Browse Articles

Does integration matter? an international cross-sectional study on the relationship between perceived public health and primary care integration and COVID-19 vaccination rates

Background Immunisation against COVID-19 is crucial for controlling the pandemic, yet global challenges persist in vaccine coverage and equitable distribution. A well-integrated primary health care approach can enhance vaccination programmes. Aim To explore the relationship between perceived PC (primary care)-PH (public health) integration, as well as other vaccination program implementation factors, and national COVID-19 vaccination coverage. Design and setting A convenience sample of self-identified primary care professionals completed an online survey on COVID-19 vaccination programme implementation and their perceptions of PC-PH integration. Methods Countries with ≥5 responses were included in the data analysis. COVID-19 vaccination implementation approach and perceived PC-PH integration against COVID-19 vaccination coverage was investigated using bivariate and subgroup analyses, Spearman correlation, and linear regression. Results A total of 394 responses from 32 countries were analysed. Participants included primary care providers, academics, and researchers. The median national COVID-19 vaccination coverage was 28.41% at time of study. Perceived barriers included patient hesitancy and vaccine supply shortages, while facilitators included vaccine product choices, equity, and community engagement. The study revealed a positive relationship between perceptions of PC-PH integration and national vaccination coverage in upper-middle and lower-middle income countries. Conclusion Perceived PC-PH integration increased with decreasing economic quartiles and this perception was linked to actual national vaccination coverage. Integration may be especially important for countries with lesser vaccine supply. High-income countries may benefit from increased collaboration between PC and PH to enhance vaccination efficiency. The findings contribute to understanding the role of PC-PH integration in vaccination programmes in different settings.

Grain boundary diffusion cannot explain the W isotope heterogeneities of the deep mantle

PGLYRP1-mediated intracellular peptidoglycan detection promotes intestinal mucosal protection

Magnetic Bloch states at integer flux quanta induced by super-moiré potential in graphene aligned with twisted boron nitride

Early Alzheimer’s Disease with frequent neuritic plaques harbors neocortical tau seeds distinct from primary age-related tauopathy

Distorted learning from local metacognition supports transdiagnostic underconfidence

Abstract Individuals experiencing symptoms of anxiety and depression have been shown to exhibit persistent underconfidence. The origin of such metacognitive biases presents a puzzle, given that individuals should be able to learn appropriate levels of confidence from observing their own performance. In two large general population samples ( N  = 230 and N  = 278), we measure both 'local' confidence in individual task instances and 'global' confidence as longer-run self-performance estimates while manipulating external feedback. Global confidence is sensitive to both local confidence and feedback valence—more frequent positive (negative) feedback increases (respectively decreases) global confidence, with asymmetries in feedback also leading to shifts in affective self-beliefs. Notably, however, global confidence exhibits reduced sensitivity to instances of higher local confidence in individuals with greater subclinical anxious-depression symptomatology, despite sensitivity to feedback valence remaining intact. Our finding of blunted sensitivity to increases in local confidence offers a mechanistic basis for how persistent underconfidence is maintained in the face of intact performance.

Entanglement growth from squeezing on the MPS manifold

Abstract Finding suitable characterizations of quantum chaos is a major challenge in many-body physics, with a central difficulty posed by the linearity of the Schrödinger equation. A possible solution for recovering non-linearity is to project the dynamics onto some variational manifold. The classical chaos induced via this procedure may be used as a signature of quantum chaos in the full Hilbert space. Here, we demonstrate analytically a previously heuristic connection between the Lyapunov spectrum from projection onto the matrix product state (MPS) manifold and the growth of entanglement. This growth occurs by squeezing a localized distribution on the variational manifold. The process qualitatively resembles the Cardy-Calabrese picture, where local perturbations to a moving MPS reference are interpreted as bosonic quasi-particles. Taking careful account of the number of distinct channels for these processes recovers the connection to the Lyapunov spectrum. Our results rigorously establish the physical significance of the projected Lyapunov spectrum, suggesting it as an alternative method of characterizing chaos in quantum many-body systems, one that is manifestly linked to classical chaos.

Facilitating alkaline hydrogen evolution kinetics via interfacial modulation of hydrogen-bond networks by porous amine cages

Abstract The electrode-electrolyte interface is pivotal in the electrochemical kinetics. However, modulating the electrochemical interface at the atomic or molecular level is challenging due to the lack of efficient interfacial regulators. Here, we employ a porous amine cage as an interfacial modifier to Pt cluster in a confining configuration, largely enhancing alkaline HER kinetics by facilitating charge transfer. In situ electrochemical surface-enhanced Raman spectra, in combination with the ab initio molecular dynamics simulation, elucidates that the interaction between water and the -NH- moiety of cage frame softens the H-bonds net of interfacial water, making it more flexible for charge transfer. Moreover, our investigation pinpointed that the -NH- moiety acted as a pump for charge transfer by Grotthuss mechanism, lowering the kinetic barrier for hydrogen adsorption. Our findings highlight the strategy of establishing a soft-confining interfacial modifier by porous cage, offering opportunities to optimize electrochemical interfaces and promote reaction kinetics in a targeted way.

Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour

Abstract Signalling at dopamine D2/D3 receptors is thought to underlie motivated behaviour, pleasure experiences and emotional expression based on animal studies, but it is unclear if this is the case in humans or how this relates to neural processing of reward stimuli. Using a randomised, double-blind, placebo-controlled, crossover neuroimaging study, we show in healthy humans that sustained dopamine D2/D3 receptor antagonism for 7 days results in negative symptoms (impairments in motivated behaviour, hedonic experience, verbal and emotional expression) and that this is related to blunted striatal response to reward stimuli. In contrast, 7 days of partial D2/D3 agonism does not disrupt reward signalling, motivated behaviour or hedonic experience. Both D2/D3 antagonism and partial agonism induce motor impairments, which are not related to striatal reward response. These findings identify a central role for D2/D3 signalling and reward processing in the mechanism underlying motivated behaviour and emotional responses in humans, with implications for understanding neuropsychiatric disorders such as schizophrenia and Parkinson’s disease.

Tandem reductive amination and deuteration over a phosphorus-modified iron center

Systematic inference of super-resolution cell spatial profiles from histology images

Increasingly efficient chromatin binding of cohesin and CTCF supports chromatin architecture formation during zebrafish embryogenesis

Abstract The three-dimensional folding of chromosomes is essential for nuclear functions such as DNA replication and gene regulation. The emergence of chromatin architecture is thus an important process during embryogenesis. To shed light on the molecular and kinetic underpinnings of chromatin architecture formation, we characterized biophysical properties of cohesin and CTCF binding to chromatin and their changes upon cofactor depletion using single-molecule imaging in live developing zebrafish embryos. We found that chromatin-bound fractions of both cohesin and CTCF increased significantly between the 1000-cell and shield stages, which we could explain through changes in both their association and dissociation rates. Moreover, increasing binding of cohesin restricted chromatin motion, potentially via loop extrusion, and showed distinct stage-dependent nuclear distribution. Polymer simulations with experimentally derived parameters recapitulated the experimentally observed gradual emergence of chromatin architecture. Our findings reveal molecular kinetics underlying chromatin architecture formation during zebrafish embryogenesis.

Author Correction: Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy

TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts

Abstract TGM6 is a natural antagonist of mammalian TGF-β signaling produced by the murine helminth parasite Heligmosomoides polygyrus. It differs from the previously described agonist, TGM1 (TGF-β Mimic-1), in that it lacks domains 1/2 that bind TGFBR1. It nonetheless retains TGFBR2 binding through domain 3 and potently inhibits TGF-β signaling in fibroblasts and epithelial cells, but does not inhibit TGF-β signaling in T cells, consistent with divergent domains 4/5 and an altered co-receptor binding preference. The crystal structure of TGM6 bound to TGFBR2 reveals an interface remarkably similar to that of TGF-β with TGFBR2. Thus, TGM6 has adapted its structure to mimic TGF-β, while engaging a distinct co-receptor to direct antagonism to fibroblasts and epithelial cells. The co-expression of TGM6, along with immunosuppressive TGMs that activate the TGF-β pathway, may minimize fibrotic damage to the host as the parasite progresses through its life cycle from the intestinal lumen to submucosa and back again. The co-receptor-dependent targeting of TGFBR2 by the parasite provides a template for the development of therapies for targeting the cancer- and fibrosis-promoting activities of the TGF-βs in humans.

Bio-inspired electronics: Soft, biohybrid, and “living” neural interfaces

Abstract Neural interface technologies are increasingly evolving towards bio-inspired approaches to enhance integration and long-term functionality. Recent strategies merge soft materials with tissue engineering to realize biologically-active and/or cell-containing living layers at the tissue-device interface that enable seamless biointegration and novel cell-mediated therapeutic opportunities. This review maps the field of bio-inspired electronics and discusses key recent developments in tissue-like and regenerative bioelectronics, from soft biomaterials and surface-functionalized bioactive coatings to cell-containing ‘biohybrid’ and ‘all-living’ interfaces. We define and contextualize key terminology in this emerging field and highlight how biological and living components can bridge the gap to clinical translation.

Kinetic cation effect in alkaline hydrogen electrocatalysis and double layer proton transfer

Tightly bonded excitons in chiral metal clusters for luminescent brilliance

Fabrication of atomically dispersed barium hydride catalysts for the synthesis of deuterated alkylarenes

Molecularly engineered supramolecular fluorescent chemodosimeter for measuring epinephrine dynamics

Abstract Accurately visualizing epinephrine (EP) activity is essential for understanding its physiological functions and pathological processes in brain. However, to the best of our knowledge, reliable, rapid, and specifical measurement of EP dynamics at cellular and in vivo level hasn’t been previously reported. Herein, we report the probe for EP imaging and biosensing in neurons and living brain of freely behaving animals, based on creating a series of supramolecular fluorescent chemodosimeters through host-guest interaction. The optimized chemodosimeter enables real-time imaging and quantifying of EP with high specificity, sensitivity, signal-to-noise ratio, and rapid kinetics (~240 ms) in neurons, brain tissues and zebrafish. More significantly, we demonstrate real-time monitoring of EP in 26 regions within deep brain of freely behaving male mice, unraveling an augmented EP concentration in the amygdala, thalamus, hypothalamus, hippocampus and striatum under fear-induced stress. These findings highlight our chemodosimeter as a powerful tool for precise measurements of EP dynamics in diverse model organisms.

Cerebellar output neurons can impair non-motor behaviors by altering development of extracerebellar connectivity