Clinicogenomic characteristics and synthetic lethal implications of germline homologous recombination-deficient hepatocellular carcinoma.

BACKGROUNDS AND AIMS: We performed an in-depth examination of pathogenic germline variants (PGVs) and somatic variants in DNA damage response (DDR) genes in hepatocellular carcinoma (HCC) to explore their clinical and genomic impacts. APPROACH AND RESULTS: We used a merged whole-exome or RNA sequencing data set derived from in-house ( n = 230) and The Cancer Genome Atlas ( n = 362) databases of multiethnic HCC samples. We also evaluated synthetic lethal approaches targeting mutations in homologous recombination (HR) genes using HCC cells selected from five genomic databases of cancer cell lines. A total of 110 PGVs in DDR pathways in 96 patients were selected. Of the PGV carriers, 44 were HR-altered and found to be independently associated with poorer disease-free survival after hepatectomy. The most frequently altered HR gene in both germline and somatic tissues was POLQ , and this variant was detected in 22.7% (10/44) and 23.8% (5/21) of all the corresponding carriers, respectively. PGVs in HR were significantly associated with upregulation of proliferation and replication-related genes and familial risk of HCC. Samples harboring PGVs in HR with loss of heterozygosity were most strongly correlated with the genomic footprints of deficient HR, such as mutation burden and denovoSig2 (analogous to Catalogue of Somatic Mutations in Cancer [COSMIC] 3), and poor outcome. Pharmacologic experiments with HCC cells defective in BRCA2 or POLQ suggested that tumors with this phenotype are synthetic lethal with poly(ADP-ribose) polymerase inhibitors. CONCLUSIONS: Our findings suggest that germline HR defects in HCC tend to confer a poor prognosis and result in distinctive genomic scarring. Tests of the clinical benefits of HR-directed treatments in the affected patients are needed.

Comprehensive characterization of viral integrations and genomic aberrations in HBV-infected intrahepatic cholangiocarcinomas.

BACKGROUND AND AIMS: Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and HBV infection, little is known about the relevant oncogenic effects. We sought to identify the landscape and mechanism of HBV integration, along with the genomic architecture of HBV-infected iCCA (HBV-iCCA) tumors. APPROACH AND RESULTS: We profiled a cohort of 108 HBV-iCCAs using whole-genome sequencing, deep sequencing, and RNA sequencing, together with preconstructed data sets of HBV-infected HCC (HBV-HCC; n = 167) and combined hepatocellular cholangiocarcinoma (HBV-cHCC/CCA; n = 59), and conventional (n = 154) and fluke-related iCCAs (n = 16). Platforms based on primary iCCA cell lines to evaluate the functional effects of chimeric transcripts were also used. We found that HBV had inserted at multiple sites in the iCCA genomes in 45 (41.7%) of the tumors. Recurrent viral integration breakpoints were found at nine different sites. The most common insertional hotspot (7 tumors) was in the TERT (telomerase reverse transcriptase) promoter, where insertions and mutations (11 tumors) were mutually exclusive, and were accompanied by promoter hyperactivity. Recurrent HBV integration events (5 tumors) were also detected in FAT2 (FAT atypical cadherin 2), and were associated with enrichment of epithelial-mesenchymal transition-related genes. A distinctive intergenic insertion (chr9p21.3), between DMRTA1 (DMRT like family A1) and LINC01239 (long intergenic non-protein coding RNA 1239), had oncogenic effects through activation of the mammalian target of rapamycin (mTOR)/4EBP/S6K pathway. Regarding the mutational profiles of primary liver cancers, the overall landscape of HBV-iCCA was closer to that of nonviral conventional iCCA, than to HBV-HCC and HBV-cHCC/CCA. CONCLUSIONS: Our findings provide insight into the behavior of iCCAs driven by various pathogenic mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.

Homo- and Heteromultinuclear Pseudocapsules Assembled from Calix[6]-mono-crown-5 and Alkali Metal Ions.

