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Joseph Anthony Tumbocon,1,2 Tina T Wong,3– 5 Thanendthire Sangapillai,6 Yung-Chang Yen,7 Sang-Woo Park,8 Hsien Han Lim,9 Ngamkae Ruangvaravate10 1Eye Institute, St. Luke’s Medical Center, Quezon City, Philippines; 2Department of Ophthalmology, St. Luke’s Medical Center College of Medicine, Quezon City, Philippines; 3Glaucoma Department, Singapore National Eye Centre, Singapore, Singapore; 4Cataract & Comprehensive Ophthalmology Department, Singapore Eye Research Institute, Singapore, Singapore; 5Ophthalmology & Visual Sciences, Duke-NUS Graduate Medical School, Singapore, Singapore; 6Tun Hussein Onn National Eye Hospital, Petaling Jaya, Selangor, Malaysia; 7Department of Ophthalmology, Chi Mei Medical Center, Tainan City, Taiwan; 8Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju, South Korea; 9Eye Centre, Sunway Medical Centre, Petaling Jaya, Selangor, Malaysia; 10Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Joseph Anthony Tumbocon, Eye Institute, St. Luke’s Medical Center, 279 E Rodriguez Sr. Ave, Quezon City, Metro Manila, 1112, Philippines, Email jatumbocon@gmail.comBackground: Preserved prostaglandin analogs (PGAs) have been linked to ocular surface disease (OSD). While the benefits of preservative-low (PL) or -free (PF) Tafluprost (Santen Inc., Japan) were reported in real-world studies in Western countries, this is the first study in Asia to assess the effectiveness and safety of switching from preserved PGA to PL or PF-Tafluprost.Methods: We conducted a meta-analysis on studies that included adults (> 18 years of age) with a Corneal Fluorescein Staining Score (CFS) > 1. These individuals had switched to PL or PF-tafluprost after using a preserved PGA therapy for at least 3 months for glaucoma and were identified from Santen’s tafluprost study database. A total of six studies from South Korea, Philippines, Malaysia, Singapore, Thailand, Taiwan were pooled for analysis.Results: An intraocular pressure (IOP) reduction of 5.9% (0.91 mmHg) was seen in 265 patients. However, this result was not statistically significant (95% CI: − 3.64, 1.81; Figure 1). Among 132 patients, a 47.9% reduction in the CFS (95% CI: − 3.65, − 1.91) was seen. Tear film break-up (n=183) significantly increased by 1.06 seconds (95% CI: 0.65, 1.47). In 88 patients, the bulbar conjunctiva score decreased by − 0.46 (95% CI: − 0.81, − 0.10) and palpebral conjunctiva score decreased by − 0.42 (95% CI: − 0.67– 0.17). One or more new adverse reactions were reported in 3% of the individuals after switching.Conclusion: Tafluprost IOP reduction is comparable to other PGAs, with significant improvements in the ocular surface and minimal adverse reactions which were already previously reported.Keywords: ocular surface disease, glaucoma, preserved prostaglandins, tafluprost, PGA, preservative-free, preservative-low, Asian population, meta analysis

Dementia is increasing dramatically with an increasing elderly population. Pharmacological interventions are proven to have limited efficacy to treat many of the features of dementia. In such a situation, non-pharmacological means become important to help people with dementia, especially music therapy. The efficacy of music intervention on cognition has been barely explored in the literature, and the few studies that are available present inconsistent results. The aim of this systematic review is to have a meta-analysis on the effect of music therapy for improvements in cognitive functions as well as neuropsychiatric symptoms in the elderly with dementia.

Moumita Rakshit,1 Archana Gautam,1 Li Zhen Toh,2 Ying Shi Lee,2 Hui Ying Lai,1 Tina T Wong,1,2 Kee Woei Ng1,3– 5 1School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore; 2Ocular Therapeutics and Drug Delivery, Singapore Eye Research Institute, Singapore 169856, Singapore; 3Environmental Chemistry and Materials Centre, Nanyang Environment & Water Research Institute, Singapore 637141, Singapore; 4Skin Research Institute of Singapore, Singapore 138648, Singapore; 5Center for Nanotechnology and Nanotoxicology, Harvard T.H. Chan School of Public Health, Cambridge, MA 02115, USACorrespondence: Tina T Wong; Kee Woei Ng Tel +65 6322 8313; +65 6513 8294Email tina.wong.t.l@singhealth.com.sg; kwng@ntu.edu.sgBackground: Hydroxyapatite (HA) [Ca5(PO4)3(OH)] is a naturally occurring calcium phosphate which makes up 60– 70% of the dry weight of human bones. Nano-scale HA particles are increasingly being used as carriers for controlled and targeted delivery of bioactive agents like drugs, proteins, and nucleic acids due to their high porosity, negative charge, and biodegradability.Purpose: Although much effort has been devoted to understanding the delivery kinetics and effects of the payloads in such carriers, a thorough understanding of the influence of the carriers themselves is lacking.Methods: HA particles (300 μg/mL) were administered to primary human dermal fibroblasts (HDFs). The uptake and intracellular localization of the particles were determined by flow cytometry, confocal imaging, and transmission electron microscopy (TEM). Immunological assays and PCR were performed to determine the levels of pro-inflammatory cytokines and collagens in cell lysates and media supernatant.Results: The current study explores the effects of poly-dispersed HA particles on primary HDFs as a model system. The majority of the particles were determined to range between 150 and 200 nm in diameter. Upon exposure to HA suspensions, primary HDFs internalized the particles by endocytosis within 6 hours of exposure, showing maximum uptake at 72 hours following which the particles were exocytosed by 168 hours. This correlated to reduced secretion of various pro-inflammatory and pro-collagenic cytokines. Biochemical analysis further revealed a reduction in Type I collagen expression and secretion.Conclusion: HA particles have an immune-modulatory effect on dermal fibroblasts and reduce collagen production, which may impact the integrity of the extracellular matrix (ECM). This study demonstrates the need to consider the secondary effects of particulate carriers like HA, beyond basic cytotoxicity, in the specific tissue environment where the intended function is to be realized.Keywords: carrier particles, collagen expression, extracellular matrix, time-weighted average exposure

