Displaying publications 61 - 80 of 85 in total

Abstract:
Sort:
  1. The value of amide proton transfer imaging in predicting parametrial invasion and lymph-vascular space invasion of cervical cancer
    Yang C, Hassan HA, Omar NF, Soo TH, Yahaya ASB, Shi T, et al.
    Magn Reson Imaging, 2024 Nov 25.
    PMID: 39603395 DOI: 10.1016/j.mri.2024.110282
    OBJECTIVE: To explore the value of amide proton transfer (APT) imaging in assessing parametrial invasion (PMI) and lymph-vascular space invasion (LVSI) of cervical cancer.

    MATERIALS AND METHODS: We retrospectively analyzed the clinical and imaging data of cervical cancer patients diagnosed pathologically at our hospital from January 2021 to April 2024. All patients underwent routine magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and APT imaging before treatment. Apparent diffusion coefficient (ADC) and APT values were measured. Based on the pathological results, patients were categorized into LVSI (+) and LVSI (-) groups, and PMI (+) and PMI (-) groups. Independent sample t-tests were used to compare the ADC and APT values between these groups. Receiver operating characteristic (ROC) curves were used to assess the sensitivity, specificity, and area under the curve (AUC) of ADC, APT, and ADC + APT in predicting PMI and LVSI. The Delong test was employed to compare the diagnostic performance among these measures.

    RESULTS: A total of 83 patients were included, with 56 in the LVSI (-) group, 27 in the LVSI (+) group, 35 in the PMI (-) group, and 16 in the PMI (+) group. The ADC values for the LVSI (+) and PMI (+) groups were significantly lower than those for the LVSI (-) and PMI (-) groups (P 

