Enhancing Origin Prediction: Deep Learning Model for Diagnosing Premature Ventricular Contractions with Dual-Rhythm Analysis Focused on Cardiac Rotation.

BACKGROUND: Several algorithms can differentiate inferior axis premature ventricular contractions (PVCs) originating from the right side and left side on 12-lead electrocardiograms (ECGs). However, it is unclear whether distinguishing the origin should rely solely on PVC or incorporate sinus rhythm (SR). AIMS: We compared the Dual-Rhythm model (incorporating both SR and PVC) to the PVC model (using PVC alone), and quantified the contribution of each ECG lead in predicting the PVC origin for each cardiac rotation. METHODS: This multicenter study enrolled 593 patients from 11 centers-493 from Japan and Germany, and 100 from Belgium, which used as the external validation dataset. Using a hybrid approach combining a Resnet50-based convolutional neural network and a Transformer model, we developed two variants-the PVC and Dual-Rhythm models-to predict PVC origin. RESULTS: In the external validation dataset, the Dual-Rhythm model outperformed the PVC model in accuracy (0.84 vs. 0.74, respectively; p < 0.01), precision (0.73 vs. 0.55, respectively; p < 0.01), specificity (0.87 vs. 0.68, respectively; p < 0.01), area under the receiver operating characteristic curve (0.91 vs. 0.86, respectively; p = 0.03), and F1-Score (0.77 vs. 0.68, respectively; p = 0.03). The contributions to PVC origin prediction were 77.3% for PVC and 22.7% for the SR. However, in patients with counterclockwise rotation, SR had a greater contribution in predicting the origin of right-sided PVC. CONCLUSIONS: Our deep learning-based model, incorporating both PVC and SR morphologies, resulted in a higher prediction accuracy for PVC origin. Considering SR is particularly important for predicting right-sided origin in patients with counterclockwise rotation.

Nanoscale thermal imaging of hot electrons by cryogenic terahertz scanning noise microscopy.

Nanoscale thermal imaging and temperature detection are of fundamental importance in diverse scientific and technological realms. Most nanoscale thermometry techniques focus on probing the temperature of lattice or phonons and are insensitive to nonequilibrium electrons, commonly referred to as "hot electrons." While terahertz scanning noise microscopy (SNoiM) has been demonstrated to be powerful in the thermal imaging of hot electrons, prior studies have been limited to room temperature. In this work, we report the development of a cryogenic SNoiM (Cryo-SNoiM) tailored for quantitative hot electron temperature detection at low temperatures. The microscope features a special two-chamber design where the sensitive terahertz detector, housed in a vacuum chamber, is efficiently cooled to ∼5 K using a pulse tube cryocooler. In a separate chamber, the atomic force microscope and the sample can be maintained at room temperature under ambient/vacuum conditions or cooled to ∼110 K via liquid nitrogen. This unique dual-chamber cooling system design enhances the efficacy of SNoiM measurements at low temperatures. It not only facilitates the pre-selection of tips at room temperature before cooling but also enables the quantitative derivation of local electron temperature without reliance on any adjustable parameters. The performance of Cryo-SNoiM is demonstrated through imaging the distribution of hot electrons in a cold, self-heated narrow metal wire. This instrumental innovation holds great promise for applications in imaging low-temperature hot electron dynamics and nonequilibrium transport phenomena across various material systems.

Visualization of Multiple-Resonance-Induced Frontier Molecular Orbitals in a Single Multiple-Resonance Thermally Activated Delayed Fluorescence Molecule.

The spatial distribution and electronic properties of the frontier molecular orbitals (FMOs) in a thermally activated delayed fluorescence (TADF) molecule contribute significantly to the TADF properties, and thus, a detailed understanding and sophisticated control of the FMOs are fundamental to the design of TADF molecules. However, for multiple-resonance (MR)-TADF molecules that achieve spatial separation of FMOs by the MR effect, the distinctive distribution of these molecular orbitals poses significant challenges for conventional computational analysis and ensemble averaging methods to elucidate the FMOs' separation and the precise mechanism of luminescence. Therefore, the visualization and analysis of electronic states with the specific energy level of a single MR-TADF molecule will provide a deeper understanding of the TADF mechanism. Here, scanning tunneling microscopy/spectroscopy (STM/STS) was used to investigate the electronic states of the DABNA-1 molecule at the atomic scale. FMOs' visualization and local density of states analysis of the DABNA-1 molecule clearly show that MR-TADF molecules also have well-separated FMOs according to the internal heteroatom arrangement, providing insights that complement existing theoretical prediction methods.

