Generalizable and transportable resting-state neural signatures characterized by functional networks, neurotransmitters, and clinical symptoms in autism.

Autism spectrum disorder (ASD) is a lifelong condition with elusive biological mechanisms. The complexity of factors, including inter-site and developmental differences, hinders the development of a generalizable neuroimaging classifier for ASD. Here, we developed a classifier for ASD using a large-scale, multisite resting-state fMRI dataset of 730 Japanese adults, aiming to capture neural signatures that reflect pathophysiology at the functional network level, neurotransmitters, and clinical symptoms of the autistic brain. Our adult ASD classifier was successfully generalized to adults in the United States, Belgium, and Japan. The classifier further demonstrated its successful transportability to children and adolescents. The classifier contained 141 functional connections (FCs) that were important for discriminating individuals with ASD from typically developing controls. These FCs and their terminal brain regions were associated with difficulties in social interaction and dopamine and serotonin, respectively. Finally, we mapped attention-deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), and major depressive disorder (MDD) onto the biological axis defined by the ASD classifier. ADHD and SCZ, but not MDD, were located proximate to ASD on the biological dimensions. Our results revealed functional signatures of the ASD brain, grounded in molecular characteristics and clinical symptoms, achieving generalizability and transportability applicable to the evaluation of the biological continuity of related diseases.

A case of hypophysitis after COVID-19 vaccination with a detection of anti-pituitary antibody, with review of literature.

COVID-19 vaccines have resulted in a remarkable reduction in both the morbidity and mortality associated with COVID-19. However, there are reports of endocrine rare clinical conditions linked to COVID-19 vaccination. In this report, we present a case of hypophysitis following COVID-19 vaccination and review the literature on this condition. This case involved a 72-year-old male with type 1 diabetes who experienced symptoms such as vomiting, appetite loss, and headaches following his fifth COVID-19 vaccine dose. He was diagnosed with secondary adrenal insufficiency; subsequent assessment revealed an enlarged pituitary gland. Unlike previous cases, our patient has partial recovery from pituitary insufficiency, and his pituitary function gradually improved over time. Anti-pituitary antibodies (APAs) against corticotrophs, thyrotrophs, gonadotrophs, and folliculo stellate cells (FSCs) were detected in serum samples taken 3 months after onset. Hypophysitis after COVID-19 vaccination is a rare clinical condition, with only eight cases reported by the end of 2023, most occurring after the initial or second vaccination. Symptoms of hypophysitis after COVID-19 vaccination are similar to those of classic pituitary dysfunction. Pituitary insufficiency is persistent, with five of the above eight patients presenting posterior pituitary dysfunction and three patients presenting only anterior pituitary dysfunction. Two of those eight patients had autoimmune diseases. Our case suggests a potential link between acquired immunity, APA production, and pituitary damage. To elucidate the etiology of hypophysitis associated with COVID-19 vaccination, detailed investigation of patients with nonspecific symptoms after vaccination against COVID-19 is necessary.

Associations of conservatism and jumping to conclusions biases with aberrant salience and default mode network.

AIM: While conservatism bias refers to the human need for more evidence for decision-making than rational thinking expects, the jumping to conclusions (JTC) bias refers to the need for less evidence among individuals with schizophrenia/delusion compared to healthy people. Although the hippocampus-midbrain-striatal aberrant salience system and the salience, default mode (DMN), and frontoparietal networks ("triple networks") are implicated in delusion/schizophrenia pathophysiology, the associations between conservatism/JTC and these systems/networks are unclear. METHODS: Thirty-seven patients with schizophrenia and 33 healthy controls performed the beads task, with large and small numbers of bead draws to decision (DTD) indicating conservatism and JTC, respectively. We performed independent component analysis (ICA) of resting functional magnetic resonance imaging (fMRI) data. For systems/networks above, we investigated interactions between diagnosis and DTD, and main effects of DTD. We similarly applied ICA to structural and diffusion MRI to explore the associations between DTD and gray/white matter. RESULTS: We identified a significant main effect of DTD with functional connectivity between the striatum and DMN, which was negatively correlated with delusion severity in patients, indicating that the greater the anti-correlation between these networks, the stronger the JTC and delusion. We further observed the main effects of DTD on a gray matter network resembling the DMN, and a white matter network connecting the functional and gray matter networks (all P < 0.05, family-wise error [FWE] correction). Function and gray/white matter showed no significant interactions. CONCLUSION: Our results support the novel association of conservatism and JTC biases with aberrant salience and default brain mode.

