Pharmacokinetics, Safety, and Immunogenicity of Intravenous and Subcutaneous Single-Dose QX002N Injection in Healthy Subjects: A Randomized, Open, Parallel, Single-Center, Phase I Study.

INTRODUCTION: Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies. METHODS: A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay. RESULTS: Pharmacokinetic analysis of the drug concentration-time data showed that the mean maximum observed serum QX002N concentration (Cmax) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration-time curves from 0 to the time of the last quantifiable concentration (AUClast) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration-time curves from 0 to infinity (AUCinf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%. CONCLUSIONS: Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects. TRIAL REGISTRATION: www.chinadrugtirals.org.cn , CTR20220430.

Heterogeneous Integration of Memristive and Piezoresistive MDMO-PPV-Based Copolymers in Nociceptive Transmission with Fast and Slow Pain for an Artificial Pain-Perceptual System.

Nociceptive pain perception is a remarkable capability of organisms to be aware of environmental changes and avoid injury, which can be accomplished by specialized pain receptors known as nociceptors with 4 vital properties including threshold, no adaptation, relaxation, and sensitization. Bioinspired systems designed using artificial devices are investigated to imitate the efficacy and functionality of nociceptive transmission. Here, an artificial pain-perceptual system (APPS) with a homogeneous material and heterogeneous integration is proposed to emulate the behavior of fast and slow pain in nociceptive transmission. Retention-differentiated poly[2-methoxy-5-(3,7-dimethyoctyoxyl)-1,4-phenylenevinylene] (MDMO-PPV) memristors with film thicknesses of 160 and 80 nm are manufactured and adopted as A-δ and C nerve fibers of nociceptor conduits, respectively. Additionally, a nociceptor mimic, the ruthenium nanoparticles (Ru-NPs)-doped MDMO-PPV piezoresistive pressure sensor, is fabricated with a noxiously stimulated threshold of 150 kPa. Under the application of pricking and dull noxious stimuli, the current flows predominantly through the memristor to mimic the behavior of fast and slow pain, respectively, in nociceptive transmission with postsynaptic potentiation properties, which is analogous to biological pain perception. The proposed APPS can provide potential advancements in establishing the nervous system, thus enabling the successful development of next-generation neurorobotics, neuroprosthetics, and precision medicine.

Recent Advances in Metal Oxide Electron Transport Layers for Enhancing the Performance of Perovskite Solar Cells.

Perovskite solar cells (PSCs) have attracted considerable interest owing to their low processing costs and high efficiency. A crucial component of these devices is the electron transport layer (ETL), which plays a key role in extracting and transmitting light-induced electrons, modifying interfaces, and adjusting surface energy levels. This minimizes charge recombination in PSCs, a critical factor in their performance. Among the various ETL materials, titanium dioxide (TiO2) and tin dioxide (SnO2) stand out due to their excellent electron mobility, suitable band alignment, high transparency, and stability. TiO2 is widely used because of its appropriate conduction band position, easy fabrication, and favorable charge extraction properties. SnO2, on the other hand, offers higher electron mobility, better stability under UV illumination, and lower processing temperatures, making it a promising alternative. This paper summarizes the latest advancements in the research of electron transport materials, including material selection and a discussion of electron collection. Additionally, it examines doping techniques that enhance electron mobility and surface modification technologies that improve interface quality and reduce recombination. The impact of these parameters on the performance and passivation behavior of PSCs is also examined. Technological advancements in the ETL, especially those involving TiO2 and SnO2, are currently a prominent research direction for achieving high-efficiency PSCs. This review covers the current state and future directions in ETL research for PSCs, highlighting the crucial role of TiO2 and SnO2 in enhancing device performance.

Using a Biofeedback-Based Mindfulness Practice System to Enhance Mindfulness and Alleviate Anxiety in College Students: A Randomized Controlled Trial.

