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.

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.

Subtle Molecular Changes Largely Modulate Chiral Helical Assemblies of Achiral Conjugated Polymers by Tuning Solution-State Aggregation.

Understanding the solution-state aggregate structure and the consequent hierarchical assembly of conjugated polymers is crucial for controlling multiscale morphologies during solid thin-film deposition and the resultant electronic properties. However, it remains challenging to comprehend detailed solution aggregate structures of conjugated polymers, let alone their chiral assembly due to the complex aggregation behavior. Herein, we present solution-state aggregate structures and their impact on hierarchical chiral helical assembly using an achiral diketopyrrolopyrrole-quaterthiophene (DPP-T4) copolymer and its two close structural analogues wherein the bithiophene is functionalized with methyl groups (DPP-T2M2) or fluorine atoms (DPP-T2F2). Combining in-depth small-angle X-ray scattering analysis with various microscopic solution imaging techniques, we find distinct aggregate in each DPP solution: (i) semicrystalline 1D fiber aggregates of DPP-T2F2 with a strongly bound internal structure, (ii) semicrystalline 1D fiber aggregates of DPP-T2M2 with a weakly bound internal structure, and (iii) highly crystalline 2D sheet aggregates of DPP-T4. These nanoscopic aggregates develop into lyotropic chiral helical liquid crystal (LC) mesophases at high solution concentrations. Intriguingly, the dimensionality of solution aggregates largely modulates hierarchical chiral helical pitches across nanoscopic to micrometer scales, with the more rigid 2D sheet aggregate of DPP-T4 creating much larger pitch length than the more flexible 1D fiber aggregates. Combining relatively small helical pitch with long-range order, the striped twist-bent mesophase of DPP-T2F2 composed of highly ordered, more rigid 1D fiber aggregate exhibits an anisotropic dissymmetry factor (g-factor) as high as 0.09. This study can be a prominent addition to our knowledge on a solution-state hierarchical assembly of conjugated polymers and, in particular, chiral helical assembly of achiral organic semiconductors that can catalyze an emerging field of chiral (opto)electronics.

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.

Differential Impact of Degree of Hypertension on Subclinical Coronary Atherosclerosis in Asymptomatic Subjects With and Without Diabetes Mellitus.

This study sought to evaluate the association between the degree of hypertension and subclinical coronary atherosclerosis in asymptomatic subjects with and without diabetes mellitus (DM). We retrospectively analyzed 7,352 asymptomatic subjects (mean age 52.8 ± 7.8 years; 4,689 [63.8%] men) with no history of coronary artery disease who voluntarily underwent coronary computed tomography angiography as part of a general health examination. The classification of hypertension was adapted from the American College of Cardiology and American Heart Association 2017 guideline. Subclinical coronary atherosclerosis was defined as the presence of coronary plaque by coronary computed tomography angiography. In subjects without DM (n = 6,598), after the adjustment for cardiovascular risk factors, subclinical coronary atherosclerosis was significantly associated with both stage 1 hypertension (adjusted odds ratio [aOR] 1.356; 95% confidence interval [CI], 1.167 to 1.575; p <0.001) and stage 2 hypertension (aOR, 1.614; 95% CI, 1.329 to 1.961; p <0.001) groups compared with the normal group. In contrast, in subjects with DM (n = 754), there was no statistical difference in the aOR of the stage 1 hypertension group for the presence of coronary plaque (aOR, 1.449; 95% CI, 0.982 to 2.136; p = 0.061). However, the stage 2 hypertension group had a significant association with subclinical coronary atherosclerosis (aOR, 2.067; 95% CI, 1.287 to 3.322; p = 0.003). In subjects without DM, both stages 1 and 2 hypertension were associated with subclinical coronary atherosclerosis. However, in subjects with DM, stage 2 hypertension was only associated with an increased risk of subclinical coronary atherosclerosis.

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.

