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Palliative care is one of the effective means to protect the rights of good death and improve the quality of life in end-stage patients. Palliative care in Singapore is developing rapidly and a comprehensive palliative service system has been gradually established, ranking in the top of Asia in the latest national quality of death ranking. This paper proposes that the social awareness, education and training of palliative care should be strengthened, the power of charities and NGOs should be utilized, the existing palliative care carrying capacity should be improved, palliative care related system and legal protection should be established in China, by sorting out the current situation of hospice care, the practical experience in public education, personnel training, charitable support, related policies and legal protection in Singapore, in order to achieve the hospice needs of end-stage patients.

[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

The in situ and ex situ temperature dependence of dielectric and piezoelectric properties of 0.1(Bi0.5K0.5)TiO3-0.6BiFeO3-0.3PbTiO3 (BKT-BFPT) ceramics were characterized, and related mechanisms were studied. The tetragonal distortion, Curie temperature Tc, depoling temperature Td, and piezoelectric coefficient d33 of BKT-BFPT are 0.06, 545 °C, 520 °C, and 205 pC/N, respectively. The in situ piezoelectric coefficient variation of BKT-BFPT ceramics from room temperature to 280 °C is only 10%, being 1/5 and 1/10 those of 0.36BiScO3-0.34PbTiO3 and Pb(Zr0.52Ti0.48)O3 ceramics. The better dielectric and piezoelectric thermal stabilities are owing to the temperature insensitive domain texture of BFPT-BKT ceramics due to their large lattice distortion. Resistivity results reflected that the higher depoling temperature derived from the ex situ measurement than that from the in situ test results from the high-temperature conductivity. [ABSTRACT FROM AUTHOR]

Extensive experimental research and hydrodynamic models have been proposed to guide the design of superior packings. However, most research has concentrated on the effective void (ε − H) of packing while ignoring the ineffective void (ε − H − HL), which causes discrepancies in hydrodynamic performance compared to actual observations. This study evaluated the hydrodynamic performance under diverse conditions considering the liquid holdup (H), pressure drop (ΔP), and gas flooding velocity (uf). A novel approach to hydrodynamic model construction is introduced by incorporating an ineffective void. The results indicate that at a constant hold‐up area, liquid flow (L) and viscosity (μ) significantly influence liquid hold up, moderated by the gas velocity in the flooding area. The pressure drop rises as the viscosity, gas flow rate, and liquid flow rate increase. Notably, a considerable pressure drop initiates flooding at the bottom of the absorber. Elevated liquid flow rates and viscosities correlate with higher ineffective void values (HL) in the packing column. At low gas flow rates, the gas flow rate marginally affects HL values. However, after the flooding point was achieved, the values of HL rapidly increased as the gas flow rate increased. Moreover, a linear relationship emerges between the liquid holdup and HL, as evidenced by the consistent variation in the liquid holdup and the F‐factor. Utilizing the ineffective void yields a more accurate fit for the experimental data, reducing the average absolute relative deviation to 10.2%, 7.4%, and 10.8%, respectively. [ABSTRACT FROM AUTHOR]

STEM education has received increasing attention in recent years. However, developing valid and reliable assessment of interdisciplinary learning in STEM has been a challenge. This study is a comprehensive review of assessment of interdisciplinary STEM education during the last two decades. A total of 49 empirical research articles were collected from an initial library of 635 articles focusing on interdisciplinary STEM education. A two-dimensional framework was developed to examine the literature. The first dimension concerns the nature of disciplines being assessed and includes three categories: monodisciplinary, interdiscipline, and transdiscipline. The second dimension concerns the learning objectives and includes four aspects: knowledge, skill, practice, and affective domain. The results show that most assessments focused on assessments of monodisciplinary knowledge, monodisciplinary affective domains, and transdisciplinary affective domains. Although many programs aimed to improve students' interdisciplinary understanding or skills, their assessments did not align with their aims. Based on the review, future directions are proposed for developing assessments for interdisciplinary STEM educational programs.

