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Jrhau Lung,1 Kuan-Liang Chen,2 Chien-Hui Hung,3 Chih-Cheng Chen,4,5 Ming-Szu Hung,5–7 Yu-Ching Lin,5–7 Ching-Yuan Wu,8 Kuan-Der Lee,9 Neng-Yao Shih,10 Ying Huang Tsai11,12 1Department of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi, 2Department of Endodontics, ChiMei Medical Center, Tainan, 3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, 4Division of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, 5Department of Medicine, Chang Gung University, Taoyuan, 6Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, 7Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, 8Department of Chinese Medicine; Chang Gung Memorial Hospital, Chiayi, 9Department of Hematology and Oncology, Taipei Medical University Hospital, Taipei, 10National Institute of Cancer Research, National Health Research Institutes, Tainan, 11Department of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan, 12Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan Abstract: Unlimited growth of cancer cells requires an extensive nutrient supply. To meet this demand, cancer cells drastically upregulate glucose uptake and metabolism compared to normal cells. This difference has made the blocking of glycolysis a fascinating strategy to treat this malignant disease. α-enolase is not only one of the most upregulated glycolytic enzymes in cancer cells, but also associates with many cellular processes or conditions important to cancer cell survival, such as cell migration, invasion, and hypoxia. Targeting α-enolase could simultaneously disturb cancer cells in multiple ways and, therefore, is a good target for anticancer drug development. In the current study, more than 22 million chemical structures meeting the criteria of Lipinski’s rule of five from the ZINC database were docked to α-enolase by virtual screening. Twenty-four chemical structures with docking scores better than that of the enolase substrate, 2-phosphoglycerate, were further screened by the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties prediction. Four of them were classified as non-mutagenic, non-carcinogenic, and capable of oral administration where they showed steady interactions to α-enolase that were comparable, even superior, to the currently available inhibitors in molecular dynamics (MD) simulation. These compounds may be considered promising leads for further development of the α-enolase inhibitors and could help fight cancer metabolically. Keywords: α-enolase inhibitor, virtual screening, molecular dynamics simulation, glycolysis, metabolism

A strong influence of ion implantation flux on the accumulation of radiation damage, the so-called dose rate effect, is observed and systematically studied in SiC. 100 keV Si[sup +] ions were implanted into bulk 4H-SiC wafers using different ion fluxes (1.9×10[sup 10]–4.9×10[sup 13] ions/cm[sup 2] s) and keeping the implantation dose constant at 5×10[sup 14] Si[sup +]/cm[sup 2]. The implants were performed both at room and elevated temperatures, up to 220 °C. Rutherford backscattering spectrometry in the channelling mode using 2 MeV He[sup +] ions was employed to measure ion implantation damage profiles in the samples. For the flux interval used the most, pronounced dynamic annealing effect was detected at 80–160 °C, having an activation energy of 1.3 eV. For example, at 100 °C the amount of disordered Si atoms at the projected ion range is reduced by a factor of 4 by decreasing the ion flux from 4.9×10[sup 13] to 1.9×10[sup 10] ions/cm[sup 2] s. The results are discussed in terms of migration and annihilation of intrinsic type defects for both the Si- and C-sublattices. In addition, two regions for the damage accumulation – at the surface and at the damage peak for 100 keV Si[sup +] ions – are observed. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Mobile beacon application leverages the beacon technology as location-based or proximity sensors to notify or interact with user via mobile apps. There are many instances of these applications especially as an engagement platform across many domains like marketing, retails, exhibitions, or public services. Mobile beacon application holds potential as an engagement tool for empowering co-curricular engagement in higher education. Integrated with personalized mobile notification, users can be notified and interact with co-curricular events within their proximity in the campus. However, literature indicates limited insights on the design applicability and empirical studies of mobile beacon application for higher education context. This new application context poses its own unique challenges, but imperative in helping researchers to discover the extents of mobile beacon potentials. This concept paper introduces a preliminary mobile beacon application framework for supporting co-curricular engagement in higher education. The framework aims to enable design applicability of a mobile beacon application integrated with personalized notification for education engagement purposes. Characterization of mobile beacon application components along with the deliberation of mobile notification features are highlighted in the framework. The presented conceptual framework offers the foundation for application designers in building a mobile beacon application for higher education engagement.

