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Phaik Ling Quah,1 Lay Kok Tan,2 Ngee Lek,3,4 Serene Thain,2 Kok Hian Tan1,4 1Deparment of Obstetrics and Gynaecology, KK Women’s and Children’s Hospital, Singapore; 2Department of Maternal Fetal Medicine, KK Women’s and Children’s Hospital, Singapore; 3Department of Pediatrics, KK Women’s and Children’s Hospital, Singapore; 4OBGYN ACP, Duke-NUS Medical School, SingaporeCorrespondence: Phaik Ling Quah, Division of Obstetrics and Gynaecology, KK Women’s and Children’s Hospital (KKH), 100 Bukit Timah Road, 229899, Singapore, Tel +65 9773-2543, Email quah.phaik.ling@kkh.com.sgPurpose: This study examined the prospective association between CGM-derived glycemic variability (GV) and glycemic control (GC) parameters in the first and second trimester, with subsequent diagnosis of GDM in the early third trimester.Methods: In a longitudinal observational study, 60 study participants in the first trimester (9– 13 weeks’ gestation), and 53 participants (18– 23 weeks’ gestation) in the second trimester of pregnancy had CGM data extracted after a minimum of 8 days’ wear time (up to 14 days). At 24– 31 weeks’ gestation, participants underwent a 75 g, 2-hour oral glucose-tolerance test as per IADPSG criteria to diagnose GDM. GV parameters examined in both first and second trimesters were mean amplitude of glycemic excursion (MAGE), standard deviation (SD), mean glucose, and coefficient of variation (CV). GC parameters measured were J-Index and percentage of time spent in glucose target ranges.Results: The first trimester SD and MAGE were significantly higher in participants subsequently diagnosed with GDM (SD adjusted median 1.31 [interquartile range 1.2– 1.3] mmol/L; MAGE 3.26 [3.2– 3.3] mmol/L) than those who were not (SD 1.01 [0.9– 1.0] mmol/L, MAGE 2.59 [2.4– 2.6] mmol/L; p< 0.05). Similarly, second trimester SD and MAGE were also significantly higher in participants subsequently diagnosed with GDM (SD 1.35 [1.3– 1.4] mmol/L; MAGE 3.32 (3.31– 3.41) mmol/L) than those who were not (SD 0.99 [0.98– 1.01] mmol/L, MAGE 2.42 [2.42– 2.55] mmol/L; p< 0.05). Associations between SD and MAGE with GDM outcomes were adjusted for prepregnancy BMI and ethnicity. There were nonsignificant trends of higher J-Index scores in the first and second trimester, higher CV in the first trimester only, and higher mean in the second trimester only in participants diagnosed with GDM. Other study parameters measured were not significantly different between groups (p> 0.003).Conclusion: Our study suggests the potential value of CGM-derived SD and MAGE in early pregnancy as potential predictors of subsequent GDM diagnosis.Keywords: continuous glucose monitoring, glycemic parameters, glycemic control, diabetes in pregnancy

Local transmission of chikungunya, a debilitating mosquito-borne viral disease, was first reported in Singapore in January 2008. After 3 months of absence, locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak that resulted in a total of 231 cases by September 2008. The circulating viruses were related to East, Central, and South African genotypes that emerged in the Indian Ocean region in 2005. The first local outbreak was due to a wild-type virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where Aedes aegypti mosquitoes were the primary vector. Strains isolated during subsequent outbreaks showed alanine to valine substitution (A226V) and largely spread in areas predominated by Ae. albopictus mosquitoes. These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas. [ABSTRACT FROM AUTHOR]

