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Magnetocapacitance (MC) effect has been observed in systems where both symmetries of time-reversal and space-inversion are broken, for examples, in multiferroic materials and spintronic devices. The effect has received increasing attention due to its interesting physics and the prospect of applications. Recently, a large tunnel magnetocapacitance (TMC) of 332% at room temperature was reported using MgO-based (001)-textured magnetic tunnel junctions (MTJs). Here, we report further enhancement in TMC beyond 420% at room temperature using epitaxial MTJs with an MgAl 2 O 4 (001) barrier with a cation-disordered spinel structure. This large TMC is partially caused by the high effective tunneling spin polarization, resulted from the excellent lattice matching between the Fe electrodes and the MgAl 2 O 4 barrier. The epitaxial nature of this MTJ system sports an enhanced spin-dependent coherent tunneling effect. Among other factors leading to the large TMC are the appearance of the spin capacitance, the large barrier height, and the suppression of spin flipping through the MgAl 2 O 4 barrier. We explain the observed TMC by the Debye-Fröhlich modelled calculation incorporating Zhang-sigmoid formula, parabolic barrier approximation, and spin-dependent drift diffusion model. Furthermore, we predict a 1000% TMC in MTJs with a spin polarization of 0.8. These experimental and theoretical findings provide a deeper understanding on the intrinsic mechanism of the TMC effect. New applications based on large TMC may become possible in spintronics, such as multi-value memories, spin logic devices, magnetic sensors, and neuromorphic computing.

Magnetic tunnel junctions (MTJs) in the field of spintronics have received enormous attention owing to their fascinating spin phenomena for fundamental physics and potential applications. MTJs exhibit a large tunnel magnetoresistance (TMR) at room temperature. However, TMR depends strongly on the bias voltage, which reduces the magnitude of TMR. On the other hand, tunnel magnetocapacitance (TMC), which has also been observed in MTJs, can be increased when subjecting to a biasing voltage, thus exhibiting one of the most interesting spin phenomena. Here we report a large voltage-induced TMC beyond 330% in MgO-based MTJs, which is the largest value ever reported for MTJs. The voltage dependence and frequency characteristics of TMC can be explained by the newly proposed Debye-Fröhlich model using Zhang-sigmoid theory, parabolic barrier approximation, and spin-dependent drift diffusion model. Moreover, we predict that the voltage-induced TMC ratio could reach over 3000% in MTJs. It is a reality now that MTJs can be used as capacitors that are small in size, broadly ranged in frequencies and controllable by a voltage. Our theoretical and experimental findings provide a deeper understanding on the exact mechanism of voltage-induced AC spin transports in spintronic devices. Our research may open new avenues to the development of spintronics applications, such as highly sensitive magnetic sensors, high performance non-volatile memories, multi-functional spin logic devices, voltage controlled electronic components, and energy storage devices.

Background Insulin-derived amyloidosis is a skin-related complication of insulin therapy that interferes with insulin therapy. Although toxicities of in vitro-formed insulin amyloid fibrils have been well studied, the toxicity of insulin-derived amyloidosis remains to be clarified. Case presentation A 58-year-old man with type 2 diabetes mellitus underwent a lower limb amputation due to diabetic gangrene. Several antibiotics including minocycline were administered for infection and sepsis. A hard mass at the insulin injection sites in the lower abdomen was discovered by chance four months later. Although no abnormal findings in the surface skin of the mass were observed, necrotic tissue was seen around the mass when a biopsy was performed. Histological and toxicity studies were performed for this patient and four other patients with abdominal masses at insulin injection sites. Histological and immunohistochemical studies showed that the masses had typical characteristics of amyloid deposits in all cases, whereas necrotic findings were seen adjacent to the amyloid deposit only in the case presented. Toxicity studies indicated that the amyloid tissue from the present case had significant cell toxicity compared to the control skin tissue or the amyloid tissues from the other four cases. Conclusions This report showed that toxic insulin-derived amyloidosis can occur. In addition, this report suggested that toxic insulin-derived amyloidosis may cause necrosis in the surrounding tissue. Although the toxic amyloid deposit of insulin-derived amyloidosis was found in only one patient, no structural differences between toxic and non-toxic deposits were seen on histological and immunohistochemical studies.

