Magnon-Phonon Coupling of Synthetic Antiferromagnets in a Surface Acoustic Wave Cavity Resonator.

We used a surface acoustic wave (SAW) cavity resonator to study the coupling of acoustic magnons in a synthetic antiferromagnet (SAF) and phonons carried by SAWs. The SAF is composed of a CoFeB/Ru/CoFeB trilayer, and the scattering matrix of the SAW resonator is studied to assess the coupling. We find that the spectral line width of the SAW resonator is modulated when the frequency of the excited magnons approaches the SAW resonance frequency. Such a change in the spectral linewidth can be well reproduced using macrospin-like model calculations. From the model analyses, we estimate the magnon-phonon coupling strength to be ∼9.9 MHz at a SAW resonance frequency of 1.8 GHz: the corresponding magnomechanical cooperativity is ∼0.66. As the spectral shape hardly changes in a CoFeB single-layer reference sample, these results show that SAF provides an ideal platform to study magnon-phonon coupling in an SAW cavity resonator.

An In Vivo Dual-Observation Method to Monitor Tumor Mass and Tumor-Surface Blood Vessels for Developing Anti-Angiogenesis Agents against Submillimeter Tumors.

Managing metastasis at the early stage and detecting and treating submillimeter tumors at early metastasis are crucial for improving cancer prognosis. Angiogenesis is a critical target for developing drugs to detect and inhibit submillimeter tumor growth; however, drug development remains challenging because there are no suitable models for observing the submillimeter tumor mass and the surrounding blood vessels in vivo. We have established a xenograft subcutaneous submillimeter tumor mouse model with HT-29-RFP by transplanting a single spheroid grown on radiation-crosslinked gelatin hydrogel microwells. Here, we developed an in vivo dual-observation method to observe the submillimeter tumor mass and tumor-surface blood vessels using this model. RFP was detected to observe the tumor mass, and a fluorescent angiography agent FITC-dextran was administered to observe blood vessels via stereoscopic fluorescence microscopy. The anti-angiogenesis agent regorafenib was used to confirm the usefulness of this method. This method effectively detected the submillimeter tumor mass and tumor-surface blood vessels in vivo. Regorafenib treatment revealed tumor growth inhibition and angiogenesis downregulation with reduced vascular extremities, segments, and meshes. Further, we confirmed that tumor-surface blood vessel areas monitored using in vivo dual-observation correlated with intratumoral blood vessel areas observed via fluorescence microscopy with frozen sections. In conclusion, this method would be useful in developing anti-angiogenesis agents against submillimeter tumors.

[Robot-assisted Thoracic Surgery for Mediastinal Tumor].

In Japan, robot-assisted thoracic surgery (RATS) was introduced in thoracic surgery in 2001, but it did not become widespread. However, surgery for mediastinal tumors and lobectomy for lung cancer with RATS were covered by insurance in 2018 and are currently becoming popular as a general practice, following video-assisted thoracic surgery(VATS). Forty-six patients with mediastinal tumors were treated by RATS from February 2014 to November 2022 in our institution. Theoretically, the RATS approach is performed from one side in a semi-supine position under CO2 insufflation as with the VATS approach of our institution. In the case of extended thymectomy, a bilateral approach is performed by changing the patient's position. The median surgery time was 88 min, and the median surgery time in unilateral and bilateral approaches were 79 and 208 min, respectively. Blood loss during surgery was quite minimum, and no patients required conversion to VATS or thoracotomy. Regarding adverse events, postoperative bleeding was observed in one patient (2.2%). RATS has been successfully introduced and expanded safely for mediastinal tumors. Considering further expansion of RATS indications while conducting verification by comparison with VATS in the future is necessary.

In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized 64Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study.