T cell acute lymphoblastic leukemia (T-ALL) is difficult to treat when it relapses after therapy or is chemoresistant; the prognosis of patients with relapsed or refractory T-ALL is generally poor. We report a case series of 17 such patients who received autologous chimeric antigen receptor (CAR) T cells expressing an anti-CD7 CAR and an anti-CD7 protein expression blocker (PEBL), which prevented CAR T cell fratricide. Despite high leukemic burden and low CAR T cell dosing, 16 of the 17 patients attained minimal residual disease-negative complete remission within 1 month. The remaining patient had CD7 - T-ALL cells before infusion, which persisted after infusion. Toxicities were mild: cytokine release syndrome grade 1 in ten patients and grade 2 in three patients; immune effector cell-associated neurotoxicity syndrome grade 1 in two patients. Eleven patients remained relapse-free (median follow-up, 15 months), including all nine patients who received an allotransplant. The first patient is in remission 55 months after infusion without further chemotherapy or transplantation; circulating CAR T cells were detectable for 2 years. T cells regenerating after lymphodepletion lacked CD7 expression, were polyclonal and responded to SARS-CoV-2 vaccination; CD7 + immune cells reemerged concomitantly with CAR T cell disappearance. In conclusion, autologous anti-CD7 PEBL-CAR T cells have powerful antileukemic activity and are potentially an effective option for the treatment of T-ALL., Competing Interests: Competing interests: B.L.Z.O., N.S., E.C., L.P., S.H.R.L., F.Y., L.K.T., L.Y.A.C., N.T., S.P.C., F.D.B. and M.B. declare no competing interests. E.C.-S.’s spouse receives royalties for patents related to the development of CAR T cell technologies and is a scientific founder and stockholder of Nkarta Therapeutics and Medisix Therapeutics. N.L.B. is a co-inventor in a pending patent for a method to monitor virus-specific T cells in biological samples. A.B. is a co-inventor in a pending patent for a method to monitor virus-specific T cells in biological samples and is a cofounder of Lion TCR. F.L. has been a consultant for Amgen, Bellicum, Novimmune and Vertex and a speaker for BluebirdBio and Amgen. A.E.J.Y. has been a consultant for Amgen. D.C. receives royalties for patents related to the development of CAR T cell technologies and is a scientific founder and stockholder of Nkarta Therapeutics and Medisix Therapeutics., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aims: Exposure to passive smoking among adolescents is a public health concern. This study aims to explore demographic and lifestyle factors associated with perception of passive smoking risk and the mediating effects of exposure to anti-smoking advertisements and education about the dangers of smoking on the relationship between grade levels and the perception., Method: Data from the Tobacco and E-Cigarette Survey among Malaysian Adolescents ( n = 13,117) were analysed. Ordered probit models were used to assess factors associated with passive smoking risk perception (i.e. not harmful, probably not harmful, probably harmful, harmful)., Results: About one-third of adolescents did not perceive that passive smoking was harmful (30.4%). Adolescents with the perception that passive smoking was not harmful were more likely to be students at low grade levels, be males, be non-Malays and be low-pocket-money recipients and those who used e-cigarettes and who smoked. Being aware of anti-smoking advertisements (direct effect = 0.174; indirect effect = 0.012) and taught on the dangers of smoking (direct effect = 0.179; indirect effect = 0.003) partially mediated the positive relationship between grade levels and perceived risk of passive smoking., Conclusion: Policies implemented to reduce exposure to passive smoking should highlight the important role of demographic factors, lifestyle profiles, anti-smoking advertisements and education about the dangers of smoking in improving passive smoking risk perception among adolescents., Competing Interests: Conflict of InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Advanced care planning (ACP) is a series of ongoing voluntary discussions between patients, families and healthcare professionals to plan for their future healthcare needs. Despite patients with rheumatic diseases having high symptom burden and disease complications, the ACP completion rates in patients with rheumatic diseases remain low. In this quality improvement project, we aimed to increase the number of completed ACP in a tertiary referral rheumatology centre in Singapore from 0 to 1 per month. We showed a statistically significant increase in ACP completion across 1 year with two Plan-Do-Study-Act cycles. Further studies are needed to explore further interventions for ACP completion in patients with rheumatic diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cytomegalovirus (CMV) is the most common congenital infection in pregnancy with potential long-term adverse effects on the fetus. There is limited data on CMV seroprevalence in pregnant women in Singapore, with last reported study dating back over two decades. We look at the latest CMV seroprevalence in antenatal population in Singapore., Methods: Between January 2021 and August 2021, 385 pregnant women receiving antenatal care at Singapore General Hospital were randomly selected for CMV IgG test to be performed on their blood samples collected during the first trimester of their pregnancies. Positivity for CMV IgG represents past exposure prior to pregnancy., Results: Overall CMV seroprevalence was 71.7% (276/385) (95% CI 067, 0.76, p value < 0.001). The trend of CMV IgG positivity increased with age, 68.3% (95% CI 0.60, 0.76, p value < 0.001) in those aged 20-29, 72.5% (95% CI 0.66, 0.78, p value < 0.001) in the 30-39 age group, and 79.0% (95% CI 0.67, 0.76, p value 0.012) in women over 40., Conclusions: There is a declining trend in CMV seroprevalence among pregnant women in Singapore, which indicates that a substantial portion of this population faces the risk of primary maternal CMV infection during pregnancy. Emerging research suggests that prenatal treatment with valacyclovir effectively reduces the likelihood of vertical transmission. Considering this evidence, it is imperative to reevaluate the recommendations for universal maternal CMV screening during pregnancy., (© 2024. The Author(s).)

Background: Fluoroscopy guided interventions (FGIs) pose a risk of prolonged radiation exposure; personalized patient dosimetry is necessary to improve patient safety during these procedures. However, current FGIs systems do not capture the precise exposure regions of the patient, making it challenging to perform patient-procedure-specific dosimetry. Thus, there is a pressing need to develop approaches to extract and use this information to enable personalized radiation dosimetry for interventional procedures., Purpose: To propose a deep learning (DL) approach for the automatic localization of 3D anatomical landmarks on randomly collimated and magnified 2D head fluoroscopy images., Materials and Methods: The model was developed with datasets comprising 800 000 pseudo 2D synthetic images (mixture of vessel-enhanced and non-enhancement), each with 55 annotated anatomical landmarks (two are landmarks for eye lenses), generated from 135 retrospectively collected head computed tomography (CT) volumetric data. Before training, dynamic random cropping was performed to mimic the varied field-size collimation in FGI procedures. Gaussian-distributed additive noise was applied to each individual image to enhance the robustness of the DL model in handling image degradation that may occur during clinical image acquisition in a clinical environment. The model was trained with 629 370 synthetic images for approximately 275 000 iterations and evaluated against a synthetic image test set and a clinical fluoroscopy test set., Results: The model shows good performance in estimating in- and out-of-image landmark positions and shows feasibility to instantiate the skull shape. The model successfully detected 96.4% and 92.5% 2D and 3D landmarks, respectively, within a 10 mm error on synthetic test images. It demonstrated an average of 3.6 ± 2.3 mm mean radial error and successfully detected 96.8% 2D landmarks within 10 mm error on clinical fluoroscopy images., Conclusion: Our deep-learning model successfully localizes anatomical landmarks and estimates the gross shape of skull structures from collimated 2D projection views. This method may help identify the exposure region required for patient-specific organ dosimetry in FGIs procedures., (© 2024 American Association of Physicists in Medicine.)

Background: Post-transplant or hematological cancer patients have a higher risk of mortality after infection with ancestral and early variants of severe acute respiratory syndrome (SARS)-CoV-2. Adoptive cell therapy (ACT) with virus-specific T cells (VSTs) could augment endogenous T cell immunity to avoid disease deterioration before viral clearance., Methods: We established a third-party SARS-CoV-2-specific T cell (COVID-T) bank in 2020 (NCT04351659) using convalescent and/or vaccinated donors. In a phase I/II study (NCT04457726), 13 adult and pediatric patients, acutely positive for SARS-CoV-2 and predicted to have a high chance of mortality, were recruited from September 2021 to February 2022. Twelve patients received a single dose of COVID-T cells, matched on at least 1 HLA., Results: A dose of either 75,000 or 150,000 IFN-γ+CD3+ cells/m 2 SARS-COV-2-specific T cells did not cause cytokine release syndrome, acute respiratory distress syndrome, or graft-versus-host disease. In the 8 patients who had detectable donor SARS-COV-2-specific T cells after ACT, none progressed to severe disease or died with COVID-19. In contrast, among the other four patients without evidence of donor micro-chimerism, two died of COVID-19., Conclusions: Long-acting third-party VSTs from convalescent or vaccinated donors could be expediently produced and might be clinically useful in future pandemics, particularly before global vaccination is implemented., Competing Interests: Declaration of competing interest W.L. is a part-time employee of Miltenyi Biotec. All authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier Inc.)