Selective Synthesis of Perovskite Oxyhydrides Using a High-Pressure Flux Method.

Oxyhydrides with multi-anions (O2- and H-) are a recently developed material family and have attracted attention as catalysts and hydride ion conductors. High-pressure and high-temperature reactions are effective in synthesizing oxyhydrides, but the reactions sometimes result in inhomogeneous products due to insufficient diffusion of the solid components. Here, we synthesized new perovskite oxyhydrides SrVO2.4H0.6 and Sr3V2O6.2H0.8. We demonstrated that the addition of SrCl2 flux promotes diffusion during high-pressure and high-temperature reactions, and can be used for selective synthesis of the oxyhydride phases. We conducted in-situ synchrotron X-ray diffraction measurements to reveal the role of this flux and reaction pathways. We also demonstrated the electronic and magnetic properties of the newly synthesized oxyhydrides and that they work as anode materials for Li-ion batteries with excellent reversibility and high-rate characteristics, the first case with an oxyhydride. Our synthesis approach would also be effective in synthesizing various types of multi-component systems.

Effects of Central Elements on the Properties of Group 13 Dialdiminate Complexes.

Novel luminescent dialdiminate complexes of the Group 13 elements were prepared to evaluate the effects of the central element on their properties. We demonstrate that their absorption wavelength and the response to Lewis bases apparently depend on the central atom. The aluminum complex exhibited the absorption band in the higher-energy region than the gallium and indium congeners. Theoretical calculations suggest that the aluminum complex has a lower-lying highest-occupied molecular orbital than the other complexes. Additionally, the emission intensity of the aluminum complex clearly changed in response to a Lewis base. Quantum chemical calculations suggest that these element-dependent optical properties could originate from the difference in the electric charges on the central elements. Interestingly, the ligand exchange reactions were observed in the indium complexes together with the changes in the optical properties and controlled by the addition of InCl3 and InMe3 . Furthermore, all the complexes showed aggregation-induced emission enhancement (AIEE) and crystallization-induced emission enhancement (CIEE) properties. These results lead to proposing a practical strategy for manipulating the optoelectronic properties coupled with the reactivities of complexes by choosing the central elements in the same group.

Effects of Central Elements on the Properties of Group 13 Dialdiminate Complexes.

Invited for the cover of this issue is the group of Kazuo Tanaka at Kyoto University. The image depicts the element-dependent properties of group 13 dialdiminate complexes Read the full text of the article at 10.1002/chem.202300654.

Generalizable brain network markers of major depressive disorder across multiple imaging sites.

Many studies have highlighted the difficulty inherent to the clinical application of fundamental neuroscience knowledge based on machine learning techniques. It is difficult to generalize machine learning brain markers to the data acquired from independent imaging sites, mainly due to large site differences in functional magnetic resonance imaging. We address the difficulty of finding a generalizable marker of major depressive disorder (MDD) that would distinguish patients from healthy controls based on resting-state functional connectivity patterns. For the discovery dataset with 713 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a machine learning MDD classifier. The classifier achieved an approximately 70% generalization accuracy for an independent validation dataset with 521 participants from 5 different imaging sites. The successful generalization to a perfectly independent dataset acquired from multiple imaging sites is novel and ensures scientific reproducibility and clinical applicability.

Examining the usefulness of the brain network marker program using fMRI for the diagnosis and stratification of major depressive disorder: a non-randomized study protocol.

