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Whilst adaptive experts have well-researched beliefs and attitudes towards learning, what is unclear are the interactions that occur within the learning environment that constitute their learning experiences. The practice of geriatric medicine emphasises the interdisciplinary care of complex frail older adults. Our study sets out to understand the learning experiences of adaptive experts in geriatric medicine by examining how interactions at the intra-personal, inter-personal and organisational levels contributed to the development of adaptive expertise. We conducted an exploratory qualitative study through semi-structured interviews of 16 geriatricians experts from a tertiary hospital in Singapore. Data were analyzed via reflexive thematic analysis. The core essence of the learning experiences was described as a journey of 'knowing when we do not know', which was characterised by three themes: (i) Anchoring ethos of person-centric care where the experts drew upon their values to develop a holistic view of the patient beyond the medical domain, (ii) Enabling stance of being curious where their curiosity and openness to learning was nurtured through the practice of reflection, and with the benefit of time as a commodity and for development of expertise, and (iii) Scaffolding organisational culture of inquiry where an environment that is supportive of learning is built on the culture of psychological safety and the culture of mentoring. Taken together, our study highlighted the importance of interactions at the intra-personal, inter-personal and organisational levels in the learning experiences of adaptive experts.

Abstract Investigations into whether playing action video games (AVGs) benefit other tasks, such as driving, have traditionally focused on gaming experience (i.e., hours played). A potential problem with this approach is that AVG experience only partially indexes the cognitive skills developed via gaming, which are presumably the source of other task benefits. Thus, a focus on experience, instead of gaming proficiency (i.e., skill level), may account for inconsistencies in existing literature. We investigated whether AVG experience or proficiency best predicts performance in simulated driving. We hypothesised that proficiency would better predict driving performance (speed control, lane maintenance, spare cognitive capacity) than experience. One-hundred-and-sixteen participants drove in a simulator and played an AVG (Quake III Arena). Proficiency predicted all aspects of driving performance, while experience only predicted lane maintenance. These findings highlight the benefits of measuring AVG proficiency, with implications for the video games literature, driving safety and the transfer of skill-based learning.

Background Functional dependency may serve as a marker for positive SARC-F screen (Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls) among older adults at the Emergency Department (ED). We compared functional dependency between SARC-F– (

Introduction: Timely detection of dementia enables early access to dementia-specific care services and interventions. Various stakeholders brought together to refine Singapore’s dementia care strategy identified a lack of a standardised cognitive screening tool and the absence of a comparative review of existing tools. We hence conducted a rapid review to evaluate the diagnostic performance of brief cognitive screening tools in identifying possible dementia among community-dwelling older adults in Singapore. Method: Brief cognitive screening tools were defined as interviews or tests administered in ≤5 minutes. Studies performed in Singapore on older adults ≥60 years, which used locally-validated comparators and reported outcomes of clinician-diagnosed dementia were included. Rapid review methodology was used in study screening and selection. Quality Assessment of Diagnostic Accuracy Studies version 2 tool was used for risk-of-bias assessment. A negative likelihood ratio (LR-) of ≤0.2 was defined a priori as having a moderate effect in shifting post-test probability. Results: Fourteen studies were included in qualitative synthesis: 3 studies evaluated self-/informant-based tools only, 4 evaluated performance-based measures only and 7 evaluated combination approaches. Eight-item Informant Interview to Differentiate Aging and Dementia (AD8) was the most studied self-/informant-based tool. One study found informant AD8 (iAD8) superior to self-rated AD8. Another study found iAD8 superior to Mini-Mental State Examination. Among performance-based measures, Abbreviated Mental Test, Visual Cognitive Assessment Test-Short form version 1 (VCAT-S1), VCAT-S2 and Mini-Cog had LR-

The EXO+ hip protector was developed to minimize the risk of hip fractures in seniors following falls. This study evaluated its usability in a Singapore nursing home from the perspective of the staff, focusing on learnability, efficiency, and satisfaction. A mixed-method design was employed, with nursing home residents wearing the EXO+ daily for eight weeks. Quantitative data on wear time were collected alongside qualitative insights from four repeated focus group discussions with care staff. In total, 15 residents (including 8 residents with cognitive impairments) and 9 staff participated. The analysis revealed six themes and fourteen subthemes related to EXO+’s usability. The residents wore the device for an average of 1.54 h per day, with those having cognitive impairments showing increased wear times, especially in the mornings and on weekdays. The findings indicated that the EXO+ was learnable and satisfactory for nursing home use, provided there are adequate supporting features. The efficiency of the EXO+ was not fully measured since no falls were reported during the study period. The study offers valuable insights for potential design modifications and workflow adaptations to enhance the implementation of hip protectors in healthcare settings, highlighting facilitators and barriers to support device uptake.

Abstract Cardiovascular disease (CVD) is a major global cause of premature mortality. While multiple studies propose CVD mortality prediction models based on regression frameworks, incorporating causal understanding through causal inference approaches can enhance accuracy. This paper demonstrates a methodology combining evidence synthesis and expert knowledge to construct a causal model for premature CVD mortality using Directed Acyclic Graphs (DAGs). The process involves three phases: (1) initial DAG development based on the Evidence Synthesis for Constructing Directed Acyclic Graphs (ESC-DAGs) framework, (2) validation and consensus-building with 12 experts using the Fuzzy Delphi method (FDM), and (3) application to data analysis using population-based survey data linked with death records. Expert input refined the initial DAG model, achieving consensus on 45 causal paths. The revised model guided selection of confounding variables for adjustment. For example, to estimate the total effect of diabetes on premature CVD mortality, the suggested adjustment set included age, dietary pattern, genetic/family history, sex hormones, and physical activity. Testing different DAG models showed agreement between expert ratings and data accuracy from regression models. This systematic approach contributes to DAG methodology, offering a transparent process for constructing causal pathways for premature CVD mortality.

Abstract Background Loss-of-function (LOF) alterations in tumour suppressor genes cannot be directly targeted. Approaches characterising gene function and vulnerabilities conferred by such mutations are required. Methods Here, we computationally map genetic networks of KMT2D, a tumour suppressor gene frequently mutated in several cancer types. Using KMT2D loss-of-function (KMT2D LOF) mutations as a model, we illustrate the utility of in silico genetic networks in uncovering novel functional associations and vulnerabilities in cancer cells with LOF alterations affecting tumour suppressor genes. Results We revealed genetic interactors with functions in histone modification, metabolism, and immune response and synthetic lethal (SL) candidates, including some encoding existing therapeutic targets. Notably, we predicted WRN as a novel SL interactor and, using recently available WRN inhibitor (HRO761 and VVD-133214) treatment response data, we observed that KMT2D mutational status significantly distinguishes treatment-sensitive MSI cell lines from treatment-insensitive MSI cell lines. Conclusions Our study thus illustrates how tumour suppressor gene LOF alterations can be exploited to reveal potentially targetable cancer cell vulnerabilities.