The HIV treatment landscape for adults has progressed dramatically in recent decades; however, paediatric populations continue to experience delayed and limited access to effective and safe antiretroviral therapy options. Despite current incentive programmes, formulation research and development and approved drug dosing for children have been limited, particularly for neonates (aged <4 wk). Regulatory approval of drug formulations and dosing in children may lag behind adult approvals by years. Formulation and trial design adjustments complicate paediatric drug development, all of which are vital to accommodate for physiological differences, organ maturation, and rapid weight gain, which are most significant in the youngest children. To facilitate more rapid anti-infective drug development for paediatric populations, regulatory agencies provide guidelines that include extrapolating efficacy and safety data from relevant populations; using pharmacokinetic (PK) bridging and modelling to reduce sample sizes and limit the number of PK studies needed before efficacy analyses; and enrolling age- or weight-based cohorts in parallel rather than sequentially for clinical trials. Ensuring access to approved drugs poses an additional challenge, as uncertainty in demand leads to manufacturing and supply complexity with potentially higher costs that can be a barrier to uptake. Here we summarise challenges in drug development for children living with HIV, which are not unique to antiretrovirals. We aim to propose strategies for how model-based approaches and global partnerships can overcome some of these barriers to accelerate paediatric drug development, with particular reference to HIV, and how lessons learnt from HIV could be extended to other anti-infectives., Competing Interests: Declaration of competing interests AMB, HC, RD, ZL, TE, CB, SM, and LKT are employees of ViiV Healthcare or GSK and own stock in GSK. AB serves on advisory boards pertaining to long-acting cabotegravir for post-natal prophylaxis and dolutegravir product rollout for ViiV Healthcare. TR has no conflicts to disclose., (Copyright © 2024 ViiV Healthcare. Published by Elsevier Ltd.. All rights reserved.)

Background/objective: We investigated the relationship between daily adequate FV intake and risk of all-cause, cardiovascular disease (CVD), and cancer mortalities among Malaysian adults., Methods: Data from a total of 18,211 Malaysian adults aged 18 years and above whom participated in the National Health and Morbidity Survey 2011 were analyzed. The participants were followed up for approximately 11 years, and mortality data were ascertained through record linkages with the death registry from the Malaysian National Registration Department. Multiple Cox regression was applied to assess the association between daily adequate FV intake and risk of all-cause, CVD, and cancer mortalities, adjusting for sociodemographic, lifestyle, and health conditions., Results: During the follow-up period, we observed a total of 1809 all-cause, 374 CVD, and 216 cancer mortalities. No significant association between daily adequate FV intake with all-cause mortality (adjusted hazard ratio (aHR): 1.01, 95% confidence interval (CI: 0.79-1.31), CVD mortality (aHR: 0.91, 95% CI: 0.57-1.47), and cancer mortality (aHR: 1.27, 95% CI: 0.74-2.17) were observed, even after excluding deaths that occurred in the first two years of observation., Conclusions: Further investigation on the type of FV intake and its preparation method with risk of mortality will provide a holistic insight into the causal relationship between FV intake and mortality.

Salmonella remains a significant foodborne pathogen globally with S . Typhimurium presenting as a frequently occurring serovar. This study aimed to characterize 67 S . Typhimurium isolates from humans, food, farms, and slaughterhouses collected in Singapore from 2016 to 2017. Using whole-genome sequencing analysis, the isolates were found to belong to either ST19 ( n = 33) or ST36 ( n = 34). ST36 predominated in human intestinal and chicken isolates, while human extra-intestinal and non-chicken food isolates belonged to ST19. Plasmids were predicted in 88.1% ( n = 59) of the isolates with the most common incompatibility group profiles being IncFIB(S), IncFII(S) and IncQ1. IncFIB(S) (adjusted p -value < 0.05) and IncFII(S) (adjusted p -value < 0.05) were significantly more prevalent in ST19 isolates, while Col156 (adjusted p -value < 0.05) was more significantly found in ST36 isolates. ST36 isolates exhibited higher resistance to multiple antibiotic classes such as penicillins, phenicols, folate pathway inhibitors, aminoglycosides, β-lactam/β-lactamase inhibitor combinations, tetracyclines, and fluoroquinolones. Phylogenetics analysis suggested potential shared routes of transmission among human, chicken, farm and slaughterhouse environments. Taken together, this study offers a cross-sectional epidemiological insight into the genomic epidemiology and antimicrobial landscape of S . Typhimurium isolates in Singapore, informing strategies for future public health and food safety surveillance., Competing Interests: The authors declare no conflicts of interest.

In March 2022, the US Food and Drug Administration expanded indications of TRIUMEQ, a once-daily fixed-dose combination (FDC) containing abacavir (ABC), dolutegravir (DTG), and lamivudine (3TC) to include pediatric patients weighing at least 10 kg for the treatment of HIV-1. Prior to this extension, the ABC 600 mg/DTG 50 mg/3TC 300 mg FDC tablet was approved for use only in the adult/adolescent population, weighing ≥40 kg while each component of the FDC was approved for its use in pediatric patients at least 3 months and older. A new child-friendly formulation was developed as an FDC dispersible tablet (DT) of ABC 60 mg/DTG 5 mg/3TC 30 mg for pediatric patients with a body weight ≥ 6 kg. The present work demonstrates the utility of applying a model-informed drug development (MIDD) approach to expedite ABC/DTG/3TC FDC approval for pediatric patients (≥10 to <40 kg) based on data from the existing individual components and formulation bridging. Population pharmacokinetic models developed for pediatric participants across all three components of ABC/DTG/3TC FDC were employed for exposure prediction and incorporated relative bioavailability data. The predicted plasma exposures of ABC, DTG, and 3TC for FDC doses were consistent with those observed for the single entities in pediatric and adult studies. Thus, safety and efficacy observed in the individual component studies could be adequately extrapolated to the FDC that results in similar exposure. The current work demonstrates the significance of MIDD approaches in facilitating expedited access to child-friendly formulations in the HIV-1 therapeutic area., (© 2024, The American College of Clinical Pharmacology.)

Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients)., Methods: A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied., Results: From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment., Conclusions: Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Aims: Radial sclerosing lesions (RSLs) are benign breast lesions composed of glandular and epithelial proliferations with stellate architecture and fibro-elastotic stroma, which can mimic invasive carcinoma on imaging. Surgical management following a core biopsy diagnosis of RSLs remains controversial., Methods and Results: We retrospectively identified core biopsies with RSLs without atypia who underwent subsequent surgical excision between 2015 and 2021. All core biopsy slides were reviewed to confirm the diagnosis. Imaging was reviewed to determine radiological-pathological concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ (DCIS) in the excision. The final cohort consisted of 130 core biopsies from 124 women (median age = 52 years, range = 27-76). The imaging modality was mammogram in 52 (40%) cases, MRI in 52 (40%) and ultrasound in 26 (20%). One hundred and seven (82%) core biopsies were vacuum-assisted and 23 (18%) were ultrasound-guided without vacuum assistance. The median lesion size on imaging was 9 mm (range = 2-41). Overall, two (1%) cases were upgraded at excision, including one microinvasive lobular carcinoma and one 2 mm focus of invasive mammary carcinoma with associated DCIS. In both cases, the upgraded foci of carcinoma were not closely associated with the biopsy site and were considered incidental upgrades., Conclusions: This study adds to the body of literature supporting observation, rather than routine excision of radial sclerosing lesions without atypia., (© 2024 John Wiley & Sons Ltd.)

