Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid-induced myopathy.

BACKGROUND: Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time. OBJECTIVES: This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors. METHODS: This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit. RESULTS: The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM. CONCLUSIONS: GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered.

Joint instability causes catabolic enzyme production in chondrocytes prior to synovial cells in novel non-invasive ACL ruptured mouse model.

OBJECTIVE: The Anterior Cruciate Ligament (ACL)-deficient model helps to clarify the mechanism of knee osteoarthritis (OA); however, the conventional ACL injury model could have included concurrent onset factors such as direct compression stress to cartilage and subchondral bone. In this study, we established a novel Non-invasive ACL-Ruptured mouse model without concurrent injuries and elucidated the relationship between OA progression and joint instability. DESIGN: We induced the ACL-Rupture non-invasively in twelve-week-old C57BL/6 male mice and evaluated histological, macroscopical, and morphological analysis at 0 days. Next, we created the ACL-R, controlled abnormal tibial translation (CATT), and Sham groups. Then, the joint stability and OA pathophysiology were analyzed at 2, 4, and 8 weeks. RESULTS: No intra-articular injuries, except for ACL rupture, were observed in the ACL-R model. ACL-R mice increased anterior tibial displacement compared to the Sham group (P < 0.001, 95% CI [-1.509 to -0.966]) and CATT group (P < 0.001, 95% CI [-0.841 to -0.298]) at 8 weeks. All mice in the ACL-R group caused cartilage degeneration. The degree of cartilage degeneration in the ACL-R group was higher than in the CATT group (P = 0.006) at 8 weeks. The MMP-3-positive cell rate of chondrocytes increased in the ACL-R group than CATT group from 4 weeks (P = 0.043; 95% CI [-28.32 to -0.364]) while that of synovial cells increased at 8 weeks (P = 0.031; 95% CI [-23.398 to -1.021]). CONCLUSION: We successfully established a Non-invasive ACL-R model without intra-articular damage. Our model revealed that chondrocytes might react to abnormal mechanical stress prior to synovial cells while the knee OA onset.

The effectiveness of dance movement therapy for individuals with Down syndrome: a pilot randomised controlled trial.

BACKGROUND: Individuals with Down syndrome (DS) exhibit deficits in static and dynamic balance abilities and maladaptive functions. This study aimed to determine the effectiveness of dance movement therapy (DMT) group intervention in individuals with DS. METHODS: The 31 participating individuals with DS, aged 5-29 years, were randomly divided into intervention (n = 16) and control (n = 15) groups. Posturography was used for static balance measurement, timed up and go test for dynamic balance measurement and the Achenbach System of Empirically Based Assessment (ASEBA) questionnaire for adaptive function and behavioural problem measurement in participants before and after the DMT interventions. The intervention group underwent 60-min DMT intervention once a week for 10 times, while the control group had usual daily activities. RESULTS: The results revealed a statistically significant difference and large effect sizes in dynamic balance [(f(1, 29) = 4.52, P = 0.04, ηp 2 = 0.14)] in the intervention group compared with the control group. There were no statistically significant differences in static balance and ASEBA scores between the groups. CONCLUSIONS: This study found that the DMT interventions helped to improve the dynamic balance in individuals with DS.

MRI features of extraocular muscle metastases compared to those of other extraocular muscle diseases of non-thyroid origin.

