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This paper focuses on the experience of international undergraduate students as they move into a university environment. Utilising a phenomenological approach with Schlossberg's Theory of Transition as the framework, data was collected through semi-structured interviews with 19 undergraduate students, all enrolled in one private university. The study found that their moving-in experiences were influenced by their aspirations, feelings and expectations. Conflicting emotions accompanied their departure from their home country: sorrow and anxiety versus excitement for their new life. Aided by a relatively smooth immigration process, the students moved on to experience memorable moments where friendships were formed and exploration of the surrounding areas was acculturated. Challenges faced include those of physical nature (weather and food), academic, and perhaps the most serious of which, psychosocial: in the form of homesickness and feeling of foreignness.

Abstract Identifying sensitive and specific measures that can quantify myelin are instrumental in characterizing microstructural changes in neurological conditions. Neuroimaging transcriptomics is emerging as a valuable technique in this regard, offering insights into the molecular basis of promising candidates for myelin quantification, such as myelin water fraction (MWF). We aimed to demonstrate the utility of neuroimaging transcriptomics by validating MWF as a myelin measure. We utilized data from a normative MWF brain atlas, comprised of 50 healthy subjects (mean age = 25 years, range = 17–42 years) scanned at 3 Tesla. Magnetic resonance imaging data included myelin water imaging to extract MWF and T1 anatomical scans for image registration and segmentation. We investigated the inter-regional distributions of gene expression data from the Allen Human Brain Atlas in conjunction with inter-regional MWF distribution patterns. Pearson correlations were used to identify genes with expression profiles mirroring MWF. The Single Cell Type Atlas from the Human Protein Atlas was leveraged to classify genes into gene sets with high cell type specificity, and a control gene set with low cell type specificity. Then, we compared the Pearson correlation coefficients for each gene set to determine if cell type-specific gene expression signatures correlate with MWF. Pearson correlation coefficients between MWF and gene expression for oligodendrocytes and adipocytes were significantly higher than for the control gene set, whereas correlations between MWF and inhibitory/excitatory neurons were significantly lower. Our approach in integrating transcriptomics with neuroimaging measures supports an emerging technique for understanding and validating MRI-derived markers such as MWF.

Glossophobia or fear of public speaking is commonly experienced by tertiary learners during classroom presentations. This study intends to examine the speech anxiety level experienced by engineering learners and the relationship between the learners' English language proficiency and their speech anxiety. The study will also identify the causes of public speaking anxiety among these engineering learners. The samples were 65 Engineering Diploma students who responded to McCroskey's Personal Report of Public Speaking Anxiety (PRPSA) questionnaire. The students' English language grades at SPM level were used as the measurement of their English language proficiency. The findings showed the students' speech anxiety is at moderate level (M= 105.9) and there was a weak negative relationship between total PRPSA scores and SPM English language grades (r = -0.149, n = 65, p > 0.05). Mere thoughts of presenting a speech with undue worries of being asked questions were the causes of their speech anxiety. Therefore, it is proposed engineering learners be given ample public speaking trainings through planned programmes and engineering curriculum planners include elements of public speaking in engineering subjects. Public speaking skills will be an added value and increase engineering graduate employability in future.

Background Surveillance for heart transplant rejection by endomyocardial biopsy is invasive and may yield false negatives. T1 and T2 mapping from cardiac magnetic resonance can demonstrate elevations with rejection. We sought to evaluate longitudinal changes in T1 and T2 mapping in pediatric patients with heart transplant. Methods and Results A cohort study was performed of pediatric patients with heart transplant who underwent concurrent endomyocardial biopsy and cardiac magnetic resonance with T1 and T2 mapping from December 2019 to July 2024. Segmental values were measured and subsegmental elevations (ie, hotspots) were identified. Subjects were categorized as either treated rejection or no rejection. Peak and mean T1 and T2 values and number of hotspots at/between each time point for patient dyads were compared between the groups. A total of 21 subjects (7 treated rejection, 14 no rejection) with 68 total encounters met inclusion criteria. Peak and mean T1 values were higher in treated rejection patients during the rejection period and decreased with treatment (peak, 1086 versus 1052; mean, 1028 versus 1021), such that at last follow‐up when their rejection had resolved, there was no significant difference in values when compared with no rejection patients (peak, 1066; mean, 1016). The number of T1 hotspots decreased after rejection treatment (2 versus 1). There were no changes in peak or mean T2 values in the treated rejection group despite treatment, and peak and mean T2 values were similar to patients with no rejection through last follow‐up. Conclusions Elevated T1 values and hotspots observed during cardiac allograft rejection decline in response to treatment. Cardiac magnetic resonance may serve as a noninvasive monitoring tool for the development and resolution of rejection, as well as the effectiveness of rejection therapy.