This study aims to assess the accuracy of automatic atlas-based contours for various key anatomical structures in prostate radiotherapy treatment planning. The evaluated structures include the bladder, rectum, prostate, seminal vesicles, femoral heads and penile bulb. CT images from 20 patients who underwent intensity-modulated radiotherapy were randomly chosen to create an atlas library. Atlas contours of the seven anatomical structures were generated using four software packages: ABAS, Eclipse, MIM, and RayStation. These contours were then compared to manual delineations performed by oncologists, which served as the ground truth. Evaluation metrics such as dice similarity coefficient (DSC), mean distance to agreement (MDA), and volume ratio (VR) were calculated to assess the accuracy of the contours. Additionally, the time taken by each software to generate the atlas contour was recorded. The mean DSC values for the bladder exhibited strong agreement (>0.8) with manual delineations for all software except for Eclipse and RayStation. Similarly, the femoral heads showed significant similarity between the atlas contours and ground truth across all software, with mean DSC values exceeding 0.9 and MDA values close to zero. On the other hand, the penile bulb displayed only moderate agreement with the ground truth, with mean DSC values ranging from 0.5 to 0.7 for all software. A similar trend was observed in the prostate atlas contours, except for MIM, which achieved a mean DSC of over 0.8. For the rectum, both ABAS and MIM atlases demonstrated strong agreement with the ground truth, resulting in mean DSC values of more than 0.8. Overall, MIM and ABAS outperformed Eclipse and RayStation in both DSC and MDA. These results indicate that the atlas-based segmentation employed in this study produces acceptable contours for the anatomical structures of interest in prostate radiotherapy treatment planning., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Introduction: There is increasing evidence demonstrating the safety and benefits of physical activity (PA) in uncomplicated pregnancies. Literature has shown that pregnant women around the world do not engage in adequate exercise. This study aims to assess the current practices of exercise among pregnant women in Singapore, determine the proportion of women meeting different PA targets and evaluate the factors influencing the practice of exercise., Methods: In this cross-sectional study, pregnant women in different trimesters of pregnancy from KK Women's and Children's Hospital and Singapore General Hospital were surveyed. Information regarding patient demographics, attitudes and perceptions of exercise, and practice of exercise was collected. The International Physical Activity Questionnaire (IPAQ) was used to determine the amount of PA., Results: A total of 201 pregnant women aged 20-44 years were surveyed. Almost all (99.0%) participants thought that exercise was beneficial in pregnancy. Only 31.6% of them engaged in any moderate or vigorous leisure-time PA (LTPA) and they were active for a median of 120 min/week. Only 12.6% of the pregnant women met the national recommendations of at least 150 min of moderate exercise per week. The amount of total PA performed was lower among women in later trimesters of pregnancy and higher among working mothers., Conclusion: Although most Singaporean pregnant women perceived exercise as beneficial, the majority did not engage in PA. Most of the participants did not meet the international PA targets and recently published national guidelines. More can be done to promote the uptake of exercise in pregnancy and optimise metabolic management of pregnant women in Singapore., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is an autoimmune central nervous system disorder in humans that commonly causes inflammatory demyelination in the optic nerves and spinal cord. Inflammation in the optic nerves is termed optic neuritis (ON). ON is a common clinical presentation; however, it is not necessarily present in all NMOSD patients. ON in NMOSD can be relapsing and result in severe vision loss. To the best of our knowledge, no study utilises deep learning to classify ON changes on MRI among patients with NMOSD. Therefore, this study aims to deploy eight state-of-the-art CNN models (Inception-v3, Inception-ResNet-v2, ResNet-101, Xception, ShuffleNet, DenseNet-201, MobileNet-v2, and EfficientNet-B0) with transfer learning to classify NMOSD patients with and without chronic ON using optic nerve magnetic resonance imaging. This study also investigated the effects of data augmentation before and after dataset splitting on cropped and whole images. Both quantitative and qualitative assessments (with Grad-Cam) were used to evaluate the performances of the CNN models. The Inception-v3 was identified as the best CNN model for classifying ON among NMOSD patients, with accuracy of 99.5%, sensitivity of 98.9%, specificity of 93.0%, precision of 100%, NPV of 99.0%, and F1-score of 99.4%. This study also demonstrated that the application of augmentation after dataset splitting could avoid information leaking into the testing datasets, hence producing more realistic and reliable results., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background/introduction: Traumatic brain injury (TBI) remains a leading cause of disability and mortality, with skull fractures being a frequent and serious consequence. Accurate and rapid diagnosis of these fractures is crucial, yet current manual methods via cranial CT scans are time-consuming and prone to error., Methods: This review paper focuses on the evolution of computer-aided diagnosis (CAD) systems for detecting skull fractures in TBI patients. It critically assesses advancements from feature-based algorithms to modern machine learning and deep learning techniques. We examine current approaches to data acquisition, the use of public datasets, algorithmic strategies, and performance metrics RESULTS: The review highlights the potential of CAD systems to provide quick and reliable diagnostics, particularly outside regular clinical hours and in under-resourced settings. Our discussion encapsulates the challenges inherent in automated skull fracture assessment and suggests directions for future research to enhance diagnostic accuracy and patient care., Conclusion: With CAD systems, we stand on the cusp of significantly improving TBI management, underscoring the need for continued innovation in this field., 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 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Objective: This study evaluated the effects of receiving glucose feedback from continuous glucose monitoring (CGM) by intermittent scanning (unblinded group), and CGM with masked feedback (blinded group) in the subsequent development of gestational diabetes mellitus (GDM)., Study Design: This was a prospective, single-center, pilot, randomized controlled trial including n  = 206 pregnant women in the first trimester of pregnancy with no prior diagnosis of type 1 or type 2 diabetes. The participants were randomized into the unblinded group or blinded group and wore the CGM in the first trimester of pregnancy (9-13 weeks), the second trimester of pregnancy (18-23 weeks), and late-second to early-third trimester (24-31 weeks). The primary outcome was GDM rate as diagnosed by the 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks., Results: Over 47 months, 206 pregnant women were enrolled at 9 to 13 weeks. The unblinded group had a higher prevalence of women who developed GDM (21.5 vs. 14.9%; p  > 0.05), compared to the blinded group. In the unblinded group compared to the blinded group, plasma glucose values were higher at 1 hour (median 7.7 [interquartile range {IQR}: 6.3-9.2] vs. 7.5 [6.3-8.7]) and 2 hours (6.3 [5.8-7.7] vs. 6.2 [5.3-7.2]), but lower at 0 hour (4.2 [4.0-4.5] vs. 4.3 [4.1-4.6]; p  > 0.05). All these differences were not statistically significant., Conclusion: Glucose feedback from CGM wear in the first to the third trimester of pregnancy without personalized patient education failed to alter GDM rate., Key Points: · Continuous glucose monitoring (CGM) is feasible for use in pregnant women.. · No significant difference in gestational diabetes rates with or without CGM feedback.. · Future clinical trials should incorporate CGM education and personalized guidance to enhance study outcomes.., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Increased afterload in aortic stenosis (AS) induces left ventricle (LV) remodeling to preserve a normal ejection fraction. This compensatory response can become maladaptive and manifest with motion abnormality. It is a clinical challenge to identify contractile and relaxation dysfunction during early subclinical stage to prevent irreversible deterioration., Purpose: To evaluate the changes of regional wall dynamics in 3D + time domain as remodeling progresses in AS., Study Type: Retrospective., Population: A total of 31 AS patients with reduced and preserved ejection fraction (14 AS&#95;rEF: 7 male, 66.5 [7.8] years old; 17 AS&#95;pEF: 12 male, 67.0 [6.0] years old) and 15 healthy (6 male, 61.0 [7.0] years old)., Field Strength/sequence: 1.5 T Magnetic resonance imaging/steady state free precession and late-gadolinium enhancement sequences., Assessment: Individual LV models were reconstructed in 3D + time domain and motion metrics including wall thickening (TI), dyssynchrony index (DI), contraction rate (CR), and relaxation rate (RR) were automatically extracted and associated with the presence of scarring and remodeling., Statistical Tests: Shapiro-Wilk: data normality; Kruskal-Wallis: significant difference (P < 0.05); ICC and CV: variability; Mann-Whitney: effect size., Results: AS&#95;rEF group shows distinct deterioration of cardiac motions compared to AS&#95;pEF and healthy groups (TI AS&#95;rEF : 0.92 [0.85] mm, TI AS&#95;pEF : 5.13 [1.99] mm, TI healthy : 3.61 [1.09] mm, ES: 0.48-0.83; DI AS&#95;rEF : 17.11 [7.89]%, DI AS&#95;pEF : 6.39 [4.04]%, DI healthy : 5.71 [1.87]%, ES: 0.32-0.85; CR AS&#95;rEF : 8.69 [6.11] mm/second, CR AS&#95;pEF : 16.48 [6.70] mm/second, CR healthy : 10.82 [4.57] mm/second, ES: 0.29-0.60; RR AS&#95;rEF : 8.45 [4.84] mm/second; RR AS&#95;pEF : 13.49 [8.56] mm/second, RR healthy : 9.31 [2.48] mm/second, ES: 0.14-0.43). The difference in the motion metrics between healthy and AS&#95;pEF groups were insignificant (P-value = 0.16-0.72). AS&#95;rEF group was dominated by eccentric hypertrophy (47.1%) with concomitant scarring. Conversely, AS&#95;pEF group was dominated by concentric remodeling and hypertrophy (71.4%), which could demonstrate hyperkinesia with slight wall dyssynchrony than healthy. Dysfunction of LV mechanics corresponded to the presence of myocardial scarring (54.9% in AS), which reverted the compensatory mechanisms initiated and performed by LV remodeling., Data Conclusion: The proposed 3D + time modeling technique may distinguish regional motion abnormalities between AS&#95;pEF, AS&#95;rEF, and healthy cohorts, aiding clinical diagnosis and monitoring of AS progression. Subclinical myocardial dysfunction is evident in early AS despite of normal EF., Level of Evidence: 4 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background Multidisciplinary simulation training in the management of acute obstetric emergencies has the potential to reduce both maternal and perinatal morbidity. It is a valuable tool that can be adapted for targeted audiences of different specialities at all experience levels from medical students to senior consultants. Methods In this study, pre- and post-course questionnaires of learners with varying levels of clinical experience from Obstetrics and Gynaecology (O&G), Anaesthesia, Neonatology, Emergency Medicine, midwifery, and nursing who undertook two simulation courses (namely the Combined Obstetrics Resuscitation Training course, CORE, and the CORE Lite), which comprised lectures and simulation drills with manikins and standardized patients, between 2015 and 2023 were compared. This also included a period when training was affected by the coronavirus disease 2019 (COVID-19) pandemic.  Results The results showed that both simulation courses increased confidence levels among all learners in the management of obstetric emergencies.  Pre-course, participants were most confident in the management of neonatal resuscitation and severe pre-eclampsia, followed by postpartum haemorrhage. They were least confident in the management of vaginal breech delivery, uterine inversion, and twin delivery. Post-course, participants were most confident in the management of neonatal resuscitation and shoulder dystocia, followed by postpartum haemorrhage. They were least confident in the management of uterine inversion and maternal sepsis, followed by vaginal breech delivery and twin delivery. Whilst we saw a huge improvement in confidence levels for all obstetric emergencies, the greatest improvement in confidence levels was noted in vaginal breech delivery ,  twin delivery ,  and uterine inversion. Conclusion The simulation courses were effective in improving the confidence in the management of obstetric emergencies. While it may be difficult to measure the improvement in clinical outcomes as a result of simulation courses alone, the increase in confidence levels of clinicians can be used as a surrogate in measuring their preparedness in facing these emergency scenarios., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Li et al.)

