Displaying publications 81 - 100 of 273 in total

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  1. Lee WC, Anton BP, Wang S, Baybayan P, Singh S, Ashby M, et al.
    BMC Genomics, 2015;16:424.
    PMID: 26031894 DOI: 10.1186/s12864-015-1585-2
    The genome of the human gastric pathogen Helicobacter pylori encodes a large number of DNA methyltransferases (MTases), some of which are shared among many strains, and others of which are unique to a given strain. The MTases have potential roles in the survival of the bacterium. In this study, we sequenced a Malaysian H. pylori clinical strain, designated UM032, by using a combination of PacBio Single Molecule, Real-Time (SMRT) and Illumina MiSeq next generation sequencing platforms, and used the SMRT data to characterize the set of methylated bases (the methylome).
  2. Wang D, Tang G, Huang Y, Yu C, Li S, Zhuang L, et al.
    J Med Case Rep, 2015;9:109.
    PMID: 25962780 DOI: 10.1186/s13256-015-0580-1
    Human infection with avian influenza A (H7N9) virus was first reported on March, 2013 in the Yangtze River Delta region of China. The majority of human cases were detected in mainland China; other regions out of mainland China reported imported human cases, including Hong Kong SAR, Taiwan (the Republic of China) and Malaysia, due to human transportation. Here, we report the first human case of H7N9 infection imported into Guizhou Province during the Spring Festival travel season in January 2014.
  3. Yang X, Wang S, King TL, Kerr CJ, Blanchet C, Svergun D, et al.
    Faraday Discuss, 2016 Jul 18.
    PMID: 27430046
    We have developed a new class of lanthanide nano-clusters that self-assemble using flexible Schiff base ligands. Cd-Ln and Ni-Ln clusters, [Ln8Cd24(L(1))12(OAc)39Cl7(OH)2] (Ln = Nd, Eu), [Eu8Cd24(L(1))12(OAc)44], [Ln8Cd24(L(2))12(OAc)44] (Ln = Nd, Yb, Sm) and [Nd2Ni4(L(3))2(acac)6(NO3)2(OH)2], were constructed using different types of flexible Schiff base ligands. These molecular nano-clusters exhibit anisotropic architectures that differ considerably depending upon the presence of Cd (nano-drum) or Ni (square-like nano-cluster). Structural characterization of the self-assembled particles has been undertaken using crystallography, transmission electron microscopy and small-angle X-ray scattering. Comparison of the metric dimensions of the nano-drums shows a consistency of size using these techniques, suggesting that these molecules may share similar structural features in both solid and solution states. Photophysical properties were studied by excitation of the ligand-centered absorption bands in the solid state and in solution, and using confocal microscopy of microspheres loaded with the compounds. The emissive properties of these compounds vary depending upon the combination of lanthanide and Cd or Ni present in these clusters. The results provide new insights into the construction of novel high-nuclearity nano-clusters and offer a promising foundation for the development of new functional nanomaterials.
  4. Chen W, Li H, Hou E, Wang S, Wang G, Panahi M, et al.
    Sci Total Environ, 2018 Sep 01;634:853-867.
    PMID: 29653429 DOI: 10.1016/j.scitotenv.2018.04.055
    The aim of the current study was to produce groundwater spring potential maps using novel ensemble weights-of-evidence (WoE) with logistic regression (LR) and functional tree (FT) models. First, a total of 66 springs were identified by field surveys, out of which 70% of the spring locations were used for training the models and 30% of the spring locations were employed for the validation process. Second, a total of 14 affecting factors including aspect, altitude, slope, plan curvature, profile curvature, stream power index (SPI), topographic wetness index (TWI), sediment transport index (STI), lithology, normalized difference vegetation index (NDVI), land use, soil, distance to roads, and distance to streams was used to analyze the spatial relationship between these affecting factors and spring occurrences. Multicollinearity analysis and feature selection of the correlation attribute evaluation (CAE) method were employed to optimize the affecting factors. Subsequently, the novel ensembles