Abstract Acanthopanax senticosus belongs to Araliaceae family and is traditionally used as a tonic. The roots and stems are mainly used as treatments for hypodynamia, rheumatism, and hypertension, but their frequent use may lead to extinction. However, comprehensive and simultaneous analysis of the remaining parts were still limited. There is a need to reorganize them for standardization of functional foods. In this study, 50 phenolic compounds and 82 triterpenoid saponins from the shoots, leaves, fruits, and stems of were characterized using UPLC-QTOF-MS and UPLC-QTRAP-MS/MS. Among them, 52 compounds were newly determined as the cis and malonyl-bound phenolic acids and were found to be structural isomers of Acanthopanax flavonoids and saponins. All compounds were absolutely/relatively quantified, and shoots had the highest content. Peroxynitrite and α-glucosidase inhibitory activities were performed, followed by evaluation of structure-activity relationships. Particularly, hederasaponin B and ciwujianoside B showed remarkable efficacy, which were affected by the C-23 hydroxylation, the C-20(29) double bond, and the presence of rhamnose. These detailed profiling can be used as fundamental data for increasing the utilization of A. senticosus and developing them into functional foods.

Despite advances in the antimicrobial treatment of sepsis and organ support in the intensive care unit (ICU), community-acquired pneumonia (CAP) remains a leading cause of mortality and disability-adjusted life years lost globally.1 Severe CAP, where CAP becomes complicated by acute hypoxaemic respiratory failure or shock, is also the most common cause of sepsis, where complex and heterogeneous biological mechanisms underlie a dysregulated inflammatory host response that ultimately leads to major organ dysfunction and death. Along with the emerging threats of respiratory pandemics, antimicrobial resistance, ageing populations and the rise of chronic diseases, much research has been conducted to improve the treatment outcomes of CAP via host immunomodulation. These efforts have focused almost exclusively on anti-inflammatory effects of corticosteroids, which have a proven track record of improving outcomes in other forms of sepsis, such as bacterial meningitis, Pneumocystis jirovecii pneumonia and severe COVID-19.

Abstract Background Although the number of teledermatology studies is increasing, not all variables have been researched in equal depth, so there remains a lack of robust evidence for some teledermatology initiatives. This review describes the landscape of teledermatology research and identifies knowledge gaps and research needs. This evidence map can be used to inform clinicians about the current knowledge about teledermatology and guide researchers for future studies. Methods Our evidence map was conducted according to the Campbell Collaboration checklist for evidence and gap maps. Eight databases were searched (CINAHL, Embase, PubMed, Scopus, Web of Science, Cochrane Library, JBI Database of Systematic Reviews and Implementation Reports, and OpenGray), and only included systematic reviews of teledermatology involving humans published in English; while excluding non-systematic reviews (i.e., abstracts, conference proceedings, editorials, commentaries, or letters). From 909 records, 14 systematic reviews published between 2004 and 2022 were included. Our analysis focused on the systematic reviews’ characteristics, dermatological conditions studied, rate of overlap and quality assessment of primary studies reviewed, and main findings reported. Results Teledermatology was reportedly comparable with clinic dermatology and generally accepted by patients as a mode of care delivery for dermatological conditions. However, there are concerns about privacy, communication, completeness of information transmitted, familiarity with the technology, and technical problems. Healthcare professionals were generally satisfied with teledermatology but found telemedicine consultations longer than face-to-face consultations, and less confident in asynchronous teledermatology than conventional consultations. Teledermatology was reportedly more cost-effective than clinic dermatology; especially considering the distance traveled by patients, referral volume to teledermatology, and clinic dermatology costs. Although patients and providers are satisfied with teledermatology, face-to-face dermatology has higher diagnostic and management accuracy. Teledermatology was also used for training medical professionals. Regarding the validity and reliability of teledermatology outcome measures, no significant discussions were found. Conclusions COVID-19 spotlighted telemedicine in clinical care, and we must ensure telemedicine continually improves with robust research. Further research is necessary for establishing a standardized outcome set, enhancing accuracy, concordance, cost-effectiveness, and safety, comparing teledermatology with non-dermatologist care, examining its effectiveness in non-Western low and middle-income countries, and incorporating patient involvement for improved study design. Systematic review registration https://www.researchregistry.com/ (Unique Identifying Number: reviewregistry878).

Abstract The prediction of stock market fluctuations is crucial for decision-making in various financial fields. Deep learning algorithms have demonstrated outstanding performance in stock market index prediction. Recent research has also highlighted the potential of the Transformer model in enhancing prediction accuracy. However, the Transformer faces challenges in multi-step stock market forecasting, including limitations in inference speed for long sequence prediction and the inadequacy of traditional loss functions to capture the characteristics of noisy, nonlinear stock history data. To address these issues, we introduce an innovative transformer-based model with generative decoding and a hybrid loss function, named “Galformer,” tailored for the multi-step prediction of stock market indices. Galformer possesses two distinctive characteristics: (1) a novel generative style decoder that predicts long time-series sequences in a single forward operation, significantly boosting the speed of predicting long sequences; (2) a novel loss function that combines quantitative error and trend accuracy of the predicted results, providing feedback and optimizing the transformer-based model. Experimental results on four typical stock market indices, namely the CSI 300 Index, S&P 500 Index, Dow Jones Industrial Average Index (DJI), and Nasdaq Composite Index (IXIC), affirm that Galformer outperforms other classical methods, effectively optimizing the Transformer model for stock market prediction.

Introduction: The global incidence of dementia is increasing, and cognitively impaired drivers are at a higher risk of crashes compared to healthy drivers. Doctors face challenges in assessing these at-risk drivers, with questionable adherence to existing guidelines. This study aimed to review and compare guidelines for managing cognitively impaired drivers from various countries. Method: A scoping review was conducted to identify relevant guidelines, which were then descriptively compared with Singapore’s guideline. Results: Eleven guidelines from 8 countries: US (n=2), Canada (n=2), UK (n=2), Ireland, Belgium, Australia, New Zealand and Singapore were reviewed. All guidelines support driving assessments and conditional licensing in ordinary (i.e. non-professional) drivers with dementia. Canada stands out for not allowing co-piloting and geographical restrictions in conditional licensing practice. Few guidelines provide indemnity for doctors reporting to licensing authorities, and communication about the impact of dementia on car insurance is rarely addressed. Most Western guidelines include evidence-based approaches, provisions for drivers with mild cognitive impairment and early discussions on transitioning from driving. A clinic-based functional screening toolbox and 2 clinical algorithms (1 with and 1 without the Clinical Dementia Rating scale) were identified as having universal applicability. Singapore’s guideline, by comparison, is outdated and lacks both developmental rigour and guidance on managing mild cognitive impairment and transitioning drivers out of driving. Conclusion: Comprehensive, evidence-based guidelines from Western countries provide valuable resources that can help Singapore design or update its guidelines.