Concentration-Driven Self-Assembly of PS-b-PLA Bottlebrush Diblock Copolymers in Solution.

Bottlebrush polymers are a class of semiflexible, hierarchical macromolecules with unique potential for shape-, architecture-, and composition-based structure-property design. It is now well-established that in dilute to semidilute solution, bottlebrush homopolymers adopt a wormlike conformation, which decreases in extension (persistence length) as the concentration and molecular overlap increase. By comparison, the solution phase self-assembly of bottlebrush diblock copolymers (BBCP) in a good solvent remains poorly understood, despite critical relevance for solution processing of ordered phases and photonic crystals. In this work, we combine small-angle X-ray scattering, coarse-grained simulation, and polymer synthesis to map the equilibrium phase behavior and conformation of a set of large, nearly symmetric PS-b-PLA bottlebrush diblock copolymers in toluene. Three BBCP are synthesized, with side chains of number-averaged molecular weights of 4500 (PS) and 4200 g/mol (PLA) and total backbone degrees of polymerization of 100, 255, and 400 repeat units. The grafting density is one side chain per backbone repeat unit. With increasing concentration in solution, all three polymers progress through a similar structural transition: from dispersed, wormlike chains with concentration-dependent (decreasing) extension, through the onset of disordered PS/PLA compositional fluctuations, to the formation of a long-range ordered lamellar phase. With increasing concentration in the microphase-separated regimes, the domain spacing increases as individual chains partially re-extend due to block immiscibility. Increases in the backbone degree of polymerization lead to changes in the scattering profiles which are consistent with the increased segregation strength. Coarse-grained simulations using an implicit side-chain model are performed, and concentration-dependent self-assembly behavior is qualitatively matched to experiments. Finally, using the polymer with the largest backbone length, we demonstrate that lamellar phases develop a well-defined photonic band gap in solution, which can be tuned across the visible spectrum by varying polymer concentration.

Outgrowing skin involvement in malakoplakia after kidney transplantation: A case report.

INTRODUCTION: Malakoplakia is a rare pseudotumor that arises in the context of recurrent infections, particularly in immunocompromised states. We report a case of renal allograft parenchymal malakoplakia. CASE REPORT: A 59-year-old woman successfully received a cadaveric renal transplant in June 2018. Two months after transplantation, she was treated for a urinary tract infection (UTI). In March 2019, she underwent allograft biopsy for increasing creatinine. The biopsy identified T cell mediated rejection and steroid pulse therapy was performed. In December 2019, she was hospitalized for right flank pain and pyuria, and her creatinine level was 1.9 mg/dL. Radiographic findings were suggestive of a hematoma or abscess in the perirenal area, and septated fluid collection was suspected. Biopsy results suggested malakoplakia, and von Kossa stain was positive for Michaelis- Gutmann bodies. Tissue culture demonstrated Escherichia coli, and this was treated with antibiotics. The dose of tacrolimus was reduced. The patient was discharged after 1 month of hospitalization and was maintained on oral antibiotics. Follow-up imaging revealed an increase in the extent of lesion into the adjacent abdominal wall. Assuming the case to be refractory, we performed surgical resection and abscess drainage. Although the renal parenchymal involvement persisted, the size showed a decreasing trend over 2 months of serial observation with ultrasonography. CONCLUSIONS: Malakoplakia should be considered as a differential diagnosis for recurrent UTI with graft dysfunction. Malakoplakia can be successfully treated with reduction in immunosuppression and medical therapy using long-term antibiotic treatment in most cases. However, early surgical treatment must be considered for refractory cases.

Not All Aggregates Are Made the Same: Distinct Structures of Solution Aggregates Drastically Modulate Assembly Pathways, Morphology, and Electronic Properties of Conjugated Polymers.