  2. Compound heterozygous mutations in TTC7A cause familial multiple intestinal atresias and severe combined immunodeficiency
    Yang W, Lee PP, Thong MK, Ramanujam TM, Shanmugam A, Koh MT, et al.
    Clin Genet, 2015 Dec;88(6):542-9.
    PMID: 25534311 DOI: 10.1111/cge.12553
    Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations.
  3. Ultrahigh-current-density niobium disulfide catalysts for hydrogen evolution
    Yang J, Mohmad AR, Wang Y, Fullon R, Song X, Zhao F, et al.
    Nat Mater, 2019 12;18(12):1309-1314.
    PMID: 31451781 DOI: 10.1038/s41563-019-0463-8
    Metallic transition metal dichalcogenides (TMDs)1-8 are good catalysts for the hydrogen evolution reaction (HER). The overpotential and Tafel slope values of metallic phases and edges9 of two-dimensional (2D) TMDs approach those of Pt. However, the overall current density of 2D TMD catalysts remains orders of magnitude lower (~10-100 mA cm-2) than industrial Pt and Ir electrolysers (>1,000 mA cm-2)10,11. Here, we report the synthesis of the metallic 2H phase of niobium disulfide with additional niobium (2H Nb1+xS2, where x is ~0.35)12 as a HER catalyst with current densities of >5,000 mA cm-2 at ~420 mV versus a reversible hydrogen electrode. We find the exchange current density at 0 V for 2H Nb1.35S2 to be ~0.8 mA cm-2, corresponding to a turnover frequency of ~0.2 s-1. We demonstrate an electrolyser based on a 2H Nb1+xS2 cathode that can generate current densities of 1,000 mA cm-2. Our theoretical results reveal that 2H Nb1+xS2 with Nb-terminated surface has free energy for hydrogen adsorption that is close to thermoneutral, facilitating HER. Therefore, 2H Nb1+xS2 could be a viable catalyst for practical electrolysers.
  4. Identifying kinase targets of PPARγ in human breast cancer
    Kandel A, Dhillon SK, Prabaharan CB, Fatnin Binti Hisham S, Rajamanickam K, Napper S, et al.
    J Drug Target, 2021 07;29(6):660-668.
    PMID: 33496213 DOI: 10.1080/1061186X.2021.1877719
    Breast cancer is the most common cancer in women. Despite advances in screening women for genetic predisposition to breast cancer and risk stratification, a majority of women carriers remain undetected until they become affected. Thus, there is a need to develop a cost-effective, rapid, sensitive and non-invasive early-stage diagnostic method. Kinases are involved in all fundamental cellular processes and mutations in kinases have been reported as drivers of cancer. PPARγ is a ligand-activated transcription factor that plays important roles in cell proliferation and metabolism. However, the complete set of kinases modulated by PPARγ is still unknown. In this study, we identified human kinases that are potential PPARγ targets and evaluated their differential expression and gene pair correlations in human breast cancer patient dataset TCGA-BRCA. We further confirmed the findings in human breast cancer cell lines MCF7 and SK-BR-3 using a kinome array. We observed that gene pair correlations are lost in tumours as compared to healthy controls and could be used as a supplement strategy for diagnosis and prognosis of breast cancer.
  5. Umbilical Cord Mesenchymal Stem Cells Conditioned Medium Promotes Aβ25-35 phagocytosis by Modulating Autophagy and Aβ-Degrading Enzymes in BV2 Cells
    Xu Z, Nan W, Zhang X, Sun Y, Yang J, Lu K, et al.
    J Mol Neurosci, 2018 Jun;65(2):222-233.
    PMID: 29845511 DOI: 10.1007/s12031-018-1075-5
    Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer's disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25-35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25-35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25-35. ucMSCs-CM also promoted the phagocytosis of Aβ25-35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25-35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25-35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia.
  6. Fulltext Genetic Modification of Mucor circinelloides for Canthaxanthin Production by Heterologous Expression of β-carotene Ketolase Gene
    Naz T, Yang J, Nosheen S, Sun C, Nazir Y, Mohamed H, et al.
    Front Nutr, 2021;8:756218.
    PMID: 34722614 DOI: 10.3389/fnut.2021.756218
    Canthaxanthin is a reddish-orange xanthophyll with strong antioxidant activity and higher bioavailability than carotenes, primarily used in food, cosmetics, aquaculture, and pharmaceutical industries. The spiking market for natural canthaxanthin promoted researchers toward genetic engineering of heterologous hosts for canthaxanthin production. Mucor circinelloides is a dimorphic fungus that produces β-carotene as the major carotenoid and is considered as a model organism for carotenogenic studies. In this study, canthaxanthin-producing M. circinelloides strain was developed by integrating the codon-optimized β-carotene ketolase gene (bkt) of the Haematococcus pluvialis into the genome of the fungus under the control of strong promoter zrt1. First, a basic plasmid was constructed to disrupt crgA gene, a negative regulator of carotene biosynthesis resulted in substantial β-carotene production, which served as the building block for canthaxanthin by further enzymatic reaction of the ketolase enzyme. The genetically engineered strain produced a significant amount (576 ± 28 μg/g) of canthaxanthin, which is the highest amount reported in Mucor to date. Moreover, the cell dry weight of the recombinant strain was also determined, producing up to more than 9.0 g/L, after 96 h. The mRNA expression level of bkt in the overexpressing strain was analyzed by RT-qPCR, which increased by 5.3-, 4.1-, and 3-folds at 24, 48, and 72 h, respectively, compared with the control strain. The canthaxanthin-producing M. circinelloides strain obtained in this study provided a basis for further improving the biotechnological production of canthaxanthin and suggested a useful approach for the construction of more valuable carotenoids, such as astaxanthin.
  7. Fulltext Asian Young Doctors Session at the 64th Annual Meeting of the Japanese Society for Gynecologic Oncology (JSGO): Educational Initiatives in the Next Generation for a New Era after the COVID-19 Pandemic
    Kobayashi Y, Komatsu H, Isobe M, Meena J, Weng CS, Kim SI, et al.
    J Gynecol Oncol, 2023 Jan;34(1):e22.
    PMID: 36509465 DOI: 10.3802/jgo.2023.34.e22
  8. Fulltext Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?
    Kou M, Huang L, Yang J, Chiang Z, Chen S, Liu J, et al.
    Cell Death Dis, 2022 Jul 04;13(7):580.
    PMID: 35787632 DOI: 10.1038/s41419-022-05034-x
    Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.
  9. Fulltext Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS
    Wu YL, Planchard D, Lu S, Sun H, Yamamoto N, Kim DW, et al.
    Ann Oncol, 2019 Feb 01;30(2):171-210.
    PMID: 30596843 DOI: 10.1093/annonc/mdy554
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.
  10. Evolving spatio-temporal data machines based on the NeuCube neuromorphic framework: Design methodology and selected applications
    Kasabov N, Scott NM, Tu E, Marks S, Sengupta N, Capecci E, et al.
    Neural Netw, 2016 Jun;78:1-14.
    PMID: 26576468 DOI: 10.1016/j.neunet.2015.09.011
