Are trait-associated genes clustered together in a gene network?

Genome-wide association studies (GWAS) have provided an abundance of information about the genetic variants and their loci that are associated to complex traits and diseases. However, due to linkage disequilibrium (LD) and noncoding regions of loci, it remains a challenge to pinpoint the causal genes. Gene network-based approaches, paired with network diffusion methods, have been proposed to prioritize causal genes and to boost statistical power in GWAS based on the assumption that trait-associated genes are clustered in a gene network. Due to the difficulty in mapping trait-associated variants to genes in GWAS, this assumption has never been directly or rigorously tested empirically. On the other hand, whole exome sequencing (WES) data focuses on the protein-coding regions, directly identifying trait-associated genes. In this study, we tested the assumption by leveraging the recently available exome-based association statistics from the UK Biobank WES data along with two types of networks. We found that almost all trait-associated genes were significantly more proximal to each other than randomly selected genes within both networks. These results support the assumption that trait-associated genes are clustered in gene networks, which can be further leveraged to boost the power of GWAS such as by introducing less stringent p value thresholds.

Interkingdom assemblages in human saliva display group-level surface mobility and disease-promoting emergent functions.

Fungi and bacteria often engage in complex interactions, such as the formation of multicellular biofilms within the human body. Knowledge about how interkingdom biofilms initiate and coalesce into higher-level communities and which functions the different species carry out during biofilm formation remain limited. We found native-state assemblages of Candida albicans (fungi) and Streptococcus mutans (bacteria) with highly structured arrangement in saliva from diseased patients with childhood tooth decay. Further analyses revealed that bacterial clusters are attached within a network of fungal yeasts, hyphae, and exopolysaccharides, which bind to surfaces as a preassembled cell group. The interkingdom assemblages exhibit emergent functions, including enhanced surface colonization and growth rate, stronger tolerance to antimicrobials, and improved shear resistance, compared to either species alone. Notably, we discovered that the interkingdom assemblages display a unique form of migratory spatial mobility that enables fast spreading of biofilms across surfaces and causes enhanced, more extensive tooth decay. Using mutants, selective inactivation of species, and selective matrix removal, we demonstrate that the enhanced stress resistance and surface mobility arise from the exopolymeric matrix and require the presence of both species in the assemblage. The mobility is directed by fungal filamentation as hyphae extend and contact the surface, lifting the assemblage with a "forward-leaping motion." Bacterial cell clusters can "hitchhike" on this mobile unit while continuously growing, to spread across the surface three-dimensionally and merge with other assemblages, promoting community expansion. Together, our results reveal an interkingdom assemblage in human saliva that behaves like a supraorganism, with disease-causing emergent functionalities that cannot be achieved without coassembly.

Coevolutionary Information Captures Catalytic Functions and Reveals Divergent Roles of Terpene Synthase Interdomain Connections.

Inferring the historical and biophysical causes of diversity within protein families is a complex puzzle. A key to unraveling this problem is characterizing the rugged topography of sequence-function adaptive landscapes. Using biochemical data from a 29 = 512 combinatorial library of tobacco 5-epi-aristolochene synthase (TEAS) mutants engineered to make the native major product of Egyptian henbane premnaspirodiene synthase (HPS) and a complementary 512 mutant HPS library, we address the question of how product specificity is controlled. These data sets reveal that HPS is far more robust and resistant to mutations than TEAS, where most mutants are promiscuous. We also combine experimental data with a sequence Potts Hamiltonian model and direct coupling analysis to quantify mutant fitness. Our results demonstrate that the Hamiltonian captures variation in product outputs across both libraries, clusters native family members based on their substrate specificities, and exposes the divergent catalytic roles of couplings between the catalytic and noncatalytic domains of TEAS versus HPS. Specifically, we found that the role of the interdomain connectivities in specifying product output is more important in TEAS than connectivities within the catalytic domain. Despite being 75% identical, this property is not shared by HPS, where connectivities within the catalytic domain are more important for specificity. By solving the X-ray crystal structure of HPS, we assessed structural bases for their interdomain network differences. Last, we calculate the product profile Shannon entropies of the two libraries, which showcases that site-site connectivities also play divergent roles in catalytic accuracy.

Construction of Ideal One-Dimensional Spin Chains by Topochemical Dehydration/Rehydration Route.

