The genome-wide association study of serum IgE levels demonstrated a shared genetic background in allergic diseases.

Immunoglobulin E (IgE) synthessis is highly related to a variety of atopic diseases, and several genome-wide association studies (GWASs) have demonstrated the association between genes and IgE level. In this study, we conducted the largest genome-wide association study of IgE involving a Taiwanese Han population. Eight independent variants exhibited genome-wide significance. Among them, an intronic SNP of CD28, rs1181388, and an intergenic SNP, rs1002957030, on 11q23.2 were identified as novel signals for IgE. Seven of the loci were replicated successfully in a meta-analysis using data on Japanese population. Among all the human leukocyte antigen (HLA) regions, HLA-DQA1*03:02 - HLA-DQB1*03:03 was the most significant haplotype (OR = 1.25, SE = 0.02, FDR = 1.6 × 10-14), corresponding to HLA-DQA1 Asp160 and HLA-DQB1 Leu87 amino acid residues. The genetic correlation showed significance between IgE and allergic diseases including asthma, atopic dermatitis, and pollinosis. IgE PRS was significantly correlated with total IgE levels. Furthermore, the top decile IgE polygenic risk score (PRS) group had the highest risk of asthma for the Taiwan Biobank and Biobank Japan cohorts. IgE PRS may be used to aid in predicting the occurrence of allergic reactions before symptoms occur and biomarkers are detectable. Our study provided a more comprehensive understanding of the impact of genomic variants, including complex HLA alleles, on serum IgE levels.

Increased Tuberculosis Reactivation Risk in Patients Receiving Immune Checkpoint Inhibitor-Based Therapy.

OBJECTIVE: Reports of tuberculosis (TB) during anticancer treatment with immune checkpoint inhibitors (ICIs) are increasing. However, it is not clear whether the use of ICIs is a significant risk factor for TB, including reactivation or latent TB infection (LTBI). METHODS: To determine the risk of TB reactivation in patients with lung cancer who use ICIs or tyrosine kinase inhibitors (TKIs), we conducted a retrospective study using a hospital-based cancer registry. In addition, we monitored patients with cancer using ICI or TKI in a multicenter prospective study to check the incidence of LTBI. RESULTS: In the retrospective study, several demographic factors were imbalanced between the ICI and TKI groups: the ICI group was younger, had more males, exhibited more squamous cell carcinoma in histology rather than adenocarcinoma, had fewer EGFR mutations, and received more chemotherapy. Propensity score matching was used to control for confounding factors, and we found that the incidence of TB was higher among patients with lung cancer who received ICIs than among those who received TKIs (2298 vs 412 per 100 000 person-years, P = .0165). Through multivariable analysis, group (ICI vs TKI) was the independent risk factor for TB development (adjusted hazard ratio (aHR): 6.29, 95% CI, 1.23-32.09, P = .0269). In the prospective cohort, which included 72 patients receiving ICIs and 50 receiving TKIs, we found that the incidence of positive seroconversion of LTBI by interferon gamma release assay (IGRA) was significantly higher in patients receiving ICIs (18% vs 0%, aHR: 9.88, P = 0.035) under multivariable Cox regression. CONCLUSION: The use of ICIs may be linked to a higher likelihood of TB reactivation and LTBI than individuals solely receiving TKIs as anticancer therapy. Consequently, the implementation of a screening program for TB reactivation and LTBI among patients undergoing ICI treatment could prove advantageous by enabling early detection and prompt treatment of the infection.

Trajectory mapping of the early Drosophila germline reveals controls of zygotic activation and sex differentiation.

Germ cells in Drosophila melanogaster are specified maternally shortly after fertilization and are transcriptionally quiescent until their zygotic genome is activated to sustain further development. To understand the molecular basis of this process, we analyzed the progressing transcriptomes of early male and female germ cells at the single-cell level between germline specification and coalescence with somatic gonadal cells. Our data comprehensively cover zygotic activation in the germline genome, and analyses on genes that exhibit germline-restricted expression reveal that polymerase pausing and differential RNA stability are important mechanisms that establish gene expression differences between the germline and soma. In addition, we observe an immediate bifurcation between the male and female germ cells as zygotic transcription begins. The main difference between the two sexes is an elevation in X Chromosome expression in females relative to males, signifying incomplete dosage compensation, with a few select genes exhibiting even higher expression increases. These indicate that the male program is the default mode in the germline that is driven to female development with a second X Chromosome.

