Inverse chirality-induced spin selectivity effect in chiral assemblies of π-conjugated polymers.

Coupling of spin and charge currents to structural chirality in non-magnetic materials, known as chirality-induced spin selectivity, is promising for application in spintronic devices at room temperature. Although the chirality-induced spin selectivity effect has been identified in various chiral materials, its Onsager reciprocal process, the inverse chirality-induced spin selectivity effect, remains unexplored. Here we report the observation of the inverse chirality-induced spin selectivity effect in chiral assemblies of π-conjugated polymers. Using spin-pumping techniques, the inverse chirality-induced spin selectivity effect enables quantification of the magnitude of the longitudinal spin-to-charge conversion driven by chirality-induced spin selectivity in different chiral polymers. By widely tuning conductivities and supramolecular chiral structures via a printing method, we found a very long spin relaxation time of up to several nanoseconds parallel to the chiral axis. Our demonstration of the inverse chirality-induced spin selectivity effect suggests possibilities for elucidating the puzzling interplay between spin and chirality, and opens a route for spintronic applications using printable chiral assemblies.

Taurodeoxycholate, a GPCR19 agonist, ameliorates atopic dermatitis in Balb/c mice.

Keratinocytes are pivotal cells in the pathogenesis of atopic dermatitis (AD) as much as Th2 cells. In this sense, regulation of pro-inflammatory features of keratinocytes might be useful for AD patients. P2X7R-mediated activation of NLRP3 inflammasome (N3I) in keratinocytes and myeloid cells plays crucial roles in AD. Nonetheless, inhibition of P2X7R has not been feasible because of polymorphisms and ubiquitous expression of P2X7R. Here, we report that GPCR19 colocalizes with P2X7R, and a GPCR19 agonist (taurodeoxycholate [TDCA]) inhibits the activation of P2X7R. Noncistronically, TDCA inhibits NF-kB activation via the adenylate cyclase-PKA pathway and BzATP-mediated Ca++ mobilization. Cistronically, TDCA suppresses the expression of P2X7R and N3I components in keratinocytes. NLRP3 oligomerization and the production of mature IL-1ß and IL-18 was suppressed by TDCA treatment in keratinocytes. Topical TDCA treatment ameliorates proinflammatory features of AD in mice induced by DNCB, MC903, or oxazolone. Taken together, a GPCR19 agonist such as TDCA might inhibit P2X7R-mediated N3I activation of keratinocytes, which is crucial for the pathogenesis of AD.

Association between food insecurity and risk of chronic diseases affecting the kidney in older Korean patients.

AIMS: This study aimed to examine the association between food insecurity and the prevalence of chronic diseases among older adults in South Korea and to compare the findings with data from the United States (US). MATERIALS AND METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey (KNHANES) V (2010 - 2012) and VI (2013 - 2015) and 4 years (2012 - 2015) of food security questionnaire data. The data of 46,189 National Health and Nutrition Examination Survey participants (1999 - 2016) were subjected to propensity score-matched (PSM) analysis. RESULTS: We included 7,914 individuals from the KNHANES. In the older group (age > 65 years), no differences were observed in the prevalence of hypertension, diabetes, chronic kidney disease (CKD), and metabolic syndrome across the income groups. Income, education, and food security had no impact on hypertension, diabetes, and CKD prevalence in the multivariate logistic analysis after PSM. CKD was not associated with food insecurity (odds ratio (OR), 1.26; 95% confidence interval (CI), 0.94 - 1.26) in the final model using the KNHANES data; however, the U.S. NHANES data showed that an increased risk of hypertension was associated with food insecurity (OR, 1.27; 95% CI, 1.04 - 1.55). CONCLUSION: As per the U.S. NHANES data, food insecurity was associated with a high prevalence of hypertension, while as per the South Korean KNHANES data, food insecurity was not found to be associated with CKD, indicating divergent relationships between food insecurity and chronic diseases in the two countries. Further research is needed to explore these differences.

Markedly Increased Mean Platelet Volume in Bacterial Meningitis.

