Successful launch of robot-assisted mitral valve repair in Japan under universal health coverage.

OBJECTIVES: We compared the clinical outcomes of mitral valve (MV) repair for mitral regurgitation via robot-assisted approach (ROBO) and small right thoracotomy approach (MINI) three years after the reimbursement of ROBO in Japan. METHODS: Patients who underwent isolated MV repair by minimally invasive approach between 2018 and 2020 from the Japanese Cardiovascular Surgery Database were included. Patients in the ROBO group were matched to the MINI group based on propensity scores estimated from patient and surgical characteristics. Perioperative outcomes were compared among all as well as in subgroups categorized based on the yearly number of ROBO or MINI cases (≥10 or not) at the hospital. RESULTS: We identified 2,443 patients who had undergone isolated MV repair at 250 institutions in the database, and analysis of propensity matched 577 patient-pairs demonstrated that operation time, cardiopulmonary bypass time, and aortic cross clamp time were significantly shorter in ROBO. Although the ICU stay was longer in ROBO, the time to discharge was significantly shorter in ROBO. There was no meaningful difference in in-hospital mortality. The incidence of postoperative stroke, renal failure, prolonged ventilation, and the number of patients who cinverted to MV replacement were similarly low. Procedural time, blood transfusions, explorative procedures for bleeding, postoperative stroke, and prolonged ventilation occurred at a lower rate in the high-volume institutions. CONCLUSIONS: The study found that ROBO is just as effective as MINI. The introduction of robot-assisted MV repair in Japan has been successful.

Norcorroles as antiaromatic π-electronic systems that form dimension-controlled assemblies.

Norcorrole derivatives with 3,4,5-trialkoxyphenyl moieties at the meso positions were synthesized to form various stacking assemblies in single crystals and thermotropic liquid crystals (LCs) depending on aliphatic chain lengths. Triple-decker stacking structures were formed via the interactions between the antiaromatic systems formed for the butoxy and dodecyloxy derivatives in the single-crystal and LC states, respectively. In particular, the LC state exhibited discotic columnar structures comprising triple deckers to exhibit high electric conductivity, as supported by molecular dynamics simulations.

Correction: Water-dispersible donor-acceptor-donor π-conjugated bolaamphiphiles enabling a humidity-responsive luminescence color change.

Correction for 'Water-dispersible donor-acceptor-donor π-conjugated bolaamphiphiles enabling a humidity-responsive luminescence color change' by Tomoya Enjou et al., Chem. Commun., 2024, https://doi.org/10.1039/d3cc05749f.

Water-dispersible donor-acceptor-donor π-conjugated bolaamphiphiles enabling a humidity-responsive luminescence color change.

Novel water-dispersible donor-acceptor-donor π-conjugated bolaamphiphiles, having dibenzophenazine as the acceptor and heteroatom-bridged amphiphilic diarylamines as the donors, have been developed. The materials displayed a distinct photoluminescence color change in response to humidity in a poly(vinylalcohol) matrix.

Grinding-Induced Water Solubility Exhibited by Mechanochromic Luminescent Supramolecular Fibers.

Most mechanochromic luminescent compounds are crystalline and highly hydrophobic; however, mechanochromic luminescent molecular assemblies comprising amphiphilic molecules have rarely been explored. This study investigated mechanochromic luminescent supramolecular fibers composed of dumbbell-shaped 9,10-bis(phenylethynyl)anthracene-based amphiphiles without any tetraethylene glycol (TEG) substituents or with two TEG substituents. Both amphiphiles formed water-insoluble supramolecular fibers via linear hydrogen bond formation. Both compounds acquired water solubility when solid samples composed of supramolecular fibers are ground. Grinding induces the conversion of 1D supramolecular fibers into micellar assemblies where fluorophores can form excimers, thereby resulting in a large redshift in the fluorescence spectra. Excimer emission from the ground amphiphile without TEG chains is retained after dissolution in water. The micelles are stable in water because hydrophilic dendrons surround the hydrophobic luminophores. By contrast, when water is added to a ground amphiphile having TEG substituents, fragmented supramolecular fibers with the same molecular arrangement as the initial supramolecular fibers are observed, because fragmented fibers are thermodynamically preferable to micelles as the hydrophobic arrays of fluorophores are covered with hydrophilic TEG chains. This leads to the recovery of the initial fluorescent properties for the latter amphiphile. These supramolecular fibers can be used as practical mechanosensors to detect forces at the mesoscale.