Peritoneal dissemination of pancreatic cancer has a poor prognosis. We have reported that intraperitoneal radioimmunotherapy using a 64Cu-labeled antibody (64Cu-ipRIT) is a promising adjuvant therapy option to prevent this complication. To achieve personalized 64Cu-ipRIT, we developed a new in vitro tumor cell-binding assay (64Cu-TuBA) system with a panel containing nine candidate 64Cu-labeled antibodies targeting seven antigens (EGFR, HER2, HER3, TfR, EpCAM, LAT1, and CD98), which are reportedly overexpressed in patients with pancreatic cancer. We investigated the feasibility of 64Cu-TuBA to select the highest-binding antibody for individual cancer cell lines and predict the treatment response in vivo for 64Cu-ipRIT. 64Cu-TuBA was performed using six human pancreatic cancer cell lines. For three cell lines, an in vivo treatment study was performed with 64Cu-ipRIT using high-, middle-, or low-binding antibodies in each peritoneal dissemination mouse model. The high-binding antibodies significantly prolonged survival in each mouse model, while low-and middle-binding antibodies were ineffective. There was a correlation between in vitro cell binding and in vivo therapeutic efficacy. Our findings suggest that 64Cu-TuBA can be used for patient selection to enable personalized 64Cu-ipRIT. Tumor cells isolated from surgically resected tumor tissues would be suitable for analysis with the 64Cu-TuBA system in future clinical studies.

[The Basic Research of Antigen-antibody Reaction in Lung Transplantation].

Lung transplantation has become popular in Japan, showing better survival rate than other countries. However, the results are still not satisfactory compared with other solid organ transplantation. One of the reasons for this might be that knowledge on donor-specific antibodies or antibody-related rejection, which has been attracting attention these days, is less than that of kidney or liver transplantation. Our laboratory has continued basic research in this field using rodent lung transplantation model. We have previously shown that type V collagen is associated in chronic rejection as an autoimmune, and that oral administration of type V collagen induces tolerance. The murine chronic rejection model of the minor antigen mismatch was developed, and involvement of the humoral immunity and role of the complement activation were shown. We are now studying the effects of immune checkpoint molecules, which play a central role in the field of cancer therapy, on rejection after lung transplantation. We are also working to verify the effects of anti-complement drugs and molecular targeted drugs in the future treatment on rejection.

[Surgical Resection and Perioperative Management of Lung Cancer Requiring Vertebrectomy].

While cases of surgical resection for primary lung cancers are increasing, lung cancer requiring vertebrectomy is rare. A high complication rate and recurrence rate have been reported after surgical resection for lung cancer with vertebral invasion. However, select patients who achieve complete resection after effective preoperative chemoradiotherapy show a better survival rate than others. Preoperative computed tomography and magnetic resonance imaging are necessary to consider surgical strategies and how to resect and reconstruct the vertebral body and chest wall with a clear margin before surgery. A 3-dimensional imaging or simulation model is useful for such ends. Several surgical approaches have been developed, such as the transmanubrial, posterior, posterolateral, or the combination thereof. Proper vertebrectomy( total, hemi, part of a vertebra, or only the transverse process of a vertebra) and reconstruction approaches should be decided in conjunction with orthopedic surgeons. While evidence is lacking, establishing proper surgical indications and developing effective strategies to achieve complete resection with a clear margin are the most critical points in lung cancer requiring vertebrectomy.

[Web Questionnaire Survey on Appetite Loss and Weight Loss Associated with Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexia(J-EPOCC)-The Understanding of Cancer Cachexia].

Cancer cachexia is multifactor syndrome that occurs in 50-80% of cancer patients and accounts for 20% of cancer deaths. We conducted a web questionnaire survey for healthcare professionals(doctors and medical staff), patients and families to clarify the understanding of cancer cachexia. As a result, it was revealed that the understanding of cancer cachexia among patients and families was low. Cancer cachexia was widely recognized by healthcare professionals, but 3 stages of EPCRC was not. Many of healthcare professionals recalled the image of terminal stage of cancer from the term "cancer cachexia", and they lack awareness that cancer cachexia was a disease complication which developed from the early stage of cancer. Furthermore, there were many doctors who were faced with the problem such as a lack of treatment options for cancer cachexia. From these facts, it is necessary to disseminate scientific concept of cancer cachexia and establish standard of care from the early stage.

[Web Questionnaire Survey on Appetite Loss and Weight Loss Associated with Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexia(J-EPOCC)-The Problem Awareness of Appetite Loss and Weight Loss].

