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Acute retinal necrosis (ARN) is a clinical syndrome featuring severe vitritis and occlusive vasculitis characterised by full thickness necrotising retinitis. ARN is usually caused by an acute infection by either varicella zoster virus or herpes simplex virus, rarely cytomegalovirus (CMV). ARN often occurs in healthy adults; occasionally affecting immunocompromised patients with poor prognosis including significant visual loss and detachment of the atrophic retina regardless of antiviral treatment. We presented a man in his early 30s with a history of left eye floaters and blurred vision. He was diagnosed with T-cell acute lymphoblastic leukaemia 1 year ago and treated with chemotherapy and allogenic haematopoietic stem cell transplant 5 months ago. His clinical diagnosis was left eye ARN caused by acute viral infection with CMV being the most likely cause, which is rarely seen in immunocompromised patients. Our case highlighted a diagnostic and therapeutic challenge in the absence of guideline or evidence-based literature to follow.

Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6− (M+2+6−) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6− percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets. Comparative bulk/single-cell transcriptomic analyses of DLBCL samples and MYC/BCL2/BCL6-transformed primary B cells identify molecular features, including cyclin D2 and PI3K/AKT as candidate regulators of M+2+6− unfavorable biology. Similar analyses evaluating oncogenic combinations at single-cell resolution in other cancers may facilitate an understanding of cancer evolution and therapy resistance. Significance: Using single-cell–resolved multiplexed imaging, we show that selected subpopulations of cells expressing specific combinations of oncogenes influence clinical outcomes in lymphoma. We describe a probabilistic metric for the estimation of cellular oncogenic coexpression from IHC or bulk transcriptomes, with possible implications for prognostication and therapeutic target discovery in cancer. This article is highlighted in the In This Issue feature, p. 1027

Precision medicine promises to transform healthcare for groups and individuals through early disease detection, refining diagnoses and tailoring treatments. Analysis of large-scale genomic-phenotypic databases is a critical enabler of precision medicine. Although Asia is home to 60% of the world's population, many Asian ancestries are under-represented in existing databases, leading to missed opportunities for new discoveries, particularly for diseases most relevant for these populations. The Singapore National Precision Medicine initiative is a whole-of-government 10-year initiative aiming to generate precision medicine data of up to one million individuals, integrating genomic, lifestyle, health, social and environmental data. Beyond technologies, routine adoption of precision medicine in clinical practice requires social, ethical, legal and regulatory barriers to be addressed. Identifying driver use cases in which precision medicine results in standardized changes to clinical workflows or improvements in population health, coupled with health economic analysis to demonstrate value-based healthcare, is a vital prerequisite for responsible health system adoption. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) We thank all investigators, staf members and study participants of the contributing cohorts and studies: (1) the HELIOS study at the Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; (2) the GUSTO study jointly hosted by the National University Hospital, KK Women’s and Children’s Hospital, the National University of Singapore and the Singapore Institute for Clinical Sciences, the Agency for Science Technology and Research (A*STAR); (3) the SEED cohort at the Singapore Eye Research Institute; (4) the MEC, National University of Singapore; (5) the PRISM cohort; and (6) the TTSH Personalised Medicine Normal Controls cohort. We also thank the National Supercomputing Centre, Singapore (https://www.ncss.sg) for computation resources. The SG10K_Health project is funded by the Industry Alignment Fund (Pre-Positioning) (IAF-PP, H17/01/a0/007); the project made use of participating study cohorts supported by the following funding sources: (1) the HELIOS study by grants from a Strategic Initiative at Lee Kong Chian School of Medicine, the Singapore MOH under its Singapore Translational Research Investigator Award (NMRC/STaR/0028/2017) and the IAF-PP (H18/01/a0/016); (2) the GUSTO study by the Singapore National Research Foundation under its Translational and Clinical Research Flagship Program and administered by the Singapore MOH’s National Medical Research Council Singapore (NMRC/TCR/004-NUS/2008, NMRC/ TCR/012-NUHS/2014) with additional funding support available through the A*STAR and the IAF-PP (H17/01/a0/005); (3) the SEED study by NMRC/CIRG/1417/2015, NMRC/CIRG/1488/2018 and NMRC/OFLCG/004/2018; (4) the MEC by individual research and clinical scientist award schemes from the Singapore National Medical Research Council (including MOH-000271-00) and the Singapore Biomedical Research Council, the Singapore MOH, the National University of Singapore and the Singapore National University Health System; (5) the PRISM cohort study by NMRC/CG/ M006/2017_NHCS, NMRC/STaR/0011/2012, NMRC/STaR/0026/2015, the Lee Foundation and the Tanoto Foundation; and (6) the TTSH cohort study by NMRC/CG12AUG2017 and CGAug16M012. This research is also supported by the National Research Foundation Singapore under its NPM program Phase II funding (MOH-000588) and administered by the Singapore MOH’s National Medical Research Council.