One-dimensional (1D) Heisenberg antiferromagnets are of great interest due to their intriguing quantum phenomena. However, the experimental realization of such systems with large spin S remains challenging because even weak interchain interactions induce long-range ordering. In this study, we present an ideal 1D S = 5/2 spin chain antiferromagnet achieved through a multistep topochemical route involving dehydration and rehydration. By desorbing three water molecules from (2,2'-bpy)FeF3(H2O)·2H2O (2,2'-bpy = 2,2'-bipyridyl) at 150 °C and then intercalating two water molecules at room temperature (giving (2,2'-bpy)FeF3·2H2O 1), the initially isolated FeF3ON2 octahedra combine to form corner-sharing FeF4N2 octahedral chains, which are effectively separated by organic and added water molecules. Mössbauer spectroscopy reveals significant dynamical fluctuations down to 2.7 K, despite the presence of strong intrachain interactions. Moreover, results from electron spin resonance (ESR) and heat capacity measurements indicate the absence of long-range order down to 0.5 K. This controlled topochemical dehydration/rehydration approach is further extended to (2,2'-bpy)CrF3·2H2O with S = 3/2 1D chains, thus opening the possibility of obtaining other low-dimensional spin lattices.

Spiky Magnetic Microparticles Synthesized from Microrod-Stabilized Pickering Emulsion.

Tailoring the microstructure of magnetic microparticles is of vital importance for their applications. Spiky magnetic particles, such as those made from sunflower pollens, have shown promise in single cell treatment and biofilm removal. Synthetic methods that can replicate or extend the functionality of such spiky particles would be advantageous for their widespread utilization. In this work, a wet-chemical method is introduced for spiky magnetic particles that are templated from microrod-stabilized Pickering emulsions. The spiky morphology is generated by the upright attachment of silica microrods at the oil-water interface of oil droplets. Spiky magnetic microparticles with control over the length of the spikes are obtained by dispersing hydrophobic magnetic nanoparticles in the oil phase and photopolymerizing the monomer. The spiky morphology dramatically enhances colloidal stability of these particles in high ionic strength solutions and physiologic media such as human saliva and saline-based biofilm suspension. To demonstrate their utility, the spiky magnetic particles are applied for magnetically controlled removal of oral biofilms and retrieval of bacteria for diagnostic sampling. This method expands the toolbox for engineering microparticle morphology and could promote the fabrication of functional magnetic microrobots.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Imaging Very Late Antigen-4 on MOLT4 Leukemia Tumors with Cysteine Site-Specific 89Zr-Labeled Natalizumab Immuno-Positron Emission Tomography.

Very late antigen-4 (VLA4; CD49d) is a promising immune therapy target in treatment-resistant leukemia and multiple myeloma, and there is growing interest in repurposing the humanized monoclonal antibody (Ab), natalizumab, for this purpose. Positron emission tomography with radiolabeled Abs (immuno-PET) could facilitate this effort by providing information on natalizumab's in vivo pharmacokinetic and target delivery properties. In this study, we labeled natalizumab with 89Zr specifically on sulfhydryl moieties via maleimide-deferoxamine conjugation. High VLA4-expressing MOLT4 human T cell acute lymphoblastic leukemia cells showed specific 89Zr-natalizumab binding that was markedly blocked by excess Ab. In nude mice bearing MOLT4 tumors, 89Zr-natalizumab PET showed high-contrast tumor uptake at 7 days postinjection. Biodistribution studies confirmed that uptake was the highest in MOLT4 tumors (2.22 ± 0.41%ID/g) and the liver (2.33 ± 0.76%ID/g), followed by the spleen (1.51 ± 0.42%ID/g), while blood activity was lower at 1.12 ± 0.21%ID/g. VLA4-specific targeting in vivo was confirmed by a 58.1% suppression of tumor uptake (0.93 ± 0.15%ID/g) when excess Ab was injected 1 h earlier. In cultured MOLT4 cells, short-term 3 day exposure to the proteasome inhibitor bortezomib (BTZ) did not affect the α4 integrin level, but BTZ-resistant cells that survived the treatment showed increased α4 integrin expression. When the effects of BTZ treatment were tested in mice, there was no change of the α4 integrin level or 89Zr-natalizumab uptake in MOLT4 leukemia tumors, which underscores the complexity of tumor VLA4 regulation in vivo. In conclusion, 89Zr-natalizumab PET may be useful for noninvasive monitoring of tumor VLA4 and may assist in a more rational application of Ab-based therapies for hematologic malignancies.