[Successful treatment of acute promyelocytic leukemia with all-trans retinoic acid on hemodialysis for acute renal failure].

All-trans retinoic acid (ATRA) is used as standard induction therapy for acute promyelocytic leukemia (APL), but it is contraindicated for patients on hemodialysis. We present a case of a patient with APL on hemodialysis, intubated, and with marked disseminated intravascular coagulation (DIC) who was successfully treated with ATRA. A 49-year-old man was transferred to our hospital and admitted into the intensive care unit due to renal dysfunction, DIC, and pneumonia. Promyelocytes were noted in the peripheral blood, and he was diagnosed with APL after bone-marrow examination. Because of renal dysfunction, only Ara-C was used but with a reduced dose. The patient's condition improved, and he was extubated and withdrawn from dialysis on the 5th day of hospitalization. The patient suffered from APL syndrome during induction therapy, which necessitated ATRA withdrawal and steroid administration. Remission was achieved after induction therapy, and the patient is currently on maintenance therapy. There are few cases of patients with APL on hemodialysis who were treated with ATRA; hence, it is necessary to review the treatment plan for these patients.

Anti-Kasha emissions of single molecules in a plasmonic nanocavity.

Kasha's rule generally holds true for solid-state molecular systems, where the rates of internal conversion and vibrational relaxation are sufficiently higher than the luminescence rate. In contrast, in systems where plasmons and matter interact strongly, the luminescence rate is significantly enhanced, leading to the emergence of luminescence that does not obey Kasha's rule. In this work, we investigate the anti-Kasha emissions of single molecules, free-base and magnesium naphthalocyanine (H2Nc and MgNc), in a plasmonic nanocavity formed between the tip of a scanning tunneling microscope (STM) and metal substrate. A narrow-line tunable laser was employed to precisely reveal the excited-state levels of a single molecule located under the tip and to selectively excite it into a specific excited state, followed by obtaining a STM-photoluminescence (STM-PL) spectrum to reveal the energy relaxation from the state. The excitation to higher-lying states of H2Nc caused various changes in the emission spectrum, such as broadening and the appearance of new peaks, implying the breakdown of Kasha's rule. These observations indicate emissions from the vibrationally excited states in the first singlet excited state (S1) and second singlet excited state (S2), as well as internal conversion from S2 to S1. Moreover, we obtained direct evidence of electronic and vibronic transitions from the vibrationally excited states, from the STM-PL measurements of MgNc. The results obtained herein shed light on the energy dynamics of molecular systems under a plasmonic field and highlight the possibility of obtaining various energy-converting functions using anti-Kasha processes.

Atomic-Scale Photon Mapping Revealing Spin-Current Relaxation.

A nanoscopic understanding of spin-current dynamics is crucial for controlling the spin transport in materials. However, gaining access to spin-current dynamics at an atomic scale is challenging. Therefore, we developed spin-polarized scanning tunneling luminescence spectroscopy (SP STLS) to visualize the spin relaxation strength depending on spin injection positions. Atomically resolved SP STLS mapping of gallium arsenide demonstrated a stronger spin relaxation in gallium atomic rows. Hence, SP STLS paves the way for visualizing spin current with single-atom precision.

Orbital-resolved visualization of single-molecule photocurrent channels.

