Consensus Guidelines on Human Epidermal Growth Factor Receptor 2 (HER2)-Low Testing in Breast Cancer in Malaysia.

Breast cancer is one of the most common cancers in Malaysia. Recently, a new nomenclature was introduced for breast cancers with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+, or 2+ with negative in situ hybridization (ISH), i.e., HER2-low breast cancer. In current clinical practice, these breast cancers are reported as HER2-negative. Clinical trials have shown that HER2-low breast cancer benefits from targeted therapy with anti-HER2 antibody-drug conjugates. Unfortunately, various challenges and obstacles are faced by local pathologists in HER2 testing, which may jeopardize the standard of care for patients with HER2-low breast cancer. This consensus guideline aims to elucidate standard practices pertaining to HER2 testing and HER2-low interpretation in Malaysia. Topics discussed among a panel of local experts include tissue sampling and handling, assay and antibody selection, result interpretation and reporting, and quality assurance. Practice recommendations made in this consensus guideline reflect current international guidelines and, where appropriate, adapted to the Malaysian landscape.

Hepatocyte-specific Epidermal Growth Factor Receptor Deletion Promotes Fibrosis but has no Effect on Steatosis in Fast-food Diet Model of Metabolic Dysfunction-associated Steatotic Liver Disease.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disorder, with no approved treatment. Our previous work demonstrated the efficacy of a pan-ErbB inhibitor, Canertinib, in reducing steatosis and fibrosis in a murine fast-food diet (FFD) model of MASLD. The current study explores the effects of hepatocyte-specific ErbB1 (ie, epidermal growth factor receptor [EGFR]) deletion in the FFD model. METHODS: EGFRflox/flox mice, treated with AAV8-TBG-CRE to delete EGFR specifically in hepatocytes (EGFR-KO), were fed either a chow-diet or FFD for 2 or 5 months. RESULTS: Hepatocyte-specific EGFR deletion reduced serum triglyceride levels but did not prevent steatosis. Surprisingly, hepatic fibrosis was increased in EGFR-KO mice in the long-term study, which correlated with activation of transforming growth factor-ß/fibrosis signaling pathways. Further, nuclear levels of some of the major MASLD regulating transcription factors (SREBP1, PPARγ, PPARα, and HNF4α) were altered in FFD-fed EGFR-KO mice. Transcriptomic analysis revealed significant alteration of lipid metabolism pathways in EGFR-KO mice with changes in several relevant genes, including downregulation of fatty-acid synthase and induction of lipolysis gene, Pnpla2, without impacting overall steatosis. Interestingly, EGFR downstream signaling mediators, including AKT, remain activated in EGFR-KO mice, which correlated with increased activity pattern of other receptor tyrosine kinases, including ErbB3/MET, in transcriptomic analysis. Lastly, Canertinib treatment in EGFR-KO mice, which inhibits all ErbB receptors, successfully reduced steatosis, suggesting the compensatory roles of other ErbB receptors in supporting MASLD without EGFR. CONCLUSIONS: Hepatocyte-specific EGFR-KO did not impact steatosis, but enhanced fibrosis in the FFD model of MASLD. Gene networks associated with lipid metabolism were greatly altered in EGFR-KO, but phenotypic effects might be compensated by alternate signaling pathways.

Gold nanomakura: nanoarchitectonics and their photothermal response in association with carrageenan hydrogels.