Predictors of Late Adverse Events in Patients with Surgically Treated Type I Aortic Dissection.

OBJECTIVE: Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. METHODS: This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within three months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. RESULTS: Of 103 participants (55.43 ± 13.94 years; 49.5% male), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The three year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). CONCLUSION: Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.

Tailored Planning of Surgical Myectomy in Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease characterized by abnormal thickening of the myocardium caused by myocardial disarray and interstitial fibrosis. HCM is associated with sudden cardiac-related events, such as ventricular fibrillation, tachycardia, and syncope. Moreover, left ventricular or midcavity obstruction due to the thickened myocardium can result in severe heart failure and mortality in patients with HCM. Surgical myectomy is a standard treatment option for patients with symptomatic obstructive HCM; however, it is a complex procedure that requires careful planning and execution to avoid complications, such as residual flow obstruction, persistent obliteration of the left ventricular cavity in systole, or iatrogenic ventricular septal defects. Therefore, a thorough understanding of the mechanics of HCM and precise evaluation of the location and extent of the hypertrophic myocardium to be removed are crucial for preoperative planning. Multiphase cardiac CT postprocessing is important for preoperative evaluation and planning of surgical myectomy in patients with HCM. In this review, the authors highlight use of multiphase cardiac CT with step-by-step postprocessing methods to simulate successful surgical myectomy. The transaortic surgeon's view on end-diastolic phase images accurately represents the surgical field. Moreover, myocardial segmentation can be used to generate volume-rendered images and three-dimensional printing. CT evaluation can also assist in identifying concurrent abnormalities, such as mitral valve or papillary muscle abnormalities. In addition to CT, other imaging modalities for preoperative evaluation of HCM and postmyectomy evaluation methods are presented. ©RSNA, 2023 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

A Single-Cell Atlas of Small Airway Disease in Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

Rationale: Emerging data demonstrate that the smallest conducting airways, terminal bronchioles, are the early site of tissue destruction in chronic obstructive pulmonary disease (COPD) and are reduced by as much as 41% by the time someone is diagnosed with mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1) COPD. Objectives: To develop a single-cell atlas that describes the structural, cellular, and extracellular matrix alterations underlying terminal bronchiole loss in COPD. Methods: This cross-sectional study of 262 lung samples derived from 34 ex-smokers with normal lung function (n = 10) or GOLD stage 1 (n = 10), stage 2 (n = 8), or stage 4 (n = 6) COPD was performed to assess the morphology, extracellular matrix, single-cell atlas, and genes associated with terminal bronchiole reduction using stereology, micro-computed tomography, nonlinear optical microscopy, imaging mass spectrometry, and transcriptomics. Measurements and Main Results: The lumen area of terminal bronchioles progressively narrows with COPD severity as a result of the loss of elastin fibers within alveolar attachments, which was observed before microscopic emphysematous tissue destruction in GOLD stage 1 and 2 COPD. The single-cell atlas of terminal bronchioles in COPD demonstrated M1-like macrophages and neutrophils located within alveolar attachments and associated with the pathobiology of elastin fiber loss, whereas adaptive immune cells (naive, CD4, and CD8 T cells, and B cells) are associated with terminal bronchiole wall remodeling. Terminal bronchiole pathology was associated with the upregulation of genes involved in innate and adaptive immune responses, the interferon response, and the degranulation of neutrophils. Conclusions: This comprehensive single-cell atlas highlights terminal bronchiole alveolar attachments as the initial site of tissue destruction in centrilobular emphysema and an attractive target for disease modification.

Microrobotics in endodontics: A perspective.

Microorganisms are the primary aetiological factor of apical periodontitis. The goal of endodontic treatment is to prevent and eliminate the infection by removing the microorganisms. However, microbial biofilms and the complex root canal anatomy impair the disinfection process. Effective and precise endodontic therapy could potentially be achieved using advanced multifunctional technologies that have the ability to access hard-to-reach surfaces and perform simultaneous biofilm killing, removal, and detection of microorganisms. Advances in microrobotics are providing novel therapeutic and diagnostic opportunities with high precision and efficacy to address current biofilm-related challenges in biomedicine. Concurrently, multifunctional magnetic microrobots have been developed to overcome the disinfection challenges of current approaches to disrupt, kill, and retrieve biofilms with the goal of enhancing the efficacy and precision of endodontic therapy. This article reviews the recent advances of microrobotics in healthcare and particularly advances to overcome disinfection challenges in endodontics, and provides perspectives for future research in the field.

