Search

To explore the value of morphology and diffusion features on CT and MRI in the characterization of external auditory canal and middle ear tumors (EAMETs).Forty-seven patients with histologically proved EAMETs (23 benign and 24 malignant) who underwent CT and MRI were retrospectively analyzed in this study. CT and MRI characteristics (including size, shape, signal intensity, border, enhancement degree, and bone changes) and apparent diffusion coefficient (ADC) value were analyzed and compared between benign and malignant EAMETs. Logistic regression, receiver operating characteristic (ROC) curve, and Delong test were performed to assess the diagnostic performance.Compared with benign tumors, the malignant EAMETs are characterized by irregular shape, ill-defined border, invasive bone destruction, and intense enhancement (all p 0.05). There were no significant differences on the size and signal intensity between benign and malignant tumors. The ADC value of malignant tumors were (879.96 ± 201.15) × 10Some CT and MRI characteristics are helpful in identifying malignant EAMETs from benign ones (especially ill-defined margin, invasive bone destruction, and low ADC value), and the combination of morphology and diffusion features on CT and MRI has best diagnostic efficiency for discriminating these two entities.

RNA-guided CRISPR (RNA-targeting clustered regularly interspaced short palindromic repeats) effector Cas13d is the smallest Class II subtype VI proteins identified so far. Here, two recently identified Cas13d effectors from Eubacterium siraeum (Es) and Ruminococcus sp. (Rsp) were characterized and applied for sensitive nucleic acid detection. We demonstrated that the special target triggered collateral cleavage of these two Cas13d orthologs could provide rapid target RNA detection in picomolar range and then the tolerance for mismatch between crRNA and target RNA was characterized as well. Finally, an additional single mismatch was introduced into crRNA to enhance the two Cas13d orthologs mediated detection of low variant allele fraction, 0.1% T790M. Overall, this study demonstrated that both EsCas13d and RspCas13d could robustly detect target RNA carrying special single-nucleotide variation with high specificity and sensitivity, thereby providing newly qualified machinery in toolbox for efficient molecular diagnostics.

This study aimed to evaluate the synthetic MRI (syMRI), its combination with diffusion-weighted imaging (DWI), and morphological features for discriminating benign from metastatic retropharyngeal lymph nodes (RLNs).Fifty-eight patients with a total of 63 RLNs (21 benign and 42 metastatic) were enrolled. The mean and standard deviation of syMRI-derived relaxometry parameters (T1, T2, PD; T1Benign RLNs had significantly higher T1, T2, PD, and T1The value of syMRI has been validated in differential diagnosis of benign and metastatic RLNs, and syMRI + DWI + morphological features can further improve the diagnostic efficiency for discriminating these two entities.• Synthetic MRI was useful in differential diagnosis of benign and metastatic RLNs. • The combination of syMRI, DWI, and morphological features can significantly improve the diagnostic efficiency.

The unique hollow nanostructures (Ni1-xFex-HP) were fabricated by the template-engaged pyrolysis from amorphous (bi)metal-organic-frameworks with tunable polyhedron-like morphology by various Fe content. Ni1-xFex-HP features as hollow polyhedron with mesoporous wall, consisting of dominant metal/alloy coupled with a small fraction of their oxides and few-layer N-graphene shell (FLNG). Thanks for the structural and compositional feature to strengthen the synergism of Ni, NiO and N-graphene on HER, as well as FeNi alloy, NiFe oxide, and N-graphene on OER, the optimal Ni-HP and Ni0.5Fe0.5-HP octahedron present good bifunctional properties for HER (overpotential of 215 mV to reach 10 mA cm−2, Tafel slope of 133 mV dec−1) and OER (overpotential of 280 mV to reach 10 mA cm−2, Tafel slope of 79 mV dec−1) on glass carbon electrode in 1.0 M alkaline solution. Moreover, the electrocatalytic performance can be further enhanced by directly coating on nickel foam (NF), where the overpotentials of Ni-HP/NF and Ni0.5Fe0.5-HP/NF is only 98 and 220 mV at current density of 10 mA cm−2 for HER and OER, respectively. The integrated asymmetrical two-electrode configuration (Ni0.5Fe0.5-HP/NF||Ni-HP/NF) displays low cell voltage of 1.57 V to reach 10 mA cm−2, accompanying with strong durability for overall alkaline water splitting. This work opens up an effectively time-saving strategy using aMOFs with well-defined structure instead of highly crystalline metal-organic frameworks (cMOFs) as precursor to design hollow and nanostructured hybrids for energy conversion.