Objective: College students experience intense anxiety, for which biofeedback mindfulness techniques show effectiveness in relief. However, typical biofeedback products often lead to user fatigue and boredom because of a single or fixed feedback and lack of focus on mindfulness enhancement. Materials and Methods: In this research, we developed Mindjourney, a VR-based respiratory feedback mindfulness system, designed to enhance mindfulness and alleviate anxiety through continuous/noncontinuous feedback and nonjudgmental reward/punishment for self-perception and attention management. A randomized controlled trial involved 72 college students, split equally into short-term (n = 34, age: 23.11 ± 1.729) and 4-week long-term (n = 38, age: 24.12 ± 1.408) groups, with equal randomization for intervention and control groups. Pre/postintervention tests were measured by using Trait Anxiety Inventory (TAI) and Five Facet Mindfulness Questionnaire (FFMQ) for long-term groups and Galvanic Skin Response and State Anxiety Inventory (SAI) for short-term groups. Results: Results showed that the long-term intervention group showed a significant increase in mindfulness (P = 0.001 for FFMQ total score). Furthermore, observe and act with awareness subscales showed significant increase after intervention (P = 0.034 for observe, P < 0.001 for act with awareness) compared with the control group. Both intervention groups demonstrated a significant decrease in anxiety levels compared with the control groups (P = 0.049 for SAI, P = 0.01 for TAI). Moreover, participants expressed high interest in this biofeedback mindfulness system and willingness for long-term usage. Conclusion: The proposed biofeedback mindfulness practice system could potentially facilitate mindfulness practice and serve as a convenient tool for anxiety relief in campus college students.

Gas-Solid Phase Reaction Derived Silver Bismuth Iodide Rudorffite: Structural Insight and Exploring Photocatalytic Potential of CO2 Reduction.

Photocatalytic reduction of CO2 is a promising strategy to mitigate the effects of global warming by converting CO2 into valuable energy-dense products. Silver bismuth iodide (SBI) is an attractive material owing to its tunable bandgap and favorable band-edge positions for efficient CO2 photoreduction. In this study, SBI materials, including AgBi2I7, AgBiI4, Ag2BiI5, and Ag3BiI6 are first synthesized, through gas-solid reaction by controlling the stoichiometric ratio of reactants. The X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) results revealed that the distance between Ag-I is proportional to the degree of Ag ions delocalization, which occupies the vacant sites. That greatly retards the charge recombination at vacant sites. In addition, the surface potential via photo-assisted Kelvin probe force measurements of various SBI catalysts shows that Ag3BiI6 exhibits the highest surface potential change due to the rich delocalized Ag ions. This results in effective charge carrier transport and prevention of charge recombination at vacant sites. Taking the above advantages, the averaged CO and CH4 production rates for Ag3BiI6 achieved 0.23 and 0.10 µmol g-1 h-1, respectively. The findings suggest that Ag3BiI6 has a high potential as a novel photocatalyst for CO2 reduction and sheds light on the possibility of solving environmental contamination and sustainable energy crises.

Decoding and reconstructing disease relations between dry eye and depression: a multimodal investigation comprising meta-analysis, genetic pathways and Mendelian randomization.

INTRODUCTION: The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined. OBJECTIVES: To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP. METHODS: A meta-analysis comprising 26 case-control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP. RESULTS: Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (rG = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein-protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained. CONCLUSION: With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.

Intramedullary Nail vs. Plate Fixation for Pathological Humeral Shaft Fracture: An Updated Narrative Review and Meta-Analysis of Surgery-Related Factors.

(1) Background: Pathological humeral shaft fracture (PHSF) is a frequently observed clinical manifestation in the later stages of tumor metastasis. Surgical interventions are typically recommended to alleviate pain and restore functionality. Intramedullary nail fixation (INF) or plate fixation (PF) is currently recommended for the treatment of PHSF. However, there is still no standard for optimal surgical treatment. Thus, we conducted a meta-analysis comparing the clinical outcomes of INF with PF for PHSF treatment. (2) Methods: We conducted searches in databases, such as Scopus, EMBASE, and PubMed, for studies published prior to May 2023. In total, nine studies with 485 patients were reviewed. (3) Results: There were no significant differences noted in the incidence of fixation failure, local recurrence, wound complication or overall complication. However, the INF group demonstrated a significantly lower incidence of postoperative radial nerve palsy than the PF group (OR, 5.246; 95% CI, 1.548-17.774; p = 0.008). A subgroup analysis indicated that there were no statistically significant differences in fixation failure or local recurrence among subgroups categorized by the design of intramedullary nail. (4) Conclusions: Considering the short life expectancy of end-stage patients, the choice of surgical method depends on the patient's individual condition, fracture and lesion patterns, the surgeon's experience, and comprehensive discussion between the surgeon and patient.

Association of chronic poststernotomy pain and health-related quality of life: a prospective cohort study.