Background:Autophagy is a programmed cell survival mechanism that has a key role in both physiologic and pathologic conditions. The relationship between autophagy and cancer is complex because autophagy can act as either a tumour suppressor or as a tumour promoter. The role of autophagy in oral squamous cell carcinoma (OSCC) is controversial. Several studies have claimed that either a high or low expression of autophagy-related proteins was associated with poor prognosis of OSCCs. The aims of the study were to compare autophagy in OSCCs, verrucous hyperplasias, and normal oral mucosas, and to inspect the prognostic role of autophagy in OSCCs.Methods:We used the autophagosome marker, LC3B, and autophagy flux marker, p62/SQSTM1 (p62), by using immunohistochemistry, and examined p62 mRNA by RNA in situ hybridization, to evaluate autophagy in 195 OSCCs, 47 verrucous hyperplasias, and 37 normal oral mucosas. The prognostic roles of LC3B and p62 protein expressions in OSCCs were investigated.Results:We discovered that the normal oral mucosa exhibited limited LC3B punctae and weak cytoplasmic p62 staining, whereas the OSCCs exhibited a marked increase in LC3B punctae and cytoplasmic p62 expression. The expression pattern of LC3B and cytoplasmic p62 of the verrucous hyperplasias were between normal oral mucosas and OSCCs. The normal oral mucosas, verrucous hyperplasias, and OSCCs presented no differences in nuclear p62 expression and the p62 mRNA level. p62 mRNA expression was elevated in a minority of cases. High p62 mRNA expression was associated with high p62 protein expression in the cytoplasm. Increased LC3B punctae, high cytoplasmic p62, and low nuclear p62 expressions in OSCCs were associated with aggressive clinicopathologic features and unfavourable prognosis. In addition, low nuclear p62 expression was an independent prognostic factor for overall and disease-specific survival rates. Furthermore, we disclosed that high cytoplasmic p62 expression accompanied with either a low or high LC3B expression, which indicated autophagy impairment under basal or activated autophagic activity, was associated with aggressive behaviour in advanced OSCCs.Conclusions:We suggested that autophagy was altered during cancer initiation and progression. Autophagy impairment contributed to cancer progression in advanced OSCCs. [ABSTRACT FROM AUTHOR]

Induction of the lysis protein of the ColE operon is known to be essential for colicin release. Thus far, the involvement of inner membrane in this unique protein exportation process has not been elucidated. In this work, fluorescent dyes were used to monitor the permeability change of both inner and outer membranes in response to induction of the lysis protein. We found that induction of permeability of the inner membrane appeared earlier than that of the outer membrane before the occurrence of the decline in culture turbidity. Interestingly, we also found that change of outer membrane permeability was alleviated in the outer membrane phospholipase A (OMPLA)-deficient mutant 135 min after induction. Thus, in this work, we show that permeability change of the inner membrane induced by the lysis protein is likely involved in the basal level of colicin release. A greater release of colicin coincided with the decline in culture turbidity and should be associated with the activation of OMPLA at the late stage of induction of the lysis protein. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the perspectives of people accessing a general medical practitioner (GP)-optometry model of collaborative care that was established to increase access to diabetes eye care., Methods: Qualitative study of patient barriers and facilitators to accessing primary diabetes eye care located in a metropolitan area in Australia. One-on-one interviews were recorded, transcribed and thematically analysed using a determinant framework on patient-centred access to health care., Results: Twenty-four people with type 2 diabetes, including 15 males and 9 females, who accessed the service between September 2021 and June 2022 agreed to participate. Mean (SD) age of the participants was 52 (12) years and 50% had been diagnosed with diabetes for <2 years. Facilitators to accessing diabetes eye care included a referral from a GP or GP nurse, fee-free consultations, availability of after-hours appointments and short waiting times. Barriers to access included perceived out-of-pocket costs, competing responsibilities and lack of awareness of diabetic retinopathy screening recommendations., Conclusion: Considering diabetic retinopathy may present asymptomatically, primary health practitioners (optometrists and GPs) are well positioned to raise patient awareness of the importance of routine eye examinations. In Australia, access to routine screening could be facilitated by fee-free eye checks and personalised text message reminders implemented at a health system level., (© 2024 The Author(s). Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Background: Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) offer the potential for long-term survival in peritoneal carcinomatosis, outcomes following CRS/HIPEC vary significantly., Aim: To identify the clinical factors associated with progression-free survival (PFS) after complete CRS/HIPEC in patients with colorectal/high-grade appendiceal, ovarian, and gastric cancers., Methods: We retrospectively evaluated the risk of recurrence within 1 year after CRS/HIPEC and its impact on overall survival (OS) in patients recruited between 2015 and 2020. Logistic regression models were used to assess the prognostic factors for the risk of recurrence within 1 year. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate the association between recurrence and OS., Results: Of the 80 enrolled patients, 39 had an unfavorable PFS (< 1 year) and 41 had a favorable PFS (≥ 1 year). Simple logistic models revealed that the patients with a completeness of cytoreduction score of 0 (CC-0) or length of CRS ≤ 6 h had a favorable PFS [odds ratio (OR) = 0.141, P = 0.004; and OR = 0.361, P = 0.027, respectively]. In multiple logistic regression, achieving CC-0 was the strongest prognostic factor for a favorable PFS (OR = 0.131, P = 0.005). A peritoneal cancer index score > 12 was associated with a lower rate of achieving CC-0 ( P = 0.027). The favorable PFS group had a significantly longer OS (median 81.7 mo vs 17.0 mo, P < 0.001)., Conclusion: Achieving CC-0 was associated with a lower early recurrence rate and improved long-term survival. This study underscores the importance of selecting appropriate candidates for CRS/HIPEC to manage peritoneal carcinomatosis., Competing Interests: Conflict-of-interest statement: The authors have no relevant financial or non-financial interests to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Macrophages, pivotal components of the immune system, orchestrate host defense mechanisms in humans and mammals. Their polarization into classically activated macrophages (CAMs or M1) and alternatively activated macrophages (AAMs or M2) dictates distinct functional roles in immunity and tissue homeostasis. While the negative regulatory role of CD32b within the FC gamma receptor (FCγR) family is recognized across various immune cell types, its influence on macrophage polarization remains elusive. This study aimed to elucidate the regulatory role of CD32b in macrophage polarization and discern the differential expression markers between the M1 and M2 phenotypes following CD32b siRNA transfection. The results revealed a decrease in the CD32b levels in lipopolysaccharide (LPS)-treated M1 and an increase in interleukin-4 (IL-4)-treated M2 macrophages, as observed in macrophage Raw264.7 cells. Furthermore, CD32b siRNA transfection significantly downregulated the M2 markers (IL-10, VEGF, Arg-1, and STAT6), while upregulating the M1 markers (IL-6, NF-κB, NOS2, and STAT1) in the Raw264.7 cells. Similar findings were recapitulated in macrophage-rich adherent cells isolated from mouse spleens. Additionally, the cytopathological analysis of pleural effusions and ascitic fluids from patients with cancer revealed a positive correlation between advanced tumor stages, metastasis, and elevated CD32b levels. In conclusion, this study highlights the regulatory influence of CD32b in suppressing M1 expression and promoting M2 polarization. Moreover, heightened M2 activation and CD32b levels appear to correlate with tumor progression. A targeted CD32b blockade may serve as a novel therapeutic strategy to inhibit M2 macrophage polarization and is promising for anti-tumor intervention.

