Generating 3D images of VMAT plans for predictive models and activation maps associated with plan deliverability.

BACKGROUND: Intensity modulation with dynamic multi-leaf collimator (MLC) and monitor unit (MU) changes across control points (CPs) characterizes volumetric modulated arc therapy (VMAT). The increased uncertainty in plan deliverability required patient-specific quality assurance (PSQA), which remained inefficient upon Quality Assurance (QA) failure. To prevent waste before QA, plan complexity metrics (PCMs) and machine learning models with the metrics were generated, which were lack of providing CP-specific information upon QA failures. PURPOSE: By generating 3D images from digital imaging and comminications in medicine in radiation therapy (DICOM RT) plan, we proposed a predictive model that can estimate the deliverability of VMAT plans and visualize CP-specific regions associated with plan deliverability. METHODS: The patient cohort consisted of 259 and 190 cases for left- and right-breast VMAT treatments, which were split into 235 and 166 cases for training and 24 cases from each treatment for testing the networks. Three-channel 3D images generated from DICOM RT plans were fed into a DenseNet-based deep learning network. To reflect VMAT plan complexity as an image, the first two channels described MLC and MU variations between two consecutive CPs, while the last channel assigned the beam field size. The network output was defined as binary classified PSQA results, indicating deliverability. The predictive performance was assessed by accuracy, sensitivity, specificity, F1-score, and area under the curve (AUC). The gradient-weighted class activation map (Grad-CAM) highlighted the regions of CPs in VMAT plans associated with deliverability, compared against PCMs by Spearman correlation. RESULTS: The DenseNet-based predictive model yielded AUCs of 92.2% and 93.8%, F1-scores of 97.0% and 93.8% and accuracies of 95.8% and 91.7% for the left- and right-breast VMAT cases. Additionally, the specificity of 87.5% for both cases indicated that the predictive model accurately detected QA failing cases. The activation maps significantly differentiated QA failing-labeled from passing-labeled classes for the non-deliverable cases. The PCM with the highest correlation to the Grad-CAM varied from patient cases, implying that plan deliverability would be considered patient-specific. CONCLUSION: This work demonstrated that the deep learning-based network based on visualization of dynamic VMAT plan information successfully predicted plan deliverability, which also provided control-point specific planning parameter information associated with plan deliverability in a patient-specific manner.

Engineering extracellular vesicles for ROS scavenging and tissue regeneration.

Stem cell therapy holds promise for tissue regeneration, yet significant challenges persist. Emerging as a safer and potentially more effective alternative, extracellular vesicles (EVs) derived from stem cells exhibit remarkable abilities to activate critical signaling cascades, thereby facilitating tissue repair. EVs, nano-scale membrane vesicles, mediate intercellular communication by encapsulating a diverse cargo of proteins, lipids, and nucleic acids. Their therapeutic potential lies in delivering cargos, activating signaling pathways, and efficiently mitigating oxidative stress-an essential aspect of overcoming limitations in stem cell-based tissue repair. This review focuses on engineering and applying EVs in tissue regeneration, emphasizing their role in regulating reactive oxygen species (ROS) pathways. Additionally, we explore strategies to enhance EV therapeutic activity, including functionalization and incorporation of antioxidant defense proteins. Understanding these molecular mechanisms is crucial for optimizing EV-based regenerative therapies. Insights into EV and ROS signaling modulation pave the way for targeted and efficient regenerative therapies harnessing the potential of EVs.

The Mohawk homeobox gene represents a marker and osteo-inhibitory factor in calvarial suture osteoprogenitor cells.