PURPOSE: Chronic poststernotomy pain (CPSP) after cardiac surgery is multifactorial and impacts patient recovery. We aimed to evaluate the association between CPSP severity and health-related quality of life at six months after cardiac surgery. METHODS: This was a single-centre prospective cohort study of patients who underwent cardiac surgery with median sternotomy between September 2020 and March 2021. Telephone interviews were conducted at six and 12 months postoperatively using the Short Form McGill Pain Questionnaire and the EQ-5D-5L. Strength of correlation was described using Spearman's correlation coefficient. Multivariable regression analysis was used to account for confounding variables. RESULTS: A total of 252 patients responded to the six-month interview (response rate, 65%). The mean (standard deviation) age of respondents was 65 (13) yr. Twenty-nine percent of respondents (72/252) reported CPSP at six months, and 14% (41/252) reported more than mild pain (score ≥ 2/5). At 12 months, of the 89% (64/72) patients who responded, 47% (30/64) still reported pain. The strength of the correlation between pain scores and EQ-5D-5L was weak (Spearman's correlation coefficient, -0.3). Risk factors for CPSP at six months included higher pain score on postoperative day 1, history of chronic pain prior to surgery, and history of depression. Intraoperative infusion of dexmedetomidine or ketamine was associated with a reduced risk of CPSP at six months. CONCLUSION: Chronic poststernotomy pain still affects patient recovery at six and 12 months after cardiac surgery. The severity of that pain is poorly correlated with patients' quality of life. STUDY REGISTRATION: www.osf.io ( https://osf.io/52rsw ); registered 14 May 2022.

RéSUMé: OBJECTIF: La douleur chronique post-sternotomie (DCPS) après une chirurgie cardiaque est multifactorielle et a un impact sur le rétablissement des patient·es. Nous avons cherché à évaluer l'association entre la sévérité de la DCPS et la qualité de vie liée à la santé six mois après la chirurgie cardiaque. MéTHODE: Il s'agissait d'une étude de cohorte prospective monocentrique portant sur des patient·es ayant bénéficié d'une chirurgie cardiaque avec sternotomie médiane entre septembre 2020 et mars 2021. Des entrevues téléphoniques ont été menées à six et 12 mois après l'opération en se servant du questionnaire abrégé de McGill sur la douleur et de l'EQ-5D-5L. La force de corrélation a été décrite à l'aide du coefficient de corrélation de Spearman. Une analyse de régression multivariée a été utilisée pour tenir compte des variables confondantes. RéSULTATS: Au total, 252 patient·es ont répondu à l'entrevue à six mois (taux de réponse de 65 %). L'âge moyen (écart type) des répondant·es était de 65 (13) ans. Vingt-neuf pour cent des personnes répondantes (72/252) ont déclaré avoir été atteintes de DCPS à six mois, et 14 % (41/252) ont signalé une douleur plus que légère (score ≥ 2/5). À 12 mois, sur les 89 % (64/72) personnes ayant répondu, 47 % (30/64) signalaient encore de la douleur. La force de la corrélation entre les scores de douleur et l'EQ-5D-5L était faible (coefficient de corrélation de Spearman, −0,3). Les facteurs de risque de DCPS à six mois comprenaient un score de douleur plus élevé au jour 1 postopératoire, des antécédents de douleur chronique avant la chirurgie et des antécédents de dépression. Une perfusion peropératoire de dexmédétomidine ou de kétamine a été associée à une réduction du risque de DCPS à six mois. CONCLUSION: La douleur chronique post-sternotomie affecte toujours le rétablissement des patient·es six et 12 mois après la chirurgie cardiaque. La sévérité de cette douleur est faiblement corrélée à la qualité de vie des patient·es. ENREGISTREMENT DE L'éTUDE: www.osf.io ( https://osf.io/52rsw ); enregistrée le 14 mai 2022.

Split Anterolateral Thigh Flap: A New Classification of Anatomical Variants and a Surgical Planning Algorithm.

