Cardiovascular hardware simulator and artificial aorta-generated central blood pressure waveform database according to various vascular ages for cardiovascular health monitoring applications.

This study presents a database of central blood pressure waveforms according to cardiovascular health conditions, to supplement the lack of clinical data in cardiovascular health research, constructed by a cardiovascular simulator. Blood pressure (BP) is the most frequently measured biomarker, and in addition to systolic and diastolic pressure, its waveform represents the various conditions of cardiovascular health. A BP waveform is formed by overlapping the forward and reflected waves, which are affected by the pulse wave velocity (PWV). The increase in vascular stiffness with aging increases PWV, and the PWV-age distribution curve is called vascular age. For cardiovascular health research, extensive data of central BP waveform is essential, but the clinical data published so far are insufficient and imbalanced in quantity and quality. This study reproduces the central BP waveform using a cardiovascular hardware simulator and artificial aortas, which mimic the physiological structure and properties of the human. The simulator can adjust cardiovascular health conditions to the same level as humans, such as heart rate of 40-100 BPM, stroke volume of 40-100 mL, and peripheral resistance of 12 steps. Also, 6 artificial aortas with vascular ages in the 20-70 were fabricated to reproduce the increase in vascular stiffness due to aging. Vascular age calculated from measured stiffness of artificial aorta and central BP waveform showed an error of less than 3 years from the clinical value. Through this, a total of 636 waveforms were created to construct a central BP waveform database according to controlled various cardiovascular health conditions.

Extensive characterization of 28 complete chloroplast genomes of Hydrangea species: A perspective view of their organization and phylogenetic and evolutionary relationships.

The tribe Hydrangeeae displays a unique, distinctive disjunct distribution encompassing East Asia, North America and Hawaii. Despite its complex trait variations and polyphyletic nature, comprehensive phylogenomic and biogeographical studies on this tribe have been lacking. To address this gap, we sequenced and characterized 28 plastomes of Hydrangeeae. Our study highlights the highly conserved nature of Hydrangeaceae chloroplast (cp) genomes in terms of gene content and arrangement. Notably, synapomorphic characteristics of tandem repeats in the conserved domain of accD were observed in the Macrophyllae, Chinenses, and Dichroa sections within the Hydrangeeae tribe. Additionally, we found lower expression of accD in these sections using structure prediction and quantitative real-time PCR analysis. Phylogenomic analyses revealed the subdivision of the Hydrangeeae tribe into two clades with robust support values. Consistent with polyphyletic relationships, sect. Broussaisia was identified as the basal group in the tribe Hydrangeeae. Our study also provides insights into the phylogenetic relationships of Hydrangea petiolaris in the Jeju and Ulleung Island populations, suggesting the need for further studies with more samples and molecular data. Divergence time estimation and biogeographical analyses suggested that the common ancestors of the tribe Hydrangeeae likely originated from North America and East Asia during the Paleocene period via the Bering Land Bridge, potentially facilitating migration within the tribe between these regions. In conclusion, this study enhances our understanding of the evolutionary history and biogeography of the tribe Hydrangeeae, shedding light on the dispersal patterns and origins of this intriguing plant group with its unique disjunct distribution.

Exploring the potential hypothalamic role in mediating cisplatin-induced negative energy balance.

Cisplatin is a chemotherapeutic drug commonly used for treating different types of cancer. However, long-term use can lead to side effects, including anorexia, nausea, vomiting, and weight loss, which negatively affect the patient's quality of life and ability to undergo chemotherapy. This study aimed to investigate the mechanisms underlying the development of a negative energy balance during cisplatin treatment. Mice treated with cisplatin exhibit reduced food intake, body weight, and energy expenditure. We observed altered neuronal activity in the hypothalamic nuclei involved in the regulation of energy metabolism in cisplatin-treated mice. In addition, we observed activation of microglia and inflammation in the hypothalamus following treatment with cisplatin. Consistent with this finding, inhibition of microglial activation effectively rescued cisplatin-induced anorexia and body weight loss. The present study identified the role of hypothalamic neurons and inflammation linked to microglial activation in the anorexia and body weight loss observed during cisplatin treatment. These findings provide insight into the mechanisms underlying the development of metabolic abnormalities during cisplatin treatment and suggest new strategies for managing these side effects.