AIM: To identify the magnetic resonance imaging (MRI) features of metastases to the extraocular muscles (EOM metastases). MATERIAL AND METHODS: The MRI features of 19 patients with EOM metastases were compared with those of 24 patients with EOM diseases of non-thyroid origin. MRI was used to assess the number of tumours, morphology, signal intensity on T2-weighted images, enhancement patterns, and apparent diffusion coefficient (ADC) values. RESULTS: Single muscular involvement was observed in 10 patients, and multiple muscular involvement was observed in nine patients. The morphology was focally discrete in nine patients, and diffuse infiltrative in 10 patients; all the nine patients with focal discrete morphology presented with single muscular lesions. On T2-weighted images, the signal intensities were intermediate or low in 15 patients and a mixture of high and intermediate in four patients. In 14 patients for whom contrast-enhanced images were available, ring enhancement (n=5), heterogeneous diffuse enhancement (n=5), and homogeneous enhancement (n=4) were seen. The mean ADC value was 0.98 × 10-3 mm2/s. Compared to other EOM diseases of non-thyroid origin, single muscular presentation, focal discrete morphology, the presence of hyperintensity on T2-weighted images, and ring or heterogeneous enhancement were significantly more frequent in EOM metastases. CONCLUSION: The MRI features of EOM metastases showed two main patterns: a single discrete mass and multiple infiltrative masses. In addition to the presentation as a single discrete mass, the presence of hyperintensity on T2-weighted images and ring or heterogeneous enhancement can aid in the differentiation of EOM metastases from other EOM diseases.

Reducing the number of accepted species in Aspergillus series Nigri.

The Aspergillus series Nigri contains biotechnologically and medically important species. They can produce hazardous mycotoxins, which is relevant due to the frequent occurrence of these species on foodstuffs and in the indoor environment. The taxonomy of the series has undergone numerous rearrangements, and currently, there are 14 species accepted in the series, most of which are considered cryptic. Species-level identifications are, however, problematic or impossible for many isolates even when using DNA sequencing or MALDI-TOF mass spectrometry, indicating a possible problem in the definition of species limits or the presence of undescribed species diversity. To re-examine the species boundaries, we collected DNA sequences from three phylogenetic markers (benA, CaM and RPB2) for 276 strains from series Nigri and generated 18 new whole-genome sequences. With the three-gene dataset, we employed phylogenetic methods based on the multispecies coalescence model, including four single-locus methods (GMYC, bGMYC, PTP and bPTP) and one multilocus method (STACEY). From a total of 15 methods and their various settings, 11 supported the recognition of only three species corresponding to the three main phylogenetic lineages: A. niger, A. tubingensis and A. brasiliensis. Similarly, recognition of these three species was supported by the GCPSR approach (Genealogical Concordance Phylogenetic Species Recognition) and analysis in DELINEATE software. We also showed that the phylogeny based on benA, CaM and RPB2 is suboptimal and displays significant differences from a phylogeny constructed using 5 752 single-copy orthologous proteins; therefore, the results of the delimitation methods may be subject to a higher than usual level of uncertainty. To overcome this, we randomly selected 200 genes from these genomes and performed ten independent STACEY analyses, each with 20 genes. All analyses supported the recognition of only one species in the A. niger and A. brasiliensis lineages, while one to four species were inconsistently delimited in the A. tubingensis lineage. After considering all of these results and their practical implications, we propose that the revised series Nigri includes six species: A. brasiliensis, A. eucalypticola, A. luchuensis (syn. A. piperis), A. niger (syn. A. vinaceus and A. welwitschiae), A. tubingensis (syn. A. chiangmaiensis, A. costaricensis, A. neoniger and A. pseudopiperis) and A. vadensis. We also showed that the intraspecific genetic variability in the redefined A. niger and A. tubingensis does not deviate from that commonly found in other aspergilli. We supplemented the study with a list of accepted species, synonyms and unresolved names, some of which may threaten the stability of the current taxonomy. Citation: Bian C, Kusuya Y, Sklenár F, D'hooge E, Yaguchi T, Ban S, Visagie CM, Houbraken J, Takahashi H, Hubka V (2022). Reducing the number of accepted species in Aspergillus series Nigri. Studies in Mycology 102: 95-132. doi: 10.3114/sim.2022.102.03.

Analysis of clinical characteristics, prognosis and antibody pathogenicity of pemphigus patients positive for anti-desmoglein IgG autoantibodies in remission: a retrospective cohort study.

