Search

Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor (VDR), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-α hydroxylase (CYP27B1) and vitamin D deactivating enzyme 24-α hydroxylase (CYP24A1). We evaluated whether 12 tagging single nucleotide polymorphisms (SNP) in CYP24A1, identified by resequencing the gene in 32 Caucasian samples, and 1 SNP in CYP27B1 were associated with colon cancer risk. In addition, we evaluated whether these two genes modify associations between colon cancer on the one hand and total vitamin D intake and UV-weighted sun exposure on the other, as well as other variants in VDR. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between polymorphisms and haplotypes in CYP27B1 and CYP24A1 in a multicenter population-based case-control study of 1,600 cases and 1,949 controls. The CYP24A1 polymorphism IVS4-66T > G showed a statistically significant association with risk of colon cancer overall, particularly for proximal colon cancer. When stratified by anatomic site, we also found statistically significant associations for three CYP24A1 polymorphisms with risk of distal colon cancer (IVS4 + 1653C > T: OR for CT/TT versus CC, 0.81; 95% CI, 0.68-0.96; IVS9 + 198T > C: OR for CC versus TT, 1.33; 95% CI, 1.03-1.73; and within whites only: +4125bp 3′ of STPC > G: OR for GG versus CC, 1.44; 95% CI, 1-2.05). In addition, a possible interaction between CYP27B1 and UV-weighted sun exposure with proximal colon cancer was observed. As this is the first study to evaluate these genes in relation to colon cancer, additional studies are needed to confirm these results. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2540–8)

Supplementary Material from Vitamin D Related Genes, CYP24A1 and CYP27B1, and Colon Cancer Risk

Supplementary Table 1 from Apolipoprotein E/C1 Locus Variants Modify Renal Cell Carcinoma Risk

Supplementary Figure 1 from Apolipoprotein E/C1 Locus Variants Modify Renal Cell Carcinoma Risk

Supplementary Table 4 from Apolipoprotein E/C1 Locus Variants Modify Renal Cell Carcinoma Risk

Supplementary Table 2 from Apolipoprotein E/C1 Locus Variants Modify Renal Cell Carcinoma Risk

Supplementary Table 3 from Apolipoprotein E/C1 Locus Variants Modify Renal Cell Carcinoma Risk

We describe a copper-catalyst that promotes the addition of phosphines to cyclopropenes at ambient temperature. A range of cyclopropylphosphines bearing different steric and electronic properties can now be accessed in high yields and enantioselectivities. A combined experimental and theoretical mechanistic study supports insertion of a Cu(I)-phosphido intermediate into the strained olefin. Density functional theory calculations reveal migratory insertion as the stereodetermining step of the pathway, with final product formation occurring via a syn-protodemetalation. Enrichment of phosphorus stereocenters is demonstrated via a DyKAT process.

As an advance in hydrofunctionalization, we herein report that alcohols add to 1,3-dienes with high regio- and enantioselectivity. Using a Ni-DuPhos, we access enantioenriched allylic ethers. Through the choice of solvent-free conditions, we control the reversibility of C-O bond formation. This work showcases a rare example of methanol as a reagent in asymmetric synthesis

Aim: The first Plan-Do-Study-Act cycle for the Veterans Affairs Pharmacogenomic Testing for Veterans pharmacogenomic clinical testing program is described. Materials & methods: Surveys evaluating implementation resources and processes were distributed to implementation teams, providers, laboratory and health informatics staff. Survey responses were mapped to the Consolidated Framework for Implementation Research constructs to identify implementation barriers. The Expert Recommendation for Implementing Change strategies were used to address implementation barriers. Results: Survey response rate was 23–73% across personnel groups at six Veterans Affairs sites. Nine Consolidated Framework for Implementation Research constructs were most salient implementation barriers. Program revisions addressed these barriers using the Expert Recommendation for Implementing Change strategies related to three domains. Conclusion: Beyond providing free pharmacogenomic testing, additional implementation barriers need to be addressed for improved program uptake.