Clinical Significance of Sphingosine 1-phosphate Receptor 2 and Takeda G Protein-coupled Receptor 5 in Extrahepatic Cholangiocarcinoma Patients.

BACKGROUND AND AIMS: In biliary epithelial cells, two bile acid receptors, sphingosine 1-phosphate receptor 2 (S1PR2) and Takeda G protein-coupled receptor 5 (TGR5) have been reported to trigger cell proliferation, as well as neoplastic cell invasiveness. In this study, we aimed to investigate the clinical significance of S1PR2/ TGR5 expression in extrahepatic cholangiocarcinoma (CCA) patients. METHODS: Patients who underwent surgical resection of extrahepatic CCA at Korea University Guro Hospital between 2002 and 2018 were included. Data on immunohistochemical staining and H-score of S1PR2 and TGR5 were evaluated using digital image analysis. RESULTS: A total of 115 cases of invasive CCA were analyzed. The H-score of S1PR2 showed a decrease in invasive CCA (p=0.052) but that of TGR5 showed a significant increase (p=0.02). Overall survival and disease-free survival were significantly lower in the low S1PR2 expression group (p<0.05) than in the control group; however, TGR5 expression was not significant (p=0.096). In multivariate analysis, low S1PR2 was only significant for poor prognosis. CONCLUSION: Low S1PR2 level was the only independent poor prognostic factor in patients with resected extrahepatic CCA.

Development of a Real-Time Pixel Array-Type Detector for Ultrahigh Dose-Rate Beams.

Although research into ultrahigh dose-rate (UHDR) radiation therapy is ongoing, there is a significant lack of experimental measurements for two-dimensional (2D) dose-rate distributions. Additionally, conventional pixel-type detectors result in significant beam loss. In this study, we developed a pixel array-type detector with adjustable gaps and a data acquisition system to evaluate its effectiveness in measuring UHDR proton beams in real time. We measured a UHDR beam at the Korea Institute of Radiological and Medical Sciences using an MC-50 cyclotron, which produced a 45-MeV energy beam with a current range of 10-70 nA, to confirm the UHDR beam conditions. To minimize beam loss during measurement, we adjusted the gap and high voltage on the detector and determined the collection efficiency of the developed detector through Monte Carlo simulation and experimental measurements of the 2D dose-rate distribution. We also verified the accuracy of the real-time position measurement using the developed detector with a 226.29-MeV PBS beam at the National Cancer Center of the Republic of Korea. Our results indicate that, for a current of 70 nA with an energy beam of 45 MeV generated using the MC-50 cyclotron, the dose rate exceeded 300 Gy/s at the center of the beam, indicating UHDR conditions. Simulation and experimental measurements show that fixing the gap at 2 mm and the high voltage at 1000 V resulted in a less than 1% loss of collection efficiency when measuring UHDR beams. Furthermore, we achieved real-time measurements of the beam position with an accuracy of within 2% at five reference points. In conclusion, our study developed a beam monitoring system that can measure UHDR proton beams and confirmed the accuracy of the beam position and profile through real-time data transmission.

Intravesical bacillus Calmette-Guérin-induced myopathy presenting as rhabdomyolysis: a case report.

Intravesical bacillus Calmette-Guérin (BCG) instillation is an adjuvant treatment for non-muscle-invasive urinary bladder cancer. Although most complications associated with BCG immunotherapy are mild and self-limiting, rare albeit serious complications have been reported. Only a few cases of BCG-related rhabdomyolysis have been reported. In this study, we present the case of a 72-year-old woman who developed severe weakness and hyperCKemia following intravesical BCG instillation. A muscle biopsy was performed, and a diagnosis of drug-induced myopathy was made.

Genes and Regulatory Mechanisms for Ginsenoside Biosynthesis.

Panax ginseng is a medicinal plant belonging to the Araliaceae family. Ginseng is known as the king of oriental medicine, which has been practiced since ancient times in East Asian countries and globally in the modern era. Ginseng is used as an adaptogen, and research shows that it has several pharmacological benefits for various ailments such as cancer, inflammation, diabetes, and neurological symptoms. The pharmacological benefits of ginseng are attributed to the triterpenoid saponin ginsenosides found throughout the Panax ginseng species, which are abundant in its root and are found exclusively in P. ginseng and Panax quinquefolius. Recently, with the completion of the entire ginseng genome sequencing and the construction of the ginseng genome database, it has become possible to access information about many genes newly predicted to be involved in ginsenoside biosynthesis. This review briefly summarizes the current progress in ginseng genome analysis and genes involved in ginsenoside biosynthesis, proposing directions for functional studies of the predicted genes related to ginsenoside production and its regulation.