BACKGROUND: The detection of serum anti-desmoglein (Dsg) IgG autoantibodies has been reported to be useful for assessment of disease activity in pemphigus. However, previous studies have reported that anti-Dsg autoantibodies remain detectable in some patients without active pemphigus lesions. OBJECTIVES: To investigate the clinical characteristics and antibody pathogenicity of pemphigus patients positive for anti-Dsg IgG autoantibodies in remission. METHODS: We retrospectively investigated pemphigus patients with a history of clinical remission who visited the Department of Dermatology of Keio University during 2019 and 2020. The antibody pathogenicity was assessed by bead aggregation assay. RESULTS: When patients were recognized as having entered remission (PDAI = 0 and PSL ≦ 10 mg/day for 2 months), serum autoantibodies against Dsg were detected in 72 of 132 patients (54.5%, positive group; PG), but were not detected in 60 patients (45.5%, negative group; NG). Anti-Dsg antibody titres in remission declined from the active phase in 33 patients in the PG for whom data were available. There were no differences in the chance of reducing PSL to 5 mg/day (P = 0.885) and rate of relapse (P = 0.279) between PG and NG, but fewer patients in PG discontinued corticosteroids (P = 0.004). The ability of patients' sera to block aggregation of Dsg/desmocollin beads was significantly reduced in remission compared to the active phase. However, our results revealed that whole sera in remission still had pathogenic activity in seven of nine patients, and the approximately equal amounts of anti-Dsg antibodies in active phase and remission showed similar pathogenicity. CONCLUSIONS: This study will provide guidance in cases where autoantibodies are found to be positive in pemphigus patients during remission or steroid reduction.

Humanized NOD/SCID/IL2rγnull mice exhibit functionally augmented human regulatory T cells associated with enzymatic up-regulation of H3K27me3 in comparison with humans.

Humanized non-obese diabetic/severe combined immunodeficiency/interleukin-2 receptor-γ-null (NOD/SCID/IL2rγnull ) [humanized (huNSG)] mice engrafted with human hematopoietic cells have been used for investigations of the human immune system. However, the epigenetic features of the human regulatory T (Treg ) cells of huNSG mice have not been studied. The objective of this study was to clarify the characteristics of human Treg cells in huNSG mice, especially in terms of the epigenetic aspects. We compared the populations, inhibitory molecule expression and suppressive capacity of human Treg cells in spleens harvested from the huNSG mice 120 days after the engraftment of human umbilical cord blood CD34+ cells with human peripheral blood mononuclear cells (PBMCs). Histone modifications and enhancer of zeste homolog 2 (Ezh2), an H3K27 methyltransferase, of human Treg cells were quantified in huNSG mice and human PBMCs. The effect of Ezh2 inhibitor on human Treg cells exposed to interleukin (IL)-6 was also compared between them. Human Treg cells in the spleens of huNSG mice showed an increased proportion among CD4+ T cells, higher expressions of forkhead box protein 3 (FoxP3), cytotoxic T lymphocyte antigen 4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor-related protein (GITR), a higher production of IL-10 and enhanced suppressive capacity when compared with those in human PBMCs. H3K27me3 and Ezh2 were specifically up-regulated in human Treg cells of huNSG mice in comparison with those of human PBMCs. The decrease in Treg cells induced by IL-6 exposure was attenuated in huNSG mice when compared with human PBMCs, while the difference between them was cancelled by addition of Ezh2 inhibitor. In conclusion, huNSG mice exhibit functionally augmented human Treg cells owing to enzymatic up-regulation of H3K27me3.

Nonmagnetic J=0 State and Spin-Orbit Excitations in K_{2}RuCl_{6}.

