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Author Correction: PDCD6 regulates lactate metabolism to modulate LC3-associated phagocytosis and antibacterial defense
Cox Regression Model in Clinical Research: Overview of Key Properties and Interpretation
Binary phase-only gallium oxide diffractive optical element for beam shaping
Abstract This study presents an experimentally validated demonstration of an inverse-optimized binary phase-only gallium oxide diffractive optical element (DOE). This DOE transforms an incident Gaussian beam into a square flat-top beam at the working plane. The design methodology for this binary phase-only DOE beam shaper is founded on an efficient process that integrates the modified Gerchberg-Saxton algorithm and the adjoint method. Experimental characterization of the fabricated device on a single crystal $$(\overline{2} \; 01)$$ gallium oxide substrate is conducted at a wavelength of 532 nm, confirming its ability to transform an incident Gaussian beam into a focused square flat-top beam. Such a device holds significant promise for various high-power laser applications, notably in laser welding and similar domains. Furthermore, because of the ultrawide bandgap of gallium oxide, DOEs operating at shorter wavelengths in the UV are also possible based on this technique.
Correction to Supporting Information for Takaki and Thirumalai, Sequence complexity and monomer rigidity control the morphologies and aging dynamics of protein aggregates
Ternary molecular switching in a single-crystal optical actuator with correlated crystal strain
Abstract A growing portfolio of single-crystal optical actuators is forging a new class of photonic materials that hold prospects for quantum technologies. Ruthenium-based complexes that exhibit this phenomenon via SO2-linkage photoisomerisation are of particular interest since they display multiple metastable states, once induced by green light; yet, complete photoconversion into each SO2-isomeric state is rarely achieved. We discover a new complex, trans-[Ru(SO2)(NH3)4(4-bromopyridine)]tosylate2, that produces 100% photoconverted η1-OSO isomeric crystal structures at 90 K, which fully transition into η2-(OS)O photoisomers upon warming to 100 K, while the dark-state η1-SO2 structure is wholly recovered by heating the crystal to room temperature. Crystal structures and optical-absorption profiles of each state are captured via in-situ light-induced single-crystal X-ray diffraction and optical-absorption spectroscopy. Results show that both photoisomeric species behave as optical switches, but with distinct optical properties. The photoisomerisation process causes thermally-reversible micro- and nanoscopic crystal strain, as characterised by optical microscopy and in-situ light-induced atomic-force microscopy.
Association of Coagulation Factor XI Level With Cardiovascular Events and Cardiac Function in Community-Dwelling Adults: From ARIC and CHS
BACKGROUND: Coagulation factor XI (FXI) inhibitors are a promising and novel class of anticoagulants, but a recent animal study found that FXI inhibition exacerbated diastolic dysfunction and heart failure (HF). In the ARIC study (Atherosclerosis Risk in Communities), we investigated whether plasma FXI level was associated with cardiovascular events and cardiac function. METHODS: ARIC was our primary analytic cohort. We included 4471 participants (median age, 75 years; 57% female; 17% Black) who attended visit 5 (2011–2013) with Somalogic-quantified plasma FXI levels and echocardiographic cardiac function. Prevalent HF and atrial fibrillation (AF) cases were defined as having HF or AF diagnosed at or before each participant’s visit 5 exam date. Incident HF and AF events were ascertained through 2021. Associations were assessed using Cox, logistic, and linear regression models. Primary prospective associations were also validated in the CHS (Cardiovascular Health Study) using an orthogonal FXI assay (enzyme-linked immunosorbent assay). RESULTS: At ARIC visit 5, there were 665 and 419 participants with prevalent HF and AF, respectively. During a median follow-up of 9 years, there were 580 and 788 incident HF and AF events, respectively. Lower FXI level was associated prospectively with higher incidence of HF (hazard ratio [HR], 1.36 [for each 1-unit decrement of log 2 -transformed FXI level] [95% CI, 1.01–1.83]) but not incident AF, and cross-sectionally with increased odds of AF (odds ratio [OR], 1.96 [95% CI, 1.23–3.07]) but not HF. In age-stratified analyses, decreased FXI was associated with higher incidence of HF in participants ≥75 years of age (HR, 1.57 [95% CI, 1.08–2.28]) but not <75 years of age (HR, 1.11 [95% CI, 0.68–1.79]). The inverse FXI–HF association was validated in CHS (HR, 1.18 [95% CI, 1.02–1.36]). At ARIC visit 5, lower FXI level was also associated with higher prevalence of diastolic dysfunction and worse E/A ratio, left atrial (LA) volume index, LA function, and left ventricular mass index, but not left ventricular ejection fraction or global longitudinal strain. CONCLUSIONS: Decreased FXI level is associated with greater incidence of HF, especially in older adults. It is also associated with prevalent AF, worse diastolic function, worse LA function, and greater LA size. More research is needed to assess potential unwanted effects of FXI inhibition on the risk of cardiovascular events and cardiac function.