    The paper describes a new type of evolving connectionist systems (ECOS) called evolving spatio-temporal data machines based on neuromorphic, brain-like information processing principles (eSTDM). These are multi-modular computer systems designed to deal with large and fast spatio/spectro temporal data using spiking neural networks (SNN) as major processing modules. ECOS and eSTDM in particular can learn incrementally from data streams, can include 'on the fly' new input variables, new output class labels or regression outputs, can continuously adapt their structure and functionality, can be visualised and interpreted for new knowledge discovery and for a better understanding of the data and the processes that generated it. eSTDM can be used for early event prediction due to the ability of the SNN to spike early, before whole input vectors (they were trained on) are presented. A framework for building eSTDM called NeuCube along with a design methodology for building eSTDM using this is presented. The implementation of this framework in MATLAB, Java, and PyNN (Python) is presented. The latter facilitates the use of neuromorphic hardware platforms to run the eSTDM. Selected examples are given of eSTDM for pattern recognition and early event prediction on EEG data, fMRI data, multisensory seismic data, ecological data, climate data, audio-visual data. Future directions are discussed, including extension of the NeuCube framework for building neurogenetic eSTDM and also new applications of eSTDM.
  11. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with locally-advanced unresectable non-small-cell lung cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS
    Park K, Vansteenkiste J, Lee KH, Pentheroudakis G, Zhou C, Prabhash K, et al.
    Ann Oncol, 2020 02;31(2):191-201.
    PMID: 31959336 DOI: 10.1016/j.annonc.2019.10.026
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries.
  12. Fulltext Mental Health among Adults during the COVID-19 Pandemic Lockdown: A Cross-Sectional Multi-Country Comparison
    Ding K, Yang J, Chin MK, Sullivan L, Demirhan G, Violant-Holz V, et al.
    Int J Environ Res Public Health, 2021 03 07;18(5).
    PMID: 33800008 DOI: 10.3390/ijerph18052686
    Despite the global impact of COVID-19, studies comparing the effects of COVID-19 on population mental health across countries are sparse. This study aimed to compare anxiety and depression symptoms during the COVID-19 lockdown among adults from 11 countries and to examine their associations with country-level COVID-19 factors and personal COVID-19 exposure. A cross-sectional survey was conducted among adults (≥18 years) in 11 countries (Brazil, Bulgaria, China, India, Ireland, North Macedonia, Malaysia, Singapore, Spain, Turkey, United States). Mental health (anxiety, depression, resilient coping, hope) and other study data were collected between June-August 2020. Of the 13,263 participants, 62.8% were female and 51.7% were 18-34 years old. Participants living in Brazil had the highest anxiety and depression symptoms while participants living in Singapore had the lowest. Greater personal COVID-19 exposure was associated with increased anxiety and depression symptoms, but country-level COVID-19 factors were not. Higher levels of hope were associated with reduced anxiety and depression; higher levels of resilient coping were associated with reduced anxiety but not depression. Substantial variations exist in anxiety and depression symptoms across countries during the COVID-19 lockdown, with personal COVID-19 exposure being a significant risk factor. Strategies that mitigate COVID-19 exposure and enhance hope and resilience may reduce anxiety and depression during global emergencies.
  13. Fulltext Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients
    Zhang XC, Wang J, Shao GG, Wang Q, Qu X, Wang B, et al.
    Nat Commun, 2019 04 16;10(1):1772.
    PMID: 30992440 DOI: 10.1038/s41467-019-09762-1
    Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.5%) compared with squamous cell carcinoma (SQCC, 54.4%). The correlation of genomic alterations with immune signatures reveals that low immune infiltration was associated with EGFR mutations in ADC samples, PI3K and/or WNT pathway activation in SQCC. While KRAS mutations are found to be significantly associated with T cell infiltration in ADC samples. The SQCC patients with high antigen presentation machinery and cytotoxic T cell signature scores are found to have a prolonged overall survival time.
  14. Fulltext Physical Activity among Adults Residing in 11 Countries during the COVID-19 Pandemic Lockdown
    Ding K, Yang J, Chin MK, Sullivan L, Durstine JL, Violant-Holz V, et al.
    Int J Environ Res Public Health, 2021 Jul 01;18(13).
    PMID: 34280992 DOI: 10.3390/ijerph18137056
    During the novel coronavirus (COVID-19) pandemic, physical activity (PA) behaviors were altered worldwide due to public health measures such as "lockdown." This study described PA among adults residing in 11 countries during COVID-19 lockdown and examined factors associated with PA engagement. We conducted a cross-sectional anonymous survey among adults (≥18 years old) in 11 countries (Brazil, Bulgaria, China, India, Ireland, Malaysia, North Macedonia, Singapore, Spain, Turkey, United States). Of 11,775 participants, 63.7% were female and 52.8% were 18-34 years old. More than 40% of participants were insufficiently active (43.9%) and reported a decrease in their PA during lockdown (44.8%). Statistically significant differences were observed in (1) proportions of participants being insufficiently active, (2) level of PA, and (3) decrease in PA across the 11 countries. More stringent governmental policy responses were associated with greater likelihood of being insufficiently active during lockdown (adjusted odds ratio = 1.22, 95% confidence interval = 1.03, 1.45). Higher depression or anxiety scores were associated with greater likelihood of decreased level of PA during lockdown.We found substantial reductions in PA levels during COVID-19 lockdown across countries. Country-specific PA promotion interventions are needed during this and similar global emergencies.
  15. Fulltext Effects of mobile health interventions on health-related outcomes in older adults with type 2 diabetes: A systematic review and meta-analysis
    Lee JJN, Abdul Aziz A, Chan ST, Raja Abdul Sahrizan RSFB, Ooi AYY, Teh YT, et al.
    J Diabetes, 2023 Jan;15(1):47-57.
    PMID: 36649940 DOI: 10.1111/1753-0407.13346
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition that is associated with multiple comorbidities. Apart from pharmacological approaches, patient self-management remains the gold standard of care for diabetes. Improving patients' self-management among the elderly with mobile health (mHealth) interventions is critical, especially in times of the COVID-19 pandemic. However, the extent of mHealth efficacy in managing T2DM in the older population remains unknown. Hence, the present review examined the effectiveness of mHealth interventions on cardiometabolic outcomes in older adults with T2DM.