BACKGROUND: Differentiating bacterial and viral meningitis is crucial, and this study explored the potential of mean platelet volume (MPV) as a marker for differentiation. METHODS: Blood samples were collected from patients with central nerve system related manifestations, and MPV was tested. Cerebrospinal fluid samples were obtained and bacterial culture and the FilmArray ME panel were performed. The distribution of MPV was compared between groups. RESULTS: The study included 8 patients in the bacterial meningitis group and 12 patients in the viral meningitis group. The bacterial meningitis group showed a significantly higher median MPV of 10.9 (9.2 - 11.6) fL compared to the viral meningitis group with 8.4 (8.1 - 8.8) fL (p < 0.0001). CONCLUSIONS: MPV could serve as a diagnostic indicator to differentiate between bacterial and viral meningitis. Larger studies are needed to validate these findings.

Role of Interfacial Interactions in the Graphene-Directed Assembly of Monolayer Conjugated Polymers.

Development of graphene-organic hybrid electronics is one of the most promising directions for next-generation electronic materials. However, it remains challenging to understand the graphene-organic semiconductor interactions right at the interface, which is key to designing hybrid electronics. Herein, we study the influence of graphene on the multiscale morphology of solution-processed monolayers of conjugated polymers (PII-2T, DPP-BTz, DPP2T-TT, and DPP-T-TMS). The strong interaction between graphene and PII-2T was manifested in the high fiber density and high film coverage of monolayer films deposited on graphene compared to plasma SiO2 substrates. The monolayer films on graphene also exhibited a higher relative degree of crystallinity and dichroic ratio or polymer alignment, i.e., higher degree of order. Raman spectroscopy revealed the increased backbone planarity of the conjugated polymers upon deposition on graphene as well as the existence of electronic interaction across the interface. This speculation was further substantiated by the results of photoelectron spectroscopy (XPS and UPS) of PII-2T, which showed a decrease in binding energy of several atomic energy levels, movement of the Fermi level toward HOMO, and an increase in work function, all of which indicate p-doping of the polymer. Our results provide a new level of understanding on graphene-polymer interactions at nanoscopic interfaces and the consequent impact on multiscale morphology, which will aid in the design of efficient graphene-organic hybrid electronics.

Serum phosphorus and subclinical coronary atherosclerosis in asymptomatic subjects without kidney dysfunction.

BACKGROUND AND AIMS: There is limited data on the association between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in low-risk asymptomatic subjects without kidney dysfunction. MATERIALS AND METHODS: We retrospectively analyzed 1,636 Korean individuals (mean age 52.6 ± 7.6 years; males: 712 (43.5%)) without traditional cardiovascular risk factors (CVRFs) and kidney dysfunction who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Traditional CVRFs were defined as follows: systolic/diastolic blood pressure ≥ 140/90 mmHg, fasting blood glucose ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5%, total cholesterol ≥ 240 mg/dL, low-density lipoprotein cholesterol ≥ 160 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL, body mass index ≥ 25.0 kg/m2, currently smoking, and medical history of hypertension, diabetes, and hyperlipidemia. Study participants were stratified into tertiles according to their SPC levels (≤ 3.2, 3.3 - 3.6, and ≥ 3.7 mg/dL). RESULTS: 297 (18.2%) study participants had subclinical coronary atherosclerosis, characterized by any coronary plaque on CCTA. In multivariable regression analysis, the risk of subclinical coronary atherosclerosis increased in the second (odds ratio (OR): 1.629; 95% confidence interval (CI): 1.149 - 2.308; p = 0.006) and third (OR: 1.645; 95% CI: 1.093 - 2.476; p = 0.017) SPC tertiles compared to the first SPC tertile. In addition, the risk of calcified plaque increased in the second (OR: 1.605; 95% CI: 1.124 - 2.292; p = 0.009) and third (OR 1.790; 95% CI 1.179 - 2.716; p = 0.006) SPC tertiles. CONCLUSION: In low-risk asymptomatic Korean individuals without kidney dysfunction, a higher SPC level was an independent predictor of subclinical coronary atherosclerosis.

Higher expression of KCNK10 (TREK-2) K+ channels and their functional upregulation by lipopolysaccharide treatment in mouse peritoneal B1a cells.

