Real-world data on the use of emicizumab in patients with haemophilia A with and without inhibitors in Singapore.

Introduction: Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII by binding to factor IXa and factor X to achieve haemostasis in haemophilia A. The long half-life and subcutaneous mode of administration makes emicizumab a compelling treatment option for bleeding prophylaxis. There is still limited real-world data on its use and management considerations, especially during surgical procedures. The objective of the study is to describe the real-world experience of emicizumab in a cohort of adult and paediatric haemophilia A patients in Singapore, including its use in the periprocedural setting. Method: This was an observational study conducted at the 2 main haemophilia treatment centres in Singapore. All haemophilia A patients who commenced treatment with emicizumab before 1 July 2022 were recruited. Results: A total of 18 patients with haemophilia A were included in this study. Ten (55.6%) patients had active inhibitors. The median annual bleeding rate for all patients before emicizumab use was 4.5 events (interquartile range [IQR] 2.8-8.3) compared with 0 events (IQR 0-0) after emicizumab was commenced (P=0). There were no adverse events of venous or arterial thrombosis, thrombotic microangiopathy, or death. A total of 6 procedures in 5 patients were performed during the study period with no major bleeding complications. Conclusion: Emicizumab effectively protects against bleeding in haemophilia A patients with and without inhibitors, including in children less than 12 years old. More studies are required to address clinical nuances, such as periprocedural management and the role of immune tolerance in patients with inhibitors on emicizumab.

Waste expanded polystyrene modified with H2SO4/biodegradable chelating agent for reuse: As a highly efficient adsorbent to remove fluoroquinolone antibiotic from water.

Untreated wastewater containing fluoroquinolone antibiotics poses serious hazards to aquatic species and human health; therefore, treatment of waste expanded polystyrene (EPS) is a crucial environmental matter. In this study, waste EPS was modified with a H2SO4/biodegradable chelating agent, [S,S]-ethylenediamine-N,N'-disuccinic acid (EDDS), and used for highly efficient adsorption of the fluoroquinolone antibiotic ciprofloxacin. When ciprofloxacin of 25 mg/L was used, the H2SO4-modified EPS (EPSH2SO4) adsorbed 60.5% of the ciprofloxacin. During sulfonation, adding a low dose of EDDS markedly improved the adsorption ability of EPSH2SO4+EDDS. The optimal modification conditions were 95% H2SO4, 0.002 M EDDS, 80 °C, and 40 min. The increased adsorbent doses enhanced the adsorption. Approximately 0.2 g/L of EPSH2SO4+EDDS could effectively adsorb 97.8% of the ciprofloxacin (554.3 mg/g) within 30 min. Solution pH0 greatly influenced the adsorption, and the most suitable pH0 was 6. The Langmuir isotherm accurately described the adsorption behaviors of both EPSH2SO4 and EPSH2SO4+EDDS (R2 = 0.997-0.998). The adsorption ability of EPSH2SO4+EDDS (qmax = 1250 mg/g) was 32 times higher than that of EPSH2SO4 (qmax = 38.6 mg/g). A total of 1 M HCl effectively regenerated the exhausted adsorbent. The optimal solid/liquid ratio and time were 0.08 g/20 mL and 60 min, respectively. The regenerated EPSH2SO4+EDDS maintained a high adsorption ability (87.2%) after 10 regeneration cycles. The results thus indicate that the EPSH2SO4+EDDS adsorption-regeneration process is a potential approach to remove ciprofloxacin from water.

A Four-Step Cascade Drug-Release Management Strategy for Transcatheter Arterial Chemoembolization (TACE) Therapeutic Applications.

