Exploring the Molecular-Scale Structures at Solid/Liquid Interfaces of Li-Ion Battery Materials: A Force Spectroscopy Analysis with Sparse Modeling.

In this study, we clarify the liquid structure formed at the interface between LiCoO2 (LCO), the cathode material of Li-ion batteries, and propylene carbonate (PC), which is used as a solvent in the electrolyte, on a molecular scale. We apply sparse modeling-based modal analysis to force spectroscopy data measured by frequency modulation atomic force microscopy (FM-AFM) and show that each component in the FM-AFM force curve, such as oscillatory solvation force, background, and noise, can be automatically decomposed. Moreover, by combining detailed force curve analysis with solid/liquid interface simulations based on first-principles calculation, we have identified that there are distinct damped vibrational modes in the force curves at the LCO/PC interface with a period of about 0.57 nm and those with shorter periods, which likely correspond to the solvation forces associated with bulk-state PC molecules and those with PC molecules in "lying down" orientations.

Establishing Optimal Control Cohorts for Phase 1 Trials: Retrospective Analysis of Clinical and Biological Outcomes in Neonates and Infants Undergoing Two-Ventricle Repair.

Phase 1 trials are primarily conducted to evaluate the safety and feasibility of new interventions, usually without recruiting control patients. This retrospective study aims to characterize clinical and biological outcomes in historical and contemporary cases of neonates and infants undergoing two-ventricle repair to facilitate future secondary endpoint analyses for such trials. This retrospective study included neonates/infants (ages ≤ 6 months) who underwent two-ventricle repair between 2015 and 2021 using the same criteria as our phase 1 trial (n = 199). Patients were allocated into the ventricular septal defect (n = 61), the Tetralogy of Fallot (TOF, n = 88), and the transposition of the great arteries (n = 50) groups with an additional comparison between two eras (2015-2019 vs. 2020-2021). Patient characteristics and most variables assessed were different between the three diagnostic groups indicating the importance of diagnostic matching for secondary analyses. Although the era did not alter cerebral/somatic oxygenation, ventricular function, neuroimaging findings, and complication rates, we observed improvement of inotropic and/or vasoactive-inotropic scores in all groups during the more recent era. In 2020-2021, the age and the body weight at the operation were higher, and hospital stay was shorter in the TOF group, suggesting the possible impact of the pandemic. Results also indicated that matching altered characteristics such as age at operation that may limit the temporal effects and optimize secondary analyses. Using optimal contemporary cases and historical data based on this study will assist in developing a comprehensive study design for a future efficacy/effectiveness trial.

Defining the optimal historical control group for a phase 1 trial of mesenchymal stromal cell delivery through cardiopulmonary bypass in neonates and infants.

OBJECTIVE: The Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery study is a prospective, open-label, single-centre, dose-escalation phase 1 trial assessing the safety/feasibility of delivering mesenchymal stromal cells to neonates/infants during cardiac surgery. Outcomes will be compared with historical data from a similar population. We aim to define an optimal control group for use in the Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery trial. METHODS: Consecutive patients who underwent a two-ventricle repair without aortic arch reconstruction within the first 6 months of life between 2015 and 2020 were studied using the same inclusion/exclusion criteria as the Phase 1 Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery trial (n = 169). Patients were allocated into one of three diagnostic groups: ventricular septal defect type, Tetralogy of Fallot type, and transposition of the great arteries type. To determine era effect, patients were analysed in two groups: Group A (2015-2017) and B (2018-2020). In addition to biological markers, three post-operative scoring methods (inotropic and vasoactive-inotropic scores and the Pediatric Risk of Mortality-III) were assessed. RESULTS: All values for three scoring systems were consistent with complexity of cardiac anomalies. Max inotropic and vasoactive-inotropic scores demonstrated significant differences between all diagnosis groups, confirming high sensitivity. Despite no differences in surgical factors between era groups, we observed lower inotropic and vasoactive-inotropic scores in group B, consistent with improved post-operative course in recent years at our centre. CONCLUSIONS: Our studies confirm max inotropic and vasoactive-inotropic scores as important quantitative measures after neonatal/infant cardiac surgery. Clinical outcomes should be compared within diagnostic groupings. The optimal control group should include only patients from a recent era. This initial study will help to determine the sample size of future efficacy/effectiveness studies.