PurposeVertical cup-disc ratio (VCDR) is used as a clinical assessment measure to identify and monitor glaucomatous damage to the optic nerve. Previous genetic studies conducted in European and Asian populations have identified many loci associated with VCDR. The genetic factors in other ethnic populations, such as Latino, influencing VCDR remain to be determined. Here, we describe the first genome-wide association study (GWAS) on VCDR in Latino individuals.MethodsWe conducted this GWAS on VCDR using 4537 Latino individuals who were genotyped by using either the Illumina OmniExpress BeadChip (∼730K markers) or the Illumina Hispanic/SOL BeadChip (∼2.5 million markers). Study subjects were 40 years of age and older. Linear regression, adjusting for age, sex, and principal components of genetic ancestry, was conducted to assess the associations between single nucleotide polymorphisms (SNPs) and VCDR. We imputed SNPs from the 1000 Genomes Project to integrate additional SNPs not directly genotyped.ResultsWe replicated two previously reported SNPs that reached GWAS significance, rs1900005 and rs7916697, in the ATOH7-PBLD region, as well as identified two suggestive associations in the CDC7-TGFBR3 region on chromosome 1p22.1 and in the ZNF770-DPH6 region on chromosome 15q14. We discovered a novel SNP, rs56238729 (P = 1.22 × 10-13), in the ATOH7-PBLD region that is significantly associated with VCDR in Latino individuals. We replicated eight previously reported regions, including COL8A1, CDKN2B-CDKN2BAS, BMP2, and CHEK2 (P < 2.17 × 10-3).ConclusionsOur results discovered a novel SNP that is significantly associated with VCDR in Latino individuals and confirmed previously reported loci, providing further insight into the genetic architecture of VCDR.

The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (∼730K markers) or the Illumina Hispanic/SOL BeadChip (∼2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P = 6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1 and ZNF469 (P

Magnetoelectric (ME) sensors are widely studied and well suited for current condition monitoring in smart grids due to their high sensitivity, low power consumption, and compact size. However, designing ME sensors that simultaneously achieve low magnetic noise and a large linear range remains challenging. In this work, we propose and systematically study a multilayered magnetoelectric sensor (MLMS). We experimentally demonstrate that the voltage noise is effectively suppressed by connecting the piezoelectric elements of the MLMS in series. Additionally, the magnetic flux concentration effect is weakened by magnetic shielding from the outer Metglas laminates, which increases the optimized bias field to 52 Oe for the MLMS. Consequently, an equivalent magnetic noise as low as 16.7 pT/rtHz at 1 Hz is obtained and an enlarged linear range from 20 pT to 2 mT is achieved. Furthermore, we demonstrate that the proposed MLMS could linearly detect a wide range of power currents from 0.1 mA to 400 A, with nonlinear error and current resolution as low as 0.05% and 0.1 mA, respectively. [ABSTRACT FROM AUTHOR]

Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D.

PurposeDiabetic retinopathy (DR) is a leading cause of blindness in working age adults. Studies have observed that Latinos have a higher prevalence of DR than whites. The purpose of this study is to test the association between genetic admixture and severe DR in Latinos with type 2 diabetes mellitus (T2DM).MethodsWe conducted a case-control study using 944 T2DM subjects from the Los Angeles Latino Eye Study. Cases (n = 135) were defined as proliferative or severe nonproliferative DR subjects. Controls (n = 809) were other diabetic subjects in the cohort. Genotyping was performed on the Illumina OmniExpress BeadChip. We estimated genetic ancestry in Latinos using STRUCTURE with the HapMap reference panels. Univariate and multivariate logistic regression analyses were used to test the relationship between the proportions of genetic ancestry and severe DR.ResultsNative American ancestry (NAA) in Latino T2DM subjects is associated significantly with severe DR (P = 0.002). The association remained significant (P = 0.005) after adjusting for age, sex, duration of diabetes, hemoglobin A1c, body mass index, systolic blood pressure, education, and income. We also validated the NAA estimates in Latinos using ADMIXTURE with the 1000 Genomes Project reference panels and obtained consistent results.ConclusionsOur results demonstrate for the first time to our knowledge that NAA is a significant risk factor for severe DR in Latinos.