Spin-orbit Mott insulators composed of t_{2g}^{4} transition metal ions may host excitonic magnetism due to the condensation of spin-orbital J=1 triplons. Prior experiments suggest that the 4d antiferromagnet Ca_{2}RuO_{4} embodies this notion, but a J=0 nonmagnetic state as a basis of the excitonic picture remains to be confirmed. We use Ru L_{3}-edge resonant inelastic x-ray scattering to reveal archetypal J multiplets with a J=0 ground state in the cubic compound K_{2}RuCl_{6}, which are well described within the LS-coupling scheme. This result highlights the critical role of unquenched orbital moments in 4d-electron compounds and calls for investigations of quantum criticality and excitonic magnetism on various crystal lattices.

Impact of Magnetic Field Configuration on Heat Transport in Stellarators and Heliotrons.

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Correlation between alterations in blood flow of malignant lymphomas after induction chemotherapies and clinical outcomes: a pilot study utilising contrast-enhanced ultrasonography for early interim evaluation of lymphoma treatment.

AIM: To clarify the utility of contrast-enhanced ultrasonography (CEUS) for interim evaluation of response to chemotherapy in lymphoma treatment. MATERIALS AND METHODS: CEUS was performed both before (day 0) and after the treatment (7 and/or 14 days), and a time-intensity curve was obtained. The patients were divided into two groups (complete remission [CR] group and non-CR group) according to the results of conventional response evaluation, and peak enhancement (PE), time to peak enhancement, perfusion index (PI), the total area under the curve during wash-in (AUC-in), and the total AUC were compared between the groups. RESULTS: Among 27 patients with various types of lymphoma, the median change ratio of PE and PI at day 7 evaluation were significantly different between the CR group and the non-CR group (0.81 versus 1.39, p=0.017 for PE and 0.92 versus 2.09, p=0.010 for PI). The change ratio of PE < 1.09 (specificity: 86%; sensitivity, 88%) and PI < 1.65 (specificity: 86%; sensitivity: 94%) distinguished CR from non-CR. Patients who achieved a PE change ratio <1.09 or a PI change ratio <1.65 had significantly better estimated progression-free survival (p<0.001). CONCLUSION: The present study demonstrated that changes in tumour perfusion parameters evaluated with CEUS at 1 week after the treatment initiation were significantly different between lymphoma patients in CR group and non-CR group. Alterations in perfusion parameters evaluated via CEUS could impact the prognosis of lymphoma patients.

Evaluation of peptones from chicken waste as a nitrogen source for micro-organisms.

In this study, chicken peptone was produced by hydrolysing inedible parts derived from chickens using endo-protease and exo-protease. The usefulness of chicken peptone as a nutrient source for bacteria was evaluated in comparison with other commercially produced peptones (animal, soy and casein-derived peptone). Escherichia coli and Bacillus subtilis were used as test strains to determine the effect of peptones from different sources on their growth ability. Both bacteria were successfully cultured in chicken peptone solution, which is similar to peptone solution containing commercial peptones apart from animal peptone. In chemical analysis, chicken peptone contained 12·0% nitrogen; this was similar to the nitrogen content from other commercial peptone sources, except for the 9·0% nitrogen found in soy peptones. The molecular weight of the peptone was determined by gel filtration chromatography, and those of all peptone, except animal-derived peptone, were found to be <5000 Da. In addition, when B. subtilis was cultured in a medium containing chicken peptone, it was shown that the protease activity was highest as compared with other commercial peptones. From these results, it is suggested that chicken peptone can be utilized for microbial culture, and this is an effective method to reuse chicken waste.

Cerebral Oxygenation Dynamics During Incremental Exercise: Comparison of Arm Cranking and Leg Cycling.

