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Abstract Background Arginine deprivation was previously shown to inhibit retinoblastoma cell proliferation and induce cell death in vitro. However, the mechanisms by which retinoblastoma cells respond to arginine deprivation remain to be elucidated. Methods The human-derived retinoblastoma cell lines Y79 and WERI-Rb-1 were subjected to arginine depletion, and the effects on inhibiting cell growth and survival were evaluated. This study investigated potential mechanisms, including autophagy, cell cycle arrest and apoptosis. Moreover, the roles of the general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1) signaling pathways in these processes were examined. Results We demonstrated that arginine deprivation effectively inhibited the growth of retinoblastoma cells in vitro. This treatment caused an increase in the autophagic response. Additionally, prolonged arginine deprivation induced G2 cell cycle arrest and was accompanied by an increase in early apoptotic cells. Importantly, arginine depletion also induced the activation of GCN2 and the inhibition of mTOR signaling. We also discovered that the activation of SLC7A11 was regulated by GCN2 upon arginine deprivation. Knockdown of SLC7A11 rendered retinoblastoma cells partially resistant to arginine deprivation. Furthermore, we found that knockdown of GCN2 led to a decrease in the autophagic response in WERI-Rb-1 cells and arrested more cells in S phase, which was accompanied by fewer apoptotic cells. Moreover, knockdown of GCN2 induced the constant expression of ATF4 and the phosphorylation of 70S6K and 4E-BP1 regardless of arginine deprivation. Conclusions Collectively, our findings suggest that the GCN2‒SLC7A11 axis regulates cell growth and survival upon arginine deprivation through coordinating autophagy, cell cycle arrest, and apoptosis in retinoblastoma cells. This work paves the way for the development of a novel treatment for retinoblastoma.

Abstract The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p

Purpose: This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. Methods: A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. Results: A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60–0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. Conclusion: TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

This study explores the potential of Artificial Intelligence (AI) in early screening and prognosis of Dry Eye Disease (DED), aiming to enhance the accuracy of therapeutic approaches for eye-care practitioners. Despite the promising opportunities, challenges such as diverse diagnostic evidence, complex etiology, and interdisciplinary knowledge integration impede the interpretability, reliability, and applicability of AI-based DED detection methods. The research conducts a comprehensive review of datasets, diagnostic evidence, and standards, as well as advanced algorithms in AI-based DED detection over the past five years. The DED diagnostic methods are categorized into three groups based on their relationship with AI techniques: (1) those with ground truth and/or comparable standards, (2) potential AI-based methods with significant advantages, and (3) supplementary methods for AI-based DED detection. The study proposes suggested DED detection standards, the combination of multiple diagnostic evidence, and future research directions to guide further investigations. Ultimately, the research contributes to the advancement of ophthalmic disease detection by providing insights into knowledge foundations, advanced methods, challenges, and potential future perspectives, emphasizing the significant role of AI in both academic and practical aspects of ophthalmology.

Objective: Brown adipose tissue (BAT) plays an important role in mammalian thermogenesis through the expression of uncoupling protein 1 (UCP1). Our previous study identified cytoplasmic polyadenylation element binding protein 2 (CPEB2) as a key regulator that activates the translation of Ucp1 with a long 3′-untranslated region (Ucp1L) in response to adrenergic signaling. Mice lacking CPEB2 or Ucp1L exhibited reduced UCP1 expression and impaired thermogenesis; however, only CPEB2-null mice displayed obesogenic phenotypes. Hence, this study aims to investigate how CPEB2-controlled translation impacts body weight. Methods: Body weight measurements were conducted on mice with global knockout (KO) of CPEB2, UCP1 or Ucp1L, as well as those with conditional knockout of CPEB2 in neurons or adipose tissues. RNA sequencing coupled with bioinformatics analysis was used to identify dysregulated gene expression in CPEB2-deficient BAT. The role of CPEB2 in regulating PRD1-BF1-RIZ1 homologous-domain containing 16 (PRDM16) expression was subsequently confirmed by RT-qPCR, Western blotting, polysomal profiling and luciferase reporter assays. Adeno-associated viruses (AAV) expressing CPEB2 or PRDM16 were delivered into BAT to assess their efficacy in mitigating weight gain in CPEB2-KO mice. Results: We validated that defective BAT function contributed to the increased weight gain in CPEB2-KO mice. Transcriptomic profiling revealed upregulated expression of genes associated with muscle development in CPEB2-KO BAT. Given that both brown adipocytes and myocytes stem from myogenic factor 5-expressing precursors, with their cell-fate differentiation regulated by PRDM16, we identified that Prdm16 was translationally upregulated by CPEB2. Ectopic expression of PRDM16 in CPEB2-deprived BAT restored gene expression profiles and decreased weight gain in CPEB2-KO mice. Conclusions: In addition to Ucp1L, activation of Prdm16 translation by CPEB2 is critical for sustaining brown adipocyte function. These findings unveil a new layer of post-transcriptional regulation governed by CPEB2, fine-tuning thermogenic and metabolic activities of brown adipocytes to control body weight.

