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Background: Exposure to traffic-related pollution is positively associated with cardiovascular diseases (CVD), but little is known about how different sources of traffic pollution (eg, gasoline-powered cars, diesel-engine vehicles) contribute to CVD. Therefore, we evaluated the association between exposure to different types of engine exhaust and CVD mortality. Methods: We recruited 12,098 participants from REVEAL-HBV cohort in Taiwan. The CVD mortality in 2000–2014 was ascertained by the Taiwan Death Certificates. Traffic pollution sources (2005–2013) were based on information provided by the Directorate General of Highway in 2005. Exposure to PM2.5 was based on a land-use regression model. We applied Cox proportional hazard models to assess the association of traffic vehicle exposure and CVD mortality. A causal mediation analysis was applied to evaluate the mediation effect of PM2.5 on the relationship between traffic and CVD mortality. Results: A total of 382 CVD mortalities were identified from 2000 to 2014. We found participants exposed to higher volumes of small car and truck exhausts had an increased CVD mortality. The adjusted hazard ratio (HR) was 1.10 for small cars (95% confidence interval [CI], 0.94–1.27; P-value = 0.23) and 1.24 for truck (95% CI, 1.03–1.51; P-value = 0.03) per one unit increment of the logarithm scale. The findings were still robust with further adjustment for different types of vehicles. A causal mediation analysis revealed PM2.5 had an over 60% mediation effect on traffic-CVD association. Conclusions: Exposure to exhaust from trucks or gasoline-powered cars is positively associated with CVD mortality, and air pollution may play a role in this association.

Background Diversity in the HLA genes might be associated with disease outcomes—the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Methods We utilized DNA from > 10 000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as homozygotes at a given locus when imputed to carry the same 4-digit allele for the 2 HLA alleles at that locus. Results Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (Ptrend = 1.18 × 10–7). Among chronic HBV carriers, increase in number of homozygous HLA class II loci was also associated with an increased risk of HBV-associated HCC (Ptrend = .031). For individual HLA loci, HLA-DQB1 homozygosity was significantly associated with HCC risk (adjusted hazard ratio = 1.40; 95% confidence interval, 1.06–1.84). We also found that zygosity affects risk of HCC through its ability to affect viral control. Conclusions Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC.

An ultra-broadband wavelength-swept laser (WSL) was generated using glass-clad Ti:sapphire crystal fiber as the gain media. Due to the low signal propagation loss of the crystal fiber, the swept laser has a tuning bandwidth of 250 nm (i.e., 683 nm to 933 nm) at a repetition rate of 1200 Hz. The steady-state and pulsed dynamics of the WSL were analyzed. The 0.018-nm instantaneous linewidth corresponds to a 3-dB coherence roll-off of 7 mm. When using the laser for swept-source optical coherence tomography, an estimated axial resolution of 1.8 µm can be achieved.

Although 5-year colleges account for 41.7% of all nursing graduates in Taiwan, most of these graduates go on to university and earn a bachelor's degree. In 2015, four universities received approval from the Ministry of Education of Taiwan and started to enroll students in the academic-hospital partnership nursing program to guide nursing graduates from 5-year colleges into the nursing workplace. The effects of this program have never been examined, especially from the perspective of the students.The aim of this study was to explore the experiences of students currently participating in the academic-hospital partnership nursing program.A qualitative approach was used in this study. Twelve students were invited to participate in a focus group that met for five sessions over 3 years to understand the motivations for and experiences of participating in the academic-hospital partnership nursing program. Data were analyzed using thematic analysis.Six themes were identified: (a) incentives for participating in the academic-hospital partnership nursing program, (b) worries about making the wrong decision, (c) worries about future adaptation, (d) facing the real workplace, (e) confusion about role perception and benefits, and (f) administrator support.The findings of this study enhance the general understanding of nursing student experiences and the changes over time in the academic-hospital partnership nursing programs. Moreover, the findings may be used to help teachers and nursing administrators at healthcare institutes better support the needs of students at each program stage. In addition, the findings may serve as a reference for the government in refining the design of these programs in the future.