The regeneration of the mammalian skeleton's craniofacial bones necessitates the action of intrinsic and extrinsic inductive factors from multiple cell types, which function hierarchically and temporally to control the differentiation of osteogenic progenitors. Single-cell transcriptomics of developing mouse calvarial suture recently identified a suture mesenchymal progenitor population with previously unappreciated tendon- or ligament-associated gene expression profile. Here, we developed a Mohawk homeobox (MkxCG; R26RtdT) reporter mouse and demonstrated that this reporter identifies an adult calvarial suture resident cell population that gives rise to calvarial osteoblasts and osteocytes during homeostatic conditions. Single-cell RNA sequencing (scRNA-Seq) data reveal that Mkx+ suture cells display a progenitor-like phenotype with expression of teno-ligamentous genes. Bone injury with Mkx+ cell ablation showed delayed bone healing. Remarkably, Mkx gene played a critical role as an osteo-inhibitory factor in calvarial suture cells, as knockdown or knockout resulted in increased osteogenic differentiation. Localized deletion of Mkx in vivo also resulted in robustly increased calvarial defect repair. We further showed that mechanical stretch dynamically regulates Mkx expression, in turn regulating calvarial cell osteogenesis. Together, we define Mkx+ cells within the suture mesenchyme as a progenitor population for adult craniofacial bone repair, and Mkx acts as a mechanoresponsive gene to prevent osteogenic differentiation within the stem cell niche.

Using Dried Blood Spots to Quantitatively Detect Anti-SARS-CoV-2 IgG Antibodies by ELISA: A Validation Study.

SARS-CoV-2 serological testing is useful to determine seroprevalence, epidemiological trends, and the extent of transmission. The collection and transport of serum samples can be logistically challenging, especially in remote underserved areas. Dried blood spots (DBSs) would allow easier sample collection and logistical handling compared with standard serum collection, particularly for extensive and repeated SARS-CoV-2 serosurveys. We evaluated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the IgG ELISA (Wantai, Beijing, China) using DBSs against sera for the quantitative detection of SARS-CoV-2 IgG antibody. The IgG ELISA was used to test paired sera and DBSs obtained from individuals with recent virologically confirmed COVID-19 illness and banked paired sera and DBSs collected before the COVID-19 pandemic. We found that 100/100 (100%) seropositive samples were positive using DBSs, and 193/194 (99%) seronegative samples were negative using DBSs. Compared with sera, the DBS method had a 100% sensitivity, 99% specificity, 99% PPV, and 100% NPV. Use of DBSs for SARS-CoV-2 household or population serosurveys may be considered in situations with limitations in sample collection, shipment, and storage.

2D Materials in Advanced Electronic Biosensors for Point-of-Care Devices.

Since two-dimensionalal (2D) materials have distinct chemical and physical properties, they are widely used in various sectors of modern technologies. In the domain of diagnostic biodevices, particularly for point-of-care (PoC) biomedical diagnostics, 2D-based field-effect transistor biosensors (bio-FETs) demonstrate substantial potential. Here, in this review article, the operational mechanisms and detection capabilities of biosensing devices utilizing graphene, transition metal dichalcogenides (TMDCs), black phosphorus, and other 2D materials are addressed in detail. The incorporation of these materials into FET-based biosensors offers significant advantages, including low detection limits (LOD), real-time monitoring, label-free diagnosis, and exceptional selectivity. The review also highlights the diverse applications of these biosensors, ranging from conventional to wearable devices, underscoring the versatility of 2D material-based FET devices. Additionally, the review provides a comprehensive assessment of the limitations and challenges faced by these devices, along with insights into future prospects and advancements. Notably, a detailed comparison of FET-based biosensors is tabulated along with various other biosensing platforms and their working mechanisms. Ultimately, this review aims to stimulate further research and innovation in this field while educating the scientific community about the latest advancements in 2D materials-based biosensors.

Cardiac Evaluation before and after Oral Propranolol Treatment for Infantile Hemangiomas.

Background: Most recent clinical practice guidelines addressing the management of infantile hemangiomas (IHs) recommend oral propranolol, a non-selective beta-adrenergic antagonist, as first-line treatment. However, few reports have provided continuous follow-up data regarding cardiac evaluations. Methods: Sixty-four patients diagnosed with IHs and treated with oral propranolol before 2 years of age at the Department of Pediatrics, Kangbuk Samsung Hospital (Seoul, Republic of Korea), with regular examinations between 2017 and 2021, were included. Cardiac evaluations, including electrocardiography, Holter monitoring, chest X-ray, and echocardiography, were performed. Results: Sixty-four patients with IHs successfully underwent continuous follow-up cardiac evaluations. The median age at diagnosis was 2 weeks (1 day to 34.3 weeks). The median age at treatment initiation was 13.6 weeks (2.4-87.9 weeks), the mean longitudinal diameter of hemangioma at diagnosis was 2.8 ± 2.1 cm (0.3-12.0 cm), and the mean percentage of size decrease after 1 year of oral propranolol treatment was 71.8%. None of the 64 patients experienced severe adverse side effects during propranolol treatment. There was no statistically significant differences in echocardiographic function and electrocardiographic data after treatment. Conclusions: Propranolol treatment ≥6 months was effective and safe without significant cardiac toxicity in the treatment of patients with infantile hemangiomas.

