Topographic Organization of Glutamatergic and GABAergic Parvalbumin-Positive Neurons in the Lateral Habenula.

Parvalbumin-expressing (PV) neurons, classified by their expression of the calcium-binding protein parvalbumin, play crucial roles in the function and plasticity of the lateral habenular nucleus (LHb). This study aimed to deepen our understanding of the LHb by collecting information about the heterogeneity of LHb PV neurons in mice. To achieve this, we investigated the proportions of the transmitter machinery in LHb PV neurons, including GABAergic, glutamatergic, serotonergic, cholinergic, and dopaminergic neurotransmitter markers, using transcriptome analysis, mRNA in situ hybridization chain reaction, and immunohistochemistry. LHb PV neurons comprise three subsets: glutamatergic, GABAergic, and double-positive for glutamatergic and GABAergic machinery. By comparing the percentages of the subsets, we found that the LHb was topographically organized anteroposteriorly; the GABAergic and glutamatergic PV neurons were preferentially distributed in the anterior and posterior LHb, respectively, uncovering the anteroposterior topography of the LHb. In addition, we confirmed the mediolateral topography of lateral GABAergic PV neurons. These findings suggest that PV neurons play distinct roles in different parts of the LHb along the anteroposterior and mediolateral axes, facilitating the topographic function of the LHb. It would be interesting to determine whether their topography is differentially involved in various cognitive and motivational processes associated with the LHb, particularly the involvement of posterior glutamatergic PV neurons.

Effects of the Addition of Tin Powder to Perovskite Precursor Solutions on Band Bending at PEDOT:PSS/Perovskite Interfaces in Mixed-Cation Mixed-Halide Tin Perovskite Solar Cells.

Using electron spin resonance (ESR) spectroscopy, we investigated the effects of the addition of tin (Sn) powder to perovskite layers on band bending at the perovskite surface near poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hole-transport layers in perovskite solar cells (PSCs) involving formamidinium (FA)-methylammonium (MA)-mixed-cation I-Br-mixed-halide tin perovskites. We performed dark ESR spectroscopy measurements of a PEDOT:PSS/FA0.75MA0.25Sn(I0.75Br0.25)3 stack and of a PEDOT:PSS/Sn-powder-added FA0.75MA0.25Sn(I0.75Br0.25)3 stack. The results indicate that FA0.75MA0.25Sn(I0.75Br0.25)3 layers have significant downward band bending near PEDOT:PSS layers. Such downward band bending is unfavorable for hole selectivity and surface passivation at the interface. However, the addition of Sn powder to the tin perovskite precursor solution was found to significantly prevent the downward band bending and rather cause upward band bending, which can improve the hole selectivity and field-effect passivation quality. This can be due to prevented oxidation of perovskite layers by Sn powder addition. These findings are crucial for developing highly efficient and stable tin perovskite solar cells.

Utility of combining multiple parameters of 123I-IMP SPECT and voxel-based morphometry MRI using a multiparametric scoring system for differentiating dementia with Lewy bodies from Alzheimer's disease.

BACKGROUND: Brain magnetic resonance imaging voxel-based morphometry (VBM) and perfusion single-photon emission computed tomography (SPECT) are useful for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). PURPOSE: To determine whether combining multiple parameters of VBM and SPECT using a multiparametric scoring system (MSS) improves diagnostic accuracy in differentiating DLB from AD. MATERIAL AND METHODS: In total, 23 patients with DLB and 57 patients with AD underwent imaging using a voxel-based specific regional analysis system for AD (VSRAD), an easy Z-score imaging system, and a Z-Graph using three-dimensional stereotactic surface projection. The cutoff values were determined using the receiver operating characteristic curve to differentiate DLB from AD for all parameters. Patients were scored 1 (DLB) or 0 (AD) for each statistically significant parameter, according to a threshold. The total score was determined for each case to obtain a cutoff value for the MSS. RESULTS: The mean Z-scores in the medial temporal lobes using the VSRAD were significantly lower in patients with DLB than in those with AD. Each Z-score of the summed Z-scores in all four segmented regions of the occipital lobes using the Z-Graph was significantly higher in patients with DLB than in those with AD. Among the five parameters, the highest accuracy was 80% for the Z-score of the summed Z-scores in the left medial occipital lobe. For the MSS, a cutoff value of four improved the diagnostic accuracy to 82%. CONCLUSION: MSS was more accurate than any single parameter of VBM or SPECT in differentiating DLB from AD.

Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma.

A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.

An open-cage bis[60]fulleroid as an electron transport material for tin halide perovskite solar cells.

An open-cage bis[60]fulleroid (OC) was applied as an electron transport material (ETM) in tin (Sn) halide perovskite solar cells (PSCs). Due to the reduced offset between the energy levels of Sn-based perovskites and ETMs, the power conversion efficiency (PCE) of Sn-based PSCs with OC reached 9.6% with an open-circuit voltage (VOC) of 0.72 V. Additionally, OC exhibited superior thermal stability and provided 75% of the material without decomposition after vacuum deposition. The PSC using vacuum-deposited OC as the ETM could afford a PCE of 7.6%, which is a big leap forward compared with previous results using vacuum-deposited fullerene derivatives as ETMs.

Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system.

BACKGROUND: Cisplatin (CDDP) plays a central role in chemotherapy for head and neck squamous cell carcinoma (HNSCC), but drug resistance in HNSCC chemotherapy remains a problem, and the mechanism of CDDP resistance is unclear. We investigated CDDP-resistance mechanisms mediated by extracellular vesicles (EVs) and ATPase copper transporting beta (ATP7B) in HNSCC. METHODS: We established CDDP-resistant sublines of HNSCC cells and verified their ATP7B expression. We used an EV secretion inhibitor (GW4869) and ATP7B short hairpin (sh)RNA transfection to examine the correlation between EV secretion and ATP7B expression. RESULTS: The CDDP-resistant HNSCC sublines showed decreased CDDP sensitivity and increased ATP7B expression. GW4869 suppressed ATP7B expression, and ATP7B shRNA transfection suppressed EV secretion. The suppressions of EV secretion and ATP7B expression both enhanced CDDP's cell-killing effect. CONCLUSIONS: EVs were involved in the ATP7B-mediated mechanism underlying CDDP resistance. Further clarification of the EV-induced CDDP-resistance mechanism may lead to novel therapeutic strategies for HNSCC.

The moment of awareness influences the content of awareness in orientation repulsion.

Through the neurally evolving process of dynamic contextual modulation of perceptual contents, it remains unclear how the content of awareness is determined. Here we quantified the visual illusion of orientation repulsion, wherein the target appears tilted against the surrounding's orientation, and examined whether its extent changed when the target awareness was quickened by a preceding flanker. Independently of spatial cueing, repulsion was reduced when the flanker preceded the target by 100 ms compared with when they appeared simultaneously. We confirmed that the preceding flanker quickened the awareness of a nearby target relative to distant ones by 40 ms. Furthermore, the preceding flanker that was greater than 7 degrees away from the target still evoked such reduction of repulsion. These findings imply that the content of awareness is determined by the temporal interaction of two distinct processes: one controls the moment of awareness, and the other represents the perceptual content.

Spontaneous Polarization Induced Optical Responses in a Two-Dimensional Ferroelectric Halide Perovskite.

Two-dimensional (2D) halide perovskites exhibit unique structural and optical properties because large organic molecular cations distort the perovskite structure and the excitons confined in the 2D layers are stable. Here, we report the temperature dependences of the absorption spectra, second harmonic generation (SHG) intensity, and lattice constants of 2D perovskite (BA)2(EA)2Pb3I10 single crystals, where BA is n-butylammonium and EA is ethylammonium. We found that the Urbach tail of the absorption spectrum significantly changes at around 200 K and that the change is correlated with the SHG intensity and the in-plane lattice distortion. We concluded that a random distribution of spontaneous polarizations in the ferroelectric phase modifies the linewidth of the band-edge exciton transition and is the cause of the anomalous temperature dependence of the steepness parameter of the Urbach tail.

Intense absorption of azulene realized by molecular orbital inversion.

The introduction of diarylamino groups at the 2- and 6-positions of azulene was found to invert the order of the orbital energy levels and allowed the HOMO-LUMO transition, resulting in a substantial increase in absorbance in the visible region. In addition, the stability of their one-electron oxidised species was improved by introducing bromine or methoxy groups at the 1- and 3-positions.

EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma.