Structured Water Molecules on Membrane Proteins Resolved by Atomic Force Microscopy.

Water structuring on the outer surface of protein molecules called the hydration shell is essential as well as the internal water structures for higher-order structuring of protein molecules and their biological activities in vivo. We now show the molecular-scale hydration structure measurements of native purple membrane patches composed of proton pump proteins by a noninvasive three-dimensional force mapping technique based on frequency modulation atomic force microscopy. We successfully resolved the ordered water molecules localized near the proton uptake channels on the cytoplasmic side of the individual bacteriorhodopsin proteins in the purple membrane. We demonstrate that the three-dimensional force mapping can be widely applicable for molecular-scale investigations of the solid-liquid interfaces of various soft nanomaterials.

Molecular-Resolution Imaging of Interfacial Solvation of Electrolytes for Lithium-Ion Batteries by Frequency Modulation Atomic Force Microscopy.

Solvation structures formed by ions and solvent molecules at solid/electrolyte interfaces affect the energy storage performance of electrochemical devices, such as lithium-ion batteries. In this study, the molecular-scale solvation structures of an electrolyte, a solution of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in propylene carbonate (PC) at the electrolyte-mica interface, were measured using frequency-modulation atomic force microscopy (FM-AFM). The spacing of the characteristic force oscillation in the force versus distance curves increased with increasing ion concentration, suggesting an increase in the effective size of molecules at the interface. Molecular dynamics simulations showed that the effective size of molecular assemblies, namely, solvated ions formed at the interface, increased with increasing ion concentrations, which was consistent with the experimental results. Knowledge of molecular-scale structures of solid/electrolyte interfaces obtained by a combination of FM-AFM and molecular dynamics simulations is important in the design of electrolytes for future energy devices and in improving their properties.

Ultrasound of shoulder and knee improves the accuracy of the 2012 EULAR/ACR provisional classification criteria for polymyalgia rheumatica.

OBJECTIVE: Recent studies suggest that the knee is frequently involved in PMR. In this study, we aimed to determine whether the US assessment of the shoulder and knee discriminates between PMR and other differential diagnoses and improves the accuracy of the 2012 EULAR/ACR provisional classification criteria for PMR. METHODS: We consecutively enrolled 81 untreated patients who received a diagnosis of PMR. These patients were divided into two groups based on the final diagnosis made at 1-year follow-up: PMR-definite group (n = 60) and PMR-mimic group (n = 21). We also enrolled age/sex-matched untreated RA patients with shoulder pain from an independent cohort (RA group, n = 60). All patients underwent comprehensive US assessment of the shoulder and knee for synovitis, bursitis, tenosynovitis, tendinitis and ligament inflammation at baseline. RESULTS: US scores for tenosynovitis, tendinitis and ligament inflammation better discriminated the PMR-definite group from the PMR-mimic and RA groups than do those for synovitis or bursitis. Among logistic regression models to identify US variables that were associated with the PMR-definite group, the best fitted model included two US variables: the bilateral involvement of the shoulder (long head of biceps, supraspinatus or subscapularis tendon) and the bilateral involvement of the knee (popliteus tendon or medial or lateral collateral ligament). Incorporating these two items into the 2012 EULAR/ACR provisional classification criteria numerically increased the accuracy to classify the PMR-definite group. CONCLUSION: US assessment of the tendon/ligament-related lesions in the shoulder and knee may improve the accuracy of the 2012 EULAR/ACR provisional classification criteria for PMR.

[A Rare Case of Primary Splenic Malignant Lymphoma Associated with Esophagogastric Junction Neuroendocrine Carcinoma(NEC)].