Objectives: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study., Methods: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied., Results: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24)., Discussion: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There is a need to study the characteristics of outbreaks via Singapore's outbreak surveillance system to understand and identify the gaps in food safety for targeted policy interventions due to the increasing trend in gastroenteritis outbreaks and consequential increase in foodborne-related deaths and economic burden on public health systems worldwide. A total of 171 gastroenteritis outbreaks were investigated in Singapore from January 2018 to December 2021. This study analyzed the annual trend of investigated gastroenteritis outbreaks, the proportion of outbreaks by implicated sources of food, and the proportion of the type of pathogens identified from human cases, food samples, and environmental swabs collected from outbreak investigations. Among the foodborne gastroenteritis outbreaks (n = 121) investigated in Singapore, approximately 42.1% of the outbreaks had food prepared by caterers, 14.9% by restaurants, and 12.4% had food prepared by in-house kitchens. Clostridium perfringens and Salmonella were the most common causative pathogens in foodborne outbreaks throughout the analysis period. The food samples and environmental swabs collected were mostly detected for Bacillus cereus . Norovirus was the most common causative pathogen in non-foodborne outbreaks and was mainly attributable to preschools. This highlights the importance of monitoring and educating the catering industry and preschools to prevent future outbreaks.

The healthy eating plate concept has been introduced in many countries, including Malaysia, as a visual guide for the public to eat healthily. The relationship between Malaysian Healthy Plate (MHP) and adequate fruit and vegetable (FV) intake among morbid Malaysian adults is unknown. Hence, we investigated the relationship between awareness of the MHP and FV intake among morbid Malaysian adults. National survey data on 9760 morbid Malaysian adults aged 18 years and above were analyzed. The relationship between awareness of MHP and FV intake among Malaysian adults with obesity, diabetes mellitus, hypertension, and hypercholesterolemia were determined using multivariable logistic regression controlling for sociodemographic characteristics and lifestyle risk factors. Our data demonstrated that MHP awareness is associated with adequate FV intake among the Malaysian adults with abdominal obesity (adjusted odds ratio (aOR): 1.86, 95% confidence interval (CI): 1.05-3.29), diabetes mellitus (aOR: 4.88, 95% CI: 2.13-22.18), hypertension (aOR: 4.39, 95% CI: 1.96-9.83), and hypercholesterolemia (aOR: 4.16, 95% CI: 1.48-11.72). Our findings indicated the necessity for ongoing efforts by policymakers, healthcare professionals, and nutrition educators to promote the concept of MHP and ensure that morbid Malaysian adults consume a sufficient intake of FV or adopt a healthy eating pattern to achieve and maintain optimal health.

In fluoroscopy-guided interventions (FGIs), obtaining large quantities of labelled data for deep learning (DL) can be difficult. Synthetic labelled data can serve as an alternative, generated via pseudo 2D projections of CT volumetric data. However, contrasted vessels have low visibility in simple 2D projections of contrasted CT data. To overcome this, we propose an alternative method to generate fluoroscopy-like radiographs from contrasted head CT Angiography (CTA) volumetric data. The technique involves segmentation of brain tissue, bone, and contrasted vessels from CTA volumetric data, followed by an algorithm to adjust HU values, and finally, a standard ray-based projection is applied to generate the 2D image. The resulting synthetic images were compared to clinical fluoroscopy images for perceptual similarity and subject contrast measurements. Good perceptual similarity was demonstrated on vessel-enhanced synthetic images as compared to the clinical fluoroscopic images. Statistical tests of equivalence show that enhanced synthetic and clinical images have statistically equivalent mean subject contrast within 25% bounds. Furthermore, validation experiments confirmed that the proposed method for generating synthetic images improved the performance of DL models in certain regression tasks, such as localizing anatomical landmarks in clinical fluoroscopy images. Through enhanced pseudo 2D projection of CTA volume data, synthetic images with similar features to real clinical fluoroscopic images can be generated. The use of synthetic images as an alternative source for DL datasets represents a potential solution to the application of DL in FGIs procedures., (© 2023. Australasian College of Physical Scientists and Engineers in Medicine.)