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, continues to pose significant global health challenges. The results demonstrated that GB-2 at 200 μg/mL effectively increased the population of 293T-ACE2 cells with low RBD binding for both SARS-CoV-2 Omicron EG.5.1 and HV.1 variants by dual-color flow cytometry, indicating its ability to inhibit virus attachment. Further investigation revealed that (+)-catechin at 25 and 50 μg/mL did not significantly alter the ACE2-RBD interaction for the EG.5.1 variant. In contrast, theaflavin showed inhibitory effects at both 25 and 50 μg/mL for EG.5.1, while only the higher concentration was effective for HV.1. Notably, theaflavin 3-gallate exhibited a potent inhibition of ACE2-RBD binding for both variants at both concentrations tested. Molecular docking studies provided insight into the binding mechanisms of theaflavin and theaflavin 3-gallate with the RBD of EG.5.1 and HV.1 variants. Both compounds showed favorable docking scores, with theaflavin 3-gallate demonstrating slightly lower scores (-8 kcal/mol) compared to theaflavin (-7 kcal/mol) for both variants. These results suggest stable interactions between the compounds and key residues in the RBD, potentially explaining their inhibitory effects on virus attachment. In conclusion, GB-2, theaflavin, and theaflavin 3-gallate demonstrate significant potential as inhibitors of the ACE2-RBD interaction in Omicron variants, highlighting their therapeutic promise against COVID-19. However, these findings are primarily based on computational and in vitro studies, necessitating further in vivo research and clinical trials to confirm their efficacy and safety in humans.

Objectives: To investigate publicly funded healthcare costs according to faller status and the periods pre- and post-cataract surgeries, and identify factors associated with higher monthly costs in older people with bilateral cataract., Methods: This prospective cohort study included community-dwelling older people aged 65 and over (between 2012 and 2019); at baseline participants had bilateral cataract and were waiting for cataract surgery in New South Wales (NSW) public hospitals. Participants were followed for 24 months. The study used self-reported and linked data (Medicare Benefits Schedule, Pharmaceutical Benefits Scheme, NSW Admitted Patient and Emergency Department Data Collections) to identify falls, cataract surgeries and healthcare costs incurred by the Australian and NSW Governments, all costs were inflated to 2018-19 Australian dollars (AUD). Median monthly healthcare costs were calculated for faller status (non-faller, non-medically treated faller, medically treated faller) and surgery periods (pre-surgery, post-first surgery, post-second surgery). Costs in the 30 days following a medically treated fall were estimated. A generalised linear model was used to investigate predictors of healthcare costs., Results: During the median follow-up period of 24 months, 274 participants suffered 448 falls, with 95 falls requiring medical treatment. For medically treated falls, the mean cost in the 30 days after treatment was A$3779 (95% confidence interval $2485, $5074). Higher monthly healthcare costs were associated with a higher number of medications, being of the male sex, having one or more medically treated falls and having bilateral cataract surgery. After excluding the cost of cataract surgery, there were no significant differences in healthcare costs between the pre-cataract surgery, post-first eye cataract surgery and post-second eye cataract surgery periods., Conclusions: To our knowledge, this is the first study investigating publicly funded costs related to falls and cataract surgery in older people with bilateral cataract. This information enhances our understanding of healthcare costs in this group. The patterns in costs associated with falls can guide future government healthcare expenditure on falls treatment and prevention, including timely cataract surgery., Competing Interests: None declared.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression., Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials., Discussion: AusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile., Competing Interests: LRG has received unrelated migraine research funding from the Australian NHMRC, US Migraine Research Foundation, US Dept of Defence and Teva. LN-S is supported by an Emerging Leadership 1 Fellowship from the Australian NHMRC. PSS is supported by a Leadership 3 Fellowship from the Australian NHMRC, and previously served on advisory committees for Biogen Australia and Roche Australia. RAS has received unrelated migraine research funding from the Australian NHMRC, US Migraine Research Foundation, and US Dept of Defence. No other authors have conflicts of interest to declare., (© 2024 The Author(s). Published by Elsevier B.V.)