Liana J Tedesco,1 Hasani W Swindell,1 Forrest L Anderson,1 Eugene Jang,1 Tony T Wong,2 Jonathan K Kazam,2 R Kumar Kadiyala,3 Charles A Popkin1 1Center for Shoulder, Elbow and Sports Medicine, Columbia University Medical Center, New York, NY, USA; 2Department of Radiology, New York Presbyterian Hospital, New York, NY, USA; 3Department of Orthopedic Surgery, Columbia University Medical Center, New York, NY, USACorrespondence: Charles A PopkinColumbia University Medical Center, 622 West 168 St, PH – 11, New York, NY 10032, USAEmail cp2654@columbia.eduAbstract: Ice hockey continues to be a popular, fast-paced, contact sport enjoyed internationally. Due to the physicality of the game, players are at a higher risk of injury. In the 2010 Winter Olympics, men’s ice hockey had the highest injury rate compared to any other sport. In this review, we present a comprehensive analysis of evaluation and management strategies of common hand, wrist, and elbow injuries in ice hockey players. Future reseach focusing on the incidence and outcomes of these hand, wrist and elbow injuries in ice hockey players is warranted.Keywords: ice hockey, dorsal ulnotriquetral ligament, olecranon bursitis, Os styloideum, gamekeeper’s thumb

Valencia Hui Xian Foo,1 Sarah En Mei Tan,2 David Ziyou Chen,3 Shamira A Perera,1,4 Charumathi Sabayanagam,4,5 Eva Katie Fenwick,4,5 Tina T Wong,1,4,5 Ecosse L Lamoureux4–6 1Singapore National Eye Centre, Singapore; 2Tan Tock Seng Hospital, Singapore; 3Department of Ophthalmology, National University of Singapore and National University Health System, Singapore; 4Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; 5Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore; 6Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia Objective: The aim of this study was to evaluate patients’ dissatisfaction with overall and specific aspects of a tertiary glaucoma service and to determine their independent factors, including intraocular pressure (IOP) and visual acuity (VA). Methods: Patients, aged ≥21 years, from a specialist glaucoma service in a tertiary eye hospital in Singapore for at least 6 months, were recruited for this cross-sectional study between March and June 2014. All consenting patients completed a 7-area glaucoma-specific satisfaction questionnaire and one item related to satisfaction with overall glaucoma care. We determined the top three areas of dissatisfaction and overall dissatisfaction with the glaucoma service. We also explored the independent factors associated with overall and specific areas of patients’ dissatisfaction with their glaucoma care, including VA and IOP by using logistic regression models. Results: Of the 518 patients recruited, 438 (84.6%) patients completed the study. Patients’ dissatisfaction with the overall glaucoma service was 7.5%. The three areas of glaucoma service with the highest dissatisfaction rates were as follows: 1) explanation of test results (24.8%); 2) explanation of glaucoma complications (23.7%); and 3) advice on managing glaucoma (23.5%). Patients who were dissatisfied with the overall service had a worse mean VA compared with satisfied patients (logarithm of the minimum angle of resolution =0.41±0.43 vs 0.27±0.49, p=0.005), whereas mean IOP remained well-controlled in both the groups (13.55±2.46 mmHg vs 14.82±2.86 mmHg, p=0.014). In adjusted models, factors associated with overall dissatisfaction with glaucoma care included a pre-university education and above (odds ratio [OR] =8.06, 95% CI =1.57–41.27) and lower IOP (OR =0.83, 95% CI =0.71–0.98). Conclusion: Although less than one tenth of glaucoma patients were dissatisfied with the overall glaucoma service, one in four patients were dissatisfied with three specific aspects of care. A lower IOP, ironically, and education level were associated with overall dissatisfaction. Improving patients’ understanding of glaucoma test results, glaucoma complications, and disease management may increase patient satisfaction levels. Keywords: physician-patient relations, perception, attitude to health, surveys and questionnaires, quality of health care