Innate-like CD5+ B1a cells localized in serous cavities are activated by innate stimuli, such as lipopolysaccharide (LPS), leading to T cell-independent antibody responses. Although ion channels play crucial roles in the homeostasis and activation of immune cells, the electrophysiological properties of B1a cells have not been investigated to date. Previously, in the mouse B cell lymphoma cells, we found that the voltage-independent two-pore-domain potassium (K2P) channels generate a negative membrane potential and drive Ca2+ influx. Here, we newly compared the expression and activities of K2P channels in mouse splenic follicular B (FoB), marginal zone B (MZB), and peritoneal B1a cells. Next-generation sequencing analysis showed higher levels of transcripts for TREK-2 and TWIK-2 in B1a cells than those in FoB or MZB cells. Electrophysiological analysis, using patch clamp technique, revealed higher activity of TREK-2 with the characteristic large unitary conductance (~ 250 pS) in B1a than that in FoB or MZB cells. TREK-2 activity was further increased by LPS treatment (>2 h), which was more prominent in B1a than that in MZB or FoB cells. The cytosolic Ca2+ concentration of B cells was decreased by high-K+-induced depolarization (ΔRKCl (%)), suggesting the basal Ca2+ influx to be driven by negative membrane potential. The LPS treatment significantly increased the ΔRKCl (%) in B1a, though not in FoB and MZB cells. Our study was the first to compare the K2P channels in mouse primary B cell subsets, elucidating the functional upregulation of TREK-2 and augmentation of Ca2+ influx by the stimulation of Toll-like receptor 4 in B1a cells.

Mean Platelet Volume in Pediatric Patients Infected with Mycoplasma pneumoniae.

BACKGROUND: Mean platelet volume (MPV) is a parameter of platelet size and activity. Research on MPV in Mycoplasma pneumoniae infection is not reported. METHODS: This study reviewed whether there was a difference in the MPV in the results of M. pneumoniae immunoglobulin M (IgM) and polymerase chain reaction (PCR) tests in 210 pediatric patients with pneumonia suspected to be caused by M. pneumoniae. RESULTS: The MPV was significantly lower in the IgM-positive group than in the IgM- negative group (p = 0.041). Among the PCR-positive patients (n = 73), the IgM-positive group showed significantly lower MPV than the IgM-negative group (p = 0.014). Meanwhile, among the PCR-negative patients (n = 137), there was no significant difference in the MPV between the IgM-positive and negative groups (p = 0.269). CONCLUSIONS: This result suggests that pneumonia caused by M. pneumoniae could be a condition associated with low MPV.

The Application of Control Materials for Ongoing Quality Management of Next-Generation Sequencing in a Clinical Genetic Laboratory.

Next-generation sequencing (NGS) has played an important role in detecting genetic variants with pathologic and therapeutic potential. The advantages of NGS, such as high-throughput sequencing capacity and massively parallel sequencing, have a significant impact on realization of genetic profiling in clinical genetic laboratories. These changes have enabled clinicians to execute precision medicine in diagnosis, prognosis, and treatment for patients. However, to adapt targeted gene panels in diagnostic use, analytical validation and ongoing quality control should be implemented and applied with both practical guidelines and appropriate control materials. Several guidelines for NGS quality control recommend usage of control materials such as HapMap cell lines, synthetic DNA fragments, and genetically characterized cell lines; however, specifications or applications of such usage are insufficient to guideline method development. This review focuses on what factors should be considered before control material selection for NGS assay and practical methods of how they could be developed in clinical genetic laboratories. This review also provides the detailed sources of critical information related to control materials.

Quantitative and Qualitative QC of Next-Generation Sequencing for Detecting Somatic Variants: An Example of Detecting Clonal Hematopoiesis of Indeterminate Potential.

