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  1. Zhou YJ, Gao F, Liu WY, Wong GL, Mahadeva S, Raihan Nik Mustapha N, et al.
    Aliment Pharmacol Ther, 2021 08;54(4):470-480.
    PMID: 34152626 DOI: 10.1111/apt.16487
    BACKGROUND: Recently, Papatheodoridi et al proposed to refine the Baveno VI elastography dual-cutoffs and introduce an algorithm for the detection of compensated advanced chronic liver disease (cACLD) in asymptomatic European patients with chronic liver diseases.

    AIMS: To validate the performance of the dual-cutoffs (8/12 kPa) and the proposed algorithm to identify patients with cACLD in three well-characterised Asian nonalcoholic fatty liver disease (NAFLD) cohorts.

    METHODS: We included 830 patients with biopsy-proven NAFLD. Liver stiffness was measured using transient elastography (FibroScan).

    RESULTS: cACLD was found in 21.8% of patients. Compared with the original Baveno VI elastography criteria (10/15 kPa), the new cutoffs showed a comparable specificity and a higher sensitivity for identifying cACLD. We developed a simplified risk model incorporating age, liver stiffness value, and platelet count, which outperformed liver stiffness measurement alone in two Chinese cohorts (P = 0.001), and was further validated in a Malaysian cohort (P = 0.04). Overall, the "two-step" screening of cACLD improved classification rates from 73.5% by the original dual-cutoffs to 86.7%. Notably, usage of our simplified risk model resulted in significantly lower false-negative rate than the refined screening approach by Papatheodoridi et al (27.1% vs 41.4%; P = 0.01).

    CONCLUSIONS: The dual elastography cutoffs of 8 and 12 kPa are more appropriate to identify cACLD in Asian patients with NAFLD. In combination with a simplified risk model in unclassified patients, the two-step approach showed a classification rate of about 85%.

  2. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
  3. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  4. Tang BH, Zhang JY, Allegaert K, Hao GX, Yao BF, Leroux S, et al.
    Clin Pharmacokinet, 2023 Aug;62(8):1105-1116.
    PMID: 37300630 DOI: 10.1007/s40262-023-01265-z
    BACKGROUND AND OBJECTIVE: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C0) and steady-state area-under-curve (AUC0-24) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict these treatment targets to calculate optimal individual dosing regimens under intermittent administration conditions.

    METHODS: C0 were retrieved from a large neonatal vancomycin dataset. Individual estimates of AUC0-24 were obtained from Bayesian post hoc estimation. Various ML algorithms were used for model building to C0 and AUC0-24. An external dataset was used for predictive performance evaluation.

    RESULTS: Before starting treatment, C0 can be predicted a priori using the Catboost-based C0-ML model combined with dosing regimen and nine covariates. External validation results showed a 42.5% improvement in prediction accuracy by using the ML model compared with the population pharmacokinetic model. The virtual trial showed that using the ML optimized dose; 80.3% of the virtual neonates achieved the pharmacodynamic target (C0 in the range of 10-20 mg/L), much higher than the international standard dose (37.7-61.5%). Once therapeutic drug monitoring (TDM) measurements (C0) in patients have been obtained, AUC0-24 can be further predicted using the Catboost-based AUC-ML model combined with C0 and nine covariates. External validation results showed that the AUC-ML model can achieve an prediction accuracy of 80.3%.

    CONCLUSION: C0-based and AUC0-24-based ML models were developed accurately and precisely. These can be used for individual dose recommendations of vancomycin in neonates before treatment and dose revision after the first TDM result is obtained, respectively.

  5. Chen Y, Liu Z, Wang Q, Gao F, Xu H, Ke L, et al.
    Crit Care, 2024 Jan 20;28(1):26.
    PMID: 38245768 DOI: 10.1186/s13054-024-04813-6
    BACKGROUND AND AIMS: Exclusive enteral nutrition (EN) is often observed during the first week of ICU admission because of the extra costs and safety considerations for early parenteral nutrition. This study aimed to assess the association between nutrition intake and 28-day mortality in critically ill patients receiving exclusive EN.

    METHODS: This is a post hoc analysis of a cluster-randomized clinical trial that assesses the effect of implementing a feeding protocol on mortality in critically ill patients. Patients who stayed in the ICUs for at least 7 days and received exclusive EN were included in this analysis. Multivariable Cox hazard regression models and restricted cubic spline models were used to assess the relationship between the different doses of EN delivery and 28-day mortality. Subgroups with varying lactate levels at enrollment were additionally analyzed to address the potential confounding effect brought in by the presence of shock-related hypoperfusion.