The advent of lung cancer screening and detection of smaller nodules amplifies the need to clarify the oncological quality of sublobar resections. Furthermore, studies comparing sublobar resections to lobectomies offer conflicting conclusions. We hypothesize that this is driven, in part, by inconsistency in reporting; that is, variable interpretation of what constitutes an operative segment. Without an established standard, 2 very different operations may be reported as segmental resections, leaving the data on sublobar approaches subject to interpretative variability.A retrospective audit was performed on all segmental resections from May 2016 to December 2019 at Brigham and Women's Hospital. Pathology and operative reports were reviewed, with particular attention to the dissection of the component artery, vein, and bronchus. Resections with dissection and division of at least 1 major vascular structure (the segmental artery or vein), as well as the segmental bronchus, met operative criteria for anatomic segmentectomy. Surgical quality metrics were compared between the 2 groups.There were 271 segmental resections: 219 (80.8%) were anatomic segmentectomies and 52 (19.2%) were nonanatomic segmentectomies. For the entire cohort, nonanatomic segmentectomies had smaller margins (1.0 vs 1.5 cm; P = .02), fewer lymph nodes (2.0 vs 6.0; P .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P .001). Similarly, there were smaller margins (1.5 vs 1.8 cm; P = .03), fewer lymph nodes (2.0 vs 6.0; P .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P .001) in nonanatomic segmentectomies for non-small cell lung cancer.Nearly 20% of reported segmentectomies may not meet criteria for true segmental resection. Therefore, prior studies may need further scrutiny to clarify outcomes and results. Establishing a professional standard may help mitigate ambiguity in published data on this subject.

Recent studies suggest that heterogeneous bilingual experiences implicate different executive functions (EF) in children. Using a latent profile analysis, we conducted a more nuanced investigation of multifaceted bilingual experiences. By concurrently considering numerous bilingual indicators – age of L1 and L2 acquisition, interactional contexts of verbal exchanges, L1 and L2 proficiency, balance of language use at home and school, and receptive vocabulary – we identified three latent profiles (subgroups): balanced dual-language, dominant single-language, and mixed-interaction. We found that the balanced dual-language and dominant single-language profiles predicted significantly better switching than the mixed-interaction profile. However, no profile differences were found in working memory, prepotent response inhibition, or inhibitory control. These results held true when multiple covariates (age, sex, household income, and nonverbal intelligence) were controlled for. Using a person-centered approach, our study underscores that disparate bilingual experiences asymmetrically predict the shifting facet of EF during early childhood.

This study aimed to explore the relationship between daily self-reported health symptoms and mental health among respiratory patients during a high-pollution period in Thailand. A cross-sectional study was conducted at the pulmonary clinic of King Chulalongkorn Memorial Hospital in Bangkok, Thailand in February 2022. Patients with respiratory diseases were enrolled and asked to self-evaluate their health via ChulaAir mobile application. Daily respiratory symptoms were assessed using a checklist for a month. The DASS21 questionnaire was used to identify depression, anxiety, and stress at the end of the month. Binary logistic regression was performed to find the associations. A total of 98 patients participated in the study, and the prevalence of depression, anxiety, and stress was 30.6%, 28.6%, and 26.5%, respectively. Cough and Phlegm were the most common health symptoms during the high-pollution period. An increase in the number of days with self-reported sore eyes was associated with depression (AOR=1.307; p=0.001), anxiety (AOR=1.261; p=0.001), and stress (AOR=1.178; p=0.001). Health symptoms are related to the presence of depression, anxiety, and stress during the high-pollution period. For individuals with respiratory symptoms, measures are required to alleviate mental health problems.