Appetite loss and weight loss associated with cancer have negative effects on the quality of life and OS of cancer patients. We conducted a web questionnaire survey for healthcare professionals(doctors and medical staff), patients and families to clarify the problem awareness for appetite loss and weight loss associated with cancer. As a result, it turned out that families were more concerned about patients' appetite loss and weight loss, and nearly half of patients haven't consulted their symptoms to healthcare professionals, and it meant that patients missed the opportunity to receive medical intervention due to no consultation. While healthcare professionals have a strong desire to provide dedicated treatment for appetite loss and weight loss in cancer patients, the proportion of patients and families who replied their symptom had improved with the intervention was low. In the near future, it will be necessary to enlighten the importance of symptom management to patients and families and pay attention to their symptom change for healthcare professionals.

Prevalence of Restless Legs Syndrome and Its Effects on Sleep and Health-Related Quality of Life in Patients With Heart Failure.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder characterized by leg restlessness and dysesthesia. Although the relationship between RLS and heart failure (HF) has been reported, the prevalence and clinical significance of RLS in patients with HF remain to be elucidated. METHODS AND RESULTS: We enrolled consecutive patients with HF who were admitted to our institutions. RLS was diagnosed using the International Restless Legs Syndrome Study Group criteria. Subjective sleepiness, sleep quality, and quality of life (QoL) were assessed using the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and 8-item Short Form (SF-8), respectively. Among the 133 patients, 18 (13.6%) had RLS and were younger than those without RLS (62.4±13.4 vs 70.0±12.2, P = .017). The RLS group had significantly disrupted sleep quality and QoL, with greater PSQI score (8.0±3.2 vs 5.9±3.3, P = .015) and lower SF-8 physical component summary (PCS) score (35.6±6.5 vs 40.7±9.5, P = .031), despite similar ESS and SF-8 mental component summary scores. In the multivariable regression analysis, RLS was associated with greater PSQI (ß=0.211; P = .014) and lower PCS score (ß=-0.177; P = .045). CONCLUSION: In the patients with HF, RLS was prevalent, and sleep quality and QoL may be disrupted by RLS.

Association between C-reactive protein levels at hospital admission and long-term mortality in patients with acute decompensated heart failure.

The C-reactive protein (CRP) levels obtained at hospital admission are associated with the prognosis of several cardiovascular diseases, including acute coronary syndrome. Although the admission CRP level is associated with in-hospital mortality in patients with acute decompensated heart failure (ADHF), there are limited data on the association between the admission CRP level and long-term mortality in patients with ADHF. This study included consecutive ADHF patients admitted to our institution from 2007 to 2011. Eligible patients were divided into four groups based on quartiles of admission CRP levels. The association between the admission CRP level and long-term mortality was assessed by multivariable Cox proportional analysis, including other independent variables with p values < 0.1 in the univariable analyses. Overall, 527 eligible patients were examined. There were 142 deaths (27%) during a median follow-up period of 2.0 years. In the multivariable analysis, the hazard ratio (HR) significantly increased with admission CRP levels in a dose-dependent manner for mortality (p for trend = 0.034). Multivariable analysis also showed a significant association between the admission CRP level, when treated as a natural logarithm-transformed continuous variable, and increased mortality (HR 1.16, p = 0.030). In patients with ADHF, the admission CRP level was associated with an increased risk of long-term mortality.

Site-specific post-imprinting modification of molecularly imprinted polymer nanocavities with a modifiable functional monomer for prostate cancer biomarker recognition.

Recognition of glycans of glycoproteins using biotic materials such as antibodies is challenging due to lack of antigenicity. Polymeric materials suitable for the molecular recognition of glycoproteins have attracted considerable attention. In this study, we aimed to develop abiotic molecular materials for the recognition of prostate-specific antigen (PSA), a known biomarker for prostate cancer. We used a non-covalent bonding-based molecular imprinting technique to introduce post-imprinting poly(ethylene glycol)-based capping agent into a low-affinity recognition cavity. Details of the binding properties of these groups were investigated to optimize their affinity and selectivity for PSA. Molecularly imprinted polymers (MIPs) were prepared using a bottom-up approach based on surface-initiated atom transfer radical polymerization from a PSA-conjugated sensor chip with a functional monomer-bearing carboxy and secondary amine groups as interaction and post-imprinting modification (PIM) sites, respectively. PSA was orientationally conjugated on the sensor chip through diesters between the immobilized 3-fluorophenyl boronic acid and the cis-diol groups of PSA glucans. Treatment with the capping agent selectively inactivated low-affinity recognition cavities while protecting high-affinity cavities with the addition of a low concentration of PSA as a dynamic protection agent. The MIP thickness is critical in the present molecular imprinting, as a value of less than 5 nm can enable high selectivity. We believe that the proposed strategy based on a non-covalent molecular imprinting approach combined with a PIM-based capping treatment provides a novel method for the development of highly sensitive and selective glycoprotein recognition materials for use in biomarker sensing.