This study aimed to compare cerebral oxyhemoglobin (O2Hb) levels during incremental exercise by cycling vs. arm cranking in 12 healthy adult men aged 20.8 ± 0.2 years old. O2Hb was measured by near-infrared spectroscopy. Regions of interest included the left and right prefrontal cortices (LtPFC and RtPFC, respectively), the left and right premotor cortices (LtPMC and RtPMC, respectively), and the supplementary motor area (SMA) bilaterally. After 4 min of rest, 4 min of warm-up was performed by using ergometer followed by incremental exercise (increasing work rate by 5 W/min for arm cranking and 20 W/min for cycling exercise). All values were averaged every tenth of the participant's exercise time period from beginning of incremental exercise to end point. At the middle exercise intensity (50% exercise time), the averaged O2Hb values obtained at all regions of interest seemed to be higher during arm cranking exercise as compared to cycling; however, there were no significant differences between two types of exercise. At the end point of incremental exercise (100% exercise time), the O2Hb obtained at all regions of interest was significantly higher during arm cranking exercise compared to cycling (LtPFC 0.081 ± 0.019 vs. -0.001 ± 0.013 mM·cm, RtPFC 0.076 ± 0.021 vs. 0.018 ± 0.015 mM·cm, SMA 0.012 ± 0.040 vs. 0.040 ± 0.016 mM·cm; arm cranking vs. cycling; p < 0.05, respectively). We conclude that exercise-induced cerebral oxygenation is greater with arm cranking than with leg cycling.

Morphological characterisation of glial and neuronal tau pathology in globular glial tauopathy (Types II and III).

AIMS: Globular glial tauopathy (GGT) is a new category within the 4-repeat tauopathies that is characterised neuropathologically by tau-positive globular glial inclusions (GGIs), namely, globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). Occurrence of tau-positive neuronal cytoplasmic inclusions (NCIs) is also a feature. GGT is classified into three pathological subtypes (Types I, II and III). We studied the tau pathology in 6 cases of GGT (Type II, n = 3; Type III, n = 3), with special reference to GAIs and NCIs. METHODS: Neuropathological examinations were conducted, along with immunohistochemistry, morphometry and three-dimensional imaging, and biochemical and genetic analysis of tau. RESULTS: The cortical GAIs in Type II and those in Type III were distinguishable from each other. In the motor cortex, GAIs were much more numerous in Type III than in Type II. Prominent occurrence of perikaryal globular structures was a feature of GAIs in Type III. By contrast, prominent occurrence of radiating process-like structures was a feature of GAIs in Type II. Overall, the GAIs were significantly smaller in Type III than in Type II. NCIs were divisible into three subgroups in terms of shape: diffuse granular, thick cord-like, and round/horseshoe-shaped structures. In all cases, NCIs were a feature of the upper and lower motor neurons. Interestingly, the round/horseshoe-shaped NCIs were observed only in Type III cases. CONCLUSIONS: These findings, which characterised GAIs and NCIs, indicated that Type II and Type III constitute two distinct pathological subtypes, and also further strengthen the concept of GGT as a distinct entity.

Basement membrane zone IgE deposition is associated with bullous pemphigoid disease severity and treatment results.