Left ventricular adaptations can be a complex process under the influence of aortic stenosis (AS) and comorbidities. This study proposed and assessed the feasibility of using a motion-corrected personalized 3D + time LV modeling technique to evaluate the adaptive and maladaptive LV response to aid treatment decision-making. A total of 22 AS patients were analyzed and compared against 10 healthy subjects. The 3D + time analysis showed a highly distinct and personalized pattern of remodeling in individual AS patients which is associated with comorbidities and fibrosis. Patients with AS alone showed better wall thickening and synchrony than those comorbid with hypertension. Ischemic heart disease in AS caused impaired wall thickening and synchrony and systolic function. Apart from showing significant correlations to echocardiography and clinical MRI measurements (r: 0.70-0.95; p < 0.01), the proposed technique helped in detecting subclinical and subtle LV dysfunction, providing a better approach to evaluate AS patients for specific treatment, surgical planning, and follow-up recovery., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tafenoquine, co-administered with chloroquine, is approved for the radical cure (prevention of relapse) of Plasmodium vivax malaria. In areas of chloroquine resistance, artemisinin-based combination therapies are used to treat malaria. This study aimed to evaluate tafenoquine plus the artemisinin-based combination therapy dihydroartemisinin-piperaquine for the radical cure of P vivax malaria., Methods: In this double-blind, double-dummy, parallel group study, glucose-6-phosphate dehydrogenase-normal Indonesian soldiers with microscopically confirmed P vivax malaria were randomly assigned by means of a computer-generated randomisation schedule (1:1:1) to dihydroartemisinin-piperaquine alone, dihydroartemisinin-piperaquine plus a masked single 300-mg dose of tafenoquine, or dihydroartemisinin-piperaquine plus 14 days of primaquine (15 mg). The primary endpoint was 6-month relapse-free efficacy following tafenoquine plus dihydroartemisinin-piperaquine versus dihydroartemisinin-piperaquine alone in all randomly assigned patients who received at least one dose of masked treatment and had microscopically confirmed P vivax at baseline (microbiological intention-to-treat population). Safety was a secondary outcome and the safety population comprised all patients who received at least one dose of masked medication. This study is registered with ClinicalTrials.gov, NCT02802501 and is completed., Findings: Between April 8, 2018, and Feb 4, 2019, of 164 patients screened for eligibility, 150 were randomly assigned (50 per treatment group). 6-month Kaplan-Meier relapse-free efficacy (microbiological intention to treat) was 11% (95% CI 4-22) in patients treated with dihydroartemisinin-piperaquine alone versus 21% (11-34) in patients treated with tafenoquine plus dihydroartemisinin-piperaquine (hazard ratio 0·44; 95% CI [0·29-0·69]) and 52% (37-65) in the primaquine plus dihydroartemisinin-piperaquine group. Adverse events over the first 28 days were reported in 27 (54%) of 50 patients treated with dihydroartemisinin-piperaquine alone, 29 (58%) of 50 patients treated with tafenoquine plus dihydroartemisinin-piperaquine, and 22 (44%) of 50 patients treated with primaquine plus dihydroartemisinin-piperaquine. Serious adverse events were reported in one (2%) of 50, two (4%) of 50, and two (4%) of 50 of patients, respectively., Interpretation: Although tafenoquine plus dihydroartemisinin-piperaquine was statistically superior to dihydroartemisinin-piperaquine alone for the radical cure of P vivax malaria, the benefit was not clinically meaningful. This contrasts with previous studies in which tafenoquine plus chloroquine was clinically superior to chloroquine alone for radical cure of P vivax malaria., Funding: ExxonMobil, Bill & Melinda Gates Foundation, Newcrest Mining, UK Government all through Medicines for Malaria Venture; and GSK., Translation: For the Indonesian translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests IS reports grants or contracts from Menzies School of Health Research, Darwin and the National Health and Medical Research Council, and funding from Medicines for Malaria Venture (MMV) and GSK. AS, KC, RN, DS, YWS, II, WB, CBP, and SL report that they or their institutions received funding from MMV to do the study and editorial support from GSK for this publication. LLE and AWS report institutional funding from Menzies School of Health Research, MMV, and GSK. CC-D reports institutional funding from MMV, GSK, and the Chan Zuckerberg Initiative. IE reports institutional funding from MMV, GSK, WHO, SPARK (University of Melbourne), and honoraria from the Indonesian Ministry of Health. SD is an employee of MMV; his institution received funding from ExxonMobil, the Bill & Melinda Gates Foundation (grant number INV-007155/19-BMGF-006), Newcrest Mining, and the UK Government to fund the INSPECTOR study. EC is a former independent contractor at GSK and holds shares in the company. EC developed the first draft of the manuscript and provided editorial services as an independent medical writer funded by GSK. KR, DF, AB, SJ, KF, HS, AM, MT, and LKT are employees of GSK and hold shares in the company. J-PK, NG, and JAG are former employees of GSK and hold shares in GSK. JKB reports institutional research funding from MMV, GSK, the Wellcome Trust, the Gates Foundation, FIND, Sanaria, UKAid, University of Oxford, US Centers for Disease Control and Prevention, and the Chinese Center for Disease Control; travel and speaking fees from the Belgian Society of Tropical Medicine, the International Conference of Tropical Medicine and Malariology, and Singapore Malaria Group Conference; and participation on the US National Health Institute Data Safety Monitoring Board., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Perinatal depression and anxiety are public health concerns affecting approximately 1 in 10 women in Singapore, with clear evidence of association with various adverse outcomes in mother and child, including low birthweight, preterm birth and negative impact on infant neurodevelopment, temperament and behaviour. A workgroup was formed to develop recommendations to address the perinatal mental health needs of women with depression and anxiety. The approach was broad-based and aimed to incorporate holistic methods that would be readily applicable to the network of care providers supporting childbearing women., Method: The Grading and Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision framework was employed to draw these guidelines. Workgroup members-comprising experts in the field of perinatal mental health and obstetric medicine-deliberated on the public health needs of the target population, and reviewed literature published from 2001 to 2022 that were relevant to improve the well-being of women with depression and anxiety during the preconception and perinatal periods., Results: A consensus meeting was held involving a wider professional network, including family physicians, paediatricians, psychiatrists, social services and the Health Promotion Board in Singapore., Conclusion: Ten consensus statements were developed, focusing on the overall aim of achieving optimal perinatal mental health for women with depression and anxiety. They relate to awareness and advice on preconception mental health, screening and assessment, optimising care and treatment. Special considerations were recommended for women who suffered severe maternal events, tailoring care for adolescents and women with special needs, and addressing infant mental health needs., Competing Interests: There was no conflict of interest for all authors.