Semra Ozdemir,1,* Hong King Wu,1,* Eric A Finkelstein,1 Tina T Wong2 1Signature Program in Health Services and Systems Research, Duke-NUS Medical School Singapore, 2Glaucoma Department, Singapore National Eye Centre, Singapore *These authors contributed equally to this work Aim: The objectives of this study were to explore parents' views about their children's use of regular eye drops and whether they would consider a sustained-release subconjunctival injection as a replacement for daily drops.Methods: A survey was conducted with 134 parents of children with chronic eye diseases at the Singapore National Eye Centre. Parents were asked their views about their children’s use of eye drops and were then presented with a discrete choice experiment that, via a series of trade-off tasks, allowed for estimating demand for a series of hypothetical subconjunctival injections that varied along product features, including interval between administrations, risk of complications, out-of-pocket cost and whether it is recommended by the patient’s treating physician.Results: Results showed that the vast majority of parents did not find administration of eye drops to be inconvenient (78%) nor did children complain about using daily eye drops (78%). Furthermore, only about half of parents whose child missed doses stated concerns about the consequences of non-compliance. The discrete choice experiment revealed that only one in five parents would consider a subconjunctival injection for their children. These parents tended to be more concerned about the consequences of non-compliance with eye drops, had children who administered the drops themselves or had other chronic disease requiring regular medication. Among these parents, risk of complications had the largest effect on injection uptake.Conclusion: This study shows that parents do not find administration of daily eye drops to be a significant burden. As a result, most would not consider a subconjunctival injection unless risk of complications was extremely small. Keywords: sustained-release subconjunctival injection, parent preferences, children’s use of eye drops

Janice Lam,1,2 Tina T Wong,1–4 Louis Tong1–3,5 1Singapore National Eye Centre, Singapore; 2Singapore Eye Research Institute, Singapore; 3Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 4School of Materials Science and Engineering, Nanyang Technological University, Singapore; 5Office of Clinical Sciences, Duke–National University of Singapore Graduate Medical School, Singapore Background: Our aim was to describe the demographics, risk factors, clinical signs, severity, and outcome of ocular surface disease (OSD) in 12 patients who had undergone trabeculectomy augmented with mitomycin C (MMC).Methods: Twelve glaucoma patients were referred to the Dry Eye Clinic (Singapore National Eye Centre) for further management of clinically significant OSD.Results: Of the 15 eyes from 12 patients, 14 were treated with MMC and one with 5-fluorouracil. Mean age was 69.3±10.6 years and two-thirds were male. The median interval before onset of dry eye symptoms after surgery was 13.5 months. Mean tear breakup time (TBUT) was 5.32 seconds and mean Schirmer score was 6.14 mm/5 min. Possible major risk factors for OSD in the cases include limbal stem cell deficiency occurring from exposure to antimetabolites, chronic use of antiglaucoma medications prior to surgery, and the preoperative status of the ocular surface prior to disease onset. Treatment of OSD resulted in improved best corrected visual acuity (BCVA) in 50% of the patients, with a median gain of two-line improvement in BCVA.Conclusion: OSD is a clinical problem often overlooked in patients who undergo antimetabolite-augmented filtration surgery. Recognition of the condition and appropriate treatment can improve patient symptoms and reduce health-care burdens on the economy. Keywords: cornea, glaucoma, ocular surface, trabeculectomy

Errol W Chan,1 Tina T Wong,2,3 Hla M Htoon,3 Ching L Ho,2 Donald T Tan,1,2,3 Jodhbir S Mehta2,3,4 1Department of Ophthalmology, National University Health System, Singapore; 2Singapore National Eye Centre, Singapore; 3Singapore Eye Research Institute, Singapore; 4Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore Objective: To compare the 3-year incidence of de novo ocular hypertension (OHT) after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). For DSAEK, to evaluate predictors for OHT and 2-year outcomes after OHT development. Methods: This was a review of the prospective Singapore Corneal Transplant Study at a single tertiary referral center. Consecutive DSAEKs and PKs for Fuchs’ endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) in eyes without pre-existing glaucoma were analyzed. OHT incidence after DSAEK and PK were compared using Kaplan–Meier survival analysis, and OHT risk factors identified using Cox proportional regression. OHT was defined: intraocular pressure (IOP) ≥ 24 mmHg or ≥ 10 mmHg from baseline. Secondary outcomes 2 years after OHT development in DSAEK were rates of glaucoma medical therapy failure, IOP success, graft failure and rejection, and best-spectacle corrected visual acuity (BSCVA). Results: There were 108 (96.4%) DSAEKs and 216 (96%) PKs. The 1-, 2- and 3-year de novo OHT incidence was not significantly different between DSAEK (36.1%, 47.2%, 47.2%, respectively) and PK (35.7%, 44.9%, 45.8%, respectively; P = 0.914). OHT incidence did not differ in subgroup analyses of multiple clinical variables (P > 0.1). OHT predictors after DSAEK were: fellow eye glaucoma (hazard ratio [HR] 3.20, P = 0.004), age