Soft Microdenticles on Artificial Octopus Sucker Enable Extraordinary Adaptability and Wet Adhesion on Diverse Nonflat Surfaces.

Bioinspired soft devices, which possess high adaptability to targeted objects, provide promising solutions for a variety of industrial and medical applications. However, achieving stable and switchable attachment to objects with curved, rough, and irregular surfaces remains difficult, particularly in dry and underwater environments. Here, a highly adaptive soft microstructured switchable adhesion device is presented, which is inspired by the geometric and material characteristics of the tiny denticles on the surface of an octopus sucker. The contact interface of the artificial octopus sucker (AOS) is imprinted with soft, microscale denticles that interact adaptably with highly rough or curved surfaces. Robust and controllable attachment of the AOS with soft microdenticles (AOS-sm) to dry and wet surfaces with diverse morphologies is achieved, allowing conformal attachment on curved and soft objects with high roughness. In addition, AOS-sms assembled with an octopus-arm-inspired soft actuator demonstrate reliable grasping and the transport of complex polyhedrons, rough objects, and soft, delicate, slippery biological samples.

High-throughput SNP markers for authentication of Korean wheat cultivars based on seven complete plastomes and the nuclear genome.

Wheat (Triticum aestivum) has diverse uses in the food industry, and different cultivars have unique properties; therefore, it is important to select the optimal cultivar for the intended end use. Here, to establish an identification system for Korean wheat cultivars, we obtained the complete plastome sequences of seven major Korean cultivars. Additionally, the open access database CerealsDB was queried to discover single-copy genomic single-nucleotide polymorphisms (SNPs) in the hexaploid wheat genome. Ten SNPs were developed into allele-specific PCR (ASP) markers, and eight of the SNPs used for ASP markers were converted into TaqMan high-throughput genotyping markers. Phylogenetic analysis using SNP genotypes revealed the genetic diversity and relationships among 137 wheat lines from around the world, including 35 Korean cultivars. This research thus presents a high-throughput authentication system for Korean wheat cultivars that may promote food industry uses of Korean wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01043-w.

Admixture of divergent genomes facilitates hybridization across species in the family Brassicaceae.

Hybridization and polyploidization are pivotal to plant evolution. Genetic crosses between distantly related species are rare in nature due to reproductive barriers but how such hurdles can be overcome is largely unknown. Here we report the hybrid genome structure of xBrassicoraphanus, a synthetic allotetraploid of Brassica rapa and Raphanus sativus. We performed cytogenetic analysis and de novo genome assembly to examine chromosome behaviors and genome integrity in the hybrid. Transcriptome analysis was conducted to investigate expression of duplicated genes in conjunction with epigenome analysis to address whether genome admixture entails epigenetic reconfiguration. Allotetraploid xBrassicoraphanus retains both parental chromosomes without genome rearrangement. Meiotic synapsis formation and chromosome exchange are avoided between nonhomologous progenitor chromosomes. Reconfiguration of transcription network occurs, and less divergent cis-elements of duplicated genes are associated with convergent expression. Genome-wide DNA methylation asymmetry between progenitors is largely maintained but, notably, B. rapa-originated transposable elements are transcriptionally silenced in xBrassicoraphanus through gain of DNA methylation. Our results demonstrate that hybrid genome stabilization and transcription compatibility necessitate epigenome landscape adjustment and rewiring of cis-trans interactions. Overall, this study suggests that a certain extent of genome divergence facilitates hybridization across species, which may explain the great diversification and expansion of angiosperms during evolution.

A Transfer Function Model Development for Reconstructing Radial Pulse Pressure Waveforms Using Non-Invasively Measured Pulses by a Robotic Tonometry System.

