Displaying publications 1 - 20 of 33 in total

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  1. Yu Y, Song Z
    PLoS One, 2023;18(12):e0289775.
    PMID: 38060468 DOI: 10.1371/journal.pone.0289775
    In the last decades, economic globalisation and the progress of ICT have promoted the international division of labour and optimisation of the global value chain. Moreover, improvements in incentives such as lower tariffs and more efficient border crossings have boosted international trade. Under this background, regional and sub-regional economic cooperation organizations, such as free trade area (FTA), have been developing rapidly and attracting many academic attentions. As the fastest growing FTA in the world, CAFTA is now the largest FTA in developing countries. This study focuses on the value-added network of various industries in the trade process inside CAFTA, and tries to explore the impact of trade facilitation on the DVA trade network of CAFTA. The results show that in the trade network of CAFTA, the proportion of added value of domestic trade in total exports keeps increasing, and the returned added value (RDV) increases significantly. Singapore, Vietnam, and Thailand hold relatively high positions in the production network, while China has a relatively low position. On the other hand, China and Thailand become the main beneficiaries after the establishment of CAFTA, while Singapore and Malaysia play a lesser role in trading networks. The results also show that trade facilitation has a significant positive effect on the DVA-INTrex and RDV trade networks, indicating that trade facilitation can significantly increase the domestic indirect value added and returned value added in the trade process. Moreover, the business environment (bus) is the most important factor, with efficiency and transparency of border administration (cus), availability, and use of ICTs (ict) contributing to the improvement.
  2. Liu Y, Yu Y, Zhao S
    Interdiscip Sci, 2022 Jan 24.
    PMID: 35067893 DOI: 10.1007/s12539-021-00492-x
    LncRNAs play a part in numerous momentous processes of biology such as disease diagnoses, preventions and treatments. The associations between various diseases and lncRNAs are one of the crucial approaches to learn the role and status of lncRNAs in human diseases. With the researches on lncRNA and diseases, multiple methods based on neural network have been employed to predict these associations. However, the deep and complicated characteristic representations of lncRNA-disease associations were failed to be extracted, and the discriminative contributions of the interactions, correlations, and similarities among miRNAs diseases, and lncRNAs for the correlation predictions were ignored. In this paper, based on the multibiology premise of lncRNAs, miRNAs, and diseases, a dual attention network was proposed to predict the model of lncRNA-disease associations for miRNAs, the disease characteristic matrix, and lncRNAs. Through two attention modules, we enable the model to learn the nonlinear, more complex and useful features of lncRNA, miRNA, and disease characteristic matrix. For the feature embedding matrix composed of lncRNA-disease, the connection between lncRNA-disease feature embedding matrix and lncRNA, miRNA, and disease characteristic matrix was enhanced through deconvolution and feature fusion layer. Compared with several latest methods, the method proposed in this paper can produce better performance. Researches on the cases of osteosarcoma, lung cancer, and gastric cancer have confirmed the effective recognition of potential lncRNA-disease associations.
  3. Yu Y, Kwong SC, Bannasilp A
    Heliyon, 2023 Nov;9(11):e22164.
    PMID: 38053914 DOI: 10.1016/j.heliyon.2023.e22164
    The marketing practice involved with virtual idols became popular, leading to the emergence of virtual idol marketing. However, there is a lack of scientific understanding of this emerging marketing field. To promote a fundamental understanding of virtual idol marketing, this study clarifies the conceptual boundary of virtual idols and provides meaningful insights into the definitions, benefits, and risks of virtual idol marketing. On this basis, this study further proposes an integrated framework established on the existing theories and research to explain the potential working mechanism of virtual idol marketing. This study can increase the accumulation of knowledge in the emerging field of virtual idol marketing, provide inspiration and decision-making assistance for brands to build connections with young consumers, especially Generation Z, and provide an avenue for future research in the field of virtual idol marketing.