BACKGROUND: Although many studies have reported the biological basis of major depressive disorder (MDD), none have been put into practical use. Recently, we developed a generalizable brain network marker for MDD diagnoses (diagnostic marker) across multiple imaging sites using resting-state functional magnetic resonance imaging (rs-fMRI). We have planned this clinical trial to establish evidence for the practical applicability of this diagnostic marker as a medical device. In addition, we have developed generalizable brain network markers for MDD stratification (stratification markers), and the verification of these brain network markers is a secondary endpoint of this study. METHODS: This is a non-randomized, open-label study involving patients with MDD and healthy controls (HCs). We will prospectively acquire rs-fMRI data from 50 patients with MDD and 50 HCs and anterogradely verify whether our diagnostic marker can distinguish between patients with MDD and HCs. Furthermore, we will longitudinally obtain rs-fMRI and clinical data at baseline and 6 weeks later in 80 patients with MDD treated with escitalopram and verify whether it is possible to prospectively distinguish MDD subtypes that are expected to be effectively responsive to escitalopram using our stratification markers. DISCUSSION: In this study, we will confirm that sufficient accuracy of the diagnostic marker could be reproduced for data from a prospective clinical study. Using longitudinally obtained data, we will also examine whether the "brain network marker for MDD diagnosis" reflects treatment effects in patients with MDD and whether treatment effects can be predicted by "brain network markers for MDD stratification". Data collected in this study will be extremely important for the clinical application of the brain network markers for MDD diagnosis and stratification. TRIAL REGISTRATION: Japan Registry of Clinical Trials ( jRCTs062220063 ). Registered 12/10/2022.

Heat stress during grain filling regulates seed germination through alterations of DNA methylation in barley (Hordeum vulgare L.).

KEY MESSAGE: Alterations in DNA methylation levels of ROS, GA and ABA related gene promoters cause transcriptional changes upon imbibition to induce seed germination in barley seeds exposed to heat stress during grain filling. Environmental changes, especially changes in temperature, during seed development affect germination in several plant species. We have previously shown that heat stress during rice grain filling alters DNA methylation, an epigenetic mark important for gene silencing, regulates transcript levels of phytohormone metabolism genes, and delays seed germination. However, whether this phenomenon is present in other plant species remained to be elucidated. In this study, we compared seeds germination of barley (Hordeum vulgare L.) plants grown at 15 °C (control) or 25 °C (heat stress) during grain filling. Heat stress during grain filling significantly promoted seed germination in comparison with the control. The phytohormone gibberellic acid (GA) and reactive oxygen species produced by NADPH oxidases promote seed germination, whereas phytohormone abscisic acid (ABA) suppresses seed germination. We found that in heat-stressed seeds, genes related to ABA biosynthesis (HvNCED1 and 2) were significantly suppressed, whereas genes related to ABA catabolism (HvABA8'OH) and GA biosynthesis (HvHA20ox, HvGA3ox), and NADPH oxidase (HvRboh) genes were significantly upregulated after imbibition. Using MeDIP-qPCR, we showed that the promoters of HvNCED were hyper-methylated, and those of HvABA8'OH1, HvABA8'OH3, HvGA3ox2, and HvRbohF2 were hypo-methylated in heat treated seeds. Taken together, our data suggest that heat stress during grain filling affects DNA methylation of germination-related genes and promotes seed germination in barley.

Harmonization of resting-state functional MRI data across multiple imaging sites via the separation of site differences into sampling bias and measurement bias.

When collecting large amounts of neuroimaging data associated with psychiatric disorders, images must be acquired from multiple sites because of the limited capacity of a single site. However, site differences represent a barrier when acquiring multisite neuroimaging data. We utilized a traveling-subject dataset in conjunction with a multisite, multidisorder dataset to demonstrate that site differences are composed of biological sampling bias and engineering measurement bias. The effects on resting-state functional MRI connectivity based on pairwise correlations because of both bias types were greater than or equal to psychiatric disorder differences. Furthermore, our findings indicated that each site can sample only from a subpopulation of participants. This result suggests that it is essential to collect large amounts of neuroimaging data from as many sites as possible to appropriately estimate the distribution of the grand population. Finally, we developed a novel harmonization method that removed only the measurement bias by using a traveling-subject dataset and achieved the reduction of the measurement bias by 29% and improvement of the signal-to-noise ratios by 40%. Our results provide fundamental knowledge regarding site effects, which is important for future research using multisite, multidisorder resting-state functional MRI data.

Realization of Negative Thermal Expansion in Lead-Free Bi0.5K0.5VO3 by the Suppression of Tetragonality.