of the WoE, LR, and FT models were constructed using the training dataset. Finally, the receiver operating characteristic (ROC) curves, standard error, confidence interval (CI) at 95%, and significance level P were employed to validate and compare the performance of three models. Overall, all three models performed well for groundwater spring potential evaluation. The prediction capability of the FT model, with the highest AUC values, the smallest standard errors, the narrowest CIs, and the smallest P values for the training and validation datasets, is better compared to those of other models. The groundwater spring potential maps can be adopted for the management of water resources and land use by planners and engineers.
  5. Zhang R, Wang S, Huang X, Yang Y, Fan H, Yang F, et al.
    Anal Chim Acta, 2020 Jan 15;1094:142-150.
    PMID: 31761041 DOI: 10.1016/j.aca.2019.10.012
    α-synuclein is a predominantly expressing neuronal protein for understanding the neurodegenerative disorders. A diagnosing system with aggregated α-synuclein encoded by SNCA gene is necessary to make the precautionary treatment against Parkinson's disease (PD). Herein, gold-nanourchin conjugated anti-α-synuclein antibody was desired as the probe and seeded on single-walled carbon nanotube (SWCN) integrated interdigitated electrode (IDE). The surface morphology of SWCN-modified IDE and gold urchin-antibody conjugates were observed under FESEM, FETEM and AFM, the existing elements were confirmed. Voltammetry analysis revealed that the limit of fibril-formed α-synuclein detection was improved by 1000 folds (1 fM) with gold-nanourchin-antibody modified surface, compared to the surface with only antibody (1 pM). Validating the interaction of α-synuclein by Enzyme-linked Immunosorbent Assay was displayed the detection limit as 10 pM. IDE has a good reproducibility and a higher selectivity on α-synuclein as evidenced by the interactive analysis with the control proteins, PARK1 and DJ-1.
  6. Li M, Han N, Zhang X, Wang S, Jiang M, Bokhari A, et al.
    Environ Res, 2022 Apr 01;205:112544.
    PMID: 34902376 DOI: 10.1016/j.envres.2021.112544
    Using solar energy to catalyse photo-driven processes to address the energy crisis and environmental pollution plays a role in the path to a sustainable society. Many oxide-based materials, especially perovskite oxides, have been widely investigated as catalysts for photocatalysis in energy and environment because of the low-cost and earth-abundant and good performance. At this stage, there is a need to present a scientific-based evaluation of the technologies developed so far and identify the most sustainable technologies and the existing limitations and opportunities for their commercialisation. This work comprehensively investigated the outcomes using various scientometric indices on perovskite oxide-based photo(electro)catalysts for water splitting, nitrogen fixation, carbon dioxide conversion, organic pollutant degradation, current trends and advances in the field. According to the results achieved, efforts in both energy and environment based on perovskite oxides have been initiated in the 1990s and accelerated since the 2010s. China and the United States were identified as the most contributing countries. Based on the results achieved in this study, the main milestones and current trends in the development of this field have been identified. The aim of this research is to provide useful guidelines for the further investigation of perovskite oxide-based catalysts for photoelectrocatalysis and photocatalysis both in energy and environment on the applications such as water splitting, nitrogen fixation, carbon dioxide conversion, and wastewater treatment.
  7. Ge P, Li Q, Dong M, Niu Y, Han X, Xiong P, et al.
    Front Public Health, 2022;10:1074559.
    PMID: 36620260 DOI: 10.3389/fpubh.2022.1074559
    OBJECTIVE: To investigate the status of Chinese residents' self-medication behavior and the important factors to consider when purchasing OTC drugs, and to explore the related factors of the possibility that Chinese residents take medical staff's suggestions as important factors to consider when purchasing OTC drugs.

