BACKGROUND The presence of entrapped lung changes the appropriate management of malignant pleural effusion from pleurodesis to insertion of an indwelling pleural catheter. No methods currently exist ...to identify entrapped lung prior to effusion drainage. Our objectives were to develop a method to identify entrapped lung using tissue movement and deformation (strain) analysis with ultrasonography and compare it to the existing technique of pleural elastance (PEL). METHODS Prior to drainage, 81 patients with suspected malignant pleural effusion underwent thoracic ultrasound using an echocardiogram machine. Images of the atelectatic lower lobe were acquired during breath hold, allowing motion and strain related to the cardiac impulse to be analyzed using motion mode (M mode) and speckle-tracking imaging, respectively. PEL was measured during effusion drainage. The gold-standard diagnosis of entrapped lung was the consensus opinion of two interventional pulmonologists according to postdrainage imaging. Participants were randomly divided into development and validation sets. RESULTS Both total movement and strain were significantly reduced in entrapped lung. Using data from the development set, the area under the receiver-operating curves for the diagnosis of entrapped lung was 0.86 (speckle tracking), 0.79 (M mode), and 0.69 (PEL). Using respective cutoffs of 6%, 1 mm, and 19 cm H2 O on the validation set, the sensitivity/specificity was 71%/85% (speckle tracking), 50%/85% (M mode), and 40%/100% (PEL). CONCLUSIONS This novel ultrasound technique can identify entrapped lung prior to effusion drainage, which could allow appropriate choice of definitive management (pleurodesis vs indwelling catheter), reducing the number of interventions required to treat malignant pleural effusion.
Vasculogenesis is the de novo formation of a vascular network from individual endothelial progenitor cells occurring during embryonic development, organogenesis, and adult neovascularization. ...Vasculogenesis can be mimicked and studied in vitro using network formation assays, in which endothelial cells (ECs) spontaneously form capillary-like structures when seeded in the appropriate microenvironment. While the biochemical regulators of network formation have been well studied using these assays, the role of mechanical and topographical properties of the extracellular matrix (ECM) is less understood. Here, we utilized both natural and synthetic fibrous materials to better understand how physical attributes of the ECM influence the assembly of EC networks. Our results reveal that active cell-mediated matrix recruitment through actomyosin force generation occurs concurrently with network formation on Matrigel, a reconstituted basement membrane matrix regularly used to promote EC networks, and on synthetic matrices composed of electrospun dextran methacrylate (DexMA) fibers. Furthermore, modulating physical attributes of DexMA matrices that impair matrix recruitment consequently inhibited the formation of cellular networks. These results suggest an iterative process in which dynamic cell-induced changes to the physical microenvironment reciprocally modulate cell behavior to guide the formation and stabilization of multicellular networks.
The mechanisms that underlie various inflammation paradoxes, metabolically healthy obesity, and increased inflammations after inflammatory cytokine blockades and deficiencies remain poorly ...determined. We performed an extensive -omics database mining, determined the expressions of 1367 innate immune regulators in 18 microarrays after deficiencies of 15 proinflammatory cytokines/regulators and eight microarray datasets of patients receiving Mab therapies, and made a set of significant findings: 1) proinflammatory cytokines/regulators suppress the expressions of innate immune regulators; 2) upregulations of innate immune regulators in the deficiencies of IFNγ/IFNγR1, IL-17A, STAT3 and miR155 are more than that after deficiencies of TNFα, IL-1β, IL-6, IL-18, STAT1, NF-kB, and miR221; 3) IFNγ, IFNγR and IL-17RA inhibit 10, 59 and 39 proinflammatory cytokine/regulator pathways, respectively; in contrast, TNFα, IL-6 and IL-18 each inhibits only four to five pathways; 4) The IFNγ-promoted and -suppressed innate immune regulators have four shared pathways; the IFNγR1-promoted and -suppressed innate immune regulators have 11 shared pathways; and the miR155-promoted and -suppressed innate immune regulators have 13 shared pathways, suggesting negative-feedback mechanisms in their conserved regulatory pathways for innate immune regulators; 5) Deficiencies of proinflammatory cytokine/regulator-suppressed, promoted programs share signaling pathways and increase the likelihood of developing 11 diseases including cardiovascular disease; 6) There are the shared innate immune regulators and pathways between deficiency of TNFα in mice and anti-TNF therapy in clinical patients; 7) Mechanistically, up-regulated reactive oxygen species regulators such as myeloperoxidase caused by suppression of proinflammatory cytokines/regulators can drive the upregulation of suppressed innate immune regulators. Our findings have provided novel insights on various inflammation paradoxes and proinflammatory cytokines regulation of innate immune regulators; and may re-shape new therapeutic strategies for cardiovascular disease and other inflammatory diseases.