OBJECTIVES: Cetuximab (Cmab) is a molecularly targeted monoclonal antibody drug for head and neck squamous cell carcinoma (HNSC), although cetuximab resistance is a serious challenge. Epithelial cell adhesion molecule (EpCAM) is an established marker for many epithelial tumors, while the soluble EpCAM extracellular domain (EpEX) functions as a ligand for epidermal growth factor receptor (EGFR). We investigated the expression of EpCAM in HNSC, its involvement in Cmab action, and the mechanism by which soluble EpEX activated EGFR and played key roles in Cmab resistance. MATERIALS AND METHODS: We first examined EPCAM expression in HNSCs and its clinical significance by searching gene expression array databases. We then examined the effects of soluble EpEX and Cmab on intracellular signaling and Cmab efficacy in HNSC cell lines (HSC-3 and SAS). RESULTS: EPCAM expression was found to be enhanced in HNSC tumor tissues compared to normal tissues, and the enhancement was correlated with stage progression and prognosis. Soluble EpEX activated the EGFR-ERK signaling pathway and nuclear translocation of EpCAM intracellular domains (EpICDs) in HNSC cells. EpEX resisted the antitumor effect of Cmab in an EGFR expression-dependent manner. CONCLUSION: Soluble EpEX activates EGFR to increase Cmab resistance in HNSC cells. The EpEX-activated Cmab resistance in HNSC is potentially mediated by the EGFR-ERK signaling pathway and the EpCAM cleavage-induced nuclear translocation of EpICD. High expression and cleavage of EpCAM are potential biomarkers for predicting the clinical efficacy and resistance to Cmab.

Wave-optics-based image synthesis for super resolution reconstruction of a FZA lensless camera.

A Fresnel Zone Aperture (FZA) mask for a lensless camera, an ultra-thin and functional computational imaging system, is beneficial because the FZA pattern makes it easy to model the imaging process and reconstruct captured images through a simple and fast deconvolution. However, diffraction causes a mismatch between the forward model used in the reconstruction and the actual imaging process, which affects the recovered image's resolution. This work theoretically analyzes the wave-optics imaging model of an FZA lensless camera and focuses on the zero points caused by diffraction in the frequency response. We propose a novel idea of image synthesis to compensate for the zero points through two different realizations based on the linear least-mean-square-error (LMSE) estimation. Results from computer simulation and optical experiments verify a nearly two-fold improvement in spatial resolution from the proposed methods compared with the conventional geometrical-optics-based method.

BAr2 -Bridged Azafulvene Dimers with Tunable Energy Levels for Photostable Near-Infrared Dyes.

Organic dyes with strong absorption in the near-infrared (NIR) region are potentially useful in medical applications, such as tumor imaging and photothermal therapy. In this work, new NIR dyes combining BAr2 -bridged azafulvene dimer acceptors with diarylaminothienyl donors in a donor-acceptor-donor configuration were synthesized. Surprisingly, it was found that in these molecules the BAr2 -bridged azafulvene acceptor adopts a 5-membered, rather than 6-membered ring structure. The influence of the aryl substituents on the HOMO and LUMO energy levels of the dye compounds was assessed from electrochemical and optical measurements. Strong electron-withdrawing fluorinated substituents (Ar=C6 F5 , 3,5-(CF3 )2 C6 H3 ) lowered the HOMO energy while preserving the small HOMO-LUMO energy gap, resulting in promising NIR dye molecules that combine strong absorption bands centered around 900 nm with good photostability.

Tripodal Triazatruxene Derivative as a Face-On Oriented Hole-Collecting Monolayer for Efficient and Stable Inverted Perovskite Solar Cells.

Hole-collecting monolayers have drawn attention in perovskite solar cell research due to their ease of processing, high performance, and good durability. Since molecules in the hole-collecting monolayer are typically composed of functionalized π-conjugated structures, hole extraction is expected to be more efficient when the π-cores are oriented face-on with respect to the adjacent surfaces. However, strategies for reliably controlling the molecular orientation in monolayers remain elusive. In this work, multiple phosphonic acid anchoring groups were used to control the molecular orientation of a series of triazatruxene derivatives chemisorbed on a transparent conducting oxide electrode surface. Using infrared reflection absorption spectroscopy and metastable atom electron spectroscopy, we found that multipodal derivatives align face-on to the electrode surface, while the monopodal counterpart adopts a more tilted configuration. The face-on orientation was found to facilitate hole extraction, leading to inverted perovskite solar cells with enhanced stability and high-power conversion efficiencies up to 23.0%.

Lactate secreted via MCT4 from bone­colonizing breast cancer excites sensory neurons via GPR81.