The formation of pseudocapsule type homo- and heteromultinuclear complexes of calix[6]-mono-crown-5 (H4L) encapsulating from 4 to 6 alkali metal ions is reported. H4L reacts with KOH to yield a hexanuclear potassium(I) complex [K6(HL)2(CH3OH)2]·CHCl3 (1) in which two bowl-shaped tripotassium(I) complex units are linked in a rim-to-rim fashion via the interligand C-H···π interactions. In the same reaction condition, RbOH afforded a tetranuclear rubidium(I) complex [Rb4(H2L)2(CH3OH)2(µ-H2O)2]·6CHCl3 (2). In 2, again two bowl-shaped dirubidium(I) complex units are held together by two bridging water molecules and C-H···π interactions that act as a glue to generate such an elegant pseudocapsule. Interestingly, a mixture of KOH and RbOH yielded a heterotetranuclear complex [K2Rb2(H2L)2(CH3OH)2(µ-H2O)2]·6CHCl3 (3). Similarly, two heterodinuclear bowl units [KRb(H2L)] in 3 are held together by two bridging water molecules and C-H···π interactions to form a heteromultinuclear pseudocapsule. In each heterodinuclear K+/Rb+ bowl unit of 3, Rb+ occupies the center of the crown loop while K+ locates inside the calix rim. Consequently, the proposed host discriminates not only on the types and numbers of the metal ions but also on their positional preferences in forming pseudocapsules. Solution studies by nuclear magnetic resonance and electrospray ionization-mass support the heterometallic (K+/Rb+) complexation by showing the superior binding affinity of Rb+ over K+ toward the crown loop. These results demonstrate how the metal-driven pseudocapsules are formed and present a new perspective on the metallosupramolecules of the calixcrown scaffold.

Comprehensive characteristics of somatic mutations in the normal tissues of patients with cancer and existence of somatic mutant clones linked to cancer development.

BACKGROUND: Somatic mutations are a major driver of cancer development and many have now been identified in various cancer types, but the comprehensive somatic mutation status of the normal tissues matched to tumours has not been revealed. METHOD: We analysed the somatic mutations of whole exome sequencing data in 392 patient tumour and normal tissue pairs based on the corresponding blood samples across 10 tumour types. RESULTS: Many of the mutations involved in oncogenic pathways such as PI3K, NOTCH and TP53, were identified in the normal tissues. The ageing-related mutational signature was the most prominent contributing signature found and the mutations in the normal tissues were frequently in genes involved in late replication time (p<0.0001). Variants were rarely overlapping across tissue types but shared variants between normal and matched tumour tissue were present. These shared variants were frequently pathogenic when compared with non-shared variants (p=0.001) and showed a higher variant-allele-fraction (p<0.0001). Normal tissue-specific mutated genes were frequently non-cancer-associated (p=0.009). PIK3CA mutations were identified in 6 normal tissues and were harboured by all of the matched cancer tissues. Multiple types of PIK3CA mutations were found in normal breast and matched cancer tissues. The PIK3CA mutations exclusively present in normal tissue may indicate clonal expansions unrelated to the tumour. In addition, PIK3CA mutation was appeared that they arose before the occurrence of the allelic imbalance. CONCLUSION: Our current results suggest that somatic mutant clones exist in normal tissues and that their clonal expansion could be linked to cancer development.

Differential characteristics of repeated polysomnography and multiple sleep latency test parameters in narcolepsy type 1 and type 2 patients: a longitudinal retrospective study.

PURPOSE: Narcolepsy is a chronic disorder and its phenotype is dichotomized into narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). The clinical course and pathophysiological mechanisms of these two clinical entities and their differences are not adequately defined. This study aimed to explore the differential longitudinal patterns of polysomnography (PSG) and multiple sleep latency test (MSLT) in NT1 and NT2. METHODS: In this retrospective study demographic characteristics, PSG, and MSLT parameters at baseline and follow-up were compared between NT1 and NT2 patients. Patients with both follow-up MSLT and PSG were selected for sub-group analysis. Baseline and follow-up MSLT and PSG parameters were compared. RESULTS: Of 55 patients with narcolepsy, mean follow-up periods were 7.4 ± 3.5 years for NT1 and 5.5 ± 2.9 for NT2. Demographic data showed increased body mass index and prevalence of sleep paralysis in NT1. Baseline PSG characteristics between NT1 and NT2 showed decreased sleep latency (p = 0.016) and REM latency (p = 0.046) in NT1 group when compared with NT2. Nocturnal SOREMP on PSG was more prevalent in NT1 (p = 0.017), and half of NT2 patients with nocturnal SOREMP on PSG changed their diagnoses to NT1. On follow-up PSG, NT1 displayed reductions in sleep stage N2 (p = 0.006) and N3 (p = 0.048), while wake after sleep onset (WASO) (p = 0.023) and apnea-hypopnea index (AHI) (p = 0.007) were significantly increased. CONCLUSION: Differential MSLT and PSG characteristics of NT1 and NT2 in at baseline and follow-up indicate that NT1 and NT2 are distinct disease phenotypes, and that they present with a contrasting course of disease.