  4. Ainoon O, Boo NY, Yu YH, Cheong SK, Hamidah HN
    Hematology, 2006 Apr;11(2):113-8.
    PMID: 16753852 DOI: 10.1080/10245330500155184
    A 2-year-old Chinese boy was referred to Hospital UKM for investigation of recurrent episodes of dark-coloured urine and pallor since birth. He was born prematurely at 34 weeks gestation and developed severe early-onset neonatal jaundice requiring exchange blood transfusion. Screening at birth showed Glucose-6-phosphate dehydrogenase (G6PD) deficiency. On admission, physical examination revealed pallor, jaundice and mild hepatomegaly. Results of laboratory investigations showed a hemoglobin level of 11.0 g/dl with a hemolytic blood picture, reticulocytosis of 20% and red cell G6PD activity reported as undetectable. The patient's DNA was analysed for G6PD mutations by PCR-based techniques and DNA sequencing and results showed a 24 bp deletion of nucleotide 953-976 in the exon 9 of the G6PD gene. DNA analysis was also performed on blood samples of the patient's mother and female sibling confirming their heterozygous status, although both showed normal red cell G6PD activity levels. The patient was discharged well and his parents were appropriately advised on the condition and the importance of taking folic acid regularly. This is a first case report in Malaysia of G6PD deficiency causing chronic-hemolytic anemia. The rare 24 bp deletion causes the G6PD Nara variant, previously reported only in two other unrelated males, a Japanese and a Portuguese both with chronic hemolytic anemia.
  5. Wang T, Sun Z, Lim JP, Yu Y
    Libyan J Med, 2019 Dec;14(1):1597327.
    PMID: 30935302 DOI: 10.1080/19932820.2019.1597327
    Many undergoing in vitro fertilization-embryo transfer (IVF-ET) procedures treatments have been tried for older infertile patients, but still can not reverse the aging effect on oocyte, and infertility treatment is expensive, even for people in developed countries. The study aimed to compare outcomes following the application of luteal phase ovulation induction (LPOI) and ultra-short gonadotropin-releasing hormone agonist (GnRH-a) protocols in patients aged more than 40 years undergoing IVF-ET and to examine the effectiveness and feasibility of LPOI. A total of 266 IVF-ET cycles in 155 patients aged 40 years and over were retrospectively analyzed. Of these patients, 105 underwent the ultra-short GnRH-a protocol (GnRH-a group) and 50 underwent LPOI (LPOI group). Various clinical outcomes were compared between these two groups using either t-tests or the chi-square test. The study showed patients in the LPOI group required a higher dosage of human menopausal gonadotropin and a lower dosage of recombinant follicle stimulating hormone than those in the GnRH-a group. Furthermore, though the total dosage of gonadotropin was higher in the LPOI, its cost was lower. Finally, fertilization rates were higher and high-quality embryo rates were lower in the LPOI group, and the live birth rate of LPOI group is higher than (GnRH-a group) . These between-group differences were all significant (P
  6. Soh HY, Hu LH, Yu Y, Wang T, Zhang WB, Peng X
    PMID: 34862088 DOI: 10.1016/j.ijom.2021.11.008
    The aim of this study was to evaluate the accuracy of navigation-assisted maxillofacial reconstruction and to identify the predictors of the clinical outcomes. A total of 112 patients who underwent navigation-assisted maxillofacial reconstruction with free flaps between 2014 and 2019, performed by a single surgical team, were assessed. Accuracy was evaluated by superimposing the postoperative computed tomography data with the preoperative virtual surgical plan. Predictors of the clinical outcomes affecting the accuracy were identified and analysed. The mean deviation and root mean square (RMS) estimate of the orbital, maxillary, and mandibular reconstructions were 0.88 ± 3.25 mm and 3.38 ± 0.73 mm, 0.77 ± 3.44 mm and 3.69 ± 0.82 mm, and 1.07 ± 4.16 mm and 4.67 ± 3.95 mm, respectively (P < 0.05). There was no significant difference in orbital volume or projection between the preoperative, postoperative, and healthy orbits (P = 0.093 and P = 0.225, respectively). Multivariate linear regression analysis confirmed significant associations between the accuracy of navigation-assisted mandibular reconstruction and preservation of the condyle, type of reconstruction, type of osteosynthesis plate, and number of bony segments. Navigation-assisted midface reconstruction yielded a higher level of accuracy in the final surgical outcome when compared to mandibular reconstruction. Computer-assisted techniques and intraoperative navigation can be an alternative or adjunct to current surgical techniques to improve the final surgical outcome, especially in more complex maxillofacial reconstructions.