Breast cancer (BC) bone metastasis causes bone pain (BP), which detrimentally damages the quality of life and outcome of patients with BC. However, the mechanism of BC­BP is poorly understood, and effective treatments are limited. The present study demonstrated a novel mechanism of BC­BP using a mouse model of bone pain, in which mouse (EO771) and human (MDA­MB­231) BC cells were injected in the bone marrow cavity of tibiae. Western blot analysis using sensory nerves, in vivo assessment of cancer pain and in vitro calcium flux analysis were performed. These mice developed progressive BC­BP in tibiae in conjunction with an upregulation of phosphorylated pERK1/2 and cAMP­response element­binding protein (pCREB), which are molecular indicators of neuron excitation, in the dorsal root ganglia (DRG) of sensory nerves. Importantly, mice injected with BC cells, in which the expression of the lactic acid transporter monocarboxylate transporter 4 (MCT4) was silenced, exhibited decreased BC­BP with downregulated expression of pERK1/2 and pCREB in the DRG and reduced circulating levels of lactate compared with mice injected with parental BC cells. Further, silencing of the cell­surface orphan receptor for lactate, G protein­coupled receptor 81 (GPR81), in the F11 sensory neuron cells decreased lactate­promoted upregulation of pERK1/2 and Ca2+ influx, suggesting that the sensory neuron excitation was inhibited. These results suggested that lactate released from BC cells via MCT4 induced BC­BP through the activation of GPR81 of sensory neurons. In conclusion, the activation of GPR81 of sensory neurons by lactate released via MCT4 from BC was demonstrated to contribute to the induction of BC­BP, and disruption of the interactions among lactate, MCT4 and GPR81 may be a novel approach to control BC­BP.

Suppressive effects of ketamine on auditory steady-state responses in intact, awake macaques: A non-human primate model of schizophrenia.

Auditory steady-state responses (ASSRs) are recurrent neural activities entrained to regular cyclic auditory stimulation. ASSRs are altered in individuals with schizophrenia, and may be related to hypofunction of the N-methyl-D-aspartate (NMDA) glutamate receptor. Noncompetitive NMDA receptor antagonists, including ketamine, have been used in ASSR studies of rodent models of schizophrenia. Although animal studies using non-human primates are required to complement rodent studies, the effects of ketamine on ASSRs are unknown in intact awake non-human primates. In this study, after administration of vehicle or ketamine, click trains at 20-83.3 Hz were presented to elicit ASSRs during recording of electroencephalograms in intact, awake macaque monkeys. The results indicated that ASSRs quantified by event-related spectral perturbation and inter-trial coherence were maximal at 83.3 Hz after vehicle administration, and that ketamine reduced ASSRs at 58.8 and 83.3 Hz, but not at 20 and 40 Hz. The present results demonstrated a reduction of ASSRs by the NMDA receptor antagonist at optimal frequencies with maximal responses in intact, awake macaques, comparable to ASSR reduction in patients with schizophrenia. These findings suggest that ASSR can be used as a neurophysiological biomarker of the disturbance of gamma-oscillatory neural circuits in this ketamine model of schizophrenia using intact, awake macaques. Thus, this model with ASSRs would be useful in the investigation of human brain pathophysiology as well as in preclinical translational research.

A Universal Surface Treatment for p-i-n Perovskite Solar Cells.

Perovskite interfaces critically influence the final performance of the photovoltaic devices. Optimizing them by reducing the defect densities or improving the contact with the charge transporting material is key to further enhance the efficiency and stability of perovskite solar cells. Inverted (p-i-n) devices can particularly benefit here, as evident from various successful attempts. However, every reported strategy is adapted to specific cell structures and compositions, affecting their robustness and applicability by other researchers. In this work, we present the universality of perovskite top surface post-treatment with ethylenediammonium diiodide (EDAI2) for p-i-n devices. To prove it, we compare devices bearing perovskite films of different composition, i.e., Sn-, Pb-, and mixed Sn-Pb-based devices, achieving efficiencies of up to 11.4, 22.0, and 22.9%, respectively. A careful optimization of the EDAI2 thickness indicates a different tolerance for Pb- and Sn-based devices. The main benefit of this treatment is evident in the open-circuit voltage, with enhancements of up to 200 mV for some compositions. In addition, we prove that this treatment can be successfully applied by both wet (spin-coating) and dry (thermal evaporation) methods, regardless of the composition. The versatility of this treatment makes it highly appealing for industrial application, as it can be easily adapted to specific processing requirements. We present a detailed experimental protocol, aiming to provide the community with an easy, universal perovskite post-treatment method for reliably improving the device efficiency, highlighting the potential of interfaces for the field.