Photothermal conversion of light into heat energy is an intrinsic optical property of metal nanoparticles when irradiated using near-infrared radiation. However, the impact of size and shape on the photothermal behaviour of gold nanomakura particles possessing optical absorption within 600-700 nm as well as on incorporation in hydrogels is not well reported. In this study, nanomakura-shaped anisotropic gold nanoparticles (AuNMs) were synthesized via a surfactant-assisted seed-mediated protocol. Quaternary cationic surfactants having variable carbon tail length (n = 16, 14, 12) were used as capping for tuning the plasmon peak of gold nanomakura within a 600-700 nm wavelength. The aspect ratio as well as anisotropy of synthesized gold nanomakura can influence photothermal response upon near-infrared irradiation. The role of carbon tail length was evident via absorption peaks obtained from longitudinal surface plasmon resonance analysis at 670, 650, and 630 nm in CTAB-AuNM, MTAB-AuNM, and DTAB-AuNM, respectively. Furthermore, the impact of morphology and surrounding milieu of the synthesized nanomakuras on photothermal conversion is investigated owing to their retention of plasmonic stability. Interestingly, we found that photothermal conversion was exclusively assigned to morphological features (i.e., nanoparticles of higher aspect ratio showed higher temperature change and vice versa irrespective of the surfactant used). To enable biofunctionality and stability, we used kappa-carrageenan- (k-CG) based hydrogels for incorporating the nanomakuras and further assessed their photothermal response. Nanomakura particles in association with k-CG were also able to show photothermal conversion, depicting their ability to interact with light without hindrance. The CTAB-AuNM, MTAB-AuNM, and DTAB-AuNM after incorporation into hydrogel beads attained up to ≈17.2, ≈17.2, and ≈15.7 °C, respectively. On the other hand, gold nanorods after incorporation into k-CG did not yield much photothermal response as compared to that of AuNMs. The results showed a promising platform to utilize nanomakura particles along with kappa-carrageenan hydrogels for enabling usage on nanophotonic, photothermal, and bio-imaging applications.

Epigenetically active chromatin in neonatal iWAT reveals GABPα as a potential regulator of beige adipogenesis.

Background: Thermogenic beige adipocytes, which dissipate energy as heat, are found in neonates and adults. Recent studies show that neonatal beige adipocytes are highly plastic and contribute to >50% of beige adipocytes in adults. Neonatal beige adipocytes are distinct from recruited beige adipocytes in that they develop independently of temperature and sympathetic innervation through poorly defined mechanisms. Methods: We characterized the neonatal beige adipocytes in the inguinal white adipose tissue (iWAT) of C57BL6 postnatal day 3 and 20 mice (P3 and P20) by imaging, genome-wide RNA-seq analysis, ChIP-seq analysis, qRT-PCR validation, and biochemical assays. Results: We found an increase in acetylated histone 3 lysine 27 (H3K27ac) on the promoter and enhancer regions of beige-specific gene UCP1 in iWAT of P20 mice. Furthermore, H3K27ac ChIP-seq analysis in the iWAT of P3 and P20 mice revealed strong H3K27ac signals at beige adipocyte-associated genes in the iWAT of P20 mice. The integration of H3K27ac ChIP-seq and RNA-seq analysis in the iWAT of P20 mice reveal epigenetically active signatures of beige adipocytes, including oxidative phosphorylation and mitochondrial metabolism. We identify the enrichment of GA-binding protein alpha (GABPα) binding regions in the epigenetically active chromatin regions of the P20 iWAT, particularly on beige genes, and demonstrate that GABPα is required for beige adipocyte differentiation. Moreover, transcriptomic analysis and glucose oxidation assays revealed increased glycolytic activity in the neonatal iWAT from P20. Conclusions: Our findings demonstrate that epigenetic mechanisms regulate the development of peri-weaning beige adipocytes via GABPα. Further studies to better understand the upstream mechanisms that regulate epigenetic activation of GABPα and characterization of the metabolic identity of neonatal beige adipocytes will help us harness their therapeutic potential in metabolic diseases.

Prevalence of test anxiety and its determinants among nursing students in Selangor, Malaysia.

The current education system significantly emphasizes tests and evaluations as crucial factors in determining a student's future career path. It has been shown that nursing students have moderate to high levels of Test Anxiety (TA), which results in decreased academic performance, low self-esteem, and an inability to complete the program and pursue a career in nursing successfully. This study aimed to determine nursing students' level of TA and its relationship with demographic characteristics. Four hundred twenty-one nursing students at seven private universities and colleges in Selangor participated in this cross-sectional study. The level of TA was measured using the TA Inventory (TAI). A total of 62.5% of the respondents had mild TA, 25.4% had moderate TA and 2.1% had severe TA. There were significant relationships between TA level and household income (χ2 = 6.70, p = 0.035) and ethnic groups (F (3,417) = 5.20, p = 0.002) where Chinese and Indians are protective from TA compared to the Malays and other ethnic groups and high anxiety was significant in the Ringgit Malaysia (RM 3000) and below group. The study's findings indicate that a significant percentage of nursing students involved in the research had mild to moderate levels of test anxiety (TA) and there is a significant association between TA and demographic characteristics. The results indicate the importance of early identification of TA and the need for interventions to overcome TA to ensure they are emotionally, physically, and academically successful.