Introduction: Psoriasis is a multisystem, chronic, inflammatory dermatological disease. In routine clinical practice, the management of psoriasis varies significantly. The current study aimed to develop a set of practice guidelines relevant to dermatology practice in Singapore. Method: The Psoriasis Therapeutic Guidelines Workgroup, comprising members of the Dermatological Society of Singapore with a subspecialisation in psoriasis, was convened to develop the guidelines. Clinical questions on selected topics were generated and refined by the workgroup. A literature search using PubMed was performed on their assigned topics from June 2013 to December 2023. The articles were included and graded based on the level of evidence. Results: The guidelines address topics ranging from clinical assessment to practical considerations in the management of mild, moderate and severe psoriasis, including delivery of care, referrals to specialists and adherence to treatment. The recommended therapies include phototherapy, methotrexate, acitretin, cyclosporine; apremilast; topical corticosteroids, calcipotriol, topical calcineurin inhibitors; and biologics (i.e. adalimumab, infliximab, secukinumab, ixekizumab, ustekinumab, etanercept) either in combination or as monotherapy. Common therapeutic concerns relating to biologic use were addressed. Recommendations on generalised pustular psoriasis, palmoplantar pustular psoriasis and psoriatic arthritis were also made. Patients on systemic therapy would receive appropriate vaccine counselling. Therapeutic implications in special populations, such as pregnant/lactating women, children, the elderly, those undergoing surgery and those suffering from specific infections and cancer were addressed. Conclusion: These guidelines were developed for dermatologists, family physicians, rheumatologists and other specialists to support their selection of appropriate management options.

Abstract Dementia significantly impacts caregivers, particularly in low and middle-income countries where support is often inadequate. Given the gap in affordable and culturally relevant digital resources for Malaysian dementia caregivers, we developed "Demensia KITA," a mobile application (app) specifically tailored to their needs. This study utilized a theoretical framework proposed from existing literature and the "Model of Carer Stress and Burden". This paper discusses our app content development, highlighting key findings and challenges. To assess caregivers’ needs, the Nominal Group Technique (NGT) with five dementia caregivers was conducted, followed by a Focus Group Discussion (FGD) with eight medical professionals. Both sessions were conducted online via Google Meet. In the NGT, ideas were generated, organized, prioritized, reviewed, and refined by medical professionals in the FGD. Content relevant to addressing the complexities of dementia caregiving was then discussed. Topics were either adapted from established modules or newly developed from credible sources. Subsequently, these were organized into modules and themes, and subsequently underwent expert validation. From the NGT, three key domains emerged: Knowledge, Services, and Support. These were further organized into two modules: 'Patient Care for Caregivers' and 'Caregiver Wellbeing'. Within these, twelve sub-modules were identified, covering a range of topics including basic knowledge on dementia, patient care, nutritional management, oral and dental care, simple exercises, daily activity and memory rehabilitation, service directories, support groups, emotional and stress management, welfare assistance, and daily motivation. This framework was developed to address the specific needs of dementia caregivers in terms of psychoeducation, psychosocial and caregiving skills, incorporating expert opinions in the field. This study corroborates the feasibility of online methods for mobile health app content development and encourages similar research. Future studies should evaluate Demensia KITA's effectiveness in alleviating caregiver burden across all regions, assess users’ acceptance, and ensure it meets the evolving needs of Malaysian caregivers with regular updates.

Abstract Single nucleotide polymorphisms (SNPs) could increase the susceptibility of individuals to develop obesity and type 2 diabetes (T2DM). Obesity and T2DM are closely related pathophysiologically, thus similar SNPs could mediate both these diseases, but this is rarely reported. Furthermore, limited studies have been performed to summarize SNP data in the Asian population compared to the Western population. In this study, we aimed to summarize SNPs that are associated with the development of obesity and T2DM among Asian populations. We searched six literature databases and Review Manager (RevMan) was used for meta-analysis. The pooled odds ratios (ORs) and 95% CIs were calculated with a random effects model for the heterogeneity among studies. The pooled analysis showed that rs9939609 (FTO gene) and rs17782313 and rs571312 (MC4R gene) are associated with obesity with an odd ratio (OR) of 1.37, 1.36 and 1.29 respectively. For T2DM, five SNPs, rs7903146 and rs12255372 (TCF7L2 gene), rs13266634 and rs11558471 (SLC30A8 gene) and rs2283228 (KCNQ1 gene) have also shown strong associations with T2DM at OR of 1.64, 1.61, 1.22, 1.29 and 1.60 respectively. This data could be used to develop a gene screening panel for assessing obesity and T2DM susceptibility.

Rotator cuff repair is a common orthopaedic procedure. Despite advancements in the mechanics of rotator cuff repair, the re-tear rate post repair remains significant. This review assesses the available literature on usage of collagen bio-inductive scaffolds for rotator cuff repairs. Augmentation of biology is a key strategy to improving success of rotator cuff repair. Current evidence suggests that augmentation of rotator cuff repairs with a collagen bio-inductive scaffold improves the thickness of the rotator cuff. There is a favourable safety profile, and its usage may improve re-tear rates. However, there is currently no consensus on whether clinical outcomes are improved by the usage of collagen bio-inductive scaffolds. Further research is necessary to increase our understanding of the clinical effects of using collagen bio-inductive scaffolds and to determine which patient profiles will best benefit from its usage.

Background: The prevalence of multidrug-resistant and extensively drug-resistant pathogens has led to increased reliance on broad-spectrum antimicrobials, such as tigecycline. This medicine is commonly used to treat complicated skin and intraabdominal infections as well as community-acquired pneumonia. However, the increasing use of tigecycline has been linked to serious complications, including acute pancreatitis. Case description: We present a case of tigecycline-induced acute pancreatitis in a 78-year-old man with complex medical conditions, including type 2 diabetes mellitus, chronic renal insufficiency, and triple vessel disease. The patient was initially treated with tigecycline for bilateral dry gangrene of his toes. Six days after initiation of the tigecycline treatment, the patient developed symptoms of acute pancreatitis with electrocardiogram changes. Magnetic resonance imaging confirmed the diagnosis of acute pancreatitis. Tigecycline was stopped promptly, and supportive treatment was initiated. The patient recovered from the acute pancreatitis and was discharged home. He later passed away at home due to his underlying cardiac disease. Conclusions: This case highlights the potential complications of tigecycline therapy, particularly in patients with significant comorbidities.