The primary goal of this study is to develop a mathematical model that can establish a transfer function relationship between the "external" pulse pressures measured by a tonometer and the "internal" pulse pressure in the artery. The purpose of the model is to accurately estimate and rebuild the internal pulse pressure waveforms using arterial tonometry measurements. To develop and validate a model without human subjects and operators for consistency, this study employs a radial pulse generation system, a robotic tonometry system, and a write model with an artificial skin and vessel. A transfer function model is developed using the results of the pulse testing and the mechanical characterization testing of the skin and vessel. To evaluate the model, the pulse waveforms are first reconstructed for various reference pulses using the model with tonometry data. They are then compared with pulse waveforms acquired by internal measurement (by the built-in pressure sensor in the vessel) the external measurement (the on-skin measurement by the robotic tonometry system). The results show that the model-produced pulse waveforms coinciding well with the internal pulse waveforms with small relative errors, indicating the effectiveness of the model in reproducing the actual pulse pressures inside the vessel.

Evaluation of skin cancer resection guide using hyper-realistic in-vitro phantom fabricated by 3D printing.

Skin cancer usually occurs in the facial area relatively exposed to sunlight. Medical imaging can confirm the invasiveness and metastasis of skin cancer, which is used to establish a surgical plan. However, there is no method of directly marking this information on the patient's skin in the operating room. We evaluated a skin cancer resection guide that marks resection areas including safety margins on the patient's skin based on medical images and in-vitro phantom fabricated via 3D printing. The in-vitro phantom, which includes the skull, skin, and five different cancer locations was designed and fabricated based on a CT image of a patient. Skin cancer resection guides were designed using a CT image of an in-vitro phantom, with a safety margin, and four injection points at each cancer. The guide was used to insert 16 cc intravenous catheters into each cancer of the phantom, which was rescanned by CT. The catheter insertion point and angle were evaluated. The accuracy of the insertion points was 2.09 ± 1.06 mm and cosine similarities was 0.980 ± 0.020. In conclusion, skin cancer resection guides were fabricated to mark surgical plans on the patient's skin in the operating room. They demonstrated reasonable accuracies in actual clinical settings.

Smoking may be more harmful to vasospastic angina patients who take antiplatelet agents due to the interaction: Results of Korean prospective multi-center cohort.

BACKGROUND: The interaction between smoking and the use of antiplatelet agents on the prognosis of vasospastic angina (VA) is rarely investigated. METHODS: VA-Korea is a nation-wide multi-center registry with prospective design (n = 1812). The primary endpoint was the composite occurrence of acute coronary syndrome (ACS), symptomatic arrhythmia, and cardiac death. Log-rank test and Cox proportional hazard model were for statistical analysis. Also, we conducted interaction analysis in both additive and multiplicative scales between smoking and antiplatelet agents among VA patients. For additive scale interaction, relative excess risk due to interaction (RERI) was calculated and for multiplicative scale interaction, the ratio of hazard ratio (HR) was calculated. All statistical analysis conducted by Stata Ver 16.1. RESULTS: Patients who were smoking and using antiplatelet agents had the highest incidence rate in the primary composite outcome. The incidence rate was 3.49 per 1,000 person-month (95% CI: 2.30-5.30, log-rank test for primary outcome p = 0.017) and HR of smoking and using antiplatelet agents was 1.66 (95%CI: 0.98-2.81). The adjusted RERI of smoking and using antiplatelet agents was 1.10 (p = 0.009), and the adjusted ratio of HR of smoking and using antiplatelet agents was 3.32 (p = 0.019). The current study observed the interaction between smoking and using antiplatelet agents in both additive and multiplicative scales. CONCLUSIONS: Smoking was associated with higher rates of unfavorable clinical outcomes among VA patients taking antiplatelet agents. This suggested that VA patients, especially those using antiplatelet agents should quit smoking.

Long-Term Left Atrial Function after Device Closure and Surgical Closure in Adult Patients with Atrial Septal Defect.