Interaction of base excision repair gene polymorphism and estrogen-DNA adducts in breast cancer risk among East Asian women.

PURPOSE: In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk. METHODS: We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer. RESULTS: Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001). CONCLUSION: APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.

Imipenem reduces the efficacy of vancomycin against Elizabethkingia species.

BACKGROUND: Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring antimicrobial combinations for coverage. However, possible antagonistic interactions between antibiotics have not been thoroughly explored. This study aimed to evaluate the effectiveness of antimicrobial combinations against Elizabethkingia infections, focusing on their impact on pathogenicity, including biofilm production and cell adhesion. METHODS: Double-disc diffusion, time-kill, and chequerboard assays were used for evaluating the combination effects of antibiotics against Elizabethkingia spp. We further examined the antagonistic effects of antibiotic combinations on biofilm formation and adherence to A549 human respiratory epithelial cells. Further validation of the antibiotic interactions and their implications was performed using ex vivo hamster precision-cut lung sections (PCLSs) to mimic in vivo conditions. RESULTS: Antagonistic effects were observed between cefoxitin, imipenem and amoxicillin/clavulanic acid in combination with vancomycin. The antagonism of imipenem toward vancomycin was specific to its effects on the genus Elizabethkingia. Imipenem further hampered the bactericidal effect of vancomycin and impaired its inhibition of biofilm formation and the adhesion of Elizabethkingia meningoseptica ATCC 13253 to human cells. In the ex vivo PCLS model, vancomycin exhibited dose-dependent bactericidal effects; however, the addition of imipenem also reduced the effect of vancomycin. CONCLUSIONS: Imipenem reduced the bactericidal efficacy of vancomycin against Elizabethkingia spp. and compromised its capacity to inhibit biofilm formation, thereby enhancing bacterial adhesion. Clinicians should be aware of the potential issues with the use of these antibiotic combinations when treating Elizabethkingia infections.

Menarche-a journey into womanhood: age at menarche and health-related outcomes in East Asians.

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

K2CO3-mediated annulation of 1,3-acetonedicarboxylates with 2-fluoro-1-nitroarenes: synthesis of indoles.

The K2CO3-mediated one-pot reaction of 1,3-acetonedicarboxylates with 2 equiv. of substituted 2-fluoro-1-nitrobenzenes has been developed to synthesize various 2,3-dicarboxylate indoles via a tandem annulation pathway. In the effective reaction, one carbon-carbon double bond, one carbon-carbon single bond and one carbon-nitrogen single bond are formed under open-vessel conditions. DFT calculations are used to rationalize the plausible mechanisms.

On the nature of two-photon transitions for a collection of molecules in a Fabry-Perot cavity.

We investigate the effect of a cavity on nonlinear two-photon transitions of a molecular system and we analyze how such an effect depends on the cavity quality factor, the field enhancement, and the possibility of dephasing. We find that the molecular response to strong light fields in a cavity with a variable quality factor can be understood as arising from a balance between (i) the ability of the cavity to enhance the field of an external probe and promote multiphoton transitions more easily and (ii) the fact that the strict selection rules on multiphoton transitions in a cavity support only one resonant frequency within the excitation range. Although our simulations use a classical level description of the radiation field (i.e., we solve Maxwell-Bloch or Maxwell-Liouville equations within the Ehrenfest approximation for the field-molecule interaction), based on experience with this level of approximation in the past studies of plasmonic and polaritonic systems, we believe that our results are valid over a wide range of external probing.

Sequential multimodal treatments with chemotherapy and surgery for advanced soft tissue sarcoma may be associated with better survival than chemotherapy.

BACKGROUND: In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear. METHODS: We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded. RESULTS: A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS. CONCLUSION: Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.

Prevalence and risk factors for chronic kidney disease among older adult patients with schizophrenia in Taiwan.