Numerous proteins initiate their folding, localization, and modifications early during translation, and emerging data show that the ribosome actively participates in diverse protein biogenesis pathways. Here we show that the ribosome imposes an additional layer of substrate selection during N-terminal methionine excision (NME), an essential protein modification in bacteria. Biochemical analyses show that cotranslational NME is exquisitely sensitive to a hydrophobic signal sequence or transmembrane domain near the N terminus of the nascent polypeptide. The ability of the nascent chain to access the active site of NME enzymes dictates NME efficiency, which is inhibited by confinement of the nascent chain on the ribosome surface and exacerbated by signal recognition particle. In vivo measurements corroborate the inhibition of NME by an N-terminal hydrophobic sequence, suggesting the retention of formylmethionine on a substantial fraction of the secretory and membrane proteome. Our work demonstrates how molecular features of a protein regulate its cotranslational modification and highlights the active participation of the ribosome in protein biogenesis pathways via interactions of the ribosome surface with the nascent protein.

Intestinal stem cells (ISCs) are responsible for intestinal proliferation, differentiation, and neoplasia, and also play a crucial role in inflammation. Thus, it is important to investigate the effect of TNF-α on the activities of NF-κB, PI3K/Akt, and Wnt/β-catenin signaling pathways.The Lgr5The Lgr5PI3K/Akt and Wnt/β-catenin signaling cross-regulate NF-κB signaling in TNF-α-induced human Lgr5

BACKGROUND AND AIMS Diabetic nephropathy (DN), a common complication of diabetic patients, usually contributes to end-stage renal failure. Accidental cell death (ACD) and regulated cell death (RCD) cause renal cell loss and deteriorate renal function during the progression of DN. MLKL is the executor of necroptosis, a major form of RCD. The multimer of phosphorylated MLKL (p-MLKL) gather at the cell membrane and form the leaking pores, performing the last step of necroptosis. This study aims to study the relationship of p-MLKL expression and the disease severity in DN patients, providing promising treatment target. METHOD A total of 30 patients who diagnosed with DN clinical-pathologically in the Peking University First Hospital from January 1998 to August 2018 were enrolled (excluding DN with primary or secondary glomerular diseases, DN combined with thrombotic microangiopathies and small vasculitis). p-MLKL were stained on renal biopsy kidney sections by immunohistochemistry. Image-Pro Plus 6.0 software (IPP) was used to analyze the expression of p-MLKL on 10 randomly taken images for each patient. The relationship between p-MLKL expression and clinical-pathological parameters was explored. Clinical parameters of plasma creatinine, peak plasma creatinine during renal biopsy period, estimated glomerular filtration rate (eGFR) were used. DN pathological changes contained: (i) glomerular lesions, (ii) arteriole lesions (iii) tubular lesions and (iv) tubules chronic interstitial lesions. RESULTS Compared with normal control, the positive expression of p-MLKL could be detected in the renal tubular interstitium of patients with DN. However, no p-MLKL positive signal was seen in the glomeruli. Patients with p-MLKL positive signals accounted for 73.33% (22/30) of the enrolled patients. Among the 30 patients, the value of p-MLKL kidney tissue IOD (integrated optical density) was positively correlated with peak serum creatinine (r = 0.373, P = 0.042), the pathological score of spherical sclerosis (r = 0.364, P = 0.048) and tubular brush border (TBB) loss (r = 0.363, P = 0.049). CONCLUSION The expression of necroptosis marker p-MLKL was significantly correlated with the clinical-pathological changes of DN patients. Its role in the progression of DN deserves further exploration.

Atopic dermatitis (AD) and food allergy (FA) are associated with respiratory comorbidities, in the concept of 'atopic march.' However, children with AD and a coexisting FA have various disease courses, and the mechanism of atopic march remains unclear. In this study, we investigated whether the phenotype of AD with coexisting FA in early life affected asthma or allergic rhinitis (AR) in school children.A total of 1,579 children from the Panel Study on Korean Children (PSKC) cohort were followed-up in 2013. The participants diagnosed with AD in this cohort were classified by the age of AD onset and persistence as well as FA history. We compared the presence of comorbidities-asthma and rhinitis-among different AD phenotypes.Asthma and AR with current symptoms within 12 months at age 6-8 years were associated with early-onset persistent AD phenotype, regardless of coexisting FA. AD with FA conferred a higher risk of recent wheezing at 8 years of age than AD without FA (adjusted odds ratio, 8.09; 95% confidence interval, 2.54-25.76). Children with early-onset persistent AD with FA manifested a distinctive trajectory with a higher prevalence of wheezing and AR at age 5-8 years than those without AD.AD with FA in early life is strongly associated with asthma and AR in school children, and the early-onset persistent AD with FA had a strong additive effect on the risk of asthma at school age. Classifying AD phenotypes regarding FA in early life will help predict and prevent asthma and AR in school children.