BACKGROUND: Studies comparing left atrial (LA) function after surgical closure or percutaneous closure in patients with an atrial septal defect (ASD) are lacking. METHODS: Between 1 and 3 years after ASD treatment, we retrospectively analyzed the medical records and transthoracic echocardiographic images of patients who had been diagnosed with an ASD after 20 years of age and who had undergone surgical closure (ASD-S) or percutaneous device closure (ASD-D). We measured LA peak systolic, early diastolic, and late diastolic strain values using 2-dimensional (2D) speckle tracking echocardiography (STE) and calculated reservoir, conduit, and contraction strain. RESULTS: The reservoir strain value of the ASD-D groups was 25.2% ± 7.4%, which was lower compared to the control group (33.6% ± 5.5%) (p = 0.004). The LA conduit strain and the LA contraction values of the ASD-D group were also lower compared to the control group (-13.8% ± 5.8% vs. -20.4% ± 4.7%, p = 0.034; -11.3% ± 4.2% vs. -13.2% ± 2.5%, p = 0.037, respectively). The reservoir, conduit, and contraction strains of the ASD-S group were 27.8% ± 8.8%, -15.3% ± 6.4%, and -12.5% ± 5.8%, respectively, and were not different from those of the control group or the ASD-D group. CONCLUSIONS: The 2D STE is a suitable method for evaluating LA function after ASD closure. Our results demonstrate that 1 year after device closure, the LA reservoir, conduit and contraction function were reduced in ASD-D group compared to healthy controls, while there was no difference between the ASD-S and ASD-D groups.

Effect of Soft Silicone Foam Dressings on Intraoperatively Acquired Pressure Injuries: A Randomized Study in Patients Undergoing Spinal Surgery.

The use of prophylactic dressings to help prevent intraoperatively acquired pressure injuries (IAPIs) merits further study. PURPOSE: To examine how the use of a soft silicone foam dressing affects the development of IAPIs in patients undergoing spinal surgery to obtain baseline data supporting evidence-based nursing care. METHODS: Using a self-controlled study design, 64 patients requiring thoracic or lumbar surgery on a Wilson frame at a hospital in Seoul, South Korea, were recruited between February 12 and September 1, 2018; 50 patients were eligible. Basic demographic, health, and surgical data were obtained. Before surgery, the left or right side chest and iliac crest areas were randomly assigned to be covered with a soft silicone foam dressing. The areas were assessed at 2 time points: immediately after and 30 minutes after surgery. If an IAPI was present at 30 minutes after surgery, all sites were reevaluated after 7 days. RESULTS: The majority of participants were male (26 participants, 52%). Average patient age was 62.54 (± 13.83) years, with a body mass index of 24.32 (± 4.23) kg/m2. Average length of surgery was 218.4 (± 137) minutes. Immediately after surgery, 26 IAPIs were observed and there was a significant difference between dressed and non-dressed chest areas for the number of IAPIs (4% vs. 28%; P = .002). After 30 minutes, the total number of IAPIs was 20 and the difference between IAPIs in the iliac crest area was significant between dressed and non-dressed areas (0% vs. 14%; P = .012). After 1 week, there were no chest or iliac crest IAPIs in the areas that had been covered by a dressing; however, 8 chest (61.5%) and 4 iliac crest (30.8%) area IAPIs remained when no dressing had been applied. The majority of IAPIs were stage 1 at all assessment times. After 1 week, 1 IAPI had evolved into a stage 3 injury. CONCLUSIONS: The results of this study show that many stage 1 IAPIs do resolve over time and that use of soft silicone foam dressings during spinal surgery can significantly reduce IAPI rates. Additional longitudinal studies are needed to help guide postoperative skin assessment intervals and increase the understanding about the evolution of stage 1 IAPIs.

Vibration Alert to the Brain: Evoked and Induced MEG Responses to High-Frequency Vibrotactile Stimuli on the Index Finger of Dominant and Non-dominant Hand.