Australian lizards are a diverse group distributed across the continent and inhabiting a wide range of environments. Together, they exhibit a remarkable diversity of reproductive morphologies, physiologies, and behaviours that is broadly representative of vertebrates in general. Many reproductive traits exhibited by Australian lizards have evolved independently in multiple lizard lineages, including sociality, complex signalling and mating systems, viviparity, and temperature-dependent sex determination. Australian lizards are thus outstanding model organisms for testing hypotheses about how reproductive traits function and evolve, and they provide an important basis of comparison with other animals that exhibit similar traits. We review how research on Australian lizard reproduction has contributed to answering broader evolutionary and ecological questions that apply to animals in general. We focus on reproductive traits, processes, and strategies that are important areas of current research, including behaviours and signalling involved in courtship; mechanisms involved in mating, egg production, and sperm competition; nesting and gestation; sex determination; and finally, birth in viviparous species. We use our review to identify important questions that emerge from an understanding of this body of research when considered holistically. Finally, we identify additional research questions within each topic that Australian lizards are well suited for reproductive biologists to address.

Level anticrossings (LACs) are ubiquitous in quantum systems and have been exploited for spin-order transfer in hyperpolarized nuclear magnetic resonance spectroscopy. This paper examines the manifestations of adiabatic passage through a specific type of LAC found in homonuclear systems of chemically inequivalent coupled protons incorporating parahydrogen (pH2). Adiabatic passage through such a LAC is shown to elicit translation of the pH2 spin order. As an example, with prospective applications in biomedicine, proton spin polarizations of at least 19.8 ± 2.6% on the methylene protons and 68.7 ± 0.5% on the vinylic protons of selectively deuterated allyl pyruvate ester are demonstrated experimentally. After ultrasonic spray injection of a precursor solution containing propargyl pyruvate and a dissolved Rh catalyst into a chamber pressurized with 99% para-enriched H2, the products are collected and transported to a high magnetic field for NMR detection. The LAC-mediated hyperpolarization of the methylene protons is significant because of the stronger spin coupling to the pyruvate carbonyl 13C, setting up an ideal initial condition for subsequent coherence transfer by selective INEPT. Furthermore, the selective deuteration of the propargyl side arm increases the efficiency and polarization level. LAC-mediated translation of parahydrogen spin order completes the first step toward a new and highly efficient route for the 13C NMR signal enhancement of pyruvate via side-arm hydrogenation with parahydrogen.

This study showcases the first enantioselective hydroselenation of styrenes. Organoselenium building blocks are accessed with selectivity for the branched isomer. Through a Rh-hydride pathway, C-Se bonds can be forged with excellent regio- and enantiocontrol.

Aims CYP2C19-guided P2Y12 inhibitor selection can reduce cardiovascular (CV) events and bleeding in patients with acute coronary syndromes (ACSs) post-percutaneous coronary intervention (PCI). The 12-month cost-effectiveness of CYP2C19-guided P2Y12 inhibitor selection for Veterans post-ACS/PCI was evaluated from the Veterans Health Administration's (VHA) perspective. Methods and results Using average annualized PCI volumes and P2Y12 inhibitor use from VA data, a decision-analytic model simulated CYP2C19 testing vs. no testing outcomes in 2800 hypothetical Veterans receiving PY212 inhibitor for 12 months post-ACS/PCI (74% clopidogrel, 5% prasugrel, and 21% ticagrelor use at baseline without testing). CYP2C19 loss-of-function (LOF) carrier prevalence was 28%. Model inputs were from studies (bleeding/ischaemic events, CYP2C19-guided therapy effect, health state utilities, CYP2C19 LOF carrier prevalence) and VHA administrative data (costs of events, drugs, CYP2C19 testing; PCI volumes, and P2Y12 inhibitor prescriptions). The primary outcome was cost (2020 US${\$}$) per quality-adjusted life year (QALY) gained. Base-case scenarios, probabilistic sensitivity analyses, and scenario analyses were completed. CYP2C19-guided therapy resulted in 496 (24%) escalations (clopidogrel to prasugrel/ticagrelor) and 465 (65%) de-escalations (prasugrel/ticagrelor to clopidogrel). CYP2C19 testing averted 1 stroke, 27 myocardial infarctions, 8 CV-related deaths, and caused 3 bleeds. CYP2C19 testing (vs. no testing) was dominant in the base-case scenario (0.0027 QALYs gained, ${\$}$527 saved/person) and in 97.1% of simulations, making it cost-effective and high-value. In scenario analyses, de-escalation in conjunction with escalation is required for CYP2C19 testing to be cost-effective and high-value. Conclusion In Veterans post-ACS/PCI, CYP2C19-guided P2Y12 inhibitor selection can improve CV outcomes and lower costs for the VHA within 12 months of implementation.

