analyzed their proliferative, migratory, and invasive properties. Strikingly, APOL1 overexpression suppressed ccRCC metastasis both in vitro and in vivo. We then explored the mechanism by which APOL1 alleviated ccRCC malignant progression by investigating its downstream pathways. APOL1 overexpression diminished the activity of focal adhesive molecules, Akt signaling pathways, and EMT processes. Furthermore, in the upstream, we discovered that miR-30a-3p could inhibit APOL1 expression. In conclusion, our study revealed that APOL1 play a role as a tumor suppressor in ccRCC and inhibit metastasis, which may provide novel potential therapeutic approaches for ccRCC patients.

Characterization of exosomal microRNAs in preterm infants fed with breast milk and infant formula.

Breastfeeding not only reduces infection-related morbidity, but also increases growth of preterm infants. Advantages of breast milk (BM) for preterm infants are significant. They continue to be studied. However, because not all preterm infants can receive breastfeeding, bovine-based infant formula (IF) is used as an alternative, which may increase the risk of several preterm complications. Exosomes isolated from biofluids are emerging as biomarkers in research of various diseases. Here, we characterized miRNA contents of exosomes in urine and serum samples of preterm infants who were BM and IF fed and performed transcriptomic analysis of small RNA libraries. We identified significantly up-regulated 6 miRNAs and 10 miRNAs, respectively. Gene Ontology (GO) analysis revealed that target genes of these miRNAs might participate in neuronal development, immunity modulation, detoxification of reactive oxygen species, and transmembrane exchange. Our data suggest that exosome-based systemic screening for preterm infants with breastfeeding might be a screening tool for identifying target molecules involved in therapy for preterm infants in neonatal intensive care unit (NICU) and for future application as nutraceutical formulations or pharmaceuticals.

A structural equation modeling approach using behavioral and neuroimaging markers in major depressive disorder.

Major depressive disorder (MDD) has consistently proven to be a multifactorial and highly comorbid disease. Despite recent depression-related research demonstrating causalities between MDD-related factors and a small number of variables, including brain structural changes, a high-statistical power analysis of the various factors is yet to be conducted. We retrospectively analyzed data from 155 participants (84 healthy controls and 71 patients with MDD). We used magnetic resonance imaging and diffusion tensor imaging data, scales assessing childhood trauma, depression severity, cognitive dysfunction, impulsivity, and suicidal ideation. To simultaneously evaluate the causalities between multivariable, we implemented two types of MDD-specified structural equation models (SEM), the behavioral and neurobehavioral models. Behavioral SEM showed significant results in the MDD group: Comparative Fit Index [CFI] = 1.000, Root Mean Square Error of Approximation [RMSEA]) = 0.000), with a strong correlation in the scales for childhood trauma, depression severity, suicidal ideation, impulsivity, and cognitive dysfunction. Based on behavioral SEM, we established neurobehavioral models showing the best-fit in MDD, especially including the right cingulate cortex, central to the posterior corpus callosum, right putamen, pallidum, whole brainstem, and ventral diencephalon, including the thalamus (CFI >0.96, RMSEA <0.05). Our MDD-specific model revealed that the limbic-associated regions are strongly connected with childhood trauma rather than depression severity, and that they independently affect suicidal ideation and cognitive dysfunction. Furthermore, cognitive dysfunction could affect impulsivity.

Childhood abuse and cortical gray matter volume in patients with major depressive disorder.

Childhood abuse is associated with brain structural alterations; however, few studies have investigated the association between specific types of childhood abuse and cortical volume in patients with major depressive disorder (MDD). We aimed to investigate the association between specific types of childhood abuse and gray matter volumes in patients with MDD. Seventy-five participants with MDD and 97 healthy controls (HCs) aged 19-64 years were included. Cortical gray matter volumes were compared between MDD and HC groups, and also compared according to exposure to each type of specific childhood abuse. Emotional, sexual, and physical childhood abuse were assessed using the 28-item Childhood Trauma Questionnaire. Patients with MDD showed a significantly decreased gray matter volume in the right anterior cingulate gyrus (ACG). Childhood sexual abuse (CSA) was associated with significantly decreased gray matter volume in the right middle occipital gyrus (MOG). In the post-hoc comparison of volumes of the right ACG and MOG, MDD patients with CSA had significantly smaller volumes in the right MOG than did MDD patients without CSA or HCs. The right MOG volume decrease could be a neuroimaging marker associated with CSA and morphological changes in the brain may be involved in the pathophysiology of MDD.