[The First Step in the Optimization of Radiation Protection of Patients in Cerebral Angiography: Investigate the Possibility of Constructing the Diagnostic Reference Level by Imaging Objective/Disease Group Using Display Value of the Blood Vessel Imaging Apparatus].

To optimize the radiation protection of patients, we investigated the possibility of constructing the diagnostic reference levels (DRLs) by imaging objective/disease group using display value of the blood vessel imaging apparatus (air kerma-area product: PKA, air kerma at the patient entrance reference point: Ka, r) in cerebral angiography. We used PKA and Ka, r recorded during surgery of 997 patients at our hospital, and classified them according to the purpose of imaging (diagnostic cerebral angiography or neuro interventional radiology) and disease group. Neuro interventional radiology (PKA: 268±155 Gy・cm2, Ka, r: 2420±1462 mGy) was significantly higher than that of diagnostic cerebral angiography (PKA: 161±70 Gy・cm2, Ka, r: 1112±485 mGy), (Mann-Whitney test, P<0.01). Significant difference was found between PKA and Ka, r for imaging purpose and disease group (Kruskal-Wallis test, P<0.05). It is highly probable that the DRL for cerebral angiography can be constructed by imaging purpose/disease group using display value (PKA, Ka, r) of the blood vessel imaging apparatus.

Relationship between blood urea nitrogen-to-creatinine ratio at hospital admission and long-term mortality in patients with acute decompensated heart failure.

Although elevated blood urea nitrogen (BUN)-to-creatinine (BUN/Cr) ratio at hospital admission has been reported to be associated with poor short-term prognosis, its association to long-term mortality in patients with acute decompensated heart failure (ADHF) remains to be elucidated. Moreover, an additive prognostic value to preexisting renal markers including creatinine and BUN has not been well described. A cohort of 557 consecutive ADHF patients admitted to the cardiac intensive care unit was studied. All cohorts were divided into high and low BUN/Cr ratios according to the median value of BUN/Cr ratio at admission. Association between admission BUN/Cr ratio and long-term all-cause mortality was assessed. There were 145 deaths (27%) observed during the follow-up period of 1.9 years in median. Patients with high BUN/Cr ratio showed with higher mortality compared to low BUN/Cr ratio (log-rank: P = 0.006). In the multivariable analysis, patients with high BUN/Cr ratio at admission were associated with high mortality independently from other covariates including BUN and creatinine (HR 1.81, 95% CI 1.16-2.80, P = 0.009). In patients with ADHF, there is a relationship between admission BUN-to-creatinine ratio and long-term mortality.

Relationship Between Serum Sodium Level Within the Low-Normal Range on Admission and Long-Term Clinical Outcomes in Patients with Acute Decompensated Heart Failure.

Although hyponatremia during hospitalization for acute decompensated heart failure (ADHF) is reportedly related with poor prognosis, the available data regarding the impact of serum sodium level within the low-normal range at admission on clinical events in patients with ADHF is limited.We studied eligible patients admitted to our institution in 2007-2011. All the patients were categorized into 3 groups according to the admission serum sodium levels of < 135 mmol/L (hyponatremia), ≥ 135 and < 140 mmol/L (low-normal range), or ≥ 140 mmol/L (normal range). The association between admission serum sodium levels and long-term clinical events, a composite of all-cause deaths and re-hospitalizations for ADHF, was assessed by multivariable Cox proportional analysis.Of the 584 eligible patients, 208 (35.6%) were in the low-normal range and 99 (16.9%) had hyponatremia on admission. On multivariable analysis, compared with those with a sodium level ≥ 140 mmol/L, patients with hyponatremia were at increased risk for clinical events (hazard ratio [HR], 1.53; P = 0.041), whereas the HR of those in the low-normal range was attenuated and insignificant (HR, 1.08; P = 0.625). However, the HR of each category increased significantly as sodium level decreased (P value for HR trend, 0.024). In addition, when serum sodium level was treated as a continuous variable, the lower the serum sodium level, the greater the risk of clinical events (P = 0.012). The cut-off value of serum sodium level to predict mortality was < 138 mmol/L.In conclusion, a low serum sodium level on admission for ADHF, even if low-normal, can increase the risk of long-term mortality and/or re-hospitalization for ADHF.