Flexible and wearable electronics have huge potential applications in human motion detection, human–computer interaction, and context identification, which have promoted the rapid development of flexible sensors. So far the sensor manufacturing techniques are complex and require a large number of organic solvents, which are harmful not only to human health but also to the environment. Here, we propose a facile solvent-free preparation toward a flexible pressure and stretch sensor based on a hierarchical layer of graphene nanoplates. The resulting sensor exhibits many merits, including near-linear response, low strain detection limits to 0.1%, large strain gauge factor up to 36.2, and excellent cyclic stability withstanding more than 1000 cycles. Besides, the sensor has an extraordinary pressure range as large as 700 kPa. Compared to most of the reported graphene-based sensors, this work uses a completely environmental-friendly method that does not contain any organic solvents. Moreover, the sensor can practically realize the delicate detection of human body activity, speech recognition, and handwriting recognition, demonstrating a huge potential for wearable sensors.

BackgroundNeonatal-onset Denys–Drash syndrome (NODDS) is a distinctive clinical entity and has a poor renal and life outcome. Early diagnosis of NODDS is important for managing disorders of sexual development and determining assigned gender. Although patients with NODDS and congenital nephrotic syndrome of the Finnish type (CNF) present with nephrotic syndrome in neonatal life or infancy, the clinical course of NODDS and factors distinguishing these diseases at onset is unknown.MethodsWe performed a retrospective cohort study of patients with NODDS and CNF between 1997 and 2017. Patients with nephrotic syndrome and WT1 or NPHS1 mutations with neonatal onset (within 30 days) were eligible.ResultsWe studied eight patients with NODDS and 15 with CNF. The median serum creatinine level at onset in the NODDS group was significantly higher (1.85 mg/dL) than that in the CNF group (0.15 mg/dL; P = 0.002). The median placental/fetal weight ratio in the NODDS and CNF group was 41.8% and 21.0%, respectively (P = 0.001). Kaplan–Meier analysis showed that the median number of days for progression to ESRD from onset in the NODDS and CNF groups was 6 and 910 days, respectively (P < 0.001). All patients in the NODDS group were alive at follow-up. Only one patient in the CNF group died of cardiac complications during follow-up.ConclusionCNS, renal dysfunction at onset, and a relatively large placenta are prominent signs of NODDS. Prognosis for patients with NODDS is satisfactory if appropriate and active management is performed.

We previously reported a case of giant cell carcinoma in the lung, in which the use of antiprogrammed death 1 (PD-1) immunotherapy resulted in substantial tumor reduction. In the present study, we describe an additional clinical course. A 69-year-old woman was diagnosed with giant cell carcinoma of the lung in clinical stage IVB (T2bN0M1c, BRA). The tumor expressed programmed death ligand 1 (PD-L1) in a high proportion. The patient received stereotactic radiotherapy for two sites of small brain metastases, followed by immunotherapy using anti-PD-1 antibodies (pembrolizumab). The treatment exerted a substantial tumor reduction through four cycles. However, treatment was withdrawn due to renal dysfunction. The primary lung tumor continued to regress for an additional four months without any further therapy, resulting in a clinical stage of T1aN0M0. Salvage thoracic surgery was then performed to remove the tumor residue in the lung. Microscopic examination of the sample revealed no residual cancer. The patient was free from recurrence at 16 months post surgery. We then comprehensively reviewed lung sarcomatoid carcinoma cases in the literature, in which anti-PD-1 antibodies were implemented. The current literature and our own findings suggest sarcomatoid carcinomas express high levels of tumoral PD-L1 and can be effectively treated with anti-PD-1 antibodies.

Purpose The aims of this study were to evaluate the safety, efficacy, and pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in Japanese patients who received highly or moderately emetogenic chemotherapy. Methods Twenty- six patients received palonosetron 0.75 mg intravenously before chemotherapy on days 1 and 3 plus dexamethasone (12–16 mg before chemotherapy on day 1 and 4–8 mg on days 2 and 3). The primary endpoints were safety and pharmacokinetics. Pharmacokinetics were evaluated in a subset of patients ( n  = 6). Complete response and complete protection were evaluated as secondary endpoints. Results The accumulation ratios for C max and AUC last after the second dose on day 3 were 1.42 and 1.37, respectively. These values were consistent with the theoretical values expected from the half-life of palonosetron on day 1. Almost all of the patients had no nausea or vomiting in the acute phase (complete response (CR) rate, 96.2 % [25/26]; CP rate, 92.3 % [24/26]). In the delayed phase (24–192 h post-chemotherapy), the complete response and complete protection rates were 76.9 % (20/26) and 61.5 % (16/26), respectively. Treatment was well tolerated. Conclusions This is the first study to report the pharmacokinetics of multiple doses of palonosetron 0.75 mg, given on days 1 and 3, in Japanese patients. Repeated treatment with palonosetron was safe and well tolerated by patients who received highly or moderately emetogenic anticancer chemotherapy.