Liraglutide combined with HIIT preserves contractile apparatus and blunts the progression of heart failure in diabetic cardiomyopathy rats
Antagonizing HFpEF by Targeting Fibrosis
Optimal scheduling and energy management of a multi-energy microgrid with electric vehicles incorporating decision making approach and demand response
Global Rounds: Advancing Cardiovascular Health in China
Interpretable deep learning of single-cell and epigenetic data reveals novel molecular insights in aging
Cardiac Reprogramming and Gata4 Overexpression Reduce Fibrosis and Improve Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. Pathological stimuli and interactions between cardiac fibroblasts (CFs) and other cell types may lead to cardiac fibrosis and diastolic dysfunction, which are hallmarks of HFpEF. Interstitial and perivascular cardiac fibrosis correlates with poor prognosis in HFpEF; however, mechanisms of fibrosis remain poorly elucidated, and targeted therapies are lacking. Cardiac reprogramming is a promising therapeutic approach for myocardial infarction that facilitates cardiac regeneration and antifibrosis action through Mef2c/Gata4/Tbx5/Hand2 (MGTH) overexpression in resident CFs. However, the efficacy of this approach on HFpEF is yet to be established. METHODS: Herein, we examined the effects of cardiac reprogramming in HFpEF using Tcf21 iCre /Tomato/MGTH2A transgenic mice, which expressed both MGTH and reporter expression in CFs for cardiac reprogramming and lineage tracing upon tamoxifen administration. To establish HFpEF model mice, we used a combination of a high-fat diet and nitric oxide synthase inhibition. Bulk RNA-sequencing, single-cell RNA-sequencing, and spatial transcriptomics were conducted to determine fibrotic mechanisms and the efficacy of cardiac reprogramming in HFpEF. We generated new tamoxifen-inducible transgenic mice overexpressing each reprogramming factor in CFs to investigate the effect of single factors. Last, we analyzed the effect of reprogramming factors in human CFs. RESULTS: Cardiac reprogramming with MGTH overexpression improved diastolic dysfunction, cardiac hypertrophy, fibrosis, inflammation, and capillary loss in HFpEF. Cardiac reprogramming converted approximately 1% of resident CFs into induced cardiomyocytes. Bulk RNA-seq indicated that MGTH overexpression upregulated genes related to heart contraction and suppressed the fetal gene program ( Nppa and Nppb ) and proinflammatory and fibrotic signatures. Single-cell RNA-sequencing and spatial transcriptomics revealed that multiple CF clusters upregulated fibrotic genes to induce diffuse interstitial fibrosis, whereas distinct CF clusters generated focal perivascular fibrosis in HFpEF. MGTH overexpression reversed these profibrotic changes. Among 4 reprogramming factors, only Gata4 overexpression in CFs reduced fibrosis and improved diastolic dysfunction in HFpEF by suppressing CF activation without generating new induced cardiomyocytes. Gata4 overexpression also suppressed profibrotic signatures in human CFs. CONCLUSIONS: Overexpressing Gata4 in CFs may be a promising therapeutic approach for HFpEF by suppressing fibrosis and improving diastolic dysfunction
Spatial differentiation and coupling between village development intensity and landscape pattern of 100 villages in Anhui, China
Abstract Spatial development and landscape pattern are fundamental elements of the land system of village. Analysing the spatial differentiation and coupling relationship between spatial development intensity and landscape pattern is of great significance for the development and protection of village land resources. In order to address the current research lack on the coupling response between village spatial development intensity and landscape pattern, a technical method for analysing the spatial differentiation and coupling relationship between village spatial development intensity and landscape pattern is constructed based on the methods of village spatial development intensity model, landscape pattern index, bivariate spatial autocorrelation model, coupling degree and coupling coordination degree model. Taking 100 villages in Anhui Province, China as an example, the spatial distribution characteristics and coupling characteristics of village spatial development intensity and landscape pattern are analysed. The results show that there are obvious regional differences in the spatial distribution of village spatial development intensity and landscape pattern in Anhui Province. The village spatial development intensity shows a pattern of the Northern Anhui plain region (NAPR) > along the Yangtze River plain region (YRPR) > Jiang-huai Hilly region (JHHR) > Southern Anhui mountainous region (SAMR) > Western Anhui mountainous region (WAMR). The village landscape pattern in NAPR and YRPR are high fragmentation, while the village in JHHR has the lowest fragmentation, and the villages in SAMR and WAMR show relatively low fragmentation. The spatial coupling relationship between village spatial development intensity and landscape pattern is mainly characterised by high-high clustering and low-high clustering. The coupling coordinated development of villages in NAPR is the best, followed by YRPR, JHHR and SAMR, and WAMR is the worst. There is only a significant multi-linear relationship between village landscape pattern and multiple spatial development intensity indicators in WAMR and NAPR. The spatial differentiation and coupling relationship are influenced by both natural geographical factors and human activity factors. Finally, the study puts forward some targeted countermeasures and suggestions. The research results can provide theoretical method and practical application reference for village land space development and protection and village planning.
