Wavefunction matching for solving quantum many-body problems.

Ab initio calculations have an essential role in our fundamental understanding of quantum many-body systems across many subfields, from strongly correlated fermions1-3 to quantum chemistry4-6 and from atomic and molecular systems7-9 to nuclear physics10-14. One of the primary challenges is to perform accurate calculations for systems where the interactions may be complicated and difficult for the chosen computational method to handle. Here we address the problem by introducing an approach called wavefunction matching. Wavefunction matching transforms the interaction between particles so that the wavefunctions up to some finite range match that of an easily computable interaction. This allows for calculations of systems that would otherwise be impossible owing to problems such as Monte Carlo sign cancellations. We apply the method to lattice Monte Carlo simulations15,16 of light nuclei, medium-mass nuclei, neutron matter and nuclear matter. We use high-fidelity chiral effective field theory interactions17,18 and find good agreement with empirical data. These results are accompanied by insights on the nuclear interactions that may help to resolve long-standing challenges in accurately reproducing nuclear binding energies, charge radii and nuclear-matter saturation in ab initio calculations19,20.

Psychedelics reopen the social reward learning critical period.

Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness1,2. These drugs have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies3-9. Nevertheless, a unifying mechanism that can account for these shared phenomenological and therapeutic properties remains unknown. Here we demonstrate in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelic drugs. Notably, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Finally, identification of differentially expressed genes in the 'open state' versus the 'closed state' provides evidence that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening. Together these results have important implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease.

Stability-limiting heterointerfaces of perovskite photovoltaics.

Optoelectronic devices consist of heterointerfaces formed between dissimilar semiconducting materials. The relative energy-level alignment between contacting semiconductors determinately affects the heterointerface charge injection and extraction dynamics. For perovskite solar cells (PSCs), the heterointerface between the top perovskite surface and a charge-transporting material is often treated for defect passivation1-4 to improve the PSC stability and performance. However, such surface treatments can also affect the heterointerface energetics1. Here we show that surface treatments may induce a negative work function shift (that is, more n-type), which activates halide migration to aggravate PSC instability. Therefore, despite the beneficial effects of surface passivation, this detrimental side effect limits the maximum stability improvement attainable for PSCs treated in this way. This trade-off between the beneficial and detrimental effects should guide further work on improving PSC stability via surface treatments.

Intravascular Imaging-Guided or Angiography-Guided Complex PCI.

BACKGROUND: Data regarding clinical outcomes after intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided PCI, are limited. METHODS: In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging-guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators' discretion. The primary end point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed. RESULTS: A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging-guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P = 0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel-related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events. CONCLUSIONS: Among patients with complex coronary-artery lesions, intravascular imaging-guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872).

Flexible and Stretchable Light-Emitting Diodes and Photodetectors for Human-Centric Optoelectronics.

Optoelectronic devices with unconventional form factors, such as flexible and stretchable light-emitting or photoresponsive devices, are core elements for the next-generation human-centric optoelectronics. For instance, these deformable devices can be utilized as closely fitted wearable sensors to acquire precise biosignals that are subsequently uploaded to the cloud for immediate examination and diagnosis, and also can be used for vision systems for human-interactive robotics. Their inception was propelled by breakthroughs in novel optoelectronic material technologies and device blueprinting methodologies, endowing flexibility and mechanical resilience to conventional rigid optoelectronic devices. This paper reviews the advancements in such soft optoelectronic device technologies, honing in on various materials, manufacturing techniques, and device design strategies. We will first highlight the general approaches for flexible and stretchable device fabrication, including the appropriate material selection for the substrate, electrodes, and insulation layers. We will then focus on the materials for flexible and stretchable light-emitting diodes, their device integration strategies, and representative application examples. Next, we will move on to the materials for flexible and stretchable photodetectors, highlighting the state-of-the-art materials and device fabrication methods, followed by their representative application examples. At the end, a brief summary will be given, and the potential challenges for further development of functional devices will be discussed as a conclusion.

Rice OsGATA16 is a positive regulator for chlorophyll biosynthesis and chloroplast development.