Bi1/2K1/2VO3 is a lead-free PbTiO3-type compound with a tetragonality (c/a = 1.054) comparable to that of typical ferroelectric PbTiO3 (c/a = 1.064) with negative thermal expansion (NTE) during the tetragonal-to-cubic phase transition; therefore, Bi1/2K1/2VO3 is a potential lead-free NTE material if its metastable perovskite structure can be maintained at high temperatures. In the present experiment, electron doping in Bi1/2K1/2VO3 was conducted through substituting K+ with La3+ to suppress the tetragonality and achieve NTE. La substitution successfully suppressed the tetragonality of Bi1/2K1/2VO3 and also improved its thermal stability. Moreover, both composition- and temperature-induced tetragonal-to-cubic phase transitions occurred. In particular, a large volume shrinkage with a large negative thermal coefficient of expansion (CTE) was obtained for Bi0.5K0.46La0.04VO3 during the tetragonal-to-cubic phase transition (ΔV = -0.66%). Hence, this study extends the NTE family and also sheds light on the exploration of lead-free piezoelectric materials with controllable thermal expansion.

Bi0.5Pb0.5FeO3 with Unusual Pb Charge Disproportionation: Indication of a Systematic Charge Distribution Change in Bi0.5Pb0.5MO3 (M: 3d Transition Metal).

Bi0.5Pb0.5FeO3 with 1:1 mixture of Bi and Pb having charge degrees of freedom at the A-site of perovskite oxide ABO3 is obtained for the first time by high-pressure synthesis. Comprehensive synchrotron X-ray powder diffraction, optical second harmonic generation, Mössbauer spectroscopy, and hard X-ray photoemission spectroscopy measurements revealed that Bi0.5Pb0.5FeO3 is a canted antiferromagnetic insulator crystalizing in a nonpolar tetragonal I4/mcm structure with √2a × âˆš2a × 2a unit cell and has unusually Pb charge disproportionated Bi3+0.5Pb2+0.25Pb4+0.25Fe3+O3 charge distribution. The valence of transition metal M in Bi0.5Pb0.5MO3 changes from 3.5+ to 3+ and finally to 2+ from Mn to Fe and to Ni, from left to right in the periodic table as the 3d-level becomes deeper. The valences of Bi and Pb increase to compensate for the decrease in the M's valence, and Pb changes from 6s2 (2+) to 6s0 (4+) before Bi changes.

Sequential Pressure-Induced B1-B2 Transitions in the Anion-Ordered Oxyhydride Ba2YHO3.

We present a detailed experimental and computational investigation of the influence of pressure on the mixed-anion oxyhydride phase Ba2YHO3, which has recently been shown to support hydride conductivity. The unique feature of this layered perovskite is that the oxide and hydride anions are segregated into distinct regions of the unit cell, in contrast to the disordered arrangement in closely related Ba2ScHO3. Density functional theory (DFT) calculations reveal that the application of pressure drives two sequential B1-B2 transitions in the interlayer regions from rock salt to CsCl-type ordering, one in the hydride-rich layer at approximately 10 GPa and another in the oxide-rich layer at 35-40 GPa. To verify the theoretical predictions, we experimentally observe the structural transition at 10 GPa using high-pressure X-ray diffraction (XRD), but the details of the structure cannot be solved due to peak broadening of the XRD patterns. We use DFT to explore the structural impact of pressure on the atomic scale and show how the pressure-dependent properties can be understood in terms of simple electrostatic engineering.

SrV0.3Fe0.7O2.8: A Vacancy-Ordered Fe-Based Perovskite Exhibiting Room-Temperature Magnetoresistance.

We report room-temperature (RT) magnetoresistance (MR) in a novel Fe-based perovskite, SrV0.3Fe0.7O2.8. This compound contains ordered oxygen vacancies in every fifth primitive perovskite (111)p plane, leading to a layered structure consisting of triple-octahedral and double-tetrahedral layers. Along with the oxygen vacancies, the transition-metal ions are also ordered: the octahedral sites are occupied by 100% of Fe ions, while the tetrahedral sites are occupied by 25% of Fe ions and 75% of V ions. As a result, SrV0.3Fe0.7O2.8 forms a magnetically striped lattice in which the octahedral layers with 100% of magnetic Fe ions are separated by the diluted magnetic layer. The compound exhibits weak ferromagnetism and shows a large negative MR (-5% at 3 T) at RT, despite the small saturation moment (0.4 µB/Fe atom). Thus, this type of layered compound is promising for further large MR by an increase of magnetization through chemical substitution.