We investigate the Sc dependence and thermal sensitivity of Al1−xScxN with the aid of Landau–Devonshire free energy recently proposed for its wurtzite ferroelectric phase. In particular, we calculate compositional and temperature dependences of the remanent polarization and the coercive field. Because the polarization is strong, surface fluctuations of the polarization are expected; we examine the nature of these fluctuations. Strong correlation is expected as the ferroelectric phase gives way to the paraelectric phase.

BackgroundAging is a risk factor for falls, frailty, and disability. The utility of wearables to screen for physical performance and frailty at the population level is an emerging research area. To date, there is a limited number of devices that can measure frailty and physical performance simultaneously. ObjectiveThe aim of this study is to evaluate the accuracy and validity of a continuous digital monitoring wearable device incorporating gait mechanics and heart rate recovery measurements for detecting frailty, poor physical performance, and falls risk in older adults at risk of falls. MethodsThis is a substudy of 156 community-dwelling older adults ≥60 years old with falls or near falls in the past 12 months who were recruited for a fall prevention intervention study. Of the original participants, 22 participants agreed to wear wearables on their ankles. An interview questionnaire involving demographics, cognition, frailty (FRAIL), and physical function questions as well as the Falls Risk for Older People in the Community (FROP-Com) was administered. Physical performance comprised gait speed, timed up and go (TUG), and the Short Physical Performance Battery (SPPB) test. A gait analyzer was used to measure gait mechanics and steps (FRAIL-functional: fatigue, resistance, and aerobic), and a heart rate analyzer was used to measure heart rate recovery (FRAIL-nonfunctional: weight loss and chronic illness). ResultsThe participants’ mean age was 74.6 years. Of the 22 participants, 9 (41%) were robust, 10 (46%) were prefrail, and 3 (14%) were frail. In addition, 8 of 22 (36%) had at least one fall in the past year. Participants had a mean gait speed of 0.8 m/s, a mean SPPB score of 8.9, and mean TUG time of 13.8 seconds. The sensitivity, specificity, and area under the curve (AUC) for the gait analyzer against the functional domains were 1.00, 0.84, and 0.92, respectively, for SPPB (balance and gait); 0.38, 0.89, and 0.64, respectively, for FRAIL-functional; 0.45, 0.91, and 0.68, respectively, for FROP-Com; 0.60, 1.00, and 0.80, respectively, for gait speed; and 1.00, 0.94, and 0.97, respectively, for TUG. The heart rate analyzer demonstrated superior validity for the nonfunctional components of frailty, with a sensitivity of 1.00, specificity of 0.73, and AUC of 0.83. ConclusionsAgreement between the gait and heart rate analyzers and the functional components of the FRAIL scale, gait speed, and FROP-Com was significant. In addition, there was significant agreement between the heart rate analyzer and the nonfunctional components of the FRAIL scale. The gait and heart rate analyzers could be used in a screening test for frailty and falls in community-dwelling older adults but require further improvement and validation at the population level.