A 75-year-old man was showed wall thickening just below esophagogastric junction(EGJ)by gastroscopy(GS). Biopsy indicated mucinous carcinoma. He was referred to our hospital. Computed tomography(CT), PET-CT showed EGJ cancer and splenic tumor. EGJ cancer was diagnosed GE, Siewert Type Ⅱ, GrePostAnt, Type 1, cT2, cN0, cM0, cStage Ⅰ. The patient underwent total gastrectomy, lower esophagectomy, D2+ #19, 20, 110, 111, 112 lymph nodes dissection, Rou-en- Y reconstruction, distal pancreatectomy, splenectomy, cholecystectomy, and enterostomy. Postoperative complication was pancreatic fistula(Grade Ⅱ). Pathological diagnosis was esophagogastric junction cancer, neuroendocrine carcinoma(NEC), GE, Siewert Type Ⅱ, GrePostAnt, Type 1, pT2(MP), pN1, pM0, pStage ⅡA. Splenic tumor was diagnosed splenic malignant lymphoma, large B-cell, diffuse(DLBCL), NOS, low-immediate risk. Patient was discharged 15 days after the operation and underwent adjuvant chemotherapy with S-1. In this case, he started taking S-1 because the prognosis of NEC is poorer than PSML. There was no evidence of recurrence after 5 months from gastrectomy. As a result of searching for"neuroendocrine tumor"and"malignant lymphoma"in the JAMAS, there was no report of NEC associated with malignant lymphoma. We experienced the rare case of primary splenic malignant lymphoma associated with EGJ NEC. In the case of gastric cancer with splenic tumor, malignant lymphoma of spleen should be concerned.

[A Case of Laparoscopic Total Gastrectomy for Juvenile Polyposis of Stomach with Synchronous Multiple Intramucosal Carcinomas].

The patient was a 57-year-old woman. She was referred to our hospital because severe anemia. Upper gastrointestinal endoscopy revealed polyposis throughout the stomach and lobulated polyps in cardia, greater curve of middle body of the stomach, and angulus. Colonoscopy and small bowel endoscopy showed no obvious abnormal findings. Based on these findings, a laparoscopic total gastrectomy with D1 lymph node dissection was performed for suspected juvenile polyposis of stomach with severe anemia. The gross examination of the resection specimen revealed diffuse polyposis throughout the stomach, and histopathological examination revealed hyperplasia of the orbital epithelium throughout the stomach and lack of edema in lamina propria of mucous and eosinophil leukocytic infiltration, leading to the diagnosis of juvenile polyposis of stomach. Two well differentiated adenocarcinomas were found in 2 locations, which remained within the mucosa. We report a case of laparoscopic total gastrectomy for juvenile polyposis of the stomach with gastric cancer, with some discussion of the literature.

Surface charge density measurement of a single protein molecule with a controlled orientation by AFM.

The spatial distribution of functional groups causes a charge distribution that often has a close relationship with its biofunctions. To understand them of the protein molecules, measurements of the charge distribution under physiological conditions are desired. Atomic force microscopy (AFM) has been utilized to measure the surface charge density by measuring the electric double layer (EDL) force caused by the overlap of the EDLs on the surfaces of the AFM tip and the biomolecule. Here, we demonstrated the surface charge density measurement of a single streptavidin (SA) protein molecule by the three-dimensional force mapping method based on frequency modulation AFM (FM-AFM). The SA has a strong affinity to biotin because of the electrostatic interactions between the molecules. Therefore, the surface charge density measurements of the biotin-binding sites and other surface areas of the molecule have been anticipated. However, the surface charge density of the surfaces other than the biotin-binding side has never been measured. We demonstrate the surface charge density measurement of the top surface of the single SA molecule, which is perpendicular to the biotin-binding sides, with a controlled orientation using DNA origami as a template by FM-AFM in an electrolyte solution. The surface charge density of the top surface of the SA molecule was estimated by fitting the experimental force curves to the Derjaguin-Landau-Verwey-Overbeck theory. We found that the surface charge density of the top surface of the SA molecule is comparable to those reported earlier for the biotin-binding sides of the molecule. We expect that, by using the DNA origami technology, one can control the orientation of a biomolecule attached to the substrate and measure the surface charge density of the specific surface areas of the biomolecule to obtain information that will help us to understand the relationship between their structures and functions.

Low-Background Tip-Enhanced Raman Spectroscopy Enabled by a Plasmon Thin-Film Waveguide Probe.