Molecular techniques that recover unknown sequences next to a known sequence region have been widely applied in various molecular studies, such as chromosome walking, identification of the insertion site of transposon mutagenesis, fusion gene partner, and chromosomal breakpoints, as well as targeted sequencing library preparation. Although various techniques have been introduced for efficiency enhancement, searching for relevant single molecular event present in a large-sized genome remains challenging. Here, the optimized ligation-mediated polymerase chain reaction (PCR) method was developed and successfully identified chromosomal breakpoints far away from the exon of the new exon junction without the need for nested PCR. In addition to recovering unknown sequences next to a known sequence region, the high efficiency of the method could also improve the performance of targeted  next-generation sequencing (NGS)., Competing Interests: All authors declare that there is no competing interests for the study., (© The Author(s) 2024. Published by Oxford University Press.)

Prcis: This systematic review has revealed that variable definitions of glaucoma continue to be used in prevalence studies, despite the introduction of the International Society of Geographic and Epidemiologic Ophthalmology (ISGEO) criteria., Purpose: To systematically review diagnostic criteria and examinations performed in glaucoma prevalence studies over time and determine the quality of reporting. Accurate estimates of glaucoma prevalence are crucial to inform resource allocation. However, diagnosis of glaucoma comprises inherently subjective examinations and the cross-sectional nature of prevalence studies precludes monitoring for progression., Methods: A systematic review of PubMed, Embase, Web of Science, and Scopus was performed to examine diagnostic protocols used by glaucoma prevalence studies and evaluate uptake of the ISGEO criteria, introduced in 2002 to standardize glaucoma diagnosis in prevalence studies. Detection bias and compliance with the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guidelines were evaluated., Results: Ten thousand five hundred forty-four articles were identified. After deduplication, 5589 articles were screened, yielding 136 articles pertaining to 123 studies. An absence of data in many countries was identified. Ninety-two percent of studies stated diagnostic criteria, and 62% used the ISGEO criteria since their publication. Weaknesses of the ISGEO criteria were identified. Temporal variations in the performance of various examinations were observed, including heterogeneity in angle assessment. Mean STROBE compliance was 82% (range 59-100%); 72 articles had a low risk of detection bias, 4 had a high risk, and 60 had some concerns., Conclusion: Heterogeneous diagnostic definitions persist in glaucoma prevalence studies, despite introduction of the ISGEO criteria. Standardization of criteria remains imperative and the development of new criteria represent a valuable opportunity to achieve this goal. In addition, methods of determining diagnoses are poorly reported, suggesting a need for improvement in study conduct and reporting. Accordingly, we propose the Reporting of quality Of GlaUcoma Epidemiological Studies (ROGUES) Checklist. We have also identified a need for further prevalence studies in regions with limited data and to update Australian angle closure glaucoma prevalence. Design and reporting of future studies can be informed by this review's insights into diagnostic protocols previously used., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To review the most recent evidence on the association of ambient air pollution with posterior segment ocular diseases., Methods: A search of the most recently published medical literature was performed in PubMed and Google Scholar on 10 December 2022. Articles published between 2018 and December 2022 were included in this rapid review. Studies that evaluated the association between ambient air pollutants (nitrogen dioxide (NO 2 ), carbon monoxide (CO), sulfur dioxide (SO 2 ), ozone (O 3 ), particulate matters (PM s ), total hydrocarbons (THC), nonmethane hydrocarbons (NMHC), benzene), and ocular posterior segment diseases (glaucoma, age-related macular degeneration (AMD), and retinal vascular diseases) were included., Results: Nineteen research articles met the inclusion criteria. Significant associations were found between PM 2.5 and glaucoma, including primary open angle, primary angle closure, and normal tension glaucoma. An increased risk of AMD was linked to increased exposure to PM 2.5 , NO 2 , and CO. Single studies suggested that increased exposure to PM 2.5 and PM 10 is associated with diabetic retinopathy; THC and NMHC increased the risk of retinal vein occlusion; and CO, NO 2 , and PM 10 are linked to an increased risk of central retinal artery occlusion., Conclusions: There is increasing evidence that toxic air pollutants have an impact on posterior segment ocular diseases, hence determining it as a potential modifiable risk factor for visual impairment.

Salvinal is a natural lignan isolated from the roots of Salvia mitorrhiza Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, with IC 50 values ranging from 4-17 µM. In this study, a series of salvinal derivatives was synthesized and evaluated for the structure-activity relationship. Among the twenty-four salvinal derivatives, six compounds showed better anticancer activity than salvinal. Compound 25 displayed excellent anticancer activity, with IC 50 values of 0.13-0.14 µM against KB, KB-Vin10 (overexpress MDR/Pgp), and KB-7D (overexpress MRP) human carcinoma cell lines. Based on our in vitro microtubule depolymerization assay, compound 25 showed depolymerization activity in a dose-dependent manner. Our findings indicate that compound 25 is a promising anticancer agent with depolymerization activity that has potential for the management of malignance.