Active offset-frequency control of optical frequency comb via sum-frequency mixing of passively mode-locked laser and continuous-wave laser.

We propose a method for actively controlling the frequency of an optical frequency comb (OFC) using sum-frequency generation (SFG) with a nonlinear crystal. For the first time, OFC generation was experimentally demonstrated via sum-frequency mixing of a narrowband continuous wave (CW) laser and a passively mode-locked fiber laser. By adjusting the optical frequency of the CW laser, we successfully controlled the offset-frequency of the SFG-OFC, which was mapped from the OFC of the pulse pump laser. Furthermore, by comparing the spectral widths of the SFG-OFC modes generated from two CW lasers with different spectral widths, we confirmed that the spectral characteristics of the SFG-OFC modes depended on the spectral features of the CW laser.

Spatial and temporal clustering of typhoid fever in an urban slum of Dhaka City: Implications for targeted typhoid vaccination.

BACKGROUND: Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce. METHODS: We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models. RESULTS: We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs [95% CI: 0.8, 1.6]) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection. CONCLUSION: In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission.

Autophagy in Osteoarthritis: A Double-Edged Sword in Cartilage Aging and Mechanical Stress Response: A Systematic Review.

Background: Although osteoarthritis (OA) development is epidemiologically multifactorial, a primary underlying mechanism is still under debate. Understanding the pathophysiology of OA remains challenging. Recently, experts have focused on autophagy as a contributor to OA development. Method: To better understand the pathogenesis of OA, we survey the literature on the role of autophagy and the molecular mechanisms of OA development. To identify relevant studies, we used controlled vocabulary and free text keywords to search the MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and SCOPUS database. Thirty-one studies were included for data extraction and systematic review. Among these studies, twenty-five studies investigated the effects of autophagy in aging and OA chondrocytes, six studies examined the effects of autophagy in normal human chondrocytes, and only one study investigated the effects of mechanical stress-induced autophagy on the development of OA in normal chondrocytes. Results: The studies suggest that autophagy activation prevents OA by exerting cell-protective effects in normal human chondrocytes. However, in aging and osteoarthritis (OA) chondrocytes, the role of autophagy is intricate, as certain studies indicate that stimulating autophagy in these cells can have a cytotoxic effect, while others propose that it may have a protective (cytoprotective) effect against damage or degeneration. Conclusions: Mechanical stress-induced autophagy is also thought to be involved in the development of OA, but further research is required to identify the precise mechanism. Thus, autophagy contributions should be interpreted with caution in aging and the types of OA cartilage.

Dimensional accuracy and surface characteristics of complete-arch cast manufactured by six 3D printers.

Objective: This in vitro study aimed to quantitatively and qualitatively evaluate and compare the horizontal and vertical accuracies of complete-arch casts produced by six 3D printers with different printing principles and resolutions using a low-viscosity resin material. Methods: A reference cast was designed by CAD software. The 3D printers used were DLPa (Asiga MAX), DLPk (cara Print 4.0), LCD2o (Ondemand 2 K Printer), LCD2p (Photon Mono X), LCD4s (SONIC 4 K), and SLA (ZENITH U). Ten casts were printed for each 3D printer using a low-viscosity resin. The accuracy of each printed cast was evaluated using shell-to-shell deviations, 12 linear, one angular, and five height deviations, with a reference cast as the control. The surface features of the casts were examined using field-emission scanning electron microscopy (FE-SEM) and digital cameras. Results: The evaluation of shell-to-shell deviation revealed that DLPa and SLA printers exhibited low trueness values, whereas LCD printers displayed high trueness values. Among the LCD printers, LCD4s and LCD2o exhibited the lowest and highest trueness values, respectively. DLPa printers showed lower trueness values for intercanine and intermolar distances, whereas LCD printers generally demonstrated high trueness values. However, LCD4s exhibited similar trueness values to those of SLA and DLPk. The height deviation was smallest in the anterior area, whereas the largest height deviation occurred in the canine teeth. The surface characteristics indicated that the SLA casts had greater light reflection and blunt canine tips. The FE-SEM observations highlighted that the LCD and DLP printers exhibited varying layer characteristics, with some presenting rough and uneven borders in the anterior lingual area. Significance: The accuracy of 3D printed casts varied among the 3D printer groups: DLPa and SLA were accurate for shell-to-shell deviation, with DLPa being the most accurate for linear and angular deviations. Regardless of the XY resolution, the DLP printers outperformed the LCD printers. Among the LCD group of 3D printers, higher-resolution LCD4s demonstrated increased accuracy. The SLA exhibited soft layer borders in the FE-SEM owing to its laser spot characteristics and prominent light reflection in the digital camera images.