The prevalence of chronic kidney disease (CKD) among Singapore residents aged 18 to 74 years rose significantly from 8.8% in 2019–2020 to 13.8% in 2021–2022.1,2 Singapore ranks third globally for treated end-stage kidney disease (ESKD), with a median survival of 6 years post-dialysis.3 Diabetic nephropathy was the leading cause of stage 5 CKD, accounting for 64.6% of new dialysis patients in 2022.4 This is particularly concerning given Singapore’s rapidly ageing population and rising lifestyle-related CKD risk factors. Notably, CKD prevalence is higher among those with pre-diabetes (21.8%), diabetes mellitus (DM) (42.3%) and hypertension (24.2%) compared to those without diabetes (10%).

Abstract Background Effective mentorship is an important component of medical education with benefits to all stakeholders. In recent years, conceptualization of mentorship has gone beyond the traditional dyadic experienced mentor-novice mentee relationship to include group and peer mentoring. Existing theories of mentorship do not recognize mentoring’s personalized, evolving, goal-driven, and context-specific nature. Evidencing the limitations of traditional cause-and-effect concepts, the purpose of this review was to systematically search the literature to determine if mentoring can be viewed as a complex adaptive system (CAS). Methods A systematic scoping review using Krishna’s Systematic Evidence-Based Approach was employed to study medical student and resident accounts of mentoring and CAS in general internal medicine and related subspecialties in articles published between 1 January 2000 and 31 December 2023 in PubMed, Embase, PsycINFO, ERIC, Google Scholar, and Scopus databases. The included articles underwent thematic and content analysis, with the themes identified and combined to create domains, which framed the discussion. Results Of 5,704 abstracts reviewed, 134 full-text articles were evaluated, and 216 articles were included. The domains described how mentoring relationships and mentoring approaches embody characteristics of CAS and that mentorship often behaves as a community of practice (CoP). Mentoring’s CAS-like features are displayed through CoPs, with distinct boundaries, a spiral mentoring trajectory, and longitudinal mentoring support and assessment processes. Conclusion Recognizing mentorship as a CAS demands the rethinking of the design, support, assessment, and oversight of mentorship and the role of mentors. Further study is required to better assess the mentoring process and to provide optimal training and support to mentors.

Abstract Honey bees are commonly co-exposed to pesticides during crop pollination, including the fungicide captan and neonicotinoid insecticide thiamethoxam. We assessed the impact of exposure to these two pesticides individually and in combination, at a range of field-realistic doses. In laboratory assays, mortality of larvae treated with captan was 80–90% greater than controls, dose-independent, and similar to mortality from the lowest dose of thiamethoxam. There was evidence of synergism (i.e., a non-additive response) from captan-thiamethoxam co-exposure at the highest dose of thiamethoxam, but not at lower doses. In the field, we exposed whole colonies to the lowest doses used in the laboratory. Exposure to captan and thiamethoxam individually and in combination resulted in minimal impacts on population growth or colony mortality, and there was no evidence of synergism or antagonism. These results suggest captan and thiamethoxam are each acutely toxic to immature honey bees, but whole colonies can potentially compensate for detrimental effects, at least at the low doses used in our field trial, or that methodological differences of the field experiment impacted results (e.g., dilution of treatments with natural pollen). If compensation occurred, further work is needed to assess how it occurred, potentially via increased queen egg laying, and whether short-term compensation leads to long-term costs. Further work is also needed for other crop pollinators that lack the social detoxification capabilities of honey bee colonies and may be less resilient to pesticides.

Abstract Background Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally has a poor prognosis for patients with limited treatment options. While incorporating immune checkpoint inhibitors (ICIs) has now become the standard of care, the efficacy is variable, with only a subset of patients responding. The complexity of the tumor microenvironment (TME) and the role of tertiary lymphoid structures (TLS) have emerged as critical determinants for immunotherapeutic response. Methods In this study, we analyzed two independently collected R/M HNSCC patient tissue cohorts to better understand the role of TLS in response to ICIs. Utilizing a multi-omics approach, we first performed targeted proteomic profiling using the Nanostring GeoMx Digital Spatial Profiler to quantify immune-related protein expression with spatial resolution. This was further characterized by spatially resolved whole transcriptome profiling of TLSs and germinal centers (GCs). Deeper single-cell resolved proteomic profiling of the TLSs was performed using the Akoya Biosciences Phenocycler Fusion platform. Results Our proteomic analysis revealed the presence of T lymphocyte markers, including CD3, CD45, and CD8, expressing cells and upregulation of immune checkpoint marker PD-L1 within tumor compartments of patients responsive to ICIs, indicative of ‘hot tumor’ phenotypes. We also observed the presence of antigen-presenting cells marked by expression of CD40, CD68, CD11c, and CD163 with upregulation of antigen-presentation marker HLA-DR, in patients responding to ICIs. Transcriptome analysis of TLS and GCs uncovered a marked elevation in the expression of genes related to immune modulation, diverse immune cell recruitment, and a potent interferon response within the TLS structure. Notably, the distribution of TLS-tumor distance was found to be significantly different across response groups (H = 9.28, p = 0.026). The proximity of TLSs to tumor cells was found to be a critical indicator of ICI response, implying that patients with TLSs located further from tumor cells have worse outcomes. Conclusion The study underscores the multifaceted role of TLSs in modulating the immunogenic landscape of the TME in R/M HNSCC, likely influencing the efficacy of ICIs. Spatially resolved multi-omics approaches offer valuable insights into potential biomarkers for ICI response and highlight the importance of profiling the TME complexity when developing therapeutic strategies and patient stratification.

Abstract Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment. In this paper, we aimed to identify immunomodulatory factors associated with colorectal PM (CPM). A publicly available colorectal single cell database (GSE183916) was analysed to identify possible immunological markers that are associated with the activation of macrophages in cancers. Immunohistochemical analysis for V-set and immunoglobin containing domain 4 (VSIG4) expression was performed on tumour microarrays (TMAs) of tumours of colorectal origin (n = 211). Expression of VSIG4 in cell-free ascites obtained from CPM patients (n = 39) was determined using enzyme-linked immunosorbent assay (ELISA). CD163-positive TAMs cluster expression was extracted from a publicly available single cell database and evaluated for the top 100 genes. From these macrophage-expressed genes, VSIG4, a membrane protein produced by the M2 macrophages, mediates the up-regulation of anti-inflammatory and down-regulation of pro-inflammatory macrophages, contributing to an overall anti-inflammatory state. CRC TMA IHC staining showed that low expression of VSIG4 in stromal tissues of primary CRC are associated with poor prognosis (p = 0.0226). CPM ascites also contained varying concentrations of VSIG4, which points to a possible role of VSIG4 in the ascites. The contribution of VSIG4 to CPM development can be further evaluated for its potential as an immunotherapeutic agent.