Given its central role in utilizing light energy, photoinduced electron transfer (PET) from an excited molecule has been widely studied1-6. However, even though microscopic photocurrent measurement methods7-11 have made it possible to correlate the efficiency of the process with local features, spatial resolution has been insufficient to resolve it at the molecular level. Recent work has, however, shown that single molecules can be efficiently excited and probed when combining a scanning tunnelling microscope (STM) with localized plasmon fields driven by a tunable laser12,13. Here we use that approach to directly visualize with atomic-scale resolution the photocurrent channels through the molecular orbitals of a single free-base phthalocyanine (FBPc) molecule, by detecting electrons from its first excited state tunnelling through the STM tip. We find that the direction and the spatial distribution of the photocurrent depend sensitively on the bias voltage, and detect counter-flowing photocurrent channels even at a voltage where the averaged photocurrent is near zero. Moreover, we see evidence of competition between PET and photoluminescence12, and find that we can control whether the excited molecule primarily relaxes through PET or photoluminescence by positioning the STM tip with three-dimensional, atomic precision. These observations suggest that specific photocurrent channels can be promoted or suppressed by tuning the coupling to excited-state molecular orbitals, and thus provide new perspectives for improving energy-conversion efficiencies by atomic-scale electronic and geometric engineering of molecular interfaces.

Visualization of Frontier Molecular Orbital Separation of a Single Thermally Activated Delayed Fluorescence Emitter by STM.

Because the spatial distribution of frontier molecular orbitals (FMOs) regulates the thermally activated delayed fluorescence (TADF) property, researchers synthesize TADF emitters by designing their FMO distribution. However, it remains challenging to clarify how the FMO distribution is altered at molecular interfaces. Thus, visualizing the FMOs at molecular interfaces helps us to understand the working behavior of TADF emitters. Using scanning tunneling microscopy (STM), we investigated the electronic structure of a single TADF emitter, hexamethylazatriangulene-triazine, at molecule-metal and molecule-insulating film interfaces. FMOs at the molecule-metal interface were not spatially confined to the donor-acceptor moieties because of hybridization. Meanwhile, FMOs at the molecule-insulator interface exhibited spatially separated filled and empty states confined to each moiety, similar to the calculated gas-phase FMOs. These observations illustrate that the molecule-environment interaction alters the spatial distribution of FMOs, proving that STM is a powerful tool for studying TADF molecules.

Single-molecule laser nanospectroscopy with micro-electron volt energy resolution.

Ways to characterize and control excited states at the single-molecule and atomic levels are needed to exploit excitation-triggered energy-conversion processes. Here, we present a single-molecule spectroscopic method with micro-electron volt energy and submolecular-spatial resolution using laser driving of nanocavity plasmons to induce molecular luminescence in scanning tunneling microscopy. This tunable and monochromatic nanoprobe allows state-selective characterization of the energy levels and linewidths of individual electronic and vibrational quantum states of a single molecule. Moreover, we demonstrate that the energy levels of the states can be finely tuned by using the Stark effect and plasmon-exciton coupling in the tunneling junction. Our technique and findings open a route to the creation of designed energy-converting functions by using tuned energy levels of molecular systems.

Chemical Identification and Bond Control of π-Skeletons in a Coupling Reaction.

Highly unsaturated π-rich carbon skeletons afford versatile tuning of structural and optoelectronic properties of low-dimensional carbon nanostructures. However, methods allowing more precise chemical identification and controllable integration of target sp-/sp2-carbon skeletons during synthesis are required. Here, using the coupling of terminal alkynes as a model system, we demonstrate a methodology to visualize and identify the generated π-skeletons at the single-chemical-bond level on the surface, thus enabling further precise bond control. The characteristic electronic features together with localized vibrational modes of the carbon skeletons are resolved in real space by a combination of scanning tunneling microscopy/spectroscopy (STM/STS) and tip-enhanced Raman spectroscopy (TERS). Our approach allows single-chemical-bond understanding of unsaturated carbon skeletons, which is crucial for generating low-dimensional carbon nanostructures and nanomaterials with atomic precision.

Ventricular tachycardia based on cardiac sarcoidosis with a narrow QRS complex, ablated on the left ventricle free-wall.