The purpose of this study was to develop a four-step cascade drug-release system for transcatheter arterial chemoembolization (TACE) therapeutic applications according to disease-driven and patient-focused design theories. The four steps underlying these strategies involve the blockage of nutrient supply, nanoparticles, codelivery and the cell cytotoxic effect. Calibrated spherical gellan gum (GG) and nanoparticle-containing gellan gum microspheres were prepared using a water-in-oil emulsification method. Self-assembled nanoparticles featuring amine-functionalized graphene oxide (AFGO) as the doxorubicin (Dox) carrier were prepared. The results confirm that, as a drug carrier, AFGO-Dox nanoparticles can facilitate the transport of doxorubicin into HepG2 liver cancer cells. Subsequently, AFGO-Dox was introduced into gellan gum (GG) microspheres, thus forming GG/AFGO-Dox microspheres with a mean size of 200-700 µm. After a drug release experiment lasting 28 days, the amount of doxorubicin released from 674 and 226 µm GG/AFGO-Dox microspheres was 2.31 and 1.18 µg/mg, respectively. GG/AFGO-Dox microspheres were applied in a rabbit ear embolization model, where ischemic necrosis was visible on the ear after 12 days. Our aim for the future is to provide better embolization agents for transcatheter arterial chemoembolization (TACE) using this device.

Theory of molecular emission power spectra. II. Angle, frequency, and distance dependence of electromagnetic environment factor of a molecular emitter in plasmonic environments.

Our previous study [S. Wang et al., J. Chem. Phys. 153, 184102 (2020)] has shown that in a complex dielectric environment, molecular emission power spectra can be expressed as the product of the lineshape function and the electromagnetic environment factor (EEF). In this work, we focus on EEFs in a vacuum-NaCl-silver system and investigate molecular emission power spectra in the strong exciton-polariton coupling regime. A numerical method based on computational electrodynamics is presented to calculate the EEFs of single-molecule emitters in a dispersive and lossy dielectric environment with arbitrary shapes. The EEFs in the far-field region depend on the detector position, emission frequency, and molecular orientation. We quantitatively analyze the asymptotic behavior of the EFFs in the far-field region and qualitatively provide a physical picture. The concept of EEF should be transferable to other types of spectra in a complex dielectric environment. Finally, our study indicates that molecular emission power spectra cannot be simply interpreted by the lineshape function (quantum dynamics of a molecular emitter), and the effect of the EEFs (photon propagation in a dielectric environment) has to be carefully considered.

Mortality in children hospitalised with respiratory syncytial virus infection in Singapore.

INTRODUCTION: This study aimed to investigate the trend and seasonality of infection due to respiratory syncytial virus (RSV) at KK Women's and Children's Hospital (KKH) in Singapore and to examine the risk factors for mortality among children with RSV infection requiring admission to the paediatric intensive care unit (PICU). METHODS: A retrospective study was conducted at KKH on children with RSV infections who were admitted to the PICU between January 2004 and December 2010. The medical records of children who died from RSV infections were reviewed. Linear regression was performed to determine the risk factors for RSV mortality. RESULTS: RSV infection was documented in 5,785 children during the study period; the infection was noted to be occurring throughout the year, with a small increase in prevalence between the months of June and August every year. Among 85 (1.5%) out of 5,785 children who were admitted to the PICU for RSV infection, 74 (1.3%) survived and 11 (0.2%) died. Multivariate logistic regression analysis showed that haemodynamically significant cardiac disease (odds ratio [OR] 12.2, 95% confidence interval [CI] 0.9-16.7, p = 0.05), immunodeficiency (OR 71.4, 95% CI 8.2-500, p < 0.001) and metabolic disease (OR 71.4, 95% CI 4.3-1,000, p = 0.003) were independent risk factors for mortality in RSV infections. Prematurity increased the risk of admission to the PICU but was not significantly associated with mortality. CONCLUSION: Children with haemodynamically significant cardiac disease, immunodeficiency and metabolic disease were at higher risk of death after hospitalisation for RSV-related illnesses. These children should be considered for palivizumab prophylaxis.

Theory of molecular emission power spectra. I. Macroscopic quantum electrodynamics formalism.