Effects of transition programmes to adulthood for adolescents and young adults with CHD: a systematic review with meta-analysis.

BACKGROUND: The increased survival rate among individuals with CHD has sparked interest in their transition to adult healthcare. Although there is a general agreement on the importance of transition interventions, the empirical evidence supporting them is insufficient. Therefore, this study aimed to conduct a systematic review and meta-analysis of transition interventions for adult healthcare in adolescents and young adults. METHODS AND RESULTS: A literature search was conducted for studies comparing the quantitative effects of transition interventions with control groups, published up to March 15, 2023, in major databases (CENTRAL, Embase, PubMed, Web of Science, CINAHL, KISS, and KMbase), major clinical trial registries, academic journal sites related to the topic, and grey literature databases. Ten studies involving a total of 1,297 participants were identified. Transition interventions proved effective in enhancing disease-related knowledge (Hedge's g = 0.89, 95% CI = 0.29-1.48) and self-management (Hedge's g = 0.67, 95% CI = 0.38-0.95), as well as reducing loss to follow-up (OR = 0.41, 95% CI = 0.22-0.77). The certainty of evidence for the estimated values of each major outcome was low or very low. CONCLUSIONS: This study supports the implementation of transition interventions by demonstrating that they can improve patients' disease knowledge and self-management, while also promoting treatment continuity. However, since the available data on transition interventions for adolescents and young adults with CHD remain limited, the widespread adoption of structured transition interventions in the future may alter the conclusions of this study. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42023399026.

Social networking at the microbiome-host interface.

Microbial species colonizing host ecosystems in health or disease rarely do so alone. Organisms conglomerate into dynamic heterotypic communities or biofilms in which interspecies and interkingdom interactions drive functional specialization of constituent species and shape community properties, including nososymbiocity or pathogenic potential. Cell-to-cell binding, exchange of signaling molecules, and nutritional codependencies can all contribute to the emergent properties of these communities. Spatial constraints defined by community architecture also determine overall community function. Multilayered interactions thus occur between individual pairs of organisms, and the relative impact can be determined by contextual cues. Host responses to heterotypic communities and impact on host surfaces are also driven by the collective action of the community. Additionally, the range of interspecies interactions can be extended by bacteria utilizing host cells or host diet to indirectly or directly influence the properties of other organisms and the community microenvironment. In contexts where communities transition to a dysbiotic state, their quasi-organismal nature imparts adaptability to nutritional availability and facilitates resistance to immune effectors and, moreover, exploits inflammatory and acidic microenvironments for their persistence.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.

Impact of new-onset arrhythmia on cardiac reverse remodeling following transcatheter aortic valve replacement: computed tomography-derived left ventricular and atrial strains.