A septuagenarian female with cardiac sarcoidosis suffered from drug refractory ventricular tachycardia (VT) requiring multiple implantable cardioverter-defibrillator shocks. The QRS complex during the VT was very similar to that during sinus rhythm although the QRS width during the VT (142 ms) was relatively wider than that during sinus rhythm (107 ms). The VT exit was located on the ventricular septum close to the His-bundle recording region. However, the critical pathway of this VT was detected on the anterior free wall of the left ventricle (LV), and a radiofrequency application at that site could terminate the VT. No Purkinje potentials were recorded there during the VT or sinus rhythm. According to the electrophysiological study, 3-D mapping, and the response to the ablation, the critical circuit of the VT was surrounded by a protected area of scar associated with cardiac sarcoidosis. As a result, the VT circuit was connected to the basal septal area close to the His-Purkinje system as an outer loop of the VT circuit. This unique trajectory of the VT might have caused a similar QRS morphology to that of sinus rhythm, and the relatively narrow QRS complex despite the critical isthmus was located on the anterior free wall of the LV.

Accessory pathway analysis using a multimodal deep learning model.

Cardiac accessory pathways (APs) in Wolff-Parkinson-White (WPW) syndrome are conventionally diagnosed with decision tree algorithms; however, there are problems with clinical usage. We assessed the efficacy of the artificial intelligence model using electrocardiography (ECG) and chest X-rays to identify the location of APs. We retrospectively used ECG and chest X-rays to analyse 206 patients with WPW syndrome. Each AP location was defined by an electrophysiological study and divided into four classifications. We developed a deep learning model to classify AP locations and compared the accuracy with that of conventional algorithms. Moreover, 1519 chest X-ray samples from other datasets were used for prior learning, and the combined chest X-ray image and ECG data were put into the previous model to evaluate whether the accuracy improved. The convolutional neural network (CNN) model using ECG data was significantly more accurate than the conventional tree algorithm. In the multimodal model, which implemented input from the combined ECG and chest X-ray data, the accuracy was significantly improved. Deep learning with a combination of ECG and chest X-ray data could effectively identify the AP location, which may be a novel deep learning model for a multimodal model.

Type 1 Diabetes, ACTH Deficiency, and Hypothyroidism Simultaneously Induced by Nivolumab Therapy in a Patient with Gastric Cancer: A Case Report.

Nivolumab, a fully human IgG4 immune checkpoint inhibitor (ICI) antibody, has been approved for a variety of cancers. Several endocrine-associated immune-related adverse events have been reported, but the incidence rate is relatively low. This is a case of a patient with gastric cancer who underwent nivolumab therapy, leading to type 1 diabetes as well as adrenocorticotropic hormone (ACTH) deficiency and hypothyroidism almost simultaneously. A 70-year-old man with no previous history of diabetes was treated with nivolumab monotherapy for gastric cancer in November 2018. After 8 courses of nivolumab, he was diagnosed with type 1 diabetes associated with ICI; consequently, insulin therapy was initiated in March 2019. In April 2019, he was transported to hospital due to suffering from prolonged hypoglycemia, disturbed consciousness, and fever. He frequently experienced episodes of hypoglycemia, with poor controlled glycemia. His disturbed consciousness and fever also sustained. Further investigation of his hormones revealed low cortisol and ACTH levels, as well as hypothyroidism. His blood glucose control was improved after the introduction of hydrocortisone and thyroid hormone; he became alert and afebrile. In January 2020, he received a followed-up in an outpatient setting under insulin, hydrocortisone, and thyroid replacement therapy. Endocrine defect associated with ICIs, especially type 1 diabetes or ACTH deficiency, is a rare condition. To the best of our knowledge, this is the 1st case of multiple endocrinopathies simultaneously induced by nivolumab. Various endocrine concomitant defects should be taken into consideration when treating with nivolumab.

Controlling the Resonance Raman Effect in Tip-Enhanced Raman Spectroscopy Using a Thin Insulating Film.