Efficient User-Serving Scheme in the User-Centric Cell-Free Massive MIMO System.

A cell-free massive multiple input multiple output (MIMO) system is an attractive network model that is in the spotlight in 5G and future communication systems. Despite numerous advantages, the cell-free massive MIMO system has a problem in that it is difficult to operate in reality due to its vast amount of calculation. The user-centric cell-free massive MIMO model has a more feasible and scalable benefit than the cell-free massive MIMO model. However, this model has the disadvantage that as the number of users in the area increases, there are users who do not receive the service. In this paper, the proposed scheme creates connections for unserved users under a user-centric scheme without additional access point (AP) installation and disconnection for existing users. A downlink user-centric cell-free massive MIMO system model in which the APs are connected to the central processing unit (CPU) and the APs and users are geographically distributed is considered. First, the downlink spectral efficiency formula is derived and applied to the user-centric cell-free massive MIMO system. Then, the proposed scheme and power control algorithm are applied to the derived formula. The simulation results show that the unserved users within the area disappear by using the proposed scheme, while the bit error rate (BER) performance and sum rate improve compared to the existing scheme. In addition, it is shown that the proposed scheme works well even with a very large number of users in the area, and a significant service performance improvement for the worst 10% of users and the overall improvement of per-user throughput for the bottom 70% of users are ensured.

Machine Learning for Intelligent-Reflecting-Surface-Based Wireless Communication towards 6G: A Review.

An intelligent reflecting surface (IRS) is a programmable device that can be used to control electromagnetic waves propagation by changing the electric and magnetic properties of its surface. Therefore, IRS is considered a smart technology for the sixth generation (6G) of communication networks. In addition, machine learning (ML) techniques are now widely adopted in wireless communication as the computation power of devices has increased. As it is an emerging topic, we provide a comprehensive overview of the state-of-the-art on ML, especially on deep learning (DL)-based IRS-enhanced communication. We focus on their operating principles, channel estimation (CE), and the applications of machine learning to IRS-enhanced wireless networks. In addition, we systematically survey existing designs for IRS-enhanced wireless networks. Furthermore, we identify major issues and research opportunities associated with the integration of IRS and other emerging technologies for applications to next-generation wireless communication.

Community-Based Multi-Site Randomized Controlled Trial of Behavioral Activation for Patients with Depressive Disorders.

Behavioral activation (BA) is a beneficial and relatively cost-effective treatment option for depression. This study utilized a pragmatic randomized controlled research design to investigate whether BA, as compared with treatment as usual (TAU), led to superior treatment effects, when delivered in community mental health settings by retrained community mental health professionals. Patients with depressive disorders (n = 64) were randomly assigned to a 10-session BA (n = 31) or TAU (n = 33) group. The depressive symptoms and behavioral engagement were assessed at the baseline, post-treatment, and a six-month follow-up. Results showed that, as compared to the TAU group, the BA group had: (1) a reduction in depression severity, as evidenced by large effect sizes and greater response rates, and (2) an increase in behavioral engagement. However, the post-treatment gains were not maintained at the six-month follow-up. The implications and limitations of the study are also discussed (KCT0004098, June 27, 2019, retrospectively registered).

Characterization of early postzygotic somatic mutations through multi-organ analysis.