Purpose This study aims to examine to what extent the Japanese financial markets are affected by the four periods of unconventional monetary policies (UMP) implemented by the Bank of Japan from 2013 to 2020. Design/methodology/approach Using the daily 10-year term spread as a proxy for monetary easing policy, this study uses four sub-sample periods from 2013 to 2020 to look into the effectiveness of UMP on the Japanese financial markets. Findings Our result shows that not all of the Bank of Japan's unconventional monetary policies are equally effective in influencing the Japanese financial markets. In particular, the QQE policy implemented from April 2013 to October 2014 effectively influenced the stock market, banking sector and foreign exchange market. However, the financial market impact of monetary policy is muted during the QQE expansion period. Likewise, the QQE with a negative interest rate policy influences only the banking sector. Finally, the QQE with its yield curve control policy effectively impacts the financial markets. Research limitations/implications This research can be expanded by studying the international spillover effect of the Bank of Japan's UMP on the financial markets in Asian countries. Practical implications The findings of this study enable investors to understand the causal relationship between the Bank of Japan's UMP and the financial market indicators, thereby helping them to position their portfolio investments. From the policy perspective, the finding is useful to inform the Bank of Japan on which policy is relatively effective in affecting the financial markets. In light of the empirical finding, the Bank of Japan should continue to pursue the QQE YCCP or revert to the initial QQE policy, as the two policies are relatively more effective than the QQE expansion and QQE NIRP in affecting the Japanese financial markets. Social implications The empirical finding highlights the importance of controlling for the impact of different QQE policies in the model. Future research may consider conducting sub-sample analysis to cater to the different QQE policy regimes. This approach provides a clearer picture and valid inferences on the financial market impact of each QQE policy. Originality/value This study provides a comprehensive analysis of the impact of Bank of Japan's QQE on the Japanese financial markets. For the market participants, the findings of this study suggest that investors should closely gauge the development of the unconventional monetary policies of the Bank of Japan because the monetary easing policy influences the decision-making process of commercial banks, pension funds, mutual funds, retail investors and other stakeholders in the financial markets. The policy twist will have future ramifications for their loan, investment and retirement fund portfolios.

The global cruise tourism industry has been significantly impacted by the COVID-19 pandemic. As a result, it is important to understand the factors that affect tourists' decision to purchase cruise holidays after the pandemic. To accomplish this, a conceptual model based on the perceived value theory and incorporating concepts such as destination image, perceived risk, and purchase intention is proposed. This framework can be utilized to investigate tourists' purchase intention for cruise holidays and assist the cruise tourism industry in devising appropriate policies and designing cruise tourism products. This study is the first to develop a model for tourists' purchase intentions for cruise holidays after the COVID-19 outbreak.