Background: In recent years, vibrotactile haptic feedback technology has been widely used for user interfaces in the mobile devices. Although functional neuroimaging studies have investigated human brain responses to different types of tactile inputs, the neural mechanisms underlying high-frequency vibrotactile perception are still relatively unknown. Our aim was to investigate neuromagnetic brain responses to high-frequency vibrotactile stimulation, using magnetoencephalography (MEG). Methods: We measured 152-channel whole-head MEG in 30 healthy, right-handed volunteers (aged 20-28 years, 15 females). A total of 300 vibrotactile stimuli were presented at the tip of either the left index finger or the right index finger in two separate sessions. Sinusoidal vibrations at 150 Hz for 200 ms were generated with random inter-stimulus intervals between 1.6 and 2.4 s. Both time-locked analysis and time-frequency analysis were performed to identify peak responses and oscillatory modulations elicited by high-frequency vibrations. The significance of the evoked and induced responses for dominant and non-dominant hand stimulation conditions was statistically tested, respectively. The difference in responses between stimulation conditions was also statistically evaluated. Results: Prominent peak responses were observed at 56 ms (M50) and at 100 ms (M100) for both stimulation conditions. The M50 response revealed clear dipolar field patterns in the contralateral side with significant cortical activations in the contralateral primary sensorimotor area, whereas the M100 response was not as prominent as the M50. Vibrotactile stimulation induced significant suppression of both alpha (8-12 Hz) and beta (20-30 Hz) band activity during the mid-latency period (0.2-0.4 s), primarily in sensorimotor areas contralateral to the stimulation side. In addition, a significant alpha enhancement effect in posterior regions was accompanied with alpha suppressions in sensorimotor regions. The alpha suppression was observed in a broader distribution of cortical areas for the non-dominant hand stimulation. Conclusion: Our data demonstrate that high-frequency tactile vibrations, which is known to primarily activate Pacinian corpuscles, elicit somatosensory M50 and M100 responses in the evoked fields and induce modulations of alpha and beta band oscillations during mid-latency periods. Our study is also consistent with that the primary sensorimotor area is significantly involved in the processing of high-frequency vibrotactile information with contralateral dominance.

Whole-genome, transcriptome, and methylome analyses provide insights into the evolution of platycoside biosynthesis in Platycodon grandiflorus, a medicinal plant.

Triterpenoid saponins (TSs) are common plant defense phytochemicals with potential pharmaceutical properties. Platycodon grandiflorus (Campanulaceae) has been traditionally used to treat bronchitis and asthma in East Asia. The oleanane-type TSs, platycosides, are a major component of the P. grandiflorus root extract. Recent studies show that platycosides exhibit anti-inflammatory, antiobesity, anticancer, antiviral, and antiallergy properties. However, the evolutionary history of platycoside biosynthesis genes remains unknown. In this study, we sequenced the genome of P. grandiflorus and investigated the genes involved in platycoside biosynthesis. The draft genome of P. grandiflorus is 680.1 Mb long and contains 40,017 protein-coding genes. Genomic analysis revealed that the CYP716 family genes play a major role in platycoside oxidation. The CYP716 gene family of P. grandiflorus was much larger than that of other Asterid species. Orthologous gene annotation also revealed the expansion of ß-amyrin synthases (bASs) in P. grandiflorus, which was confirmed by tissue-specific gene expression. In these expanded gene families, we identified key genes showing preferential expression in roots and association with platycoside biosynthesis. In addition, whole-genome bisulfite sequencing showed that CYP716 and bAS genes are hypomethylated in P. grandiflorus, suggesting that epigenetic modification of these two gene families affects platycoside biosynthesis. Thus whole-genome, transcriptome, and methylome data of P. grandiflorus provide novel insights into the regulation of platycoside biosynthesis by CYP716 and bAS gene families.

Impact of the National Perinatal Hepatitis B Prevention Programme in the Republic of Korea: A retrospective registry-based cohort study.

INTRODUCTION: Hepatitis B is a major preventable cause of morbidity and mortality from chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. We aimed to evaluate the performance and outcomes of the Korean Perinatal Hepatitis B Prevention Programme (PHBPP) and to investigate the impact of the current post-exposure immunoprophylaxis protocol. METHODS: A retrospective cohort study was performed based on electronic data registry of infants born to hepatitis B virus (HBV)-infected mothers between July 2002 and 2013. RESULTS: During the study period, 159,983 Korean infants were registered with the PHBPP, with an overall programme coverage of 92.8%. Despite receiving timely post-exposure immunoprophylaxis, 8.6% of infants born to mothers aged <25 years and hepatitis B e antigen (HBeAg)-positive, and 0.7% of infants born to mothers aged ≥25 years and HBeAg-negative were infected. An estimated 14,123 infants were directly protected from perinatal HBV transmission by the PHBPP during the 11.5-year period, at a cost of 1157 US dollars per case averted. The incidence of paediatric hepatocellular carcinoma declined dramatically during the period. CONCLUSIONS: A substantial number of infants have been prevented from hepatitis B since the PHBPP was launched in the Republic of Korea. Continued efforts to promote the programme, an integrated approach to maximising its coverage, a risk-stratified strategy, and innovations in logistics could further reduce perinatal HBV transmission.