    METHODS: A systematic search from the inception till May 31, 2021, in the MEDLINE, Embase, and PubMed databases was conducted, and 16 randomized controlled trials were included in the analysis.

    RESULTS: The results showed significant benefits on glycosylated hemoglobin (HbA1c) (mean difference -0.24%; 95% confidence interval [CI]: -0.44, -0.05; p = 0.01), postprandial blood glucose (-2.91 mmol/L; 95% CI: -4.78, -1.03; p = 0.002), and triglycerides (-0.09 mmol/L; 95% CI: -0.17, -0.02; p = 0.010), but not on low-density lipoprotein cholesterol (-0.06 mmol/L; 95% CI: -0.14, 0.02; p = 0.170), high-density lipoprotein cholesterol (0.05 mmol/L; 95% CI: -0.03, 0.13; p = 0.220), and blood pressure (systolic blood pressure -0.82 mm Hg; 95% CI: -4.65, 3.00; p = 0.670; diastolic blood pressure -1.71 mmHg; 95% CI: -3.71, 0.29; p = 0.090).

    CONCLUSIONS: Among older adults with T2DM, mHealth interventions were associated with improved cardiometabolic outcomes versus usual care. Its efficacy can be improved in the future as the current stage of mHealth development is at its infancy. Addressing barriers such as technological frustrations may help strategize approaches to further increase the uptake and efficacy of mHealth interventions among older adults with T2DM.

  16. Influence of Time to Achieve Target Systolic Blood Pressure on Outcome After Intracerebral Hemorrhage: The Blood Pressure in Acute Stroke Collaboration
    Wang X, Yang J, Moullaali TJ, Sandset EC, Woodhouse LJ, Law ZK, et al.
    Stroke, 2024 Apr;55(4):849-855.
    PMID: 38410986 DOI: 10.1161/STROKEAHA.123.044358
    OBJECTIVE: To investigate whether an earlier time to achieving and maintaining systolic blood pressure (SBP) at 120 to 140 mm Hg is associated with favorable outcomes in a cohort of patients with acute intracerebral hemorrhage.