The interaction between influenza A virus (IAV) and host proteins is an important process that greatly influences viral replication and pathogenicity. PB2 protein is a subunit of viral ribonucleoprotein (vRNP) complex playing distinct roles in viral transcription and replication. BAG6 (BCL2-associated athanogene 6) as a multifunctional host protein participates in physiological and pathological processes. Here, we identify BAG6 as a new restriction factor for IAV replication through targeting PB2. For both avian and human influenza viruses, overexpression of BAG6 reduced viral protein expression and virus titers, whereas deletion of BAG6 significantly enhanced virus replication. Moreover, BAG6-knockdown mice developed more severe clinical symptoms and higher viral loads upon IAV infection. Mechanistically, BAG6 restricted IAV transcription and replication by inhibiting the activity of viral RNA-dependent RNA polymerase (RdRp). The co-Immunoprecipitation assays showed BAG6 specifically interacted with the N-terminus of PB2 and competed with PB1 for RdRp complex assembly. The ubiquitination assay indicated that BAG6 promoted PB2 ubiquitination at K189 residue and targeted PB2 for K48-linked ubiquitination degradation. The antiviral effect of BAG6 necessitated its N-terminal region containing a ubiquitin-like (UBL) domain (17-92aa) and a PB2-binding domain (124-186aa), which are synergistically responsible for viral polymerase subunit PB2 degradation and perturbing RdRp complex assembly. These findings unravel a novel antiviral mechanism via the interaction of viral PB2 and host protein BAG6 during avian or human influenza virus infection and highlight a potential application of BAG6 for antiviral drug development. Author summary: Influenza A virus (IAV) is a major public health threat worldwide. The viral polymerase subunit PB2 of IAV is not only responsible for transcription and replication of viral RNA but also acts as a key determinant for host adaptation, making it a key target of host defense system. In this study, we report BAG6 as a novel negative regulator of viral PB2 protein. It interacts with the N-terminus of PB2 and promotes PB2 ubiquitination at the K189 residue, which is highly conserved in all IAV subtypes, resulting in the competitive inhibition of RdRp assembly and the ubiquitination degradation of PB2. These findings emphasize the potent antiviral activity of BAG6 against both avian and human influenza viruses and provide a detailed insight to facilitate antivirals targeting PB2 protein. [ABSTRACT FROM AUTHOR]

Directional sound radiation focuses sound in a specific direction and reduces sound radiation in other directions. This study uses a flat panel driven by an actuator array to realize two-dimensional directional sound radiation by the acoustic contrast control algorithm. The aliasing effect at higher frequencies is analyzed based on the modal vibration of the panel, and a method for estimating the high frequency limit is proposed. Actuator arrays with different parameters are simulated to verify the efficacy of the proposed method and compare the acoustic contrast response with the conventional loudspeaker arrays. [ABSTRACT FROM AUTHOR]

Introduction: Our understanding of the genetic predisposition for age‐at‐onset (AAO) of Alzheimer's disease (AD) is limited. Here, we sought to identify genes modifying AAO and examined whether any have sex‐specific effects. Methods: Genome‐wide association analysis were performed on imputed genetic data of 9219 AD cases and 10,345 controls from 20 cohorts of the Alzheimer's Disease Genetics Consortium. AAO was modeled from cases directly and as a survival outcome. Results: We identified 11 genome‐wide significant loci (P < 5 × 10−8), including six known AD‐risk genes and five novel loci, UMAD1, LUZP2, ARFGEF2, DSCAM, and 4q25, affecting AAO of AD. Additionally, 39 suggestive loci showed strong association. Twelve loci showed sex‐specific effects on AAO including CD300LG and MLX/TUBG2 for females and MIR4445 for males. Discussion: Genes that influence AAO of AD are excellent therapeutic targets for delaying onset of AD. Several loci identified include genes with promising functional implications for AD. [ABSTRACT FROM AUTHOR]

Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, the leading cause of irreversible blindness worldwide. In this review, we summarize the findings of genome-wide association studies (GWASs) of IOP published in the past 10 years and prior to December 2022. Over 190 genetic loci and candidate genes associated with IOP have been uncovered through GWASs, although most of these studies were conducted in subjects of European and Asian ancestries. We also discuss how these common variants have been used to derive polygenic risk scores for predicting IOP and glaucoma, and to infer causal relationship with other traits and conditions through Mendelian randomization. Additionally, we summarize the findings from a recent large-scale exome-wide association study (ExWAS) that identified rare variants associated with IOP in 40 novel genes, six of which are drug targets for clinical treatment or are being evaluated in clinical trials. Finally, we discuss the need for future genetic studies of IOP to include individuals from understudied populations, including Latinos and Africans, in order to fully characterize the genetic architecture of IOP. [ABSTRACT FROM AUTHOR]