Deep Learning Method for Precise Landmark Identification and Structural Assessment of Whole-Spine Radiographs.

This study measured parameters automatically by marking the point for measuring each parameter on whole-spine radiographs. Between January 2020 and December 2021, 1017 sequential lateral whole-spine radiographs were retrospectively obtained. Of these, 819 and 198 were used for training and testing the performance of the landmark detection model, respectively. To objectively evaluate the program's performance, 690 whole-spine radiographs from four other institutions were used for external validation. The combined dataset comprised radiographs from 857 female and 850 male patients (average age 42.2 ± 27.3 years; range 20-85 years). The landmark localizer showed the highest accuracy in identifying cervical landmarks (median error 1.5-2.4 mm), followed by lumbosacral landmarks (median error 2.1-3.0 mm). However, thoracic landmarks displayed larger localization errors (median 2.4-4.3 mm), indicating slightly reduced precision compared with the cervical and lumbosacral regions. The agreement between the deep learning model and two experts was good to excellent, with intraclass correlation coefficient values >0.88. The deep learning model also performed well on the external validation set. There were no statistical differences between datasets in all parameters, suggesting that the performance of the artificial intelligence model created was excellent. The proposed automatic alignment analysis system identified anatomical landmarks and positions of the spine with high precision and generated various radiograph imaging parameters that had a good correlation with manual measurements.

Small graft size and hepatocellular carcinoma outcomes in living donor liver transplantation: a retrospective multicentric cohort study.

INTRODUCTION: This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and HCC outcomes. MATERIALS AND METHODS: Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014-2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR<0.7% vs. GRWR≥0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. RESULTS: The eligible cohort consisted of 2005 LDLT recipients (GRWR<0.7 [n=59] vs. GRWR≥0.7 [n=1946]). In the entire cohort, 5-year RFS was significantly lower in the GRWR<0.7 than in the GRWR≥0.7 group (66.7% vs. 76.7%, P =0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P =0.234). This trend was similar in the matched cohort ( P =0.014 for RFS and P =0.096 for HCC recurrence). In multivariable analyses, GRWR<0.7 was an independent risk factor for RFS (adjusted HR [aHR] 1.89, P =0.012), but the result was marginal for HCC recurrence (aHR 1.61, P =0.066). In the pretransplant tumor burden subgroup analysis, GRWR<0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P <0.001 for RFS; aHR 2.92, P =0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P <0.001 for RFS; aHR 2.61, P =0.019 for HCC recurrence). CONCLUSIONS: A GRWR<0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high.

Liver Transplantation from Brain-Dead Donors with Hepatitis B or C in South Korea: A 2014-2020 Korean Organ Transplantation Registry Data Analysis.