BACKGROUND: Because next-generation sequencing (NGS) for detecting somatic mutations has been adopted in clinical fields, both qualitative and quantitative QC of the somatic variants through whole coding regions detected by NGS is crucial. However, specific applications or guidelines, especially for quantitative QC, are currently insufficient. Our goal was to devise a practical approach for both quantitative and qualitative QC using an example of detecting clonal hematopoiesis of indeterminate potential (CHIP). METHODS: We applied the QC scheme using commercial reference materials and in-house QC materials (IQCM) composed of haplotype map and cancer cell lines for monitoring CHIP. RESULTS: This approach efficiently validated a customized CHIP NGS assay. Accuracy, analytical sensitivity, analytical specificity, qualitative precision (concordance), and limit of detection achieved were 99.87%, 98.53%, 100.00%, 100.00%, and 1.00%, respectively. The quantitative precision analysis also had a higher CV percentage at a lower alternative read depth (R2 = 0.749∼0.858). Use of IQCM ensured more than 100-fold reduction in the cost per run compared with that achieved using commercial reference materials. CONCLUSION: Our approach determined the general analytical performance of NGS for detecting CHIP and recognized limitations such as lower precision at a lower level of variant burden. This approach could also be theoretically expanded to a general NGS assay for detecting somatic variants. Considering the reliable NGS results and cost-effectiveness, we propose the use of IQCM for QC of NGS assays at clinical laboratories.

Association of baseline histopathology and kidney donor risk index with graft outcomes in deceased donor kidney transplantation
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BACKGROUND: Donor organ quality is a key determinant of graft outcomes in deceased donor kidney transplantation (DDKT). The predictive values of baseline histopathology and several clinical scoring systems for long-term graft outcomes have been evaluated, but the results remain controversial. MATERIALS AND METHODS: We screened 167 patients who underwent DDKT at Ulsan University Hospital from April 2003 to June 2016. Among them, 66 patients who underwent baseline kidney biopsy and whose kidney donor risk index (KDRI) was available were included in this analysis. All baseline biopsies were rescored according to the updated Banff classification. RESULTS: Median follow-up was 22 months. Mean age of recipients and donors was 51.4 and 44.7 years, respectively. Mean KDRI was 1.40 ± 0.44. During follow-up, delayed graft function and biopsy-proven acute rejection (BPAR) developed in 7 and 11 patients, respectively. Graft failure occurred in 2 patients. In Cox regression analysis, interstitial fibrosis/tubular atrophy (IFTA) (hazard ratio (HR) = 3.59; p = 0.049) was a significant risk factor for BPAR. In multivariate linear regression, age (standardized ß (SB) = -0.282; p = 0.002), BPAR (SB = -0.406; p < 0.001), KDRI (SB = -0.277; p = 0.003), and IFTA (SB = -0.298; p = 0.001) were significant predictors of last-visit estimated glomerular filtration rate (eGFR). CONCLUSION: Several clinical and pathologic parameters, such as KDRI and IFTA, may be helpful for predicting long-term graft outcomes, including BPAR and last-visit eGFR, in DDKT.
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Ultra Gas-Proof Polymer Hybrid Thin Layer.

Hermetic sealing is an important technology for isolating and protecting air-sensitive materials and is key in the development of foldable and stretchable electronic devices. Here we report an ultra gas-proof polymer hybrid thin layer prepared by filling the free volume of the polymer with Al2O3 using gas-phase atomic layer infiltration. The high-density polymer-inorganic hybrid shows extremely low gas transmission rate, below the detection limit of the Ca corrosion test (water vapor transmission rate <10-7 g m-2 day-1). Furthermore, because of the remarkable nanometer-scale thinness of the complete polymer-inorganic hybrid, it is highly flexible, which makes it useful for hermetic sealing of stretchable and foldable devices.

DeviCNV: detection and visualization of exon-level copy number variants in targeted next-generation sequencing data.

BACKGROUND: Targeted next-generation sequencing (NGS) is increasingly being adopted in clinical laboratories for genomic diagnostic tests. RESULTS: We developed a new computational method, DeviCNV, intended for the detection of exon-level copy number variants (CNVs) in targeted NGS data. DeviCNV builds linear regression models with bootstrapping for every probe to capture the relationship between read depth of an individual probe and the median of read depth values of all probes in the sample. From the regression models, it estimates the read depth ratio of the observed and predicted read depth with confidence interval for each probe which is applied to a circular binary segmentation (CBS) algorithm to obtain CNV candidates. Then, it assigns confidence scores to those candidates based on the reliability and strength of the CNV signals inferred from the read depth ratios of the probes within them. Finally, it also provides gene-centric plots with confidence levels of CNV candidates for visual inspection. We applied DeviCNV to targeted NGS data generated for newborn screening and demonstrated its ability to detect novel pathogenic CNVs from clinical samples. CONCLUSIONS: We propose a new pragmatic method for detecting CNVs in targeted NGS data with an intuitive visualization and a systematic method to assign confidence scores for candidate CNVs. Since DeviCNV was developed for use in clinical diagnosis, sensitivity is increased by the detection of exon-level CNVs.