Chloroplasts are essential organelles in plants that contain chlorophylls and facilitate photosynthesis for growth and development. As photosynthetic efficiency significantly impacts crop productivity, understanding the regulatory mechanisms of chloroplast development has been crucial in increasing grain and biomass production. This study demonstrates the involvement of OsGATA16, an ortholog of Arabidopsis GATA, NITRATE INDUCIBLE, CARBON-METABOLISM INVOLVED (GNC), and GNC-LIKE/CYTOKININ-RESPONSIVE GATA FACTOR 1 (GNL/CGA1), in chlorophyll biosynthesis and chloroplast development in rice (Oryza sativa). The osgata16-1 knockdown mutants produced pale-green leaves, while OsGATA16-overexpressed plants (OsGATA16-OE1) generated dark-green leaves, compared to their parental japonica rice. Reverse transcription and quantitative PCR analysis revealed downregulation of genes related to chloroplast division, chlorophyll biosynthesis, and photosynthesis in the leaves of osgata16-1 and upregulation in those of OsGATA16-OE1. Additionally, in vivo binding assays showed that OsGATA16 directly binds to the promoter regions of OsHEMA, OsCHLH, OsPORA, OsPORB, and OsFtsZ, and upregulates their expression. These findings indicate that OsGATA16 serves as a positive regulator controlling chlorophyll biosynthesis and chloroplast development in rice.

A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine's behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.

Validation of the Texas Hepatocellular Carcinoma Risk Index Predictive Model for Hepatocellular Carcinoma in Asian Cohort.

Hepatocellular carcinoma (HCC) represents a significant global health burden, with its incidence and mortality rates varying significantly across different geographic regions. This variance is largely attributed to differences in the prevalence of risk factors such as hepatitis B and C infections, and alcohol consumption, as well as genetic predispositions that are distinct between Eastern and Western populations. Moreover, the impact of racial and ethnic diversity on the disease's epidemiology further complicates the global understanding and prediction of HCC. Such disparities highlight the critical need to evaluate the applicability of predictive models across diverse populations, acknowledging that a model developed in one region may not necessarily translate with the same accuracy or effectiveness when applied to another, because of these underlying epidemiologic and genetic differences. In this study, we aimed to assess the cross-regional applicability and accuracy of an HCC prediction model (Texas hepatocellular carcinoma risk index [THCC-RI] predictive model) originally developed in Western populations, within an Eastern context.1,2.

Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study.

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.

Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation.

BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Oxidative stress and vascular dysfunction: Potential therapeutic targets and therapies in peripheral artery disease.

Peripheral artery disease (PAD) is the manifestation of atherosclerosis characterized by the accumulation of plaques in the arteries of the lower limbs. Interestingly, growing evidence suggests that the pathology of PAD is multifaceted and encompasses both vascular and skeletal muscle dysfunctions, which contributes to blunted physical capabilities and diminished quality of life. Importantly, it has been suggested that many of these pathological impairments may stem from blunted reduction-oxidation (redox) handling. Of note, in those with PAD, excessive production of reactive oxygen species (ROS) outweighs antioxidant capabilities resulting in oxidative damage, which may have systemic consequences. It has been suggested that antioxidant supplementation may be able to assist in handling ROS. However, the activation of various ROS production sites makes it difficult to determine the efficacy of these antioxidant supplements. Therefore, this review focuses on the common cellular mechanisms that facilitate ROS production and discusses how excessive ROS may impair vascular and skeletal muscle function in PAD. Furthermore, we provide insight for current and potential antioxidant therapies, specifically highlighting activation of the Kelch-like ECH-associated protein 1 (Keap1) - Nuclear Factor Erythroid 2-related factor 2 (Nrf2) pathway as a potential pharmacological therapy to combat ROS accumulation and aid in vascular function, and physical performance in patients with PAD. Altogether, this review provides a better understanding of excessive ROS in the pathophysiology of PAD and enhances our perception of potential therapeutic targets that may improve vascular function, skeletal muscle function, walking capacity, and quality of life in patients with PAD.

Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Non-ST-Elevation Myocardial Infarction.

BACKGROUND: Limited data exist regarding the prognostic implications of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with non-ST-elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI). METHODS AND RESULTS: Of 13,104 patients in the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health, 3,083 patients with NSTEMI who underwent PCI were included in the present study. The primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction, unplanned repeat revascularization, and admission for heart failure. NT-proBNP was measured at the time of initial presentation for the management of NSTEMI, and patients were divided into a low (<700 pg/mL; n=1,813) and high (≥700 pg/mL; n=1,270) NT-proBNP group. The high NT-proBNP group had a significantly higher risk of MACE, driven primarily by a higher risk of cardiac death or admission for heart failure. These results were consistent after confounder adjustment by propensity score matching and inverse probability weighting analysis. CONCLUSIONS: In patients with NSTEMI who underwent PCI, an initial elevated NT-proBNP concentration was associated with higher risk of MACE at 3 years, driven primarily by higher risks of cardiac death or admission for heart failure. These results suggest that the initial NT-proBNP concentration may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

Association between intensive care unit nursing grade and mortality in patients with cardiogenic shock and its cost-effectiveness.