    STUDY DESIGN: A cross-sectional survey.

    METHODS: A questionnaire was developed for exploring the sociodemographic characteristics of the respondents, their self-medication status, and important considerations. The questionnaire includes several scales including Health Literacy Scale-Short Form (HLS-SF), EQ-5D Visual Analog Scale (EQ-5D-VAS), Big Five Inventary-10 Items (BFI-10), and New General Self Efficacy Scale (NGSES). After carrying out a multi-stage sampling method, the questionnaire was conducted nationwide from July 10 to September 15, 2021. Next, descriptive statistics were conducted to analyze the general features. Logistic regression was then used to analyze the related factors of the possibility that the respondents took the suggestions of medical staff as an important consideration when purchasing OTC drugs.

    RESULTS: Nine thousand two hundred fifty-six qualified questionnaires were received. 99.06% of Chinese adults had self-medication behaviors. The types of OTC drugs purchased most by the respondents were NSAIDs (5,421/9,256 people, 58.57%) and vitamins/minerals (4,851/9,256 people, 52.41%). 86.2% of the respondents took the suggestions of medical staff as an important consideration when purchasing OTC drugs. The results of multi-factor logistic regression showed that women, those living in the central and western regions of China, those suffering from chronic diseases, those with high agreeableness, high conscientiousness, high neuroticism and openness, high health literacy, high EQ-5D-VAS, and those with high self-efficacy are more likely to take medical staff's suggestions as important factors to consider.

    CONCLUSION: The vast majority of Chinese adults have self-medication behavior. Important considerations when purchasing OTC drugs include medical staff's suggestions, drug safety and drug efficacy. Whether residents take the suggestions of medical staff as an important consideration is related to their sociological characteristics, agreeableness, conscientiousness, neuroticism, openness, health literacy, self-assessment health status, and self-efficacy. When purchasing and using OTC drugs, residents should carefully listen to the suggestions from medical staff. They should also carefully consider their own conditions before buying OTC drugs.