OBJECTIVES: There is an increasing incidence and prevalence of patients with chronic kidney disease (CKD) worldwide. Little is known the prevalence of CKD among older patients with schizophrenia. The purpose of this study was to investigate the prevalence of CKD and its risk factors in older adults with schizophrenia. METHODS: In this cross-sectional study, a convenience sample of 240 patients with schizophrenia age 50 or older were recruited. In addition to demographic and clinical data, participants' estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation based on age, sex, ethnicity, and serum creatinine level determined from a blood sample taken from participants. RESULTS: The overall prevalence of CKD was 11.3%. Those with CKD group were older, had a longer duration of psychiatric illness, a higher body mass index (BMI), and diagnoses of hypertension compared to those in the non-CKD group. Independent of other risk factors, older age and BMI were significantly associated with CKD. CONCLUSIONS: This study found that the overall prevalence of CKD in older patients with schizophrenia was 11.3%. Risk factors for CKD in this population were older age and higher BMI. In addition to early identification and early treatment of CKD in older patients with schizophrenia, clinicians should actively manage the risk factors identified in this study, such as higher BMI and older age.

DFT study on the catalytic decomposition of hydrogen peroxide by iron complexes of nitrilotriacetate.

The Fenton system in the presence of nitrilotriacetate (NTA) ligand is studied by DFT approach. The calculations show that complexation of Fe(II) with NTA significantly facilitates the H2 O2 activation. The ferric-hydroperoxo intermediate NTAFe(III)OOH predominantly decays via the disproportionation into NTAFe(II)OH2 and NTAFe(IV)O involving the formation of a µ-1,2-hydroperoxo-bridged biferric intermediate. In this mechanism, the bridged hydroperoxo is reduced by hydroperoxo ligand rather than by Fe(III). On the one hand, the NTAFe(III)OOH is sluggish to undergo hydrogen abstraction; on the other hand, it is a good nucleophile that may perform aldehyde deformylation. The present calculations suggest that both ˙OH and Fe(IV)O are generated in the NTA-assisted Fenton system. However, the polycarboxylate ligand provides a favorable environment for H2 O2 to accumulate around iron ion through hydrogen bonding. This promotes the quenching of Fe(IV)O by H2 O2 , rationalizing why the Fe(IV)O species is hardly detected in the NTA-assisted Fenton system.

Ganciclovir as a potential treatment for glioma: a systematic review and meta-analysis.

BACKGROUND: Glioma is a challenging malignant tumor with a low survival rate and no effective treatment. Recently, ganciclovir, an antiviral drug, combined with gene therapy and its own antiviral ability, has been proposed as a potential treatment for glioma. However, there are differences in the results of various clinical trials. In this study, we conducted a systematic review and meta-analysis to evaluate the efficacy of ganciclovir in treating glioma. METHODS: We searched databases such as PubMed, EMBASE, and Cochrane Library before March 30, 2023. The search terms included glioma, ganciclovir, valganciclovir and treatment. Calculated 1, 2 and 4-year survival rate by risk difference (RD), and overall survival (OS) by odds ratio (OR). RESULTS: Five randomized controlled trials (RCTs) with a total of 606 high-grade glioma patients were included. The results showed that ganciclovir can improve 2-yeaer (RD = 0.179, 95% CI 0.012-0.346, P = 0.036) and 4-year survival rate (RD = 0.185, 95% CI 0.069-0.3, P = 0.002) and OS (OR 2.393, 95% CI 1.212-4.728, P = 0.012) compared with the control group. CONCLUSIONS: This meta-analysis showed that ganciclovir significantly improved the prognosis of glioma patients. Therefore, we suggest that more cases of ganciclovir as a glioma treatment can be conducted, or a large clinical trial can be designed.

Impact of asymmetric electrodes on ferroelectricity of sub-10 nm HZO thin films.

In this study, platinum (Pt) and tungsten (W), two materials with dissimilar coefficients of thermal expansion (CTE) and work functions (WF), are used as the top electrode (TE) and the bottom electrode (BE) in metal/ferroelectric/metal (MFM) structures to explore the ferroelectricity of hafnium zirconium oxide (HZO) with a thickness less than 10 nm. The electrical measurements indicate that a higher CTE mismatch between HZO and TE/BE is beneficial for enhancing the ferroelectric properties of nanoscale HZO thin films. The different WFs of TE and BE generate a built-in electric field in the HZO layer, leading to shifts in the hysteresis loops and the capacitance-voltage characteristics. The structural characterizations reveal that the preferred formation of the orthorhombic phase in HZO is dominated by the W BE. The device in which W is used as the TE and BE (the W/HZO/W MFM structure) presents the optimal ferroelectric performance of a high remanent polarization (2Pr= 55.2µC cm-2). The presence of tungsten oxide (WOx) at the W/HZO interfaces, as revealed by high-resolution transmission microscopy, is also responsible for the enhancement of ferroelectric properties. This study demonstrates the significant effects of different CTEs and WFs of TE and BE on the properties of ferroelectric HZO thin films.