Feng-Yi Yang1, Ming-Che Teng1, Maggie Lu2, Hsiang-Fa Liang2, Yan-Ru Lee1, Chueh-Chuan Yen3, Muh-Lii Liang4,5, Tai-Tong Wong51Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 2Drug Delivery Laboratory, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 3Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, 4Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, 5Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, TaiwanBackground: High-dose tissue-specific delivery of therapeutic agents would be a valuable clinical strategy. We have previously shown that repeated transcranial focused ultrasound is able to increase the delivery of Evans blue significantly into brain tissue. The present study shows that repeated pulsed high-intensity focused ultrasound (HIFU) can be used to deliver high-dose atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes selectively to brain tumors.Methods: Firefly luciferase (Fluc)-labeled human GBM8401 glioma cells were implanted into NOD-scid mice. AP-1-conjugated liposomal doxorubicin or liposomal doxorubicin alone was administered followed by pulsed HIFU and the doxorubicin concentration in the treated brains quantified by fluorometer. Growth of the labeled glioma cells was monitored through noninvasive bioluminescence imaging and finally the brain tissue was histologically examined after sacrifice.Results: Compared with the control group, the animals treated with 5 mg/kg injections of AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin followed by repeated pulsed HIFU not only showed significantly enhanced accumulation of drug at the sonicated tumor site but also a significantly elevated tumor-to-normal brain drug ratio (P < 0.001). Combining repeated pulsed HIFU with AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin has similar antitumor effects.Conclusion: This study demonstrates that targeted or untargeted liposomal doxorubicin, followed by repeated pulsed HIFU, is a promising high-dose chemotherapy method that allows the desired brain tumor region to be targeted specifically.Keywords: repeated focused ultrasound, interleukin-4 receptor, blood-brain barrier, brain tumor, target drug delivery

Feng-Yi Yang1,*, Hsin-Ell Wang1,*, Guan-Liang Lin1, Hui-Hsien Lin1, Tai-Tong Wong21Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang-Ming University, 2Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan *These authors contributed equally to this workPurpose: The purpose of this study was to evaluate the permeability of the blood–brain barrier after sonication by pulsed high-intensity focused ultrasound and to determine if such an approach increases the tumor:ipsilateral brain permeability ratio.Materials and methods: F98 glioma-bearing Fischer 344 rats were injected intravenously with Evans blue with or without blood–tumor barrier disruption induced by transcranial pulsed high-intensity focused ultrasound. Sonication was applied at a frequency of 1 MHz with a 5% duty cycle and a repetition frequency of 1 Hz. The permeability of the blood–brain barrier was assessed by the extravasation of Evans blue. Contrast-enhanced magnetic resonance images were used to monitor the gadolinium deposition path associated with transcranial pulsed high-intensity focused ultrasound, and the influencing size and location was also investigated. In addition, whole brain histological analysis was performed. The results were compared by two-tailed unpaired t-test.Results: The accumulation of Evans blue in brains and the tumor:ipsilateral brain permeability ratio of Evans blue were significantly increased after pulsed high-intensity focused ultrasound exposure. Evans blue injection followed by sonication showed an increase in the tumor:ipsilateral brain ratio of the target tumors (9.14:1) of about 2.23-fold compared with the control tumors (x4.09) on day 6 after tumor implantation. Magnetic resonance images showed that pulsed high-intensity focused ultrasound locally enhances the permeability of the blood–tumor barrier in the glioma-bearing rats.Conclusion: This method could allow enhanced synergistic effects with respect to other brain tumor treatment regimens.Keywords: focused ultrasound, blood–brain barrier, permeability, brain tumor, glioma

Jayaganesh V Natarajan1*, Marcus Ang2*, Anastasia Darwitan1, Sujay Chattopadhyay3, Tina T Wong2, Subbu S Venkatraman1 1Materials Science and Engineering, Nanyang Technological University, Singapore; 2Singapore Eye Research Institute, Singapore; 3Polymer Division, Indian Institute of Technology Roorkee, India*These authors contributed equally to this workPurpose: To report the development and therapeutic evaluation of a liposomal nanocarrier for sustained release of latanoprost, in the rabbit eye.Methods: We fabricated latanoprost-loaded egg-phosphatidylcholine (EggPC) liposomes using the film hydration technique. The delivery vehicles were nano-sized (Z avg = 109 ± 18 nm), had a narrow poly dispersity index (PDI = 0.19 ± 0.04), and a very high loading efficiency (94% ± 5%). Based on in vitro data, we evaluated this formulation for lowering intraocular pressure (IOP) in rabbit eyes. Following a single subconjunctival injection of the latanoprost loaded formulation, the eyes were clinically monitored and the IOP recorded.Results: Latanoprost-loaded EggPC liposomes demonstrated a high drug/lipid mole ratio of 0.181, remained stable for at least 6 months on storage (4°C), and at least 1 month at 25°C. A slow and sustained release of 60% of latanoprost was achieved by 14 days in the in vitro release study. The same formulation demonstrated a greater sustained IOP lowering effect compared with daily administration of topical latanoprost beyond 90 days (4.8 ± 1.5 vs 2.5 ± 0.9 mmHg; P < 0.001). No signs of inflammation were evident in the eyes from slit-lamp examination analysis.Conclusion: The loading required for a long-term sustained delivery of latanoprost for up to 90 days in the rabbit eyes was achieved with EggPC liposomes. A single injection of latanoprost-loaded EggPC liposomes can lower the IOP for up to 90 days, with a greater IOP lowering effect than daily topical administration of latanoprost.Keywords: nanomedicine, nanoliposomes, EggPC, latanoprost, sustained ocular delivery, glaucoma