  7. Bajuri MY, Kim J, Yu Y, Shahul Hameed MS
    Gels, 2023 Jan 13;9(1).
    PMID: 36661832 DOI: 10.3390/gels9010066
    Adipose tissue is an abundant source of extracellular substances that support the tissue repair process. This pilot study was carried out to determine the efficacy of 3D-bioprinted autologous adipose tissue grafts on diabetic foot ulcers (DFUs), with fibrin gel used to stabilise the graft. This was a single-arm pilot study in a tertiary hospital that provides diabetic wound care services. A total of 10 patients with a DFU were enrolled, and the primary endpoint was complete healing within 12 weeks. The secondary endpoints were wound size reduction, time to healing, and adverse events. Seven out of ten patients showed complete healing of their DFU within 12 weeks (at 2, 4, 5, 10, and 12 weeks, respectively). The wound size reduction rate was significantly and progressively reduced over time. According to our data, autologous adipose tissue grafting using a 3D bioprinter, with the addition of fibrin gel that acts as a scaffold, promotes wound healing with high-quality skin reconstruction. Throughout this study period, no adverse events were observed.
  8. Yao Y, Fu W, Yu Y, Wan S, Zhang W, Ming R
    Plant Reprod, 2023 Nov 15.
    PMID: 37966580 DOI: 10.1007/s00497-023-00486-3
    Papaya is a tropical fruit crop renowned for its rich nutrition, particularly pro-vitamin A. Aroma substances are a major component of fruit quality. While extensive research has been conducted on papaya aroma, there has been a notable lack of in-depth research into a specific class of substances. To bridge this gap, our study focused on analyzing the aroma components of various papaya varieties and their biosynthesis pathways. We compared the volatile components of three papaya varieties with distinct flavors at various ripeness stages. A continuous accumulation of linalool, a volatile compound, in the 'AU9' fruit was detected as it matured. The linalool content reached 56% of the total volatile components upon full ripening. Notably, this percentage was significantly higher than that observed in the other two varieties, 'ZhongBai' and 'Malaysian 7', indicating that linalool serves as the primary component influencing the papaya's odor. Subsequently, we identified CpTPS18, a gene associated with linalool biosynthesis, and demonstrated its ability to catalyze linalool production from GPP and enhance its accumulation through overexpression in papaya fruits, both in vivo and in vitro. Based on transcriptomic analysis, it was predicted that CpMYB56 and CpNAC56 may transcriptionally activate the expression of CpTPS18. Subsequent yeast one-hybrid assay and dual luciferase analysis revealed that CpNAC56 activates the transcription of CpTPS18. Transient overexpression in vivo demonstrated that this gene could upregulate the expression of CpTPS18 and promote linalool accumulation. These results uncovered the primary volatile molecule responsible for papaya fruit odor and identified two major genes influencing its biosynthesis. The genomic resources and information obtained from this study will expedite papaya improvement for fruit quality.
  9. Ainoon O, Yu YH, Amir Muhriz AL, Boo NY, Cheong SK, Hamidah NH
    Hum Mutat, 2003 Jan;21(1):101.