Human leukocyte antigen (HLA) gene variation is associated with risk of cancers, particularly those with infectious etiology or hematopoietic origin, given its role in immune presentation. Previous studies focused primarily on HLA allele/haplotype-specific associations. To answer whether associations are driven by HLA class I (essential for T-cell cytotoxicity) or class II (important for T-cell helper responses) genes, we analyzed GWAS from 24 case–control studies and consortia comprising 27 cancers (totaling >71,000 individuals). Associations for most cancers with infectious etiology or of hematopoietic origin were driven by multiple HLA regions, suggesting that both cytotoxic and helper T-cell responses are important. Notable exceptions were observed for nasopharyngeal carcinoma, an EBV-associated cancer, and CLL/SLL forms of non-Hodgkin lymphomas; these cancers were associated with HLA class I region only and HLA class II region only, implying the importance of cytotoxic T-cell responses for the former and CD4+ T-cell helper responses for the latter. Our findings suggest that increased understanding of the pattern of HLA associations for individual cancers could lead to better insights into specific mechanisms involved in cancer pathogenesis. Significance: GWAS of >71,000 individuals across 27 cancer types suggest that patterns of HLA Class I and Class II associations may provide etiologic insights for cancer.

Dual-specificity phosphatases (DUSPs) comprise a unique group of enzymes that dephosphorylate signaling proteins at both phospho-serine/threonine and phospho-tyrosine residues. Since Notch signaling is an essential pathway for neuronal cell fate determination and development that is also upregulated in Alzheimer's disease tissues, we sought to explore whether and how DUSPs may impact Notch processing. Our results show that overexpression of DUSP15 concomitantly and dose-dependently increased the steady-state levels of recombinant Notch (extracellular domain-truncated Notch, NotchΔE) protein and its cleaved product, Notch intracellular domain (NICD). The overall ratio of NotchΔE to NICD was unchanged by overexpression of DUSP15, suggesting that the effect is independent of γ-secretase. Interestingly, overexpression of DUSP15 also dose-dependently increased phosphorylated ERK1/2. Phosphorylated ERK1/2 is known to be positively correlated with Notch protein level, and we found that DUSP15-mediated regulation of Notch was dependent on ERK1/2 activity. Together, our findings reveal the existence of a previously unidentified DUSP15-ERK1/2-Notch signaling axis, which could potentially play a role in neuronal differentiation and neurological disease.

Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization’s goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions. We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan–Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria. Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03–1.57% among noncirrhotic males and 2.57–6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment. Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.

Main text This is the final report of CCT-K7.2021 key comparison of water-triple-point (TPW) cells. The primary objective of CCT-K7.2021 was a comparison of the participant national realizations of the TPW temperature. Each participant laboratory selected one of its TPW cells for use as a transfer cell, directly compared it against its national reference and delivered it to the pilot (NRC). The pilot then compared all transfer cells against two NRC reference cells and, finally, each participant laboratory retrieved its transfer cell and directly re-compared it against its TPW national reference. The initial measurements at the participant laboratories were started in April 2021. The final measurements at the participants' laboratories were completed in September 2022. The final report was approved by the CCT WG-KC in April 2023. The adaptive weighted average procedure was adopted to compute the Key Comparison Reference Value (KCRV) and the degrees of equivalence (DoEs) were reported for the participant laboratories. The maximum difference between two transfer cells was 92 μK with a standard deviation of 26 µK (almost a factor of two improvement compared to CCT-K7 results (2002-2004). The maximum difference between two TPW national realizations was 111 µK, with a standard deviation of 28 µK (improvement similar to the one reported for the transfer cells). While the pooled distribution of CCT-K7 results was bimodal, indicating the presence of two different sub-populations (the population of laboratories that referred to ocean water definition and the population of laboratories that did not consider it), the pooled distribution of CCT-K7.2021 results was no longer bimodal, but slightly asymmetrical, indicating a more harmonized approach to water isotopic corrections. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/. The final report has been peer-reviewed and approved for publication by the CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