Quality of life of patients with hematological malignancies and factors affecting health state utility values.

PURPOSE: It is well studied that physical function and social background affect the quality of life (QoL) of cancer patients. However, differences in QoL by age and factors affecting health state utility values (HSUV) of patients with hematological malignancies have not yet been sufficiently investigated. Our aim is to investigate the factors that affect QoL and HSUV in such patients. METHODS: A total of 32 patients with hematological malignancies on outpatient chemotherapy were included. QoL and HSUV were evaluated using the EuroQol-5 Dimension 5-level (EQ-5D-5L). Physical function was assessed using grip strength, knee extension strength, 6-min walking distance, and Short Physical Performance Battery (SPPB). Fatigue was assessed using Brief Fatigue Inventory (BFI), and nutritional status was assessed using Mini Nutritional Assessment-Short Form (MNA-SF). RESULTS: In the EQ-5D-5L, a high percentage of the patients were aware of mobility problems and pain/discomfort, and mobility problems were more common in the older-aged group (≥ 65 years old, n = 16) than in the middle-aged group (< 65 years old, n = 16). In addition, the older-aged group showed lower HSUV and physical function. SPPB (ß = 0.38, p < 0.01), BFI (ß = - 0.58, p < 0.01), and MNA-SF (ß = 0.29, p = 0.02) were independent factors affecting HSUV (adjusted R2 = 0.65, p < 0.01). BFI was correlated with HSUV in both older and middle-aged groups. CONCLUSION: Comprehensive supports, to improve lower extremity function, fatigue, and nutritional status, are required to augment QoL and HSUV in patients with hematological malignancies.

Clinical outcomes of 34 patients with resistance to thyroid hormone beta: a twenty-year experience in Japan.

Resistance to thyroid hormone beta (RTHß) caused by germline mutations in genes encoding thyroid hormone receptor beta (TRß) is a rare disorder. Little information is available regarding the clinical experience of this syndrome in Japan. We retrospectively reviewed the records of 34 patients with RTHß (21 adult females and 13 adult males) with positive TRß mutations identified at our division between 2000 and 2020. Of the 24 patients with available clinical history, 10 (41.7%) received inappropriate treatments such as antithyroid drugs, thyroidectomy, or radioactive iodine. Diagnostic delay and inappropriate management of RTHß are still present in Japan. Every patient except one demonstrated thyroid hormone profiles indicative of syndrome of inappropriate secretion of thyrotropin (SITSH), characterized by a hormonal profile of hyperthyroxinemia with a non-suppressed TSH concentration. Since the most common forms of hyperthyroidism including Graves' disease feature elevated thyroid hormone levels with suppressed TSH concentrations, early diagnosis of SITSH is critical for preventing inappropriate management. One patient positive for anti-thyroglobulin antibody (Tg-Ab) and anti-thyroperoxidase antibody (TPO-Ab) showed remarkably elevated TSH (>200 µIU/mL) despite thyroid hormone concentrations within the reference ranges. At least one thyroid autoantibody (Tg-Ab, TPO-Ab, or thyrotropin receptor antibodies) was identified in 37.9% (11/29) of the patients tested. One patient developed overt Graves' disease nine years after RTHß diagnosis. These findings suggest that RTHß is frequently comorbid with additional autoimmune thyroid disorders. Further research is required to identify the most appropriate treatments for RTHß patients who develop a second thyroid disorder.

A Facile α-Glucuronidation Using Methyl 1,2,3,4-Tetra-O-acetyl-D-glucuronate as Glycosyl Donor.

Some terpenyl 2,3,4-tri-O-acetyl-α-D-glucuronide methyl esters were facilely synthesized from commercially available methyl 1,2,3,4-tetra-O-acetyl-ß-D-glucuronate and terpenoid alcohols in the presence of bis(trifluoromethanesulfonyl)imide (Tf2NH) in dichloromethane (DCM) in good yields. The predominant α-selectivity at the anomer position is caused via transition state in which the neighboring group participation of the methoxycarbonyl group at C-6 stabilizes the oxonium intermediate by forming 1C4 conformation. The intermediate accelerates the glucuronidation reaction despite the use of the acetyl group, which is not a good activating group in general glycosylation reactions, as the activating group.

Intermetallic Charge Transfer in V-Substituted PbCrO3.