    PMID: 12497642 DOI: 10.1002/humu.9103
    We performed DNA analysis using cord blood samples on 86 male Malay neonates diagnosed as G6PD deficiency in the National University of Malaysia Hospital by a combination of rapid PCR-based techniques, single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing. We found 37.2% were 871G>A (G6PD Viangchan), 26.7% were nt 563 C>T (G6PD Mediterranean) and 15.1% were 487G>A (G6PD Mahidol) followed by 4.7% 1376G>T (G6PD Canton), 3.5% 383T>C (G6PD Vanua Lava), 3.5% 592C>T (G6PD Coimbra), 2.3% 1388G>A (G6PD Kaiping), 2.3% 1360C>T (G6PD Union), 2.3% 1003G>A (G6PD Chatham), 1.2% 131C>G (G6PD Orissa) and 1.2% 1361G>A (G6PD Andalus). Seventy-one (82.6%) of the 86 G6PD-deficient neonates had neonatal jaundice. Fifty seven (80%) of the 71 neonates with jaundice required phototherapy with only one neonate progressing to severe hyperbilirubinemia (serum bilirubin >340 micromol/l) requiring exchange transfusion. There was no significant difference in the incidence of neonatal jaundice, mean serum bilirubin level, mean age for peak serum bilirubin, percentage of babies requiring phototherapy and mean number of days of phototherapy between the three common variants. In conclusion, the molecular defects of Malay G6PD deficiency is heterogeneous and G6PD Viangchan, Mahidol and Mediterranean account for at least 80% of the cases. Our findings support the observation that G6PD Viangchan and Mahidol are common Southeast Asian variants. Their presence in the Malays suggests a common ancestral origin with the Cambodians, Laotians and Thais. Our findings together with other preliminary data on the presence of the Mediterranean variant in this region provide evidence of strong Arab influence in the Malay Archipelago.
  10. Ainoon O, Alawiyah A, Yu YH, Cheong SK, Hamidah NH, Boo NY, et al.
    PMID: 12971572
    Neonatal screening for G6PD deficiency has long been established in many countries. The aim of the study was to determine whether the routine semiquantitative fluorescent spot test could detect all cases of G6PD deficiency, including those cases with partial deficiency (residual red cell G6PD activity between 20-60% of normal). We compared the results of G6PD screening by the semiquantitative fluorescent spot test and quantitative G6PD activity assay on a group of 976 neonates and 67 known female heterozygotes. The values for mean G6PD activity of G6PD-normal neonates and 293 healthy adult females were determined. There was no significant difference in the mean normal G6PD activity between the two racial groups in the neonates (669 Malays, 307 Chinese) and in the 293 healthy adult females (150 Malays, 143 Chinese) group. The values for the upper limits of total deficiency (20% of normal residual activity) for neonates and adult females were 2.92 U/gHb and 1.54 U/gHb, respectively. The upper limits of partial deficiency (60% of normal residual activity) were 8.7 U/gHb and 4.6 U/gHb respectively. The prevalence of G6PD deficiency among the male neonates was 5.1% (26) by both the fluorescent spot test and the enzyme assay method. The G6PD activity levels of all 26 cases of G6PD-deficient male neonates were < 20% normal (severe enzyme deficiency). In the female neonate group, the frequency of G6PD deficiency was 1.3% (6 of 472) by the fluorescent spot test and 9.35% (44 of 472) by enzyme assay. The 6 cases diagnosed as deficient by the fluorescent spot test showed severe enzyme deficiency (< 2.92 U/gHb). The remaining 38 female neonates had partial enzyme deficiency and all were misdiagnosed as normal by the fluorescent spot test. In the female heterozygote group, G6PD deficiency was diagnosed in 53% (35 of 67) by enzyme assay and in 7.5% (4 of 67) of cases by the fluorescent spot test. The 4 cases detected by fluorescent spot test had severe enzyme deficiency (<1.6 U/gHb). The remaining 31 (46.3%) cases, diagnosed as normal by fluorescent spot test, showed partial G6PD deficiency. In conclusion, we found that the semiquantitative fluorescent spot test could only diagnose cases of total G6PD deficiency and misclassified the partially-deficient cases as normal. In this study, the overall prevalence of G6PD deficiency was 3.28% by the semiquantitative fluorescent spot test and 7.17% by enzyme assay. This means that 3.9% of G6PD-deficient neonates were missed by the routine fluorescent spot test and they were found to be exclusively females. This study demonstrates a need to use a method that can correctly classify female heterozygotes with partial G6PD deficiency. The clinical implication is that these individuals may be at risk of the hemolytic complication of G6PD deficiency.