IntroductionIn DBS for patients with PD, STN is the most common DBS target with the sweet point located dorsal ipsilaterally adjacent to the pyramidal tract. During awake DBS lead implantation, macrostimulation is performed to test the clinical effects and side effects especially the pyramidal tract side effect (PTSE) threshold. A too low PTSE threshold will compromise the therapeutic stimulation window. When DBS lead implantation is performed under general anaesthesia (GA), there is a lack of real time feedback regarding the PTSE. In this study, we evaluated the macrostimulation-induced PTSE by electromyography (EMG) during DBS surgery under GA. Our aim is to investigate the prediction of post-operative programming PTSE threshold using EMG-based PTSE threshold, and its potential application to guide intra-operative lead implantation.Methods44 patients with advanced PD received STN DBS under GA were studied. Intra-operative macrostimulation via EMG was assessed from the contralateral upper limb. EMG signal activation was defined as the amplitude doubling or greater than the base line. In the first programming session at one month post-operation, the PTSE threshold was documented. All patients were followed up for one year to assess clinical outcome.ResultsAll 44 cases (88 sides) demonstrated activations of limb EMG via increasing amplitude of macrostimulation the contralateral STN under GA. Revision tracts were explored in 7 patients due to a low EMG activation threshold (

Abstract Concrete is commonly employed in construction for its tremendous compressive strength, despite its low tensile strength. This study aimed at analyzing the strength of concrete when mixed with water of varying qualities. Before concrete is formulated, tests are done on the aggregates to ascertain the right proportions but not on water used. Dreux-Gorrise concrete formulation method was employed. CAMWATER (tap water), rain water and water from a free-flowing river was used to cast concrete samples after which it was crushed to obtain 7 and 28 day resistances. The water qualities varied were pH and hardness. Hydrochloric acid and sodium hydroxide were used to vary the pH of water. Results showed an increase in concrete strength as a function of increase in water pH. Water with a high pH resulted in concrete with an appreciable strength value while acidic water resulted in very low strength values. The usage of hard water for mixing concrete resulted in a strength value lower than with soft water. Conclusively, water quality has an effect on the strength of concrete. Therefore, it is advisable to use water with a high pH value for mixing concrete, preferring rainwater over tap water when mixing concrete due to hardness of water.

Abstract Background Patient experiences and survival outcomes can be influenced by the circumstances related to dialysis initiation and subsequent modality choices. This systematic review and meta-analysis aimed to explore the rate and reasons for peritoneal dialysis (PD) dropout following haemodialysis (HD) to PD switch. Method This systematic review conducted searches in four databases, including Medline, PubMed, Embase, and Cochrane. The protocol was registered on PROSPERO (study ID: CRD42023405718). Outcomes included factors leading to the switch from HD to PD, the rate and reasons for PD dropout and mortality difference in two groups (PD first group versus HD to PD group). The Critical Appraisal Skills Programme (CASP) checklist and the GRADE tool were used to assess quality. Results 4971 papers were detected, and 13 studies were included. On meta-analysis, there was no statistically significant difference in PD dropout in the PD first group (OR: 0.81; 95%CI: 0.61, 1.09; I2 = 83%; P = 0.16), however, there was a statistically significant reduction in the rate of mortality (OR: 0.48; 95%CI: 0.25, 0.92; I2 = 73%; P = 0.03) compared to the HD to PD group. The primary reasons for HD to PD switch, included vascular access failure, patient preference, social issues, and cardiovascular disease. Causes for PD dropout differed between the two groups, but inadequate dialysis and peritonitis were the main reasons for PD dropout in both groups. Conclusion Compared to the PD first group, a previous HD history may not impact PD dropout rates for patients, but it could impact mortality in the HD to PD group. The reasons for PD dropout differed between the two groups, with no statistical differences. Psychosocial reasons for PD dropout are valuable to further research. Additionally, establishing a consensus on the definition of PD dropout is crucial for future studies.

ABSTRACTIn the automotive industry, the extended design and iteration cycles for integrated chassis typically span 2–3 years, creating a misalignment with swiftly changing market demands. Wire arc additive manufacturing (WAAM) technology presents a viable alternative, overcoming the limitations of conventional chassis production. Our holistic framework significantly condenses the design, optimisation, and validation stages for automotive chassis. Initially, a ground structure method is utilised to outline and generate a skeleton chassis. We then utilise the OpenCV image processing method to select a hollow skeleton chassis with minimal material occupancy (0.476) and suspension printing. Subsequently, we assess the influence of printing radian variations by the robotic arm on the microstructure and stress, employing a cellular automaton-finite element (CA-FE) model at the 150th and 200th layer benchmarks. A Kalman filter (KF) is also implemented to fine-tune the printing radian in regions with coarse grain structures and elevated solute concentrations. The process concludes with collision and modal simulation verifications of the skeleton chassis, affirming the optimisation's success. This streamlined methodology allows the completion of the chassis design and manufacturing cycle within a remarkably condensed time frame of one week, accelerating the development process by a factor of 120.

Investing in climate change mitigation and adaptation has become a promising approach to address the negative impacts of climate change on the environment and to encourage efforts to adjust to changing conditions. Climate funding is a kind of foreign aid that seeks to reduce carbon dioxide emissions and promote ecologically sustainable economic development. However, it is not quite clear to what extent it helps recipient countries transition to low-carbon pathways. This research examines the worldwide flow of climate finance from 1999 to 2017 to determine the impact of climate funds on reducing carbon emissions and promoting sustainable development in recipient countries. The data suggest a potential correlation between climate funding and the reduction of carbon emissions, with investments in mitigation seeming to have a greater impact than spending on adaptation. Furthermore, countries that have achieved significant economic progress and Small Island developing states stand to benefit more from climate aid aimed at reducing emissions. This is due to the fact that both sorts of nations exhibit greater rates of economic growth. These results are significant for policymakers, who may use them to accelerate the transition to net-zero combustion levels and enhance environmental sustainability.

Breast cancer (BC) is the prevailing malignancy among women, with HER2 overexpression observed in 20–30 % of all BC, thereby serving as a prognostic indicator for unfavorable outcomes in affected individuals. There is a necessity to establish innovative treatment protocols to expand the therapeutic alternatives accessible for managing HER2-positive BC. In this study, we report a case of HER2-positive BC that was managed in our department using a combination of three targeted drugs (Trastuzumab, Pertuzumab and Pyrotinib) along with chemotherapy. The treatment resulted in a pathological complete response (pCR) and was observed to be well-tolerated, without any significant adverse reactions. Hence, the combination of Pyrotinib and Dual HER2 blockade treatment shows promise as a neoadjuvant therapy for locally advanced HER2-positive BC to achieve a pCR in surgery. Nevertheless, this conclusion necessitates additional validation via meticulously designed clinical research investigations encompassing larger patient populations.