Mosaicisms caused by postzygotic mutational events are of increasing interest because of their potential association with various human diseases. Postzygotic somatic mutations have not been well characterized however in terms of their developmental lineage in humans. We conducted whole-genome sequencing (WGS) and targeted deep sequencing in 15 organs across three developmental lineages from a single male fetus with polycystic kidney disease (PKD) of 21 weeks gestational age. This fetus had no detectable neurological abnormalities at autopsy but germline mutations in the PKHD1 gene were identified that may have been associated with the PKD. Eight early embryonic mosaic variants with no alteration of protein function were detected. These variants were thought to have occurred at the two or four cell stages after fertilization with a mutational pattern involving frequent C>T and T>C transitions. In our current analyses, no tendency toward organ-specific mutation occurrences was found as the eight variants were detected in all 15 organs. However different allele fractions of these variants were found in different organs, suggesting a tissue-specific asymmetric growth of cells that reflected the developmental germ layer of each organ. This indicated that somatic mutation occurrences, even in early embryogenesis, can affect specific organ development or disease. Our current analyses demonstrate that multi-organ analysis is helpful for understanding genomic mosaicism. Our results also provide insights into the biological role of mosaicism in embryonic development and disease.

Prognostic Molecular Indices of Resectable Hepatocellular Carcinoma: Implications of S100P for Early Recurrence.

BACKGROUND: Although hepatocellular carcinomas (HCCs) often recur in patients undergoing hepatectomy, there are no reliable biomarkers of this undesirable event. Recent RNA-based efforts have developed valuable genetic indices prognostic of cancer outcomes. We aimed to identify molecular predictors of early recurrence after resection of HCC, and reveal the genomolecular structure of the resected tumors. METHOD: Based on the transcriptomic and genomic datasets of 206 HCC samples surgically resected in the Asan Medical Center (AMC), we performed a differential gene expression analysis to identify quantitative markers associated with early recurrence and used the unsupervised clustering method to classify genomolecular subtypes. RESULTS: Differential gene expression profiling revealed that S100P was the highest-ranked overexpressed gene in HCCs that recurred within 2 years of surgery. This trend was reproduced in immunohistochemical studies of the original cohort and an independent AMC cohort. S100P expression also independently predicted HCC-specific mortality post-resection (adjusted hazard ratio 1.09, 95% confidence interval 1.01-1.19; p = 0.042). Validation in a Chinese cohort and in in vitro experiments confirmed the prognostic value of S100P in HCC. We further identified five discrete molecular subtypes of HCC; a subtype with stem cell features ('AMC-C4') was associated with the worst prognosis, both in our series and another two Asian datasets, and S100P was most strongly upregulated in that subtype. CONCLUSION: We identified a promising prognostic biomolecule, S100P, associated with early recurrence after HCC resection, and established the genomolecular architecture of tumors affecting clinical outcomes, particularly in Asian patients. These new insights into molecular mediators should contribute to effective care for affected patients.

Clinicopathological and molecular characterization of chromophobe hepatocellular carcinoma.

BACKGROUND AND AIMS: Chromophobe hepatocellular carcinoma (HCC) is a newly included subtype of HCC in the 5th edition of the WHO classification with distinctive histological features (chromophobic cytoplasm with anaplastic nuclei and pseudocyst formation) and is strongly associated with the alternative lengthening of telomeres (ALT) phenotype. However, the clinicopathologic characterization and molecular features of chromophobe HCC are unknown. METHODS: To comprehensively characterize chromophobe HCC, whole exome sequencing, copy number variation, and transcriptomic analyses were performed in 224 surgically resected HCC cases. Additionally, telomere-specific fluorescence in situ hybridization was used to assess ALT. These genomic profiles and ALT status were compared with clinicopathological features among subtypes of HCC, particularly chromophobe HCC and conventional HCC. RESULTS: Chromophobe HCC was observed in 10.3% (23/224) cases and, compared to conventional HCC, was more frequent in females (P = .023). The overall and recurrence-free survival outcomes were similar between patients with chromophobe HCC and conventional HCC. However, chromophobe HCC displayed significantly more upregulated genes involving cell cycle progression and DNA repair. Additionally, ALT was significantly enriched in chromophobe HCC (87%; 20/23) compared to conventional HCC (2.2%, 4/178; P < .001). Somatic mutations in ALT-associated genes, including ATRX, SMARCAL1, FANCG, FANCM, SP100, TSPYL5, and RAD52 were more frequent in chromophobe HCC (30.4%, 7/23 cases) compared to conventional HCC (11.8%, 21/178 cases; P = .024). CONCLUSIONS: Chromophobe HCC is a unique subtype of HCC with a prevalence of ~10%. Compared to conventional HCC, chromophobe HCC is associated with female predominance and ALT, although overall and recurrence-free outcomes are similar to conventional HCC.