Clinical Relevance: Despite evidence showing that optometry-led collaborative glaucoma care can be delivered at reduced cost compared to ophthalmology-based care without compromising patient outcomes, such models of care are not widely practiced in Australia. Ensuring glaucoma patients have equitable access to effective and cost-effective care is a matter of public health importance., Background: This study examined the feasibility and business case assessment for providing glaucoma care from a community optometry perspective., Methods: Nine optometrists were interviewed in a semi-structured format, focusing on the economic feasibility, barriers, and benefits of collaborative glaucoma care. The Consolidated Framework for Intervention Research was used for thematic data analysis. Costs and revenues associated with providing glaucoma care were sourced from the literature and interviews. A business case model assessing the profitability of glaucoma care in optometric practice was developed., Results: Thematic analysis revealed concerns over financial viability such that current Medicare Benefits Schedule fees are not sufficient to justify the cost of running a community optometry glaucoma clinic. All participants received a supplementary source of revenue. This finding was confirmed by the business case assessment. Inter-professional trust was perceived to be a key barrier to initiation of collaborative care however was able to be overcome quickly upon commencement of a collaborative care relationship. Optometrists perceived that collaborative care was beneficial to all involved, including patients, ophthalmologists, optometrists, and health payers. There was a perception of a growing divide between clinical and retail optometry, which was thought by most participants to be appropriate., Conclusion: This study is the first to explore the feasibility and business case for community-based optometrists to provide collaborative glaucoma care in Australia. Our findings show that current public funding is insufficient to justify the business case to private optometry practice, despite being perceived by optometrists as beneficial to all involved.

For rapid and unlimited cell growth and proliferation, cancer cells require large quantities of nutrients. Many metabolic pathways and nutrient uptake systems are frequently reprogrammed and upregulated to meet the demand from cancer cells, including the demand for lipids. The lipids for most adult normal cells are mainly acquired from the circulatory system. Whether different cancer cells adopt identical mechanisms to ensure sufficient lipid supply, and whether the lipid demand and supply meet each other, remains unclear, and was investigated in lung cancer cells. Results showed that, despite frequent upregulation in de novo lipogenesis and the lipid transporter system, different lung cancer cells adopt different proteins to acquire sufficient lipids, and the lipid supply frequently exceeds the demand, as significant amounts of lipids stored in the lipid droplets could be found within lung cancer cells. Lipid droplet surface protein, PLIN3, was found frequently overexpressed since the early stage in lung cancer tissues. Although the expression is not significantly associated with a specific gender, age, histology type, disease stage, and smoking habit, the frequently elevated expression of PLIN3 protein indicates the importance of lipid droplets for lung cancer. These lipid droplets are not only for nutrient storage, but are also crucial for tumor growth and proliferation, as well as survival in starvation. These results suggest that manipulation of lipid droplet formation or TG storage in lung cancer cells could potentially decrease the progression of lung cancer. Further exploration of lipid biology in lung cancer could help design novel treatment strategies.

Cataract surgery is a safe, effective and common elective procedure in Australia but access is inequitable. True waiting times for cataract care are undisclosed or inconsistently reported by governments. Estimates of true waiting times range from 4 to 30 months and have been extended during the coronavirus disease 2019 (COVID-19) pandemic. Comparative analysis revealed that reducing waiting periods from 12 to 3 months would result in estimated public health system cost savings of $6.6 million by preventing 50 679 falls. Investment in public cataract services to address current unmet needs would prevent avoidable vision impairment and associated negative consequences., Competing Interests: None declared

Objective: To compare fall incidence, and visual acuity and refractive status, before surgery and after first and second eye cataract surgery., Design, Setting: Prospective observational study in eight tertiary referral ophthalmology clinics in public hospitals in Sydney, Melbourne, and Perth., Participants: People aged 65 years or more referred for bilateral age-related cataract surgery during 2013-16, followed for maximum of 24 months after study entry or until six months after second eye surgery, whichever was shorter., Main Outcome Measures: Primary outcome: age- and sex-adjusted incidence of falls., Secondary Outcomes: visual acuity and refractive error., Results: The mean age of the 409 included participants was 75.4 years (SD, 5.4 years); 220 were women (54%). Age- and sex-adjusted fall incidence prior to surgery was 1.17 (95% CI, 0.95-1.43) per year, 0.81 (95% CI, 0.63-1.04) per year after first eye surgery, and 0.41 (95% CI, 0.29-0.57) per year after second eye surgery. For the 118 participants who underwent second eye surgery and participated in all follow-up visits, age- and sex-adjusted incidence before (0.80 [95% CI, 0.55-1.15] falls per year) and after first eye surgery (0.81 [95% CI, 0.57-1.15] falls per year) was similar, but was lower after second eye surgery (0.32 [95% CI 0.21-0.50] falls per year). Mean habitual binocular visual acuity (logMAR) was 0.32 (SD, 0.21) before surgery, 0.15 (SD, 0.17) after first eye surgery, and 0.07 (SD, 0.15) after second eye surgery., Conclusions: First eye surgery substantially improves vision in older people with cataract, but second eye surgery is required to minimise fall incidence. Timely cataract surgery for both eyes not only optimises vision in older people with cataract, but also reduces their risk of injury from falls., (© 2022 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

ROS1 fusion genes are rare but important driver genes in lung cancer. Owing to their rarity, many clinicopathological features and treatment responses for each ROS1 fusion variant are still largely unknown and require further investigation. RNA is the preferable template for the ROS1 fusion gene screening, but deterioration of RNA in FFPE often makes the detection challenging. To resolve the difficulty, a targeted chromosomal breakpoint sequencing method was developed for searching the ROS1 fusion gene, and was compared with fluorescence in situ hybridization, immunohistochemistry, RT-qPCR using 260 lung cancer samples of Southern Taiwan. The results showed that ROS1 -altered cases were present at low frequencies, did not share distinct clinicopathological features, and often carried other driver mutations. The performance of the targeted sequencing assay was superior to the RT-qPCR in ROS1 fusion gene identification when the cDNAs were from FFPE samples, but long-read DNA sequencing and fresh-frozen samples would be better to revolve all fusion genes. Precise determination of all ROS1 fusion variants and concomitant driver mutations using both genomic DNA and RNA would be required to help improve the treatment of patients with ROS1 alterations., Competing Interests: None., (AJCR Copyright © 2022.)

