Displaying publications 1 - 20 of 113 in total

  1. Di J, Xiong Y, Li D, Li X, Wang W, Cheng Y, et al.
    Malays J Pathol, 2022 Dec;44(3):509-516.
    PMID: 36591718
    Hyalinising clear cell carcinoma (HCCC) of the lung is an extremely rare tumour that is just recently recognised as one of the salivary gland-type tumours (SGTT) in the latest WHO classification of thoracic tumours. Eleven cases have been reported in English literature since Joaquín et al. reported the first case. Given the very limited number of cases, the clinical and histological features of pulmonary HCCC are equivocal. Herein, we present two cases of pulmonary HCCC. The patients were a 66-year-old man and a 48-year-old woman. The mass was located on the right main bronchus and right middle lobar bronchus separately. One was 2 cm and the other was 3.3 cm in the greatest dimension. The tumours were comprised of small monomorphic cells with clear or eosinophilic cytoplasm and infiltrated in a hyalinising stroma arranged in nests, cords, sheets and trabeculae. Their morphology resembled their head and neck counterparts. Immunohistochemically, the tumour cells were positive for AE1/AE3, P63, while negative for TTF1, Calponin, S-100, HMB45 and PAX8. Ki-67 labeling ranges from 3% to 10%. Fluorescence in situ hybridisation (FISH) demonstrated EWSR1 rearrangement and Next-generation sequencing (NGS) demonstrated EWSR1- ATF1 (exon 11: exon 3) fusion in case one and EWSR1- ATF1 (exon 2: exon 12) fusion in case two. This is the first time to report the EWSR1-ATF1fusion point other than exon 11: exon 3 in pulmonary HCCC. Case one recurred two years after local resection but didn't metastasise during follow-up 36 months. Case two is alive without disease after lobectomy during follow-up 14 months.
  2. Shahrizaila N, Goh KJ, Kokubun N, Tan AH, Tan CY, Yuki N
    Muscle Nerve, 2014 Apr;49(4):558-63.
    PMID: 23893512 DOI: 10.1002/mus.23973
    Differing patterns of neurophysiological abnormalities have been reported in patients with Fisher syndrome. Fisher syndrome is rare, and few series have incorporated prospective serial studies to define the natural history of nerve conduction studies in Guillain-Barré syndrome.
  3. Yip KW, Cheng YKY, Leung TY
    Med J Malaysia, 2017 04;72(2):126-127.
    PMID: 28473678 MyJurnal
    In-utero intestinal volvulus is a rare but potential life threatening foetal complications. It is a surgical emergency and delay in diagnosis or treatment can increase the morbidity and mortality to the foetus. We report a case of mild foetal bowel dilatation diagnosed at 21 weeks of gestation. She was closely follow up and at 31 weeks of gestation, in-utero intestinal volvulus was diagnosed with the characteristic 'whirlpool' sign on ultrasound examination. This case emphasises the importance of early recognition and quick decision to delivery when intestinal volvulus is diagnosed. This enabled early surgical intervention to prevent further foetal morbidity.
  4. Li S, Li W, Cheng Y, Liu J, Wei G, Wang B
    Biodivers Data J, 2024;12:e113427.
    PMID: 38235166 DOI: 10.3897/BDJ.12.e113427
    BACKGROUND: The Asian leaf litter toads of the genus Leptobrachella Smith, 1925 (Anura, Megophryidae) inhabit the forest floor and rocky streams in hilly evergreen forests and are widely distributed from southern China, west to north-eastern India and Myanmar, through mainland Indochina to Peninsular Malaysia and the Island of Borneo.