Impact on Clinical Outcomes of Periodic Leg Movements During Sleep in Hospitalized Patients Following Acute Decompensated Heart Failure.

BACKGROUND: Periodic leg movements during sleep (PLM) are characterized by regularly recurring movement of the legs during sleep. Although PLM is common and a predictor of death in patients with chronic heart failure, the clinical significance of PLM in hospitalized patients with a reduced left ventricular ejection fraction (LVEF) following acute decompensated heart failure (ADHF) remains unknown.Methods and Results:After initial improvement of acute signs and symptoms of ADHF, 94 consecutive patients with reduced LVEF who underwent polysomnography were enrolled. They were divided into 2 groups based on the presence or absence of severe PLM defined as PLM index ≥30. The risks for clinical events, composite of all-cause death and rehospitalization, were assessed using a stepwise multivariable Cox proportional model including variables showing P<0.10 in univariate analyses. Severe PLM was observed in 21 patients (22%). At a median follow-up of 5.2 months, 30 patients experienced clinical events (32%). In the multivariable analysis, the presence of severe PLM was significantly associated with increasing clinical events (hazard ratio, 2.16; 95% confidence interval, 1.03-4.54; P=0.042) independent of hemoglobin level and the severity of sleep-disordered breathing. CONCLUSIONS: In hospitalized patients with systolic dysfunction following ADHF, severe PLM was prevalent and significantly associated with increased risk of death and/or rehospitalization.

Template Synthesis of Decaphyrin without Meso-Bridges: Cyclo[10]pyrrole.

An acenaphthylene-fused cyclo[10]pyrrole 1b was selectively synthesized via an oxidative coupling reaction of the corresponding 2,2'-bipyrrole with the appropriate dianion template, croconate anion. The structure of 1b as the isolated largest cyclo[n]pyrrole was elucidated by X-ray crystallographic analysis. The absorption spectrum exhibited a markedly red-shifted, intensified L band at 1982 nm, which was interpreted by application of Michl's perimeter and Gouterman's 4-orbital models, supported by magnetic circular dichroism (MCD) data and theoretical calculations.

Soluble Dietary Fibers Can Protect the Small Intestinal Mucosa Without Affecting the Anti-inflammatory Effect of Indomethacin in Adjuvant-Induced Arthritis Rats.

BACKGROUND/AIM: How to prevent the small intestinal damage induced by NSAIDs is an urgent issue to be resolved. In the present study, we examined the effects of soluble dietary fibers on both anti-inflammatory and ulcerogenic effects of indomethacin in arthritic rats. METHODS: Male Wistar rats weighing 180-220 g were used. Arthritis was induced by injecting Freund's complete adjuvant (killed M. tuberculosis) into the plantar region of the right hindpaw. The animals were fed a regular powder diet for rats or a diet supplemented with soluble dietary fibers such as pectin or guar gum. Indomethacin was administered once a day for 3 days starting 14 days after the adjuvant injection, when marked arthritis was observed. The volumes of the hindpaw were measured before and after indomethacin treatment to evaluate the effect of indomethacin on edema. The lesions in the small intestine were examined 24 h after the final dosing of indomethacin. RESULTS: Hindpaw volume was increased about 3 times 14 days after injection of the adjuvant. Indomethacin (3-10 mg/kg, p.o.) decreased hindpaw volume dose-dependently, but caused severe lesions in the small intestine at doses of 6 and 10 mg/kg. The addition of pectin (1-10 %) or guar gum (10 %) to the diet markedly decreased the lesion formation without affecting the anti-edema action of indomethacin. The same effects of pectin were observed when indomethacin was administered subcutaneously. CONCLUSIONS: It is suggested that soluble dietary fibers can prevent intestinal damage induced by NSAIDs without affecting the anti-inflammatory effect of these agents.