Resources recovery of calcium and phosphates from respective green mussel shells and bovine bones by calcination and chemically extracting are viable precursors for carbonate-rich apatite biomedical material applications. Because of their high osteoconductivity, carbonate-rich apatite bioceramics are being studied intensively for synthetic bone transplants. In the study, powder processing routes of calcination and following chemical dissolution in MgCl2 and H2SO4 were each for recovering calcium of mussel shells and phosphate of bovine bones yielding a crystal-forming solution feedstock for use in microwave-irradiated synthesis. FTIR spectra and XRD patterns validated the crystallinity and phase identification for as-synthesized powders. As a result, the presence of CO3, PO43-, and OH- bands in carbonate-calcium phosphate complexes were present in FTIR spectra. According to the XRD Rietveld method, the as-synthesized powder product contained brushite, carbonated hydroxyapatite (CHA), calcite, and gypsum. The recoverable CHA crystallites' size was 40 nm. This present study demonstrated that microwave irradiation synthesis of CHA powder with calcium and phosphates derived from mussel shells and bovine bones is the potential to yield a large amount of CHA for bioceramics and would aid in the design of a powder processing step for preparing the CHA powder precursor in biomedical applications.

Abstract For decades, many marine animals have been considered to exhibit cosmopolitan or transoceanic distribution. This situation is prevalent in Asia, where many species were collected and named by American or European experts in the 1700s to early 1900s. Using the windowpane oysters Placuna—a small genus of bivalves with five recognized species—we show that careful analysis is required to reassess the validity of these species. Currently, only two species of Placuna (P. placenta and P. ephippium) widely reported in the Indo‐Pacific region have been recorded from Chinese coastal waters. Here, we described two new species of Placuna from China. Placuna vitream sp. nov. can be distinguished from P. placenta by its larger ridge angle. Phylogenetic analysis using five gene fragments fully supported that P. vitream sp. nov. is a sister to the specimen from Singapore identified as P. placenta and more distant from other Placuna species with available molecular data. Besides, based on subfossil shells, we describe Placuna aestuaria sp. nov. that differs from its congeneric species by its broad hinge, medium ridge angle, and nearly straight ridges. Finally, we suggest a combination of hinge structure and ridge angle that can be used for identifying Placuna species and preparing a key to this genus. Our findings of two new species expand the diversity of Placuna and prompt reassessment of the many presumably widely distributed marine species in Asia.

Abstract Background Mesenchymal stem cells (MSCs) have garnered significant interest for their tumor-tropic property, making them potential therapeutic delivery vehicles for cancer treatment. We have previously shown the significant anti-tumour activity in mice preclinical models and companion animals with naturally occurring cancers using non-virally engineered MSCs with a therapeutic transgene encoding cytosine deaminase and uracil phosphoribosyl transferase (CDUPRT) and green fluorescent protein (GFP). Clinical studies have shown improved response rate with combinatorial treatment of 5-fluorouracil and Interferon-beta (IFNb) in peritoneal carcinomatosis (PC). However, high systemic toxicities have limited the clinical use of such a regime. Methods In this study, we evaluated the feasibility of intraperitoneal administration of non-virally engineered MSCs to co-deliver CDUPRT/5-Flucytosine prodrug system and IFNb to potentially enhance the cGAS-STING signalling axis. Here, MSCs were engineered to express CDUPRT or CDUPRT-IFNb. Expression of CDUPRT and IFNb was confirmed by flow cytometry and ELISA, respectively. The anti-cancer efficacy of the engineered MSCs was evaluated in both in vitro and in vivo model. ES2, HT-29 and Colo-205 were cocultured with engineered MSCs at various ratio. The cell viability with or without 5-flucytosine was measured with MTS assay. To further compare the anti-cancer efficacy of the engineered MSCs, peritoneal carcinomatosis mouse model was established by intraperitoneal injection of luciferase expressing ES2 stable cells. The tumour burden was measured through bioluminescence tracking. Results Firstly, there was no changes in phenotypes of MSCs despite high expression of the transgene encoding CDUPRT and IFNb (CDUPRT-IFNb). Transwell migration assays and in-vivo tracking suggested the co-expression of multiple transgenes did not impact migratory capability of the MSCs. The superiority of CDUPRT-IFNb over CDUPRT expressing MSCs was demonstrated in ES2, HT-29 and Colo-205 in-vitro. Similar observations were observed in an intraperitoneal ES2 ovarian cancer xenograft model. The growth of tumor mass was inhibited by ~ 90% and 46% in the mice treated with MSCs expressing CDUPRT-IFNb or CDUPRT, respectively. Conclusions Taken together, these results established the effectiveness of MSCs co-expressing CDUPRT and IFNb in controlling and targeting PC growth. This study lay the foundation for the development of clinical trial using multigene-armed MSCs for PC.