Ultrathin nickel-iron carbonate hydroxides nanosheets/sulfides (denoted as NixFeyS/CH) are fabricated by sulfurizing treatment of nickel-iron carbonate hydroxide (NixFeyCH). The partial sulfuration of NiFe carbonate hydroxides by replacing the CO3/OH groups with the S group can well remain the hexagonal morphology, regulate the electronic structure and expose more electrochemical active sites. Benefiting from the ultrathin-layered sheet with mesoporous structure for more available active sites, the strong coupling between metal carbonate hydroxides/sulfides, as well as bimetal synergism for modulation the composition and electronic structure, the optimal NixFeyS/CH exhibits excellent OER catalytic performance, which reaches 20 mA cm−2 at an ultra-small overpotential of 261 mV, lower Tafel slope (103 mV dec−1) and outstanding stability. This work highlights the importance regarding the modulation of composition and electronic structure by the interface coupling and bimetal synergism for boosting OER performance.

Background Transcatheter aortic-valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis who are at increased risk for death from surgery; less is know...

A lamellar reverse micelle directed assembly strategy was proposed to integrate NiCo layered hydroxides (NiCoDH) nanodots and NiCo sulfide (NiCoS) nanosheets (NiCoDH/NiCoS) by one-step solvothermal method. The NiCoDH/NiCoS features with an interconnected 3D architecture composed of ultrathin amorphous NiCoS nanosheets (∼1.5 nm), decorated by ultra-small NiCoDH nanodots (2–3 nm). The optimal NiCoDH/NiCoS exhibits a low overpotential of 303 mV at current density of 20 mA cm−2, together with a small Tafel slope of 77.6 mV dec−1, the high Faraday efficiency of about 95% as well as good stability. The excellent OER performance and enhanced stability should be ascribed to the strong interface-coupling of NiCoDH nanodots/NiCoS nanosheets, highly synergistic effect of bimetal Co and Ni, amorphous-like structure to expose more active sites, and interconnected 3D architecture for effective mass transport and structural stability. This work provides a significant insight regarding the strong interface-coupling effect on OER electrocatalysis, and offers a new strategy to design highly efficient OER catalysts.

The development of designing and searching inexpensive electrocatalysts with high activity for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is significant to enable water splitting as a future renewable energy source. Herein, we synthesize a new CoP(MoP)-CoMoO3 heterostructure coated by a N-doped carbon shell [CoP(MoP)-CoMoO3@CN] via thermal decomposition and phosphatizing of the CoMoO4·0.9H2O nanowires encapsulated in N-doped carbon. At 10 mA·cm–2, this CoP(MoP)-CoMoO3@CN nanocomposite exhibits superior electrocatalytic activity at low overpotentials of 296 mV for OER and 198 mV for HER in alkaline media. More importantly, we achieve a current density of 10 mA·cm–2 at 1.55 V by using this CoP(MoP)-CoMoO3@CN as both cathode and anode for overall water splitting. This promising performance could be due to the high activity of CoP(MoP)-CoMoO3 and the good conductivity of the external mesoporous N-carbon shell, which makes the CoP(MoP)-CoMoO3@CN nanowires a competitive alternati...

Fragmented DNA from blood plasma, i.e., cell-free DNA, has received great interest as a noninvasive diagnostic biomarker for "point-of-care" testing or liquid biopsy. Here, we present a new approach for accurate genotyping of highly fragmented DNA. Based on toehold-mediated strand displacement, a toehold-assisted padlock probe and toehold blocker were designed and demonstrated with new controllability in significantly suppressing undesired cross-reaction, promoting target recycling and point mutation detection by tuning the thermodynamic properties. Furthermore, toehold-assisted padlock probe systems were elaborately designed for 14 different single-nucleotide variants (SNVs) and were demonstrated to be able to detect low concentration of variant alleles (0.1%). In addition, a target, spanning a narrow sequence window of 29 nucleotides on average is sufficient for the toehold-assisted padlock probe system, which is valuable for the analysis of highly fragmented DNA molecules from clinical samples. We further demonstrated that the toehold-assisted padlock probe, in combination with a unique asymmetric PCR technique, could detect more target SNVs at low allele fractions (1%) in highly fragmented cfDNA. This allows accurate genotyping and provides a new commercial approach for high-resolution analysis of genetic variation.

In DNA data storage, the massive sequence complexity creates challenges in repeatable and efficient information readout. Here, our study clearly demonstrated that PCR created significant DNA amplification biases due to its inherent mechanism of inefficient priming, product-as-template, and error-spreading prone, which greatly hinder subsequent applications such as data retrieval in DNA-based storage. To mitigate the amplification bias, we recruited an isothermal DNA amplification by combining strand displacement amplification (SDA) with magnetic beads (MB) DNA immobilization for robust, repeated, and low-bias amplification of DNA oligo pool, comprising over 100 thousand oligos, in a primer-free and low-error-spreading fashion. Furthermore, we introduced oligo pool normalization (OPN), a cost-effective and scalable method for normalizing an oligo pool, by which oligo pools comprising from 256 to 1024 distinct oligos were simply modified with improved Gini-index. Therefore, we believe that the combination of SDA and OPN can provide an ideal amplification mechanism for a low-bias copy of a large oligo pool, which is of vital importance for successful data retrieval in DNA information storage.