Characteristics of children hospitalized through the pediatric emergency department and effects of pediatric emergency ward hospitalization

Purpose@#To evaluate the efficiency of the pediatric emergency ward (PEW) through the outcomes of children hospitalized to the ward by the department of pediatric emergency medicine (PEM). @*Methods@#A chart review was completed for children (< 15 years) who were hospitalized to the PEW via the pediatric emergency center from March through May 2021. We compared the general characteristics and details regarding the outcomes depending on the departments they were hospitalized to, namely PEM, pediatrics (PED), and others. @*Results@#We analyzed a total of 606 hospitalized children: PEM, 91; PED, 456; and others, 59. In the order listed above, their median ages were 2 years (interquartile range, 1-6), 1 year (0-4), and 9 years (7-14) (P < 0.001). The numbers of children with Korean Triage and Acuity Scale of 1-3 were 71 (78.0%), 400 (87.7%), and 33 (55.9%) (P < 0.001). Median length of stay (LOS) in the emergency department (ED) and hospital tended to be shorter in PEM (ED LOS: PEM, 4.3 hours vs. PED and others, 4.0-6.3 hours; hospital LOS: PEM, 19.0 hours vs. PED and others, 58.5-63.8 hours; all Ps < 0.001). The differences in the LOS were prominent between others and PEM (ED LOS, 1.538 [95% confidence interval, 1.353-1.749]; hospital LOS, 3.375 [2.741-4.157]). Transfers to other departments occurred only in PEM (4.4%) and PED (3.9%) whereas intensive care was performed only in others (27.1%). Return visits showed no difference among the 3 departments. Top 5 chief complaints and primary diagnoses of the children hospitalized to PEM were vomiting, fever, abdominal pain, head injury, and poisoning, and gastroenteritis, concussion, syncope, poisoning, and upper respiratory infection, respectively. @*Conclusion@#Hospitalization to PEWs for short-term treatment or observation may relieve overcrowding in EDs or in hospitals, with comparable frequency of return visits.

Network analysis for estimating standardization trends in genomics using MEDLINE.

BACKGROUND: Biotechnology in genomics, such as sequencing devices and gene quantification software, has proliferated and been applied to clinical settings. However, the lack of standards applicable to it poses practical problems in interoperability and reusability of the technology across various application domains. This study aims to visualize and identify the standard trends in clinical genomics and to suggest areas on which standardization efforts must focus. METHODS: Of 16,538 articles retrieved from PubMed, published from 1975 to 2020, using search keywords "genomics and standard" and "clinical genomic sequence and standard", terms were extracted from the abstracts and titles of 15,855 articles. Our analysis includes (1) network analysis of full phases (2) period analysis with five phases; (3) statistical analysis; (4) content analysis. RESULTS: Our research trend showed an increasing trend from 2003, years marked by the completion of the human genome project (2003). The content analysis showed that keywords related to such concepts as gene types for analysis, and analysis techniques were increased in phase 3 when US-FDA first approved the next-generation sequencer. During 2017-2019, oncology-relevant terms were clustered and contributed to the increasing trend in phase 4 of the content analysis. In the statistical analysis, all the categories showed high regression values (R2 > 0.586) throughout the whole analysis period and phase-based statistical analysis showed significance only in the Genetics terminology category (P = .039*) at phase 4. CONCLUSIONS: Through comprehensive trend analysis from our study, we provided the trend shifts and high-demand items in standardization for clinical genetics.