    NEW INFORMATION: A new species of the Asian leaf litter toad genus Leptobrachella from Guizhou Province, China is described. Molecular phylogenetic analyses, based on mitochondrial 16S rRNA and COI genes and nuclear RAG1 gene sequences indicated that the new species is genetically divergent from its congeners. The new species could be distinguished from its congeners by a combination of the following characters: (1) body of medium size in males (SVL 31.9 - 32.9 mm); (2) distinct black spots present on flanks; (3) toes rudimentarily webbed, with wide lateral fringes; (4) skin on dorsum shagreened with fine tiny granules and short ridges; (5) heels overlapped when thighs are positioned at right angles to the body; (6) tibia-tarsal articulation reaching interior corner of the eye.A new species of the Asian leaf litter toad genus Leptobrachella from Guizhou Province, China is described. Molecular phylogenetic analyses, based on mitochondrial 16S rRNA and COI genes and nuclear RAG1 gene sequences indicated that the new species is genetically divergent from its congeners. The new species could be distinguished from its congeners by a combination of the following characters: (1) body of medium size in males (SVL 31.9 - 32.9 mm); (2) distinct black spots present on flanks; (3) toes rudimentarily webbed, with wide lateral fringes; (4) skin on dorsum shagreened with fine tiny granules and short ridges; (5) heels overlapped when thighs are positioned at right angles to the body; (6) tibia-tarsal articulation reaching interior corner of the eye.

  5. Bao D, Mydin F, Surat S, Lyu Y, Pan D, Cheng Y
    Psychol Res Behav Manag, 2024;17:1115-1128.
    PMID: 38505350 DOI: 10.2147/PRBM.S448844
    BACKGROUND: Improving academic engagement of medical postgraduates is crucial for enhancing the quality of learning and the development of medical education. Due to medical postgraduates face high levels of stress and rigorous demands, yet the mechanisms linking challenge-hindrance stressors to academic engagement in this context remain largely unexplored. This study aims to explore the comprehensive relationship between challenge-hindrance stressors and academic engagement among medical postgraduates in China.

    METHODS: Data were collected from 437 medical postgraduates in China, to investigate their challenge-hindrance stressors, emotional exhaustion, learning, relaxation and academic engagement. Among these postgraduates, 40.3% were male and 59.7% were female, with the mean age of the participants being 25.71 years. Statistical procedures were conducted using Mplus 8.3, ensuring a robust analysis of the data collected.

    RESULTS: Our study showed that both challenge and hindrance stressors are significantly positively correlated with emotional exhaustion among Chinese medical postgraduates, and emotional exhaustion is negatively associated with academic engagement. Emotional exhaustion mediates the relationship between challenge-hindrance stressors and academic engagement. Learning plays a protective role, moderating the challenge stressors and emotional exhaustion relationship and its indirect effect on academic engagement. However, relaxation was not identified as a significant moderating factor in this context.

    CONCLUSION: Our findings not only revealed emotional exhaustion as a potential mechanism underlying the relationship between challenge-hindrance stressors and academic engagement but also validated the moderating role of learning in mitigating the adverse effects of challenge stressors on emotional exhaustion and academic engagement among Chinese medical postgraduates. This comprehensive insight into the complex dynamics between different stressors and academic engagement provides both theoretical and empirical evidence for medical universities. It underscores the importance of interventions to enhance academic engagement in stressful environments and serves as a valuable reference for the development of reasonable assessment systems. These contributions are crucial for fostering a supportive educational atmosphere and promoting the well-being of medical postgraduates.