BACKGROUND According to the current guidelines for liver transplantation (LT) of brain-dead donors with hepatitis B or C virus (HBV or HCV) in Korea, grafts from hepatitis B surface antigen (HBsAg)(+) or HCV antibody (anti-HCV)(+) donors must be transplanted only to HBsAg(+) or anti-HCV(+) recipients, respectively. We aimed to determine the current status and outcomes of brain-dead donor LT with HBV or HCV in Korea. MATERIAL AND METHODS This retrospective observational study included all LTs from brain-dead donors in the Korean Organ Transplantation Registry between April 2014 and December 2020. According to donor hepatitis status, 24 HBV(+), 1 HCV(+), and 1010 HBV(-)/HCV(-) donors were included. RESULTS Baseline/final model for end-stage liver disease score (MELD) for HBV(+), HCV(+), and HBV(-)/HCV(-) were 22.4±9.3/27.8±7.8, 16/11, and 33.0±15.4/35.5±7.1, respectively. MELD score of HBV (+) were lower than those of HBV(-)/HCV(-) (P<0.01). Five-year graft and patient survival rates of HBV(+) and HBV(-)/HCV(-) recipients were 81.7%/85.6%, and 76.6%/76.7%, respectively (P=0.73 and P=0.038). One-year graft and patient survival rates of HCV (+) graft recipients were both 100%. CONCLUSIONS No differences in graft and patient survival rates between HBV(+) and HBV(-)/HCV(-) groups were observed. Although accumulating the results of transplants from HBV (+) or HCV(+) grafts to HBV(-) or HCV(-) recipients is not possible owing to domestic regulations, Korea should conditionally permit transplantations from HBV(+) or HCV(+) grafts to HBV(-) or HCV(-) recipients by considering the risks and benefits based on foreign studies. Thereafter, we can accumulate the data from Korea and analyze the outcomes.

Efficacy of live and inactivated recombinant Newcastle disease virus vaccines expressing clade 2.3.4.4b H5 hemagglutinin against H5N1 highly pathogenic avian influenza in SPF chickens, Broilers, and domestic ducks.

A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA).

Cholera and diarrheal diseases in Cuamba District, Niassa Province, Mozambique: Systematic healthcare facility-based surveillance strengthening, characteristics of suspected cholera and diarrheal patients, and incidence of diarrheal diseases.

BACKGROUND: Mozambique is one of the countries in Africa that is continuously at risk of cholera outbreaks due to poor sanitation, hygiene, and limited access to potable water in some districts. The Mozambique Cholera Prevention and Surveillance (MOCA) project was implemented in Cuamba District, Niassa Province to prevent and control cholera outbreaks through a preemptive cholera vaccination, strengthened surveillance system for cholera and diarrheal diseases, and better understanding of cholera-related healthcare seeking behavior of local populations, which may further guide the national cholera control and prevention strategies. This article presents the surveillance component of the MOCA project. METHODOLOGY/PRINCIPAL FINDINGS: A prospective healthcare facility (HCF)-based surveillance of cholera and diarrheal disease was conducted in six HCFs in the District of Cuamba from March 2019 to December 2020. A systematic surveillance procedure has been put in place with capacity building in selected sentinel HCFs and a basic microbiology laboratory established on-site. Patients presenting with suspected cholera or other diarrheal symptoms were eligible for enrollment. Clinical data and rectal swab samples were collected for laboratory confirmation of Vibrio Cholerae and other pathogens. A total of 419 eligible patients from six HCFs were enrolled. The median age was 19.8 years with a similar age distribution between sentinel sites. The majority were patients who exhibited diarrhea symptoms not suspected of cholera (88.8%; n = 410). Among those, 59.2% (210/397) were female and 59.9% (235/392) were 15 years and above. There were 2 cholera cases, coming outside of the catchment area. The incidence of diarrheal diseases ranged from 40-103 per 100,000 population. No Vibrio cholerae was isolated among surveillance catchment population and Escherichia coli spp. (82/277; 29.6%) was the most common pathogen isolated. CONCLUSION/SIGNIFICANCE: Efforts were made to strengthen the systematic surveillance of suspected cholera with standardised patient screening, enrolment, and diagnostics. The first basic microbiology laboratory in Niassa Province established in Cuamba District under the MOCA project needs to be integrated into the national network of laboratories for sustainability. No reports of laboratory confirmed cholera cases from the surveillance catchment area may be highly related to the pre-emptive oral cholera vaccine (OCV) mass vaccination campaign conducted in 2018 and the use of drugs by local populations prior to visiting the sentinel HCFs. Continued systematic cholera surveillance is needed to closely monitor the cholera endemicity and epidemics, and further evaluate the long-term impact of this vaccination. High incidence of diarrheal illnesses needs to be addressed with improved water, sanitation, and hygiene (WaSH) conditions in Cuamba District. Efforts integrated with the prioritization of prevention measures are fundamental for the control of cholera in the country.