Urinary tract infection (UTI) is a common presentation in primary care, but gaps of care have not been well established in Singapore. UTIs are one of the most common bacterial infections worldwide,1 constituting around 1% of all ambulatory clinic visits.2 The healthcare burden of UTIs remains highly significant, with billions per year lost in societal costs (e.g. healthcare costs and time missed from work) alone.2 In Singapore, genitourinary infections were the second most common group of conditions for which antibiotics were prescribed in 2021.3

Abstract Late Holocene relative sea-level (RSL) data are important to understand the drivers of RSL change, but there is a lack of precise RSL records from the Sunda Shelf. Here, we produced a Late Holocene RSL reconstruction from coral microatolls in Singapore, demonstrating for the first time the utility of Diploastrea heliopora microatolls as sea-level indicators. We produced 12 sea-level index points and three marine limiting data with a precision of

Abstract The mechanism and predictive biomarkers of sinonasal inverted papilloma (IP) transformation into squamous cell carcinoma (SCC) are still unclear. We investigated the genetic mutations involved and the predictive biomarkers. Fourteen patients with SCC arising from IP and six patients with IPs without malignant transformation (sIP) were included. DNA was extracted separately from areas of normal tissue, IP, dysplasia, and SCC. Whole exome sequencing and immunohistochemistry was performed. Major oncogenic mutations were observed in the progression from IP to SCC. The most frequently mutated genes were TP53 (39%) and CDKN2A (27%). Mutations in TP53 and/or CDKN2A were observed in three of six IPs with malignant transformation (cIP); none were observed in sIPs. Tumor mutational burden (TMB) increased from IP to SCC (0.64/Mb, 1.11/Mb, and 1.25 for IP, dysplasia, and SCC, respectively). TMB was higher in the cIPs than in the sIPs (0.64/Mb vs 0.3/Mb). Three cIPs showed a diffuse strong or null pattern in p53, and one showed a total loss of p16, a distinct pattern from sIPs. Our result suggests that TP53 and CDKN2A status can be predictive markers of malignant transformation of IP. Furthermore, immunohistochemistry of p53 and p16 expression can be surrogate markers for TP53 and CDKN2A status.

Abstract Background We previously reported changes in the serum metabolome associated with impaired myocardial relaxation in an asymptomatic older community cohort. In this prospective parallel-group randomized control pilot trial, we subjected community adults without cardiovascular disease to exercise intervention and evaluated the effects on serum metabolomics. Methods Between February 2019 to November 2019, thirty (83% females) middle-aged adults (53 ± 4 years) were randomized with sex stratification to either twelve weeks of moderate-intensity exercise training (Intervention) (n = 15) or Control (n = 15). The Intervention group underwent once-weekly aerobic and strength training sessions for 60 min each in a dedicated cardiac exercise laboratory for twelve weeks (ClinicalTrials.gov: NCT03617653). Serial measurements were taken pre- and post-intervention, including serum sampling for metabolomic analyses. Results Twenty-nine adults completed the study (Intervention n = 14; Control n = 15). Long-chain acylcarnitine C20:2-OH/C18:2-DC was reduced in the Intervention group by a magnitude of 0.714 but increased in the Control group by a magnitude of 1.742 (mean difference −1.028 age-adjusted p = 0.004). Among Controls, alanine correlated with left ventricular mass index (r = 0.529, age-adjusted p = 0.018) while aspartate correlated with Lateral e’ (r = −764, age-adjusted p = 0.016). C20:3 correlated with E/e’ ratio fold-change in the Intervention group (r = −0.653, age-adjusted p = 0.004). Among Controls, C20:2/C18:2 (r = 0.795, age-adjusted p = 0.005) and C20:2-OH/C18:2-DC fold-change (r = 0.742, age-adjusted p = 0.030) correlated with change in E/A ratio. Conclusions Corresponding relationships between serum metabolites and cardiac function in response to exercise intervention provided pilot observations. Future investigations into cellular fuel oxidation or central carbon metabolism pathways that jointly impact the heart and related metabolic systems may be critical in preventive trials.

Abstract The biogeographical range shift of insect pests is primarily governed by temperature. However, the range shift of seasonal long-distance migratory insects may be very different from that of sedentary insects. Nilaparvata lugens (BPH), a serious rice pest, can only overwinter in tropical-to-subtropical regions, and some populations migrate seasonally to temperate zones with the aid of low-level jet stream air currents. This study utilized the CLIMEX model to project the overwintering area under the climate change scenarios of RCP2.6 and RCP8.5, both in 2030s and 2080s. The overwintering boundary is predicted to expand poleward and new overwintering areas are predicted in the mid-latitude regions of central-to-eastern China and mid-to-southern Australia. With climate change, the habitable areas remained similar, but suitability decreased substantially, especially in the near-equatorial regions, owing to increasing heat stress. The range shift is similar between RCP2.6-2030s, RCP2.6-2080s, and RCP8.5-2030s, but extreme changes are projected under RCP8.5-2080s with marginal areas increasing from 27.2 to 38.8% and very favorable areas dropping from 27.5 to 3.6% compared to the current climate. These findings indicate that climate change will drive range shifts in BPH and alter regional risks differently. Therefore, international monitoring programs are needed to effectively manage these emerging challenges.

Abstract It is essential to delve into the strategy of multimodal model pre-training, which is an obvious impact on downstream tasks. Currently, clustering learning has achieved noteworthy benefits in multiple methods. However, due to the availability of open image-text pairs, it is challenging for multimodal with clustering learning. In this paper, we propose an approach that utilizes clustering swap prediction strategy to learn image-text clustering embedding space by interaction prediction between image and text features. Unlike existing models with clustering learning, our method (Clus) allows for an open number of clusters for web-scale alt-text data. Furthermore, in order to train the image and text encoders efficiently, we introduce distillation learning approach and evaluate the performance of the image-encoder in downstream visual tasks. In addition, Clus is pre-trained end-to-end by using large-scale image-text pairs. Specifically, both text and image serve as ground truth for swap prediction, enabling effective representation learning. Concurrently, extensive experiments demonstrate that Clus achieves state-of-the-art performance on multiple downstream fine-tuning and zero-shot tasks (i.e., Image-Text Retrieval, VQA, NLVR2, Image Captioning, Object Detection, and Semantic Segmentation).