Sternal lifting technique for patients with sternal depression during robotic mitral repair.

INTRODUCTION: Traditional surgical methods have been difficult for patients with chest wall deformities, but the use of the Electrical Sternum Lifting System (ESLS) has made the surgery easier. MATERIALS AND SURGICAL TECHNIQUE: Patients with a sternum-to-vertebral distance of less than 80 mm on preoperative computed tomography (CT) scan routinely underwent sternal lift using the ESLS. The ESLS was effective in securing the operative field while suspending the sternum, allowing adequate observation of the left atrium, left ventricle, and the mitral valve, and safe mitral valve plasty. The use of the lifting device did not interfere with the robot arms, and the space between the sternum and vertebrae was widened with only a 3 mm wound to move the mitral valve surface in the sagittal plane, making the repair easy and accurate under robotic assistance. The effort to attach the ESLS was not difficult, and the postoperative cosmetic outcomes were excellent. Sixty-three out of 1002 patients (6.3%) underwent sternal elevation using ESLS. There were 19 males and 44 females with a mean age of 50.9 ± 14.0 years. The average of sternum-to-vertebral (S/V) distance was 72.4 ± 8.9 cm. Two patients had S/V distance of more than 80 mm but ESLS was used because of scoliosis.

Aquatic Functional Liquid Crystals: Design, Functionalization, and Molecular Simulation.

Aquatic functional liquid crystals, which are ordered molecular assemblies that work in water environment, are described in this review. Aquatic functional liquid crystals are liquid-crystalline (LC) materials interacting water molecules or aquatic environment. They include aquatic lyotropic liquid crystals and LC based materials that have aquatic interfaces, for example, nanoporous water treatment membranes that are solids preserving LC order. They can remove ions and viruses with nano- and subnano-porous structures. Columnar, smectic, bicontinuous LC structures are used for fabrication of these 1D, 2D, 3D materials. Design and functionalization of aquatic LC sensors based on aqueous/LC interfaces are also described. The ordering transitions of liquid crystals induced by molecular recognition at the aqueous interfaces provide distinct optical responses. Molecular orientation and dynamic behavior of these aquatic functional LC materials are studied by molecular dynamics simulations. The molecular interactions of LC materials and water are key of these investigations. New insights into aquatic functional LC materials contribute to the fields of environment, healthcare, and biotechnology.

Triplet dynamic nuclear polarization of pyruvate via supramolecular chemistry.

Dynamic nuclear polarization (DNP) significantly improves the sensitivity of magnetic resonance imaging, and its most important medical application is cancer diagnosis via hyperpolarized 13C-labeled pyruvate. Unlike cryogenic DNP, triplet-DNP uses photoexcited triplet electrons under mild conditions. However, triplet-DNP of pyruvate has not been observed because of incompatibility of the hydrophobic polarizing agent with hydrophilic pyruvate. This work demonstrates that supramolecular complexation with ß-cyclodextrin can disperse 4,4'-(pentacene-6,13-diyl)dibenzoate (NaPDBA), a pentacene derivative with hydrophilic substituents, even in the presence of high sodium pyruvate concentrations. The polarization of photoexcited triplet electron spins in NaPDBA was transferred to the 13C spins of sodium pyruvate via triplet-DNP of 1H spins in water and 1H-to-13C cross-polarization. This provides an important step toward the widespread use of ultra-sensitive MRI for cancer diagnosis.

Outcomes of Barlow mitral valve repaired by robot-assisted keyhole surgery.