OBJECTIVE Intracranial pressure (ICP) monitoring is a widely utilized and essential tool for tracking neurosurgical patients, but there are limitations to the use of a solely ICP-based paradigm for guiding management. It has been suggested that ICP variability (ICPV), in addition to mean ICP, may be a useful predictor of neurological outcomes, as it represents an indirect measure of intact cerebral pressure autoregulation. However, the current literature regarding the applicability of ICPV shows conflicting associations between ICPV and mortality. Thus, the authors aimed to investigate the effect of ICPV on intracranial hypertensive episodes and mortality using the eICU Collaborative Research Database version 2.0. METHODS The authors extracted from the eICU database 1,815,676 ICP readings from 868 patients with neurosurgical conditions. ICPV was computed using two methods: the rolling standard deviation (RSD) and the absolute deviation from the rolling mean (DRM). An episode of intracranial hypertension was defined as at least 25 minutes of ICP > 22 mm Hg in any 30-minute window. The effects of mean ICPV on intracranial hypertension and mortality were computed using multivariate logistic regression. A recurrent neural network with long short-term memory was used for time-series predictions of ICP and ICPV to prognosticate future episodes of intracranial hypertension. RESULTS A higher mean ICPV was significantly associated with intracranial hypertension using both ICPV definitions (RSD: aOR 2.82, 95% CI 2.07–3.90, p < 0.001; DRM: aOR 3.93, 95% CI 2.77–5.69, p < 0.001). ICPV was significantly associated with mortality in patients with intracranial hypertension (RSD: aOR 1.28, 95% CI 1.04–1.61, p = 0.026, DRM: aOR 1.39, 95% CI 1.10–1.79, p = 0.007). In the machine learning models, both definitions of ICPV achieved similarly good results, with the best F1 score of 0.685 ± 0.026 and an area under the curve of 0.980 ± 0.003 achieved with the DRM definition over 20 minutes. CONCLUSIONS ICPV may be useful as an adjunct for the prognostication of intracranial hypertensive episodes and mortality in neurosurgical critical care as part of neuromonitoring. Further research on predicting future intracranial hypertensive episodes with ICPV may help clinicians react expediently to ICP changes in patients.

To provide a comprehensive narrative review of the published data on the impact of hydrogel spacers on rectal dosimetry and toxicity and to outline the practicalities of inserting hydrogel spacers.A growing body of evidence suggests that the administration of hydrogel spacers is safe and is associated with limited peri-operative morbidity. The impact on rectal dosimetry has been clearly established and use of hydrogel spacers is associated with reduced rectal morbidity. These results have been corroborated by several Phase II and III clinical trials and subsequent meta-analysis. There are several areas for future research, including the role of hydrogel spacers in prostate stereotactic beam radiotherapy and post-radiotherapy local recurrence.Hydrogel spacers provide a low-morbidity method to potential reduce rectal toxicity after radiation therapy in men with prostate cancer. Data outlining sexual function and oncological outcomes are limited to date. Future studies, currently being conducted, may provide further clarification of the role of hydrogel spacers in prostate cancer management.

The skin manifestations of Langerhans cell histiocytosis (LCH) in the neonate have a heterogenous presentation and can mimic other causes of neonatal rashes. We report an uncommon case of LCH in a term female neonate presenting with non-specific papules and vesicles from the first day of life. There was a maternal history of genital herpes simplex virus (HSV) infection in the third trimester. Blood, cerebrospinal fluid, surface swabs and vesicular fluid were negative for HSV by PCR, and a skin biopsy confirmed the diagnosis of LCH. Further investigations for systemic involvement returned negative. Our case emphasises the variable and non-specific presentation of neonatal cutaneous LCH, which can progress to or be part of multisystem disease.