Associations of urinary phthalate metabolites with household environments among mothers and their preschool-age children.

Phthalates have become a matter of public health concern due to their extensive use worldwide and negative health effects. The evaluation of potential sources of phthalate exposure is crucial to design prevention strategies, especially for vulnerable populations. This study included 528 mother-child pairs in the Taiwan Mother Infant Cohort Study who were followed up at ages 3-6 years between 2016 and 2020. Each mother was interviewed by using a structured questionnaire containing questions on demographic characteristics and household environment factors, such as the use of plastic food packaging, residential visible mold, insecticide sprays, and electric mosquito repellents. Eleven phthalate metabolites were analyzed in urine samples simultaneously collected from the mother-child pairs. The phthalate metabolite urinary concentrations were higher among the children than among their mothers, except those of mono-ethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Multiple linear regression analyses showed that urine samples collected during the summer showed higher concentrations of phthalate metabolites than those collected during the winter. Family income levels had negative associations with the concentrations of MnBP and metabolites of di-2-ethylhexyl phthalate (DEHP) in children. The use of plastic food packaging was positively associated with mono-n-butyl phthalate (MnBP) and metabolites of DEHP in mothers. Residential visible mold or mold stains were significantly associated with higher MnBP and DEHP metabolite concentrations in children. The use of insecticide sprays was positively associated with MnBP concentrations in children. Significant associations between household environmental factors and phthalate exposure were mostly found in children, potentially indicating different exposure pathways between mothers and their children. Findings from this study provide additional information for the design of prevention strategies to protect the health of children and women.

Association of clinical factors to functional outcomes in patients with stroke with large-vessel occlusion after endovascular thrombectomy.

BACKGROUND/PURPOSE: Multiple clinical factors have been reported to be associated with functional outcomes in patients with stroke. However, little is known about prognostic predictors of functional independence in patients with stroke undergoing endovascular thrombectomy (EVT). Our study aimed to investigate the correlation between multiple prognostic variables (including EVT and rehabilitation-related parameters) and functional outcomes in patients post-EVT. METHODS: This retrospective cohort study recruited patients hospitalized between December 2018 and March 2022. Patients with stroke with large-vessel occlusion who underwent EVT were eligible for inclusion in the study. Prognostic factors, including premorbid characteristics, laboratory data, EVT- and rehabilitation-related parameters, functional activity level, balance ability, swallowing, and sphincter function, were collected. Logistic regression and generalized linear models were used to analyze their correlations with functional outcomes. RESULTS: A total of 148 patients were included. In the univariate logistic regression analysis, younger age, premorbid functional independence, higher hemoglobin (Hb) level, lower National Institute of Health Stroke Scale (NIHSS) score, absence of hemorrhagic transformation in 14 days, no nasogastric (NG) tube placement, earlier rehabilitation, frequent daily rehabilitation sessions, more out-of-bed rehabilitation, better ability of sitting up, better initial sitting balance, higher Barthel index (BI), absence of immobility, and neurological complications were associated with favorable outcomes at 3 months. In the stepwise regression model, the predictors of favorable function at 3 months included age, ability to sit up, and frequency of daily rehabilitation sessions; favorable outcomes at 6 months were associated with age, ability to sit up, and swallowing function. CONCLUSION: In patients with stroke post-EVT, better functional outcomes were associated with prognostic variables, including younger age, better ability to sit up, normal swallowing function, and frequent daily rehabilitation sessions.

A Blockchain and IPFS-Based Anticounterfeit Traceable Functionality of Car Insurance Claims System.

Due to frequent traffic accidents around the world, people often take out car insurance to mitigate their losses and receive compensation in a traffic accident. However, in the existing car insurance claims process, there are problems such as insurance fraud, inability to effectively track and transmit insurance data, cumbersome insurance procedures, and high insurance data storage costs. Since the immutability and traceability features of blockchain technology can prevent data manipulation and trace past data, we have used the Elliptic Curve Digital Signature Algorithm (ECDSA) to sign and encrypt car insurance data, ensuring both data integrity and security. We propose a blockchain and IPFS-based anticounterfeiting and traceable car insurance claims system to improve the above problems. We incorporate the Interplanetary File System (IPFS) to reduce the cost of storing insurance data. This study also attempts to propose an arbitration mechanism in the event of a car insurance dispute.