Objective: To present our strategy and the clinical outcomes of robot-assisted Barlow mitral valve keyhole surgery. Methods: From May 2015 to March 2022, a total of 1281 patients underwent mitral valve repair at our institution, including 763 with robotics surgeries. Of these, 124 patients with Barlow mitral valve (49 ± 12 years, male/female ratio = 81:43) were treated using robotic assistance and included in this study. Results: All operations were completed using 3 to 5 keyholes. Neochordae implantation using the loop technique was the first option, and resection was performed only in cases with an intrinsic risk of developing systolic anterior motion. Neochordae implantation was performed in 118 cases (95.1%) using 6.6 ± 3.0 neochordae. Posterior leaflet resection was performed in 27 (21.7%) patients. Operation time was 177 ± 42 minutes, cardiopulmonary bypass time was 127 ± 25 minutes, and aorta crossclamp time was 76 ± 16 minutes. Blood transfusion was required in 5 cases (4%). None of the patients required a conversion to valve replacement. The postoperative complications included bleeding (n = 4), stroke (n = 1), and infection (n = 2). Mitral valve regurgitation 1 week after repair was none or trivial in 122 cases (98.3%), mild in 2 cases (1.7%), and more than moderate in 0 cases. Freedom from reoperation was 99.2% during the follow-up period of 36 ± 21 months. One patient required reoperation due to infective endocarditis. Conclusions: Robot-assisted keyhole surgery using the loop-first concept was adequate to help achieve satisfactory and safe perioperative outcomes for Barlow mitral valve.

Asymmetrically Functionalized Electron-Deficient π-Conjugated System for Printed Single-Crystalline Organic Electronics.

Large-area single-crystalline thin films of n-type organic semiconductors (OSCs) fabricated via solution-processed techniques are urgently demanded for high-end electronics. However, the lack of molecular designs that concomitantly offer excellent charge-carrier transport, solution-processability, and chemical/thermal robustness for n-type OSCs limits the understanding of fundamental charge-transport properties and impedes the realization of large-area electronics. The benzo[de]isoquinolino[1,8-gh]quinolinetetracarboxylic diimide (BQQDI) π-electron system with phenethyl substituents (PhC2 -BQQDI) demonstrates high electron mobility and robustness but its strong aggregation results in unsatisfactory solubility and solution-processability. In this work, an asymmetric molecular design approach is reported that harnesses the favorable charge transport of PhC2 -BQQDI, while introducing alkyl chains to improve the solubility and solution-processability. An effective synthetic strategy is developed to obtain the target asymmetric BQQDI (PhC2 -BQQDI-Cn ). Interestingly, linear alkyl chains of PhC2 -BQQDI-Cn (n = 5-7) exhibit an unusual molecular mimicry geometry with a gauche conformation and resilience to dynamic disorders. Asymmetric PhC2 -BQQDI-C5 demonstrates excellent electron mobility and centimeter-scale continuous single-crystalline thin films, which are two orders of magnitude larger than that of PhC2 -BQQDI, allowing for the investigation of electron transport anisotropy and applicable electronics.

Robotic Surgery for Triple Valve Insufficiency: A Case Report.

A 63-year-old woman was referred to our institution for surgical treatment of triple valve (aortic, mitral, and tricuspid) insufficiency and underwent a robot-assisted endoscopic procedure. Three intercostal ports were placed in the right lateral chest for robotic instruments and a retrograde cardioplegic cannula, and a 5 cm thoracotomy was made for the procedure, which was a mitral valve repair with neochords and ring annuloplasty, an aortic valve replacement with bioprosthetic valve, and a ring tricuspid annuloplasty. Surgery was successfully achieved without blood transfusion or any complications.

Off-Pump Neochordae Implantation via Left Minithoracotomy for Recurrent Regurgitation Following Mitral Valve Repair: The First Case in Japan.