    RESULTS: Overall, 1322 patients were included in the analysis. The median (interquartile range) daily energy and protein delivery during the first week of enrollment were 14.6 (10.3-19.6) kcal/kg and 0.6 (0.4-0.8) g/kg, respectively. An increase of 5 kcal/kg energy delivery was associated with a significant reduction (approximately 14%) in 28-day mortality (adjusted hazard ratio [HR] = 0.865, 95% confidence interval [CI]: 0.768-0.974, P = 0.016). For protein intake, a 0.2 g/kg increase was associated with a similar mortality reduction with an adjusted HR of 0.868 (95% CI 0.770-0.979). However, the benefits associated with enhanced nutrition delivery could be observed in patients with lactate concentration ≤ 2 mmol/L (adjusted HR = 0.804 (95% CI 0.674-0.960) for energy delivery and adjusted HR = 0.804 (95% CI 0.672-0.962) for protein delivery, respectively), but not in those > 2 mmol/L.

    CONCLUSIONS: During the first week of critical illness, enhanced nutrition delivery is associated with reduced mortality in critically ill patients receiving exclusive EN, only for those with lactate concentration ≤ 2 mmol/L.

    TRIAL REGISTRATION: ISRCTN12233792, registered on November 24, 2017.

  6. de Carvalho LP, Gao F, Chen Q, Hartman M, Sim LL, Koh TH, et al.
    Eur Heart J Acute Cardiovasc Care, 2014 Dec;3(4):354-62.
    PMID: 24598820 DOI: 10.1177/2048872614527007
    the purpose of this study was to investigate differences in long-term mortality following acute myocardial infarction (AMI) in patients from three major ethnicities of Asia.
  7. Gao F, Chui PL, Che CC, Mao XR
    Florence Nightingale J Nurs, 2023 Oct;31(3):152-159.
    PMID: 37847013 DOI: 10.5152/FNJN.2023.23023
    AIM: To investigate the level of burnout and resilience, and the associated factors when the coronavirus disease 2019 infection hit a peak in the community in Sichuan, China.

    METHOD: This was a descriptive cross-sectional design study. Data were collected from 25 to 31 December 2022, at six hospitals in Sichuan province. Using convenience sampling, a total of 717 participants were recruited, using the revised version of the Maslach Burnout InventoryGeneral Survey, and the Resilience Assessment Scale for healthcare workers.

    RESULTS: More than half of nurses reported a moderate level of emotional exhaustion (66.50%, n = 484), cynicism (68.20%, n = 489), and personal accomplishment (68.76%, n = 493); nearly one-third and one-fourth of nurses experienced a high level of emotional exhaustion (27.48%, n = 197) and cynicism (20.78%, n = 149), respectively. In resilience, the highest scoring dimension was interpersonal connectedness, followed by decisional coping, flexible self-adaptation, and rational thinking. Satisfaction with work income, patient-nurse conflict, frequency of overtime work, age, and marital status were significant factors influencing burnout among nurses (p < .05).

    CONCLUSION: The findings of the study enlighten nursing administrators on the level of burnout and resilience and associated factors among nurses during the peak of coronavirus disease 2019 infection in China. This would be of immense help in planning a welfare program to support the nurses.