BackgroundBreast cancer is a significant public health issue, exhibiting the most pronounced occurrence and fatality rates among malignant neoplasms globally. Targeted therapy is a medical intervention that focuses on specific molecular markers. This study aims to investigate and evaluate the current research trends and directions in the field of targeted therapy for breast cancer using bibliometric analysis.MethodThe Web of Science database was utilized to retrieve relevant articles published between 2003 and 2022. The VOSviewer software and Bibliometrix package in the R language were employed to conduct co-occurrence and clustering analyses of authors, countries, institutions, journals, references, and the CiteSpace tool was utilized for keyword burst detection.ResultsA total of 2,258 articles were included and the annual number of publications increased rapidly. The most prolific country on this topic was the USA (n=898, 39.77%) and the University of Texas MD Anderson Cancer Center published most papers (n=93). Dennis J. Slamon and Gabriel N. Hortobagyi stood out in the field, with Dennis J. Slamon leading in terms of co-citations(n=653) and Gabriel N. Hortobagyi topping the list in terms of published articles(n=18). The most productive journal was Breast Cancer Research and Treatment and the most cited journal was Journal of Clinical Oncology. The clustering of keywords indicated that the primary focus of researches in the past two decades was on the development and clinical evaluation of tumor-targeted drugs associated with the epidermal growth factor receptor (EGFR) family signaling pathway, and explored mechanisms related to biological behavior of breast cancer. Keywords co-occurrence and burst analysis identified current research hotspots and potential research trends.ConclusionThis study employed bibliometric analysis to examine research on targeted therapy for breast cancer over a span of 20 years, and identified development trends of research and elucidated potential research trajectories in the domain of this topic. This study helps in the identification of prospective collaborators and partner institutions for researchers.

Background It has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine the effect of lung function impairments on lung cancer risks.Methods This was a retrospective cohort study (1 January 1994 to 31 December 2017) of individuals from a health surveillance programme in Taiwan who underwent baseline spirometry tests at the entry point. PRISm was defined as an FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >0.7 and FEV1

Chuqian Chen,1,&ast; Qinglu Wu,2,&ast; Junfeng Zhao,3 Guoxiang Zhao,4 Xiaoming Li,5 Hongfei Du,2 Peilian Chi6,7 1Department of Medical Humanities, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Institute of Advanced Studies in Humanities and Social Sciences, Beijing Normal University, Zhuhai, Guangdong, People’s Republic of China; 3Institute of Psychology and Behavior, Henan University, Kaifeng, Henan, People’s Republic of China; 4Department of Psychology, Henan Normal University, Xinxiang, Henan, People’s Republic of China; 5Department of Health Promotion, Education, and Behavior, University of South Carolina, Columbia, SC, USA; 6Department of Psychology, Faculty of Social Sciences, University of Macau, Macau, People’s Republic of China; 7Centre for Cognitive and Brain Sciences, University of Macau, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peilian Chi, Department of Psychology, Faculty of Social Sciences, University of Macau, Mailing: E21-3049, Macau, 999078, People’s Republic of China, Tel +853 8822-4025, Email peilianchi@um.edu.moPurpose: The study aims to understand how enacted stigma influences bereavement coping at the style (scale) level and the specific pathways at the strategy (item) level.Methods: The longitudinal data of 755 children orphaned by parental Acquired Immune Deficiency Syndrome (AIDS) in rural China were used. Grief processing and deliberate grief avoidance were measured at wave 1 (baseline) and wave 2 (one-year follow-up) to reflect bereavement coping in the contexts of being with family members, being with friends, being with community members, and being alone. Enacted stigma that measured at wave 1 was used to assess the experienced stigma of these AIDS-orphaned children. Network analyses were run following regressions.Results: Controlling for demographics and baseline-level bereavement coping, multivariate regressions revealed that enacted stigma at wave 1 significantly predicted grief processing and deliberate grief avoidance at wave 2. Network analyses showed that, for grief processing, stigma increased searching for meaning alone and with friends and expressing feelings to community members, which then provoked the same strategy across contexts. Meanwhile, stigma triggered the deliberate grief avoidance network by initially suppressing the expression of feelings to community members.Conclusion: Enacted stigma contributes to bereavement coping. Stigma stirs up complex feelings but forces AIDS-orphaned children to suppress expressions, and it increases needs to process grief through meaning making but cuts supporting forces by promoting avoidance. Interventions are imperative to reduce stigma, improve emotion regulation, and facilitate meaning making for people bereaved by stigmatized deaths.Keywords: enacted stigma, bereavement coping, AIDS, orphans, network analysis, parental loss

Abstract Introduction The aim of this work is to determine the interocular differences in peripapillary retinal nerve fiber layer (p-RNFL) thickness and its associations among school children in Hong Kong. Methods We conducted a population-based study including 4034 children aged 6–8 years from the Hong Kong Children Eye Study (HKCES). All participants received comprehensive ocular examinations where p-RNFL thickness was measured using spectral-domain optical coherence tomography (SD-OCT). The degree of symmetry between both eyes was analyzed and represented by intraclass correlation coefficient (ICC) values. Multivariable linear regression analysis was used to investigate the associations between ocular and systemic factors with p-RNFL thickness difference. Results The study included 4034 children with a mean age of 7.61 ± 0.98 years. The mean global p-RNFL thickness was 106.60 ± 9.41 μm in right eyes and 105.99 ± 9.30 μm in left eyes. The ICC for global p-RNFL difference was 0.866 (95% CI 0.858–0.873, p

Abstract Failure to recognize samples from the classes unseen during training is a major limitation of artificial intelligence in the real-world implementation for recognition and classification of retinal anomalies. We establish an uncertainty-inspired open set (UIOS) model, which is trained with fundus images of 9 retinal conditions. Besides assessing the probability of each category, UIOS also calculates an uncertainty score to express its confidence. Our UIOS model with thresholding strategy achieves an F1 score of 99.55%, 97.01% and 91.91% for the internal testing set, external target categories (TC)-JSIEC dataset and TC-unseen testing set, respectively, compared to the F1 score of 92.20%, 80.69% and 64.74% by the standard AI model. Furthermore, UIOS correctly predicts high uncertainty scores, which would prompt the need for a manual check in the datasets of non-target categories retinal diseases, low-quality fundus images, and non-fundus images. UIOS provides a robust method for real-world screening of retinal anomalies.