Enhanced Dichotic Listening and Temporal Sequencing Ability in Early-Blind Individuals.

Several studies have reported the better auditory performance of early-blind subjects over sighted subjects. However, few studies have compared the auditory functions of both hemispheres or evaluated interhemispheric transfer and binaural integration in blind individuals. Therefore, we evaluated whether there are differences in dichotic listening, auditory temporal sequencing ability, or speech perception in noise (all of which have been used to diagnose central auditory processing disorder) between early-blind subjects and sighted subjects. The study included 23 early-blind subjects and 22 age-matched sighted subjects. In the dichotic listening test (three-digit pair), the early-blind subjects achieved higher scores than the sighted subjects in the left ear (p = 0.003, Bonferroni's corrected α = 0.05/6 = 0.008), but not in the right ear, indicating a right ear advantage in sighted subjects (p < 0.001) but not in early-blind subjects. In the frequency patterning test (five tones), the early-blind subjects performed better (both ears in the humming response, but the left ear only in the labeling response) than the sighted subjects (p < 0.008, Bonferroni's corrected α = 0.05/6 = 0.008). Monosyllable perception in noise tended to be better in early-blind subjects than in sighted subjects at a signal-to-noise ratio of -8 (p = 0.054), the results at signal-to-noise ratios of -4, 0, +4, and +8 did not differ. Acoustic change complex responses to/ba/in babble noise, recorded with electroencephalography, showed a greater N1 peak amplitude at only FC5 electrode under a signal-to-noise ratio of -8 and -4 dB in the early-blind subjects than in the sighted subjects (p = 0.004 and p = 0.003, respectively, Bonferroni's corrected α = 0.05/5 = 0.01). The results of this study revealed early-blind subjects exhibited some advantages in dichotic listening, and temporal sequencing ability compared to those shown in sighted subjects. These advantages may be attributable to the enhanced activity of the central auditory nervous system, especially the right hemisphere function, and the transfer of auditory information between the two hemispheres.

Emotions and sensory processing in adolescents: The effect of childhood traumatic experiences.

Reportedly, maltreated children are more likely to have a mental illness, interpersonal violence, and other social behavior problems than those without trauma experience. However, there are few studies regarding childhood trauma and sensory processing relationship and the relationship is not clear until today. To verify the association between childhood trauma emotions and sensory processing in adolescents is the aim of this study. To gather traumatized adolescents, we conducted survey questionnaires from six alternative schools and one general high school in South Korea. A total of 260 students has answered the questions: trauma/parenting/school adaptation factors, childhood trauma, the difficulty of emotion regulation, positive and negative emotional measure, shortened self-control measure, and adolescent/adult sensory profile. We analyzed linear regression between childhood trauma and other emotions/sensory processing in total subjects and conducted group comparisons between general school and alternative school. With childhood trauma, negative emotion, emotion dysregulation, sensory profile including subscales showed positive correlations. A significant negative correlation was observed between the self-control scale and childhood trauma score. In group comparison results, trauma factors, primary caregiver, custody transfer, and school life adaptation factors were significantly higher in alternative school students (p < 0.002) while the parental relationship did not show a difference. Childhood trauma score, vision, and tactile were significantly higher in alternative school students. To summarize, our results present a direct effect of childhood trauma on sensory function in adolescents and was confirmed the importance of family environments in adolescents.

Single-Session of Combined tDCS-TMS May Increase Therapeutic Effects in Subjects With Tinnitus.