Response by Shen et al to Letter Regarding Article, “Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF”
Particle swarm optimization based analysis to unlocking the neutrino mass puzzle using $$SU(2)_L \times U(1)_Y \times A_{4}\times S_2\times Z_{10} \times Z_{3}$$ flavor symmetry
Abstract New research has highlighted a shortfall in the Standard Model (SM) because it predicts neutrinos to have zero mass. However, recent experiments on neutrino oscillation have revealed that the majority of neutrino parameters indeed indicate their significant mass. In response, scientists are increasingly incorporating discrete symmetries alongside continuous ones for the observed patterns of neutrino mixing. In this study, we have examined a model within $$SU(2)_L \times U(1)_Y \times A_{4}\times S_2\times Z_{10} \times Z_{3}$$ symmetry to estimate the neutrino masses using particle swarm optimization technique for both mass hierarchy of neutrino. This model employed a hybrid seesaw mechanism, a combination of seesaw mechanism of type-I and type-II, to establish the effective Majorana neutrino mass matrix. After calculating the mass eigenvalues and lepton mixing matrix upto second order perturbation theory in this framework, this study seeks to investigate the scalar potential for vacuum expectation values (VEVs), optimize the parameters, $$U_{PMNS}$$ matrix, neutrino masses: $${m_{1}^{\prime }}^{(N)}(upper)=4.0000 \times 10^{-2}\ eV,$$ $${m_{2}^{\prime }}^{(N)}(upper)=4.0000 \times 10^{-2}\ eV,$$ $${m_{3}^{\prime }}^{(N)}(upper)=4.0000 \times 10^{-2}\ eV,$$ $${m_{1}^{\prime }}^{(I)}(upper)=3.8628\times 10^{-2}\ eV,$$ $${m_{2}^{\prime }}^{(I)}(upper)=4.0548\times 10^{-2}\ eV,$$ $${m_{3}^{\prime }}^{(I)}(upper)=3.8532\times 10^{-2}\ eV,$$ $${m_{1}^{\prime }}^{(N)}(lower)=2.0000 \times 10^{-2}\ eV,$$ $${m_{2}^{\prime }}^{(N)}(lower)=2.0000 \times 10^{-2}\ eV,$$ $${m_{3}^{\prime }}^{(N)}(lower)=2.0000 \times 10^{-2}\ eV,$$ $${m_{1}^{\prime }}^{(I)}(lower)=1.1049\times 10^{-2}\ eV,$$ $${m_{2}^{\prime }}^{(I)}(lower)=3.9298\times 10^{-2}\ eV$$ and $${m_{3}^{\prime }}^{(I)}(lower)=9.6381\times 10^{-3}\ eV,$$ effective neutrino mass parameters: $$\langle {m_{ee}} \rangle ^{N}(upper)=40.0050 \ meV,$$ $$\langle {m_{\beta }} \rangle ^{N}(upper)=40.0025\ meV,$$ $$\langle {m_{ee}} \rangle ^{I}(upper)=39.2181\ meV,$$ $$\langle {m_{\beta }} \rangle ^{I}(upper)=39.2257\ meV,$$ $$\langle {m_{ee}} \rangle ^{N}(lower)=20.0024\ meV,$$ $$\langle {m_{\beta }} \rangle ^{N}(lower)=20.0012\ meV,$$ $$\langle {m_{ee}} \rangle ^{I}(lower)=19.6608\ meV,$$ $$\langle {m_{\beta }} \rangle ^{I}(lower)=23.5908\ meV,$$ are predicted for both mass hierarchy through particle swarm optimization (PSO), showing strong agreement with recent experimental findings. The Dirac CP-violating phase $$\delta$$ is measured to be $$-\pi /2$$ .