Purpose: This study investigates the impact of intertalker variations on the process of mapping acoustic variations on tone categories in two different tone languages. Method: Pitch stimuli ...manipulated from four voice ranges were presented in isolation through a blocked-talker design. Listeners were instructed to identify the stimuli that they heard as lexical tones in their native language. Results: Tone identification of Mandarin listeners exhibited relatively stable normalization regardless of the voice, whereas tone identification of Cantonese listeners was unstable and susceptible to the influence of intertalker variations. In the case of Cantonese listeners, intertalker variations had a larger effect on the perception of F0 height dimension than of F0 slope dimension. Conclusion: The comparison between Cantonese and Mandarin listeners' performances reveals an interaction of intertalker variations and the types of tone contrasts in each language. For Cantonese tones, which depend heavily on F0 height distinctions, intertalker variations result in F0 overlapping and, consequently, ambiguities among them in isolated tone perception. For Mandarin tones, which are distinctive in terms of their F0 contours, the differences in F0 contours alone seem sufficient to elicit reliable tone identification. Intertalker variations therefore have relatively limited effect on Mandarin tone perception.
•Ultrasound vaporizes the PFC phase in phase shift emulsions via ADV.•Classical nucleation theory predicted the stability of ADV-generated bubbles against condensation.•Bubble stability was dependent ...on the PFC species and ultrasound parameters.•Sequential payload delivery was achieved by generating transient and stable bubbles.•This technique could stimulate tissue regeneration via delivery of biomolecules.
Acoustically-responsive scaffolds (ARSs), which are fibrin hydrogels containing monodispersed perfluorocarbon (PFC) emulsions, respond to ultrasound in an on-demand, spatiotemporally-controlled manner via a mechanism termed acoustic droplet vaporization (ADV). Previously, ADV has been used to control the release of bioactive payloads from ARSs to stimulate regenerative processes. In this study, we used classical nucleation theory (CNT) to predict the nucleation pressure in emulsions of different PFC cores as well as the corresponding condensation pressure of the ADV-generated bubbles. According to CNT, the threshold bubble radii above which ADV-generated bubbles remain stable against condensation were 0.4 µm and 5.2 µm for perfluoropentane (PFP) and perfluorohexane (PFH) bubbles, respectively, while ADV-generated bubbles of any size in perfluorooctane (PFO) condense back to liquid at ambient condition. Additionally, consistent with the CNT findings, stable bubble formation from PFH emulsion was experimentally observed using confocal imaging while PFO emulsion likely underwent repeated vaporization and recondensation during ultrasound pulses. In further experimental studies, we utilized this unique feature of ADV in generating stable or transient bubbles, through tailoring the PFC core and ultrasound parameters (excitation frequency and pulse duration), for sequential delivery of two payloads from PFC emulsions in ARSs. ADV-generated stable bubbles from PFH correlated with complete release of the payload while transient ADV resulted in partial release, where the amount of payload release increased with the number of ultrasound exposure. Overall, these results can be used in developing drug delivery strategies using ARSs.