Abstract Background A recent prospective demonstrated that cardiovascular risk factors in early childhood were associated with later cardiovascular events. However, the impact of secondhand smoke (SHS) on children is unclear. The aims of this study is to determine the effects of SHS exposure on the retinal vasculature of children. Methods This is a population-based cross-sectional study of children aged 6 to 8 years. All participants received comprehensive ophthalmic examinations and retinal photography. Data on SHS exposure was derived from a validated questionnaire. A validated deep-learning system was used to automatically estimate retinal arteriolar and venular calibers from retinal photographs. Associations of quantitative retinal vessel caliber values with SHS exposure, number of smokers in the household, and total number of cigarettes smoked were determined by analyses of covariance (ANCOVA) after adjusting for potential confounders. Test of trend was determined by treating categorical risk factors as continuous ordinal variables. Results Here we show children exposed to SHS have wider retinal arteriolar (CRAE 152.1 µm vs. 151.3 µm, p

Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.

Abstract Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.

Abstract Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ( $$P \, < \, 1.19\times {10}^{-8}$$ P < 1.19 × 10 − 8 ). Substantial genetic sharing between PCV and typical nAMD is noted (r g = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; $$P=1.05\times {10}^{-6}$$ P = 1.05 × 10 − 6 ) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.

In order to address the potential collision issue arising from multiple fixed-wing unmanned aerial vehicles (UAVs) intercepting targets in n-on-n and n-on-1 pursuit-evasion scenarios, we propose a collision-avoidance guidance strategy for UAVs based on high-order control barrier functions (HOCBFs). Initially, a two-dimensional model of multiple UAVs and targets is established, and the interaction between UAVs is determined. Subsequently, the collision-avoidance problem within a UAV swarm is formulated as a mathematical problem involving multiple constraints in the form of higher-order control obstacle functions. Multiple HOCBF constraints are then simplified into a single linear constraint for computational convenience. By integrating HOCBF constraints with quadratic programming problems, we obtain a closed-form solution for UAVs that incorporates collision-avoidance guidance terms alongside nominal guidance terms. Simulations with different numbers of pursuers and different target motion states are conducted. The results demonstrate an excellent experimental effect, ensuring that the multi-UAVs consistently remain above the minimum safe distance and ultimately hit the targets accurately.

Microwave-assisted de-emulsification is attractive in the processes of petroleum production and refining. The main advantage of microwaves is their direct influence on the surfactant layer at the oil/water interface. Previously, an effective interfacial modification was demonstrated by pulsed microwave irradiation. However, the effect of the modification diminished during the off interval of the pulse irradiation. In this study, two-stage microwave irradiation with different powers and durations was applied as a method to maintain an interfacial effect. The power of the second stage was changed to optimise the modification. Quick modification was obtained by high-power irradiation followed by low-power irradiation. It was confirmed a sustained modification was maintained by a moderate power of the second irradiation. This observation indicates a re-adsorption or re-structure process after the first irradiation is suppressed by the second irradiation. The results open new opportunities to optimise microwave operation in oil/water systems.

Abstract Background Aging is a dynamic and heterogeneous process that may better be captured by trajectories of aging biomarkers. Biological age has been advocated as a better biomarker of aging than chronological age, and plant-based dietary patterns have been found to be linked to aging. However, the associations of biological age trajectories with mortality and plant-based dietary patterns remained unclear. Methods Using group-based trajectory modeling approach, we identified distinctive aging trajectory groups among 12,784 participants based on a recently developed biological aging measure acquired at four-time points within an 8-year period. We then examined associations between aging trajectories and quintiles of plant-based dietary patterns assessed by overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) among 10,191 participants who had complete data on dietary intake, using multivariable multinomial logistics regression adjusting for sociodemographic and lifestyles factors. Cox proportional hazards regression models were applied to investigate the association between aging trajectories and all-cause mortality. Results We identified three latent classes of accelerated aging trajectories: slow aging, medium-degree, and high-degree accelerated aging trajectories. Participants who had higher PDI or hPDI had lower odds of being in medium-degree (OR = 0.75, 95% CI: 0.65, 0.86 for PDI; OR = 0.73, 95% CI: 0.62, 0.85 for hPDI) or high-degree (OR = 0.63, 95% CI: 0.46, 0.86 for PDI; OR = 0.62, 95% CI: 0.44, 0.88 for hPDI) accelerated aging trajectories. Participants in the highest quintile of uPDI were more likely to be in medium-degree (OR = 1.72, 95% CI: 1.48, 1.99) or high-degree (OR = 1.70, 95% CI: 1.21, 2.38) accelerated aging trajectories. With a mean follow-up time of 8.40 years and 803 (6.28%) participants died by the end of follow-up, we found that participants in medium-degree (HR = 1.56, 95% CI: 1.29, 1.89) or high-degree (HR = 3.72, 95% CI: 2.73, 5.08) accelerated aging trajectory groups had higher risks of death than those in the slow aging trajectory. Conclusions We identified three distinctive aging trajectories in a large Asian cohort and found that adopting a plant-based dietary pattern, especially when rich in healthful plant foods, was associated with substantially lowered pace of aging.