Objective: The aim of this study was to establish the incidence of liver abnormalities in psoriatic arthritis patients and identify the factors that contributed to this condition., Methods: This is a longitudinal cohort study. Psoriatic arthritis (PsA) patients with liver enzymes abnormalities were identified. Our control group consisted of PsA patient from the same cohort who had no history of liver abnormalities. Factors associated with liver abnormalities were identified using univariate and multivariate analysis., Results: A total of 247 of PsA patients were included and out of those, 99 developed liver enzymes abnormalities. The mean age of the patients was 56 years old (±13.5) with 56.1% female and 39.4% Indian descendants. The univariate logistic regression demonstrated that disease duration of PsA (OR=1.06, 95% CI=1.01 - 1.10, p=0.012), diabetes mellitus (OR=2.16, 95% CI=1.26 - 3.70, 0.005) and non-alcoholic fatty liver disease (NAFLD) (OR=3.90, 95% CI = 1.44 - 10.53, p=0.007) were associated with abnormal liver function in PsA patients. No association was found with both conventional synthetic disease-modifying antirheumatic drugs or biologics., Conclusion: Liver enzymes abnormalities in PsA patients were linked to disease duration, diabetes mellitus and NAFLD. For these high-risk populations, vigilant monitoring of liver function tests is vital for early detection and intervention., Competing Interests: None., (© 2024 The Mediterranean Journal of Rheumatology (MJR).)

Accurate methods for meat speciation and quantification are essential for ensuring the supply of safe and wholesome meat and composite products with animal origins to negate the potential associated hazards, aid classification of consignments at the import control system, and thwart food fraud committed for financial gain. To better enhance meat safety control and combat food fraud, this study developed two duplex real-time polymerase chain reaction (real-time PCR) systems specifically designed for chicken, pork, sheep, and beef, using single-copy, chromosomally encoded, species-specific gene sequences to accurately measure the content of each meat type in meat products. DNA extracted from the raw and boiled reference materials prepared in varying proportions (ranging from 1% to 75%) were used in the development of the duplex assay to derive calibration factors to determine the meat content in different meat products. The method was further validated using proficiency test samples and market monitoring samples. Our findings showed that this method exhibits high specificity and sensitivity, with a significant accuracy range of 0.14% to 24.07% in quantifying the four meat types in both raw and processed meat products. Validation results further confirmed the effectiveness of our method in accurately quantifying meat content. Thus, we have demonstrated the duplex qPCR assays as promising approaches for implementation in routine analysis to strengthen meat safety control systems and combat meat fraud, thereby safeguarding consumer health and trust in the meat industry.

This study investigates the feasibility of using texture radiomics features extracted from mammography images to distinguish between benign and malignant breast lesions and to classify benign lesions into different categories and determine the best machine learning (ML) model to perform the tasks. Six hundred and twenty-two breast lesions from 200 retrospective patient data were segmented and analysed. Three hundred fifty radiomics features were extracted using the Standardized Environment for Radiomics Analysis (SERA) library, one of the radiomics implementations endorsed by the Image Biomarker Standardisation Initiative (IBSI). The radiomics features and selected patient characteristics were used to train selected machine learning models to classify the breast lesions. A fivefold cross-validation was used to evaluate the performance of the ML models and the top 10 most important features were identified. The random forest (RF) ensemble gave the highest accuracy (89.3%) and positive predictive value (66%) and likelihood ratio of 13.5 in categorising benign and malignant lesions. For the classification of benign lesions, the RF model again gave the highest likelihood ratio of 3.4 compared to the other models. Morphological and textural radiomics features were identified as the top 10 most important features from the random forest models. Patient age was also identified as one of the significant features in the RF model. We concluded that machine learning models trained against texture-based radiomics features and patient features give reasonable performance in differentiating benign versus malignant breast lesions. Our study also demonstrated that the radiomics-based machine learning models were able to emulate the visual assessment of mammography lesions, typically used by radiologists, leading to a better understanding of how the machine learning model arrive at their decision., (© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Adenosine-to-inosine RNA editing, which is catalyzed by adenosine deaminases acting on RNA (ADAR) family of enzymes, ADAR1 and ADAR2, has been shown to contribute to multiple cancers. However, other than the chronic myeloid leukemia blast crisis, relatively little is known about its role in other types of hematological malignancies. Here, we found that ADAR2, but not ADAR1 and ADAR3, was specifically downregulated in the core-binding factor (CBF) acute myeloid leukemia (AML) with t(8;21) or inv(16) translocations. In t(8;21) AML, RUNX1-driven transcription of ADAR2 was repressed by the RUNX1-ETO additional exon 9a fusion protein in a dominant-negative manner. Further functional studies confirmed that ADAR2 could suppress leukemogenesis specifically in t(8;21) and inv16 AML cells dependent on its RNA editing capability. Expression of 2 exemplary ADAR2-regulated RNA editing targets coatomer subunit α and component of oligomeric Golgi complex 3 inhibits the clonogenic growth of human t(8;21) AML cells. Our findings support a hitherto, unappreciated mechanism leading to ADAR2 dysregulation in CBF AML and highlight the functional relevance of loss of ADAR2-mediated RNA editing to CBF AML., (© 2023 by The American Society of Hematology.)