ImportanceTurbinate surgery is an effective treatment for allergic rhinitis (AR) refractory to medical treatment. However, the long-term outcomes of turbinate surgery are still unclear and have not yet been confirmed by a meta-analysis and systematic review of the literature.ObjectiveTo investigate the long-term outcomes and safety of turbinate surgery in AR by performing a meta-analysis.Data SourcesMEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were searched through April 2021.Study SelectionStudies that analyzed turbinate surgery alone, had a follow-up period of more than 1 year, examined long-term efficacy of turbinate surgery, used current turbinate surgery methods, and were published in a peer-reviewed journal were included. Full-text reviews were performed by 2 independent reviewers. Conflicts were resolved by a third reviewer.Data Extraction and SynthesisDescriptive and quantitative data were extracted; weighted mean difference (WMD) was synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and the I2 metric. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines.Main Outcomes and MeasuresThe long-term outcomes of turbinate surgery on subjective nasal symptoms and objective parameters.ResultsOf the 3962 citations retrieved, 18 studies comprising 1411 patients were included. Findings showed significantly decreased symptom scores in nasal obstruction (WMD, 4.60, 95% CI, 3.43-5.76), rhinorrhea (WMD, 3.12; 95% CI, 1.97-4.28), sneezing (WMD, 2.64; 95% CI, 1.74-3.54), itching (WMD, 1.75; 95% CI, 1.20-2.30), and nasal resistance (WMD, 0.16; 95% CI, 0.08-0.24) and a significant increased total nasal volume (WMD, 0.96; 95% CI, 0.73-1.19). There was no significant difference in the occurrence of any complication. More than 1 year after surgery, the improvements in nasal obstruction (WMD, 5.18; 95% CI, 3.00-7.37), rhinorrhea (WMD, 3.57; 95% CI, 1.78-5.37), and sneezing (WMD, 2.95; 95% CI, 1.58-4.32) were maintained.Conclusions and RelevanceIn this systematic review and meta-analysis, turbinate surgery was associated with positive outcomes in AR and maintained the association during long-term follow-up. The rate of complications is also low. These findings can guide the preoperative counseling of patients with AR being considered for turbinate surgery.

The presented paper discusses the summary of the special issue consisting of 13 peer-reviewed papers regarding Redefinition of SI Units and Its Implications. The papers discuss state-of-the-art reviews and progress made as of now and ongoing progress regarding the redefinition of SI units at different National Metrology Institutes (NMIs) and academic/research institutes across the globe. Different methodologies adopted while investigating redefinition of SI units have been discussed and summarized by the researchers, which will serve as a pivotal point in guiding the researchers in upcoming time.

Exposure to particulate matter (PM) has been known to develop asthma in children and the oxidative stress-related mechanisms are suggested. For the development of asthma, not only the exposure dose but also the critical window and the risk modifying factors should be evaluated.We investigated whether prenatal exposure to PM10 increases the risk of childhood asthma and evaluated the modifying factors, such as gender and reactive oxidative stress-related gene.A general population-based birth cohort, the Panel Study of Korean Children (PSKC), including 1572 mother-baby dyads was analyzed. Children were defined to have asthma at age 7 when a parent reported physician-diagnosed asthma. Exposure to PM10 during pregnancy was estimated by land-use regression models based on national monitoring system. TaqMan method was used for genotyping nuclear factor, erythroid 2-related factor, NRF2 (rs6726395). A logistic Bayesian distributed lag interaction model (BDLIM) was used to evaluate the associations between prenatal PM10 exposure and childhood asthma by gender and NRF2.Exposure to PM10 during pregnancy was associated with the development of asthma (aOR 1.03, 95% CI 1.001.06). Stratifying by gender and NRF2 genotype, exposure to PM10 during 26-28 weeks gestation increased the risk of childhood asthma, especially in boys with NRF2 GG genotype.A critical window for PM10 exposure on the development of childhood asthma was during 26-28 weeks of gestation, and this was modified by gender and NRF2 genotype.

In chronic hepatitis B virus (HBV) infection, earlier seroclearance of hepatitis B e antigen (HBeAg) is associated with more favorable outcomes. Soluble programmed cell death 1 (sPD-1) has been implicated in higher viral load and hepatocellular carcinoma. We investigated the association between sPD-1 levels and spontaneous HBeAg seroclearance.Baseline serum samples from 488 HBeAg-seropositive patients in the REVEAL-HBV cohort were tested for sPD-1 levels. Among them, 329 with available follow-up serum samples were further assayed. Multivariate Cox regression analysis was used to estimate the adjusted rate ratio (aRR) and 95% confidence interval (CI) with adjustment of host and viral factors. The 66th percentile and an annual reduction of ≥ 10% were used as the cut-off point for baseline sPD-1 levels (high/low) and sPD-1 trajectory (decline/no decline), respectively.Lower baseline sPD-1 levels [aRR (95% CI): 2.19 (1.47-3.27)] and long-term decline in sPD-1 levels [aRR (95% CI): 4.08 (2.79-5.97)] were both independent predictors for HBeAg seroclearance. However, further stratification analysis by HBV genotype showed that lower baseline sPD-1 levels were significantly associated with HBeAg seroclearance only in genotype C infection [aRR (95% CI): 4.47 (2.38-8.37)] but not in genotype B infection. On the other hand, long-term decline in sPD-1 levels was predictive for HBeAg seroclearance regardless of HBV genotype with aRR (95% CI) of 4.62 (2.71-7.88) and 2.95 (1.68-5.17), respectively, for genotypes B and C.Serum sPD-1 levels may serve as a novel immunological predictor for spontaneous HBeAg seroclearance in patients with chronic hepatitis B.