BACKGROUND: Despite the high workload of cardiac intensive care unit (ICU), there is a paucity of evidence on the association between nurse workforce and mortality in patients with cardiogenic shock (CS). This study aimed to evaluate the prognostic impact of the ICU nursing grade on mortality and cost-effectiveness in CS. METHODS: A nationwide analysis was performed using the K-NHIS database. Patients diagnosed with CS and admitted to the ICU at tertiary hospitals were enrolled. ICU nursing grade was defined according to the bed-to-nurse ratio: grade1 (bed-to-nurse ratio < 0.5), grade2 (0.5 ≤ bed-to-nurse ratio < 0.63), and grade3 (0.63 ≤ bed-to-nurse ratio < 0.77) or above. The primary endpoint was in-hospital mortality. Cost-effective analysis was also performed. RESULTS: Of the 72,950 patients with CS, 27,216 (37.3%) were in ICU nursing grade 1, 29,710 (40.7%) in grade 2, and 16,024 (22.0%) in grade ≥ 3. The adjusted-OR for in-hospital mortality was significantly higher in patients with grade 2 (grade 1 vs. grade 2, 30.6% vs. 37.5%, adjusted-OR 1.14, 95% CI1.09-1.19) and grade ≥ 3 (40.6%) with an adjusted-OR of 1.29 (95% CI 1.23-1.36) than those with grade 1. The incremental cost-effectiveness ratio of grade1 compared with grade 2 and ≥ 3 was $25,047/year and $42,888/year for hospitalization and $5151/year and $5269/year for 1-year follow-up, suggesting that grade 1 was cost-effective. In subgroup analysis, the beneficial effects of the high-intensity nursing grade on mortality were more prominent in patients who received CPR or multiple vasopressors usage. CONCLUSIONS: For patients with CS, ICU grade 1 with a high-intensity nursing staff was associated with reduced mortality and more cost-effectiveness during hospitalization compared to grade 2 and grade ≥ 3, and its beneficial effects were more pronounced in subjects at high risk of CS.

Is transmucosal healing of an implant as effective as submerged healing when simultaneous guided bone regeneration is performed? A preclinical study.

AIM: To investigate whether transmucosal healing is as effective as submerged healing in terms of buccal bone regeneration when guided bone regeneration (GBR) is performed simultaneously with implant placement. MATERIALS AND METHODS: In six dogs, buccal dehiscence defects were created in the edentulous mandibular ridge, sized 5 × 5 × 3 mm (length × height × depth). In each defect, a bone-level implant was placed, and four experimental groups were randomly assigned as follows: (i) transmucosal healing with GBR (T-GBR), (ii) transmucosal healing without GBR (T-control), (iii) submerged healing with GBR (S-GBR) and (iv) submerged healing without GBR (S-control). Data analyses were based on histological slides 5 months after implant placement. RESULTS: The T-GBR group showed significant differences compared to the control groups regarding defect height resolution, buccal bone thickness and mineralized tissue area (p < .05), but showed no significant differences when compared with the S-GBR group (p > .05). CONCLUSIONS: The mode of healing (transmucosal vs. submerged) does not influence bone regeneration at implant sites. The clinician may therefore choose the approach based on further clinical and patient-specific parameters.

Flapless early implant placement into the uncalcified provisional matrix-Does it lead to osseointegration of the implant? A preclinical study.

AIM: To test whether early implant placement into the extraction socket containing an uncalcified provisional matrix leads to successful osseointegration and stable marginal bone levels. MATERIALS AND METHODS: In six mongrel dogs, the mandibular molars were extracted. Three weeks later, early implant placement was performed according to three experimental protocols: (i) flapless implant placement with preservation of the provisional matrix; (ii) flap elevation, socket debridement and implant placement; and (iii) flap elevation, socket debridement, implant placement and guided bone regeneration (GBR). One untreated extraction socket served as a control group. Data analyses were based on histologic slides 3 months after implant placement. RESULTS: There were no differences in bone-to-implant contact between the three experimental groups (66.97%, 58.89% and 60.89%, respectively) (inter-group comparison p = .42). Marginal bone levels, first bone-to-implant contact as well as the thickness of the connective tissue did not reveal any significant differences between the groups (p = .85, .60 and .65, respectively). CONCLUSIONS: Flapless early implant placement into posterior extraction sockets was as effective as an open flap approach in conjunction with GBR. Mineralization of the socket seems to occur irrespective of the presence of dental implants or biomaterials.

Disrupting FKF1 homodimerization increases FT transcript levels in the evening by enhancing CO stabilization.