Avian influenza virus (AIV) can evolve multiple strategies to combat host antiviral defenses and establish efficient infectivity in mammals, including humans. H9N2 AIV and its reassortants (such as H5N6 and H7N9 viruses) pose an increasing threat to human health; however, the mechanisms involved in their increased virulence remain poorly understood. We previously reported that the M1 mutation T37A has become predominant among chicken H9N2 isolates in China. Here, we report that, since 2010, this mutation has also been found in the majority of human isolates of H9N2 AIV and its emerging reassortants. The T37A mutation of M1 protein enhances the replication of H9N2 AIVs in mice and in human cells. Interestingly, having A37 instead of T37 increases the M1 protein stability and resistance to proteasomal degradation. Moreover, T37 of the H9N2 M1 protein is phosphorylated by protein kinase G (PKG), and this phosphorylation induces the rapid degradation of M1 and reduces viral replication. Similar effects are also observed in the novel H5N6 virus. Additionally, ubiquitination at K187 contributes to M1-37T degradation and decreased replication of the virus harboring T37 in the M1 protein. The prevailing AIVs thereby evolve a phospho-resistant mutation in the M1 protein to avoid viral protein degradation by host factors, which is advantageous in terms of replication in mammalian hosts. Author summary: H9N2 avian influenza virus (AIV) and its reassortants (such as H5N6 and H7N9 viruses) pose an increasing threat to human health, but the mechanisms involved in their increased virulence remain poorly understood. Notably, the role of viral M1 protein in increasing the mammalian infection of AIV has been rarely reported. Here, we demonstrate that a phospho-resistant T37A mutation, encoded by the M1 protein of recently prevalent chicken H9N2 virus, increases M1 protein stability and viral replication in mammalian cells. The T37, but not the A37, in H9N2 M1 protein can be phosphorylated by protein kinase G (PKG). Through the T37A mutation, viral M1 protein evades phosphorylation-mediated proteasomal degradation, resulting in increased avian H9N2 virus replication in mice and in human cells. Similar effects were also observed for the novel H5N6 virus. This study provides insight into a novel strategy by which AIV evades mammalian host defenses. It is necessary to pay close attention to the epidemiological and public health implications of AIVs carrying this mutant M1 protein. [ABSTRACT FROM AUTHOR]

Background: Several studies have attempted to identify genes for age‐at‐onset (AAO) of Alzheimer's disease (AD) through genome‐wide linkage and genome‐wide association studies (GWAS). While these efforts have thus far focused predominantly on non‐Hispanic white (NHW) populations, we present here the first GWAS to identify genetic contributors to AAO in African Americans (AA) using AA genotype and phenotype data from the Alzheimer's Disease Genetics Consortium (ADGC). Method: We combined data from 13 AA prospective and case‐control ADGC datasets, excluding family‐based datasets. Genotype data underwent standard quality control and were imputed to the TOPMed R5 reference panel using the Michigan Imputation Server. Data were merged across cohorts using QCTOOL and GTOOL, filtering out variants with MAF≤0.005). We performed two analyses: case‐only linear mixed‐model regression with AAO as outcome (LMM); and survival analysis using Cox proportional‐hazards frailty modeling (COXPHF) with time‐to‐AD‐onset (AAO in cases and censoring of controls at age‐at‐last‐exam). Both models were adjusted for sex, principal components capturing population substructure, and APOE‐ε4 dosage with a random cohort effect. Result: We examined 2,262 AA AD cases, including 1,561 females (69%) with mean (SD) AAO of 77.7 (8.1) years. The APOE‐adjusted COXPHF analyses identified twelve genome‐wide significant regions (P<5×10−8), the most significant in ABCA7 (P = 3.57×10−10), known to be associated with AD risk in AAs. In the LMM analysis, we observed strong novel associations with variants in CCDC141 on chr2q31.2 (Pmin = 2.93×10−9). In silico analyses of LD structure and functional potential suggest SESTD1, a gene involved in synaptic regulation, as driving the CCDC141 locus signal. Nine of 12 COXPHF loci were driven by African‐specific variants (MAF<0.0002 in gnomAD Non‐Finish Europeans). These significant loci identified in the AA COXPHF or LMM analyses were not significant (P>0.05) in equivalent analyses in NHW ADGC cohorts (9,220 AD cases/10,350 controls; Li et al. Alz Dement 2023), except for the ABCA7 locus (NHW P<0.0002). Conclusion: In a large ADGC African American dataset, we confirmed AAO associations in the APOE region and ABCA7 and observed evidence for potential novel AD AAO loci including SESTD1; many of which might be African‐ancestry specific. [ABSTRACT FROM AUTHOR]