Raven's Coloured Progressive Matrices (CPM) is a widely used assessment tool for measuring general cognitive ability in developmental and educational research, particularly in studies involving young children. However, administering the full set of the 36-item CPM can be burdensome for young participants, hindering its practicality in large-scale studies and reducing research efficiency. In the current study, a short form of the CPM was developed based on a sample of preschoolers (n = 336, mean age = 5.8 years) using penalised regression, a machine learning approach that allows for variable selection. The resulting 12-item CPM short form demonstrated a very strong correlation with the total score of the 36-item full form (r = .94). Further investigations into the short form's item stability, content validity, and concurrent validity collectively supported its psychometric properties as a reliable and valid alternative to the full form. The significance of the CPM short form is also discussed., (© 2025 The Author(s). British Journal of Developmental Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Evaluating whether someone's behavior is praiseworthy or blameworthy is a fundamental human trait. A seminal study by Hamlin and colleagues in 2007 suggested that the ability to form social evaluations based on third-party interactions emerges within the first year of life: infants preferred a character who helped, over hindered, another who tried but failed to climb a hill. This sparked a new line of inquiry into the origins of social evaluations; however, replication attempts have yielded mixed results. We present a preregistered, multi-laboratory, standardized study aimed at replicating infants' preference for Helpers over Hinderers. We intended to (1) provide a precise estimate of the effect size of infants' preference for Helpers over Hinderers, and (2) determine the degree to which preferences are based on social information. Using the ManyBabies framework for big team-based science, we tested 1018 infants (567 included, 5.5-10.5 months) from 37 labs across five continents. Overall, 49.34% of infants preferred Helpers over Hinderers in the social condition, and 55.85% preferred characters who pushed up, versus down, an inanimate object in the nonsocial condition; neither proportion differed from chance or from each other. This study provides evidence against infants' prosocial preferences in the hill paradigm, suggesting the effect size is weaker, absent, and/or develops later than previously estimated. As the first of its kind, this study serves as a proof-of-concept for using active behavioral measures (e.g., manual choice) in large-scale, multi-lab projects studying infants., (© 2024 John Wiley & Sons Ltd.)

Purpose: TRK fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients., Experimental Design: We conducted an international retrospective cohort study of patients with TRK fusion-driven CNS tumors., Results: 119 patients were identified. The median age at time of diagnosis was 4.5 years. The majority were reported to have a histology consistent with a diagnosis of high-grade glioma (HGG) (57.1%) followed by low-grade glioma (LGG) (27.7%). Pediatric patients had a better prognosis with a median overall survival of 185.5 months compared to 24.8 months in adults (p<.0001). Patients with LGG also had a better outcome when compared to HGG (p=0.0012). The objective response was 68.8% with larotrectinib compared to 38.1% for non-targeted treatment., Conclusions: Children with LGG glioma had a favorable outcome compared to adult and HGG. TRK inhibitors appear to improve tumor control.