Purpose: To project the prevalence, causes, associated factors of vision-related disability and demand for orientation and mobility (O&M) services in Australia from 2020 to 2060., Methods: The age-specific prevalence and main causes of vision-related disability were estimated based on primary data of 74,862 participants in 2015 Survey of Disability, Ageing and Carers. Logistic regression analyses were performed to identify associated factors for the outcome variables including vision-related disability, cataract, macular degeneration and glaucoma. Future prevalence of vision-related disability and demand for O&M services were forecasted using the population projections by the Australian Bureau of Statistics through 2060., Results: The main causes of vision-related disability are non-specific sight loss, cataracts, macular degeneration and glaucoma. Health-related associations for vision-related disability are older age, having a history of stroke, having diabetes, depression, heart disease and hearing impairment. The number of Australians with vision-related disability (283,650, 1.10%) and demand for O&M services (123,317, 0.48%) in 2020 will increase to 559,161 (1.38%) and 237,694 (0.59%) respectively in 2060., Conclusions: The number of people with vision-related disability and in need of O&M services in Australia will grow exponentially over the coming decades. General health promotion and specific strategies of early detection and timely treatments of the major eye diseases may ameliorate the trend in vision-related disability.

Cullin 4A (Cul4A) reportedly has oncogenic roles in several cancer types by regulating tumor suppressors through the ubiquitination and proteolysis of the tumor suppressor. In addition, Cul4A is associated with chemosensitivity to chemotherapy drugs. This study investigated the association between Cul4A and lung cancer cell chemosensitivity to paclitaxel, particularly with respect to the role of the p33 inhibitor of the growth 1 (p33ING1b) tumor suppressor. The results showed that the Cul4A knockdown upregulated the p33ING1b expression in lung cancer cells and increased the lung cancer cell and mice tumor xenograft chemosensitivity to paclitaxel. The Cul4A knockdown also inhibited the growth and increased the apoptosis in the tumor xenografts treated with paclitaxel. Notably, the p33ING1b overexpression increased the lung cancer cell chemosensitivity to paclitaxel, but the p33ING1b knockdown reduced the chemosensitivity. A further analysis demonstrated that Cul4A regulates the expression of p33ING1b through protein-protein interactions, ubiquitination, and protein degradation. In conclusion, the present findings suggest that Cul4A mediates the chemosensitivity of lung cancer cells to paclitaxel by regulating p33ING1b. These findings may offer novel insights into future therapeutic strategies for lung cancer that target Cul4A., Competing Interests: None., (AJTR Copyright © 2021.)

Genetic mutations accumulated overtime could generate many growth and survival advantages for cancer cells, but these mutations also mark cancer cells as targets to be eliminated by the immune system. To evade immune surveillance, cancer cells adopted different intrinsic molecules to suppress immune response. PD-L1 is frequently overexpressed in many cancer cells, and its engagement with PD-1 on T cells diminishes the extent of cytotoxicity from the immune system. To resume immunity for fighting cancer, several therapeutic antibodies disrupting the PD-1/PD-L1 interaction have been introduced in clinical practice. However, their immunogenicity, low tissue penetrance, and high production costs rendered these antibodies beneficial to only a limited number of patients. PD-L1 dimer formation shields the interaction interface for PD-1 binding; hence, screening for small molecule compounds stabilizing the PD-L1 dimer may make immune therapy more effective and widely affordable. In the current study, 111 candidates were selected from over 180,000 natural compound structures through virtual screening, contact fingerprint analysis, and pharmacological property prediction. Twenty-two representative candidates were further evaluated in vitro. Two compounds were found capable of inhibiting the PD-1/PD-L1 interaction and promoting PD-L1 dimer formation. Further structure optimization and clinical development of these lead inhibitors will eventually lead to more effective and affordable immunotherapeutic drugs for cancer patients.

Mutations that lead to constitutive activation of key regulators in cellular processes are one of the most important drivers behind vigorous growth of cancer cells, and are thus prime targets in cancer treatment. BRAF V600E mutation transduces strong growth and survival signals for cancer cells, and is widely present in various types of cancers including lung cancer. A combination of BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) has recently been approved and significantly improved the survival of patients with advanced NSCLC harboring BRAF V600E/K mutation. To improve the detection of BRAF V600E/K mutation and investigate the incidence and clinicopathological features of the mutation in lung cancer patients of southern Taiwan, a highly sensitive and specific real-time quantitative PCR (RT-qPCR) method, able to detect single-digit copies of mutant DNA, was established and compared with BRAF V600E-specific immunohistochemistry. Results showed that the BRAF V600E mutation was present at low frequency (0.65%, 2/306) in the studied patient group, and the detection sensitivity and specificity of the new RT-qPCR and V600E-specific immunohistochemistry both reached 100% and 97.6%, respectively. Screening the BRAF V600E/K mutation with the RT-qPCR and V600E-specific immunohistochemistry simultaneously could help improve detection accuracy.

An outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan and it has rapidly spread to almost all parts of the world. For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an important polymerase that catalyzes the replication of RNA from RNA template and is an attractive therapeutic target. In this study, we screened these chemical structures from traditional Chinese medicinal compounds proven to show antiviral activity in severe acute respiratory syndrome coronavirus (SARS-CoV) and the similar chemical structures through a molecular docking study to target RdRp of SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS-CoV-2 (-9.11 kcal/mol), SARS-CoV (-8.03 kcal/mol), and MERS-CoV (-8.26 kcal/mol) from idock. To confirm the result, we discovered that theaflavin has lower binding energy of -8.8 kcal/mol when it docks in the catalytic pocket of SARS-CoV-2 RdRp by using the Blind Docking server. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp. Moreover, one π-cation interaction was formed between theaflavin and Arg553 from the Blind Docking server. Our results suggest that theaflavin could be a potential SARS-CoV-2 RdRp inhibitor for further study., (© 2020 Wiley Periodicals, Inc.)

Somatic mutations of MET gene are emerging as important driver mutations for lung cancers. To identify the common clinicopathological features of MET exon 14 skipping mutations and amplification and clarify whether the two MET gene alterations cause protein overexpression were investigated using 196 lung cancer samples of Taiwan through real time-qPCR/sequencing, fluorescence in situ hybridization, and immunohistochemistry. The two MET gene alterations are both present in low frequency, ~1%, in the studied lung cancer population of Taiwan. MET exon 14 skipping mutations were identified from two early-stage patients, who were both relatively advanced in age, and did not carry other driver mutations. One was an adenocarcinoma and the other was a rare carcinosarcoma. Three gene amplifications cases were identified. Neither of the two MET gene alterations would lead to protein overexpression; hence, direct detection in nucleic acid level would be a preferred and straightforward solution for the identification of skipping mutations. The presence of MET exon 14 mutations in minor histological types of lung cancers urge to extend screening scope of this mutation in lung cancer and treatment response evaluation in clinical trials. These would be important next steps for the success of MET target therapy in clinical practice., Competing Interests: The authors have declared that no competing interests exist.

Introduction: A 22-year-old female presented with a large abdominal mass that was revealed to be a primary retroperitoneal mucinous cystadenoma., Presentation of Case: A 22-year-old female presented with a two day history of bloating, mid-epigastric pain, and nausea without vomiting. A CT scan of her abdomen/pelvis showed a large left retroperitoneal mass, possibly a mesenteric cyst. The patient underwent laparoscopic surgery for mass excision. Once the cystic mass was completely dissected laparoscopically, it was placed in a large endobag. The fluid was then aspirated while in the bag to decompress and then completely taken out through a port site. She was discharged the following day. Final pathology revealed a benign mucinous cystadenoma/cystadenofibroma of mesenteric origin., Discussion: Primary retroperitoneal mucinous cysts are rare occurrences and benign mucinous cystadenomas are the rarest subtype. We use an innovative laparoscopic technique with complete excision of the cyst without spillage of content, thus preventing possible seeding in case of malignancy., Conclusion: There is some previous caution in using a laparoscopic approach for cystic masses due to potential seeding intra-operatively, in case of fluid spillage of a possible malignant neoplasm. We show through our case that it is possible to efficiently and safely use such an approach., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: The aim of the present study was to determine the prevalence of temporomandibular disorder (TMD) symptoms among dentistry students at James Cook University in Australia, and to determine the associations of TMD symptoms with demographic parameters and compare the prevalence to that of the Australian general population., Methods: The study was conducted at the School of Dentistry, James Cook University. Axis I symptom questionnaire of diagnostic criteria for TMD was used to assess the prevalence of TMD symptoms. Additional questions were included to gather demographic information on the participants. Data were collected anonymously via the online survey tool, SurveyMonkey., Results: The overall prevalence of TMD symptoms in this cohort was 77.2%. The most common TMD symptoms were pain (48.5%) and joint noises (48.5%). Females reported a significantly higher prevalence of TMD symptoms than males, with 73 of 88 female respondents (83%) and 32 of 48 male respondents (66.7%) reporting at least one symptom of TMD (P = .030)., Conclusions: The overall prevalence of TMD symptoms in the population studied was 77.2%, with female preponderance of TMD symptoms (83%). This is higher than the estimated prevalence (23%) in the Australian general population., (© 2018 John Wiley & Sons Australia, Ltd.)

In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the in vivo protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive compound in danshen, exerts anticancer effects through many pathways. First, 10 μM DT substantially inhibited the migration ability of lung cancer cells in both macrophage and macrophage/lung cancer direct mixed coculture media. Second, 10 μM DT repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), the protein expression of S-phase kinase associated protein-2 (Skp2), and the mRNA levels of STAT3-related genes, including chemokine (C-C motif) ligand 2 (CCL2). In addition, 10 μM DT suppressed the macrophage recruitment ability of lung cancer cells by reducing CCL2 secretion from both macrophages and lung cancer cells. Third, 20 μM DT induced apoptosis in lung cancer cells. Furthermore, DT treatment significantly inhibited the final tumor volume in a xenograft nude mouse model. In conclusion, danshen exerts protective efforts in patients with advanced lung cancer. These effects can be attributed to DT-mediated interruption of the cross talk between lung cancer cells and macrophages and blocking of lung cancer cell proliferation., Competing Interests: CONFLICTS OF INTERESTS The authors declare no competing financial interests.