Background Paravalvular regurgitation (PVR) following transcatheter aortic valve replacement (TAVR) is associated with increased morbidity and mortality. PVR continues to plague TAVR jeopardizing long-term results. New device iterations, such as the self-expandable Evolut PRO valve, aim to decrease PVR while maintaining optimal hemodynamics. This study sought to evaluate clinical and hemodynamic performance of the Evolut PRO system at 3 years. Methods The Evolut PRO US Clinical Study included 60 patients at high or extreme surgical risk undergoing TAVR with the Evolut PRO valve at 8 centers in the United States. Clinical outcomes were evaluated using Valve Academic Research Consortium (VARC)-2 criteria and included all-cause mortality, cardiovascular mortality , disabling stroke and valve complications. An independent core laboratory centrally assessed all echocardiographic measures. Results At 3 years, all-cause mortality was 25.8% (cardiovascular mortality 16.5%) and the disabling stroke rate was 10.7%. There were no cases of repeat valve intervention, endocarditis or coronary obstruction . Valve thrombosis was identified in 1 patient 2 years post-procedure and was treated medically. Hemodynamics at 3 years included a mean gradient of 7.2 ± 4.5 mm Hg, an effective orifice area of 2.0 ± 0.5 cm 2 , and 88.2% of patients had no or trace PVR. The remaining patients had mild PVR. Most of the surviving patients (80.6%) had New York Heart Association class I symptoms at 3 years. Conclusion Outcomes at 3-years following TAVR with a contemporary self-expanding prosthesis are favorable, with no signal of valve deterioration , excellent hemodynamics including very low prevalence of PVR.

DNA emerged as a novel potential material for mass data storage, offering the possibility to cheaply solve a great data storage problem. Large oligonucleotide pools demonstrated high potential of large-scale data storage in test tube, meanwhile, living cell with high fidelity in information replication. Here we show a mixed culture of bacterial cells carrying a large oligo pool that was assembled in a high-copy-number plasmid was presented as a stable material for large-scale data storage. The underlying principle was explored by deep bioinformatic analysis. Although homology assembly showed sequence context dependent bias, the large oligonucleotide pools in the mixed culture were constant over multiple successive passages. Finally, over ten thousand distinct oligos encompassing 2304 Kbps encoding 445 KB digital data, were stored in cells, the largest storage in living cells reported so far and present a previously unreported approach for bridging the gap between in vitro and in vivo systems., Hao, Qiao, Gao et al. show that over ten thousand oligonucleotides encoding 445 KB of digital data can be stored in cultured bacterial cells. Data storage in living cells increases the information storage capacity while enabling its economical propagation.

DNA emerged as novel material for mass data storage, the serious problem human society is facing. Taking advantage of current synthesis capacity, massive oligo pool demonstrated its high-potential in data storage in test tube. Herein, mixed culture of bacterial cells carrying mass oligo pool that was assembled in a high copy plasmid was presented as a stable material for large scale data storage. Living cells data storage was fabricated by a multiple-steps process, assembly, transformation and mixed culture. The underlying principle was explored by deep bioinformatic analysis. Although homology assembly showed sequence context dependent bias but the massive digital information oligos in mixed culture were constant over multiple successive passaging. In pushing the limitation, over ten thousand distinct oligos, totally 2304 Kbps encoding 445 KB digital data including texts and images, were stored in bacterial cell, the largest archival data storage in living cell reported so far. The mixed culture of living cell data storage opens up a new approach to simply bridge the in vitro and in vivo storage system with combined advantage of both storage capability and economical information propagation.

As a key element of genome editing, donor DNA introduces the desired exogenous sequence while working with other crucial machinery such as CRISPR-Cas or recombinases. However, current methods for the delivery of donor DNA into cells are both inefficient and complicated. Here, we developed a new methodology that utilizes rolling circle replication and Cas9 mediated (RC-Cas-mediated) in vivo single strand DNA (ssDNA) synthesis. A single-gene rolling circle DNA replication system from Gram-negative bacteria was engineered to produce circular ssDNA from a Gram-positive parent plasmid at a designed sequence in Escherichia coli. Furthermore, it was demonstrated that the desired linear ssDNA fragment could be cut out using CRISPR-associated protein 9 (CRISPR-Cas9) nuclease and combined with lambda Red recombinase as donor for precise genome engineering. Various donor ssDNA fragments from hundreds to thousands of nucleotides in length were synthesized in E. coli cells, allowing successive genome editing in growing cells. We hope that this RC-Cas-mediated in vivo ssDNA on-site synthesis system will be widely adopted as a useful new tool for dynamic genome editing.