  8. Patil M, Hunasikai SG, Mathad SN, Patil AY, Hegde CG, Sudeept MA, et al.
    Heliyon, 2023 Nov;9(11):e21992.
    PMID: 38034709 DOI: 10.1016/j.heliyon.2023.e21992
    The air separation (O2/N2) based on polymeric membranes is critical because it is more energy efficient than traditional methods. Dense polymeric membranes are now the main stay of industrial processes that generate oxygen and nitrogen enriched gas. Though, regular polymeric membranes often fall short of selective pressure demands because O2 and N2 gases have such comparable equivalent diameters. While polymer composites have their benefits, nanocomposite (NCs) allows for the production of high-performance barriers. Utilising Matrimid® 5218 (Matrimid) as the base framework and multiwall carbon nanotube (MWCNT) as the filler, a novel NCs for O2/N2 separation was developed. Both matrimid and MWCNTs were chemically modified quaternization and functionalizing the MWCNTs. The membranes were casted using solution casting with a combination of quaternized matrimid and functionalized multi-walled carbon nanotubes (f-MWCNT). When f-MWCNT was added to quaternized matrimid, it created interfacial compatibility, which increased O2/N2 selectivity and permeability by 65 % and 35 %, respectively. In the current study, increasing O2 diffusivity and O2/N2 solubility selectivity resulted in improved performance, this paves a way for manufacturing innovation.
  9. Khosravi Y, Rehvathy V, Wee WY, Wang S, Baybayan P, Singh S, et al.
    Gut Pathog, 2013;5:25.
    PMID: 23957912 DOI: 10.1186/1757-4749-5-25
    Helicobacter pylori is a Gram-negative bacterium that persistently infects the human stomach inducing chronic inflammation. The exact mechanisms of pathogenesis are still not completely understood. Although not a natural host for H. pylori, mouse infection models play an important role in establishing the immunology and pathogenicity of H. pylori. In this study, for the first time, the genome sequences of clinical H. pylori strain UM032 and mice-adapted derivatives, 298 and 299, were sequenced using the PacBio Single Molecule, Real-Time (SMRT) technology.
  10. Zhou X, Li Y, Wang W, Wang S, Hou J, Zhang A, et al.
    Theranostics, 2020;10(21):9443-9457.
    PMID: 32863938 DOI: 10.7150/thno.46078
    Objective: Esophageal squamous cell carcinoma (ESCC) is one of the most commonly diagnosed cancer types in China. Recent genomic sequencing analysis indicated the over-activation of Hippo/YAP signaling might play important roles for the carcinogenic process and progression for ESCC patients. However, little is known about the molecular mechanisms that controls Hippo signaling activity in ESCC. Our previous studies indicated that PLCE1-an important risk factor for ESCC-linked to ESCC progression through snail signaling, during this period, we found PARK2 was an important downstream target of PLCE1-snail axis. PARK2 was decreased in ESCC human samples, and correlated with good prognosis in ESCC patients. Further research showed that PARK2 could inhibit YAP, which functions as key downstream effectors of the Hippo pathway. Here, we aim to reveal the molecular mechanisms of PARK2 modulated Hippo pathway in ESCC. Methods: To evaluate the function of PARK2 in ESCC, we used a tissue microarray (TMA) of 223 human ESCC patients and immunohistochemistry to analyze the correlation between PARK2 expression and clinicopathologic variables. Depletion of endogenous PARK2 and YAP from ESCC cells using CRISPR/Cas9 technologies. Flow cytometry and EdU cell proliferation assay were used to detect proliferation of ESCC cells. Nude mice subcutaneous injection and Ki-67 staining were used to evaluate tumor growth in vivo. Migration and invasion assays were performed. In addition, lung metastasis models in mice were used to validate the function of PARK2 in vivo. Identification of PARK2 involved in hippo pathway was achieved by expression microarray screening, double immunofluorescence staining and co-immunoprecipitation assays. The RNA-seq analysis results were validated through quantitative real-time PCR (qRT-PCR) analysis. The protein half-life of YAP was analyzed by Cycloheximide assay, and the TEAD activity was detected by Luciferase reporter assays. Results: Clinical sample of ESCC revealed that low PARK2 expression correlated with late tumor stage (P < 0.001), poor differentiation (P < 0.04), lymph node (P < 0.001) and distant metastasis (P = 0.0087). Multivariate Cox proportional regression analysis further revealed that PARK2 expression (P = 0.032) is an independent prognostic factor for the overall survival of ESCC patients. Besides, the immunohistochemistry results showed that PARK2 negatively correlated with YAP protein level (P < 0.001). PARK2 depletion promotes ESCC progression both through Hippo/YAP axis, while PARK2 overexpression suppresses ESCC tumor progression by Hippo signaling. Co-IP and ubiquitination assays revealed that PARK2 could interact with YAP in the cytosol and promotes YAP K48-linked ubiquitination at K90 sites. Conclusion: Clinical sample analysis and mechanistic study have validated PARK2 as a tumor suppressor for ESCC. Multivariate Cox proportional regression analysis further revealed that PARK2 is an independent prognostic factor for the overall survival of ESCC patients. Cellular and molecular mechanisms in this study showed that PARK2 associated with YAP protein in the cytosol, promoted YAP ubiquitination and proteasome-dependent degradation in ESCC cells. Therefore, as a novel modulator for Hippo signaling, modulation of PARK2 activity or gene expression level could be an appealing strategy to treat esophageal.
  11. Shen D, Qi H, Lin W, Zhang W, Bian D, Shi X, et al.
    Sci Adv, 2021 Jun;7(23).
    PMID: 34088662 DOI: 10.1126/sciadv.abf0614
    Balancing the biodegradability and mechanical integrity of a bioresorbable scaffold (BRS) with time after implantation to match the remodeling of the scaffolded blood vessel is important, but a key challenge in doing so remains. This study presents a novel intercalated structure of a metallic BRS by introducing a nanoscale Zn sacrificial layer between the nitrided Fe platform and the sirolimus-carrying poly(d,l-lactide) drug coating. The PDLLA-Zn-FeN BRS shows a multistage biodegradation behavior, maintaining mechanical integrity at the initial stage and exhibiting accelerated biodegradation at the subsequent stage in both rabbit abdominal aortas and human coronary arteries, where complete biodegradation was observed about 2 years after implantation. The presence of the nanoscale Zn sacrificial layer with an adjustable thickness also contributes to the tunable biodegradation of BRS and allows the reduction of the metallic strut thickness to 53 μm, with radial strength as strong as that of the current permanent drug-eluting stents.
  12. Chang GC, Lam DC, Tsai CM, Chen YM, Shih JY, Aggarwal S, et al.
    Int J Clin Oncol, 2021 May;26(5):841-850.
    PMID: 33783657 DOI: 10.1007/s10147-021-01869-0
    BACKGROUND: This study evaluated outcomes among patients with advanced/metastatic non-small-cell lung cancer (NSCLC) treated at Asian centers participating in the global named-patient-use (NPU) program for afatinib.