  6. Zheng B, Xing G, Bi Y, Yan G, Wang J, Cheng Y, et al.
    Saudi J Biol Sci, 2016 Jan;23(1):54-65.
    PMID: 26858539 DOI: 10.1016/j.sjbs.2015.08.009
    As a novel oral drug delivery system, proliposome was applied to improve the solubility of active components of Ginkgo biloba extract (GbE). There are currently few reports focusing on the pharmacokinetic characteristics of proliposome of GbE (GbP). A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of active components of GbP and a commercial tablet product (Ginaton) in rat plasma was developed and successfully validated. The method was applied to the comparative pharmacokinetic evaluation of GbP and Ginaton in rat plasma. The results indicated that GbP has a significant effect on absorption, elimination and bioavailability of flavonoids and terpenoid lactones in comparison with Ginaton. The obtained results would be helpful for evaluating the absorption mechanism in the gastrointestinal tract in pharmacokinetic level and guiding the development of the novel oral drug delivery system.
  7. Cheng Y, Lai OM, Tan CP, Panpipat W, Cheong LZ, Shen C
    ACS Appl Mater Interfaces, 2021 Jan 27;13(3):4146-4155.
    PMID: 33440928 DOI: 10.1021/acsami.0c17134
    Immobilization can be used to improve the stability of lipases and enhances lipase recovery and reusability, which increases its commercial value and industrial applications. Nevertheless, immobilization frequently causes conformational changes of the lipases, which decrease lipase catalytic activity. in the present work, we synthesized UIO-66 and grafted UIO-66 crystals with proline for immobilization of Candida rugosa lipase (CRL). As indicated by steady-state fluorescence microscopy, grafting of proline onto UIO-66 crystals induced beneficial conformational change in CRL. CRL immobilized on UIO-66/Pro (CRL@UIO-66/Pro) demonstrated higher enzyme activity and better recyclability than that immobilized on UIO-66 (CRL@UIO-66) in both hydrolysis (CRL@UIO-66/Pro: 0.34 U; CRL@UIO-66: 0.15 U) and transesterification (CRL@UIO-66/Pro: 0.93 U; CRL@UIO-66: 0.25 U) reactions. The higher values of kcat and kcat/Km of CRL@UIO-66/Pro also showed that it had better catalytic efficiency as compared to CRL@UIO-66. It is also worth noting that CRL@UIO-66/Pro (0.93 U) demonstrated a much higher transesterification activity as compared to free CRL (0.11 U), indicating that UIO-66/Pro has increased the solvent stability of CRL. Both CRL@UIO-66 and CRL@UIO-66/Pro were also used for the fabrication of biosensors for nitrofen with a wide linear range (0-100 μM), lower limit of detection, and good recovery rate.
  8. Yang Y, Li X, Li B, Mu L, Wang J, Cheng Y, et al.
    Immunol Invest, 2021 Feb;50(2-3):184-200.
    PMID: 32208776 DOI: 10.1080/08820139.2020.1718693
    BACKGROUND: Tumor necrosis factor superfamily member 4 (TNFSF4) has significant role in modulating autoimmune diseases (ADs) and single nucleotide polymorphism (SNP) is also related with the susceptibility to some diseases. So a meta-analysis aimed at systematically assessing the associations between TNFSF4 polymorphisms (rs2205960 G > A, rs704840 T > G and rs844648 G > A) and ADs risk was performed in Asians.

    METHODS: Total 14 eligible articles published before March 2019 involving 35 studies, of which 21 studies (16,109 cases and 26,378 controls) for rs2205960 G > A, 8 studies (2,424 cases and 3,692 controls) for rs704840 T > G, and 6 studies (3,839 cases and 5,867 controls) for rs844648 G > A were included. Effects of the three respective polymorphisms on the susceptibility to ADs were estimated by pooling the odds ratios (ORs) with their corresponding 95% confidence interval (95% CI) in allelic, dominant, recessive, heterozygous and homozygous models.

    RESULTS: The overall analysis revealed that all the rs2205960 G > A, rs704840 T > G and rs844648 G > A polymorphisms could increase the risk of ADs in allelic, dominant, recessive, heterozygous and homozygous models. Furthermore, subgroup analysis showed that both rs2205960 G > A and rs704840 T > G were significantly associated with the susceptibility to systemic lupus erythematosus (SLE). What's more, statistically significant association between rs2205960 G > A polymorphism and primary Sjögren's syndrome (pSS) susceptibility was also observed in allelic, dominant and heterozygous models.