Tuning structures of solution-state aggregation and aggregation-mediated assembly pathways of conjugated polymers is crucial for optimizing their solid-state morphology and charge-transport property. However, it remains challenging to unravel and control the exact structures of solution aggregates, let alone to modulate assembly pathways in a controlled fashion. Herein, aggregate structures of an isoindigo-bithiophene-based polymer (PII-2T) are modulated by tuning selectivity of the solvent toward the side chain versus the backbone, which leads to three distinct assembly pathways: direct crystallization from side-chain-associated amorphous aggregates, chiral liquid crystal (LC)-mediated assembly from semicrystalline aggregates with side-chain and backbone stacking, and random agglomeration from backbone-stacked semicrystalline aggregates. Importantly, it is demonstrated that the amorphous solution aggregates, compared with semicrystalline ones, lead to significantly improved alignment and reduced paracrystalline disorder in the solid state due to direct crystallization during the meniscus-guided coating process. Alignment quantified by the dichroic ratio is enhanced by up to 14-fold, and the charge-carrier mobility increases by a maximum of 20-fold in films printed from amorphous aggregates compared to those from semicrystalline aggregates. This work shows that by tuning the precise structure of solution aggregates, the assembly pathways and the resulting thin-film morphology and device properties can be drastically tuned.

Marital Status and Subclinical Coronary Atherosclerosis in Asymptomatic Individuals.

Background Data are limited on the association between marital status and subclinical coronary atherosclerosis. This study investigated the influence of marital status on subclinical coronary atherosclerosis detected by coronary computed tomographic angiography in an asymptomatic population. Methods and Results This retrospective study analyzed 9288 asymptomatic individuals (mean age, 53.7±8.0 years; 6041 [65%] men) with no history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography during a general health examination. Marital categories were married (n=8481) versus unmarried (n=807), comprising never married (n=195), divorced (n=183), separated (n=119), and widowed (n=310) individuals. The degree and extent of subclinical coronary atherosclerosis were evaluated by coronary computed tomographic angiography; ≥50% diameter stenosis was defined as significant. Logistic regression and propensity score matching analyses were used to determine the association between marital status and subclinical coronary atherosclerosis. After adjustment for cardiovascular risk factors, no significant differences were observed in the adjusted odds ratio (OR) of unmarried status for any coronary plaque (OR, 1.077; 95% CI, 0.899-1.291), calcified plaque (OR, 1.058; 95% CI, 0.881-1.271), noncalcified plaque (OR, 0.966; 95% CI, 0.691-1.351), mixed plaque (OR, 1.301; 95% CI, 0.884-1.917), and significant coronary artery stenosis (OR, 1.066; 95% CI, 0.771-1.474). Similarly, in the 2:1 propensity-score matched population (n=2398), no statistically significant differences were observed for the OR of marital status for any subclinical coronary atherosclerosis (P>0.05 for all). Conclusions In this large cross-sectional study, marital status was not associated with an increased risk of subclinical coronary atherosclerosis.

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.

Chiral emergence in multistep hierarchical assembly of achiral conjugated polymers.

Intimately connected to the rule of life, chirality remains a long-time fascination in biology, chemistry, physics and materials science. Chiral structures, e.g., nucleic acid and cholesteric phase developed from chiral molecules are common in nature and synthetic soft materials. While it was recently discovered that achiral but bent-core mesogens can also form chiral helices, the assembly of chiral microstructures from achiral polymers has rarely been explored. Here, we reveal chiral emergence from achiral conjugated polymers, in which hierarchical helical structures are developed through a multistep assembly pathway. Upon increasing concentration beyond a threshold volume fraction, dispersed polymer nanofibers form lyotropic liquid crystalline (LC) mesophases with complex, chiral morphologies. Combining imaging, X-ray and spectroscopy techniques with molecular simulations, we demonstrate that this structural evolution arises from torsional polymer molecules which induce multiscale helical assembly, progressing from nano- to micron scale helical structures as the solution concentration increases. This study unveils a previously unknown complex state of matter for conjugated polymers that can pave way to a field of chiral (opto)electronics. We anticipate that hierarchical chiral helical structures can profoundly impact how conjugated polymers interact with light, transport charges, and transduce signals from biomolecular interactions and even give rise to properties unimagined before.