Incomplete Recovery from the Radiocontrast-Induced Dysregulated Cell Cycle, Adhesion, and Fibrogenesis in Renal Tubular Cells after Radiocontrast (Iohexol) Removal.

Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-ß1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further.

Preorthodontic functional long-term trial restoration of a worn dentition for optimizing outcomes: A clinical report.

Orthodontic tooth movement is often required before restorative treatment to maximize the esthetic and functional outcomes. Diagnostic waxing is a crucial step before active treatment to validate the optimal tooth position for future restorations. In this clinical report, a bonded prototype of the diagnostic waxing was used to guide and facilitate orthodontic treatment with the definitive restorations mind. The orthodontic treatment created the required space between the teeth for the ceramic restorations, improved dental and facial features, and restored appropriate incisal guidance.

Prevalence, complete genome, and metabolic potentials of a phylogenetically novel cyanobacterial symbiont in the coral-killing sponge, Terpios hoshinota.

Terpios hoshinota is an aggressive, space-competing sponge that kills various stony corals. Outbreaks of this species have led to intense damage to coral reefs in many locations. Here, the first large-scale 16S rRNA gene survey across three oceans revealed that bacteria related to the taxa Prochloron, Endozoicomonas, SAR116, Ruegeria, and unclassified Proteobacteria were prevalent in T. hoshinota. A Prochloron-related bacterium was the most dominant and prevalent cyanobacterium in T. hoshinota. The complete genome of this uncultivated cyanobacterium and pigment analysis demonstrated that it has phycobiliproteins and lacks chlorophyll b, which is inconsistent with the definition of Prochloron. Furthermore, the cyanobacterium was phylogenetically distinct from Prochloron, strongly suggesting that it should be a sister taxon to Prochloron. Therefore, we proposed this symbiotic cyanobacterium as a novel species under the new genus Candidatus Paraprochloron terpiosi. Comparative genomic analyses revealed that 'Paraprochloron' and Prochloron exhibit distinct genomic features and DNA replication machinery. We also characterized the metabolic potentials of 'Paraprochloron terpiosi' in carbon and nitrogen cycling and propose a model for interactions between it and T. hoshinota. This study builds a foundation for the study of the T. hoshinota microbiome and paves the way for better understanding of ecosystems involving this coral-killing sponge.

Your height affects your health: genetic determinants and health-related outcomes in Taiwan.

BACKGROUND: Height is an important anthropometric measurement and is associated with many health-related outcomes. Genome-wide association studies (GWASs) have identified hundreds of genetic loci associated with height, mainly in individuals of European ancestry. METHODS: We performed genome-wide association analyses and replicated previously reported GWAS-determined single nucleotide polymorphisms (SNPs) in the Taiwanese Han population (Taiwan Biobank; n = 67,452). A genetic instrument composed of 251 SNPs was selected from our GWAS, based on height and replication results as the best-fit polygenic risk score (PRS), in accordance with the clumping and p-value threshold method. We also examined the association between genetically determined height (PRS251) and measured height (phenotype). We performed observational (phenotype) and genetic PRS251 association analyses of height and health-related outcomes. RESULTS: GWAS identified 6843 SNPs in 89 genomic regions with genome-wide significance, including 18 novel loci. These were the most strongly associated genetic loci (EFEMP1, DIS3L2, ZBTB38, LCORL, HMGA1, CS, and GDF5) previously reported to play a role in height. There was a positive association between PRS251 and measured height (p < 0.001). Of the 14 traits and 49 diseases analyzed, we observed significant associations of measured and genetically determined height with only eight traits (p < 0.05/[14 + 49]). Height was positively associated with body weight, waist circumference, and hip circumference but negatively associated with body mass index, waist-hip ratio, body fat, total cholesterol, and low-density lipoprotein cholesterol (p < 0.05/[14 + 49]). CONCLUSIONS: This study contributes to the understanding of the genetic features of height and health-related outcomes in individuals of Han Chinese ancestry in Taiwan.