Background: Acute kidney injury (AKI) occurs frequently in septic patients and correlates with increased mortality. Because clinical studies investigating hydrocortisone, ascorbic acid, and thiamine (HAT) have demonstrated discordant results, studies were performed using mortality stratification for therapy to identify candidates for therapy and determine mechanisms of organ injury. Methods: Sepsis was induced using the cecal ligation and puncture (CLP) model of sepsis with fluid and antibiotic support. Heart rate (HR) measurements obtained 6 hours after CLP stratified mice into live predicted (P-Live) or die predicted (P-Die). Stratified mice were then randomized for treatment with HAT or vehicle given 7 hours after CLP. Physiologic measurements were taken again at 24 hours, and mice were killed to collect blood and organs. Results: The following five groups were created: (1) P-Live vehicle, (2) P-Live HAT, (3) P-Die vehicle, (4) P-Die HAT, and (5) naive mice. Comparisons were made to test the hypotheses that (1) P-Die vehicle mice will have significant deterioration compared with P-Live mice targeting the kidney and (2) HAT will correct these deleterious changes in P-Die mice. Compared with P-Live, P-Die mice had a significant decline in all measured physiologic parameters (HR, cardiac output, breath rate, and temperature), which were corrected with HAT therapy (P0.05 for all parameters). The P-Die mice had declines in the ascorbic acid within the blood, peritoneal lavage, and kidney homogenate compared with P-Live mice indicating consumption, and the decline was corrected with HAT. Elevated IL-6, KC, Macrophage Inflammatory Protein-2, and IL-1RA were found in P-Die mice and decreased with HAT. Markers of endothelial cell injury (glypican 1 and glypican 4) were elevated in the P-Die mice, and these values were decreased with HAT therapy. Low oxygen levels with subsequent oxidative stress (OS) in the kidney were visualized in histologic sections using hypoxyprobe and also with carbonyl proteins and 8-iso-prostaglandin F2α in kidney homogenates. The P-Die mice had significant elevations of renal OSs, which was ameliorated with HAT. Kidney injury was evident in the P-Die mice compared with P-Live mice with elevations in blood urea nitrogen and cystatin C, which were significantly reduced with HAT. There was no evidence of global hypoxia or organ injury because hepatic parameters remained normal. Conclusions: Our data show that in CLP-induced sepsis, P-Die mice have increased inflammation, OS, and kidney injury. Hydrocortisone, ascorbic acid, and thiamine therapy decreased renal OS and injury in the P-Die group when given after the onset of sepsis-induced physiologic changes.

Computer vision techniques are widely applied to the object detection, license plate recognition, remote sensing, and outdoor monitoring system. The performance of these applications mainly relies on the high quality of outdoor image. However, an outdoor image can be led to contrast decrease, color distortion, and unclear structure by poor weather conditions and human factors such as haze, fog, and air pollution. These issues may lower down the sharpness of a photo. Despite of the single-image dehazing is used to solve these issues, it cannot achieve a satisfactory result when the method deals with the bright scene and sky area. In this article, we aim to design an adaptive dehazing technique based on fusion transmission and sky weight detection. The sky weight detection is employed to distinguish the foreground and background, while detected results are applied to the fusion strategy to calculate deep and shallow transmissions. Thus, this can get rids of the subject of over-adjustment. Experimental results have demonstrated that the new method can outperform the latest state-of-the-art methods in terms of subjective and the objective assessments. &nbsp

Glioblastomas (GBM) are aggressive brain tumors with extensive intratumoral heterogeneity that contributes to treatment resistance. Spatial characterization of GBMs could provide insights into the role of the brain tumor microenvironment in regulating intratumoral heterogeneity. Here, we performed spatial transcriptomic and single-cell analyses of the mouse and human GBM microenvironment to dissect the impact of distinct anatomical regions of brains on GBM. In a syngeneic GBM mouse model, spatial transcriptomics revealed that numerous extracellular matrix (ECM) molecules, including biglycan, were elevated in areas infiltrated with brain tumor–initiating cells (BTIC). Single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin using sequencing showed that ECM molecules were differentially expressed by GBM cells based on their differentiation and cellular programming phenotypes. Exogeneous biglycan or overexpression of biglycan resulted in a higher proliferation rate of BTICs, which was associated mechanistically with low-density lipoprotein receptor-related protein 6 (LRP6) binding and activation of the Wnt/β-catenin pathway. Biglycan-overexpressing BTICs developed into larger tumors and displayed mesenchymal phenotypes when implanted intracranially in mice. This study points to the spatial heterogeneity of ECM molecules in GBM and suggests that the biglycan–LRP6 axis could be a therapeutic target to curb tumor growth. Significance: Characterization of the spatial heterogeneity of glioblastoma identifies regulators of brain tumor–initiating cells and tumor growth that could serve as candidates for therapeutic interventions to improve the prognosis of patients.