It has been shown that anti-inflammatory cytokines interleukin-35 (IL-35) and IL-10 could inhibit acute endothelial cell (EC) activation, however, it remains unknown if and by what pathways IL-35 and ...IL-10 could block atherogenic lipid lysophosphatidylcholine (LPC)-induced sustained EC activation; and if mitochondrial reactive oxygen species (mtROS) can differentiate mediation of EC activation from trained immunity (innate immune memory). Using RNA sequencing analyses, biochemical assays, as well as database mining approaches, we compared the effects of IL-35 and IL-10 in LPC-treated human aortic ECs (HAECs). Principal component analysis revealed that both IL-35 and IL-10 could similarly and partially reverse global transcriptome changes induced by LPC. Gene set enrichment analyses showed that while IL-35 and IL-10 could both block acute EC activation, characterized by upregulation of cytokines/chemokines and adhesion molecules, IL-35 is more potent than IL-10 in suppressing innate immune signatures upregulated by LPC. Surprisingly, LPC did not induce the expression of trained tolerance itaconate pathway enzymes but induced trained immunity enzyme expressions; and neither IL-35 nor IL-10 was found to affect LPC-induced trained immunity gene signatures. Mechanistically, IL-35 and IL-10 could suppress mtROS, which partially mediate LPC-induced EC activation and innate immune response. Therefore, anti-inflammatory cytokines could reverse mtROS-mediated acute and innate immune trans-differentiation responses in HAECs, but it could spare metabolic reprogramming and trained immunity signatures, which may not fully depend on mtROS. Our characterizations of anti-inflammatory cytokines in blocking mtROS-mediated acute and prolonged EC activation, and sparing trained immunity are significant for designing novel strategies for treating cardiovascular diseases, other inflammatory diseases, and cancers.
Congenital amusia is a lifelong neurodevelopmental disorder of fine-grained pitch processing. In this fMRI study, we examined the neural bases of congenial amusia in speakers of a tonal language – ...Cantonese. Previous studies on non-tonal language speakers suggest that the neural deficits of congenital amusia lie in the music-selective neural circuitry in the right inferior frontal gyrus (IFG). However, it is unclear whether this finding can generalize to congenital amusics in tonal languages. Tonal language experience has been reported to shape the neural processing of pitch, which raises the question of how tonal language experience affects the neural bases of congenital amusia. To investigate this question, we examined the neural circuitries sub-serving the processing of relative pitch interval in pitch-matched Cantonese level tone and musical stimuli in 11 Cantonese-speaking amusics and 11 musically intact controls. Cantonese-speaking amusics exhibited abnormal brain activities in a widely distributed neural network during the processing of lexical tone and musical stimuli. Whereas the controls exhibited significant activation in the right superior temporal gyrus (STG) in the lexical tone condition and in the cerebellum regardless of the lexical tone and music conditions, no activation was found in the amusics in those regions, which likely reflects a dysfunctional neural mechanism of relative pitch processing in the amusics. Furthermore, the amusics showed abnormally strong activation of the right middle frontal gyrus and precuneus when the pitch stimuli were repeated, which presumably reflect deficits of attending to repeated pitch stimuli or encoding them into working memory. No significant group difference was found in the right IFG in either the whole-brain analysis or region-of-interest analysis. These findings imply that the neural deficits in tonal language speakers might differ from those in non-tonal language speakers, and overlap partly with the neural circuitries of lexical tone processing (e.g. right STG).
•Cantonese amusics show abnormal neural activities in a widely distributed network;•Relative pitch processing deficit in right superior temporal gyrus and cerebellum;•Working memory and/or attention deficit in right middle frontal gyrus and precuneus;•Neural bases of Cantonese amusics partly overlap with brain network of lexical tone;•Neural bases of amusia in tonal languages differ from those in non-tonal languages.