Abstract Background Parasitic helminths influence the composition of the gut microbiome. However, the microbiomes of individuals living in helminth-endemic regions are understudied. The Orang Asli, an indigenous population in Malaysia with high burdens of the helminth Trichuris trichiura, display microbiotas enriched in Clostridiales, an order of spore-forming obligate anaerobes with immunogenic properties. We previously isolated novel Clostridiales that were enriched in these individuals and found that a subset promoted the Trichuris life cycle. In this study, we aimed to further characterize the functional properties of these bacteria. Results Clostridiales isolates were profiled for their ability to perform 57 enzymatic reactions and produce short-chain fatty acids (SCFAs) and hydrogen sulfide, revealing that these bacteria were capable of a range of activities associated with metabolism and host response. Consistent with this finding, monocolonization of mice with individual isolates identified bacteria that were potent inducers of regulatory T-cell (Treg) differentiation in the colon. Comparisons between variables revealed by these studies identified enzymatic properties correlated with Treg induction and Trichuris egg hatching. Conclusion We identified Clostridiales species that are sufficient to induce high levels of Tregs. We also identified a set of metabolic activities linked with Treg differentiation and Trichuris egg hatching mediated by these newly isolated bacteria. Altogether, this study provides functional insights into the microbiotas of individuals residing in a helminth-endemic region. Video Abstract

Human peptidylarginine deiminase isoform VI (PAD6), which is predominantly limited to cytoplasmic lattices in the mammalian oocytes in ovarian tissue, is essential for female fertility. It belongs to the peptidylarginine deiminase (PAD) enzyme family that catalyzes the conversion of arginine residues to citrulline in proteins. In contrast to other members of the family, recombinant PAD6 was previously found to be catalytically inactive. We sought to provide structural insight into the human homologue to shed light on this observation. We report here the first crystal structure of PAD6, determined at 1.7 Å resolution. PAD6 follows the same domain organization as other structurally known PAD isoenzymes. Further structural analysis and size-exclusion chromatography show that PAD6 behaves as a homodimer similar to PAD4. Differential scanning fluorimetry suggests that PAD6 does not coordinate Ca2+ which agrees with acidic residues found to coordinate Ca2+ in other PAD homologs not being conserved in PAD6. The crystal structure of PAD6 shows similarities with the inactive state of apo PAD2, in which the active site conformation is unsuitable for catalytic citrullination. The putative active site of PAD6 adopts a non-productive conformation that would not allow protein–substrate binding due to steric hindrance with rigid secondary structure elements. This observation is further supported by the lack of activity on the histone H3 and cytokeratin 5 substrates. These findings suggest a different mechanism for enzymatic activation compared with other PADs; alternatively, PAD6 may exert a non-enzymatic function in the cytoplasmic lattice of oocytes and early embryos.

In this article, we showcase the pilot scenario of The Trojan War, an educational self-directed game that combines text inspired by ancient Greek (as well as Roman) literature with graphics based on the ‘Geometric style’, an authentic Greek style of painting contemporary with the composition of the Homeric epics. Our game uses interactive scenarios to support active learning strategies of students interested in Classical Studies in both tertiary and secondary education. Players can take on the role of key characters, making choices that can prevent, start, or stop the Trojan War, as well as determine their own personal outcomes. The learners are thus presented with the opportunity to explore alternative pathways to rewrite the history of the War. In the process, they can apply their subject knowledge and develop their intellectual and critical skills. They also become familiar with a distinctive and expressive early Greek artistic style, the so-called Geometric. Rather than focusing on winning, the game aims to give students the opportunity to engage with important ideas and values of ancient Greek culture by exploring multiple perspectives on the topic. It also provides a valuable lesson on the potentially wide-ranging consequences of individual choices, which is a core element of responsible citizenship.