KEY MESSAGE: FKF1 dimerization is crucial for proper FT levels to fine-tune flowering time. Attenuating FKF1 homodimerization increased CO abundance by enhancing its COP1 binding, thereby accelerating flowering under long days. In Arabidopsis (Arabidopsis thaliana), the blue-light photoreceptor FKF1 (FLAVIN-BINDING, KELCH REPEAT, F-BOX 1) plays a key role in inducing the expression of FLOWERING LOCUS T (FT), encoding the main florigenic signal in plants, in the late afternoon under long-day conditions (LDs) by forming dimers with FT regulators. Although structural studies have unveiled a variant of FKF1 (FKF1 I160R) that disrupts homodimer formation in vitro, the mechanism by which disrupted FKF1 homodimer formation regulates flowering time remains elusive. In this study, we determined that the attenuation of FKF1 homodimer formation enhances FT expression in the evening by promoting the increased stability of CONSTANS (CO), a primary activator of FT, in the afternoon, thereby contributing to early flowering. In contrast to wild-type FKF1, introducing the FKF1 I160R variant into the fkf1 mutant led to increased FT expression under LDs. In addition, the FKF1 I160R variant exhibited diminished dimerization with FKF1, while its interaction with GIGANTEA (GI), a modulator of FKF1 function, was enhanced under LDs. Furthermore, the FKF1 I160R variant increased the level of CO in the afternoon under LDs by enhancing its binding to COP1, an E3 ubiquitin ligase responsible for CO degradation. These findings suggest that the regulation of FKF1 homodimerization and heterodimerization allows plants to finely adjust FT expression levels around dusk by modulating its interactions with GI and COP1.

Enhancing guided bone regeneration with cross-linked collagen-conjugated xenogeneic bone blocks and membrane fixation: A preclinical in vivo study.

OBJECTIVE: To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model. MATERIALS AND METHODS: Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks. RESULTS: At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm2, mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm2; p < .0083), NCL + fix (3.97 ± 1.39 mm2) and CL + unfix (2.55 ± 1.04 mm2) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083). CONCLUSION: Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR.

Ridge preservation using a self-retaining block type bone substitute for extraction sockets with buccal dehiscence defects - A preclinical study.

OBJECTIVE: To evaluate the effect of a self-retaining block-type bone substitute (srBB) on the dimensional stability of the horizontal ridge width at the coronal level in a buccal dehiscence model. MATERIALS AND METHODS: Four box-shaped bone defects with a buccal dehiscence were surgically prepared in the partially edentulous mandible (n = 6). Experimental biomaterials were randomly assigned to each site: (1) Control group: no treatment, (2) particle-type bone substitute (PBS) group, (3) collagenated soft block bone substitute (csBB) group, and (4) self-retaining synthetic block bone (srBB) group. In all grafted groups, a collagen membrane covered the biomaterials. At 16 weeks, clinical, histological, and radiographic analyses were performed. RESULTS: Three of the six blocks in the srBB group became exposed and fell out during the first week after surgery. Therefore, the remaining three specimens were renamed RsrBB group. The RsrBB group showed an increase horizontal ridge compared to the pristine bone width at 2-4 mm below the CEJ, while the other groups showed resorption (augmented width at 2 mm below: 4.2, 42.4, 36.2, and 110.1% in the control, PBS, csBB, and RsrBB groups, respectively). The mineralized bone area was largest in the RsrBB group (4.74, 3.44, 5.67, and 7.77 mm2 in the control, PBS, csBB, and RsrBB groups, respectively.). CONCLUSIONS: The srBB group demonstrated the highest volume stability at the coronal level. These findings would potentially suggest that self-retaining block bone substitute might be a good candidate for alveolar ridge preservation.

Does an untreated peri-implant dehiscence defect affect the progression of peri-implantitis?: A preclinical in vivo experimental study.

OBJECTIVE: To investigate the early impact of plaque accumulation in a buccal dehiscence defect on peri-implant marginal bone resorption. MATERIALS AND METHODS: In six male Mongrel dogs, four dental implants were placed in the posterior maxilla on both sides (two implants per side). Based on the group allocation, each implant was randomly assigned to one of the following four groups to decide whether buccal dehiscence defect was prepared and whether silk ligation was applied at 8 weeks post-implant placement for peri-implantitis induction: UC (no defect without ligation); UD (defect without ligation); LC (no defect with ligation); and LD (defect with ligation) groups. Eight weeks after disease induction, the outcomes from radiographic and histologic analyses were statistically analyzed (p < .05). RESULTS: Based on radiographs, the exposed area of implant threads was smallest in group UC (p < .0083). Based on histology, both the distances from the implant platform to the first bone-to-implant contact point and to the bone crest were significantly longer in the LD group (p < .0083). In the UD group, some spontaneous bone fill occurred from the base of the defect at 8 weeks after implant placement. The apical extension of inflammatory cell infiltrate was significantly more prominent in the LD and LC groups compared to the UC group (p < .0083). CONCLUSION: Plaque accumulated on the exposed implant surface had a negative impact on maintaining the peri-implant marginal bone level, especially when there was a dehiscence defect around the implant.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.

BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.