GPCR19 Regulates P2X7R-Mediated NLRP3 Inflammasomal Activation of Microglia by Amyloid ß in a Mouse Model of Alzheimer's Disease.

Amyloid ß (Aß) and/or ATP activate the NLRP3 inflammasome (N3I) via P2X7R in microglia, which is crucial in neuroinflammation in Alzheimer's disease (AD). Due to polymorphisms, subtypes, and ubiquitous expression of P2X7R, inhibition of P2X7R has not been effective for AD. We first report that taurodeoxycholate (TDCA), a GPCR19 ligand, inhibited the priming phase of N3I activation, suppressed P2X7R expression and P2X7R-mediated Ca++ mobilization and N3I oligomerization, which is essential for production of IL-1ß/IL-18 by microglia. Furthermore, TDCA enhanced phagocytosis of Aß and decreased the number of Aß plaques in the brains of 5x Familial Alzheimer's disease (5xFAD) mice. TDCA also reduced microgliosis, prevented neuronal loss, and improved memory function in 5xFAD mice. The pleiotropic roles of GPCR19 in P2X7R-mediated N3I activation suggest that targeting GPCR19 might resolve neuroinflammation in AD patients.

Clinical application of an algorithm to screen for malignant cells in body fluids using an automated hematology analyzer.

INTRODUCTION: The detection of malignant cells in body fluids (BF) with an automated hematology analyzer has been proposed as an alternative to morphological examination owing to its various advantages; however, its limitations have also been highlighted. In this study, we devised a practical algorithm to screen for malignant cells in BFs using an automated hematology analyzer. METHODS: A total of 558 BF samples, including 232 cerebrospinal fluid (CSF) samples and 326 non-CSF samples, were consecutively collected. Thereafter, the results obtained using the BF mode of Sysmex XN-350 (Sysmex, Kobe, Japan) were compared with the cytological diagnosis. A cutoff was also established to screen for malignant cells using receiver operating characteristic (ROC) curve analysis based on the final clinical judgment. RESULTS: The automated hematology analyzer showed a moderate correlation or good agreement with the existing cytological diagnosis. Further, of the ROC curves for detecting malignant cells, the absolute value of highly fluorescent cells on BF (HF-BF) in total body fluids showed the highest area under the curve (0.85 [95% confidence interval 0.82-88], p < .0001, Youden index >7×106 /L, sensitivity 93%, and specificity 65%). CONCLUSION: An automated hematology analyzer could function as a complement to cytological examination. We propose a practical and comprehensive algorithm for cytological examination that requires low- and high-resolution microscopy based on the absolute value of HF-BF in BF samples suspected of malignancy. This algorithm can more usefully detect malignant cells while taking advantage of the automated analyzer and cytological examination.

Lipoprotein(a) and subclinical coronary atherosclerosis in asymptomatic individuals.