Both surface-enhanced Raman spectroscopy (SERS) and tip-enhanced Raman spectroscopy (TERS) are widely used for the investigation of nanoscale materials. One of the most critical aspects of both SERS and TERS is the control of both the plasmon and molecular resonance precisely. Here, we demonstrate single-molecule TERS under molecular resonance conditions using a scanning tunneling microscope. This was achieved by placing the molecule on a sodium chloride (NaCl) film in order to directly compare the absorption with Raman excitation spectra. Varying the NaCl film thickness changes the degree of screening effect from the metal surface, which leads to a variation of the molecular resonance phenomena. Although it is generally accepted that the target molecule should be directly attached to the metal surface in SERS, our observation using TERS suggests that this is not always optimal, especially under molecular resonance Raman conditions. Our work demonstrates the possibility of controlling molecular resonance by carefully modifying the local environment. This will be useful for future investigation of isolated single molecules or even two-dimensional molecular assemblies.

Long-Term Results of High-Dose 2-Fraction Carbon Ion Radiation Therapy for Hepatocellular Carcinoma.

PURPOSE: Carbon ion beams have several physical and biological advantages compared with conventional radiation for cancer therapy. The objective of this study is to evaluate the safety and effectiveness of 2-fraction carbon ion radiation therapy (CIRT) in patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Between December 2008 and March 2013, 57 patients with localized HCC were treated with CIRT at a total dose of 45 Gy (relative biological effectiveness) in 2 fractions and retrospectively analyzed after long-term observation. The main endpoints of this study were treatment-related toxicity and local tumor control. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Changes in the Child-Pugh score from before to after CIRT were also examined to evaluate hepatic toxicity. Local control was defined as no progression of the irradiated lesion according to the modified Response Evaluation Criteria in Solid Tumors. RESULTS: The median age of the patients was 75 years (range, 49-89 years). Of these patients, 41 had a newly diagnosed lesion, and 16 had residual or recurrent lesions after previous treatments. The median follow-up duration was 54 months (range, 7-103 months). All surviving patients were followed for more than 51 months. Two patients experienced grade 3 acute skin reactions, but no other grade 3 or higher toxicities were observed in any organ. No patient exhibited an increase in the Child-Pugh score of 2 or more points after CIRT. The local tumor control rates at 1, 3, and 5 years were 98%, 91%, and 91% after CIRT, respectively. All lesions that failed to respond to previous treatments were successfully controlled by CIRT. The 1-, 3-, and 5-year overall survival rates were 97%, 67%, and 45%, respectively. CONCLUSIONS: Two-fraction CIRT was a well-tolerated and effective treatment for patients with HCC.

Single-molecule resonance Raman effect in a plasmonic nanocavity.

Tip-enhanced Raman spectroscopy (TERS) is a versatile tool for chemical analysis at the nanoscale. In earlier TERS experiments, Raman modes with components parallel to the tip were studied based on the strong electric field enhancement along the tip. Perpendicular modes were usually neglected. Here, we investigate an isolated copper naphthalocyanine molecule adsorbed on a triple-layer NaCl on Ag(111) using scanning tunnelling microscope TERS imaging. For flat-lying molecules on NaCl, the Raman images present different patterns depending on the symmetry of the vibrational mode. Our results reveal that components of the electric field perpendicular to the tip should be considered aside from the parallel components. Moreover, under resonance excitation conditions, the perpendicular components can play a substantial role in the enhancement. This single-molecule study in a well-defined environment provides insights into the Raman process at the plasmonic nanocavity, which may be useful in the nanoscale metrology of various molecular systems.

Selective triplet exciton formation in a single molecule.