  11. Zhang WB, Soh HY, Yu Y, Guo CB, Yu GY, Peng X
    Comput Assist Surg (Abingdon), 2021 12;26(1):9-14.
    PMID: 33503386 DOI: 10.1080/24699322.2021.1876168
    Reconstruction of Brown's Class III maxillary defect can be challenging due to the complex geometry of maxilla. We aimed to introduce an improved method for maxillary reconstruction with a composite deep circumflex iliac artery (DCIA) flap aided by virtual surgical planning and intraoperative navigation. A 27-year-old woman diagnosed with left maxillary fibromyxoma was admitted to our institution in December 2018. Pre-operative facial and iliac computed tomography data were obtained for virtual surgical planning. Personalized cutting template, tooth-supported surgical guide, and rapid prototype model with reconstructed orbital floor were printed for pre-operative preparation. Surgery was completely guided by the intraoperative navigation system. The root mean square estimate of the reconstructed area was 3.68 mm. The average errors measured on the lateral and medial DCIA segments were 0.61 and 0.85 mm, respectively. Application of virtual surgical planning and intraoperative navigation could potentially enhance the reconstruction outcomes.
  12. Sun YP, Zhu LL, Liu JS, Yu Y, Zhou ZY, Wang G, et al.
    Fitoterapia, 2018 Mar;125:141-146.
    PMID: 29325928 DOI: 10.1016/j.fitote.2018.01.004
    Five new limonoids, swieteliacates A-E (1-5) and a tirucallane-type triterpenoid, swietesenin (6), together with four known compounds (7-10) were isolated from fruit of Swietenia macrophylla. Their structures were determined by spectroscopic analyses. The new compounds were tested in vitro for their cytotoxic effects against five human cancer cell lines. Compound 2 exhibited moderate cytotoxic activities against SW480 and HL-60 cancer cell lines with IC50 values of 30.6 and 32.9μM, respectively.
  13. Tang ZN, Hu LH, Soh HY, Yu Y, Zhang WB, Peng X
    Front Oncol, 2021;11:715484.
    PMID: 35096559 DOI: 10.3389/fonc.2021.715484
    Objective: To evaluate the feasibility and accuracy of mixed reality combined with surgical navigation in oral and maxillofacial tumor surgery.

    Methods: Retrospective analysis of data of seven patients with oral and maxillofacial tumors who underwent surgery between January 2019 and January 2021 using a combination of mixed reality and surgical navigation. Virtual surgical planning and navigation plan were based on preoperative CT datasets. Through IGT-Link port, mixed reality workstation was synchronized with surgical navigation, and surgical planning data were transferred to the mixed reality workstation. Osteotomy lines were marked with the aid of both surgical navigation and mixed reality images visualized through HoloLens. Frozen section examination was used to ensure negative surgical margins. Postoperative CT datasets were obtained 1 week after the surgery, and chromatographic analysis of virtual osteotomies and actual osteotomies was carried out. Patients received standard oncological postoperative follow-up.