Purpose: We wished to evaluate if an open-source artificial intelligence (AI) algorithm ( https://www.childfx.com ) could improve performance of (1) subspecialized musculoskeletal radiologists, (2) radiology residents, and (3) pediatric residents in detecting pediatric and young adult upper extremity fractures., Materials and Methods: A set of evaluation radiographs drawn from throughout the upper extremity (elbow, hand/finger, humerus/shoulder/clavicle, wrist/forearm, and clavicle) from 240 unique patients at a single hospital was constructed (mean age 11.3 years, range 0-22 years, 37.9% female). Two fellowship-trained musculoskeletal radiologists, three radiology residents, and two pediatric residents were recruited as readers. Each reader interpreted each case initially without and then subsequently 3-4 weeks later with AI assistance and recorded if/where fracture was present., Results: Access to AI significantly improved area under the receiver operator curve (AUC) of radiology residents (0.768 [0.730-0.806] without AI to 0.876 [0.845-0.908] with AI, P < 0.001) and pediatric residents (0.706 [0.659-0.753] without AI to 0.844 [0.805-0.883] with AI, P < 0.001) in identifying fracture, respectively. There was no evidence of improvement for subspecialized musculoskeletal radiology attendings in identifying fracture (AUC 0.867 [0.832-0.902] to 0.890 [0.856-0.924], P = 0.093). There was no evidence of difference between overall resident AUC with AI and subspecialist AUC without AI (resident with AI 0.863, attending without AI AUC 0.867, P = 0.856). Overall physician radiograph interpretation time was significantly lower with AI (38.9 s with AI vs. 52.1 s without AI, P = 0.030)., Conclusion: An openly accessible AI model significantly improved radiology and pediatric resident accuracy in detecting pediatric upper extremity fractures., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background: Atypical teratoid rhabdoid tumor (ATRT) is an aggressive brain tumor that mainly affects young children. Our recent study reported a promising therapeutic strategy to trigger DNA damage, impede homologous recombination repair, and induce apoptosis in ATRT cells by targeting ribonucleotide reductase regulatory subunit M2 (RRM2). COH29, an inhibitor of RRM2, effectively reduced tumor growth and prolonged survival in vivo. Herein, we explored the underlying mechanisms controlling these functions to improve the clinical applicability of COH29 in ATRT., Methods: Molecular profiling of ATRT patients and COH29-treated cells was analyzed to identify the specific signaling pathways, followed by validation using a knockdown system, flow cytometry, q-PCR, and western blot., Results: Elevated E2F1 and its signaling pathway were correlated with poor prognosis. RRM2 inhibition induced DNA damage and activated ATM, which reduced Rb phosphorylation to promote Rb-E2F1 interaction and hindered E2F1 functions. E2F1 activity suppression led to decreased E2F1-dependent target expressions, causing cell cycle arrest in the G1 phase, decreased S phase cells, and blocked DNA damage repair., Conclusion: Our study highlights the role of ATM/Rb/E2F1 pathway in controlling cell cycle arrest and apoptosis in response to RRM2 inhibition-induced DNA damage. This provides insight into the therapeutic benefits of COH29 and suggests targeting this pathway as a potential treatment for ATRT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background/aims: To investigate whether compensating retinal nerve fibre layer (RNFL) thickness measurements for demographic and anatomical ocular factors can strengthen the structure-function relationship in patients with glaucoma., Methods: 600 eyes from 412 patients with glaucoma (mean deviation of the visual field (MD VF) -6.53±5.55 dB) were included in this cross-sectional study. Participants underwent standard automated perimetry and spectral-domain optical coherence tomography imaging (Cirrus; Carl Zeiss Meditec). Compensated RNFL thickness was computed considering age, refractive error, optic disc parameters and retinal vessel density. The relationship between MD VF and RNFL thickness measurements, with or without demographic and anatomical compensation, was evaluated sectorally and focally., Results: The superior arcuate sector exhibited the highest correlation between measured RNFL and MD VF, with a correlation of 0.49 (95% CI 0.37 to 0.59). Applying the compensated RNFL data increased the correlation substantially to 0.62 (95% CI 0.52 to 0.70; p<0.001). Only 61% of the VF locations showed a significant relationship (Spearman's correlation of at least 0.30) between structural and functional aspects using measured RNFL data, and this increased to 78% with compensated RNFL measurements. In the 10°-20° VF region, the slope below the breakpoint for compensated RNFL thickness demonstrated a more robust correlation (slope=1.66±0.18 µm/dB; p<0.001) than measured RNFL (slope=0.27±0.67 µm/dB; p=0.688)., Conclusion: Compensated RNFL data improve the correlation between RNFL measurements and VF parameters. This indicates that creating structure-to-function maps that consider anatomical variances may aid in identifying localised structural and functional loss in glaucoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The study aimed to evaluate the impact of compensating retinal nerve fiber layer (RNFL) thickness for demographic and anatomical factors on glaucoma detection in Chinese and Indian adults. A population-based study included 1995 healthy participants (1076 Chinese and 919 Indians) to construct a multivariable linear regression compensation model. This model was applied to 357 Chinese glaucoma patients, 357 healthy Chinese, and 357 healthy Indians using Cirrus spectral-domain optical coherence tomography (OCT). The compensated RNFL thickness considered age, refractive error, optic disc parameters, and retinal vessel density. Results showed that although the average RNFL thickness was significantly higher in Chinese participants compared to Indians, the compensation model reduced this difference to nonsignificance. Moreover, the compensation model significantly improved the area under the receiver operating characteristic curve (0.90 vs. 0.78; p<0.001), sensitivity (75% vs. 51%), and specificity (67% vs. 32%) in distinguishing Chinese glaucoma patients from healthy Indian individuals. The compensation model significantly enhanced the diagnostic accuracy of RNFL thickness in distinguishing glaucoma in the Chinese ethnic group compared to the OCT instrument's default values. These results suggest that modifying RNFL measurements based on individual characteristics can yield substantial benefits for glaucoma detection across ethnicities., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