PbCrO3 features an unusual charge distribution Pb0.52+Pb0.54+Cr3+O3 with Pb charge disproportionation at ambient pressure. A charge transfer between Pb and Cr is induced by the application of pressure resulting in Pb2+Cr4+O3 charge distribution and a large volume collapse. Here, structural and charge distribution changes in PbCr1-xVxO3 are investigated. Despite a cubic crystal structure in 0 ≤ x ≤ 0.60, discontinuous reduction in the unit cell volume was observed between x = 0.35 and 0.40. Hard X-ray photoemission spectroscopy confirmed the change in Pb charge state from the coexisting Pb2+ and Pb4+ at x = 0.35 to single Pb2+ at x = 0.40. This indicates that V substitution stabilizes the high pressure cubic Pb2+Cr4+O3-type phase. With further increase in the V substitution, the PbVO3-type polar tetragonal phase appeared at x = 0.80.

Image quality improvement with deep learning-based reconstruction on abdominal ultrahigh-resolution CT: A phantom study.

PURPOSE: In an ultrahigh-resolution CT (U-HRCT), deep learning-based reconstruction (DLR) is expected to drastically reduce image noise without degrading spatial resolution. We assessed a new algorithm's effect on image quality at different radiation doses assuming an abdominal CT protocol. METHODS: For the normal-sized abdominal models, a Catphan 600 was scanned by U-HRCT with 100%, 50%, and 25% radiation doses. In all acquisitions, DLR was compared to model-based iterative reconstruction (MBIR), filtered back projection (FBP), and hybrid iterative reconstruction (HIR). For the quantitative assessment, we compared image noise, which was defined as the standard deviation of the CT number, and spatial resolution among all reconstruction algorithms. RESULTS: Deep learning-based reconstruction yielded lower image noise than FBP and HIR at each radiation dose. DLR yielded higher image noise than MBIR at the 100% and 50% radiation doses (100%, 50%, DLR: 15.4, 16.9 vs MBIR: 10.2, 15.6 Hounsfield units: HU). However, at the 25% radiation dose, the image noise in DLR was lower than that in MBIR (16.7 vs. 26.6 HU). The spatial frequency at 10% of the modulation transfer function (MTF) in DLR was 1.0 cycles/mm, slightly lower than that in MBIR (1.05 cycles/mm) at the 100% radiation dose. Even when the radiation dose decreased, the spatial frequency at 10% of the MTF of DLR did not change significantly (50% and 25% doses, 0.98 and 0.99 cycles/mm, respectively). CONCLUSION: Deep learning-based reconstruction performs more consistently at decreasing dose in abdominal ultrahigh-resolution CT compared to all other commercially available reconstruction algorithms evaluated.

Impairment of the Hypothalamus-Pituitary-Thyroid Axis Caused by Naturally Occurring GATA2 Mutations In Vitro.

The transcription factor GATA2 regulates gene expression in several cells and tissues, including hematopoietic tissues and the central nervous system. Recent studies revealed that loss-of-function mutations in GATA2 are associated with hematological disorders. Our earlier in vitro studies showed that GATA2 plays an essential role in the hypothalamus-pituitary-thyroid axis (HPT axis) by regulating the genes encoding prepro-thyrotropin-releasing hormone (preproTRH) and thyroid-stimulating hormone ß (TSHß). However, the effect of GATA2 mutants on the transcriptional activity of their promoters remains unelucidated. In this study, we created five human GATA2 mutations (R308P, T354M, R396Q, R398W, and S447R) that were reported to be associated with hematological disorders and analyzed their functional properties, including transactivation potential and DNA-binding capacity toward the preproTRH and the TSHß promoters. Three mutations (T354M, R396Q, and R398W) within the C-terminal zinc-finger domain reduced the basal GATA2 transcriptional activity on both the preproTRH and the TSHß promoters with a significant loss of DNA binding affinity. Interestingly, only the R398W mutation reduced the GATA2 protein expression. Subsequent analysis demonstrated that the R398W mutation possibly facilitated the GATA2 degradation process. R308P and S447R mutants exhibited decreased transcriptional activity under protein kinase C compared to the wild-type protein. In conclusion, we demonstrated that naturally occurring GATA2 mutations impair the HPT axis through differential functional mechanisms in vitro.