Malarmugila Manimaran,1,* Yin Yin Teo,2 James Chen Yong Kah,3 Adilet Beishenaliev,1 Yean Leng Loke,2 Yiing Yee Foo,1 Shiow-Fern Ng,4 Chin Fei Chee,5 Sek Peng Chin,6 Farid Nazer Faruqu,1 Chia-Yu Chang,7 Misni Misran,2 Lip Yong Chung,6 Bey Fen Leo,8,* Shih-Hwa Chiou,9,10 Chia-Ching Chang,7,11– 13 Sun Tee Tay,14 Lik Voon Kiew1,7 1Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 2Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia; 3Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore; 4Centre for Drug Delivery Technology and Vaccine, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 5Nanotechnology Catalysis Research Centre, Universiti Malaya, Kuala Lumpur, Malaysia; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia; 7Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 8Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 9Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 10Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China; 11Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 12Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 13Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan, Republic of China; 14Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia*These authors contributed equally to this workCorrespondence: Chia-Ching Chang; Lik Voon Kiew, Email ccchang01@nycu.edu.tw; lvkiew@um.edu.myIntroduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections.Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV–Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied.Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 μM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy.Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.Keywords: biofilm, gold nanorod, S. aureus, PDADMAC, MRSA, MSSA

Objective(s): The complexity of aortic arch reconstruction due to diverse 3-dimensional geometrical abnormalities is a major challenge. This study introduces 3-dimensional printed tissue-engineered vascular grafts, which can fit patient-specific dimensions, optimize hemodynamics, exhibit antithrombotic and anti-infective properties, and accommodate growth. Methods: We procured cardiac magnetic resonance imaging with 4-dimensional flow for native porcine anatomy (n = 10), from which we designed tissue-engineered vascular grafts for the distal aortic arch, 4 weeks before surgery. An optimal shape of the curved vascular graft was designed using computer-aided design informed by computational fluid dynamics analysis. Grafts were manufactured and implanted into the distal aortic arch of porcine models, and postoperative cardiac magnetic resonance imaging data were collected. Pre- and postimplant hemodynamic data and histology were analyzed. Results: Postoperative magnetic resonance imaging of all pigs with 1:1 ratio of polycaprolactone and poly-L-lactide-co-ε-caprolactone demonstrated no specific dilatation or stenosis of the graft, revealing a positive growth trend in the graft area from the day after surgery to 3 months later, with maintaining a similar shape. The peak wall shear stress of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft portion did not change significantly between the day after surgery and 3 months later. Immunohistochemistry showed endothelization and smooth muscle layer formation without calcification of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft. Conclusions: Our patient-specific polycaprolactone/poly-L-lactide-co-ε-caprolactone tissue-engineered vascular grafts demonstrated optimal anatomical fit maintaining ideal hemodynamics and neotissue formation in a porcine model. This study provides a proof of concept of patient-specific tissue-engineered vascular grafts for aortic arch reconstruction.