Purpose: To describe the long-term outcomes of phacotrabeculectomy from a tertiary glaucoma service in Singapore., Design: Retrospective case series., Methods: Seven hundred ninety-six eyes of 698 patients who underwent phacotrabeculectomy surgery at the Singapore National Eye Centre between 2005 and 2007 with a minimum follow-up of three years were included. The primary outcome measure was intraocular pressure (IOP). Secondary outcomes included best-corrected visual acuity (BCVA), number of glaucoma medications, and surgical complications., Results: The mean age was 69.5 years, 51 % were male, and 86 % were Chinese. Most eyes had primary glaucoma (90.6 %). The mean follow-up duration was 9.4 years. The overall success rate at three years was 97 % if surgical success was defined as IOP ≤ 21 mm Hg, 92 % if IOP ≤ 18 mm Hg, 66 % if IOP ≤ 15 mm Hg. By Kaplan-Meier survival analysis over 13 years, the cumulative success rate fell from 98.1 % to 89.1 % if IOP ≤ 21 mm Hg, 98.1-76.9 % if IOP ≤ 18 mm Hg, 98-50.3 % if IOP ≤ 15 mm Hg. The postoperative IOP improved significantly at all time points (P < 0.05) and 72 % had at least 20 % IOP reduction. There was a slight improvement in postoperative BCVA (P < 0.05). The mean number of glaucoma medications was reduced postoperatively (P < 0.001). There were no significant risk factors for surgical failure., Conclusions: Phacotrabeculectomy was found to be safe, resulting in clinically significant IOP lowering for 13 years with reduced dependency on glaucoma medications and improved BCVA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Traditional halftoning usually drops colors when dithering images with binary dots, which makes it difficult to recover the original color information. We proposed a novel halftoning technique that converts a color image into a binary halftone with full restorability to its original version. Our novel base halftoning technique consists of two convolutional neural networks (CNNs) to produce the reversible halftone patterns, and a noise incentive block (NIB) to mitigate the flatness degradation issue of CNNs. Furthermore, to tackle the conflicts between the blue-noise quality and restoration accuracy in our novel base method, we proposed a predictor-embedded approach to offload predictable information from the network, which in our case is the luminance information resembling from the halftone pattern. Such an approach allows the network to gain more flexibility to produce halftones with better blue-noise quality without compromising the restoration quality. Detailed studies on the multiple-stage training method and loss weightings have been conducted. We have compared our predictor-embedded method and our novel method regarding spectrum analysis on halftone, halftone accuracy, restoration accuracy, and the data embedding studies. Our entropy evaluation evidences our halftone contains less encoding information than our novel base method. The experiments show our predictor-embedded method gains more flexibility to improve the blue-noise quality of halftones and maintains a comparable restoration quality with a higher tolerance for disturbances.

Sporadic vestibular schwannomas (VSs) are rare in children. When occurred in the pediatric population, they usually appear bilaterally and are related to neurofibromatosis type 2 (NF2). The current study reports a 4-year-old boy without family history of VS or NF2 who presented with a large (5.7-cm) VS involving the right cerebellopontine angle and internal auditory canal. Through seven-staged surgical interventions and two stereotactic γ‑knife radiosurgery, the disease was stabilized. At 2-year follow-up, the child had right ear hearing loss, grade IV facial palsy, and normal motor function and gait. No definite evidence of gene mutation regarding NF2 can be identified after sequence analysis and deletion/duplication testing. This case highlights the significance of considering the possibility of sporadic VSs, even in very young children. It emphasizes the importance of not overlooking initial symptoms, as they may indicate the presence of a large tumor and could potentially result in delayed diagnosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vasoactive-intestinal peptide (Vip) is a pleiotropic peptide with a wide range of distribution and functions. Zebrafish possess 2 isoforms of Vip (a and b), in which Vipa is most homologous to the mammalian form. In female zebrafish, Vipa can stimulate LH secretion from the pituitary but is not essential for female reproduction, as vipa-/- females display normal reproduction. In contrast, we have found that vipa-/- males are severely subfertile and sex ratio of offspring is female-biased. By analyzing all aspects of male reproduction with wild-type (WT) males, we show that the testes of vipa-/- are underdeveloped and contain ∼70% less spermatids compared to WT counterparts. The sperm of vipa-/- males displayed reduced potency in terms of fertilization (by ∼80%) and motility span and duration (by ∼50%). In addition, vipa-/- male attraction to WT females was largely nonexistent, indicating decreased sexual motivation. We show that vipa mRNA and protein is present in Leydig cells and in developing germ cells in the testis of WT, raising the possibility that endogenous Vipa contributes to testicular function. Absence of Vipa in vipa-/- males resulted in downregulation of 3 key genes in the androgen synthesis chain in the testis, 3β-hsd, 17β-hsd1, and cyp11c1 (11β-hydrogenase), associated with a pronounced decrease in 11-ketotestosterone production and, in turn, compromised reproductive fitness. Altogether, this study establishes a crucial role for Vipa in the regulation of male reproduction in zebrafish, like in mammals, with the exception that Vipa is also expressed in zebrafish testis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: The decision to treat children with benign epilepsy with centrotemporal spikes (BECTS) using antiseizure medications (ASM) is controversial. Our goal is to compare the effect of ASM treatment on the alteration of electroencephalographic (EEG) functional connectivity and power across four frequency bands in children with BECTS., Methods: Children with BECTS with two-year follow-up were retrospectively divided into ASM versus non-ASM groups. The network properties of the EEGs as based on network-based statistic and graph theory were evaluated by the following indices: global efficiency, clustering coefficient, betweenness centrality, and nodal strength in four frequency bands (delta, theta, alpha, and beta). EEG power including absolute power (AP) and relative power (RP) was analyzed in four frequency bands., Results: In children with BECTS with ASM treatment, there was no significant change in EEG connectivity across all bands before and after two years of ASM. In children with BECTS without ASM treatment, there was a significant increase of global efficiency, clustering coefficient, and nodal strength but not the betweenness centrality in the delta band after two years of follow-up. A decrease in AP in the delta and theta bands and a decrease in RP in the theta band were found in the ASM group after two years of treatment., Conclusions: Our results suggest that ASM may play a role in modulating the development of increasing overall brain connectivity and in downregulating overt synaptic activity, but not intrinsic focal connectivity, in the early years of BECTS. The changes in the EEG power indicate that ASM significantly normalized slow-wave band power., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The NG-Test CARBA 5 and Carbapenem-resistant K.N.I.V.O. Detection K-Set are lateral flow assays (LFAs) that rapidly detect five carbapenemases (KPC, NDM, IMP, VIM and OXA-48-like). We evaluated the effect of inoculum size on the performance of these two assays using 27 Enterobacterales isolates. Whole-genome sequencing (WGS) was used as the reference method. Using the NG-Test CARBA 5, eight Serratia spp. and six M. morganii isolates showed false-positive NDM results with a high inoculum. Using the Carbapenem-resistant K.N.I.V.O. Detection K-Set, eight M. morganii , four Serratia spp. and one K. pneumoniae isolates showed false-positive NDM and/or OXA-48-like bands at large inoculum sizes, while the other two M. morganii isolates demonstrated false-positive NDM and OXA-48-like results at all inoculum sizes. The false-positive bands varied in intensity. WGS confirmed that no carbapenemase gene was present. No protein sequence with a ≥50% identity to NDM or OXA-48-like enzymes was found. This study emphasizes the importance of assessing inoculum size in the diagnostic evaluation of LFAs.