We study the emission power spectrum of a molecular emitter with multiple vibrational modes in the framework of macroscopic quantum electrodynamics. The theory we present is general for a molecular spontaneous emission spectrum in the presence of arbitrary inhomogeneous, dispersive, and absorbing media. Moreover, the theory shows that the molecular emission power spectra can be decomposed into the electromagnetic environment factor and lineshape function. In order to demonstrate the validity of the theory, we investigate the lineshape function in two limits. In the incoherent limit (single molecules in a vacuum), the lineshape function exactly corresponds to the Franck-Condon principle. In the coherent limit (single molecules strongly coupled with single polaritons or photons) together with the condition of high vibrational frequency, the lineshape function exhibits a Rabi splitting, the spacing of which is exactly the same as the magnitude of exciton-photon coupling estimated by our previous theory [S. Wang et al., J. Chem. Phys. 151, 014105 (2019)]. Finally, we explore the influence of exciton-photon and electron-phonon interactions on the lineshape function of a single molecule in a cavity. The theory shows that the vibronic structure of the lineshape function does not always disappear as the exciton-photon coupling increases, and it is related to the loss of a dielectric environment.

Controllable Frequency Dependence of Resonance Energy Transfer Coupled with Localized Surface Plasmon Polaritons.

We investigate the intrinsic characteristics of resonance energy transfer (RET) coupled with localized surface plasmon polaritons (LSPPs) from the perspective of macroscopic quantum electrodynamics. To quantify the effect of LSPPs, we propose a numerical scheme that allows us to accurately calculate the rate of RET between a donor-acceptor pair near a nanoparticle. Our study shows that LSPPs can be used to enhance the RET rate significantly and control its frequency dependence by modifying a core/shell structure, which indicates the possibility of RET rate optimization. Moreover, we systematically explore the angle (distance) dependence of the RET rate and analyze its origin. According to different frequency regimes, the angle dependence of RET is dominated by different mechanisms, such as LSPPs, surface plasmon polaritons (SPPs), and anti-resonance. For the proposed core/shell structure, the characteristic distance of RET coupled with LSPPs (approximately 0.05 emission wavelength) is shorter than that of RET coupled with SPPs (approximately 0.1 emission wavelength), which may provide promising applications in energy science.

Perspectives on Palliative Care Among Duchenne Muscular Dystrophy Patients and Their Families in Singapore.

INTRODUCTION: With better medical care, patients with Duchenne muscular dystrophy (DMD) now live longer but face more complex medical and social needs. This study described the perceptions of DMD patients and their families of disease-specific palliative care services in Singapore. MATERIALS AND METHODS: A multicentre, cross-sectional study involving DMD patients and their families was carried out. Structured questionnaires were administered to them to collect data on their understanding of palliative care, health services accessed and desired by them and quality of life. RESULTS: A total of 30 pairs of DMD patients and their caregivers responded. Most patients were >13 years old (70%) and non-ambulant (86%). Most of them and their families (70%) were also not aware of palliative care and support services that were available to them in Singapore. Additionally, they perceived greater financial assistance and better transport services as resources that could better meet their care needs. The presence of scoliosis and need for ventilatory support were associated with lower quality of life in patients. CONCLUSION: There is a need to improve awareness and provision of palliative care services for DMD patients in Singapore where discussion of end-of-life care is often considered taboo. Prevention and correction of scoliosis and provision of appropriate ventilatory support may improve quality of life in DMD patients.

A low-count reconstruction algorithm for Compton-based prompt gamma imaging.

The Compton camera is an imaging device which has been proposed to detect prompt gammas (PGs) produced by proton-nuclear interactions within tissue during proton beam irradiation. Compton-based PG imaging has been developed to verify proton ranges because PG rays, particularly characteristic ones, have strong correlations with the distribution of the proton dose. However, accurate image reconstruction from characteristic PGs is challenging because the detector efficiency and resolution are generally low. Our previous study showed that point spread functions can be incorporated into the reconstruction process to improve image resolution. In this study, we proposed a low-count reconstruction algorithm to improve the image quality of a characteristic PG emission by pooling information from other characteristic PG emissions. PGs were simulated from a proton beam irradiated on a water phantom, and a two-stage Compton camera was used for PG detection. The results show that the image quality of the reconstructed characteristic PG emission is improved with our proposed method in contrast to the standard reconstruction method using events from only one characteristic PG emission. For the 4.44 MeV PG rays, both methods can be used to predict the positions of the peak and the distal falloff with a mean accuracy of 2 mm. Moreover, only the proposed method can improve the estimated positions of the peak and the distal falloff of 5.25 MeV PG rays, and a mean accuracy of 2 mm can be reached.