Abstract Background Higher fasting plasma glucose (FPG) levels were associated with an increased risk of all-cause mortality; however, the associations between long-term FPG trajectory groups and mortality were unclear, especially among individuals with a normal FPG level at the beginning. The aims of this study were to examine the associations of FPG trajectories with the risk of mortality and identify modifiable lifestyle factors related to these trajectories. Methods We enrolled 50,919 individuals aged ≥ 20 years old, who were free of diabetes at baseline, in the prospective MJ cohort. All participants completed at least four FPG measurements within 6 years after enrollment and were followed until December 2011. FPG trajectories were identified by group-based trajectory modeling. We used Cox proportional hazards models to examine the associations of FPG trajectories with mortality, adjusting for age, sex, marital status, education level, occupation, smoking, drinking, physical activity, body mass index, baseline FPG, hypertension, dyslipidemia, cardiovascular disease or stroke, and cancer. Associations between baseline lifestyle factors and FPG trajectories were evaluated using multinomial logistic regression. Results We identified three FPG trajectories as stable (n = 32,481), low-increasing (n = 17,164), and high-increasing (n = 1274). Compared to the stable group, both the low-increasing and high-increasing groups had higher risks of all-cause mortality (hazard ratio (HR) = 1.18 (95% CI 0.99–1.40) and 1.52 (95% CI 1.09–2.13), respectively), especially among those with hypertension. Compared to participants with 0 to 1 healthy lifestyle factor, those with 6 healthy lifestyle factors were more likely to be in the stable group (ORlow-increasing = 0.61, 95% CI 0.51–0.73; ORhigh-increasing = 0.20, 95% CI 0.13–0.32). Conclusions Individuals with longitudinally increasing FPG had a higher risk of mortality even if they had a normal FPG at baseline. Adopting healthy lifestyles may prevent individuals from transitioning into increasing trajectories.

Abstract Background Thyroid eye disease is an extrathyroidal manifestation of Graves’ disease and is associated with dry eye disease. This is the first systematic review and meta-analysis to evaluate the role of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease diagnosis, activity grading, and therapeutic responses prediction. Methods Up to 23 August, 2022, 504 studies from PubMed and Cochrane Library were analyzed. After removing duplicates and imposing selection criteria, nine eligible studies were included. Risk of bias assessment was done. Meta-analyses were performed using random-effect model if heterogeneity was significant. Otherwise, fixed-effect model was used. Main outcome measures include seven structural magnetic resonance imaging parameters (lacrimal gland herniation, maximum axial area, maximum coronal area, maximum axial length, maximum coronal length, maximum axial width, maximum coronal width), and three functional magnetic resonance imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-apparent diffusion coefficient or mean diffusivity, diffusion-weighted imaging-apparent diffusion coefficient). Results Thyroid eye disease showed larger maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width, diffusion tensor imaging-apparent diffusion coefficient/ mean diffusivity, and lower diffusion tensor imaging-fractional anisotropy than controls. Active thyroid eye disease showed larger lacrimal gland herniation, maximum coronal area, diffusion-weighted imaging-apparent diffusion coefficient than inactive. Lacrimal gland dimensional (maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width) and functional parameters (diffusion tensor imaging-apparent diffusion coefficient, diffusion tensor imaging-apparent diffusion coefficient) could be used for diagnosing thyroid eye disease; lacrimal gland herniation, maximum coronal area, and diffusion-weighted imaging-apparent diffusion coefficient for differentiating active from inactive thyroid eye disease; diffusion tensor imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-mean diffusivity) and lacrimal gland herniation for helping grading and therapeutic responses prediction respectively. Conclusions Magnetic resonance imaging lacrimal gland parameters can detect active thyroid eye disease and differentiate thyroid eye disease from controls. Maximum coronal area is the most effective indicator for thyroid eye disease diagnosis and activity grading. There are inconclusive results showing whether structural or functional lacrimal gland parameters have diagnostic superiority. Future studies are warranted to determine the use of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease.

Abstract During the multistage fracturing of shale gas horizontal wells, casing damage frequently occurs, making it essential to evaluate casing stress and deformation. This paper establishes a mathematical model of thermo‐hydro‐mechanical coupling and a finite element model of casing‐cement sheath‐formation (CCF). This paper examines the effects of temperature, casing thickness, nonuniform in situ stress, mechanical properties of cement sheath, and treating pressure on the stress and deformation of CCF. Finally, the study investigates the variation of local in situ stress at the heel and casing stress from toe to heel. The results show that the low temperature of CCF, high elastic modulus of cement sheath, small casing thickness, high treating pressure, and large nonuniform in situ stress can exacerbate casing stress. After pumping off, the local in situ stress and its nonuniformity near heel gradually increased, and the effective stress of casing increases compared with the pumping on the process. As the fracturing stages increase, the effective stress of casing at heel increases, and the casing at heel preferentially damages. The results provide a theoretical basis and guidance for maintaining wellbore integrity and preventing casing damage in the multistage fracturing of shale gas horizontal wells.