    METHODS: We pooled individual patient data from randomized controlled trials registered in the Blood Pressure in Acute Stroke Collaboration. Time was defined as time form symptom onset plus the time (hour) to first achieve and subsequently maintain SBP at 120 to 140 mm Hg over 24 hours. The primary outcome was functional status measured by the modified Rankin Scale at 90 to 180 days. A generalized linear mixed models was used, with adjustment for covariables and trial as a random effect.

    RESULTS: A total of 5761 patients (mean age, 64.0 [SD, 13.0], 2120 [36.8%] females) were included in analyses. Earlier SBP control was associated with better functional outcomes (modified Rankin Scale score, 3-6; odds ratio, 0.98 [95% CI, 0.97-0.99]) and a significant lower risk of hematoma expansion (0.98, 0.96-1.00). This association was stronger in patients with bigger baseline hematoma volume (>10 mL) compared with those with baseline hematoma volume ≤10 mL (0.006 for interaction). Earlier SBP control was not associated with cardiac or renal adverse events.

    CONCLUSIONS: Our study confirms a clear time relation between early versus later SBP control (120-140 mm Hg) and outcomes in the one-third of patients with intracerebral hemorrhage who attained sustained SBP levels within this range. These data provide further support for the value of early recognition, rapid transport, and prompt initiation of treatment of patients with intracerebral hemorrhage.

  17. Fulltext Whole-genome noncoding sequence analysis in T-cell acute lymphoblastic leukemia identifies oncogene enhancer mutations
    Hu S, Qian M, Zhang H, Guo Y, Yang J, Zhao X, et al.
    Blood, 2017 Jun 15;129(24):3264-3268.
    PMID: 28408461 DOI: 10.1182/blood-2017-03-771162
    Publisher's Note: There is an Inside Blood Commentary on this article in this issue.
  18. The rubber tree genome reveals new insights into rubber production and species adaptation
    Tang C, Yang M, Fang Y, Luo Y, Gao S, Xiao X, et al.
    Nat Plants, 2016 05 23;2(6):16073.
    PMID: 27255837 DOI: 10.1038/nplants.2016.73
    The Para rubber tree (Hevea brasiliensis) is an economically important tropical tree species that produces natural rubber, an essential industrial raw material. Here we present a high-quality genome assembly of this species (1.37 Gb, scaffold N50 = 1.28 Mb) that covers 93.8% of the genome (1.47 Gb) and harbours 43,792 predicted protein-coding genes. A striking expansion of the REF/SRPP (rubber elongation factor/small rubber particle protein) gene family and its divergence into several laticifer-specific isoforms seem crucial for rubber biosynthesis. The REF/SRPP family has isoforms with sizes similar to or larger than SRPP1 (204 amino acids) in 17 other plants examined, but no isoforms with similar sizes to REF1 (138 amino acids), the predominant molecular variant. A pivotal point in Hevea evolution was the emergence of REF1, which is located on the surface of large rubber particles that account for 93% of rubber in the latex (despite constituting only 6% of total rubber particles, large and small). The stringent control of ethylene synthesis under active ethylene signalling and response in laticifers resolves a longstanding mystery of ethylene stimulation in rubber production. Our study, which includes the re-sequencing of five other Hevea cultivars and extensive RNA-seq data, provides a valuable resource for functional genomics and tools for breeding elite Hevea cultivars.
  19. Fulltext The Tsinghua-Lancet Commission on Healthy Cities in China: unlocking the power of cities for a healthy China
    Yang J, Siri JG, Remais JV, Cheng Q, Zhang H, Chan KKY, et al.
    Lancet, 2018 05 26;391(10135):2140-2184.
    PMID: 29678340 DOI: 10.1016/S0140-6736(18)30486-0
  20. Fulltext Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA
    Felip E, Cho BC, Gutiérrez V, Alip A, Besse B, Lu S, et al.
    Ann Oncol, 2024 Sep;35(9):805-816.
    PMID: 38942080 DOI: 10.1016/j.annonc.2024.05.541
    BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups.

    PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR).

    RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004].

    CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

Related Terms
    Try searching for something
Filters
Contact Us

Please provide feedback to Administrator ([email protected])

External Links