To treat motor and psychiatric disorders, transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are used in clinics worldwide. We combined these two types of neuromodulation technique to increase the effective response of a single session of neuromodulation in subjective tinnitus. Eighty tinnitus subjects were split into four different treatment groups: tDCS, tDCS with sham TMS, tDCS-TMS, and TMS group. Subjects were given 1.5 mA tDCS on the bi-frontal area and TMS stimulated the contralateral single side of the temporo-parietal cortex with 200 pulses at 1 Hz stimulation. Comparing pre-treatment questionnaire scores to post-treatment questionnaire scores, all four groups showed statistically significant improvements. Although there was no significant difference among group comparison, the largest mean difference was shown in the combined group, especially for tinnitus intensity and tinnitus-related distress. Responders in the combined group were the highest for VAS intensity, with a maximum of 80% of twenty subjects. To summarize, dual-neuromodulation responders could consist of responders of frontal tDCS and temporal TMS. In addition, abnormal activity in the frontal or temporal area of the responders is presumed to be modulated by treatment and will be suggested as the target areas in future studies.

Severe Temporal Hyper-Activated States Caused by Noise in Tinnitus and Hyperacusis with Normal Hearing.

Lots of neuroimaging and animal studies have revealed that tinnitus and hyperacusis share the same patterns in the bottom up central auditory process. The aim was to identify the abnormal central patterns commonly observed in both tinnitus and hyperacusis in humans. We investigated two cases of normal hearing: a tinnitus patient and a hyperacusis patient. We compared the differences between the severe temporal hyper-activated state (STHS), with spikes, fast beta and gamma frequencies after noise exposure, and the mild temporal hyper-activated state (MTHS), in no sound exposed condition. The power of the gamma band in the two cases was increased in both auditory cortices compared to the other brain regions. Our results of human with normal hearing were the first to identify how tinnitus and hyperacusis caused by sound are abnormally active and how they maintain constant pathological states.

Severe Temporal Hyper-Activated States Caused by Noise in Tinnitus and Hyperacusis with Normal Hearing

Lots of neuroimaging and animal studies have revealed that tinnitus and hyperacusis share the same patterns in the bottom up central auditory process. The aim was to identify the abnormal central patterns commonly observed in both tinnitus and hyperacusis in humans. We investigated two cases of normal hearing: a tinnitus patient and a hyperacusis patient. We compared the differences between the severe temporal hyper-activated state (STHS), with spikes, fast beta and gamma frequencies after noise exposure, and the mild temporal hyper-activated state (MTHS), in no sound exposed condition. The power of the gamma band in the two cases was increased in both auditory cortices compared to the other brain regions. Our results of human with normal hearing were the first to identify how tinnitus and hyperacusis caused by sound are abnormally active and how they maintain constant pathological states.

Deinococcus ruber sp. nov., a radiation-resistant bacterium isolated from soil.

Two gamma- and UVC-resistant bacterial strains, designated JSH3-1T and 9-2-2, were isolated from garden soil in South Korea. Cells were Gram-stain-positive, aerobic, non-motile and spherical. A polyphasic approach was used to study the taxonomic properties of strains JSH3-1T and 9-2-2. Phylogenetic analysis based on nearly full-length 16S rRNA gene sequences of strains JSH3-1T and 9-2-2 indicated highest similarity with Deinococcus radiomollis PO-04-20-132T (94.7 and 94.9 %, respectively); levels of sequence similarity with the type strains of other Deinococcus species were less than 94.0 %. Strains JSH3-1T and 9-2-2 shared relatively high 16S rRNA gene sequence similarity (98.7 %) and had a high DNA reassociation value of 81±0.5 %. Meanwhile, they showed low levels of DNA reassociation (<25 %) with other closely related species of the genus Deinococcus. The two strains showed chemotaxonomic features typical of the genus Deinococcus, with the presence of menaquinone 8 as the respiratory quinone. The predominant fatty acids were iso-C17 : 0, iso-C13 : 0 and anteiso-C13 : 0. The polar lipids comprised phosphoglycolipid, aminophospholipid, glycolipid and unknown aminolipids. The DNA G+C contents of strains JSH3-1T and 9-2-2 were 62.0 and 61.9 mol%, respectively. On the basis of their phenotypic and genotypic characteristics, and phylogenetic distinction, strains JSH3-1T (=KCTC 33790T=JCM 31311T) and 9-2-2 (=KCTC 33789=JCM 31310) should be classified within a novel species of the genus Deinococcus, for which the name Deinococcus ruber sp. nov. is proposed.