Abstract Clinical relevance The Keratoconus International Consortium (KIC) will allow better understanding of keratoconus. Background Keratoconus is a disorder characterised by corneal elevation and thinning, leading to reduced vision. The current gaps in understanding of this disease will be discussed and the need for a multi-pronged and multi-centre engagement to enhance our understanding of keratoconus will be highlighted. Design KIC has been established to address the gaps in our understanding of keratoconus with the aim of collecting baseline as well as longitudinal data on several fields. Participants Keratoconus and control (no corneal condition) subjects from different sites globally will be recruited in the study. Methods KIC collects data using an online, secure database, which enables standardised data collection at member sites. Data fields collected include medical history, clinical features, quality of life and economic burden questionnaires and possible genetic sample collection from patients of different ethnicities across different geographical locations. Results There are currently 40 Australian and international clinics or hospital departments who have joined the KIC. Baseline data has so far been collected on 1130 keratoconus patients and indicates a median age of 29.70 years with 61% being male. A total of 15.3% report a positive family history of keratoconus and 57.7% self-report a history of frequent eye rubbing. Conclusion The strength of this consortium is its international, collaborative design and use of a common data collection tool. Inclusion and analyses of cross-sectional and longitudinal data will help answer many questions that remain in keratoconus, including factors affecting progression and treatment outcomes.

Abstract Background Urothelial carcinoma is a major subtype of bladder cancer and small cell carcinoma (SCC) is a rare type of cancer in clinical practice. Pathologic collision of urinary bladder urothelial carcinoma with SCC is not common in clinical settings. Case presentation Here, we report a patient with high-grade papillary carcinoma which changed to collision tumor with SCC. The patient underwent radical cystectomy; however, neck and mediastinum lymph nodes metastases were detected 11 months after the operation. The lymph nodes were diagnosed pathologically as SCC. Chemoradiotherapy was subsequently prescribed. Unfortunately, this patient died of COVID-19 in early 2023. Discussion We hypothesized the mechanism underlying this pathological transformation. For patients with urothelial bladder cancer, pathological analysis should be conducted to allow standardized and persistent treatment. Moreover, drugs should be selected depending on the type of pathology, especially for patients who develop relapse, since collision tumor or other pathological tumors may be present. Conclusions We recommend that radical cystectomy be performed early enough for patients with non-muscle invasive bladder cancer, who are at a high risk of tumor recurrence. However, this conclusion needs to be validated in a larger number of patients.

Improper drilling parameters may cause severe vibration of drill string which leads to reduce the rate of penetration and drilling tool premature failure accidents in the drilling process of ultra-deep well. The study on dynamic characteristics of drill string plays an important role in increasing the safety of drilling tool and optimizing the drilling parameters. Considering the influences of real borehole trajectory, interaction between bit and formation, contact between drill string and borehole wall, stiction of drilling fluid and other factors, a comprehensive drill string dynamic model was established to simulate the changes of wellhead hook load, torque, equivalent stress of drill string and BHA (bottom-hole assembly) section acceleration and motion trajectory with time at different WOBs (weights on bit) and rotary speeds. The safety factor and overpull margin of wellhead drill string were calculated and the strength of drilling tool in ultra-deep well was checked using the fourth strength theory. The analysis results show that, in the drilling process of ultra-deep well, the transverse motion amplitude of the drill string near the wellhead is relatively small and vibration of drill string mainly occurs in the lower well section. As the rotary speed increases, the number of collision between lower drilling tool and borehole wall increases, wellhead transverse stress increases, change in torque is not large and change in wellhead equivalent stress is relatively small. As the WOB increases, wellhead torque will increase, axial load and equivalent stress will decrease and vibration acceleration of BHA will increase sharply. Wellhead overpull margin and safety factor will decrease with the increase of rotary speed and increase with the increase of WOB. Wellhead safety factor of S135 drilling tool in an Φ190.5 mm ultra-deep well on the south margins of Junggar basin changes around 1.8. The drilling tool is safe and has relatively sufficient ability to deal with the downhole accidents if a large size high steel grade drill string (Φ139.7 mm S135) is used. However, in view of BHA safety, neither rotary speed shall be too high nor WOB shall be too large.

Abstract Dysregulation of Th17 cell differentiation and pathogenicity contributes to multiple autoimmune and inflammatory diseases. Previously growth hormone releasing hormone receptor (GHRH-R) deficient mice have been reported to be less susceptible to the induction of experimental autoimmune encephalomyelitis. Here, we show GHRH-R is an important regulator of Th17 cell differentiation in Th17 cell-mediated ocular and neural inflammation. We find that GHRH-R is not expressed in naïve CD4+ T cells, while its expression is induced throughout Th17 cell differentiation in vitro. Mechanistically, GHRH-R activates the JAK-STAT3 pathway, increases the phosphorylation of STAT3, enhances both non-pathogenic and pathogenic Th17 cell differentiation and promotes the gene expression signatures of pathogenic Th17 cells. Enhancing this signaling by GHRH agonist promotes, while inhibiting this signaling by GHRH antagonist or GHRH-R deficiency reduces, Th17 cell differentiation in vitro and Th17 cell-mediated ocular and neural inflammation in vivo. Thus, GHRH-R signaling functions as a critical factor that regulates Th17 cell differentiation and Th17 cell-mediated autoimmune ocular and neural inflammation.

Background. Radiation therapy is an effective local therapy for lung cancer. However, the interaction between genes and radiotherapy is multifaceted and intricate. Therefore, we explored the role of miR-93-5p in the proliferation, apoptosis, and migration abilities of A549 cells. Simultaneously, we also investigated the interactions between miR-93-5p and ionizing radiation (IR). Methods. Cell Counting Kit-8, transwell, and apoptotic assay were performed to measure the proliferation, migration, and apoptosis abilities. The expression levels of miR-93-5p and its target gene in lung cancer were predicted using starBase v3.0. Then, data were validated using qPCR and western blot. Results. miR-93-5p significantly promoted the proliferation (P

AbstractPlatelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients. Statistical analysis reveals that the α-granule/mitochondrion-to-plateletvolume ratio is significantly greater in COVID-19 patient platelets indicating a denser packing of organelles, and a more compact platelet. The COVID-19 patient platelets were significantly smaller –by 35% in volume – with most of the difference in organelle packing density being due to decreased platelet size. There was little to no 3D ultrastructural evidence for differential activation of the platelets from COVID-19 patients. Though limited by sample size, our studies suggest that factors outside of the platelets themselves are likely responsible for COVID-19 complications. Our studies show how deep learning 3D methodology can become the gold standard for 3D ultrastructural studies of platelets.