Abstract Hereditary cancer syndromes constitute approximately 10% of all cancers. Cascade testing involves testing of at-risk relatives to determine if they carry the familial pathogenic variant. Despite growing efforts targeted at improving cascade testing uptake, current literature continues to reflect poor rates of uptake, typically below 30%. This study aims to systematically review current literature on intervention strategies to improve cascade testing, assess the quality of intervention descriptions and evaluate the implementation outcomes of listed interventions. We searched major databases using keywords and subject heading of “cascade testing”. Interventions proposed in each study were classified according to the Effective Practice and Organization of Care (EPOC) taxonomy. Quality of intervention description was assessed using the TIDieR checklist, and evaluation of implementation outcomes was performed using Proctor’s Implementation Outcomes Framework. Improvements in rates of genetic testing uptake was seen in interventions across the different EPOC taxonomy strategies. The average TIDieR score was 7.3 out of 12. Items least reported include modifications (18.5%), plans to assess fidelity/adherence (7.4%) and actual assessment of fidelity/adherence (7.4%). An average of 2.9 out of 8 aspects of implementation outcomes were examined. The most poorly reported outcomes were cost, fidelity and sustainability, with only 3.7% of studies reporting them. Most interventions have demonstrated success in improving cascade testing uptake. Uptake of cascade testing was highest with delivery arrangement (68%). However, the quality of description of interventions and assessment of implementation outcomes are often suboptimal, hindering their replication and implementation downstream. Therefore, further adoption of standardized guidelines in reporting of interventions and formal assessment of implementation outcomes may help promote translation of these interventions into routine practice.

Introduction: Learners frequently benefit from modalities such as small-group, case-based teaching and interactive didactic experiences rather than passive learning methods. These contemporary techniques are features of Foundations of Emergency Medicine (FoEM) curricula, and particularly the Foundations I (F1) course, which targets first-year resident (PGY-1) learners. The American Board of Emergency Medicine administers the in-training exam (ITE) that provides an annual assessment of EM-specific medical knowledge. We sought to assess the effect of F1 implementation on ITE scores. Methods: We retrospectively analyzed data from interns at four EM residency programs accredited by the Accreditation Council for Graduate Medical Education. We collected data in 2021. Participating sites were geographically diverse and included three- and four-year training formats. We collected data from interns two years before (control group) and two years after (intervention group) implementation of F1 at each site. Year of F1 implementation ranged from 2015–2018 at participating sites. We abstracted data using a standard form including program, ITE raw score, year of ITE administration, US Medical Licensing Exam Step 1 score, Step 2 Clinical Knowledge (CK) score, and gender. We performed univariable and multivariable linear regression to explore differences between intervention and control groups. Results: We collected data for 180 PGY-1s. Step 1 and Step 2 CK scores were significant predictors of ITE in univariable analyses (both with P

Background: Hypertension is frequently studied in epidemiological studies that have been conducted using retrospective observational data, either as an outcome or a variable. However, there are few validation studies investigating the accuracy of hypertension phenotyping algorithms in aggregated electronic health record (EHR) data. Methods: Utilizing a centralized repository of inpatient EHR data from Singapore for the period of 2019–2020, a new algorithm that incorporates both diagnostic codes and medication details (Diag+Med) was devised. This algorithm was intended to supplement and improve the diagnostic code-only model (Diag-Only) for the classification of hypertension. We computed various metrics (sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)) to assess the algorithm’s effectiveness in identifying hypertension on 2813 chart-reviewed records. This pool was composed of two patient cohorts: a random sampling of all inpatient admissions (Random Cohort) and a targeted group with atrial fibrillation diagnoses (AF Cohort). Results: The Diag+Med algorithm was more sensitive at detecting hypertension patients in both cohorts compared to the Diag-Only algorithm (83.8 and 87.6% vs. 68.2 and 66.5% in the Random and AF Cohorts, respectively). These improvements in sensitivity came at minimal costs in terms of PPV reductions (88.2 and 90.3% vs. 91.4 and 94.2%, respectively). Conclusion: The combined use of diagnosis codes and specific antihypertension medication exposure patterns facilitates a more accurate capture of patients with hypertension in a database of aggregated EHRs from diverse healthcare institutions in Singapore. The results presented here allow for the bias correction of risk estimates derived from observational studies involving hypertension.