    CONCLUSIONS: This current meta-analysis suggested that all of the three TNFSF4 polymorphisms may be associated with ADs susceptibility in Asians.

  9. Yang X, Ikhwanuddin M, Li X, Lin F, Wu Q, Zhang Y, et al.
    Mar Biotechnol (NY), 2018 Feb;20(1):20-34.
    PMID: 29152671 DOI: 10.1007/s10126-017-9784-2
    The molecular mechanism underlying sex determination and gonadal differentiation of the mud crab (Scylla paramamosain) has received considerable attention, due to the remarkably biological and economic differences between sexes. However, sex-biased genes, especially non-coding genes, which account for these differences, remain elusive in this crustacean species. In this study, the first de novo gonad transcriptome sequencing was performed to identify both differentially expressed genes and long non-coding RNAs (lncRNAs) between male and female S. paramamosain by using Illumina Hiseq2500. A total of 79,282,758 and 79,854,234 reads were generated from ovarian and testicular cDNA libraries, respectively. After filtrating and de novo assembly, 262,688 unigenes were produced from both libraries. Of these unigenes, 41,125 were annotated with known protein sequences in public databases. Homologous genes involved in sex determination and gonadal development pathways (Sxl-Tra/Tra-2-Dsx/Fru, Wnt4, thyroid hormone synthesis pathway, etc.) were identified. Three hundred and sixteen differentially expressed unigenes were further identified between both transcriptomes. Meanwhile, a total of 233,078 putative lncRNAs were predicted. Of these lncRNAs, 147 were differentially expressed between sexes. qRT-PCR results showed that nine lncRNAs negatively regulated the expression of eight genes, suggesting a potential role in sex differentiation. These findings will provide fundamental resources for further investigation on sex differentiation and regulatory mechanism in crustaceans.
  10. Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al.
    Ann Oncol, 2015 Sep;26(9):1883-1889.
    PMID: 26105600 DOI: 10.1093/annonc/mdv270
    BACKGROUND: The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

    PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.

    RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.

    CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

  11. 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.
  12. Cho BC, Chewaskulyong B, Lee KH, Dechaphunkul A, Sriuranpong V, Imamura F, et al.
    J Thorac Oncol, 2019 01;14(1):99-106.
    PMID: 30240852 DOI: 10.1016/j.jtho.2018.09.004
    INTRODUCTION: Here we report efficacy and safety data of an Asian subset of the phase III FLAURA trial (NCT02296125), which compares osimertinib with standard of care (SoC) EGFR tyrosine kinase inhibitors (TKIs) in patients with previously untreated advanced NSCLC with tumors harboring exon 19 deletion (Ex19del)/L858R EGFR TKI-sensitizing mutations.

    METHODS: Eligible Asian patients (enrolled at Asian sites) who were at least 18 years of age (≥20 years in Japan) and had untreated EGFR-mutated advanced NSCLC were randomized 1:1 to receive osimertinib (80 mg, orally once daily) or an SoC EGFR TKI (gefitinib, 250 mg, or erlotinib, 150 mg, orally once daily). The primary end point was investigator-assessed progression-free survival (PFS). The key secondary end points were overall survival, objective response rate, central nervous system efficacy, and safety.

    RESULTS: The median PFS was 16.5 versus 11.0 months for the osimertinib and SoC EGFR TKI groups, respectively (hazard ratio = 0.54, 95% confidence interval: 0.41-0.72, p < 0.0001). The overall survival data were immature (24% maturity). The objective response rates were 80% for osimertinib and 75% for an SoC EGFR TKI. The median central nervous system PFS was not calculable for the osimertinib group and was 13.8 months for the SoC EGFR TKI group (hazard ratio = 0.55, 95% confidence interval: 0.25-1.17, p = 0.118). Fewer adverse events of grade 3 or higher (40% versus 48%) and fewer adverse events leading to treatment discontinuation (15% versus 21%) were reported with osimertinib versus with an SoC EGFR TKI, respectively.