Probing Inherent Optical Anisotropy in Substrates via Direct Nanoimaging of Mie Scattering.

In this study, we investigated the optical properties of a transition metal dichalcogenide (TMD) substrate via Mie-scattering-induced surface analysis (MISA). Employing near-field optical microscopy and finite-difference time-domain (FDTD) simulations, we systemically prove and directly visualize the Mie scattering of superspherical gold nanoparticles (s-AuNPs) at the nanoscale. Molybdenum disulfide substrates exhibited optical isotropy, while rhenium disulfide (ReS2) substrates showed anisotropic behavior attributed to the interaction with incident light's electric field. Our study revealed substantial anisotropic trends in Mie scattering, particularly in the near-infrared energy range, with ReS2 exhibiting more pronounced spectral and angular responses in satellite peaks. Our results emphasize the application of Mie scattering, exploring the optical properties of substrates and contributing to a deeper understanding of nanoscale light-matter interactions.

Antiplatelet agent for the prevention of late hepatic vascular complications in living donor liver transplant dominant population.

BACKGROUND: Evidence for the long-term use of antiplatelet drugs to prevent hepatic vascular complications (HVC) is scarce in liver transplantation (LT). METHODS: From national claim data, LT recipients (about 80 % of living donor LT [LDLT]) without graft loss, HVC, or cardiovascular events within 1 year, were classified into those who took antiplatelets for ≥1 year (n = 1744) and for <1 year (n = 1975). Outcomes were compared after the 1-postoperative year index time point. RESULTS: During a mean follow up of 4.5 years, the risk of graft loss was similar between the groups (aHR 1.16, P = 0.23). However, ≥1-year antiplatelet therapy was associated with a higher risk of graft loss after 3 years (aHR 2.19, P < 0.01). HVC (aHR 0.94, P = 0.87) and major adverse cardiac events (aHR 1.20, P = 0.46) did not correlate with antiplatelet therapy for both groups. In contrast, ≥1-year antiplatelet therapy showed a significantly higher risk of severe bleeding compared to <1-year antiplatelet therapy (aHR 2.24, P < 0.01). This trend was similar in the LDLT subgroup. In our cohort, antiplatelet therapy for ≥1 year did not improve graft survival or HVC; however, it increased the risk of severe bleeding. CONCLUSION: We recommend against antiplatelet therapy for more than 1 year in clinically stable LT recipients.

Trueness, physical properties, and surface characteristics of additive-manufactured zirconia crown.

OBJECTIVE: This study aimed to conduct a comparison of trueness and physical and surface properties among five distinct types of additive manufactured (AM) zirconia crowns and zirconia crowns produced using the subtractive manufacturing (SM). MATERIAL AND METHODS: Zirconia crowns were fabricated using five distinct techniques, each varying in the method of slurry transfer and photocuring source. Each experimental group utilized either one of the four digital light processing (DLP)-based techniques (DLP spreading, DLP spreading gradation, DLP vat and DLP circular spreading) or the stereolithography (SLA)-based technique (SLA spreading). The control (CON) group employed SM. To assess accuracy, trueness was measured between the scan and reference data. To analyze the physical properties, voids were examined using high-energy spiral micro-computed tomography scans, and the crystal structure analysis was performed using X-ray diffraction (XRD). Surface roughness was assessed through laser scanning microscopy. RESULTS: Differences in the trueness of internal surfaces of crowns were found among the groups (P < 0.05). Trueness varied across the measurement surfaces (occlusal, lateral, and marginal) in all the groups except for the DLP spreading gradation group (P < 0.05). Voids were observed in all AM groups. All groups showed similar XRD patterns. All AM groups showed significantly greater surface roughness compared to the CON group (P < 0.001). CONCLUSION: The AM zirconia crowns showed bubbles and a rougher surface compared to the SM crowns. All groups exhibited typical zirconia traits and trueness levels within clinically acceptable limits, suggesting that current zirconia AM techniques could be suitable for dental applications.

Safety and immunogenicity of the Euvichol-S oral cholera vaccine for prevention of Vibrio cholerae O1 infection in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial.