Derivation and Validation of the PRECISE-HBR Score to Predict Bleeding After Percutaneous Coronary Intervention
BACKGROUND: Accurate bleeding risk stratification after percutaneous coronary intervention is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of patients at high bleeding risk. We derived and validated a novel bleeding risk score by augmenting the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. METHODS: The derivation cohort comprised 29 188 patients undergoing percutaneous coronary intervention, of whom 1136 (3.9%) had Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from 4 contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis ( P <0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) and 5970 patients from the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy-2) total cohort. RESULTS: The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white blood cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71–0.74) at apparent validation, 0.72 (95% CI, 0.70–0.73) at cross-validation, 0.74 (95% CI, 0.68–0.80) in MASTER DAPT, and 0.73 (95% CI, 0.66–0.79) in STOPDAPT-2, with superior discrimination compared with PRECISE-DAPT (cross-validation: ΔAUC, 0.01; P =0.02; MASTER DAPT: ΔAUC, 0.05; P =0.004; STOPDAPT-2: ΔAUC, 0.02; P =0.20) and other risk scores. In the derivation cohort, a cutoff of 23 points identified 11 414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white blood cell count, showed similar predictive ability. CONCLUSIONS: The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after percutaneous coronary intervention, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice.
Response of Red Sea phytoplankton biomass to marine heatwaves and cold-spells
Abstract In tropical oceans, phytoplankton experience significant alterations during marine heatwaves (MHWs), yet the consequences of reduced or absent marine cold-spells (MCSs) on these microscopic algae are currently overlooked. Synergistically combining in situ measurements, Argo-float data, remotely-sensed observations, and hydrodynamic model outputs, we explore such relationships in the Red Sea. Results show a long-term (1982 to 2018) gradual increase in MHW days (5–20 days/decade) and a clear decrease in MCS days (10–30 days/decade). Compound extreme temperature and chlorophyll-a events (Chl-a – an index of phytoplankton biomass) exhibit consistently lower Chl-a concentrations during MHWs and higher ones during MCSs, particularly in the northern and southern Red Sea. In these regions, during the main phytoplankton-growth period, the presence of MHWs/MCSs leads to respective Chl-a anomalies in 94% of the cases. Yet, phytoplankton responses in the central Red Sea are more complex, most likely linked to the region’s highly dynamic circulation (e.g., mesoscale anti-cyclonic eddies), and multiple nutrient sources. In the naturally warm and stratified ecosystem of the Red Sea, where deeper mixed layers enhance the transfer of nutrient-rich waters to the lit zone, the substantial reduction of MCSs could be more impactful for phytoplankton than the gradual rise of MHWs.
Touching the classical scaling in penetrative convection
The Cassini missions have identified the tiger stripes on Enceladus as the source of both thermal emission and plume jets. The hot spots in the tiger stripes are highly localized, and the plumes suggest active hydrothermal processes within the subglacial ocean of Enceladus. However, understanding the mechanism responsible for the heat anomalies in the tiger stripes remains a challenge. About 60 y ago, geoscientist George Veronis proposed a model for cold water oceans, along with the classical notion of a 1/3 scaling relationship between vertical heat transfer and the Rayleigh number ( Ra ), a dimensionless number representing the strength of buoyancy driving the convection within the fluid body. In this study, by delving into the steady coherent rolls arising in Veronis’ model, we first confirm the existence of the classical scaling as proposed. We identify two distinct pathways, characterized by different flow patterns, that converge to the unified classical scaling. In scenarios where stratification resulting from the density’s nonlinear temperature dependence is insignificant, convection rolls with fixed (width-to-height) aspect ratios achieve the classical scaling as Ra approaches infinity. Conversely, under high stratification levels, convection rolls with a heat-transport-maximizing aspect ratio achieve the classical scaling. This investigation also reveals a notable correspondence between optimal coherent rolls and turbulent flow patterns. Based on these coherent rolls, we offer insights into the formation of heat anomalies in the tiger stripes. The predicted heat flux through the ocean and the lateral flow length, are consistent with the measurements obtained by the Cassini spacecraft.