Abstract Background Empirical evidence suggests that lack of blinding may be associated with biased estimates of treatment benefit in randomized controlled trials, but the influence on medication-related harms is not well-recognized. We aimed to investigate the association between blinding and clinical trial estimates of medication-related harms. Methods We searched PubMed from January 1, 2015, till January 1, 2020, for systematic reviews with meta-analyses of medication-related harms. Eligible meta-analyses must have contained trials both with and without blinding. Potential covariates that may confound effect estimates were addressed by restricting trials within the comparison or by hierarchical analysis of harmonized groups of meta-analyses (therefore harmonizing drug type, control, dosage, and registration status) across eligible meta-analyses. The weighted hierarchical linear regression was then used to estimate the differences in harm estimates (odds ratio, OR) between trials that lacked blinding and those that were blinded. The results were reported as the ratio of OR (ROR) with its 95% confidence interval (CI). Results We identified 629 meta-analyses of harms with 10,069 trials. We estimated a weighted average ROR of 0.68 (95% CI: 0.53 to 0.88, P

This paper investigates the application of three nature-inspired optimisation algorithms – SHO, MFO, and GOA – combined with four machine learning methods – Gaussian Processes, Linear Regression, MLP, and Random Forest – to enhance carbon dioxide emission prediction in the OECD – Asia and Oceania region. The study uses historical carbon dioxide emissions data, socioeconomic indicators such as GDP, population density, energy consumption, and urbanisation rates, and environmental indicators such as temperature, precipitation, and forest cover. Through comprehensive experimentation, the study evaluates the performance of each combination, revealing varying effectiveness levels. The MFO-MLP combination achieved the highest accuracy with R2 values of 0.9996 and 0.9995 and RMSE values of 11.7065 and 12.8890 for the training and testing datasets, respectively. The GOA-MLP configuration achieved R2 values of 0.9994 and 0.99934 and RMSE values of 15.01306 and 14.59333. The SHO-MLP combination, while effective, showed lower performance with R2 values of 0.9915 and 0.9946 and RMSE values of 55.4516 and 41.575. The findings suggest hybrid techniques can significantly enhance prediction accuracy compared to conventional methods. This research provides valuable insights for policymakers and stakeholders, indicating that optimised machine learning models can support more informed and effective environmental policy-making and sustainability efforts in the OECD – Asia and Oceania region. Future research should explore additional optimisation algorithms and ensemble techniques to improve prediction robustness and accuracy. These findings offer a robust tool for policymakers to forecast emissions more accurately, aiding in developing targeted strategies to reduce carbon footprints and achieve climate goals.

Purpose Evidence about the associations of migraine features with cardiovascular risk profiles in Chinese population is lacking. The Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK) cohort was constructed to investigate longitudinal migraine features and their cardiovascular implications in Hong Kong Chinese women.Participants We enrolled 4221 Hong Kong Chinese women aged 30 years or above from October 2019 to December 2020. Demographics, reproductive information, lifestyle factors, disease history, blood lipids and glucose, anthropometrics and body compositions were measured during baseline and follow-up. Migraine diagnosis followed the International Classification of Headache Disorders-3 criteria. Migraine features were longitudinally tracked using a migraine diary and summarised by a wide range of epidemiological metrics. Cardiovascular health was assessed using the Framingham risk score (FRS).Findings to date From October 2021 to June 2023, 3455 women completed the first follow-up measurement. The retention rate was 81.9%. The average age at baseline was 54.40 years. The mean blood glucose, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were 6.44 mmol/L, 65.06 mg/dL and 102.40 mg/dL, respectively. The average FRS was 0.06. Participants had a 10.3% prevalence of migraine or probable migraine. After 1.27 years of follow-up, the median migraine attack frequency was 0.99 attacks/month, with an incidence rate of 2.55 attacks/person-month and a median duration of 7.70 hours/attack. Sleep problems (64.7%) and stress (54.0%) were the top triggers, while prevalent accompanying symptoms were nausea (67.4%), photophobia (39.9%), phonophobia (30.0%) and vomiting (26.2%). Migraine auras included blurred visions (59.6%), flashing lights (41.3%), blind spots (33.0%), pins and needles (6.4%) and halo (1.8%).Future plans The follow-up for the cohort will be implemented every 2 years. MECH-HK will provide unique longitudinal data on migraine features in Hong Kong women. The linkage between migraine features and cardiovascular disease risk progression will be identified by a long-term observation.

