Browse Articles

Medical multimodal multitask foundation model for lung cancer screening

Retraction Note: Lateral palatal foramina do not indicate baleen in fossil whales

Correction for Baekgaard et al., Long-term employment and health effects of active labor market programs

FTO-associated osteoclastogenesis promotes alveolar bone resorption in apical periodontitis male rat via the HK1/USP14/RANK pathway

Retraction Note: Study of defensive behavior of a venomous snake as a new approach to understand snakebite

Splicing diversity enhances the molecular classification of pituitary neuroendocrine tumors

SNARE genes CcSec22 and CcSso1 coordinate fungal growth, sporulation, cell wall stress tolerance, endocytosis and full virulence in Cytospora chrysosperma

Correction to Doruska et al., Modeling how and why aquatic vegetation removal can free rural households from poverty-disease traps

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