BACKGROUND AND AIMS: There are limited data regarding the association between lipoprotein(a) (Lp[a]) and subclinical coronary atherosclerosis. This study investigated the association between Lp(a) and subclinical coronary atherosclerosis detected by coronary computed tomographic angiography (CCTA) in an asymptomatic population. METHODS: We retrospectively analyzed 7201 asymptomatic individuals (mean age 54.4 ± 7.9 years; 65.3% men with no prior history of coronary artery disease who voluntarily underwent CCTA as part of a general health examination). The degree and extent of subclinical coronary atherosclerosis were evaluated by CCTA. Study participants were stratified into quartiles according to their Lp(a) levels (<4.3, 4.3-8.9, 9.0-20.1, and ≥20.2 mg/dL). RESULTS: Of the study participants, any coronary plaque on CCTA was observed in 2557 (35.5%). Specifically, calcified, non-calcified, and mixed plaques were observed in 2411 (33.5%), 363 (5.0%) and 249 (3.5%) participants, respectively. After adjustment for the presence of cardiovascular risk factors, the fourth Lp(a) quartile was significantly associated with any coronary (odds ratio [OR] 1.212; 95% confidence interval [CI] 1.038-1.416), calcified (1.205, 95% CI 1.030-1.410), non-calcified (1.588, 95% CI 1.152-2.189), or mixed (1.674, 95% CI 1.172-2.391) plaque compared with the first Lp(a) quartile. In addition, 442 (6.1%) had significant coronary artery stenosis (≥50% diameter stenosis). The odds ratio for significant stenosis (1.537, 95% CI 1.153-2.048) was higher in the fourth quartile compared with the first quartile. CONCLUSIONS: In this large cross-sectional study with asymptomatic individuals undergoing CCTA, higher Lp(a) level was associated with subclinical coronary atherosclerosis.

Two Approaches for a Genetic Analysis of Pompe Disease: A Literature Review of Patients with Pompe Disease and Analysis Based on Genomic Data from the General Population.

In this study, two different approaches were applied in the analysis of the GAA gene. One was analyzed based on patients with Pompe disease, and the other was analyzed based on GAA genomic data from unaffected carriers in a general population genetic database. For this, GAA variants in Korean and Japanese patients reported in previous studies and in patients reported in the Pompe disease GAA variant database were analyzed as a model. In addition, GAA variants in the Korean Reference Genome Database (KRGDB), the Japanese Multi Omics Reference Panel (jMorp), and the Genome Aggregation Database (gnomAD) were analyzed. Overall, approximately 50% of the pathogenic or likely pathogenic variants (PLPVs) found in unaffected carriers were also found in real patients with Pompe disease (Koreans, 57.1%; Japanese, 46.2%). In addition, there was a moderate positive correlation (Spearman's correlation coefficient of 0.45-0.69) between the proportion of certain PLPVs in patients and the minor allele frequency of their variants in a general population database. Based on the analysis of general population databases, the total carrier frequency for Pompe disease in Koreans and Japanese was estimated to be 1.7% and 0.7%, respectively, and the predicted genetic prevalence was 1:13,657 and 1:78,013, respectively.

Analysis of Worldwide Carrier Frequency and Predicted Genetic Prevalence of Autosomal Recessive Congenital Hypothyroidism Based on a General Population Database.

To assess how genomic information of the general population reflects probabilities of developing diseases and the differences in those probabilities among ethnic groups, a general population database was analyzed with an example of congenital hypothyroidism. Twelve candidate genes that follow an autosomal recessive inheritance pattern in congenital hypothyroidism (SLC5A5, TPO, TG, IYD, DUOXA2, DUOX2, TSHR, SLC26A7, GLIS3, FOXE1, TSHB, TRHR) in the gnomAD database (v2.1.1) were analyzed. The carrier frequency (CF) and predicted genetic prevalence (pGP) were estimated. The total CF in the overall population was 3.6%. DUOX2 showed the highest CF (1.8%), followed by TG (0.46%), TPO (0.44%), TSHR (0.31%), SLC26A7 (0.144%), DUOXA2 (0.141%), IYD (0.08%), SLC5A5 (0.06%), TRHR (0.059%), GLIS3 (0.059%), TSHB (0.04%), and FOXE1 (0%). The pGP in the overall population was 10.01 individuals per 100,000 births (1:9992). The highest pGP was in the East Asian population at 52.48 per 100,000 births (1:1905), followed by Finnish (35.96), Non-Finnish European (9.56), African/African American (4.0), Latino/Admixed American (3.89), South Asian (3.56), and Ashkenazi Jewish (1.81) groups. Comparing the pGP with the real incidence of congenital hypothyroidism, the pGP in East Asian populations was highly consistent with the real incidence.