Acute copper sulfate poisoning resulting from dermal absorption.

We report a Korean worker who experienced dermal exposure to a hot copper sulfate solution at his workplace and developed severe acute copper sulfate poisoning. A 53-year-old male worker, who was employed in a lead smelter for 5 years, slipped, and his right lower leg entered a copper sulfate solution, leading to severe burns of the right lower leg. Two days later, he developed severe intravascular hemolysis with methemoglobinemia. He also suffered from acute kidney injury, had an asymptomatic cerebral ischemic stroke, and melena due to multiple shallow gastric ulcers. His serum copper level was mildly elevated (153.6 µg/dL, reference: 64.0-134 µg/dL). He was transfused with red blood cell concentrate and supported by hemodialysis. After 13 sessions of hemodialysis and several blood transfusions, he completely recovered. Most previously reported incidents of severe acute copper sulfate poisoning were from accidental or suicidal oral intake. There are few previous reports of systemic copper sulfate toxicity following exposure through burned skin.

Mutations in DNA Gyrase and Topoisomerase IV in Ciprofloxacin-Nonsusceptible Extended-Spectrum -Lactamase-Producing Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: We investigated mutations in the quinolone resistance-determining region (QRDR) of ciprofloxacinnonsusceptible extended-spectrum -lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae by a statistical analysis. METHODS: We collected 97 clinical isolates of ciprofloxacin-nonsusceptible ESBL-producing E. coli (55 strains) and K. pneumoniae (42 strains) from a tertiary-care university hospital in Seoul, Republic of Korea, between 2006 and 2008. The QRDR of the gyrA, gyrB, parC, and parE genes were amplified by PCR and sequenced. RESULTS: Most E. coli isolates (53/55; 96.4%) with a minimum inhibitory concentration of ≥ 64 mg/L against ciprofloxacin had double mutations in gyrA (Ser-83Leu and Asp-87Asn) and at least one mutation in parC (Ser-80 Ile or Glu-84Val), with or without one in parE. Fifty E. coli (90.9%) isolates had a mutation in parE, of which Ile-529Leu (70.9%) was the most frequent. However, we could not find statistically significant variables in increasing ciprofloxacin resistance in E. coli isolates. Thirty-six K. pneumoniae isolates (36/42; 85.7%) had at least one mutation in gyrA, gyrB, or parC, and the mutation in gyrA might have been associated with plasmid-mediated quinolone-resistance (PMQR). Ser-80Ile in parC and aac(6')-Ib-cr in the K. pneumoniae isolates were significantly associated with an increased MIC of ciprofloxacin by ordinal logistic regression analysis. CONCLUSIONS: The Ser-80Ile in parC and aac(6')-Ib-cr in K. pneumoniae are supposed to play an important role in increased ciprofloxacin resistance, but statistically significant variables could not be found in E. coli isolates in the present study.

Comparative analysis of BRCA1 and BRCA2 variants of uncertain significance in patients with breast cancer: a multifactorial probability-based model versus ACMG standards and guidelines for interpreting sequence variants.

PURPOSE: To investigate variants of uncertain significance (VUS) in BRCA1 and BRCA2, we assessed the multifactorial posterior probability of VUS in BRCA1 and BRCA2 and compared these analyses with interpretations according to the recently released American College of Medical Genetics and Genomics (ACMG) standards and guidelines. METHODS: The analysis involved 715 Korean patients with breast cancer. The multifactorial probability of a VUS was analyzed using the prior probability and combined likelihoods of personal and family history, the pathologic profile of the breast cancer, and co-occurrence with pathogenic variants. Results were compared with those obtained according to the ACMG standards/guidelines. RESULTS: Sixteen VUS from 51 BRCA1 VUS carriers and 28 VUS from 62 BRCA2 VUS carriers were analyzed. There was a slight agreement between the two analyses, with a kappa value of 0.14 (95% confidence interval (CI) = -0.34 to 0.62) for the BRCA1 VUS and a kappa value of 0.17 (95% CI = -0.10 to 0.49) for the BRCA2 VUS. CONCLUSION: We propose that genetic counseling should be based on the concordant results between these two analyses. When discrepancies are found, those variants are still considered VUS and careful counseling should be provided.Genet Med 18 12, 1250-1257.