    Results: Of the seven patients, four had maxillary tumors and three had mandibular tumors. There were total of 13 osteotomy planes. Mean deviation between the planned osteotomy plane and the actual osteotomy plane was 1.68 ± 0.92 mm; the maximum deviation was 3.46 mm. Chromatographic analysis showed error of ≤3 mm for 80.16% of the points. Mean deviations of maxillary and mandibular osteotomy lines were approximate (1.60 ± 0.93 mm vs. 1.86 ± 0.93 mm). While five patients had benign tumors, two had malignant tumors. Mean deviations of osteotomy lines was comparable between patients with benign and malignant tumors (1.48 ± 0.74 mm vs. 2.18 ± 0.77 mm). Intraoperative frozen pathology confirmed negative resection margins in all cases. No tumor recurrence or complications occurred during mean follow-up of 15.7 months (range, 6-26 months).

    Conclusion: The combination of mixed reality technology and surgical navigation appears to be feasible, safe, and effective for tumor resection in the oral and maxillofacial region.

  14. Soh HY, Zhang WB, Yu Y, Zhang R, Chen Y, Gao Y, et al.
    World J Clin Cases, 2023 Mar 16;11(8):1878-1887.
    PMID: 36970007 DOI: 10.12998/wjcc.v11.i8.1878
    BACKGROUND: Sclerosing odontogenic carcinoma is a rare primary intraosseous neoplasm that was featured recently as a single entity in the World Health Organization classification of Head and Neck Tumors 2017, with only 14 cases published to date. The biological characteristics of sclerosing odontogenic carcinoma remain indistinct because of its rarity; however, it appears to be locally aggressive, with no regional or distant metastasis reported to date.

    CASE SUMMARY: We reported a case of sclerosing odontogenic carcinoma of the maxilla in a 62-year-old woman, who presented with an indolent right palatal swelling, which progressively increased in size over 7 years. Right subtotal maxillectomy with surgical margins of approximately 1.5 cm was performed. The patient remained disease free for 4 years following the ablation surgery. Diagnostic workups, treatment, and therapeutic outcomes were discussed.

    CONCLUSION: More cases are needed to further characterize this entity, understand its biological behavior, and justify the treatment protocols. Resection with wide margins of approximately 1.0 to 1.5 cm is proposed, while neck dissection, post-operative radiotherapy, or chemotherapy are deemed unnecessary.

  15. Yu Y, Tham SK, Roslan FF, Shaharuddin B, Yong YK, Guo Z, et al.
    Front Cardiovasc Med, 2023;10:1011880.
    PMID: 37008331 DOI: 10.3389/fcvm.2023.1011880
    Myocardial infarction is the most common cause of heart failure, one of the most fatal non-communicable diseases worldwide. The disease could potentially be treated if the dead, ischemic heart tissues are regenerated and replaced with viable and functional cardiomyocytes. Pluripotent stem cells have proven the ability to derive specific and functional cardiomyocytes in large quantities for therapy. To test the remuscularization hypothesis, the strategy to model the disease in animals must resemble the pathophysiological conditions of myocardial infarction as in humans, to enable thorough testing of the safety and efficacy of the cardiomyocyte therapy before embarking on human trials. Rigorous experiments and in vivo findings using large mammals are increasingly important to simulate clinical reality and increase translatability into clinical practice. Hence, this review focus on large animal models which have been used in cardiac remuscularization studies using cardiomyocytes derived from human pluripotent stem cells. The commonly used methodologies in developing the myocardial infarction model, the choice of animal species, the pre-operative antiarrhythmics prophylaxis, the choice of perioperative sedative, anaesthesia and analgesia, the immunosuppressive strategies in allowing xenotransplantation, the source of cells, number and delivery method are discussed.
  16. Yu Y, Chen D, Lee YY, Chen N, Wang Y, Qiu C
    Foods, 2023 May 18;12(10).