In DNA data storage, the huge sequence complexity is challenging for repeatable and efficient information reading from massive DNA oligo pool. Here, we demonstrated that synthetic oligo pool comprising over ten thousand strands was largely skewed by PCR process due to its inherent mechanism of inefficient priming, product-as-template, error-spreading prone, which caused serious oligos dropout, over 50% oligos lost in repeated PCR amplification, much more fatal than base mutant for correct information retrieve. Therefore, we developed a new biochemical framework isothermal DNA reading (iDR) from large-scale oligo pool normalization (OPN) and isothermal amplification. Due to its priming-free and error-spreading proof, it achieved low-biased and stable amplification even for successive 10 times deep-reading without performance lost, the first repeatable DNA storage. Furthermore, the skewed oligo pool with uneven molecule copy number of each oligos was rectified by a total 1280 chemically synthesized OPN-probes, the largest scale oligo normalization so far, and the necessary amount of sequencing reads for perfect oligos retrieve was further largely decreased. These advanced features enable the iDR chemical framework being ideal for manipulating the huge sequence complexity and building the sustainable and efficient DNA storage "hardware".

Electrochemical water splitting is a promising way for the sustainable production of hydrogen, but the efficiency of the overall water-splitting reaction largely depends on the oxygen evolution reaction (OER) because of its sluggish kinetics. Herein, a series of hierarchical ZnCo2 O4 /Co3 O4 /NC-CNT (NC-CNT=nitrogen-rich carbon nanotube) mesoporous dodecahedrons grafted to carbon nanotubes have been synthesized from ZnCo bimetallic zeolitic imidazolate frameworks (ZnCo-ZIFs) through sequential pyrolysis in nitrogen and mild oxidation in air. The simultaneous modulation of oxygen vacancies, composition, and hierarchical mesoporous architecture remarkably enhanced their electronic conduction and the amount and reactivity of accessible actives; thus boosting their intrinsic activity in the OER. The optimal ZnCo2 O4 /Co3 O4 /NC-CNT-700 sample exhibited a large current density of 50 mA cm-2 at a potential of 1.65 V, a small Tafel slope of 88.5 mV dec-1 , and superior stability in alkaline media. This work should provide a facile strategy for the rational design of advanced OER catalysts by simultaneous engineering of oxygen vacancies and composition.

Water electrolysis provides a promising way to achieve sustainable hydrogen production, which strongly depends on highly effective electrocatalysts for industrial application. Herein, Mo2C/MoO2 heteronanorods have been synthesized by means of a simple self-templated carbothermal reduction of polymolybdate-melamine precursor. Through manipulating the pyrolysis temperature, the optimal Mo2C/MoO2-650 heteronanorods show a low overpotential (168, 290, and 204 mV) to achieve current density of 10 mA cm–2 in 0.5 M H2SO4, 0.1 M PBS, and 1.0 KOH, respectively, which also presents a small Tafel slope (∼58 and 87 mV dec–1), high mass activity (115.4 and 33.8 A g–1 at η = 200 mA), and outstanding stability in 0.5 M H2SO4 and 1.0 KOH. The superior performance is mainly ascribed to the heterointerfaces between Mo2C and MoO2 promoting synergistic effects, quasi 1D nanostructures facilitating fast charge/mass transfer, and high electrochemical active surface area (ECSA) providing a large number of available sites. This ...

Improving the C2+ alcohols selectivity is highly desirable for higher alcohols synthesis in CO hydrogenation. Herein, an effective method was developed for Mo-based supported catalysts by the combination of tungsten-doping and surfactant-assisted hydrothermal strategy. The tungsten-doping enhanced the interaction between Ni and W/Mo metal species to form more of the Ni-MoW-S phase with tunable slab size and stacking layers, and thus promoted the chain growth of alcohol to form a greater amount of higher alcohols in CO hydrogenation. The optimal K,Ni–Mo0.75W0.25/MMO-S exhibited a dominant double-layer structure (∼39.0%) and highly synergetic effects between Ni and W/Mo species, resulting in the highest total alcohol selectivity (76.1%) and in higher alcohols selectivity. This work provides a new route for tuning the morphology of MoS2/WS2 and synergetic effects between Ni and W/Mo species in supported catalysts to improve the selectivity of higher alcohols.