ABSTRACTTo evaluate the effectiveness of smartphone ophthalmoscope (SO) in teaching ophthalmoscopy, compared with direct ophthalmoscope (DO). In this cross-over study, 45 final-year medical students attending sessions at a single institution were randomly allocated to two groups (A and B). Both groups attended two training sessions. In the first session, Group A students were taught ophthalmoscopy using DO and Group B students using SO. In the second session, the training sessions were crossed over. A series of eye models with 10 letters placed on the inner surface were designed to assess the students’ skill on ophthalmoscopy. Students performed ophthalmoscopy on the eye models, recorded their findings, and completed a questionnaire of feedback on DO and SO. The main outcome measure was the score of ophthalmoscopy, assessed by the student correctly recording each letter (score 1 for each letter). For Group A, the mean score of ophthalmoscopy on the eye model using DO and SO was 3.9±2.4 and 8.2±2.2, respectively. For Group B, the mean score of ophthalmoscopy on the eye model using SO and DO 8.7±1.8 and 5.7±3.5 . Students scored significantly higher in ophthalmoscopy when using SO than DO (P

Abstract Background Reducing delays along the acute stroke pathway significantly improves clinical outcomes for acute ischemic stroke patients eligible for reperfusion treatments. The economic impact of different strategies reducing onset to treatment (OTT) is crucial information for stakeholders in acute stroke management. This systematic review aimed to provide an overview on the cost-effectiveness of several strategies to reduce OTT. Methods A comprehensive literature search was conducted in EMBASE, PubMed, and Web of Science until January 2022. Studies were included if they reported 1/ stroke patients treated with intravenous thrombolysis and/or endovascular thrombectomy, 2/ full economic evaluation, and 3/ strategies to reduce OTT. The Consolidated Health Economic Evaluation Reporting Standards statement was applied to assess the reporting quality. Results Twenty studies met the inclusion criteria, of which thirteen were based on cost-utility analysis with the incremental cost-effectiveness ratio per quality-adjusted life year gained as the primary outcome. Studies were performed in twelve countries focusing on four main strategies: educational interventions, organizational models, healthcare delivery infrastructure, and workflow improvements. Sixteen studies showed that the strategies concerning educational interventions, telemedicine between hospitals, mobile stroke units, and workflow improvements, were cost-effective in different settings. The healthcare perspective was predominantly used, and the most common types of models were decision trees, Markov models and simulation models. Overall, fourteen studies were rated as having high reporting quality (79%-94%). Conclusions A wide range of strategies aimed at reducing OTT is cost-effective in acute stroke care treatment. Existing pathways and local characteristics need to be taken along in assessing proposed improvements.

Abstract Introduction This study aimed to evaluate the habitual reading distance among non-myopic children and also myopic children with undercorrection and with full correction. Methods This was a population-based cross-sectional study with a total of 2363 children aged 6–8 years who were recruited from the Hong Kong Children Eye Study. Cycloplegic autorefraction, subjective refraction, habitual visual acuity, and best corrected visual acuity were measured. The entire reading process (9 min) was recorded using a hidden video camera placed 5 m away from the reading desk. Reading distances were taken at 6, 7, 8, and 9 min after the child began reading and were measured using a customized computer program developed in MATLAB. The main outcome was the association of habitual reading distances with refraction status. Habitual reading distances of children were documented via video camera footage. Results The habitual reading distances of undercorrected myopic children (23.37 ± 4.31 cm) were the shortest when compared to non-myopic children (24.20 ± 4.73 cm, P = 0.002) and fully corrected myopic children (24.81 ± 5.21 cm, P

Retinal detachment (RD) can result in the loss of photoreceptors that cause vision impairment and potential blindness. This study explores the protective effects of the oral administration of green tea extract (GTE) in a rat model of RD. Various doses of GTE or epigallocatechin gallate (EGCG), the most active ingredient in green tea catechins, were administered to Sprague Dawley (SD) rats with experimentally induced retinal detachment. The rats received sub-retinal injections of hyaluronic acid (0.1%) to induce RD and were given different doses of GTE and EGCG twice daily for three days. Notably, a low dose of GTE (142.9 mg/kg) caused significantly higher signal amplitudes in electroretinograms (ERGs) compared to higher GTE doses and any doses of EGCG. After administration of a low dose of GTE, the outer nuclear layer thickness, following normalization, of the detached retina reduced to 82.4 ± 8.2% (Mean ± SEM, p < 0.05) of the thickness by RD treatment. This thickness was similar to non-RD conditions, at 83.5 ± 4.7% (Mean ± SEM) of the thickness following RD treatment. In addition, the number of TUNEL-positive cells decreased from 76.7 ± 7.4 to 4.7 ± 1.02 (Mean ± SEM, p < 0.0001). This reduction was associated with the inhibition of apoptosis through decreased sphingomyelin levels and mitigation of oxidative stress shown by a lowered protein carbonyl level, which may involve suppression of HIF-1α pathways. Furthermore, GTE showed anti-inflammatory effects by reducing inflammatory cytokines and increasing resolving cytokines. In conclusion, low-dose GTE, but not EGCG, significantly alleviated RD-induced apoptosis, oxidative stress, inflammation, and energy insufficiency within a short period and without affecting energy metabolism. These findings suggest the potential of low-dose GTE as a protective agent for the retina in RD.