BACKGROUND: Split anterolateral thigh flap is a versatile reconstruction option, yet long underestimated as no practical perforator classification and no optimal strategy were present. Harvesting "capillary nonsizable perforators" could potentially expand flap splits to those with no existing multiple sizable perforators. Concerns over defect characteristics, recipient vessels, pedicle length, and split timing should all be weighted equally in designing the suitable flap. Refinement is thus required to enable precise reconstructions. METHODS: All patients undergoing anterolateral thigh flap harvests between 2014 and 2021 performed by a single surgeon were included. The perforator patterns of sizable pedicle, course, origin, and further successful flap-split methods were documented. Surgical outcome of flap survival was analyzed. RESULTS: Anatomical variants of 134 (48.4%) dual, 123 (44.4%) single, and 20 (7.2%) no sizable perforators were found in a total of 277 anterolateral thigh flaps. The overall flap survival rate was 97.5%. Flap split was performed in 82 flaps, including 29 single and 5 no sizable perforator cases previously considered "unsplittable," by utilizing a series of direct skin paddle split, capillary nonsizable perforators harvesting, and flow-through anastomosis technique. Comparable flap survivals were found between split and nonsplit flaps as well as between split segments supplied by sizable and capillary nonsizable perforators. Primary closure was achieved in 98.9% of the thigh donor sites. CONCLUSION: A new classification of the common anterolateral thigh flap anatomical variants was proposed and a comprehensive algorithm of split flap strategy was developed along with the innovative "fabricate" concept.

Safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of Exendin-4-IgG4-Fc in healthy subjects: A phase 1, single-centre, randomized, double-blind, dose escalation study.

AIM: Novel long-acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin-4-IgG4-Fc (E4F4) is a long-acting glucagon-like peptide-1 receptor agonist. This first-in-human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects. METHODS: This single-centre, randomized, double-blind, placebo-controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0.45, 0.9, 1.8, 3.15, 4.5, 6.3, 8.1, 10.35, 12.6 and 14.85 mg) or placebo (ChinaDrugTrials.org.cn: ChiCTR2100049732). The primary endpoint was safety and tolerability of E4F4. Secondary endpoints were pharmacokinetic, pharmacodynamic and immunogenicity profiles of E4F4. Safety data to day 15 after the final subject in a cohort had been dosed were reviewed before commencing the next dose level. RESULTS: E4F4 was safe and well tolerated among healthy Chinese participants in this study. There was no obvious dose-dependent relationship between frequency, severity or causality of treatment-emergent adverse events. Cmax and area under the curve of E4F4 were dose proportional over the 0.45-14.85 mg dose range. Median Tmax and t1/2 ranged from 146 to 210 h and 199 to 252 h, respectively, across E4F4 doses, with no dose-dependent trends. For the intravenous glucose tolerance test, area under the curve of glucose in plasma from time 0 to 180 min showed a dose-response relationship in the 1.8-10.35 mg dose range, with an increased response at the higher doses. CONCLUSION: E4F4 exhibited an acceptable safety profile and linear pharmacokinetics in healthy subjects. The recommended phase 2 dose is 4.5-10.35 mg once every 2 weeks.

Calcitriol suppresses gastric cancer progression and cisplatin resistance by inhibiting glycolysis and M2 macrophage polarization through inhibition of mTOR activation.

The tumor microenvironment (TME) plays a critical role in tumor progression, with macrophages and tumor cells interacting within the TME, influencing cancer development. Despite the known anticancer properties of calcitriol, its role in the TME remains uncertain. This study aimed to explore the effects of calcitriol on macrophages and cancer cells in the TME and its impact on gastric cancer cell proliferation and cisplatin resistance. In vitro TME models were established using conditioned medium from gastric cancer cells (CCM) and macrophages (MCM) treated with or without calcitriol. The results revealed that calcitriol treatment suppressed the expression of glycolysis-related genes and proteins (GLUT1, HKII, LDHA) in MCM-induced gastric cancer cells, leading to increased cancer cell apoptosis and reduced viability, along with decreased Cyclin D1 gene expression. Moreover, calcitriol treatment inhibited mTOR activation in MCM-induced gastric cancer cells. Additionally, calcitriol hindered CCM-induced M2 macrophage polarization by reducing CD206 expression and increasing TNFα gene expression in THP1-derived macrophages, attenuating cisplatin resistance. These findings suggest that calcitriol may impede gastric cancer progression by targeting glycolysis and M2 macrophage polarization through the regulation of mTOR activation in the TME.

Safety and immunogenicity of primary vaccination with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants aged 18 years or more: Two randomized, observer-blinded, placebo-controlled and dose-escalation phase 1 clinical trials.