Summary: The properties of complex bodily fluids are linked to their biological functions through natural selection. Velvet worms capture their prey by ensnaring them with a proteinaceous fluid (slime). We examined the electrical conductivity of slime and found that dry slime is an insulator. However, its conductivity can increase by up to 106 times in its hydrated state, which can be further increased by an order in magnitude under acidic hydration (pH ≈ 2.3). The transient current measured using ion-blocking electrodes showed a continuous decay for up to 7 h, revealing slime’s nature as a proton conducting material. Slime undergoes a spontaneous fibrilization process producing high aspect ratio ≈ 105 fibers that exhibit an average conductivity ≈2.4 ± 1.1 mS cm−1. These findings enhance our understanding of slime as a natural biopolymer and provide molecular-level guidelines to rationally design biomaterials that may be employed as hygroscopic conductors.

Coral reefs provide a multitude of ecosystem functions owing to the high levels of biodiversity they host. Coral species, as the foundation of shallow-water reefs, differ in their contributions toward the functioning of the ecosystem due in part to the disparate phylogenetic histories of scleractinian lineages. Understanding the spatial patterns and temporal trajectories of these biodiversity facets, as well as their interrelationships, is critical for more targeted conservation strategies in the face of widespread habitat degradation and climate change. Here, we analyse long-term benthic data spanning 1986 through 2020 on coral reefs in Singapore, which have been impacted by decades of urbanisation-related and thermal stressors, to test for differences between coral biodiversity facets—specifically, taxonomic, phylogenetic (evolutionary relatedness between species), and functional (occupancy of functional trait space) richness and diversity. Analyses show that taxonomic and phylogenetic richness and diversity measures increased over the 35-year period despite declines during major bleaching events. Yet, while taxonomic and phylogenetic diversity increased, functional richness and diversity declined over the same period. Community-weighted trait measures indicate a shift towards dominance of more stress-tolerant traits such as slower growth rates, smaller corallite sizes, and massive colony forms. Together, these trends highlight the effects of chronic urban stressors alongside major bleaching events impacting reef assemblages. Critically, such assemblage shifts and functional diversity declines were masked by increasing taxonomic diversity, which is most commonly assessed, and could erode ecosystem resilience. The temporal decoupling of the biodiversity facets examined here underscore the need for more comprehensive monitoring of reefs through a combination of trait-based approaches alongside traditional field surveys at finer taxonomic resolution.

Introduction Effective treatment of severe asthma requires patient adherence to inhaled and biological medications. Previous work has shown that patient support programmes (PSP) can improve adherence in patients with chronic diseases, but the impact of PSPs in patients with severe asthma treated with biologics has not been thoroughly investigated.Methods We conducted a systematic literature review to understand the impact of PSPs on treatment adherence, asthma control and health-related quality of life (HRQoL) in patients with severe asthma. Embase, MEDLINE and EconLit databases were searched for studies published from 2003 (the year of the first biological approval for severe asthma) to June 2023 that described PSP participation among patients with severe asthma on biological treatment. Direct pooling of outcomes was not possible due to the heterogeneity across studies, so an indirect treatment comparison (ITC) was performed to determine the effect of PSP participation on treatment discontinuation. The ITC used patient-level data from patients treated with benralizumab either enrolled in a PSP (VOICE study, Connect 360 PSP) or not enrolled in a PSP (Benralizumab Patient Access Programme study) in the UK.Findings 25 records of 21 studies were selected. Six studies investigated the impact of PSPs on treatment adherence, asthma control or HRQoL. All six studies reported positive outcomes for patients enrolled in PSPs; the benefits of each PSP were closely linked to the services provided. The ITC showed that patients in the Connect 360 PSP group were less likely to discontinue treatment compared with the non-PSP group (OR 0.26, 95% CI 0.11 to 0.57, p