The main objective of this research was to study the factors influencing the science and environment of education program for blind students at the elementary level. This research used mixed methods (quantitative and qualitative approaches), specifically a questionnaire survey was conducted to better understand the current situation on Science and Environmental Education Learning among 192 blind students in 14 primary schools for the blind in Thailand and in-depth interviews with the directors, science and Environmental teachers, and students’ parents, 30 interviewees in total. The data were collected and analyzed into frequency and percentage (and K-means clustering) using SPSS software. The research findings from data collection from 192 blind students illustrated that the importance of facilitator that involve teaching materials (43%) was support appropriate to Science and Environmental Education teaching materials for blind students, 34% students had a good relationship with their classmates and teachers. A total of (32%) were provided more Braille textbooks for Science and Environmental Education teaching. K-means cluster analysis showed four clusters of science and environmental education learning blind students. The study concluded that the factors influencing effectiveness of science and environmental education learning of blind students consisted of facilitators, the creation of scientific learning processes, media and technology as the medium for communicating scientific knowledge, appropriate curriculum for blind students, and cognitive abilities of blind students in physical, mental, intelligence, and emotion terms.

Covalent organic framework nanosheets (COF nanosheets) are two-dimensional crystalline porous polymers with in-plane covalent bonds and out-of-plane Van der Waals forces. Owing to the customizable structure, chemical modification, and ultra-high porosity, COF nanosheets show many fascinating properties unique to traditional two-dimensional materials, and have shown potential applications in gas separation, sensors, electronic, and optoelectronic devices. This minireview aims to illustrate recent progress on two-dimensional covalent organic framework nanosheets, from two aspects of on-surface synthesis and potential applications. We first review the synthesis of COF nanosheets at the gas–solid interface. On-surface synthesis under ultrahigh vacuum and on-surface synthesis under vapor are highlighted. In addition, we also review the liquid–solid interface synthesis of COF nanosheets at various substrates, i.e., both crystalline and amorphous substrates. Beyond the synthesis, we highlight state-of-the-art applications of the COF nanosheets, particularly in charge transport, chemical sensors, and gas separation.

In an earlier publication (Van Wee & Banister, 2016), we explained that literature review papers (LRP) should explicitly report on the search and selection process of documents included. In this paper, we present two approaches for reporting the methodology for doing this: a basic approach and a reasoned approach. The basic approach includes reporting databases(s), keywords, search strings, snowballing, the selection of documents, presenting an overview of documents included and reporting additional selection criteria (if applicable). The reasoned approach adds to the basic approach (what was done) by explicitly explaining the motivation for choices and showing the selection process graphically (why it was done). The two approaches should be seen as options, and not the only alternatives. We recommend that authors of LRPs depart from these approaches and modify them where appropriate. The important lesson is that authors should be explicit about the approach adopted, as this enables the reader to understand the thinking behind the LRP and the conclusions drawn.

Ferroelectric materials are fascinating for their non-volatile switchable electric polarizations induced by the spontaneous inversion-symmetry breaking. However, in all of the conventional ferroelectric compounds, at least two constituent ions are required to support the polarization switching1,2. Here, we report the observation of a single-element ferroelectric state in a black phosphorus-like bismuth layer3, in which the ordered charge transfer and the regular atom distortion between sublattices happen simultaneously. Instead of a homogenous orbital configuration that ordinarily occurs in elementary substances, we found the Bi atoms in a black phosphorous-like Bi monolayer maintain a weak and anisotropic sp orbital hybridization, giving rise to the inversion-symmetry-broken buckled structure accompanied with charge redistribution in the unit cell. As a result, the in-plane electric polarization emerges in the Bi monolayer. Using the in-plane electric field produced by scanning probe microscopy, ferroelectric switching is further visualized experimentally. Owing to the conjugative locking between the charge transfer and atom displacement, we also observe the anomalous electric potential profile at the 180° tail-to-tail domain wall induced by competition between the electronic structure and electric polarization. This emergent single-element ferroelectricity broadens the mechanism of ferroelectrics and may enrich the applications of ferroelectronics in the future.