Immunogenomic landscape of hepatocellular carcinoma with immune cell stroma and EBV-positive tumor-infiltrating lymphocytes.

BACKGROUND & AIMS: The immunogenomic characteristics of hepatocellular carcinomas (HCCs) with immune cell stroma (HCC-IS), defined histologically, have not been clarified. We investigated the clinical and molecular features of HCC-IS and the prognostic impact of Epstein-Barr virus (EBV) infection. METHODS: We evaluated 219 patients with conventional HCC (C-HCC) and 47 with HCC-IS using in situ hybridization for EBV, immunohistochemistry, multiplex immunofluorescence staining, and whole exome and transcriptome sequencing. Human leukocyte antigen types were also extracted from the sequencing data. Genomic and prognostic parameters were compared between HCC-IS and C-HCC. RESULTS: CD8 T cell infiltration was more frequent in HCC-IS than C-HCC (mean fraction/sample, 22.6% vs. 8.9%, false discovery rate q <0.001), as was EBV positivity in CD20-positive tumor-infiltrating lymphocytes (TILs) (74.5% vs. 4.6%, p <0.001). CTNNB1 mutations were not identified in any HCC-IS, while they were present in 24.1% of C-HCC (p = 0.016). Inhibitory and stimulatory immune modulators were expressed at similar levels in HCC-IS and EBV-positive C-HCC. Global hypermethylation, and expression of PD-1 and PD-L1 in TILs, and PD-L1 in tumors, were also associated with HCC-IS (p <0.001), whereas human leukocyte antigen type did not differ according to HCC type or EBV positivity. HCC-IS was an independent factor for favorable recurrence-free survival (adjusted hazard ratio [aHR] 0.23; p = 0.002). However, a subgroup of tumors with a high density of EBV-positive TILs had poorer recurrence-free (aHR 25.48; p <0.001) and overall (aHR 9.6; p = 0.003) survival, and significant enrichment of CD8 T cell exhaustion signatures (q = 0.0296). CONCLUSIONS: HCC-IS is a distinct HCC subtype associated with a good prognosis and frequent EBV-positive TILs. However, paradoxically, a high density of EBV-positive TILs in tumors is associated with inferior prognostic outcomes. Patients with HCC-IS could be candidates for immunotherapy. LAY SUMMARY: Hepatocellular carcinomas with histologic evidence of abundant immune cell infiltration are characterized by frequent activation of Epstein-Barr virus in tumor-infiltrating lymphocytes and less aggressive clinical behavior. However, a high density of Epstein-Barr virus-positive tumor-infiltrating lymphocytes is associated with inferior prognostic outcomes, possibly as a result of immune escape due to significant CD8 T cell exhaustion.

Anaerosacchariphilus polymeriproducens gen. nov., sp. nov., an anaerobic bacterium isolated from a salt field.

A Gram-stain-negative oval-rod-shaped, spore-forming anaerobic bacterium, designated as strain MCWD5T, was isolated from sediment of a salt pond in the Republic of Korea (35° 7' 18″ N 126° 19' 4″ E). The 16S rRNA gene sequence analysis revealed that strain MCWD5T had low similarity values to members in the family Lachnospiraceae, such as Robinsoniella peoriensis PPC31T (94.8 %), Ruminococcusgauvreauii CCRI-16110T (94.2 %) and Lachnotalea glycerini DLD10T (94.0 %), and its phylogenetic position is unstable. The strain could grow at 20-42 °C (optimum, 38-42 °C), pH 5.5-10.0 (pH 7.0) and with 0-6 % (2.0 %) NaCl. Strain MCWD5T could not use nitrate, nitrite, sulfate or sulfite as electron acceptors. The strain could utilize various carbohydrates, such as arabinose, cellobiose, glucose, etc., and polymers such as pectin and starch. The major fatty acids of strain MCWD5T were C14 : 0, C16 : 0, C16 : 1ω7c, C18 : 1ω7c DMA and summed feature 8 (C17 : 1ω8c and/or C17 : 2), which was clearly different from those of related genera. The major polar lipids were diphosphatidyglycerol, phosphatidyglycerol and an unknown phospholipid. Based on the results of phylogenetic, physiologic and chemotaxonomic studies, Anaerosacchariphilus polymeriproducens gen. nov., sp. nov. with the type strain MCWD5T (=KCTC 15595T=DSM 105757T) is proposed in the family Lachnospiraceae.