To engineer low-cost, high-efficiency, and stable oxygen evolution reaction (OER) catalysts, structure effects should be primarily understood. Focusing on this, we systematically investigated the relationship between structures of materials and their OER performances by taking four 2D α-Ni(OH)2 as model materials, including layer-stacked bud-like Ni(OH)2-NB, flower-like Ni(OH)2-NF, and petal-like Ni(OH)2-NP as well as the ultralarge sheet-like Ni(OH)2-NS. For the first three (layer-stacking) catalysts, with the decrease of stacked layers, their accessible surface areas, abilities to adsorb OH–, diffusion properties, and the intrinsic activities of active sites increase, which accounts for their steadily enhanced activity. As expected, Ni(OH)2-NP shows the lowest overpotential (260 mV at 10 mA cm–2) and Tafel slope (78.6 mV dec–1) with a robust stability over 10 h among the samples, which also outperforms the benchmark IrO2 (360 mV and 115.8 mV dec–1) catalyst. Interestingly, Ni(OH)2-NS relative to Ni(OH)2...

Background Clinical outcomes in large patient populations from real-world clinical practice with a next-generation self-expanding transcatheter aortic valve are lacking. Objectives This study sought to document the clinical and device performance outcomes of transcatheter aortic valve replacement (TAVR) with a next-generation, self-expanding transcatheter heart valve (THV) system in patients with severe symptomatic aortic stenosis (AS) in routine clinical practice. Methods The FORWARD (CoreValve Evolut R FORWARD) study is a prospective, single-arm, multinational, multicenter, observational study. An independent clinical events committee adjudicated safety endpoints based on Valve Academic Research Consortium-2 definitions. An independent echocardiographic core laboratory evaluated all echocardiograms. From January 2016 to December 2016, TAVR with the next-generation self-expanding THV was attempted in 1,038 patients with symptomatic, severe AS at 53 centers on 4 continents. Results Mean age was 81.8 ± 6.2 years, 64.9% were women, the mean Society of Thoracic Surgeons Predicted Risk of Mortality was 5.5 ± 4.5%, and 33.9% of patients were deemed frail. The repositioning feature of the THV was applied in 25.8% of patients. A single valve was implanted in the proper anatomic location in 98.9% of patients. The mean aortic valve gradient was 8.5 ± 5.6 mm Hg, and moderate or severe aortic regurgitation was 1.9% at discharge. All-cause mortality was 1.9%, and disabling stroke occurred in 1.8% at 30 days. The expected-to-observed early surgical mortality ratio was 0.35. A pacemaker was implanted in 17.5% of patients. Conclusions TAVR using the next-generation THV is clinically safe and effective for treating older patients with severe AS at increased operative risk. (CoreValve Evolut R FORWARD Study [FORWARD]; NCT02592369)

Despite the significant progress in the preparation of hollow structures, it is a challenge to build high-quality complex hollow structures with controllable morphology, particularly for multicomponent materials. Herein, a facile strategy was first developed to tune the morphology of coordinated transition bimetal complexes via controlling the growth rates of {111} and {100} facets using sulfur as a morphological modulator and template-engaged pyrolysis to form a unique hollow polyhedron (S–FeNi@NC). By virtue of the structural and compositional features, the optimized S–FeNi@NC hollow cuboctahedron shows excellent activities with a remarkably small overpotential of 272 mV to reach 20 mA cm−2, a lower Tafel slope with 84 mA dec−1, and an excellent durability without degradation after 5000 CV cycles toward oxygen evolution reaction (OER) in an alkaline medium. The strategy developed here provides a new path to prepare hollow transition metal hybrids with a tunable polyhedral structure for catalysis and energy conversion.

Mixed metal oxide (MMO)-supported MoS2 catalysts with tunable size and morphology of active phases for higher alcohol synthesis (HAS) were prepared by using encapsulated Mo-based precursors with cetyltrimethylammonium bromide (CTAB). The Ni–KMoS/MMO catalysts show enhanced activity and superior selectivity towards higher alcohols to those prepared by the multiple impregnation method and co-impregnation method. That is, the K,Ni–30Mo/MMO catalyst exhibits a high space time yield (STY) of 253 mg per g catalyst per h for C2+ alcohols, which is about 3.2 and 1.51 times higher than those of IM-K,Ni–30Mo/MMO and co-IM-K,Ni–30Mo/MMO. The compromise between the dispersion and stacking of supported MoS2 slabs via adjusting the metal–support interaction is crucial to providing abundant Mo edges for dispersing Ni species to achieve more accessible active sites. The remarkable increase in the number of highly dispersed and contacted NiSx and Ni–KMoSx dual active sites will provide highly effective synergism, and thus gives this catalyst enhanced activity and exceptional selectivity towards higher alcohols in CO hydrogenation.

Hydrogen produced from electrocatalytic water splitting is a promising route due to the sustainable powers derived from the solar and wind energy. However, the sluggish kinetics at the anode for water splitting makes the highly effective and inexpensive electrocatalysts desirable in oxygen evolution reaction (OER) by structure and composition modulations. Metal–organic frameworks (MOFs) have been intensively used as the templates/precursors to synthesize complex hollow structures for various energy-related applications. Herein, an effective and facile template-engaged strategy originated from bimetal MOFs is developed to construct hollow microcubes assembled by interconnected nanopolyhedron, consisting of intimately dominant FeNi alloys coupled with a small NiFe2O4 oxide, which was confined within carbonitride outer shell (denoted as FeNi/NiFe2O4@NC) via one-step annealing treatment. The optimized FeNi/NiFe2O4@NC exhibits excellent electrocatalytic performances toward OER in alkaline media, showing 10 mA·...