    CONCLUSION: In this Asian population, first-line osimertinib demonstrated a clinically meaningful improvement in PFS over an SoC EGFR TKI, with a safety profile consistent with that for the overall FLAURA study population.

  13. Liam CK, Ahmad AR, Hsia TC, Zhou J, Kim DW, Soo RA, et al.
    Clin Cancer Res, 2023 May 15;29(10):1879-1886.
    PMID: 36971777 DOI: 10.1158/1078-0432.CCR-22-3318
    PURPOSE: The final analyses of the INSIGHT phase II study evaluating tepotinib (a selective MET inhibitor) plus gefitinib versus chemotherapy in patients with MET-altered EGFR-mutant NSCLC (data cut-off: September 3, 2021).

    PATIENTS AND METHODS: Adults with advanced/metastatic EGFR-mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) ≥5, MET:CEP7 ≥2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemotherapy. Primary endpoint was investigator-assessed progression-free survival (PFS). MET-amplified subgroup analysis was preplanned.

    RESULTS: Overall (N = 55), median PFS was 4.9 months versus 4.4 months [stratified HR, 0.67; 90% CI, 0.35-1.28] with tepotinib plus gefitinib versus chemotherapy. In 19 patients with MET amplification (median age 60.4 years; 68.4% never-smokers; median GCN 8.8; median MET/CEP7 2.8; 89.5% with MET IHC 3+), tepotinib plus gefitinib improved PFS (HR, 0.13; 90% CI, 0.04-0.43) and overall survival (OS; HR, 0.10; 90% CI, 0.02-0.36) versus chemotherapy. Objective response rate was 66.7% with tepotinib plus gefitinib versus 42.9% with chemotherapy; median duration of response was 19.9 months versus 2.8 months. Median duration of tepotinib plus gefitinib was 11.3 months (range, 1.1-56.5), with treatment >1 year in six (50.0%) and >4 years in three patients (25.0%). Seven patients (58.3%) had treatment-related grade ≥3 adverse events with tepotinib plus gefitinib and five (71.4%) had chemotherapy.

    CONCLUSIONS: Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.

  14. Liew JES, Chong Cheng Y, Tai NL, Pereira A, Manivannan V, Khoo SL, et al.
    Int J Pharm Pract, 2024 Feb 15;32(1):83-90.
    PMID: 38289996 DOI: 10.1093/ijpp/riad083
    OBJECTIVES: This study aimed to evaluate the effectiveness of workflow redesign (eaST system) on pharmacy waiting time and near-missed events. We also investigated other factors that may potentially affect these study outcomes.

    METHODS: A quasi-experimental (before-after) study design was adopted. Pre-intervention data were collected over 7 months (January-July 2017). Subsequently, the workflow redesign (eaST system) was implemented and the effect of the intervention (August 2017-February 2018) was evaluated. Univariate analysis was used to compare the differences between pre-intervention and post-intervention of pharmacy waiting time and near-missed events. Significant factors affecting study outcomes were analysed using linear regression analysis.

    KEY FINDINGS: A total of 210,530 prescriptions were analysed. The eaST system significantly increases the percentage of prescriptions dispensed within 30 min per day (median = 68 (interquartile range (IQR) = 41) vs. median = 93 (IQR = 33), P < 0.001) and reduced the mean percentage of near-missed events (mean = 50.71 (standard deviation (SD) = 23.95) vs. mean = 27.87 (SD = 12.23), P < 0.001). However, the eaST system's effects on related outcomes were conditional on a three-way interaction effect. The eaST system's effects on pharmacy waiting time were influenced by the number of prescriptions received and the number of PhIS server disruptions. Conversely, the eaST system's effects on near-missed events were influenced by the number of pharmacy personnel and number of controlled medications.