BACKGROUND: In October, 2017, WHO launched a strategy to eliminate cholera by 2030. A primary challenge in meeting this goal is the limited global supply capacity of oral cholera vaccine and the worsening of cholera outbreaks since 2021. To help address the current shortage of oral cholera vaccine, a WHO prequalified oral cholera vaccine, Euvichol-Plus was reformulated by reducing the number of components and inactivation methods. We aimed to evaluate the immunogenicity and safety of Euvichol-S (EuBiologics, Seoul, South Korea) compared with an active control vaccine, Shanchol (Sanofi Healthcare India, Telangana, India) in participants of various ages in Nepal. METHODS: We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Nepal. Eligible participants were healthy individuals aged 1-40 years without a history of cholera vaccination. Individuals with a history of hypersensitivity reactions to other preventive vaccines, severe chronic disease, previous cholera vaccination, receipt of blood or blood-derived products in the past 3 months or other vaccine within 4 weeks before enrolment, and pregnant or lactating women were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block sizes of two, four, six, or eight) to one of four groups (groups A-D); groups C and D were stratified by age (1-5, 6-17, and 18-40 years). Participants in groups A-C were assigned to receive two 1·5 mL doses of Euvichol-S (three different lots) and participants in group D were assigned to receive the active control vaccine, Shanchol. All participants and site staff (with the exception of those who prepared and administered the study vaccines) were masked to group assignment. The primary immunogenicity endpoint was non-inferiority of immunogenicity of Euvichol-S (group C) versus Shanchol (group D) at 2 weeks after the second vaccine dose, measured by the seroconversion rate, defined as the proportion of participants who had achieved seroconversion (defined as ≥four-fold increase in V cholerae O1 Inaba and Ogawa titres compared with baseline). The primary immunogenicity endpoint was assessed in the per-protocol analysis set, which included all participants who received all their planned vaccine administrations, had no important protocol deviations, and who provided blood samples for all immunogenicity assessments. The primary safety endpoint was the number of solicited adverse events, unsolicited adverse events, and serious adverse events after each vaccine dose in all ages and each age stratum, assessed in all participants who received at least one dose of the Euvichol-S or Shanchol. Non-inferiority of Euvichol-S compared with Shanchol was shown if the lower limit of the 95% CI for the difference between the seroconversion rates in Euvichol-S group C versus Shanchol group D was above the predefined non-inferiority margin of -10%. The trial was registered at ClinicalTrials.gov, NCT04760236. FINDINGS: Between Oct 6, 2021, and Jan 19, 2022, 2529 healthy participants (1261 [49·9%] males; 1268 [50·1%] females), were randomly assigned to group A (n=330; Euvichol-S lot number ES-2002), group B (n=331; Euvichol-S ES-2003), group C (n=934; Euvichol-S ES-2004]), or group D (n=934; Shanchol). Non-inferiority of Euvichol-S versus Shanchol in seroconversion rate for both serotypes at 2 weeks after the second dose was confirmed in all ages (difference in seroconversion rate for V cholerae O1 Inaba -0·00 [95% CI -1·86 to 1·86]; for V cholerae O1 Ogawa -1·62 [-4·80 to 1·56]). Treatment-emergent adverse events were reported in 244 (9·7%) of 2529 participants in the safety analysis set, with a total of 403 events; 247 events were reported among 151 (9·5%) of 1595 Euvichol-S recipients and 156 events among 93 (10·0%) of 934 Shanchol recipients. Pyrexia was the most common adverse event in both groups (57 events among 56 [3·5%] of 1595 Euvichol-S recipients and 37 events among 35 [3·7%] of 934 Shanchol recipients). No serious adverse events were deemed to be vaccine-related. INTERPRETATION: A two-dose regimen of Euvichol-S vaccine was non-inferior to the active control vaccine, Shanchol, in terms of seroconversion rates 2 weeks after the second dose. The simplified formulation and production requirements of the Euvichol-S vaccine have the potential to increase the supply of oral cholera vaccine and reduce the gap between the current oral cholera vaccine supply and demand. FUNDING: The Bill & Melinda Gates Foundation. TRANSLATION: For the Nepali translation of the abstract see Supplementary Materials section.