Background/aims: To assess pupillary light responses (PLRs) in eyes with high myopia (HM) and evaluate the ability of handheld chromatic pupillometry (HCP) to identify glaucomatous functional loss in eyes with HM., Methods: This prospective, cross-sectional study included 28 emmetropes (EM), 24 high myopes without glaucoma (HM) and 17 high myopes with confirmed glaucoma (HMG), recruited at the Singapore National Eye Center. Monocular PLRs were evaluated using a custom-built handheld pupillometer that recorded changes in horizontal pupil radius in response to 9 s of exponentially increasing blue (469.1 nm) and red (640.1 nm) lights. Fifteen pupillometric features were compared between groups. A logistic regression model (LRM) was used to distinguish HMG eyes from non-glaucomatous eyes (EM and HM)., Results: All pupillometric features were similar between EM and HM groups. Phasic constriction to blue (p<0.001) and red (p=0.006) lights, and maximum constriction to blue light (p<0.001) were reduced in HMG compared with EM and HM. Pupillometric features of melanopsin function (postillumination pupillary response, PIPR area under the curve (AUC) 0-12 s (p<0.001) and PIPR 6 s (p=0.01) to blue light) were reduced in HMG. Using only three pupillometric features, the LRM could classify glaucomatous from non-glaucomatous eyes with an AUC of 0.89 (95% CI 0.77 to 1.00), sensitivity 94.1% (95% CI 82.4% to 100.0%) and specificity 78.8% (95% CI 67.3% to 90.4%)., Conclusion: PLRs to ramping-up light stimuli are unaltered in highly myopic eyes without other diagnosed ocular conditions. Conversely, HCP can distinguish glaucomatous functional loss in eyes with HM and can be a useful tool to detect/confirm the presence of glaucoma in patients with HM., Competing Interests: Competing interests: RPN, DM and TA have a patent application based on the handheld pupillometer used in this study (PCT/SG2018/050204): Handheld ophthalmic and neurological screening device. The rest of the authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Determine the utility of ZTE as an adjunct to routine MR for assessing degenerative disease in the cervical spine., Methods: Retrospective study on 42 patients with cervical MR performed with ZTE from 1/1/2022 to 4/30/22. Fellowship trained radiologists evaluated each cervical disc level for neural foraminal (NF) narrowing, canal stenosis (CS), facet arthritis (FA), and presence of ossification of the posterior longitudinal ligament (OPLL). When NF narrowing and CS were present, the relative contributions of bone and soft disc were determined and a confidence level for doing so was assigned. Comparisons were made between assessments on routine MR without and with ZTE., Results: With ZTE added, bone contribution as a cause of NF narrowing increased in 47% (n = 110) of neural foramina and decreased in 12% (n = 29) (p =  < 0.001). Bone contribution as a cause of CS increased in 25% (n = 33) of disc levels and decreased in 10% (n = 13) (p = 0.013). Confidence increased in identifying the cause of NF narrowing (p =  < 0.001)) and CS (p = 0.009) with ZTE. The cause of NF narrowing (p = 0.007) and CS (p = 0.041) changed more frequently after ZTE was added when initial confidence in making the determination was low. There was no change in detection of FA or presence of OPLL with ZTE., Conclusion: Addition of ZTE to a routine cervical spine MR changes the assessment of the degree of bone involvement in degenerative cervical spine pathology., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)