    CONCLUSIONS: Overall, the eaST system improved the pharmacy waiting time and reduced near-missed events.

  15. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al.
    N Engl J Med, 2018 01 11;378(2):113-125.
    PMID: 29151359 DOI: 10.1056/NEJMoa1713137
    BACKGROUND: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).

    METHODS: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival.

    RESULTS: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%).

    CONCLUSIONS: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).

  16. Gray JE, Okamoto I, Sriuranpong V, Vansteenkiste J, Imamura F, Lee JS, et al.
    Clin Cancer Res, 2019 Nov 15;25(22):6644-6652.
    PMID: 31439584 DOI: 10.1158/1078-0432.CCR-19-1126
    PURPOSE: To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR-mutated (EGFRm; Ex19del and/or L858R) advanced or metastatic non-small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125).

    EXPERIMENTAL DESIGN: Tumor tissue EGFRm status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFRm status was retrospectively determined with the central cobas plasma test.

    RESULTS: Of 994 patients screened, 556 were randomized (289 and 267 with central and local EGFR test results, respectively) and 438 failed screening. Of those randomized from local EGFR test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed EGFRm positive by central cobas tissue test. Using reference central cobas tissue test results, positive percent agreements with cobas plasma test results for Ex19del and L858R detection were 79% [95% confidence interval (CI), 74-84] and 68% (95% CI, 61-75), respectively. Progression-free survival (PFS) superiority with osimertinib over comparator EGFR-TKI remained consistent irrespective of randomization route (central/local EGFRm-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFRm-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months).

    CONCLUSIONS: Our results support utility of cobas tissue and plasma testing to aid selection of patients with EGFRm advanced NSCLC for first-line osimertinib treatment. Lack of EGFRm detection in plasma was associated with prolonged PFS versus patients plasma EGFRm positive, potentially due to patients having lower tumor burden.

  17. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2020 Sep 04;125(10):102001.
    PMID: 32955327 DOI: 10.1103/PhysRevLett.125.102001
    The first study of charm quark diffusion with respect to the jet axis in heavy ion collisions is presented. The measurement is performed using jets with p_{T}^{jet}>60  GeV/c and D^{0} mesons with p_{T}^{D}>4  GeV/c in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=5.02  TeV, recorded by the CMS detector at the LHC. The radial distribution of D^{0} mesons with respect to the jet axis is sensitive to the production mechanisms of the meson, as well as to the energy loss and diffusion processes undergone by its parent parton inside the strongly interacting medium produced in Pb-Pb collisions. When compared to Monte Carlo event generators, the radial distribution in pp collisions is found to be well described by pythia, while the slope of the distribution predicted by sherpa is steeper than that of the data. In Pb-Pb collisions, compared to the pp results, the D^{0} meson distribution for 4
  18. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Oct 09;125(15):152001.
    PMID: 33095627 DOI: 10.1103/PhysRevLett.125.152001
    Using a data sample of proton-proton collisions at sqrt[s]=13  TeV, corresponding to an integrated luminosity of 140  fb^{-1} collected by the CMS experiment in 2016-2018, the B_{s}^{0}→X(3872)ϕ decay is observed. Decays into J/ψπ^{+}π^{-} and K^{+}K^{-} are used to reconstruct, respectively, the X(3872) and ϕ. The ratio of the product of branching fractions B[B_{s}^{0}→X(3872)ϕ]B[X(3872)→J/ψπ^{+}π^{-}] to the product B[B_{s}^{0}→ψ(2S)ϕ]B[ψ(2S)→J/ψπ^{+}π^{-}] is measured to be [2.21±0.29(stat)±0.17(syst)]%. The ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{0}→X(3872)K^{0}] is found to be consistent with one, while the ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{+}→X(3872)K^{+}] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B^{0} and B_{s}^{0} meson decays compared to B^{+}. The reported observation may shed new light on the nature of the X(3872) particle.
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