Vaccination plays a key role in preventing morbidity and mortality caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the safety and immunogenicity of a SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine SYS6006. In the two randomized, observer-blinded, placebo-controlled phase 1 trials, 40 adult participants aged 18-59 years and 40 elderly participants aged 60 years or more were randomized to receive two doses of SYS6006 or placebo (saline). Adverse events (AEs) were collected through 30 days post the second vaccination. Immunogenicity was assessed by live-virus neutralizing antibody (Nab), spike protein (S1) binding antibody (S1-IgG), and cellular immunity. The result showed that 7/15, 9/15 and 4/10 adult participants, and 9/15, 8/15 and 4/10 elderly participants reported at least one AE in the 20-µg, 30-µg and placebo groups, respectively. Most AEs were grade 1. Injection-site pain was the most common AE. Two adults and one elder reported fever. No vaccination-related serious AE was reported. SYS6006 elicited wild-type Nab response with a peak geometric mean titer of 232.1 and 130.6 (adults), and 48.7 and 66.7 (elders), in the 20-µg and 30-µg groups, respectively. SYS6006 induced moderate-to-robust Nab response against Delta, and slight Nab response against Omicron BA.2 and BA.5. Robust IgG response against wild type and BA.2 was observed. Cellular immune response was induced. In conclusion, two-dose primary vaccination with SYS6006 demonstrated good safety and immunogenicity during a follow-up period of 51 days in immunologically naive population aged 18 years or more. (Trial registry: Chictr.org.cn ChiCTR2200059103 and ChiCTR2200059104).

Current Management and Volar Locking Plate Fixation with Bone Cement Augmentation for Elderly Distal Radius Fractures-An Updated Narrative Review.

Distal radius fractures (DRFs) are the most common among all kinds of fractures with an increase in incidence due to the rapidly expanded size of the elderly population in the past decades. Both non-surgical and surgical treatments can be applied for this common injury. Nowadays, more and more elderly patients with DRFs undergo surgical treatments to restore pre-injury activity levels faster. However, optimal treatment for geriatric DRFs is still debated, and careful evaluation and selection of patients are warranted considering clinical and functional outcomes, and complications following surgical treatments. Furthermore, osteoporosis is a predominant factor in elderly DRFs mostly deriving from a low-energy trauma, so many treatment modalities are developed to enhance better bone healing. Among various options for bone augmentation, bone cement is one of the most widely used measures. Bone cement such as calcium phosphate theoretically improves fracture stability and healing, but whether the elderly patients with DRFs can significantly benefit from surgical fixation with bone cement augmentation (BCA) remains controversial. Hence, in the present review, the latest literature regarding current concepts of management and evidence about volar locking plate fixation (VLPF) with BCA for elderly DRFs was searched in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science; out of >1000 articles, full texts of 48 and 6 articles were then examined and analyzed separately for management and VLPF with BCA for elderly DRFs. We aim to provide the readers with updates concerning the above issues.

Electrospun SnO2/WO3 Heterostructure Nanocomposite Fiber for Enhanced Acetone Vapor Detection.

Volatile organic compounds (VOCs), often invisible but potentially harmful, are prevalent in industrial and laboratory settings, posing health risks. Detecting VOCs in real-time with high sensitivity and low detection limits is crucial for human health and safety. The optical sensor, utilizing the gasochromic properties of sensing materials, offers a promising way of achieving rapid responses in ambient environments. In this study, we investigated the heterostructure of SnO2/WO3 nanoparticles and employed it as the primary detection component. Using the electrospinning technique, we fabricated a sensing fiber containing Ag NPs, poly(methyl methacrylate) (PMMA), and SnO2/WO3 (PMMA-Ag-SnO2/WO3) for acetone vapor detection. Following activation via UV/ozone treatment, we observed charge migration between WO3 and SnO2, resulting in a substantial generation of superoxide radicals on SnO2 nanoparticles. This phenomenon facilitates structural deformation of the fiber and alters the oxidation state of tungsten ions, ultimately leading to a significant change in extinction when exposed to acetone vapor. As a result, PMMA-Ag-SnO2/WO3 fiber achieves a detection limit of 100 ppm and a response time of 1.0 min for acetone detection. These findings represent an advancement in the development of sensitive and selective VOC sensing devices.

Phase I study of a non-S2P SARS-CoV-2 mRNA vaccine LVRNA009 in Chinese adults.