OBJECTIVE: Patients who undergo transcatheter aortic valve replacement (TAVR) are at risk for new-onset arrhythmia (NOA) that may require permanent pacemaker (PPM) implantation, resulting in decreased cardiac function. We aimed to investigate the factors that are associated with NOA after TAVR and to compare pre- and post-TAVR cardiac functions between patients with and without NOA using CT-derived strain analyses. METHODS: We included consecutive patients who underwent pre- and post-TAVR cardiac CT scans six months after TAVR. New-onset left bundle branch block, atrioventricular block, and atrial fibrillation/flutter lasting over 30 days after the procedure and/or the need for PPM diagnosed within 1 year after TAVR were regarded as NOA. Implant depth and left heart function and strains were analyzed using multi-phase CT images and compared between patients with and without NOA. RESULTS: Of 211 patients (41.7% men; median 81 years), 52 (24.6%) presented with NOA after TAVR, and 24 (11.4%) implanted PPM. Implant depth was significantly deeper in the NOA group than in the non-NOA group (- 6.7 ± 2.4 vs. - 5.6 ± 2.6 mm; p = 0.009). Left ventricular global longitudinal strain (LV GLS) and left atrial (LA) reservoir strain were significantly improved only in the non-NOA group (LV GLS, - 15.5 ± 4.0 to - 17.3 ± 2.9%; p < 0.001; LA reservoir strain, 22.3 ± 8.9 to 26.5 ± 7.6%; p < 0.001). The mean percent change of the LV GLS and LA reservoir strains was evident in the non-NOA group (p = 0.019 and p = 0.035, respectively). CONCLUSIONS: A quarter of patients presented with NOA after TAVR. Deep implant depth on post-TAVR CT scans was associated with NOA. Patients with NOA after TAVR had impaired LV reserve remodeling assessed by CT-derived strains. CLINICAL RELEVANCE STATEMENT: New-onset arrhythmia (NOA) following transcatheter aortic valve replacement (TAVR) impairs cardiac reverse remodeling. CT-derived strain analysis reveals that patients with NOA do not show improvement in left heart function and strains, highlighting the importance of managing NOA for optimal outcomes. KEY POINTS: • New-onset arrhythmia following transcatheter aortic valve replacement (TAVR) is a concern that interferes with cardiac reverse remodeling. • Comparison of pre-and post-TAVR CT-derived left heart strain provides insight into the impaired cardiac reverse remodeling in patients with new-onset arrhythmia following TAVR. • The expected reverse remodeling was not observed in patients with new-onset arrhythmia following TAVR, given that CT-derived left heart function and strains did not improve.

K2Mn3O(OH)(VO4)(V2O7) with Sawtooth Chains of Multivalent Manganese Triangular Trimer Units: Magnetic Susceptibility Shrouding a Long-Range Antiferromagnetic Order of Ferromagnetic Triangles.

ortho-Pyrovanadate (or ortho-diorthovanadate) K2Mn23+Mn2+O(OH)(VO4)(V2O7) synthesized hydrothermally crystallizes in the orthorhombic space group Pnma with a = 17.9155(5), b = 5.8940(2), c = 10.9971(3) Å, V = 1161.23(6) Å3, and Z = 4. Its crystal structure features linear chains of edge-sharing Mn3+O6 octahedra with every second pair of Mn3+O6 octahedra condensed with a Mn2+O6 octahedron on one side of a chain in a sawtooth pattern so that each sawtooth chain consists of a triangular trimer. These sawtooth chains, running parallel to the b axis and linked by the VO4 and V2O7 groups, form a framework with channels populated by K atoms. The new compound is a structural analogue of the mineral zoisite Ca2Al3O(OH)(SiO4)(Si2O7), showing a striking example of very different chemical compositions. K2Mn3O(OH)(VO4)(V2O7) undergoes a phase transition into an ordered antiferromagnetic (AFM) state at TN = 14.4 K, which was detected by high-frequency electron spin resonance as well as by both specific heat Cp and Fisher's specific heat d(χT)/dT measurements. However, this phase transition was not detected by magnetic susceptibility measurements. The origin of this puzzling observation was resolved by evaluating the spin exchanges of K2Mn3O(OH)(VO4)(V2O7), which revealed that each triangular trimer is a ferromagnetically coupled cluster, and the observed ordering involves an AFM ordering between the ferromagnetic (FM) clusters. This ordering is shrouded in magnetic susceptibility measurements due to the susceptibility contributions from the individual FM triangular trimers even below TN. We showed that the magnetic susceptibility of K2Mn3O(OH)(VO4)(V2O7) between ∼30 K and room temperature is satisfactorily described by an AFM chain made up of ferromagnetically coupled triangular clusters, as described by a few spin-exchange parameters.

Spatial mapping of polymicrobial communities reveals a precise biogeography associated with human dental caries.

Tooth decay (dental caries) is a widespread human disease caused by microbial biofilms. Streptococcus mutans, a biofilm-former, has been consistently associated with severe childhood caries; however, how this bacterium is spatially organized with other microorganisms in the oral cavity to promote disease remains unknown. Using intact biofilms formed on teeth of toddlers affected by caries, we discovered a unique 3D rotund-shaped architecture composed of multiple species precisely arranged in a corona-like structure with an inner core of S. mutans encompassed by outer layers of other bacteria. This architecture creates localized regions of acidic pH and acute enamel demineralization (caries) in a mixed-species biofilm model on human teeth, suggesting this highly ordered community as the causative agent. Notably, the construction of this architecture was found to be an active process initiated by production of an extracellular scaffold by S. mutans that assembles the corona cell arrangement, encapsulating the pathogen core. In addition, this spatial patterning creates a protective barrier against antimicrobials while increasing bacterial acid fitness associated with the disease-causing state. Our data reveal a precise biogeography in a polymicrobial community associated with human caries that can modulate the pathogen positioning and virulence potential in situ, indicating that micron-scale spatial structure of the microbiome may mediate the function and outcome of host-pathogen interactions.