Heterostructured photocatalysis is a significant issue owing to the unique band alignment, improved spectrum absorption, and enhanced photocatalytic activity. However, the construction of uniform, controllable, and effective heterojunctions is still a huge challenge. Herein, NaNbO3 /Nb3 O7 F heterojunctions are fabricated through an in situ corrosion technique for the first time. The influence of phase transformation on the hydrogen evolution reaction (HER) activity is investigated systematically in terms of photocatalytic water splitting for H2 production. Interestingly, the band realignment and good interfacial contact endow the NaNbO3 /Nb3 O7 F heterojunctions with a high HER activity (43.3 mmol g-1 h-1 ), which is about 2.4 times that of pure Nb3 O7 F and 1.36 times that of pure NaNbO3 . The results may provide some new insights into the corrosion technique and HER activity of novel heterostructured catalysts.

By using transition metal catalysts, chemists have altered the ‘logic of chemical synthesis’ by enabling the functionalization of carbon-hydrogen bonds, which have traditionally been considered inert. Within this framework, our laboratory has been fascinated by the potential for aldehyde C–H bond activation. Our approach focused on generating acyl-metal-hydrides by oxidative addition of the formyl C–H bond, which is an elementary step first validated by Tsuji in 1965. In this Account, we review our efforts to overcome limitations in hydroacylation. Initial studies resulted in new variants of hydroacylation and ultimately spurred the development of related transformations (e.g., carboacylation, cycloisomerization, and transfer hydroformylation). Sakai and coworkers demonstrated the first hydroacylation of olefins when they reported that 4-pentenals cyclized to cyclopentanones, using stoichiometric amounts of Wilkinson’s catalyst. This discovery sparked significant interest in hydroacylation, especially for the enantioselective and catalytic construction of cyclopentanones. Our research focused on expanding the asymmetric variants to access medium-sized rings (e.g., seven- and eight-membered rings). In addition, we achieved selective intermolecular couplings by incorporating directing groups onto the olefin partner. Along the way, we identified Rh and Co catalysts that transform dienyl aldehydes into a variety of unique carbocycles, such as cyclopentanones, bicyclic ketones, cyclohexenyl aldehydes, and cyclobutanones. Building on the insights gained from olefin hydroacylation, we demonstrated the first highly enantioselective hydroacylation of carbonyls. For example, we demonstrated that ketoaldehydes can cyclize to form lactones with high region- and enantioselectivity. Following these reports, we reported the first intermolecular example that occurs with high stereocontrol. Ketoamides undergo intermolecular carbonyl hydroacylation to furnish α-acyloxyamides that contain a depsipeptide linkage. Finally, we describe how the key acyl-metal-hydride species can be diverted to achieve a C–C bond cleaving process. Transfer hydroformylation enables the preparation of olefins from aldehydes by a dehomologation mechanism. Release of ring strain in the olefin acceptor offers a driving force for the isodesmic transfer of CO and H(2). Mechanistic studies suggest that the counterion serves as a proton-shuttle to enable transfer hydroformylation. Collectively, our studies showcase how transition metal catalysis can transform a common functional group, in this case aldehydes, into structurally distinct motifs. Fine-tuning the coordination sphere of an acyl-metal-hydride species can promote C–C and C–O bond forming reactions, as well as C–C bond cleaving processes.

In 2019, the Veterans Affairs (VA), the largest integrated US healthcare system, started the Pharmacogenomic Testing for Veterans (PHASER) clinical program that provides multi-gene pharmacogenomic (PGx) testing for up to 250,000 veterans at approximately 50 sites. PHASER is staggering program initiation at sites over a 5-year period from 2019 to 2023, as opposed to simultaneous initiation at all sites, to facilitate iterative program quality improvements through Plan-Do-Study-Act cycles. Current resources in the PGx field have not focused on multisite, remote implementation of panel-based PGx testing. In addition to bringing large scale PGx testing to veterans, the PHASER program is developing a roadmap to maximize uptake and optimize the use of PGx to improve drug response outcomes.

Constructing two-dimensional (2D)/2D heterojunctions with intimate interfacial contact is of great importance to achieve high photocatalytic efficiency for hydrogen evolution. Herein, 2D/2D niobium...

Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography (MIBI-SPECT/CT) is a common technology used for primary hyperparathyroidism (PHPT) localization in clinical practice. However, the clinicopathologic factors affecting the accuracy of MIBI-SPECT/CT and the potential limitations remain unclear. Retrospectively enrolled PHPT patients (n = 280) were analyzed from August 2017 to December 2019. Of 96 patients with PHPT (mean age, 54 years; 63 females), 17 had discordance between MIBI-SPECT/CT and intraoperative findings. Among the 17 patients with discordance, 58.8% had major discordance, which occurred in most patients with multigland disease (MGD). Compared with concordant patients, discordant patients exhibited increased frequencies of autoimmune thyroid disease (29.4% vs 10.1%, p = 0.035), MDG (41.2% vs 3.8%, p = 0.035), higher PTH (296 pg/mL vs 146 pg/mL; p = 0.012),and lower phosphorus levels (0.77 mmol/L vs 0.90 mmol/L; p = 0.024). MDG (odds ratio [OR], 16.95; 95% CI 2.10–142.86), parathyroid lesion size of 12 mm or less (OR, 6.93; 95% CI 1.41–34.10), and a PTH level higher than 192.5 pg/mL (OR, 12.66; 95% CI 2.17–71.43) were independently associated with discordant MIBI-SPECT/CT results. MGD was most strongly associated with discordance between MIBI-SPECT/CT and intraoperative findings followed by a PTH level higher than 192.5 pg/mL and parathyroid lesion size of 12 mm or less. Surgeons should recognize these potential limitations, which may improve the preoperative procedure by encouraging further localization imaging and promptly facilitate intraoperative troubleshooting.

Bronchial asthma (asthma) is one of the most common chronic airway diseases, with more than 300 million people worldwide suffering from this disease. In recent years, studies have shown that compared with healthy people, the airway microecological structure and relative abundance of various flora of asthmatic patients have changed, and are related to the airway inflammatory phenotype of asthma. Airway microecology can affect the occurrence and development of asthma through immune response. The mechanism of interaction between airway microecology and asthma can provide new ideas for the accurate treatment of asthma. This article mainly reviewed the current research on airway microecology in asthma, and puts forward prospects for the accurate treatment of asthma in the future.支气管哮喘（简称哮喘）是最常见的慢性气道疾病之一，全球3亿多人患有哮喘。近年来，有研究表明，与健康人相比，哮喘患者的气道微生态结构以及各菌群的相对丰度均发生了改变，且与哮喘气道炎症表型相关。气道微生态可以通过免疫反应影响哮喘的发生发展。气道微生态与哮喘相互作用的机制可以为哮喘精准治疗提供新的思路。本文主要对目前气道微生态在哮喘中的研究进行综述，并对未来哮喘的精准治疗提出展望。.

This study aimed to explore the application value of new biological specimen oral fluid in SARS-CoV-2 nucleic acid and antibody detection. Oral fluid and paired respiratory and blood specimens from 7 confirmed cases of two COVID-19 cluster epidemic were collected in Beijing from October to November 2021. SARS-CoV-2 virus and IgG antibody were detected by real time PCR kits and serum antibody detection reagents, and SARS-CoV-2 IgG antibody in oral fluids was detected by a new established method of magnetic particle chemiluminescence. The results showed that the nucleic acid amplification test of SARS-CoV-2 on nasopharyngeal swabs, throat swabs and oral fluid specimens from 3 confirmed cases of COVID-19 was positive, among which the为探讨新型生物标本口腔液在新型冠状病毒（SARS-CoV-2）核酸和抗体检测中的应用价值，采集2021年10—11月北京两起新型冠状病毒肺炎（简称“新冠肺炎”）聚集性疫情的7例确诊病例的口腔液及配对的呼吸道和血液样本。采用荧光定量PCR和血清抗体检测试剂盒分别检测SARS-CoV-2核酸和IgG抗体，同时采用新建的磁微粒化学发光法检测口腔液标本SARS-CoV-2 IgG抗体。结果显示，3例新冠肺炎确诊病例鼻咽拭子、咽拭子和口腔液标本SARS-CoV-2核酸检测结果均为阳性，其中2例病例口腔液双基因循环阈值（