Molecular characterization of single-chain antibody variable fragments (scFv) specific to Pep27 from Streptococcus pneumoniae.

Pep27 from Streptococcus pneumoniae is reported to initiate pneumococcal autolysis, thereby constituting a major virulence factor. Although a few antisera recognizing Pep27 have been reported, no monoclonal, well-characterized antibody for Pep27 has been developed. Here we screened two single-chain antibody variable fragments (scFv) using a phage display from a large human synthetic scFv library to select clones E2 and F9. Dissociation constants (Kd) of E2 and F9 were 1.1 µM and 0.50 µM, respectively. E2 and F9 did not cross-react with other pneumococcal and unrelated proteins. The epitopes of Pep27 were localized to residues 24, 26 and 27 by alanine scanning. Molecular docking analysis supported the experimentally investigated epitope. The E2 and F9 clones specifically detected Pep27 in an environment mimicking in vivo conditions, demonstrated in human serum. The scFv clones characterized here represent molecular tools for the detection of pneumococcal diseases with potential for further improvement in affinity.

Molecular characterization of a single-chain antibody variable fragment (scFv) specific for PspA from Streptococcus pneumoniae.

Streptococcus pneumoniae is a major infectious agent responsible for pneumonia, otitis media, sepsis and meningitis. Pneumococcal surface protein A (PspA) is a well-characterized virulence factor localized on the surface and a target for vaccine development. In this study, we screened a single-chain antibody variable fragment (scFv) using phage display from a human synthetic library to select a clone 2B11. Affinity (Kd) of 2B11 was measured to be 5 nM using biolayer interferometry. 2B11 exhibited a dose-dependent recognition of recombinant PspA with no cross-reactivity towards pneumococcal antigens. The epitope on PspA was defined to residues 231-242 by mutational analysis. Molecular docking analysis supported the experimentally determined epitope, suggesting that the helix spanning residues 231-242 can bind to 2B11 with residues in the CDR-H3 (complementarity determining region 3 in the heavy chain) actively participating in the molecular contacts. Comparison of 2B11 with a commercial PspA antibody revealed that 2B11 exhibited a better specificity towards recombinant PspA antigen. 2B11 was capable of detecting endogenous PspA from pneumococcal lysates with affinity similar to that of the commercial antibody. Our study provides a molecular tool for biosensors detecting pneumococcal diseases.

Temporal changes in physiological parameters of systemic inflammatory response syndrome during the three days prior to a diagnosis of sepsis: a case-control study.

AIMS AND OBJECTIVES: This study was conducted to determine temporal patterns of early changes in physiological parameters of systemic inflammatory response syndrome over three days prior to a diagnosis of sepsis. BACKGROUND: Early detection and timely management of systemic inflammatory response syndrome are often not implemented due to a failure to recognise or diagnose systemic inflammatory response syndrome. DESIGN: A retrospective case-control study design was adopted. METHODS: All 81 study subjects in an intensive care unit were included: 33 case subjects who received a definitive diagnosis of sepsis and 48 control patients who were not diagnosed with systemic inflammatory response syndrome or sepsis. Vital signs (temperatures, heart rates, blood pressures and respiratory rates) and white blood cell count, urine output, serum creatinine concentration, platelet count and serum glucose level data were collected for one, two and three days prior to sepsis diagnosis. RESULTS: Homogeneity test revealed greater proportions of the aged and subjects with diabetes mellitus, hypertension and wound in the case group. Analysis also showed significant intergroup differences in systemic inflammatory response syndrome criteria score, heart rates, platelet counts and blood glucose levels, but no intergroup differences in body temperatures, blood pressures, respiratory rates, urine outputs or serum creatinine levels. A larger proportion of case subjects were fitted with a central venous or Foley catheter. CONCLUSIONS: The presence of a wound, hypertension or diabetes mellitus, and the use of an invasive medical device may increase the risk of systemic inflammatory response syndrome. Of the physiological parameters examined, heart rate, platelet counts, and blood glucose levels might serve as significant early signs of systemic inflammatory response syndrome. RELEVANCE TO CLINICAL PRACTICE: Caution should be observed whenever diabetic or hypertension patients develop sudden and persistent hyperglycaemia or tachycardia, and nurses should also be aware of the potential for systemic inflammatory response syndrome in patients with a central venous or indwelling urinary catheter.