The formation of excitons in organic molecules by charge injection is an essential process in organic light-emitting diodes (OLEDs)1-7. According to a simple model based on spin statistics, the injected charges form spin-singlet (S1) excitons and spin-triplet (T1) excitons in a 1:3 ratio2-4. After the first report of a highly efficient OLED2 based on phosphorescence, which is produced by the decay of T1 excitons, more effective use of these excitons has been the primary strategy for increasing the energy efficiency of OLEDs. Another route to improving OLED energy efficiency is reduction of the operating voltage2-6. Because T1 excitons have lower energy than S1 excitons (owing to the exchange interaction), use of the energy difference could-in principle-enable exclusive production of T1 excitons at low OLED operating voltages. However, a way to achieve such selective and direct formation of these excitons has not yet been established. Here we report a single-molecule investigation of electroluminescence using a scanning tunnelling microscope8-20 and demonstrate a simple method of selective formation of T1 excitons that utilizes a charged molecule. A 3,4,9,10-perylenetetracarboxylicdianhydride (PTCDA) molecule21-25 adsorbed on a three-monolayer NaCl film atop Ag(111) shows both phosphorescence and fluorescence signals at high applied voltage. In contrast, only phosphorescence occurs at low applied voltage, indicating selective formation of T1 excitons without creating their S1 counterparts. The bias voltage dependence of the phosphorescence, combined with differential conductance measurements, reveals that spin-selective electron removal from a negatively charged PTCDA molecule is the dominant formation mechanism of T1 excitons in this system, which can be explained by considering the exchange interaction in the charged molecule. Our findings show that the electron transport process accompanying exciton formation can be controlled by manipulating an electron spin inside a molecule. We anticipate that designing a device taking into account the exchange interaction could realize an OLED with a lower operating voltage.

Percutaneous Pericardiocentesis With the Anterior Approach: Demonstration of the Precise Course With Computed Tomography.

OBJECTIVES: This study aimed to confirm the precise course of a pericardiocentesis with the anterior approach using post-procedural computed tomography (CT). BACKGROUND: Percutaneous epicardial ventricular tachycardia (VT) ablation has been increasingly performed. Although the inferior approach has been the common method, the feasibility of the anterior approach has subsequently been reported. However, the precise course of the anterior approach has not been presented. METHODS: An epicardial ablation with the anterior approach was performed in 15 patients. At the end of the procedure, the epicardial sheath was exchanged for a drainage tube to monitor bleeding. Of those patients, in 9 procedures in 8 patients a CT scan was performed just after the procedure to confirm the course of the drainage tube and to rule out any complications. Epicardial ablation was indicated for a failed endocardial VT ablation in 7 patients and epicardial substrate modification in 1 patient with Brugada syndrome. RESULTS: Volume-rendered images reconstructed from CT demonstrated each course of the drainage tubes and their relation to the surrounding organs. These images revealed that the tube had a curved trace, and did not penetrate the diaphragm or pass through the abdominal cavity. No injury to the surrounding organs was detected in any of the cases. CONCLUSIONS: The precise course of the drainage tube placed along the trajectory of the anterior approach was able to be confirmed using post-procedural CT images. These images support the safety and feasibility of the anterior approach from the anatomic standpoint with a low incidence of abdominal viscera injury.

Acute Adrenal Insufficiency Precipitated by the Discontinuation of a Betamethasone and Dextrochlorpheniramine Combination: The Diagnostic Utility of an Echocardiographic Assessment of Systemic Vascular Resistance.

A 72-year-old woman with primary biliary cholangitis was admitted to our hospital with heart failure with a preserved ejection fraction. An accidental right ventricular perforation that occurred during an endomyocardial biopsy precipitated cardiogenic shock. Despite successful surgical treatment, she demonstrated progressive hemodynamic deterioration, which was resistant to the administration of high-dose catecholamines. She was diagnosed with acute adrenal insufficiency, which was attributed to the discontinuation of Celestamine® (betamethasone/dextrochlorpheniramine combination) just after the perforation. Prompt intravenous administration of hydrocortisone (150 mg/day) led to hemodynamic stabilization. The serial noninvasive assessment of systemic vascular resistance using transthoracic echocardiography was instrumental in detecting acute adrenal insufficiency in this case.

Successful Triple Combination Immunosuppressive Therapy with Prednisolone, Cyclosporine, and Mycophenolate Mofetil to Treat Recurrent Giant Cell Myocarditis.

A 59-year-old man with a history of giant cell myocarditis was admitted to our hospital with recurrent giant cell myocarditis triggered by a 1 mg/day taper in his prednisolone dose. During the initial episode, he had undergone rescue implantation of a temporary left ventricular assist device followed by the administration of dual immunosuppressive therapy with prednisolone and concomitant cyclosporine. Triple combination immunosuppressive therapy maintained with additional mycophenolate mofetil successfully controlled recurrent myocarditis, enabled a reduction in the prednisolone dose, and achieved the functional recovery of the left ventricle.