Invasive mucinous adenocarcinoma (IMA), formerly referred to as mucinous bronchioloalveolar carcinoma, is a rare variant form of invasive adenocarcinoma and is radiologically characterized by dense pneumonic consolidation, ground-glass opacity and nodules. By contrast, large, thin-walled cysts are rare. We herein report the case of a 75-year-old man with IMA presenting as a large, irregularly shaped cystic lesion. The histological diagnosis was based on specimens obtained during a bronchoscopy. The patient underwent lobectomy followed by anticancer chemotherapy for residual intrapulmonary metastases. Of note, the small metastatic nodules transformed into cystic lesions with thin walls and fused, forming a large, multiloculated cystic lesion. Typical pneumonic consolidation appeared in the pericystic parenchyma later during the clinical course. The available literature on this rare radiological manifestation was also reviewed and discussed. Clinicians should be aware of thin-walled cystic lesions as they may be an unusual radiological finding in IMA.

Background The long-term outcome of pediatric IgA nephropathy (IgAN) is unclear. Objective IgAN remission criteria were proposed by the Japanese Society of Nephrology in 2013. Methods Children with newly developed IgAN followed for >5 years were analyzed. They were divided into two groups based on histological findings at initial kidney biopsy: the focal mesangial proliferation group (Focal group) and diffuse mesangial proliferation group (Diffuse group). The primary outcome was the remission rate according to the newly proposed IgAN remission criteria. Results The patients comprised 53 children (31 boys; mean age at IgAN onset, 10.0 years). The Focal and Diffuse groups comprised 21 and 32 patients, respectively. No significant differences in patient characteristics were found between the groups except for steroid administration. The median follow-up period from onset was 9.9 years. Sixteen patients in the Diffuse group and 10 in the Focal group had not achieved remission at the last observation. Patient conditions 2 years after the initial treatment were almost identical to those at the last observation. Multivariate analysis revealed that proteinuria, particularly <0.5 g/g Cr at 2 years, was significantly associated with remission at the last observation regardless of proteinuria status at the start of treatment. Conclusions Pediatric IgAN has a prolonged course that is longer than expected regardless of severity at diagnosis. Patient conditions 2 years after initial treatment predicted their conditions at the last observation. Although the final renal function of these patients is presently unclear, children with IgAN should be followed beyond adolescence and further into adulthood.

Catechol-O-methyltransferase (COMT) inhibitors are used to alleviate motor fluctuations, such as wearing-off, in people with Parkinson’s disease (PwPD). Opicapone, a COMT inhibitor has long-lasting efficacy when administered once daily, but there is limited real-world clinical data in Japanese participants. This study aimed to evaluate the one-year continuation rate of opicapone in Japanese PwPD in real-world clinical practice and to identify factors influencing this continuation rate. This retrospective study analyzed data from 58 Japanese PwPD treated with opicapone at the Department of Neurology, Fukuoka University Hospital. We compared patients who continued opicapone for one year with those who discontinued it and examined factors influencing the continuation rate. Among the 58 PwPD, 26 (44.8%) continued opicapone for one year. Binomial logistic regression analysis identified male sex (odds ratio: 0.223, 95 % confidence interval: 0.056-0.878) and switching from entacapone (odds ratio: 0.215, 95 % confidence interval: 0.056-0.825) as significant factors influencing the one-year continuation rate. Switching to opicapone in patients with suboptimal responses to entacapone may enhance the continuation rate. •One-year continuation rate of opicapone in Japanese patients with Parkinson's disease was 44.8 %.•Patients of male sex and those who switched from entacapone had higher continuation rates of opicapone.•Poor efficacy was the most common reason for opicapone discontinuation.•Adverse events, including dyskinesia and hallucinations, occurred mostly within the first three months of starting opicapone.•Opicapone may improve motor symptoms in patients inadequately controlled with entacapone.