Singapore faces a rapidly ageing population with its median age projected to be above 45 years by 2030. Our greying demographics is accompanied by a rise in chronic diseases and medication use, including polypharmacy. Longer life expectancy and increased activity levels have contributed to higher incidence of geriatric trauma locally, with a three-fold rise between 2004 and 2015. Older patients are at greater risk of poorer outcomes following trauma.3 However, the impact of comorbidities and medication use on post-trauma outcomes in Singapore’s ageing population remains unclear.

Carbon-ion radiotherapy (CIRT) offers superior dose distributions and greater biological effectiveness than conventional photon-based radiotherapy (RT). Due to its higher linear energy transfer and relative biological effectiveness, CIRT is particularly effective against radioresistant tumors and those located near critical organs. Since the first dedicated CIRT facility was established in Japan in 1994, CIRT has demonstrated remarkable efficacy against various malignancies, including head and neck tumors, skull base and upper cervical spine tumors, non-small-cell lung cancer, hepatocellular carcinoma, pancreatic cancer, prostate cancer, and bone and soft tissue sarcomas. This narrative review provides a comprehensive overview of the current status of CIRT, highlighting its clinical indications and future directions. According to clinical studies, CIRT achieves high local control rates with manageable toxicity across multiple cancer types. For instance, in head and neck tumors (e.g., adenoid cystic carcinoma and mucosal melanoma), CIRT has achieved local control rates exceeding 80%. In early-stage non-small-cell lung cancer, CIRT has resulted in local control rates over 90% with minimal toxicity. Moreover, CIRT has shown promise in treating challenging cases of hepatocellular carcinoma and pancreatic cancer, where conventional therapies are limited. Nonetheless, the global adoption of CIRT remains limited due to high costs and complexity. Future directions include conducting randomized controlled trials to establish high-level evidence, integrating new technologies such as ultrahigh-dose-rate (FLASH) therapy, and expanding CIRT facilities globally with strategic planning and cost-effectiveness analyses. If these challenges are addressed, CIRT is poised to play a transformative role in cancer treatment, improving survival rates and the quality of life.

IntroductionWith the goal of patient engagement, an initiative was formulated to equip each patient in the general wards with a tablet whereby they can access their health information and patient education materials and communicate with their healthcare team. This paper presented the methodology of the implementation efforts as well as an evaluation of the preliminary outcomes.MethodsThe process of hospital-wide implementation was shared using the implementation research logic model. The bedside tablets were rolled out hospital-wide in a step-wedge manner over 12 months. Barriers and facilitators to this implementation were discussed together with strategies to optimize the situation. Preliminary outcomes of the implementation were evaluated using the RE-AIM framework.ResultsThe initial adoption rate for the bedside tablet was low. Additional strategies, such as survey audits and provision of feedback, development of education materials for patients, facilitation, and purposefully re-examining the implementation strategies, were used to improve adoption. The trend of adoption increased over the course of 2 years from the start of implementation.DiscussionThe initial lower adoption rates may reflect Singapore's paternalistic healthcare culture. While this implementation was driven by the need to move away from paternalism and toward patient engagement, more time is required for significant cultural change.

Background Primary ciliary dyskinesia (PCD) is a rare multisystem genetic disease caused by dysfunctional motile cilia. Despite PCD being the second most common inherited airway disease after cystic fibrosis, PCD continues to be under-recognised globally owing to nonspecific clinical features and the lack of a gold standard diagnostic test. Commonly repeated prevalence estimates range from one in 10 000 to one in 20 000, based on regional epidemiological studies with known limitations. The purpose of this scoping review was to appraise the PCD literature, to determine the best available global PCD prevalence estimate and to inform the reader about the potential unmet health service needs in PCD. The primary objective of the present study was to systematically review the literature about PCD prevalence estimates. Methods A scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) methodology. Included studies estimated PCD prevalence and used cohort, clinical or genomic data. Case reports, conference abstracts, review articles, animal studies or non-English articles were excluded. Results A literature review identified 3484 unique abstracts; 34 underwent full-text review and eight met the inclusion/exclusion criteria. Seven articles were based on epidemiological studies of specific geographical regions and provided prevalence estimates that ranged from approximately one to 44.1 in 100 000. Only one study estimated global prevalence, using two large genomic databases, and calculated it to be ∼13.2 in 100 000 (based on pathogenic variants in 29 disease-causing genes). Conclusions A population-based genomic approach for estimating global prevalence has found that PCD is much more prevalent than previously cited in the literature. This highlights the potential unmet health service needs of people living with PCD.

Abstract Predictive modelling of cancer outcomes using radiomics faces dimensionality problems and data limitations, as radiomics features often number in the hundreds, and multi-institutional data sharing is ()often unfeasible. Federated learning (FL) and feature selection (FS) techniques combined can help overcome these issues, as one provides the means of training models without exchanging sensitive data, while the other identifies the most informative features, reduces overfitting, and improves model interpretability. Our proposed FS pipeline based on FL principles targets data-driven radiomics FS in a multivariate survival study of non-small cell lung cancer patients. The pipeline was run across datasets from three institutions without patient-level data exchange. It includes two FS techniques, Correlation-based Feature Selection and LASSO regularization, and Cox Proportional-Hazard regression with Overall Survival as endpoint. Trained and validated on 828 patients overall, our pipeline yielded a radiomic signature comprising "intensity-based energy" and "mean discretised intensity". Validation resulted in a mean Harrell C-index of 0.59, showcasing fair efficacy in risk stratification. In conclusion, we suggest a distributed radiomics approach that incorporates preliminary feature selection to systematically decrease the feature set based on data-driven considerations. This aims to address dimensionality challenges beyond those associated with data constraints and interpretability concerns.

In Singapore, nasopharyngeal cancer (NPC) is among the top 3 cancers afflicting middle-aged males (30–49 years old).1 Unfortunately, patients with early-stage NPC are often asymptomatic, and most patients (approx. 70%) are diagnosed with advanced disease with adversely reduced survival. First-degree relatives of NPC patients have about 4 to 10 times increased risk of developing NPC,2 and strategies for reducing NPC-specific mortality among this high-risk group are feasible. Herein, a working group from the Chapter Board of Otorhinolaryngologists Singapore proposed a screening algorithm for these high-risk individuals of NPC based on existing available evidence.