Questionnaire Development to Assess Risk Factors for Environmental Diseases of Children in Daejeon.

Background: Allergic diseases are common in children and adolescents. It is important to assess the prevalence and risk factors of environmental diseases to implement tailored countermeasures. Methods: This questionnaire study investigated factors associated with environmental diseases in elementary school children with an environmental disease from 150 households in Daejeon Metropolitan City, South Korea in 2021. Results: The participants comprised 55.7% girls and 44.3% boys, and the mean age was 10.1 years with an even age distribution. The typical risk factors observed were the type of roads nearby, the presence of mold or stains within the residence, pet ownership, and frequency of indoor ventilation and cleaning. Notably, 73.2% of the households had an eight-lane road nearby, 40.2% reported leaks, stains, or mold within their homes during the past year, and 37.1% ventilated their homes for less than 30 min. After education on preventing and managing environmental diseases, significant changes were observed in bedding washing frequency, average ventilation duration per session, and duration of humidifier usage (p < 0.05-0.001), with improvements in lifestyle. Conclusions: Our study can be used as a reference for expanding indoor air quality control education for parents with children with an environmental disease and providing tailored environmental consultations.

Graph-Based Conditional Generative Adversarial Networks for Major Depressive Disorder Diagnosis With Synthetic Functional Brain Network Generation.

Major Depressive Disorder (MDD) is a pervasive disorder affecting millions of individuals, presenting a significant global health concern. Functional connectivity (FC) derived from resting-state functional Magnetic Resonance Imaging (rs-fMRI) serves as a crucial tool in revealing functional connectivity patterns associated with MDD, playing an essential role in precise diagnosis. However, the limited data availability of FC poses challenges for robust MDD diagnosis. To tackle this, some studies have employed Deep Neural Networks (DNN) architectures to construct Generative Adversarial Networks (GAN) for synthetic FC generation, but this tends to overlook the inherent topology characteristics of FC. To overcome this challenge, we propose a novel Graph Convolutional Networks (GCN)-based Conditional GAN with Class-Aware Discriminator (GC-GAN). GC-GAN utilizes GCN in both the generator and discriminator to capture intricate FC patterns among brain regions, and the class-aware discriminator ensures the diversity and quality of the generated synthetic FC. Additionally, we introduce a topology refinement technique to enhance MDD diagnosis performance by optimizing the topology using the augmented FC dataset. Our framework was evaluated on publicly available rs-fMRI datasets, and the results demonstrate that GC-GAN outperforms existing methods. This indicates the superior potential of GCN in capturing intricate topology characteristics and generating high-fidelity synthetic FC, thus contributing to a more robust MDD diagnosis.

Obstructive Sleep Apnea and Medical Comorbidities in the Asian Population: Evidence From a Nationwide Healthcare System Data in South Korea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a breathing disorder characterized by recurrent airway obstruction during sleep. Previous western studies have investigated the link between medical disorders and the pathophysiology of OSA. The prevalence and comorbidity rates of OSA; however, vary across different countries and racial groups. This study aimed to delve into medical comorbidities in patients with OSA using a large nationwide healthcare database in Korea. METHODS: This nationwide study used the Korean National Health Insurance claims database (2010-2019). The effect of OSA on the incidence of medical disorders was estimated using the Cox proportional hazard ratio (HR) model. The results were reported as crude and adjusted HRs with 95% confidence intervals (CI). Subgroup analysis was conducted by sex and age. RESULTS: In total, 103,785 patients with OSA and 207,570 patients without OSA were included. OSA group had significantly higher HRs for ischemic heart disease and stroke even after adjusting for hypertension, dyslipidemia, and diabetes. The OSA group also showed an increased risk of metabolic syndrome-related diseases, chronic kidney disease, and gastroesophageal reflux disease. Female patients with OSA exhibited notably higher rates of comorbid liver cirrhosis, chronic obstructive pulmonary disease, and asthma. The cardiovascular burden of patients increased in accordance with the patients' age. CONCLUSION: Korean patients with OSA have a significantly increased risk of cardio-cerebrovascular diseases, which aligns with the previous studies conducted in the western countries. This result holds particular significance as it represents the first nationwide, population-based study conducted in Asia.