    METHODS: Patients had progressed after initial benefit with erlotinib or gefitinib, and/or had an EGFR or HER2 mutation, had no other treatment options, and were ineligible for afatinib trials. The recommended starting dose of afatinib was 50 mg/day. Dose modifications were allowed, and afatinib was continued as long as deemed beneficial. Response and survival information was provided voluntarily. Safety reporting was mandatory.

    RESULTS: 2242 patients (26% aged ≥ 70 years, 96% with adenocarcinoma) received afatinib at centers in 10 Asian countries. Most were heavily pre-treated, including prior treatment with erlotinib or gefitinib. Of 1281 patients tested, 1240 had EGFR mutations (common: 1034/1101; uncommon: 117/1101). There were no new safety signals, the most common adverse events being rash and diarrhea. Objective response rate (ORR) was 24% overall (n = 431 with data available), 27% for patients with common EGFR mutations (n = 230) and 28% for those with uncommon mutations (n = 32); median time to treatment failure (TTF) in these groups was 7.6 months (n = 1550), 6.4 months (n = 692) and 8.4 months (n = 83), respectively. In patients with EGFR exon 20 insertions (n = 23) and HER2 mutations (n = 12), median TTF exceeded 12 months.

    CONCLUSIONS: Patient outcomes in this study were similar to those reported in the analysis of the global NPU. Afatinib achieved clinical benefits in patients with refractory NSCLC. ORR and TTF were similar between patients with tumors harboring uncommon and common EGFR mutations.

  13. Li Q, Zhang K, Li R, Yang L, Yi Y, Liu Z, et al.
    Sci Total Environ, 2023 May 10;872:162071.
    PMID: 36775179 DOI: 10.1016/j.scitotenv.2023.162071
    Biomass burning (BB) has significant impacts on air quality and climate change, especially during harvest seasons. In previous studies, levoglucosan was frequently used for the calculation of BB contribution to PM2.5, however, the degradation of levoglucosan (Lev) could lead to large uncertainties. To quantify the influence of the degradation of Lev on the contribution of BB to PM2.5, PM2.5-bound biomass burning-derived markers were measured in Changzhou from November 2020 to March 2021 using the thermal desorption aerosol gas chromatography-mass spectrometry (TAG-GC/MS) system. Temporal variations of three anhydro-sugar BB tracers (e.g., levoglucosan, mannosan (Man), and galactosan (Gal)) were obtained. During the sampling period, the degradation level of air mass (x) was 0.13, indicating that ~87 % of levoglucosan had degraded before sampling in Changzhou. Without considering the degradation of levoglucosan in the atmosphere, the contribution of BB to OC were 7.8 %, 10.2 %, and 9.3 % in the clean period, BB period, and whole period, respectively, which were 2.4-2.6 times lower than those (20.8 %-25.9 %) considered levoglucosan degradation. This illustrated that the relative contribution of BB to OC could be underestimated (~14.9 %) without considering degradation of levoglucosan. Compared to the traditional method (i.e., only using K+ as BB tracer), organic tracers (Lev, Man, Gal) were put into the Positive Matrix Factorization (PMF) model in this study. With the addition of BB organic tracers and replaced K+ with K+BB (the water-soluble potassium produced by biomass burning), the overall contribution of BB to PM2.5 was enhanced by 3.2 % after accounting for levoglucosan degradation based on the PMF analysis. This study provides useful information to better understand the effect of biomass burning on the air quality in the Yangtze River Delta region.
  14. Chang Y, Liu H, Liu M, Liao X, Sahu SK, Fu Y, et al.
    Gigascience, 2019 03 01;8(3).
    PMID: 30535374 DOI: 10.1093/gigascience/giy152
    BACKGROUND: The expanding world population is expected to double the worldwide demand for food by 2050. Eighty-eight percent of countries currently face a serious burden of malnutrition, especially in Africa and south and southeast Asia. About 95% of the food energy needs of humans are fulfilled by just 30 species, of which wheat, maize, and rice provide the majority of calories. Therefore, to diversify and stabilize the global food supply, enhance agricultural productivity, and tackle malnutrition, greater use of neglected or underutilized local plants (so-called orphan crops, but also including a few plants of special significance to agriculture, agroforestry, and nutrition) could be a partial solution.