Introduction: Autism is a neurodevelopmental condition that is increasing in prevalence worldwide. There has been an exponential increase in autism-related research since 2010, when the first Singapore Clinical Practice Guidelines (CPG) on autism was published. Understanding of autism has since evolved to adopt a lifespan approach beyond that of a childhood condition. The aim of this CPG was to provide an updated set of recommendations for children and adolescents to aid clinical practice for professionals. Method: A multidisciplinary workgroup that comprised representatives from various sectors worked on this CPG. Clinical questions were organised into 10 different sections, each with its own subgroup of members. Seventeen existing international guidelines were evaluated using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE-II) framework, of which 4 met criteria to act as references. Literature review across multiple databases was conducted between January 2011 to 2023; Grading of Recommendations, Assessment, Development and Evaluation (GRADE-like) methodology was used to synthesise evidence. Recommendation statements were derived, following Delphi-style consensus surveys among the workgroup. The draft guidelines underwent external review and public consultation before being formalised. Results: Recommendation and good practice statements pertaining to care of children and adolescents on the autism spectrum across 10 different sections were developed. Evidence matrices complement these recommendations and detail relevant evidence behind each recommendation statement. Conclusion: It is intended for these guidelines to promote effective management and healthcare services for children and adolescents on the autism spectrum, by reinforcing good and evidence-based clinical practice within our national context.

Abstract The growing Human Immunodeficiency Virus (HIV) incidences and insufficient HIV knowledge among Malaysian late adolescents necessitate immediate attention to HIV prevention via education. This study aims to develop and validate an Information-Motivation-Behavioural skills (IMB) model-based education kit for adolescents, PREM-Kit, to educate on HIV prevention among Malaysian late adolescents. Utilizing the Analysis, Design, Development, Implementation, and Evaluation model, we conducted the study in three phases: needs assessment, development of PREM-Kit, and validation of PREM-Kit by applying the IMB model to map the PREM-Kit’s contents. PREM-Kit, developed in Malay language, consisted of an infographic flip chart and videos. Five multi-disciplinary experts validated the PREM-Kit using the content validity index (CVI), and 13 end-users validated the PREM-Kit using the Malay version of the Patient Education Materials Assessment Tool for Printable and Audiovisual Materials. The infographic flip chart comprised three modules covering 15 topics, and an animated video accompanied each module. PREM-Kit achieved CVI scores of 1.0 and median scores of over 80% for understandability and actionability. Overall, the newly developed IMB model-based HIV education kit has good content validity, is simple to comprehend and apply, and is ready for testing its effectiveness in improving adolescents’ knowledge, attitudes, and practices for HIV prevention.

Background We compared the diagnostic performance of the short five-item and full seven-item Mini Sarcopenia Risk Assessment Questionnaire (MSRA-5 and MSRA-7) against the Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F) and SARC-F with calf circumference (SARC-CalF) scales for sarcopenia in healthy community-dwelling older adults. Methods We conducted a post-hoc cross-sectional secondary data analysis of a prospective cohort study, using data from 230 older adults (mean age 67.2±7.4 years, 92% Chinese, and 73% female) from the “Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and Osteosarcopenic Obesity in predicting frailty and functional decline in community-dwelling Asian older adults Study” (GeriLABS-2) conducted between December 2017 and March 2019 in Singapore. We performed receiver operating characteristic curve analysis to ascertain the area under the curve (AUC) for sarcopenia diagnosis using the Asian Working Group for Sarcopenia 2019 consensus criteria. We applied the DeLong method to compare the AUCs of the four instruments. Results The MSRA-5 and MSRA-7 demonstrated poor diagnostic performance (AUC of 0.511, 95% confidence interval [CI] 0.433–0.589 and AUC of 0.526, 95% CI 0.445–0.606, respectively), compared to that in SARC-CalF (AUC of 0.739, 95% CI 0.671–0.808) and SARC-F (AUC of 0.564, 95% CI 0.591–0.636). The SARC-CalF demonstrated significantly superior discriminatory ability compared to that in the SARC-F, MSRA-5, and MSRA-7 (all p

Abstract Horseshoe crabs are among the most studied invertebrates due to their unique, innate immune system and biological processes. The metabolomics study was conducted on lipopolysaccharide (LPS)-stimulated and non-stimulated hemocytes isolated from the Malaysian Tachypleus gigas and Carcinoscorpius rotundicauda. LC–TOF–MS, multivariate analyses, principal component analysis (PCA), and partial least squares-discriminant analysis (PLS-DA) were included in this study to profile the metabolites. A total of 37 metabolites were identified to be differentially abundant and were selected based on VIP > 1. However, of the 37 putative metabolites, only 23 were found to be significant with ANOVA at p

Studies have repeatedly demonstrated the real-world effectiveness of oral antivirals (OAVs) in preventing hospitalisation and death in patients with mild-to-moderate COVID-19 at high risk for progression to severe COVID-19 when initiated within 5 days of symptom onset, even during waves of Omicron transmission.1 However, there is a need to determine if OAVs are reaching recommended groups, particularly among older adults and socioeconomically disadvantaged groups at higher risk of severe COVID-19. Disparities in access to OAVs based on area-level socioeconomic status (SES) have been documented in the US, UK and Australia,2-4 with substantially lower dispensing rates reported from more deprived areas. However, to the best of our knowledge, no studies have evaluated disparities in OAV access among urbanised Asian populations, including Singapore.

Background Alzheimer’s disease (AD) is the most common type of dementia that affects the elderly population. Lately, blood-based proteomics have been intensively sought in the discovery of AD biomarkers studies due to the capability to link external environmental factors with the development of AD. Demographic differences have been shown to affect the expression of the proteins in different populations which play a vital role in the degeneration of cognitive function. Method In this study, a proteomic study focused on Malaysian Chinese and Malay prospects was conducted. Differentially expressed proteins (DEPs) in AD patients and normal controls for Chinese and Malays were identified. Functional enrichment analysis was conducted to further interpret the biological functions and pathways of the DEPs. In addition, a survey investigating behavioural practices among Chinese and Malay participants was conducted to support the results from the proteomic analysis. Result The variation of dysregulated proteins identified in Chinese and Malay samples suggested the disparities of pathways involved in this pathological condition for each respective ethnicity. Functional enrichment analysis supported this assumption in understanding the protein-protein interactions of the identified protein signatures and indicate that differentially expressed proteins identified from the Chinese group were significantly enriched with the functional terms related to Aβ/tau protein-related processes, oxidative stress and inflammation whereas neuroinflammation was associated with the Malay group. Besides that, a significant difference in sweet drinks/food intake habits between these two groups implies a relationship between sugar levels and the dysregulation of protein APOA4 in the Malay group. Additional meta-analysis further supported the dysregulation of proteins TF, AHSG, A1BG, APOA4 and C4A among AD groups. Conclusion These findings serve as a preliminary understanding in the molecular and demographic studies of AD in a multi-ethnic population.