BACKGROUND: A subset of patients with bullous pemphigoid (BP) show deposition of IgE in the basement membrane zone (BMZ), yet the relationship between BMZ IgE and the clinical presentation of BP remains unclear. OBJECTIVES: To investigate the relationship between IgE deposition, IgE levels in serum, and disease severity in patients with BP. METHODS: We investigated IgE autoantibodies in 53 patients with BP by direct immunofluorescence (DIF), indirect immunofluorescence and enzyme-linked immunosorbent assay. RESULTS: Of 53 patients with BP, 23 (43%) had IgE deposition, 10 (19%) of whom were IgE+ and 13 (25%) IgE± according to DIF analyses. Erosion/blister (E/B) Bullous Pemphigoid Disease Area Index (BPDAI) scores were significantly higher in IgE+ patients than in IgE- patients (n = 15), while no significant differences were found for urticaria/erythema BPDAI scores. IgE+ and IgE± patients took longer to reduce their E/B BPDAI score by 75% after systemic corticosteroid treatment. BP180-IgE levels were significantly higher among IgE+ patients than IgE± or IgE- patients (n = 10). Total IgE levels in the serum and blood eosinophil counts did not differ between IgE+, IgE± and IgE- patients. A significant correlation was detected between BP180-IgG and BP180-IgE, but not between BPDAI scores and any of BP180-IgG, BP180-IgE or blood eosinophil count. CONCLUSIONS: IgE deposition in the BMZ is associated with higher E/B BPDAI scores and longer treatment periods. We conclude that IgE binding in the BMZ may contribute to BP pathogenesis by promoting blister formation. What's already known about this topic? BP180-IgE autoantibodies have an important role in the pathogenesis of bullous pemphigoid (BP). A subset of patients with BP display deposition of IgE within the basement membrane zone (BMZ) of skin tissue. What does this study add? Patients with in vivo IgE deposition in the BMZ displayed higher erosion/blister Bullous Pemphigoid Disease Area Index (BPDAI) scores, while urticaria/erythema BPDAI scores were not significantly different. Patients with in vivo IgE deposition in the BMZ took longer to reduce their erosion/blister BPDAI score by 75% after systemic corticosteroid treatment. BP180-specific IgE levels in serum were higher among patients with linear IgE deposition in the BMZ than in those with granular or no IgE deposition.

Clinical and pathological features affecting cardiac sympathetic denervation in autopsy-confirmed dementia with Lewy bodies.

BACKGROUND AND PURPOSE: The aim was to clarify the features affecting cardiac sympathetic denervation in autopsy-confirmed dementia with Lewy bodies (DLB) patients. METHODS: Fifty-four autopsy-confirmed DLB patients were enrolled. Tissue samples of the left ventricular anterior wall were immunostained with anti-tyrosine hydroxylase antibody to identify catecholaminergic nerve axons. Immunostained areas were quantified as residual cardiac sympathetic nerve (CSN) axons and the relationship between the degree of residual CSN axons and clinical and neuropathological features was examined. RESULTS: Virtually all patients showed small amounts of residual CSN axons (0.87%, range 0.02%-9.98%), with 50 patients (92.6%) showing <2.0% of residual axons. The patients who showed psychological symptoms within the first year of the disease had significantly more residual CSN axons than the remaining patients did (1.50% vs. 0.40%, P < 0.01). Patients with a short disease duration and neocortical-type Lewy body pathology tended to have more preserved CSN axons, although this difference was not statistically significant. Fifty-three patients (98.1%) who had neurofibrillary tangles in the brain and strong concomitant Alzheimer's disease pathology also had statistically significantly more preserved CSN axons. The patient with the most preserved CSN axons showed different characteristics from the results, except for the first symptom. CONCLUSION: Psychological symptoms within the first year of the disease, a short disease duration, neocortical-type Lewy body pathology and strong concomitant Alzheimer's disease pathology may be related to mild CSN degeneration in DLB patients. Thus, DLB patients with broad Lewy body pathology in the brain in the early stages may show mild CSN degeneration.

Magnetic Resonance Force Microscopy with a One-Dimensional Resolution of 0.9 Nanometers.

Magnetic resonance force microscopy (MRFM) is a scanning probe technique capable of detecting MRI signals from nanoscale sample volumes, providing a paradigm-changing potential for structural biology and medical research. Thus far, however, experiments have not reached sufficient spatial resolution for retrieving meaningful structural information from samples. In this work, we report MRFM imaging scans demonstrating a resolution of 0.9 nm and a localization precision of 0.6 nm in one dimension. Our progress is enabled by an improved spin excitation protocol furnishing us with sharp spatial control on the MRFM imaging slice, combined with overall advances in instrument stability. From a modeling of the slice function, we expect that our arrangement supports spatial resolutions down to 0.3 nm given sufficient signal-to-noise ratio. Our experiment demonstrates the feasibility of subnanometer MRI and realizes an important milestone toward the three-dimensional imaging of macromolecular structures.