In patients with severe aortic stenosis at increased risk for surgery, self-expanding transcatheter aortic valve replacement (TAVR) is associated with improved 2-year survival compared with surgery.This study sought to determine whether this clinical benefit was sustained over time.Patients with severe aortic stenosis deemed at increased risk for surgery by a multidisciplinary heart team were randomized 1:1 to TAVR or open surgical valve replacement (SAVR). Three-year clinical and echocardiographic outcomes were obtained in those patients with an attempted procedure.A total of 797 patients underwent randomization at 45 U.S. centers; 750 patients underwent an attempted procedure. Three-year all-cause mortality or stroke was significantly lower in TAVR patients (37.3% vs. 46.7% in SAVR; p = 0.006). Adverse clinical outcome components were also reduced in TAVR patients compared with SAVR patients, including all-cause mortality (32.9% vs. 39.1%, respectively; p = 0.068), all stroke (12.6% vs. 19.0%, respectively; p = 0.034), and major adverse cardiovascular or cerebrovascular events (40.2% vs. 47.9%, respectively; p = 0.025). At 3 years aortic valve hemodynamics were better with TAVR patients (mean aortic valve gradient 7.62 ± 3.57 mm Hg vs. 11.40 ± 6.81 mm Hg in SAVR; p0.001), although moderate or severe residual aortic regurgitation was higher in TAVR patients (6.8% vs. 0.0% in SAVR; p0.001). There was no clinical evidence of valve thrombosis in either group.Patients with severe aortic stenosis at increased risk for surgery had improved 3-year clinical outcomes after TAVR compared with surgery. Aortic valve hemodynamics were more favorable in TAVR patients without differences in structural valve deterioration. (Safety and Efficacy Study of the Medtronic CoreValve(®) System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902).

Electrochemical water splitting is a promising way for the sustainable production of hydrogen, but the efficiency of the overall water-splitting reaction largely depends on the oxygen evolution reaction (OER) because of its sluggish kinetics. Herein, a series of hierarchical ZnCo

Objectives This study sought to evaluate the Medtronic Evolut PRO Transcatheter Aortic Valve System in patients with severe symptomatic aortic stenosis. Background A next-generation self-expanding transcatheter aortic valve was designed with an external pericardial wrap with the intent to reduce paravalvular leak while maintaining the benefits of a low-profile, self-expanding, and repositionable supra-annular valve. Methods The Medtronic Evolut PRO Clinical Study included 60 patients undergoing transcatheter aortic valve replacement with the Evolut PRO valve at 8 investigational sites in the United States. Clinical outcomes at 30 days were evaluated using Valve Academic Research Consortium-2 criteria. The 2 primary safety endpoints were the incidence of all-cause mortality at 30 days and the incidence of disabling stroke at 30 days. The primary efficacy endpoint was the proportion of patients with no or trace prosthetic valve regurgitation at 30 days. An independent echocardiographic core laboratory (Mayo Clinic, Rochester, Minnesota) was used to adjudicate all echocardiographic assessments. Results All 60 patients received the Evolut PRO valve. At 30 days, 1 patient (1.7%) died and 1 patient (1.7%) experienced a nonfatal disabling stroke. Paravalvular regurgitation at 30 days was absent or trace in 72.4% of patients and was mild in the remainder of patients, with no patients having worse than mild paravavlular leak. The mean atrioventricular gradient was 6.4 ± 2.1 mm Hg and effective orifice area was 2.0 ± 0.5 cm2 at 30 days. Conclusions The safety and efficacy results of this study support the use of the Evolut PRO System for the treatment of severe symptomatic aortic stenosis in patients who are at increased surgical risk, resulting in excellent hemodynamics and minimal paravalvular leak (The Medtronic TAVR 2.0 US Clinical Study; NCT02738853)

Hydrogen produced from electrocatalytic water splitting is a promising route due to the sustainable powers derived from the solar and wind energy. However, the sluggish kinetics at the anode for water splitting makes the highly effective and inexpensive electrocatalysts desirable in oxygen evolution reaction (OER) by structure and composition modulations. Metal-organic frameworks (MOFs) have been intensively used as the templates/precursors to synthesize complex hollow structures for various energy-related applications. Herein, an effective and facile template-engaged strategy originated from bimetal MOFs is developed to construct hollow microcubes assembled by interconnected nanopolyhedron, consisting of intimately dominant FeNi alloys coupled with a small NiFe