  8. Wang L, Ang LH, Gao F, Abdul Halim H
    Humanit Soc Sci Commun, 2023;10(1):104.
    PMID: 36938578 DOI: 10.1057/s41599-023-01603-3
    The corporate profile translations of multinational corporations (MNCs) in emerging economies such as China possess rich information for narrative analysis. Nevertheless, how the parts of a corporate profile translation form a whole narrative remains undertheorized. This study, therefore, examines the relationality of parts in the corporate profile translations of China's MNCs by integrating William Labov's narrative structure with Margaret Somers' narrative identity theory. Specifically, we conduct a theoretical thematic analysis of how constituents form a whole narrative in relevant corporate profiles, of the shifts in the relationality of parts from the Chinese source texts (STs) to the English target texts (TTs) of these profiles, and of the influences of these shifts on the constitution of corporate identities in the target texts. Our results show that in the corporate profiles of Chinese MNCs, episodes are not randomly selected and related to each other but follow predominant patterns. However, we find no unified patterns in the shifts in the relationality of parts via the corporate profile translation of China's MNCs. We thus reveal how corporations' identities are constituted in diverse ways that reflect their fluid and unique features. Accordingly, our findings have implications for translation studies and corporate communications.
  9. Wang Y, Gao F, Ooi KK, Tai Q, Zhang J, Zhu Y, et al.
    J Environ Pathol Toxicol Oncol, 2019;38(4):297-311.
    PMID: 32464002 DOI: 10.1615/JEnvironPatholToxicolOncol.2019030482
    Early development of liver cancer is usually asymptomatic. The overall survival rate of patients is relatively low due to late diagnosis, despite hepatocellular carcinoma being a common diagnosis. The high mortality rate of liver cancer was due to its overactivated cellular mitochondrial activities, namely thioredoxin reductase enzymatic activities and its downstream activation of nuclear factor kappa B (NF-κB) signaling pathways for cancer cell migration. Our previous study on this candidate compound on A2780 ovarian cancer cells and MCF-7 breast cancer cells, through modulation of cell-cycle checkpoints and respective targeted apoptosis pathways. The current study used HepG2 hepatocellular carcinoma cell lines as a representative in vitro liver cancer cell model. The half maximal inhibitory concentration (IC50) value was obtained via incubation of PTZ compound for 24 h yield of 37.03 μM, whereby it was three-fold more potent than the standard control tested, cisplatin (109.23 μM). The subsequent application of IC50 dosage of PTZ onto HepG2 cells illustrated a growth-static effect via activation of S-phase cell-cycle checkpoints, immediately followed by regulation of apoptosis. Increased cellular concentration of reactive oxygen species eventually generated oxidative damages on mitochondria, hence resulting in the release of cytochrome c protein and suppression of TrxR enzymatic activity, in conjunction with the suppression on invasion of cancer cells via Matrigel invasion chamber. In conclusion, PTZ was hypothesized to act effectively on mitochondria of HepG2 cells; hence it should proceed into detailed drug targeting mechanism research.
  10. Gao F, Huang JF, Zheng KI, Pan XY, Ma HL, Liu WY, et al.
    J Gastroenterol Hepatol, 2020 Oct;35(10):1804-1812.
    PMID: 32246876 DOI: 10.1111/jgh.15055
    BACKGROUND AND AIM: There is an immediate need for non-invasive accurate tests for diagnosing liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). Previously, it has been suggested that MACK-3 (a formula that combines homeostasis model assessment-insulin resistance with serum serum aspartate aminotransferase and cytokeratin [CK]18-M30 levels) accurately identifies patients with fibrotic NASH. Our aim was to assess the performance of MACK-3 and develop a novel, non-invasive algorithm for diagnosing fibrotic NASH.

    METHODS: Six hundred and thirty-six adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration-controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.

    RESULTS: Metabolic syndrome (MetS), platelet count and MACK-3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75-0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74-0.87) than that of MACK-3 (AUROC: 0.75, 95%CI 0.68-0.82; P 

  11. Gao F, Lam CS, Yeo KK, Machin D, de Carvalho LP, Sim LL, et al.
    J Am Heart Assoc, 2016 10 06;5(10).
    PMID: 27792637
    BACKGROUND: We examined the influence of sex, ethnicity, and time on competing cardiovascular and noncardiovascular causes of death following acute myocardial infarction in a multiethnic Asian cohort.

    METHODS AND RESULTS: For 12 years, we followed a prospective nationwide cohort of 15 151 patients (aged 22-101 years, median age 63 years; 72.3% male; 66.7% Chinese, 19.8% Malay, 13.5% Indian) who were hospitalized for acute myocardial infarction between 2000 and 2005. There were 6463 deaths (4534 cardiovascular, 1929 noncardiovascular). Compared with men, women had a higher risk of cardiovascular death (age-adjusted hazard ratio [HR] 1.3, 95% CI 1.2-1.4) but a similar risk of noncardiovascular death (HR 0.9, 95% CI 0.8-1.0). Sex differences in cardiovascular death varied by ethnicity, age, and time. Compared with Chinese women, Malay women had the greatest increased hazard of cardiovascular death (HR 1.4, 95% CI 1.2-1.6) and a marked imbalance in death due to heart failure or cardiomyopathy (HR 3.4 [95% CI 1.9-6.0] versus HR 1.5 [95% CI 0.6-3.6] for Indian women). Compared with same-age Malay men, Malay women aged 22 to 49 years had a 2.5-fold (95% CI 1.6-3.8) increased hazard of cardiovascular death. Sex disparities in cardiovascular death tapered over time, least among Chinese patients and most among Indian patients; the HR comparing cardiovascular death of Indian women and men decreased from 1.9 (95% CI 1.5-2.4) at 30 days to 0.9 (95% CI 0.5-1.6) at 10 years.