Spirosoma swuense sp. nov., isolated from wet soil.

Strain JBM2-3T, a pale-yellow-coloured, aerobic, catalase-negative, oxidase-positive and Gram-stain-negative bacterium, was isolated from wet soil. The isolate grew aerobically at 25-30 °C (optimum 25 °C), pH 6.0-8.0 (optimum pH 7.0) and in the presence of 0-0.5 % (w/v) NaCl (optimum 0 % NaCl). Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain JBM2-3T belonged to the genus Spirosoma, with a sequence similarity of 96.2 % with Spirosoma panaciterrae Gsoil 1519T. The strain showed the typical chemotaxonomic characteristics of the genus Spirosoma, with the presence of menaquinone 7 as the respiratory quinone; the major fatty acids were summed feature 3 (composed of C16: 1ω6c/ω7c), C16: 1ω5c and iso-C15: 0. The DNA G+C content of strain JBM2-3T was 47.4 mol%. The polar lipid profile contained major amounts of phosphatidylethanolamine and aminophospholipids. On the basis of its phenotypic and genotypic properties, and phylogenetic distinctiveness, strain JBM2-3T should be classified as a representative of a novel species in the genus Spirosoma, for which the name Spirosoma swuense sp. nov. is proposed. The type strain is JBM2-3T (=KCTC 52176T=JCM 31298T).

Deinococcus persicinus sp. nov., a radiation-resistant bacterium from soil.

Two Gram-stain-negative, oxidase-negative, catalase-positive, aerobic and coccus-shaped bacterial strains, KSY3-6T and JSH6-18, were isolated from soil in South Korea. Strains KSY3-6T and JSH6-18 showed high resistance to gamma-ray and UVC irradiation. The 16S rRNA gene sequences of strains KSY3-6T and JSH6-18 showed a novel subline within the genus Deinococcus in the family Deinococcaceae. They shared 94.8-86.4 % nucleotide similarities with other species of the genus Deinococcus. Strain KSY3-6T exhibited high DNA-DNA hybridization values with JSH6-18 (77±0.8 %). The two strains showed typical chemotaxonomic characteristics of the genus Deinococcus, including the presence of menaquinone 8 (MK-8) as predominant respiratory quinone and C16 : 0, C17 : 0cyclo and summed feature 3 (C16 : 1ω7c/C16: 1ω6c) as major fatty acids. The G+C content of the DNA of strains KSY3-6T and JSH6-18 was 62.0 and 62.4 mol%, respectively. Polar lipids in strains KSY3-6T and JSH6-18 were mainly phosphoglycolipids. Based on their phenotypic and genotypic properties, strains KSY3-6T and JSH6-18 should be classified as representatives of a novel species in the genus Deinococcus, for which the name Deinococcus persicinus sp. nov. is proposed. The type strain is KSY3-6T (=KCTC 33787T=JCM 31313T). The reference strain is JSH6-18 (=KCTC 33788=JCM 31312).

Complete genome sequence of Deinococcus actinosclerus BM2(T), a bacterium with Gamma-radiation resistance isolated from soil in South Korea.

A Gram-positive, short-rod shaped and non-motile bacterium Deinococcus actinosclerus BM2(T), resistant to gamma and UV radiation, was isolated from a soil sample collected in South Korea. Strain BM2(T) showed high resistance to gamma radiation with D10 value of 9 kGy. The complete genome of D. actinosclerus BM2(T) consists of a single chromosome (3,264,334bp). The genome features showed the presence of intracellular proteases that help to eliminate radiation-induced ROS during recovery from ionizing radiation damage.

Altererythrobacter terrae sp. nov., isolated from mountain soil.