This study sought to evaluate this transcatheter aortic valve (TAV) bioprosthesis in patients who are poorly suitable for surgical aortic valve (AV) replacement.A novel self-expandable TAV bioprosthesis was designed to provide a low-profile delivery system, conformable annular sealing, and the ability to resheath and reposition during deployment.The Evolut R U.S. study included 241 patients with severe aortic stenosis who were deemed to be at least high risk for surgery treated at 23 clinical sites in the United States. Clinical outcomes at 30 days were evaluated using Valve Academic Research Consortium-2 criteria. An independent echocardiography laboratory was used to evaluate hemodynamic outcomes.Patients were elderly (83.3 ± 7.2 years of age) and had high surgical risk (Society of Thoracic Surgeons predicted risk of mortality of 7.4 ± 3.4%). The majority of patients (89.5%) were treated by iliofemoral access. Resheathing or recapturing was performed in 22.6% of patients; more than 1 valve was required in 3 patients (1.3%). The 30-day outcomes included all-cause mortality (2.5%), disabling stroke (3.3%), major vascular complications (7.5%), life-threatening or disabling bleeding (7.1%), and new permanent pacemaker (16.4%). AV hemodynamics were markedly improved at 30 days: the mean AV gradient was reduced from 48.2 ± 13.0 mm Hg to 7.8 ± 3.1 mm Hg (p 0.001) and AV area increased from 0.6 ± 0.2 cmWe conclude that this novel self-expanding TAV bioprosthesis is safe and effective for the treatment of patients with severe aortic stenosis who are suboptimal for surgery. (Medtronic CoreValve Evolut R U.S. Clinical Study; NCT02207569).

The primary goal of this study was to establish a rigorous approach for determining and comparing the NMR detection sensitivity of in vivo 31P MRS at different field strengths (B0). This was done by calculating the signal-to-noise ratio (SNR) achieved within a unit sampling time at a given field strength. In vivo 31P spectra of human occipital lobe were acquired at 4 and 7 T under similar experimental conditions. They were used to measure the improvement of the human brain 31P MRS when the field strength increases from 4 to 7 T. The relaxation times and line widths of the phosphocreatine (PCr) resonance peak and the RF coil quality factors (Q) were also measured at these two field strengths. Their relative contributions to SNR at a given field strength were analyzed and discussed. The results show that in vivo 31P sensitivity was significantly improved at 7 T as compared with 4 T. Moreover, the line-width of the PCr resonance peak showed less than a linear increase with increased B0, which leads to a significant improvement in 31P spectral resolution. These findings indicate the advantage of high-field strength to improve in vivo 31P MRS quality in both sensitivity and spectral resolution. This advantage should improve the reliability and applicability of in vivo 31P MRS in studying high-energy phosphate metabolism, phospholipid metabolism and cerebral biogenetics in the human at both normal and diseased states noninvasively. Finally, the approach used in this study for calculating in vivo 31P MRS sensitivity provides a general tool in estimating the relative NMR detection sensitivity for any nuclear spin at a given field strength.

ATP metabolism is controlled mainly by ATP synthase (ATP(ase)) and creatine kinase (CK) reactions that regulate cerebral ATP production, transportation, and utilization. These coupled reactions constitute a chemical exchange metabolic network of PCr--ATP--Pi characterized by two forward and two reverse reaction fluxes, which can be studied noninvasively by in vivo (31)P MRS combined with magnetization transfer (MT). However, it is still debated whether current MT approaches can precisely determine all of these fluxes. We developed and tested a modified in vivo (31)P MT approach based on a multiple single-site saturation (MSS) technique to study the entire PCr--ATP--Pi network in human occipital lobe at 7T. Our results reveal that 1) the MSS MT approach can explicitly determine all four reaction fluxes with a minimal number of (31)P spectra; 2) the three-spin exchange model accurately determines reverse reaction fluxes, resulting in equal forward and reverse fluxes for both CK and ATP(ase) reactions; and 3) the ATP synthesis rate (8.8 +/- 1.9 micromol/g/min, N = 11) measured in the human brain reflects cerebral oxidative phosphorylation. The MSS MT approach should provide an important modality for noninvasively studying the essential roles of ATP metabolism in brain bioenergetics, function, and diseases.