Hyaluronic acid-based nano-sized drug carrier-containing Gellan gum microspheres as potential multifunctional embolic agent.

The purpose of this study was to develop a gellan gum-based multifunctional embolic agent. Calibrated spherical gellan gum and nanoparticle-containing gellan gum microspheres were prepared via water-in oil emulsification method. Self-assembled nanoparticles composed of short-chain hyaluronic acid and polyethylenimine as the doxorubicin carrier were prepared. The short-chain hyaluronic acid/polyethylenimine/ doxorubicin (sHH/PH/Dox) with the mean size was 140 ± 8 nm. To examine sHH/PH/Dox nanoparticle uptake into cells, the results confirmed that sHH/PH nanoparticles as drug carrier can facilitate the transport of doxorubicin into HepG2 liver cancer cells. Subsequently, sHH/PH/Dox merged into the gellan gum (GG) microspheres forming GG/sHH/PH/Dox microsphere. After a drug release experiment lasting 45 days, the amount of released doxorubicin from 285, 388, and 481 µm GG/sHH/PH/Dox microspheres were approximately 4.8, 1.8 and 1.1-fold above the IC50 value of the HepG2 cell. GG/sHH/PH/Dox microspheres were performed in rabbit ear embolization model and ischemic necrosis on ear was visible due to the vascular after 8 days. Regarding the application of this device in the future, we aim to provide better embolization agents for transcatheter arterial chemoembolization (TACE).

PSF reconstruction for Compton-based prompt gamma imaging.

Compton-based prompt gamma (PG) imaging has been proposed for in vivo range verification in proton therapy. However, several factors degrade the image quality of PG images, some of which are due to inherent properties of a Compton camera such as spatial resolution and energy resolution. Moreover, Compton-based PG imaging has a spatially variant resolution loss. In this study, we investigate the performance of the list-mode ordered subset expectation maximization algorithm with a shift-variant point spread function (LM-OSEM-SV-PSF) model. We also evaluate how well the PG images reconstructed using an SV-PSF model reproduce the distal falloff of the proton beam. The SV-PSF parameters were estimated from simulation data of point sources at various positions. Simulated PGs were produced in a water phantom irradiated with a proton beam. Compared to the LM-OSEM algorithm, the LM-OSEM-SV-PSF algorithm improved the quality of the reconstructed PG images and the estimation of PG falloff positions. In addition, the 4.44 and 5.25 MeV PG emissions can be accurately reconstructed using the LM-OSEM-SV-PSF algorithm. However, for the 2.31 and 6.13 MeV PG emissions, the LM-OSEM-SV-PSF reconstruction provides limited improvement. We also found that the LM-OSEM algorithm followed by a shift-variant Richardson-Lucy deconvolution could reconstruct images with quality visually similar to the LM-OSEM-SV-PSF-reconstructed images, while requiring shorter computation time.

MAGEA10 gene expression in non-small cell lung cancer and A549 cells, and the affinity of epitopes with the complex of HLA-A(∗)0201 alleles.