A Gram-negative, non-motile, non-spore-forming, ovoid-shaped bacterium designated as SWU3(T) was isolated from mountain soil collected at Seoul Women's University, South Korea. Based on 16S rRNA sequence analysis, strain SWU3(T) was found to belong to the genus Altererythrobacter. It shares high sequence similarities with A. dongtanensis JM27(T) (96.6 %), A. epoxidivorans JCS350(T) (96.6 %), and A. troitsensis KMM 6042(T) (96.5 %). Growth was observed between 15 and 37 °C (optimum, 30 °C) with pH of 6-9 (optimum, pH 7.0). It could tolerate 0-2 % (w/v) NaCl. Its predominant quinone was found to be ubiquinone (Q-10). Its major cellular fatty acids were determined to be C17:1 ω6c, C18:1 ω7c, and summed featured 3 (C16:1 ω7c/C16:1 ω6c), all of which are similar characteristics to those of species within the genus Altererythrobacter. Its G + C molar content was found to be 58.4 mol%. Phylogenetic evidence, together with phenotypic characteristics showed that strain SWU3(T) represents a new species of the genus Altererythrobacter. The name Altererythrobacter terrae sp. nov. is proposed and the type strain is SWU3(T) (=KEMB 9004-128(T) = JCM 19177(T)).

Hymenobacter rubidus sp. nov., bacterium isolated from a soil.

Strain DG7B(T) was isolated from a soil sample collected in Seoul, Republic of Korea and was observed to be a gram-negative, short-rod shaped and non-motile bacterium. Its 16S rRNA gene sequence is closely related to those of Hymenobacter terrae DG7A(T) (97.8 % similarity), H. soli PB17(T) (97.5 %), H. glaciei VUG-A130(T) (96.4 %), H. saemangeumensis GSR0100(T) (95.7 %), H. ruber PB156(T) (95.3 %), and H. antarcticus VUG-A42aa(T) (95.3 %). The low levels of DNA-DNA relatedness (<50.3 %) with the above species identified strain DG7B(T) as a novel species in the genus Hymenobacter. The genomic DNA G+C content was determined to be 54.9 %. Growth of strain DG7B(T) was observed at 12-30 °C (optimum at 25 °C) and pH 6.0-11.0 (optimum at pH 7). The cells tolerate <0.5 % NaCl. A UV-visible scan of an ethanol extract of the whole cell pigment showed absorbance peaks at 264.5, 320.0, and 481.5 nm, so the pigment type was determined to be 2'-hydroxyflexixanthin. Chemotaxonomic data showed that strain DG7B(T) possesses menaquinone-7 as the predominant isoprenoid quinone, sym-homospermidine as the major polyamine, phosphatidylethanolamine as the predominant polar lipid and iso-C15:0, anteiso-C15:0 and summed feature 3 (C16:1 ω7c/C16:1 ω7c) as the major fatty acids. Strain DG7B(T) showed low-level resistance to ultraviolet C. Based on the polyphasic analysis, it is concluded that strain DG7B(T) (=KCTC 32553(T) = KEMB 9004-166(T) = JCM 30008(T)) should be classified as the type strain of a novel Hymenobacter species, for which the name Hymenobacter rubidus sp. nov. is proposed.

Complete genome sequence of Deinococcus soli N5(T), a gamma-radiation- resistant bacterium isolated from rice field in South Korea.

A Gram-negative, non-motile and short-rod shaped and gamma-radiation-resistant bacterium Deinococcus soli N5(T), isolated from a rice field soil in South Korea. The complete genome of D. soli N5(T) consists of a chromosome (3,236,984bp). The key enzymes for the central DNA repair mechanisms were present in the genome. The enzyme coding genes has been identified which is involving in the nucleotide excision repair (NER) pathway. The gene cluster in the genome sequence suggest that the D. soli N5(T) use (NER) pathways for efficient removal of pyrimidine dimers that are the most abundant type of UV- induced damage.

Chloride transport activities of trans- and cis-amide-linked bisureas.

Of the bisurea compounds linked through trans- and cis-benzanilide spacers, the cis-amide derivatives were found to be effective in chloride transport, using which a stimuli-responsive mobile carrier was devised.