Despite the essential role of the brain energy generated from ATP hydrolysis in supporting cortical neuronal activity and brain function, it is challenging to noninvasively image and directly quantify the energy expenditure in the human brain. In this study, we applied an advanced in vivo(31)P MRS imaging approach to obtain regional cerebral metabolic rates of high-energy phosphate reactions catalyzed by ATPase (CMR(ATPase)) and creatine kinase (CMR(CK)), and to determine CMR(ATPase) and CMR(CK) in pure gray mater (GM) and white mater (WM), respectively. It was found that both ATPase and CK rates are three times higher in GM than WM; and CMR(CK) is seven times higher than CMR(ATPase) in GM and WM. Among the total brain ATP consumption in the human cortical GM and WM, 77% of them are used by GM in which approximately 96% is by neurons. A single cortical neuron utilizes approximately 4.7 billion ATPs per second in a resting human brain. This study demonstrates the unique utility of in vivo(31)P MRS imaging modality for direct imaging of brain energy generated from ATP hydrolysis, and provides new insights into the human brain energetics and its role in supporting neuronal activity and brain function.

The greatest merit of in vivo magnetic resonance spectroscopy (MRS) methodology used in biomedical research is its ability for noninvasively measuring a variety of metabolites inside a living organ. It, therefore, provides an invaluable tool for determining metabolites, chemical reaction rates and bioenergetics, as well as their dynamic changes in the human and animal. The capability of in vivo MRS is further enhanced at higher magnetic fields because of significant gain in detection sensitivity and improvement in the spectral resolution. Recent progress of in vivo MRS technology has further demonstrated its great potential in many biomedical research areas, particularly in brain research. Here, we provide a review of new developments for in vivo heteronuclear 31P and 17O MRS approaches and their applications in determining the cerebral metabolic rates of oxygen and ATP inside the mitochondria, in both animal and human brains.

Objectives The purpose of this study was to evaluate remote pacemaker interrogation for the earlier diagnosis of clinically actionable events compared with traditional transtelephonic monitoring and routine in-person evaluation. Background Pacemaker patient follow-up procedures have evolved from evaluating devices with little programmability and diagnostic information solely in person to transtelephonic rhythm strip recordings that allow monitoring of basic device function. More recently developed remote monitoring technology leverages expanded device capabilities, augmenting traditional transtelephonic monitoring to evaluate patients via full device interrogation. Methods The time to first diagnosis of a clinically actionable event was compared in patients who were followed by remote interrogation (Remote) and those who were followed per standard of care with office visits augmented by transtelephonic monitoring (Control). Patients were randomized 2:1. Remote arm patients transmitted pacemaker information at 3-month intervals. Control arm patients with a single-chamber pacemaker transmitted at 2-month intervals. Control arm patients with dual-chamber devices transmitted at 2-month intervals with an office visit at 6 months. All patients were seen in office at 12 months. Results The mean time to first diagnosis of clinically actionable events was earlier in the Remote arm (5.7 months) than in the Control arm (7.7 months). Three (2%) of the 190 events in the Control arm and 446 (66%) of 676 events in the Remote arm were identified remotely. Conclusions The strategic use of remote pacemaker interrogation follow-up detects actionable events that are potentially important more quickly and more frequently than transtelephonic rhythm strip recordings. The use of transtelephonic rhythm strips for pacemaker follow-up is of little value except for battery status determinations. (PREFER [Pacemaker Remote Follow-up Evaluation and Review]; NCT00294645)

Objectives The purpose of this study was to prospectively evaluate the safety and clinical performance of the CoreValve Evolut R transcatheter aortic valve replacement (TAVR) system (Medtronic, Inc., Minneapolis, Minnesota) in a single-arm, multicenter pivotal study in high- or extreme-risk patients with symptomatic aortic valve stenosis. Background Although outcomes following TAVR are improving, challenges still exist. The repositionable 14-F equivalent CoreValve Evolut R TAVR system was developed to mitigate some of these challenges. Methods Suitable patients (n = 60) underwent TAVR with a 26- or 29-mm Evolut R valve. Primary safety endpoints were mortality and stroke at 30 days. Primary clinical performance endpoints were device success per the VARC-2 (Valve Academic Research Consortium-2) and the percent of patients with mild or less aortic regurgitation 24 h to 7 days post-procedure. Results Patients (66.7% female; mean age 82.8 ± 6.1 years; Society of Thoracic Surgeons Score 7.0 ± 3.7%) underwent TAVR via the transfemoral route in 98.3%, using a 29-mm valve in 68.3% of patients. All attempts at repositioning were successful. No death or stroke was observed up to 30 days. The VARC-2 overall device success rate was 78.6%. Paravalvular regurgitation post TAVR was mild or less in 96.6%, moderate in 3.4%, and severe in 0% at 30 days. Major vascular complications occurred in 8.3%, and permanent pacemaker implantation was required in 11.7% of patients. Conclusions The repositionable 14-F equivalent Evolut R TAVR system is safe and effective at treating high-risk symptomatic aortic stenosis patients. Repositioning was successful when required in all patients, with low rates of moderate or severe paravalvular aortic regurgitation and low permanent pacemaker implantation. (The Medtronic CoreValve™ Evolut R™ CE Mark Clinical Study; NCT01876420 )