Tip-enhanced Raman spectroscopy (TERS) is a nano-optical approach to extract spatially resolved chemical information with nanometer precision. However, in the case of direct-illumination TERS, which is often employed in commercial TERS instruments, strong fluorescence or far-field Raman signals from the illuminated areas may be excited as a background. They may overwhelm the near-field TERS signal and dramatically decrease the near-field to far-field signal contrast of TERS spectra. It is still challenging for TERS to study the surface of fluorescent materials or a bulk sample that cannot be placed on an Au/Ag substrate. In this study, we developed an indirect-illumination TERS probe that allows a laser to be focused on a flat interface of a thin-film waveguide located far away from the region generating the TERS signal. Surface plasmon polaritons are generated stably on the waveguide and eventually accumulated at the tip apex, thereby producing a spatially and energetically confined hotspot to ensure stable and high-resolution TERS measurements with a low background. With this thin-film waveguide probe, TERS spectra with obvious contrast from a diamond plate can be acquired. Furthermore, the TERS technique based on this probe exhibits excellent TERS signal stability, a long lifetime, and good spatial resolution. This technique is expected to have commercial potential and enable further popularization and development of TERS technology as a powerful analytical method.

The Effect of Auditory Residual Inhibition on Tinnitus and the Electroencephalogram.

OBJECTIVES: Tinnitus is the perception of sound in the absence of an external physical sound source, for some people it can severely reduce the quality of life. Acoustic residual inhibition (ARI) is a suppression of tinnitus following the cessation of a sound. The present study investigated the effect of ARI on brain activity measured using EEG. DESIGN: Thirty adult participants (mean age of 58 years) experiencing chronic tinnitus (minimum 2 years) participated. Participants were presented broad band noise at 10 dB above minimum masking level (1 min followed by 4 min of silence, 4 times) counterbalanced with a control treatment of broad band noise at threshold (1 min followed by 4 min of silence, 4 times) while 64-channel EEG was simultaneously recorded. Tinnitus loudness was measured using a 9-point tinnitus loudness rating scale. RESULTS: The ARI stimulation resulted in a self-reported reduction in tinnitus loudness in 17 of the 30 participants. Tinnitus rating reduced following stimulation but gradually returned to near baseline during 4 min of silence post sound exposure; successive sound exposures resulted in lower loudness ratings. No significant reductions in loudness rating were found with the control stimulation. The EEG showed increases in power spectral density, particularly in the alpha and gamma bands, during ARI compared to the control periods. CONCLUSIONS: These results contribute to the understanding of ARI and tinnitus. We recommend that there be a closer examination of the relationship between onset and offset of sound in both tinnitus and nontinnitus control participants to ascertain if EEG changes seen with ARI relate to tinnitus suppression or general postsound activity.

Right arch with prostaglandin-dependent coarctation and aberrant left carotid artery in a 22q11.2 deletion infant.

Right aortic arch in association with coarctation of the aorta and vascular ring is a rare anatomy. We present an infant with chromosome 22q11.2 deletion, who had the right aortic arch with retroesophageal aberrant left subclavian artery and left internal carotid artery. The left external carotid artery and right common carotid artery originated together from the ascending aorta as a bovine branch. The infant also had severe coarctation, which was prostaglandin dependent.

Entropy-Regularized Optimal Transport on Multivariate Normal and q-normal Distributions.

The distance and divergence of the probability measures play a central role in statistics, machine learning, and many other related fields. The Wasserstein distance has received much attention in recent years because of its distinctions from other distances or divergences. Although computing the Wasserstein distance is costly, entropy-regularized optimal transport was proposed to computationally efficiently approximate the Wasserstein distance. The purpose of this study is to understand the theoretical aspect of entropy-regularized optimal transport. In this paper, we focus on entropy-regularized optimal transport on multivariate normal distributions and q-normal distributions. We obtain the explicit form of the entropy-regularized optimal transport cost on multivariate normal and q-normal distributions; this provides a perspective to understand the effect of entropy regularization, which was previously known only experimentally. Furthermore, we obtain the entropy-regularized Kantorovich estimator for the probability measure that satisfies certain conditions. We also demonstrate how the Wasserstein distance, optimal coupling, geometric structure, and statistical efficiency are affected by entropy regularization in some experiments. In particular, our results about the explicit form of the optimal coupling of the Tsallis entropy-regularized optimal transport on multivariate q-normal distributions and the entropy-regularized Kantorovich estimator are novel and will become the first step towards the understanding of a more general setting.