Development and evaluation of case video-based debriefing on a simulation of high-risk neonatal care for nursing students in South Korea: a mixed-methods study.

BACKGROUND: The debriefing process after health care simulations should provide a psychologically safe learning environment for nursing students. Case video-based debriefing on a simulation of high-risk neonatal care can help nursing students feel psychologically safe and make learning more effective. In this study, we developed case video-based debriefing materials for a simulation of high-risk neonatal care for nursing students in South Korea and evaluated their effects. METHODS: This mixed-methods study, consisting of a survey and an in-depth interview, was conducted between August and December 2022. The participants were 27 nursing students for the development of the case video-based debriefing and 51 nursing students for the evaluation of its effects (25 in the experimental group and 26 in the control group) at a university in South Korea. A case video-based debriefing on a simulation of high-risk neonatal care was developed, and the experimental group took part in case video-based debriefing. The participants' self-efficacy, critical thinking, state anxiety, and satisfaction with practice were examined. The experimental group's learning experiences were explored. Quantitative data were analyzed using the chi-square test, the unpaired t-test, and repeated-measures analysis of variance. Qualitative content analysis was conducted. RESULTS: In the experimental group, critical thinking and satisfaction with practice increased to a greater extent than in the control group. However, the changes in self-efficacy and state anxiety were not significantly different between the experimental and control groups. Four categories were extracted from nursing students who participated in the case video-based debriefing: "learning facilitated by the simulation," "expanded learning," "safe learning environment," and "efficient utilization of case videos." CONCLUSIONS: Case video-based debriefing on a simulation of high-risk neonatal care effectively enhanced nursing students' critical thinking and satisfaction with practice, and it will be utilized to improve nursing students' competency in high-risk neonatal care.

High-Spin Orbital Interactions Across van der Waals Gaps Controlling the Interlayer Ferromagnetism in van der Waals Ferromagnets.

We examined what interactions control the sign and strength of the interlayer coupling in van der Waals ferromagnets such as Fe3-xGeTe2, Cr2Ge2Te6, CrI3, and VI3 to find that high-spin orbital interactions across the van der Waals gaps are a key to understanding their ferromagnetism. Interlayer ferromagnetic coupling in Fe3-xGeTe2, Cr2Ge2Te6, and CrI3 is governed by the high-spin two-orbital two-electron destabilization, but that in VI3 by the high-spin four-orbital two-electron stabilization. These interactions explain a number of seemingly puzzling observations in van der Waals ferromagnets.

Spin-Peierls Distortion of TiPO4 Causing a Transition from a Magnetic to a Nonmagnetic Insulating State and Its Effect on the Thermoelectric Properties: Density Functional Theory Analysis.

Density functional theory calculations were carried out to probe the nature of the electronic structure change in TiPO4 before and after its spin-Peierls distortion at 74.5 K, which is characterized by the dimerization in the chains of Ti3+ (d1) ions present in TiPO4. These calculations suggest strongly that the electronic state of TiPO4 is magnetic insulating before the distortion, but becomes nonmagnetic insulating after the distortion. Consistent with this suggestion, the phonon dispersion relations calculated for TiPO4 show that the undistorted TiPO4 is stable, while the distorted TiPO4 is not, if each Ti3+ ion has a spin moment, and that the opposite is true if each Ti3+ ion has no spin moment. These observations suggest that the driving force for the spin-Peierls distortion is the formation of direct metal-metal bonds leading to the dimerized chains of Ti3+ ions. The abrupt change in the electronic structures from a magnetic insulating state to a nonmagnetic insulating state explains why the spin-Peierls distortion of TiPO4 exhibits a first-order character. Although the two electronic states of TiPO4 before and after the distortion have a band gap, the substantial spin-Peierls distortion is found to enhance the thermoelectric properties of TiPO4.