A vast number of materials properties and phenomena are regulated by diffusion. However, diffusion coefficients from experiments and calculations are far from complete. Here, we report a compilation ...of vacancy formation energies (HVaF), vacancy migration energies (HVaM), vacancy activation energies (HVaQ), vacancy concentrations (CVa), and vacancy-mediated self-diffusion coefficients (DVa) as a function of temperature for 82 pure elements in bcc, fcc, and hcp structures by means of a comprehensive first-principles study. We assess the accuracy of four exchange-correlation (X–C) functionals for first-principles calculations, including the local density approximation (LDA), two generalized gradient approximations (PW91 and PBE), and PBEsol – the focus of the present work. To gain temperature-dependent diffusion properties, transition state structure searches are performed by the climbing image nudged elastic band method; and the needed equilibrium properties of energy (E0), volume (V0), bulk modulus (B0) and its pressure derivative (B′) for each structure of each element are estimated via an energy versus volume equation of state. Examination of the predicted quantities and available experimental data indicates that (i) PBEsol is a better selection in terms of getting accurate equilibrium and diffusion properties; (ii) the facility of vacancy migration can be understood from the redistribution of differential charge density, and anomalous energy pathways for vacancy migration are found for hcp Ce, La, Pr, Ti, and Zr within the basal plane; (iii) HVaQ can be predicted well from the melting point of a pure element and in particular a new relationship (HVaQ=B0V0/6), suggesting diffusivity is governed by interatomic bonding strength; and (iv) the computed quantities such as CVa, DVa, HVaF, HVaM, and HVaQ are in favorable accord with available experiments for most elements, but fall short for entropy-related properties. The present study of pure elements provides not only diffusion-related properties and a new understanding of diffusivity, but also a benchmark of first-principles calculations and a foundational dataset for the Materials Genome Initiative.
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Background
Patients with cardiac implantable electronic devices (CIEDs) frequently undergo transthoracic echocardiography (TTE). As a result, incidental mobile echodensities (MEDs) attached to device ...leads are commonly detected. The aim of this study was to estimate the incidence and clinical outcomes of incidental MEDs on CIED leads.
Methods
A retrospective analysis performed between 2011 and 2018 identified 3548 TTE studies performed on 1849 patients with CIEDs.
Results
MEDs were identified in 30 patients (1.6%) without clinical suspicion of infective endocarditis (IE). Patients with incidental MEDs were apyrexial, and those tested demonstrated low inflammatory markers and negative blood cultures (BC). In this group, the majority (83%) of MEDs were in the right atrium and no MEDs were detected near the tricuspid valve. Transesophageal echocardiography (TEE) did not influence clinical outcomes. No patient required long‐term antibiotics or lead extraction and no IE‐related deaths were identified from electronic health records during a mean follow‐up period of 43 months (1‐89). In contrast, nine patients with suspected IE were all pyrexial with elevated inflammatory markers, had positive BC, and had proven IE. In these cases, the majority of MEDs were at the device lead/tricuspid valve interface. MEDs close to the tricuspid valve were strongly associated with IE (P < .0001).
Conclusions
The incidence of MEDs on CIED leads detected on routine TTE was 1.6%. Conservative management of asymptomatic patients with normal inflammatory markers and BC without TEE, antibiotics, or lead extraction did not reveal any signal for long‐term adverse events within the limitations of the study.
Engineering surfaces that enable the dynamic tuning of their wetting state is critical to many applications including integrated microfluidics systems, flexible electronics, and smart fabrics. ...Despite extensive progress, most of the switchable surfaces reported are based on ordered structures that suffer from poor scalability and high fabrication costs. Here, a robust and facile bottom‐up approach is demonstrated that allows for the dynamical and reversible switching between lotus leaf (repulsive) and rose petal (adhesive) states by strain engineering of wave‐like nanofiber layers. Interestingly, it is found that the controlled switching between these two distinctive states is sensitive to the shape of the nanofibers. Moreover, it is observed that the structural integrity of the nanofibers is fully preserved during multicycle dynamic switching. The application of these optimal structures is showcased as mechanical hands demonstrating the capture of water microdroplets and their subsequent release in a well‐controlled manner. It is envisioned that this low‐cost and highly scalable surface texture is a powerful platform for the design of portable microfluidics systems, and the fabrication of large‐scale devices for ambient humidity harvesting and water purification.
A disordered surface texture that enables robust dynamic and reversible tuning of its wetting state from adhesive rose petal to highly repulsive lotus leaf superhydrophobicity is presented. This optimal wave‐like nanofiber morphology demonstrates multicycle hand‐like manipulation of microdroplets with mechanically actuated lift‐off and release. The tunable structure offers a low‐cost and scalable solution for fabrication of switchable water adhesive/repulsive surfaces.
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