Surgical fixation after recurrent regurgitation following surgical mitral repair has been technically demanding and associated with high morbidity and mortality. Avoiding reopening the adhesive site or limiting the usage of cardiopulmonary bypass are solutions for reducing the operative risk. We report a case of recurrent mitral regurgitation treated by off-pump neochordae implantation via left minithoracotomy. A 69-year-old woman with a history of conventional mitral repair via median sternotomy developed heart failure due to mitral regurgitation from recurrent posterior leaflet P2 prolapse. Four neochordaes were implanted off-pump via left minithoracotomy using a NeoChord DS1000 in the seventh intercostal space. No transfusion was required. The patient was discharged a week after the procedure with no complications. The regurgitation remains trivial 6 months after the NeoChord procedure.

Effects of Lenvatinib on Skeletal Muscle Volume and Cardiac Function in Patients with Hepatocellular Carcinoma.

INTRODUCTION: Previously, we reported that the tyrosine kinase inhibitor (TKI) sorafenib decreases serum levels of carnitine and reduces skeletal muscle volume. Moreover, others reported that TKIs might lead to cardiomyopathy or heart failure. Therefore, this study aimed to evaluate the effects of lenvatinib (LEN) on skeletal muscle volume and cardiac function in patients with hepatocellular carcinoma (HCC). METHODS: This retrospective study included 58 adult Japanese patients with chronic liver diseases and HCC treated with LEN. Blood samples were collected before and after 4 weeks of treatment, and serum carnitine fraction and myostatin levels were measured. Before and after 4-6 weeks of treatment, the skeletal muscle index (SMI) was evaluated from computed tomography images and cardiac function was assessed by ultrasound cardiography. RESULTS: After treatment, SMI, serum levels of total carnitine, and global longitudinal strain were significantly lower, but serum levels of myostatin were significantly higher. Left ventricular ejection fraction showed no significant change. CONCLUSION: In patients with HCC, LEN decreases serum levels of carnitine, skeletal muscle volume, and worsens cardiac function.

The flexible and iterative steps within the NHEJ pathway.

Cellular and biochemical studies of nonhomologous DNA end joining (NHEJ) have long established that nuclease and polymerase action are necessary for the repair of a very large fraction of naturally-arising double-strand breaks (DSBs). This conclusion is derived from NHEJ studies ranging from yeast to humans and all genetically-tractable model organisms. Biochemical models derived from recent real-time and structural studies have yet to incorporate physical space or timing for DNA end processing. In real-time single molecule FRET (smFRET) studies, we analyzed NHEJ synapsis of DNA ends in a defined biochemical system. We described a Flexible Synapsis (FS) state in which the DNA ends were in proximity via only Ku and XRCC4:DNA ligase 4 (X4L4), and in an orientation that would not yet permit ligation until base pairing between one or more nucleotides of microhomology (MH) occurred, thereby allowing an in-line Close Synapsis (CS) state. If no MH was achievable, then XLF was critical for ligation. Neither FS or CS required DNA-PKcs, unless Artemis activation was necessary to permit local resection and subsequent base pairing between the two DNA ends being joined. Here we conjecture on possible 3D configurations for this FS state, which would spatially accommodate the nuclease and polymerase processing steps in an iterative manner. The FS model permits repeated attempts at ligation of at least one strand at the DSB after each round of nuclease or polymerase action. In addition to activation of Artemis, other possible roles for DNA-PKcs are discussed.

Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8+ T cell cytotoxicity and proliferation.

Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms in mice, although the role of human Sema4A in the tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non-small cell lung cancer (NSCLC) responded significantly better to anti-programmed cell death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly, SEMA4A expression in human NSCLC was mainly derived from tumor cells and was associated with T cell activation. Sema4A promoted cytotoxicity and proliferation of tumor-specific CD8+ T cells without terminal exhaustion by enhancing mammalian target of rapamycin complex 1 and polyamine synthesis, which led to improved efficacy of PD-1 inhibitors in murine models. Improved T cell activation by recombinant Sema4A was also confirmed using isolated tumor-infiltrating T cells from patients with cancer. Thus, Sema4A might be a promising therapeutic target and biomarker for predicting and promoting ICI efficacy.

Reentrant 2D Nanostructured Liquid Crystals by Competition between Molecular Packing and Conformation: Potential Design for Multistep Switching of Ionic Conductivity.