Multicenter, Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Serelaxin in Japanese Patients With Acute Heart Failure.

BACKGROUND: Serelaxin, a recombinant form of human relaxin-2, is in development for treating acute heart failure (AHF) and a Phase II study in Japanese AHF patients was conducted. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled study of serelaxin at 10 and 30 µg·kg(-1)·day(-1)continuous intravenous infusion for up to 48 h, added to standard care for Japanese AHF patients. Primary endpoints were adverse events (AEs) through Day 5, serious AEs (SAEs) through Day 14, and serelaxin pharmacokinetics. Secondary endpoints included changes in systolic blood pressure (SBP) and cardiorenal biomarkers. A total of 46 patients received the study drug and were followed for 60 days. The observed AE profile was comparable between the groups, with no AEs of concern. Dose-dependent increase in the serum concentration of serelaxin was observed across the 2 dose rates of serelaxin. A greater reduction in SBP was observed with serelaxin 30 µg·kg(-1)·day(-1)vs. placebo (-7.7 [-16.4, 1.0] mmHg). A greater reduction in NT-proBNP was noted with serelaxin (-50.8% and -54.9% for 10 and 30 µg·kg(-1)·day(-1), respectively at Day 2). CONCLUSIONS: Serelaxin was well tolerated in this study with Japanese AHF patients, with no AEs of concern and favorable beneficial trends on efficacy. These findings support further evaluation of serelaxin 30 µg·kg(-1)·day(-1)in this patient population.

[The Need for Lens Radiation Protection for Healthcare Provider in Open and Internal Fixation of the Hip Joint].

Increased occupational exposure of radiation workers is a major problem during open reduction and internal fixation (ORIF) of the hip joint, as the surgeon's eye lens is in close proximity to the patient and the X-ray tube. The purposes of this study were to clarify the occupational exposure of radiation workers during ORIF of the hip joint and to examine the need for radiation protection measures. The radiation exposure of radiation workers was evaluated by making an airborne dose distribution map using phantom experiments. The radiation goggles attached with a small optically stimulated luminescence dosimeter were used in clinical practice to measure the lens dose received by the surgeon, and the necessity of radiation goggles was examined. The airborne dose distribution in ORIF of the hip joint showed a wider area of high dose rate during axial fluoroscopy of the femoral neck than during posterior-anterior fluoroscopy. In axial fluoroscopy of the femoral neck, the surgeon was always in the high dose rate range of 10 µGy/min or higher, the nurses were in the dose rate range of 4 to 10 µGy/min, and the radiologic technologists were in the dose rate range of 0.5 µGy/min or lower. The maximum 3 mm dose equivalent to the surgeon per case was 0.38 mSv. In contradiction, radiation goggles were useful in ORIF because they provided approximately 60% shielding. It is advisable to work with radiation goggles to avoid cataracts.

Addiction-related brain networks identification via Graph Diffusion Reconstruction Network.

Functional magnetic resonance imaging (fMRI) provides insights into complex patterns of brain functional changes, making it a valuable tool for exploring addiction-related brain connectivity. However, effectively extracting addiction-related brain connectivity from fMRI data remains challenging due to the intricate and non-linear nature of brain connections. Therefore, this paper proposed the Graph Diffusion Reconstruction Network (GDRN), a novel framework designed to capture addiction-related brain connectivity from fMRI data acquired from addicted rats. The proposed GDRN incorporates a diffusion reconstruction module that effectively maintains the unity of data distribution by reconstructing the training samples, thereby enhancing the model's ability to reconstruct nicotine addiction-related brain networks. Experimental evaluations conducted on a nicotine addiction rat dataset demonstrate that the proposed GDRN effectively explores nicotine addiction-related brain connectivity. The findings suggest that the GDRN holds promise for uncovering and understanding the complex neural mechanisms underlying addiction using fMRI data.