High mobility group AT-hook 2 (HMGA2) is an architectural transcription factor that is negatively regulated by let-7 microRNA through binding to it's 3'-untranslated region. Transgenic mice expressing Hmga2 with a truncation of its 3'-untranslated region has been shown to exhibit a myeloproliferative phenotype. To decipher the let-7-HMGA2 axis in myeloproliferative neoplasms, we employed an in vitro model supplemented with clinical correlation. Ba/F3 cells with inducible JAK2 V617F expression (Ton.JAK2.V617F cells) showed upregulation of HMGA2 with concurrent let-7a repression. Ton.JAK2.V617F cells treated with a let-7a inhibitor exhibited further escalation of Hmga2 expression, while a let-7a mimic diminished the Hmga2 transcript level. Hmga2 overexpression conferred JAK2 -mutated cells with a survival advantage through inhibited apoptosis. A pan-JAK inhibitor, INC424, increased the expression of let-7a , downregulated the level of Hmga2 , and led to increased apoptosis in Ton.JAK2.V617F cells in a dose-dependent manner. In samples from 151 patients with myeloproliferative neoplasms, there was a modest inverse correlation between the expression levels of let-7a and HMGA2 Overexpression of HMGA2 was detected in 29 (19.2%) of the cases, and it was more commonly seen in patients with essential thrombocythemia than in those with polycythemia vera (26.9% vs 12.7%, P =0.044). Patients with upregulated HMGA2 showed an increased propensity for developing major thrombotic events, and they were more likely to harbor one of the 3 driver myeloproliferative neoplasm mutations in JAK2 , MPL and CALR Our findings suggest that, in a subset of myeloproliferative neoplasm patients, the let-7-HMGA2 axis plays a prominent role in the pathogenesis of the disease that leads to unique clinical phenotypes., (Copyright© Ferrata Storti Foundation.)

Objectives: Complex and multiple mechanisms are involved in the etiology of Hepatitis C virus-associated immune thrombocytopenia (HCV-ITP). Many hematopoietic growth factors affect the thrombopoiesis. The aim of this study was to clarify the interaction of the thrombopoietic factors in patients with HCV-ITP., Methods: We selected 33 patients with HCV-ITP and 17 normal individuals. We compare serum interleukin (IL)-3, IL-6, IL-11, thrombopoietin (Tpo), stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-α (TNFα), and spleen size between these two groups., Results: Our study shows that Tpo, IL-6, and TNFα significantly increased in patients with HCV-ITP compared to the normal population (Tpo:122.577 vs. 40.602; IL-6: 2.175 vs. 0.943; TNFα: 2.460 vs. 1.322). IL-11 was significantly lower in the HCV-ITP group (10.829 vs. 15.042). HCV-ITP patients had a higher spleen index (21.121 vs 13.498, P = 0.003). According to regression analysis and multiple linear regression analysis, only IL-11 had a significantly positive correlation with platelet count, while TNFα showed a negative correlation., Discussions: Tpo and IL-6 increased in patients with HCV-ITP, suggesting a positive feedback of low platelet count. TNFα-associated immune response is suspected to have an impact on low platelet count. IL-11 is assumed to directly affect thrombopoiesis., Conclusions: This study is the most comprehensive study to evaluate the interaction between platelet count and the important thrombopoetic factors in patients with HCV-ITP. The thrombopoietic factors clearly play an important role in HCV-ITP.

Background: Somatic mutations of Janus kinase 2 (JAK2V617F), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) are the major clonal molecules that drive the pathogenesis of myeloproliferative neoplasms (MPN). It is well recognized that MPN patients carry an excessive risk of thrombohemorrhagic complications. However, little is known about the prevalence of these clonal markers in patients with cerebral vascular disease., Methods: To address this issue, 153 consecutive stroke patients in Taiwan were enrolled in the study. Allele-specific PCR (AS-PCR), real-time AS-PCR, and Illumina paired-end sequencing were employed to detect the presence of MPL, JAK2V617F, and CALR exon 9 mutations, respectively., Results: JAK2V617F mutation was detectable in 13 samples (8.5%), but the allele burdens (AB) were greater than 1% in only six (3.9%) of them. Compared to JAK2-unmutated patients, those with JAK2V617F AB &gt; 1% had significantly higher white blood count (p = 0.01), although four of the six did not exhibit MPN phenotypes. Two patients had a heterozygous CALR exon9 mutation locating outside the coding region and did not alter the amino acid sequence of this protein. On the other hand, there were no patients carrying the MPL mutations. Using patient age, baseline hemogram, and stroke-relevant risk factors, we developed a predictive model that could successfully identify stroke patients at risk of carrying clonal JAK2V617F mutation., Conclusion: The prevalence of JAK2V617F mutation in stroke patients was higher than that seen in general population. Based on our newly developed probability stratification model, genotyping of JAK2V617F mutation in selected patients with stroke might be warranted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)