    PMID: 37238863 DOI: 10.3390/foods12102045
    Curcumin-loaded solid lipid nanoparticles (Cur-SLN) were prepared using medium- and long chain diacylglycerol (MLCD) or glycerol tripalmitate (TP) as lipid matrix and three kinds of surfactants including Tween 20 (T20), quillaja saponin (SQ) and rhamnolipid (Rha). The MLCD-based SLNs had a smaller size and lower surface charge than TP-SLNs with a Cur encapsulation efficiency of 87.54-95.32% and the Rha-based SLNs exhibited a small size but low stability to pH decreases and ionic strength. Thermal analysis and X-ray diffraction results confirmed that the SLNs with different lipid cores showed varying structures, melting and crystallization profiles. The emulsifiers slightly impacted the crystal polymorphism of MLCD-SLNs but largely influenced that of TP-SLNs. Meanwhile, the polymorphism transition was less significant for MLCD-SLNs, which accounted for the better stabilization of particle size and higher encapsulation efficiency of MLCD-SLNs during storage. In vitro studies showed that emulsifier formulation greatly impacted on the Cur bioavailability, whereby T20-SLNs showed much higher digestibility and bioavailability than that of SQ- and Rha-SLNs possibly due to the difference in the interfacial composition. Mathematical modeling analysis of the membrane release further confirmed that Cur was mainly released from the intestinal phase and T20-SLNs showed a faster release rate compared with other formulations. This work contributes to a better understanding of the performance of MLCD in lipophilic compound-loaded SLNs and has important implications for the rational design of lipid nanocarriers and in instructing their application in functional food products.
  17. Lu S, Shih JY, Jang TW, Liam CK, Yu Y
    Adv Ther, 2021 May;38(5):2038-2053.
    PMID: 33730350 DOI: 10.1007/s12325-021-01696-9
    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are a standard of care in the first-line treatment of patients with EGFR mutation-positive metastatic non-small-cell lung cancer (NSCLC). EGFR mutations are relatively common in Asian patients with NSCLC, and there is an increasing number of studies supporting the effectiveness of the second-generation TKI afatinib in routine clinical practice in Asia. This article reviews these real-world studies investigating afatinib as first-line treatment for EGFR mutation-positive NSCLC in Asian patients. Evidence from real-world studies with afatinib in this patient population supports findings from randomized controlled trials (RCTs) showing that afatinib is associated with more favorable outcomes compared with the first-generation EGFR TKIs. The effectiveness of afatinib has also been shown in real-world studies in Asian patients with poor prognostic factors, who are often under-represented or excluded from RCTs, such as those with uncommon EGFR mutations, brain metastases, or poor performance status, and elderly patients. The tolerability profile of afatinib in the real-world setting reflects that seen in RCTs, with no new safety signals reported in real-world studies in Asian patients with EGFR mutation-positive NSCLC. Dose-modification strategies also seem to be effective in the real world, with results of the RealGido study, which included 44% Asian patients, confirming findings from prospective clinical trials showing that tolerability-guided afatinib dose modifications can reduce the incidence of adverse events without adversely affecting clinical outcomes. While further research, including clinical trial data, is needed, real-world data have also demonstrated the feasibility of sequential afatinib followed by the third-generation TKI osimertinib in T790M-positive EGFR mutation-positive patients, which showed longer overall survival. Together, these real-world results demonstrate the real-world clinical effectiveness of afatinib as first-line treatment for patients with EGFR mutation-positive NSCLC.
  18. Pang T, Wong JHD, Ng WL, Chan CS, Wang C, Zhou X, et al.
    Phys Med Biol, 2024 Feb 19.
    PMID: 38373345 DOI: 10.1088/1361-6560/ad2a95
    OBJECTIVE: Generally, due to a lack of explainability, radiomics based on deep learning has been perceived as a black-box solution for radiologists. Automatic generation of diagnostic reports is a semantic approach to enhance the explanation of deep learning radiomics (DLR).