Cross-stacked single-crystal organic nanowire p-n nanojunction arrays by nanotransfer printing.

We fabricated cross-stacked organic p-n nanojunction arrays made of single-crystal 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-PEN) and fullerene (C60) nanowires as p-type and n-type semiconductors, respectively, by using a nanotransfer printing technique. Single-crystal C60 nanowires were synthesized inside nanoscale channels of a mold and directly transferred onto a desired position of a flexible substrate by a lubricant liquid layer. In the consecutive printing process, single-crystal TIPS-PEN nanowires were grown in the same way and then perpendicularly aligned and placed onto the C60 nanowire arrays, resulting in a cross-stacked single-crystal organic p-n nanojunction array. The cross-stacked single-crystal TIPS-PEN/C60 nanowire p-n nanojunction devices show rectifying behavior with on/off ratio of ∼ 13 as well as photodiode characteristic with photogain of ∼ 2 under a light intensity of 12.2 mW/cm(2). Our study provides a facile, solution-processed approach to fabricate a large-area array of organic crystal nanojunction devices in a desired arrangement for future nanoscale electronics.

Observation of Charge Separation and Space-Charge Region in Single-Crystal P3HT/C60 Heterojunction Nanowires.

We directly observed charge separation and a space-charge region in an organic single-crystal p-n heterojunction nanowire, by means of scanning photocurrent microscopy. The axial p-n heterojunction nanowire had a well-defined planar junction, consisted of P3HT (p-type) and C60 (n-type) single crystals and was fabricated by means of the recently developed inkjet-assisted nanotransfer printing technique. The depletion region formed at the p-n junction was directly observed by exploring the spatial distribution of photogenerated carriers along the heterojunction nanowire under various applied bias voltages. Our study provides a facile approach toward the precise characterization of charge transport in organic heterojunction systems as well as the design of efficient nanoscale organic optoelectronic devices.

Effects of streptozotocin and unilateral nephrectomy on L-type Ca²âº channels and membrane capacitance in arteriolar smooth muscle cells.

Diabetes mellitus and hypertension are common diseases frequently coexisting. Although augmentation of L-type Ca(2+) channel (ICaL) activity has been reported in vascular smooth muscle cells (VSMCs) of a spontaneously hypertensive rat model, no study on ICaL has been conducted for coexisting hypertension and diabetes. Sprague Dawley rats were assigned to four groups: a sham-operated control group (CG), a unilateral nephrectomy group (UNG), a streptozotocin (STZ)-induced type 1 diabetic group (SDG) and a coexisting hypertension and diabetes group (DHG), which underwent nephrectomy and received STZ injection. Blood pressure (BP) was significantly lower in the CG than in the other three groups. The membrane capacitance of VSMCs was nearly doubled in the SDG and DHG but not in the UNG. The ICaL was increased approximately 2-fold in both the UNG and SDG and approximately 4-fold in the DHG. The current density of ICaL was increased approximately 2-fold in the UNG and DHG, while no significant increase was seen in the SDG. The rate of Ca(2+) removal was inhibited significantly, by ~33 %, in the DHG. In conclusion, the effects of hypertension and diabetes on ICaL were apparently additive, and the vascular consequences of combined diabetes and hypertension may be caused by an elevated ICaL and slowed Ca(2+) removal.

Evaluation of performance of the Real-Q NTM-ID kit for rapid identification of eight nontuberculous mycobacterial species.

We evaluated a multiplex real-time PCR and melting curve analysis assay (Real-Q NTM-ID kit; Biosewoom, Seoul, South Korea) for the identification of eight common nontuberculous mycobacterial species, using 30 type strains and 230 consecutive clinical isolates. The concordance rate of this assay with multigene sequence-based typing was 97.0% (223/230 isolates).