MAGEA10, a cancer/testis antigens expressed in tumors but not in normal tissues with the exception of testis and placenta, represents an attractive target for cancer immunotherapy. However, suppressive cytoenvironment and requirement of specific HLA-alleles presentation frequently led to immunotherapy failure. In this study MAGEA10 was scarcely expressed in cancer patients, but enhanced by viili polysaccharides, which indicates a possibility of increasing epitopes presentation. Furthermore the correlation of gene expression with methylation, indicated by R(2) value for MAGEA10 that was 3 times higher than the value for other MAGE genes tested, provides an explanation of why MAGEA10 was highly inhibited, this is also seen by Kaplan-Meier analysis because MAGEA10 did not change the patients' lifespan. By using Molecular-Docking method, 3 MAGEA10 peptides were found binding to the groove position of HLA-A(∗)0210 as same as MAGEA4 peptide co-crystallized with HLA-A(∗)0210, which indicates that they could be promising for HLA-A(∗)0201 presentation in immunotherapy.

Effects of Reductants on Phytoextraction of Chromium (VI) by Ipomoea aquatica.

Reductants are often used to reduce Cr(VI) in chemical treatments, yet the effects of the reductants on Cr(VI) phytoremediation are not fully understood. This study investigates the effects of different reductants on Cr(VI) phytoremediation by Ipomoea aquatica in simulated solution with 3 mg L(-1) of Cr(VI), pH0 of 6, and an incubation time of 5 days. Results indicate that the applications of S2O3(2-), Fe0, and Fe2+ at low doses notably increased root Cr concentrations, which were obviously higher than that those in the control (Cr6+ alone). However, high reductant concentrations decreased bioaccumulation of Cr in the roots and shoots of the plant. Statistical results indicate that Cr concentrations were significantly and negatively correlated with Fe concentrations in the roots and shoots of the plant (p<0.05). This suggest that Fe accumulation inhibited Cr accumulation in the plant. A Cr(VI) concentration of 3 mg L(-1) caused short, brown lateral roots with tip necrosis, leaf chlorosis, and noticeable shoot wilting. The leaf necrosis and shoot wilting is caused by oxidative damage of lateral roots by Cr(VI) rather than by the reactive oxygen species generated by the oxidative stress. Addition of the reductants effectively reduced these plant injuries.

A linear gradient line source facilitates the use of diffusion models with high order approximation for efficient, accurate turbid sample optical properties recovery.

In this paper, we demonstrate that a scanning MEMS mirror can be employed to create a linear gradient line source that is equivalent to a planar source. This light source setup facilitates the use of diffusion models of increased orders of approximation having closed form solution, and thus enhance the efficiency and accuracy in sample optical properties recovery. In addition, compared with a regular planar light source, the linear gradient line source occupies much less source area and has an elevated measurement efficiency. We employed a δ-P1 diffusion equation with a closed form solution and carried out a phantom study to understand the performance of this new method in determining the absorption and scattering properties of turbid samples. Moreover, our Monte Carlo simulation results indicated that this geometry had probing depths comparable to those of the conventional diffuse reflectance measurement geometry with a source-detector separation of 3 mm. We expect that this new source setup would facilitate the investigating of superficial volumes of turbid samples in the wavelength regions where tissue absorption coefficients are comparable to scattering coefficients.

Preparation and evaluation of collagen I/ gellan gum/ß-TCP microspheres as bone graft substitute materials.

Collagen I is the main component of protein in bone and exhibits many excellent applications in biomedical fields. Gellan gum possesses good biocompatible, biodegradable and good mechanical property, and shows great potentials as tissue engineering scaffold or cell culture substrate. Therefore, the aim of this study was to use collagen I, gellan gum and ß-TCP to prepare collagen I/gellan gum/ß-TCP microspheres by emulsion method as bone graft substitute materials. The preliminary results showed that collagen I/gellan gum/ß-TCP microspheres had particle size distribution between 500-1000 µP in diameter and exhibited better mechanical strength. These microspheres also showed good biocompatibility in cell activity test.

Synthesis of a disulfide cross-linked polygalacturonic acid hydrogel for biomedical applications.