    APPROACH: In this paper, we propose a novel model called radiomics-reporting network (Radioport), which incorporates text attention. This model aims to improve the interpretability of deep learning radiomics in mammographic calcification diagnosis. Firstly, it employs convolutional neural networks (CNN) to extract visual features as radiomics for multi-category classification based on Breast Imaging Reporting and Data System (BI-RADS). Then, it builds a mapping between these visual features and textual features to generate diagnostic reports, incorporating an attention module for improved clarity.

    MAIN RESULTS: To demonstrate the effectiveness of our proposed model, we conducted experiments on a breast calcification dataset comprising mammograms and diagnostic reports. The results demonstrate that our model can: (i) semantically enhance the interpretability of deep learning radiomics; and, (ii) improve the readability of generated medical reports.

    SIGNIFICANCE: Our interpretable textual model can explicitly simulate the mammographic calcification diagnosis process.

  19. Merlot AM, Shafie NH, Yu Y, Richardson V, Jansson PJ, Sahni S, et al.
    Biochem Pharmacol, 2016 06 01;109:27-47.
    PMID: 27059255 DOI: 10.1016/j.bcp.2016.04.001
    The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca(2+)) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins in the ER, leading to ER stress and the activation of the unfolded protein response (UPR). In the stressful tumor microenvironment, the UPR maintains ER homeostasis and enables tumor survival. Thus, a novel strategy for cancer therapeutics is to overcome chronically activated ER stress by triggering pro-apoptotic pathways of the UPR. Considering this, the mechanisms by which the novel anti-cancer agent, Dp44mT, can target the ER stress response pathways were investigated in multiple cell-types. Our results demonstrate that the cytotoxic chelator, Dp44mT, which forms redox-active metal complexes, significantly: (1) increased ER stress-associated pro-apoptotic signaling molecules (i.e., p-eIF2α, ATF4, CHOP); (2) increased IRE1α phosphorylation (p-IRE1α) and XBP1 mRNA splicing; (3) reduced expression of ER stress-associated cell survival signaling molecules (e.g., XBP1s and p58(IPK)); (4) increased cleavage of the transcription factor, ATF6, which enhances expression of its downstream targets (i.e., CHOP and BiP); and (5) increased phosphorylation of CaMKII that induces apoptosis. In contrast to Dp44mT, the iron chelator, DFO, which forms redox-inactive iron complexes, did not affect BiP, p-IRE1α, XBP1 or p58(IPK) levels. This study highlights the ability of a novel cancer therapeutic (i.e., Dp44mT) to target the pro-apoptotic functions of the UPR via cellular metal sequestration and redox stress. Assessment of ER stress-mediated apoptosis is fundamental to the understanding of the pharmacology of chelation for cancer treatment.
  20. Yu Y, Gao L, Niu X, Liu K, Li R, Yang D, et al.
    Adv Mater, 2023 Mar;35(12):e2210157.
    PMID: 36732915 DOI: 10.1002/adma.202210157
    Hot-carrier devices are promising alternatives for enabling path breaking photoelectric conversion. However, existing hot-carrier devices suffer from low efficiencies, particularly in the infrared region, and ambiguous physical mechanisms. In this work, the competitive interfacial transfer mechanisms of detrapped holes and hot electrons in hot-carrier devices are discovered. Through photocurrent polarity research and optical-pump-THz-probe (OPTP) spectroscopy, it is verified that detrapped hole transfer (DHT) and hot-electron transfer (HET) dominate the low- and high-density excitation responses, respectively. The photocurrent ratio assigned to DHT and HET increases from 6.6% to over 1133.3% as the illumination intensity decreases. DHT induces severe degeneration of the external quantum efficiency (EQE), especially at low illumination intensities. The EQE of a hot-electron device can theoretically increase by over two orders of magnitude at 10 mW cm-2 through DHT elimination. The OPTP results show that competitive transfer arises from the carrier oscillation type and carrier-density-related Coulomb screening. The screening intensity determines the excitation weight and hot-electron cooling scenes and thereby the transfer dynamics.
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