Autistic traits are associated with the functional connectivity of between-but not within-attention systems in the general population.

BACKGROUND: Previous studies have demonstrated that individuals with autism spectrum disorder (ASD) exhibit dysfunction in the three attention systems (i.e., alerting, orienting, and executive control) as well as atypical relationships among these systems. Additionally, other studies have reported that individuals with subclinical but high levels of autistic traits show similar attentional tendencies to those observed in ASD. Based on these findings, it was hypothesized that autistic traits would affect the functions and relationships of the three attention systems in a general population. Resting-state functional magnetic resonance imaging (fMRI) was performed in 119 healthy adults to investigate relationships between autistic traits and within- and between-system functional connectivity (FC) among the three attention systems. Twenty-six regions of interest that were defined as components of the three attention systems by a previous task-based fMRI study were examined in terms of within- and between-system FC. We assessed autistic traits using the Autism-Spectrum Quotient. RESULTS: Correlational analyses revealed that autistic traits were significantly correlated with between-system FC, but not with within-system FC. CONCLUSIONS: Our results imply that a high autistic trait level, even when subclinical, is associated with the way the three attention systems interact.

High-throughput phenotypic screening of random genomic fragments in transgenic rice identified novel drought tolerance genes.

KEY MESSAGE: Novel drought tolerance genes were identified by screening thousands of random genomic fragments from grass species in transgenic rice. Identification of agronomically important genes is a critical step for crop breeding through biotechnology. Multiple approaches have been employed to identify new gene targets, including comprehensive screening platforms for gene discovery such as the over-expression of libraries of cDNA clones. In this study, random genomic fragments from plants were introduced into rice and screened for drought tolerance in a high-throughput manner with the aim of finding novel genetic elements not exclusively limited to coding sequences. To illustrate the power of this approach, genomic libraries were constructed from four grass species, and screening a total of 50,825 transgenic rice lines for drought tolerance resulted in the identification of 12 reproducibly efficacious fragments. Of the twelve, two were from the mitochondrial genome of signal grass and ten were from the nuclear genome of buffalo grass. Subsequent sequencing and analyses revealed that the ten fragments from buffalo grass carried a similar genetic element with no significant homology to any previously characterized gene. The deduced protein sequence was rich in acidic amino acid residues in the C-terminal half, and two of the glutamic acid residues in the C-terminal half were shown to play an important role in drought tolerance. The results demonstrate that an open-ended screening approach using random genomic fragments could discover trait genes distinct from gene discovery based on known pathways or biased toward coding sequence over-expression.

Efficacy of rituximab for anti-neutrophil cytoplasmic antibody-associated hypertrophic pachymeningitis: a case series.

OBJECTIVES: This study researched the efficacy of rituximab (RTX) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated hypertrophic pachymeningitis (HP). METHODS: Eight patients were identified by retrospective chart review from local registries at four hospitals in Japan. All patients met the Chapel Hill 2012 Consensus Conference definitions of ANCA-associated vasculitis and had disease complicated with HP. We assessed the dose of glucocorticoids, C-reactive protein (CRP) levels, Birmingham vasculitis activity score (BVAS) and contrast-enhanced magnetic resonance imaging (MRI) findings of HP before and after RTX administration. RESULTS: Three of eight patients were female. The median age was 68 years. No patients had HP at onset of vasculitis. Two patients had a relapse of HP before RTX administration. RTX was used as the initial treatment for HP in three patient. The daily dose of glucocorticoids, CRP levels and BVAS decreased from baseline to 6 months after RTX treatment in all patients. Evaluation of HP by contrast-enhanced MRI showed improvement in seven of eight cases. All of seven patients achieved sustained remission at 6 months after RTX treatment. No serious adverse events were observed in any patient. CONCLUSIONS: Our case series highlights the efficacy of RTX in patients with difficult-to-treat ANCA-associated HP. Future prospective studies are warranted to establish B-cell depletion therapy by RTX as a treatment option for ANCA-associated HP.

Atomic-Level Viscosity Distribution in the Hydration Layer.