The front cover artwork is provided by Takashi Kato at the University of Tokyo. The image shows three assembled structures of smectic liquid crystals that show reentrant behavior. Read the full text of the Research Article at 10.1002/cphc.202200927.

Singlet fission as a polarized spin generator for dynamic nuclear polarization.

Singlet fission (SF), converting a singlet excited state into a spin-correlated triplet-pair state, is an effective way to generate a spin quintet state in organic materials. Although its application to photovoltaics as an exciton multiplier has been extensively studied, the use of its unique spin degree of freedom has been largely unexplored. Here, we demonstrate that the spin polarization of the quintet multiexcitons generated by SF improves the sensitivity of magnetic resonance of water molecules through dynamic nuclear polarization (DNP). We form supramolecular assemblies of a few pentacene chromophores and use SF-born quintet spins to achieve DNP of water-glycerol, the most basic biological matrix, as evidenced by the dependence of nuclear polarization enhancement on magnetic field and microwave power. Our demonstration opens a use of SF as a polarized spin generator in bio-quantum technology.

Reentrant 2D Nanostructured Liquid Crystals by Competition between Molecular Packing and Conformation: Potential Design for Multistep Switching of Ionic Conductivity.

Reentrant phenomena in soft matter and biosystems have attracted considerable attention because their properties are closely related to high functionality. Here, we report a combined experimental and computational study on the self-assembly and reentrant behavior of a single-component thermotropic smectic liquid crystal toward the realization of dynamically functional materials. We have designed and synthesized a mesogenic molecule consisting of an alicyclic trans,trans-bicyclohexyl mesogen and a polar cyclic carbonate group connected by a flexible tetra(oxyethylene) spacer. The molecule exhibits an unprecedented sequence of layered smectic phases, in the order: smectic A-smectic B-reentrant smectic A. Electron density profiles and large-scale molecular dynamics simulations indicate that competition between the stacking of bicyclohexyl mesogens and the conformational flexibility of tetra(oxyethylene) chains induces this unusual reentrant behavior. Ion-conductive reentrant liquid-crystalline materials have been developed, which undergo the multistep conductivity changes in response to temperature. The reentrant liquid crystals have potential as new mesogenic materials exhibiting switching functions.

Diketopiperazine cyclo(-l-Leu-l-Phe) with plant elicitation activity and anti-oomycete activity against Plasmopara viticola.

The aim of this study was to contribute to the reduction of synthetic chemical fungicide application in viticulture by using cyclo(-l-Leu-l-Phe) (cLF) produced by Bacillus subtilis KS1, a candidate for biological control agent. cLF is a diketopiperazine and belongs to the family of 2,5-diketopiperazines. KS1 secreted micromolar levels of cLF into culture medium. Micromolar concentrations of cLF structure-dependently decreased by ∼90% both disease severity and lesion density of downy mildew in grapevine cultivated in a growth chamber. Microscopic observation demonstrated that cLF inhibited Plasmopara viticola haustorium formation by 80% but not zoospore germination on leas disks. Interestingly, millimolar concentrations of cLF induced plant defense response, such as expression of genes encoding chitinase and ß-1,3-glucanase, in grapevine leaves through the salicylic acid and jasmonate signaling pathways. We demonstrated that cLF was a weapon against P. viticola infection. Further evaluation of cLF in field trials is required to uncover its inherent characteristics.

Robot-Assisted Totally Endoscopic Mitral Valve Plasty and Coronary Artery Bypass Grafting.

We experienced 3 cases of port-access robot-assisted totally endoscopic technique for mitral valve repair and concomitant coronary artery bypass. The right internal mammary artery was harvested, mitral valve was fixed, and the right internal mammary artery to right coronary artery anastomosis was carried out on the arrested heart. The use of cardiac arrest and a V-shaped hook technique facilitated the coronary anastomosis and the da Vinci Firefly test (Intuitive Surgical Inc., Sunnyvale, CA) could confirm patency of the graft.