    CONCLUSION: Age, ethnicity, and time strongly influence the association between sex and specific cardiovascular causes of mortality, suggesting that health care policy to reduce sex disparities in acute myocardial infarction outcomes must consider the complex interplay of these 3 major modifying factors.

  12. Cao Y, Chen L, Chen H, Cun Y, Dai X, Du H, et al.
    Natl Sci Rev, 2023 Apr;10(4):nwac287.
    PMID: 37089192 DOI: 10.1093/nsr/nwac287
  13. Hora B, Keating SM, Chen Y, Sanchez AM, Sabino E, Hunt G, et al.
    PLoS One, 2016;11(6):e0157340.
    PMID: 27314585 DOI: 10.1371/journal.pone.0157340
    HIV-1 subtypes and drug resistance are routinely tested by many international surveillance groups. However, results from different sites often vary. A systematic comparison of results from multiple sites is needed to determine whether a standardized protocol is required for consistent and accurate data analysis. A panel of well-characterized HIV-1 isolates (N = 50) from the External Quality Assurance Program Oversight Laboratory (EQAPOL) was assembled for evaluation at seven international sites. This virus panel included seven subtypes, six circulating recombinant forms (CRFs), nine unique recombinant forms (URFs) and three group O viruses. Seven viruses contained 10 major drug resistance mutations (DRMs). HIV-1 isolates were prepared at a concentration of 107 copies/ml and compiled into blinded panels. Subtypes and DRMs were determined with partial or full pol gene sequences by conventional Sanger sequencing and/or Next Generation Sequencing (NGS). Subtype and DRM results were reported and decoded for comparison with full-length genome sequences generated by EQAPOL. The partial pol gene was amplified by RT-PCR and sequenced for 89.4%-100% of group M viruses at six sites. Subtyping results of majority of the viruses (83%-97.9%) were correctly determined for the partial pol sequences. All 10 major DRMs in seven isolates were detected at these six sites. The complete pol gene sequence was also obtained by NGS at one site. However, this method missed six group M viruses and sequences contained host chromosome fragments. Three group O viruses were only characterized with additional group O-specific RT-PCR primers employed by one site. These results indicate that PCR protocols and subtyping tools should be standardized to efficiently amplify diverse viruses and more consistently assign virus genotypes, which is critical for accurate global subtype and drug resistance surveillance. Targeted NGS analysis of partial pol sequences can serve as an alternative approach, especially for detection of low-abundance DRMs.
  14. Lian X, Hong WCH, Gao F, Kolletar-Zhu K, Wang J, Cai C, et al.
    Res Dev Disabil, 2023 Oct;141:104602.
    PMID: 37757565 DOI: 10.1016/j.ridd.2023.104602
    Traditional picture books for children come with colourful images and a multitude of elements to attract attention and increase the reading interest of typical-developing (TD) children. However, children with Autism Spectrum Disorder (ASD) are less capable of filtering out unimportant elements in pictures and focusing on social items (e.g., human faces). This study proposed that the removal of background and less important elements in the pictures of children's storybooks could facilitate better attention and enhance children with ASD's focus on the main object and thus the intended meaning of the storybook. We adopted pictures from a well-known children's book and modified them by removing the inessential background elements. Then, ASD children with intellectual disabilities (ASD+ID) (n = 40), children with ID (n = 38) and TD (n = 40) were asked to view the original and modified pictures in an eye-tracking experiment, respectively. Additionally, brain activation of ASD+ID participants (n = 10) was recorded as they were viewing those pictures in an fMRI scan. Eye-tracking found that ASD+ID children viewed the modified pictures with significantly longer average fixations, fewer fixations, fewer saccades, and higher fixation/saccade duration ratio. Contrary to the original pictures, no significant differences were found among ASD+ID, ID only and TD. Especially, ASD+ID group showed highly similar visual patterns to the TD participants when viewing the modified pictures and particularly focusing on the main character in the pictures. Additional fMRI evidence on ASD+ID group also revealed that modified pictures were associated with enhanced activation in bilateral fusiform gyri as compared to those from original pictures, which might suggest increased visual attention. Theoretical and practical implications were discussed in light of our findings.
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