The viscosity of solvation structures is crucial for the development of energy-efficient biofunctional and electrochemical devices. Elucidating their subnanoscale distributions can cause the formation of a sustainable energy society. Here, we visualize the site-specific three-dimensional damping distribution on a CaCO_{3} surface composed of binary ion species using ultra-low-noise frequency modulation atomic force microscopy. With the support from molecular dynamics simulation, we found a strikingly large damping at the calcium sites, which demonstrates the capability of this methodology to visualize atomic-scale viscosity in the hydration layers. Our finding will expedite the evolutions of various functional devices.

Auditory Streaming and Prediction in Tinnitus Sufferers.

OBJECTIVES: The aim of this study was to determine whether auditory streaming (segregation of incoming sounds into separate sound sources) and the ability to anticipate future auditory events are affected in tinnitus sufferers compared with nontinnitus controls with matched levels of hearing. It was hypothesized that tinnitus would result in abnormal electroencephalography responses to tone deviants and tone omissions compared to controls for frequencies near the pitch of tinnitus, and this should correspond with increased levels of cortical γ and θ oscillatory rhythms. DESIGN: Sixteen individuals with tinnitus (10 men and 6 women; age, 53.44; SD, 12.92 years) and 14 control participants (8 men and 6 women; age, 50.25; SD, 18.54 years) took part in the study. A modified version of the ABA streaming paradigm, with repeating triplet pattern of two frequencies (A and B) presented as A-B-A, was used to examine deviant-related prediction error. Omission-related prediction errors were examined using a modified version of a tone-omission paradigm. Regions of interest were frontocentral, left frontal, right frontal, and temporal lobes. RESULTS: A larger N1c waveform was elicited in the absence of any tone deviation within the left primary auditory cortex of tinnitus participants. No differences were present between groups for omissions. The only difference in oscillatory band activity between the two groups in this study was in response to tones 7 semitones different from tinnitus pitch, with significantly lower ß-2 band activity present for the tinnitus group, correlating most with activity within the right inferior occipital gyrus. CONCLUSIONS: The findings from this study imply that cortical-level auditory stream segregation is altered among individuals with tinnitus.

Investigation of Local Hydration Structures of Alkanethiol Self-Assembled Monolayers with Different Molecular Structures by FM-AFM.

Hydration structures play crucial roles in a wide variety of chemical and biological phenomena. However, the key factors that determine a hydration structure remain an open question. Most recent studies have focused on the electrostatic interactions between the surface charges and dipoles of water molecules, which are determined by the atomic/ionic species of the outermost solid surface, as the dominating factor. The number of studies on the correlation between the hydration structure and the atomic-scale surface corrugation has been limited. In this study, we investigated the hydration structures of alkanethiol self-assembled monolayers terminated with a hydroxyl group using frequency-modulated atomic force microscopy. We observed two molecular structures, namely, the (√3 × âˆš3) R30° structure and the c(4 × 2) superlattice structure, and found that their hydration structures are different mainly because of the slight differences in their molecular arrangements. This result suggests that a slight difference in the molecular/atomic arrangements as well as the atomic/ionic species in the outermost solid surface strongly influences the local hydration structures.

Atomic-Scale 3D Local Hydration Structures Influenced by Water-Restricting Dimensions.

Hydration structures at solid-liquid interfaces mediate between the atomic-level surface structures and macroscopic functionalities in various physical, chemical, and biological processes. Atomic-scale local hydration measurements have been enabled by ultralow noise three-dimensional (3D) frequency-modulation atomic force microscopy. However, for their application to complicated surface structures, e.g., biomolecular devices, understanding the relationship between the hydration and surface structures is necessary. Herein, we present a systematic study based on the concept of the structural dimensionality, which is crucial in various scientific fields. We performed 3D measurements and molecular dynamics simulations with silicate surfaces that allow for 0, 1, and 2 degrees of freedom to water molecules. Consequently, we found that the 3D hydration structures reflect the structural dimensions and the hydration contrasts decrease with increasing dimension due to the enlarged water self-diffusion coefficient and increased embedded hydration layers. Our results provide guidelines for the analysis of complicated hydration structures, which will be exploited in extensive fields.