Polygalacturonic acid (PGA) hydrogel cross-linked via disulfide bonds was synthesized using a thiol oxidation reaction. PGA was grafted with cysteine to yield thiolated PGA (denoted PGAcys). Per gram, PGA-conjugated cysteine was 725 ± 77 µmol, and the degree of modification was 16.24 %. A PGAcys hydrogel film was fabricated under physiological conditions, with gel content 91.6 % and water content 43.3 %. The PGAcys hydrogel was used as a drug carrier for rosmarinic acid (RA) (denoted PGAcys/RA) and to prevent postsurgical adhesion. The in vitro dynamic release behavior of RA from the PGAcys hydrogel was analyzed. The profiles showed that 80 % of the total RA was released from the hydrogel within 15 min, followed by zero-order kinetic release. Animal implant studies showed that PGAcys and PGAcys/RA hydrogel films reduced adhesion incidence by over 90 %, significantly higher than did Hyaluronate/Carboxymethylcellulose (analogous Seprafilm™) (42 %). The PGAcys/RA hydrogel film also reduced the early inflammatory reaction.

Photocrosslinkable gellan gum film as an anti-adhesion barrier.

The purpose of this study was to develop a gellan gum-based film which could be photocrosslinked for medical applications. Gellan gum was grafted with cinnamate to yield the photo crosslinkable polymer (gellan gum-cin). This material had 14.7% of its D-galacturonic residues reacted with cinnamate groups and displayed maximum absorption at 254 nm. Investigation of the photochemical properties showed that the crosslinking efficiency was 82% after 16 min of UV irradiation. The anti-adhesion films prepared from gellan gum-cin polymers exhibited high gel contents (88 ± 2%) and suitable mechanical properties. When implanted into rats, the gellan gum-cin film exhibited the most promising anti-adhesion potential in 2 out of 10 rats without forming any tissue adhesion. Furthermore, the gellan gum-cin film could effectively inhibit inflammation in rats based on the results of fluid leukocyte analyses. The gellan gum-cin film thus has potential in clinical applications.

House dust mite sensitization in toddlers predict persistent wheeze in children between eight to fourteen years old

BACKGROUND: Identifying toddlers at increased risk of developing persistent wheeze provides an opportunity for risk-reducing interventions. House dust mite (HDM) allergen sensitization might identify this group of high-risk children. OBJECTIVE: We examined whether a positive skin prick test (SPT) to at least 1 of the 3 HDMs in wheezing toddlers, would serve as a predictor for persistent wheeze at age 8 to 14 years old. METHODS: A cohort of 78 children, who had wheezing episodes, and underwent SPT to 3 HDMs between the ages of 2 to 5 years old, were enrolled. SPT results were obtained from the National University Hospital database. Four to 9 years later, the children, currently between 8 to 14 years old, were re-assessed for persistence of asthma symptoms and other atopic disorders via a telephone interview. A validated questionnaire on current wheezing and asthma, developed by the International Study of Asthma and Allergies in Childhood, was used. Fisher's exact test was used to evaluate the association between persistence of asthma and a positive SPT. RESULTS: Of the 78 children who participated in the study, 42 (53.8%) had a positive SPT and 36 (46.2%) had a negative SPT. Of these, 18 (42.9%) of SPT positive and 7 (19.4%) of SPT negative children had persistence of asthma symptoms. There is a significant association between a positive SPT during the preschool years, and persistence of asthma (p = 0.0314 [<0.05]). CONCLUSION: HDM sensitization at ages 2 to 5 years old in wheezing children predicts persistence of asthma after 4 to 9 years. This in turn may have benefits for management of asthma in this high-risk group.

Rhythmic alternation and the optional complementiser in English: new evidence of phonological influence on grammatical encoding.

In a recall-based spoken production experiment, native English-speaking participants' variable use of the complementiser that to introduce the sentential complement in sentences like Henry knew (that) Lucy/Louise washed the dishes was found to be related to whether that inclusion/omission resulted in an alternating sequence of stressed and unstressed syllables between the verb of the main clause and the subject of the complement clause. This finding is discussed in relation to the question of whether and how phonological encoding can influence grammatical encoding in spoken language production.