Abstract Background To determine the association of the ANGPT2 gene with primary open-angle glaucoma (POAG) in Chinese. Methods Six single-nucleotide polymorphisms (SNPs) in ANGPT2 (rs2515487, rs2922869, rs13255574, rs4455855, rs13269021, and rs11775442) were genotyped in a total of 2601 study subjects from two cohorts. One is a Hong Kong Chinese cohort of 484 high tension glaucoma (HTG) and 537 normal tension glaucoma (NTG) patients, and 496 non-glaucoma control subjects. Another cohort is a Shantou Chinese cohort of 403 HTG and 135 NTG patients, and 543 non-glaucoma control subjects. Subgroup analysis by sex was conducted. Outcomes from different cohorts were combined for meta-analysis. Results The association of SNP rs11775442 with NTG in the Hong Kong cohort [P = 0.0498, OR = 1.24, 95% confidence interval (CI) 1.00–1.55] after adjusting for age and sex did not reach statistical significance after Bonferroni correction. Other SNPs were not significantly associated with NTG, HTG and POAG in individual cohort or in the combined analyses (P > 0.05). In the subgroup analysis by sex, SNP rs13269021 in the Shantou cohort, but not in the Hong Kong cohort, was significantly associated with NTG in males (P = 0.0081, OR = 1.67, 95% CI: 1.14–2.43) but not in females (P = 0.874). In the combined analyses by sex, no SNPs were significantly associated with NTG, HTG and POAG. Conclusions In the subgroup analysis by sex, a significant association was shown in SNP rs13269021 with NTG in Shantou males, but not in Hong Kong males. Further studies are needed to verify the association between ANGPT2 locus (rs13269021) and NTG in Chinese males.

Abstract Microwaves, long used as a convenient household appliance, have been increasingly used in industrial processes such as organic synthesis and oil processing. It has been proposed that microwaves can enhance these chemical processes via a non-thermal effect. Here we report the instantaneous effect of microwaves on the permittivity and phase velocity of light in water through the in-situ measurement of changes in refractive index. Microwave irradiation was found to reduce the water refractive index (RI) sharply. The reduction increased as a function of microwave power to a far greater extent than expected from the change in temperature. The phase velocity of light in water increases up to ~ 5% (RI of 1.27) during microwave irradiation. Upon stopping irradiation, the return to the equilibrium RI was delayed by up to 30 min. Our measurement shows that microwaves have a profound non-thermal and long-lasting effect on the properties of water. Further investigation is planned to verify if the observed RI reduction is restricted to the region near the surface or deep inside water bulk. The observation suggests a relationship between microwave-induced and the enhanced aqueous reactions.

Abstract Objective Our study aimed to identify predictors as well as develop machine learning (ML) models to predict the risk of 30-day mortality in patients with sepsis-associated encephalopathy (SAE). Materials and methods ML models were developed and validated based on a public database named Medical Information Mart for Intensive Care (MIMIC)-IV. Models were compared by the area under the curve (AUC), accuracy, sensitivity, specificity, positive and negative predictive values, and Hosmer–Lemeshow good of fit test. Results Of 6994 patients in MIMIC-IV included in the final cohort, a total of 1232 (17.62%) patients died following SAE. Recursive feature elimination (RFE) selected 15 variables, including acute physiology score III (APSIII), Glasgow coma score (GCS), sepsis related organ failure assessment (SOFA), Charlson comorbidity index (CCI), red blood cell volume distribution width (RDW), blood urea nitrogen (BUN), age, respiratory rate, PaO2, temperature, lactate, creatinine (CRE), malignant cancer, metastatic solid tumor, and platelet (PLT). The validation cohort demonstrated all ML approaches had higher discriminative ability compared with the bagged trees (BT) model, although the difference was not statistically significant. Furthermore, in terms of the calibration performance, the artificial neural network (NNET), logistic regression (LR), and adapting boosting (Ada) models had a good calibration—namely, a high accuracy of prediction, with P-values of 0.831, 0.119, and 0.129, respectively. Conclusions The ML models, as demonstrated by our study, can be used to evaluate the prognosis of SAE patients in the intensive care unit (ICU). Online calculator could facilitate the sharing of predictive models.

Abstract The retinoblastoma protein (pRb) functions as a cell cycle regulator controlling G1 to S phase transition and plays critical roles in tumour suppression. It is frequently inactivated in various tumours. The functions of pRb are tightly regulated, where post-translational modifications (PTMs) play crucial roles, including phosphorylation, ubiquitination, SUMOylation, acetylation and methylation. Most PTMs on pRb are reversible and can be detected in non-cancerous cells, playing an important role in cell cycle regulation, cell survival and differentiation. Conversely, altered PTMs on pRb can give rise to anomalies in cell proliferation and tumourigenesis. In this review, we first summarize recent findings pertinent to how individual PTMs impinge on pRb functions. As many of these PTMs on pRb were published as individual articles, we also provide insights on the coordination, either collaborations and/or competitions, of the same or different types of PTMs on pRb. Having a better understanding of how pRb is post-translationally modulated should pave the way for developing novel and specific therapeutic strategies to treat various human diseases.

FGFR3-TACC3 fusions have been identified in patients with multiple cancer types, and tumors with these alterations are potentially sensitive to selective FGFR inhibitors. However, there are no FGFR inhibitors approved by the U.S. Food and Drug Administration for the treatment of patients with NSCLC with FGFR alterations. Here, we report a case of a patient with FGFR3-TACC3 fusion squamous NSCLC who achieved a radiographic response and disease control for 11 months on initial treatment with erdafitinib and subsequently obtained an additional 8 months of disease control after erdafitinib retreatment after 5 months of intervening chemotherapy. Further investigation into FGFR inhibitor treatment specifically and targeted therapy retreatment for patients with NSCLC may increase our therapeutic options for these patients.

PurposeThis study aims to investigate the effectiveness of interventions to control myopia progression. In this systematic review, the primary outcomes were mean differences (MD) between treatment and control groups in myopia progression (D) and axial length (AL) elongation (mm).ResultsThe following interventions were found to be effective (p