BACKGROUND: COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009). METHODS: In the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18-59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 µg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009. RESULTS: All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination. CONCLUSION: LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349.

Virtual Dental Articulation Using Computed Tomography Data and Motion Tracking.

Dental articulation holds crucial and fundamental importance in the design of dental restorations and analysis of prosthetic or orthodontic occlusions. However, common traditional and digital articulators are difficult and cumbersome in use to effectively translate the dental cast model to the articulator workspace when using traditional facebows. In this study, we have developed a personalized virtual dental articulator that directly utilizes computed tomography (CT) data to mathematically model the complex jaw movement, providing a more efficient and accurate way of analyzing and designing dental restorations. By utilizing CT data, Frankfurt's horizontal plane was established for the mathematical modeling of virtual articulation, eliminating tedious facebow transfers. After capturing the patients' CT images and tracking their jaw movements prior to dental treatment, the jaw-tracking information was incorporated into the articulation mathematical model. The validation and analysis of the personalized articulation approach were conducted by comparing the jaw movement between simulation data (virtual articulator) and real measurement data. As a result, the proposed virtual articulator achieves two important functions. Firstly, it replaces the traditional facebow transfer process by transferring the digital dental model to the virtual articulator through the anatomical relationship derived from the cranial CT data. Secondly, the jaw movement trajectory provided by optical tracking was incorporated into the mathematical articulation model to create a personalized virtual articulation with a small Fréchet distance of 1.7 mm. This virtual articulator provides a valuable tool that enables dentists to obtain diagnostic information about the temporomandibular joint (TMJ) and configure personalized settings of occlusal analysis for patients.

Effects of music therapy on cognition, quality of life, and neuropsychiatric symptoms of patients with dementia: A systematic review and meta-analysis of randomized controlled trials.

Dementia is a major cause of disability and dependency. Pharmacological interventions are commonly provided to patients with dementia to delay the deterioration of cognitive functions but cannot alter the course of disease. Nonpharmacological interventions are now attracting increasing scholarly interest. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we aim to assess the effectiveness of music-based therapies on the cognition, quality of life (QoL), and neuropsychiatric symptoms of patients with dementia through a systematic review and meta-analysis of randomized controlled trials (RCTs). The PubMed, Embase, and Cochrane databases were searched for reports of RCTs examining the effectiveness of music-based therapies for dementia published as of April 2023. A total of 674 articles were screened, and 22 trials from 21 studies (1780 patients) met the eligibility criteria. In 15 trials, music-based therapies significantly improved the cognition of patients with dementia compared with non-music therapies. In 11 trials, music-based therapies also significantly improved the QoL of patients with dementia compared with non-music therapies. In six trials, music-based therapies significantly improved patients' neuropsychiatric symptoms compared with non-music therapies. In conclusion, music-based therapy is recognized as a safe and effective alternative approach for patients with dementia.

The genetic and environmental contributions to variation in the permanent dental arch form: a twin study.

OBJECTIVE: The objective of this study was to examine the relative contributions of genetic and environmental influences on variation in dental arch form in individuals who have largely completed their craniofacial growth. MATERIAL AND METHODS: The subjects of this study comprised dental casts of 50 monozygotic twins and 24 dizygotic twins from the collection of records of twins housed at the Adelaide Dental School, Australia. The subjects were of Western European descent, with an average age of 20.93 ±â€…5.58 years. Dental casts were scanned using a 3D scanner to analyse the dental arch form. Landmark-based inter-arch and intra-arch measurements were performed. Structural equation modelling was employed to analyse the quantitative data using the normal assumptions of the twin model. RESULTS: Genetic modelling revealed that additive genetic and unique environmental factors best explained the observed variation for all occlusal traits measured, except for mandibular intercanine width. High heritability was observed for most intra-arch occlusal variables (0.61-0.85) including the maxillary and mandibular intercanine and intermolar widths, arch depth and perimeter. In contrast, moderate heritability was found for inter-arch occlusal variables (0.52-0.59) such as overjet and overbite. Sexual dimorphism was evident, with males displaying larger posterior arch width than females (P < 0.05). LIMITATIONS: Our sample was limited to individuals of Western European ancestry. CONCLUSION: The predominant source of occlusal variation within this group of Australian twins of Western European descent was controlled by genetic effects, and most were highly heritable. Generally, intra-arch occlusal variables showed greater heritability compared with inter-arch occlusal variables.