Observation of a Magnetopiezoelectric Effect in the Antiferromagnetic Metal EuMnBi_{2}.

We have experimentally studied a magnetopiezoelectric effect predicted recently for magnetic metals with low crystal symmetries. In EuMnBi_{2} with antiferromagnetic Mn moments at 77 K, dynamic displacements emerge along the a direction upon application of ac electric fields in the c direction and increase in proportion to the applied electric fields. Such displacements are not observed along the c direction of EuMnBi_{2} or EuZnBi_{2} with nonmagnetic Zn ions. As temperature increases from 77 K, the displacement signals decrease and disappear at about 200 K, above which electric conduction changes from coherent to incoherent. These results demonstrate the emergence of the magnetopiezoelectric effect in a magnetic metal lacking inversion and time-reversal symmetries.

Bendamustine-120 plus rituximab therapy for relapsed or refractory follicular lymphoma: a multicenter phase II study.

The optimal dose, schedule, and other aspects of bendamustine plus rituximab treatment remain unclear for patients with relapsed or refractory follicular lymphoma (FL). Herein, we analyzed the efficacy of bendamustine combined with rituximab (RB-120) treatment for Japanese patients with relapsed or refractory FL. This phase II clinical trial included patients with relapsed or refractory FL who received 375 mg/m2 rituximab on day 1 and 120 mg/m2 bendamustine on days 2 and 3 every 28 days for up to 6 cycles. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included the complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety. Thirty-seven patients were enrolled in the trial (median age 62 years, range 42-75 years). All patients were previously treated with rituximab-containing chemotherapy, and 83.8% were previously treated with the R-CHOP regimen. A median of 5 cycles (range 1-6) and 48.6% of patients completed 6 cycles. The ORR was 91.9% (95% confidence interval [CI] 78.1-98.3%), with a CR rate of 86.5% (95% CI 71.2-95.5%). The 3-year PFS and OS were 70.9% (95% CI 52.3-83.3%) and 88.9% (95% CI 73.1-95.7%), respectively, with the median 39.5 months follow-up duration. The most-frequently observed grade 3/4 adverse events were hematologic: lymphopenia (95%) and neutropenia (70%). No treatment-related deaths were observed. RB-120 showed a good efficacy with equivalent toxicities, compared with the bendamustine 120 mg/m2 monotherapy. However, the problem of high drop-out incidences cannot be ignored.

A case with good response to belimumab for lupus nephritis complicated by IgG4-related disease.

Immunoglobulin (Ig)G4-related disease (IgG4-RD) is an unusual complication of systemic lupus erythematosus (SLE). We report a case in which belimumab proved efficacious for not only SLE, but also IgG4-RD. A 58-year-old Japanese woman had suffered from photodermatosis and erythema on the limbs for 20 years. She presented in slight fever and fatigue since 2016. Laboratory data showed hypergammaglobulinemia, proteinuria and positive results for anti-nuclear antibody and anti-double-stranded DNA antibody. Furthermore, elevated levels of serum IgG4 were detected. Contrast-enhanced computed tomography disclosed multiple areas of poor enhancement in the kidneys. The patient was diagnosed with lupus nephritis and IgG4-RD from renal biopsy. Treatment was started with prednisolone at 40 mg/day and mycophenolate mofetil. Proteinuria and serological findings improved initially, but tapering the dose of glucocorticoid proved difficult. After treatment was started with belimumab, clinical symptoms and proteinuria resolved completely. The dose of glucocorticoid was successfully tapered and serum concentration of IgG4 fell further. This appears to represent the first report of a case in which both SLE and IgG4-RD were effectively treated using belimumab.

A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma.

Background: There is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC). Patients and methods: We conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities. Results: Thirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval (CI), 25.5%-59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%-87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3-12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient. Conclusion: This study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study. Clinical Trial Registration: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.