    RESULTS: Here, we present draft genome information for five agriculturally, biologically, medicinally, and economically important underutilized plants native to Africa: Vigna subterranea, Lablab purpureus, Faidherbia albida, Sclerocarya birrea, and Moringa oleifera. Assembled genomes range in size from 217 to 654 Mb. In V. subterranea, L. purpureus, F. albida, S. birrea, and M. oleifera, we have predicted 31,707, 20,946, 28,979, 18,937, and 18,451 protein-coding genes, respectively. By further analyzing the expansion and contraction of selected gene families, we have characterized root nodule symbiosis genes, transcription factors, and starch biosynthesis-related genes in these genomes.

    CONCLUSIONS: These genome data will be useful to identify and characterize agronomically important genes and understand their modes of action, enabling genomics-based, evolutionary studies, and breeding strategies to design faster, more focused, and predictable crop improvement programs.

  15. Jovanović V, Rudnev M, Arslan G, Buzea C, Dimitrova R, Góngora V, et al.
    Appl Res Qual Life, 2022 Jan 24.
    PMID: 35096193 DOI: 10.1007/s11482-021-10024-w
    Measurement of adolescent life satisfaction across cultures has not received much attention in previous empirical research. The present study evaluated measurement invariance of the Satisfaction with Life Scale (SWLS) among adolescents in 24 countries and regions (N = 22,710; age range = 13-19 years; 53% female). A single-factor model with residual covariance between a pair of items tapping past life satisfaction fitted well in 19 countries and regions and showed a partial metric invariance. In a subset of nine countries and regions, partial scalar invariance was supported. Partial metric invariance across all 24 countries and regions was achieved when custom model modifications in five countries and regions were included. Three SWLS items showed evidence of noninvariance across cultures. The measurement model was found to operate similarly across gender and age. Our findings suggest that caution is needed when using the SWLS for measuring life satisfaction among adolescents from different cultures.

    Supplementary Information: The online version contains supplementary material available at 10.1007/s11482-021-10024-w.

  16. Im SA, Gennari A, Park YH, Kim JH, Jiang ZF, Gupta S, et al.
    ESMO Open, 2023 Jun;8(3):101541.
    PMID: 37178669 DOI: 10.1016/j.esmoop.2023.101541
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.
  17. Xiao L, Parolia A, Qiao Y, Bawa P, Eyunni S, Mannan R, et al.
    Nature, 2022 Jan;601(7893):434-439.
    PMID: 34937944 DOI: 10.1038/s41586-021-04246-z
    The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling1 and is altered in over 20% of cancers2,3. Here we developed a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4, called AU-15330. Androgen receptor (AR)+ forkhead box A1 (FOXA1)+ prostate cancer cells are exquisitely sensitive to dual SMARCA2 and SMARCA4 degradation relative to normal and other cancer cell lines. SWI/SNF ATPase degradation rapidly compacts cis-regulatory elements bound by transcription factors that drive prostate cancer cell proliferation, namely AR, FOXA1, ERG and MYC, which dislodges them from chromatin, disables their core enhancer circuitry, and abolishes the downstream oncogenic gene programs. SWI/SNF ATPase degradation also disrupts super-enhancer and promoter looping interactions that wire supra-physiologic expression of the AR, FOXA1 and MYC oncogenes themselves. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide, even inducing disease remission in castration-resistant prostate cancer (CRPC) models without toxicity. Thus, impeding SWI/SNF-mediated enhancer accessibility represents a promising therapeutic approach for enhancer-addicted cancers.
  18. Cui Y, Hada K, Kawashima T, Kino M, Lin W, Mizuno Y, et al.
    Nature, 2023 Sep;621(7980):711-715.
    PMID: 37758892 DOI: 10.1038/s41586-023-06479-6
    The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.
  19. Qian F, Wang S, Mitchell J, McGuffog L, Barrowdale D, Leslie G, et al.
    J Natl Cancer Inst, 2019 Apr 01;111(4):350-364.
    PMID: 30312457 DOI: 10.1093/jnci/djy132
    BACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear.

    METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided.

    RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer.

    CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.

  20. Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al.
    Anesthesiology, 2014 Mar;120(3):564-78.
    PMID: 24534856 DOI: 10.1097/ALN.0000000000000113
    BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS.

    METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria.

    RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom.

    CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

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