The odd���odd nucleus �����Na is studied via a one-proton, one-proton���one-neutron and one-neutron removal reaction using an intermediate-energy ����Mg, ����Mg and ����Na radioactive ion beam, respectively. Combining high-resolution ��-ray spectroscopy with the selectivity of the three reaction mechanisms, we are able to distinguish multiple particle���hole configurations. Negative-parity states in �����Na are observed for the first time, providing an important measure of the excitation of the 1p1h/3p3h configuration and hence the sd���pf shell gap. The extracted band structures and level energies serve as invaluable input for the theoretical refinement of the effective interactions used in this region.

Self-conjugate nuclei in the A ��� 70���80 region have attracted a great deal of attention due to phenomena such as shape coexistence and increasing collectivity along the N=Zline. We investigate the structure of nuclei in this region through lifetime measurements using the GRETINA array. The first implementation of the Differential Recoil Distance Doppler Shift technique with fast radioactive beams is demonstrated and verified through a measurement of the well-known B(E2; 2��������� 0������)transition strength in ������Kr. The method is then applied to determine the B(E2; 2��������� 0������) transition strength in ������Rb, the heaviest odd���odd N=Z nucleus for which this quantity has been determined. This result and extended systematics along N=Z suggest the dominance of the isoscalar part of the quadrupole transition strengths in self-conjugate nuclei, as well as the possible presence of shape coexistence in ������Rb.

Glass-clad Ti:sapphire-core fibers have been used in cellular-resolution optical coherence tomography and greater than 240-nm swept laser sources in the near-infrared wavelength range. The development of Ti:sapphire-core fibers toward single-mode transmission is addressed.

Rigid fixation using a three-point skull clamp is a common practice during cranial surgery. Despite its frequency of use, rigid fixation is not without risk of complications including hemodynamic changes, skull fractures and venous thromboembolism. Given this, alternative head fixation should be considered when clinically appropriate.We sought to demonstrate a safe and effective "pinless" head fixation system during endoscopic microvascular decompression (E-MVD).Patients undergoing E-MVD were placed in the lateral position with a doughnut pillow under the head, providing support and reducing lateral neck flexion. The vertex of the cranium was angled 10 degrees downward and tape placed circumferentially in an X-shaped fashion around the head, avoiding direct pressure on the ears or eyes. The ipsilateral shoulder was pulled caudally away from the operative field and taped in place to ensure a maximal working corridor.Fifty-two patients underwent the E-MVD procedure with pinless head fixation without any clinical complications. Indications included trigeminal neuralgia type 1 (63.5%), trigeminal neuralgia type 2 (5.8%), hemifacial spasm (19.2%), geniculate neuralgia (7.7%) and glossopharyngeal neuralgia (3.8%). There were no intraoperative or post operative complications and operative time for patients with three-point skull clamp fixation were similar compared to pinless head fixation.Pinless head fixation is a suitable alternative for certain patients undergoing E-MVD and provides a way to minimize complications that can occur secondary to rigid fixation. If pinless fixation is used, diligent and continued communication with the anesthetist is necessary to ensure there is no intraoperative patient movement.

Self-conjugate nuclei in the A ≈ 70–80 region have attracted a great deal of attention due to phenomena such as shape coexistence and increasing collectivity along the N=Zline. We investigate the structure of nuclei in this region through lifetime measurements using the GRETINA array. The first implementation of the Differential Recoil Distance Doppler Shift technique with fast radioactive beams is demonstrated and verified through a measurement of the well-known B(E2; 2₁⁺→ 0₁⁺)transition strength in ⁷⁴Kr. The method is then applied to determine the B(E2; 2₁⁺→ 0₁⁺) transition strength in ⁷⁴Rb, the heaviest odd–odd N=Z nucleus for which this quantity has been determined. This result and extended systematics along N=Z suggest the dominance of the isoscalar part of the quadrupole transition strengths in self-conjugate nuclei, as well as the possible presence of shape coexistence in ⁷⁴Rb.