In Singapore, an ageing population with increasing chronic disease burden and complex social circumstances have strained the healthcare system. For the health system to run more efficiently, patients should be appropriately sited according to their medical needs. In Singapore, community hospitals serve as an intermediate inpatient facility managing patients with sub-acute and rehabilitation care needs. Our policy brief uncovers the gaps in transforming community hospital care models and offers actionable steps to unlock the community hospital chokepoints in Singapore's health system. The future community hospitals can accommodate higher acuity but medically stable patients, while patients who do not require inpatient rehabilitation care can be appropriately sited to community partners, if policy, resourcing and technology factors are addressed. An evidence-based, stepwise approach involving all stakeholders will be required to pilot and evaluate new models before large-scale change.

Background Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice.Methods Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform’s Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups.Ethics and dissemination Approved by each trial’s ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases.Prospero registration CRD42022330532.

Introduction Cholecystectomy is one of the most common operations performed worldwide. Although laparoscopic surgery has been the ‘gold-standard’ approach for this operation, there is a paucity of global evidence around the variations of safe provision of cholecystectomy, including low-income and middle-income countries. This international collaborative study will allow contemporaneous data collection on the quality of cholecystectomies using measures covering infrastructure, care processes and outcomes, with the primary aim define the global variation in compliance with preoperative, intraoperative and postoperative audit standards.Methods and analysis Global Evaluation of Cholecystectomy Knowledge and Outcomes is a prospective, international, multicentre, observational cohort study delivered by the GlobalSurg Collaborative. Consecutive patients undergoing cholecystectomy between 31 July 2023 and 19 November 2023 will be recruited, with follow-up at 30 days and 1-year postoperatively. The study will be undertaken at any hospital providing emergency or elective surgical services for biliary disease. The primary endpoint of this study is compliance with preoperative, intraoperative and postoperative audit standards. Secondary outcomes include rates of 30-day complications, achievement of critical view of safety and rates of gallbladder cancer.Ethics and dissemination This project will not affect clinical practice and has been classified as clinical audit following research ethics review at University Hospital Birmingham NHS Trust. The protocol will be disseminated through the international GlobalSurg and CovidSurg network.Trial registration number NCT06223061.

Background and objectives Vaginal digital examination and transvaginal ultrasound are routinely for clinical assessment. Many women find these procedures uncomfortable, embarrassing, and stressful. Negative experiences increase anxiety and discomfort experienced during subsequent examinations. Emotional distress and fear of pain result in women avoiding gynaecological screening and follow-up. This study uses qualitative methods to evaluate the experience of patients who have undergone both vaginal digital and transvaginal ultrasound examinations, collectively called pelvic examinations (PE) in the outpatient setting of a tertiary hospital in Singapore. Methods Qualitative semi-structured interviews were conducted on 12 participants aged 30-57 years. Interviews were audio-recorded, transcribed, audited, and analysed iteratively based on grounded theory. Emergent themes were first externally validated and finalized after rounds of deliberations amongst the investigators. This included descriptions and concepts reflecting the most important matters experienced by participants. Results Majority of participants found PE unpleasant and uncomfortable especially when providers were perceived to have poor communication and examination skills. Factors that improve their experience include a conducive environment that is, privacy, dim lights, and warm lubricant. Having adequate information before and during the procedure was important especially for first time. Conclusion Patient-centred care ensures a positive experience in relation to the themes found in this study. Gaps in HCP training on communication and procedure skills should be addressed. Efforts should be made improve the clinic environment and provide adequate information to patients.

Objectives To evaluate asthma characteristics and treatment patterns, including short-acting β2-agonist (SABA) prescriptions, in primary and specialist care in the Singapore cohort of the SABA use IN Asthma (SABINA III) study.Design Cross-sectional, observational study.Setting Multicentre study conducted at five sites across Singapore.Methods In patients with asthma (aged ≥12 years), data on demographics, disease characteristics and asthma treatment prescriptions were collected using electronic case report forms. Patients were classified by investigator-defined asthma severity (guided by 2017 Global Initiative for Asthma recommendations) and practice type (primary/specialist care).Results Of the 205 patients analysed (mean (SD) age, 53.6 (16.8) years; female, 62%), 55.9% were enrolled by specialists and 44.1% by primary care physicians. Most study patients (80.5%) had moderate-to-severe asthma (86.0% in specialist care and 74.4% in primary care). In the 12 months before study enrolment, 18.0% of patients experienced ≥1 severe exacerbation. Asthma was well or partly controlled in 78.0% of patients. Overall, 17.1% of all patients were overprescribed SABA (≥3 SABA canisters/year) in the preceding 12 months, and overprescription was greater in specialist versus primary care (26.3% vs 5.6%). Only 2.9% of patients were prescribed SABA monotherapy, while 41.0% received SABA in addition to maintenance therapy. Among the latter, 40.5% were overprescribed SABA. Overall, a higher percentage of patients prescribed ≥3 SABA canisters (vs 0–2 SABA canisters) were assessed as having uncontrolled asthma during the study visit (42.9% vs 17.6%). Maintenance therapy in the form of inhaled corticosteroids (ICS) or ICS/long-acting β2 agonist fixed-dose combinations were prescribed to 14.1% and 84.9% of patients, respectively, in the 12 months before enrolment.Conclusions In this Singapore cohort, ~17% of all patients and more than 40% of patients prescribed SABA in addition to maintenance therapy were overprescribed SABA. These findings emphasise the need to align clinical practices with the latest evidence-based treatment recommendations.Trial registration NCT03857178.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Abstract Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

Abstract CT imaging under external valgus and varus loading conditions and consecutive image analysis can be used to detect tibial implant loosening after total knee arthroplasty. However, the applied load causes the tibia to deform, which could result in an overestimation of implant displacement. This research evaluates the extent of tibia deformation and its effect on measuring implant displacement. Ten cadaver specimen with TKA were CT-scanned under valgus/varus loading (20 Nm), first implanted without bone cement fixation (mimicking a loose implant) and subsequently with bone cement fixation (mimicking a fixed implant). By means of image analysis, three relative displacements were assessed: (1) between the proximal and distal tibia (measure of deformation), (2) between the implant and the whole tibia (including potential deformation effect) and (3) between the implant and the proximal tibia (reduced deformation effect). Relative displacements were quantified in terms of translations along, and rotations about the axes of a local coordinate system. As a measure of deformation, the proximal tibia moved relative to the distal tibia by, on average 1.27 mm (± 0.50 mm) and 0.64° (± 0.25°). Deformation caused an overestimation of implant displacement in the cemented implant. The implant displaced with respect to the whole tibia by 0.45 mm (± 0.22 mm) and 0.79° (± 0.38°). Relative to the proximal tibia, the implant moved by 0.23 mm (± 0.10 mm) and 0.62° (± 0.34°). The differentiation between loose and fixed implants improved when tibia deformation was compensated for by using the proximal tibia rather than the whole tibia.