Lip pleomorphic adenomas: case series and literature review.

Background: Pleomorphic adenoma (PA) is the most frequent benign salivary gland tumor, but a lip PA is rare. Although this tumor may be definitively diagnosed by imaging or a tissue biopsy if it is reasonably large, PAs on the lip are relatively small, and they present findings that are similar to those of other lip lesions, which can make a preoperative diagnosis difficult. Methods: We analyzed all PAs in the oral region and lesions on the lips treated in our department over the past 20 years, and we discuss them together with the relevant literature. Results: We found that 11.8% (n=6) of the PAs occurred on a lip (upper lip: 9.8%, lower lip: 2.0%), and ~1% of all mass lesions of the lips were PAs. The average size of the lip PAs was 1.5±0.7 cm (range, 0.7-2.2 cm). For preoperative diagnostic assistance, ultrasonography (US) (n=4), magnetic resonance (MR) (n=3), or no imaging (n=2) was used. An excisional biopsy was performed in all cases, and to date, no recurrence or malignant transformation has been observed. Conclusions: Lip PA is relatively rare. Because almost all of these lesions are small, a preoperative diagnosis is more difficult compared to palatal lesions. This tumor is also prone to long-term neglect and has the potential for recurrence and malignant transformation. It is thus necessary to perform an excision that includes the capsule and surrounding tissues, and careful postoperative follow-up should be continued.

Computational see-through screen camera based on a holographic waveguide device.

This study proposes a novel computational imaging system that integrates a see-through screen (STS) with volume holographic optical elements (vHOEs) and a digital camera unit. Because of the unique features of the vHOE, the STS can function as a holographic waveguide device (HWD) and enable the camera to capture the frontal image when the user gazes at the screen. This system not only provides an innovative solution to a high-quality video communication system by realizing eye-contact but also contributes to other visual applications due to its refined structure. However, there is a dilemma in the proposed imaging system: for a wider field of view, a larger vHOE is necessary. If the size of the vHOE is larger, the light rays from the same object point are diffracted at different Bragg conditions and reflect a different number of times, which causes blurring of the captured image. The system imaging process is analyzed by ray tracing, and a digital image reconstruction method was employed to obtain a clear picture in this study. Optical experiments confirmed the effectiveness of the proposed HWD-STS camera.

Characteristics of auditory steady-state responses to different click frequencies in awake intact macaques.

BACKGROUND: Auditory steady-state responses (ASSRs) are periodic evoked responses to constant periodic auditory stimuli, such as click trains, and are suggested to be associated with higher cognitive functions in humans. Since ASSRs are disturbed in human psychiatric disorders, recording ASSRs from awake intact macaques would be beneficial to translational research as well as an understanding of human brain function and its pathology. However, ASSR has not been reported in awake macaques. RESULTS: Electroencephalograms (EEGs) were recorded from awake intact macaques, while click trains at 20-83.3 Hz were binaurally presented. EEGs were quantified based on event-related spectral perturbation (ERSP) and inter-trial coherence (ITC), and ASSRs were significantly demonstrated in terms of ERSP and ITC in awake intact macaques. A comparison of ASSRs among different click train frequencies indicated that ASSRs were maximal at 83.3 Hz. Furthermore, analyses of laterality indices of ASSRs showed that no laterality dominance of ASSRs was observed. CONCLUSIONS: The present results demonstrated ASSRs, comparable to those in humans, in awake intact macaques. However, there were some differences in ASSRs between macaques and humans: macaques showed maximal ASSR responses to click frequencies higher than 40 Hz that has been reported to elicit maximal responses in humans, and showed no dominant laterality of ASSRs under the electrode montage in this study compared with humans with right hemisphere dominance. The future ASSR studies using awake intact macaques should be aware of these differences, and possible factors, to which these differences were ascribed, are discussed.

Craniomaxillofacial Fibrous Dysplasia Improved Cosmetic and Occlusal Problem by Comprehensive Treatment: A Case Report and Review of Current Treatments.

Fibrous dysplasia (FD) is a fibrous lesion of immature bone, with an incidence of 10-20% in the head and neck region. Most cases are monostotic, but when a lesion occurs on the maxillofacial region and spreads to the surrounding bone, it is classified as polyostotic, despite its localized occurrence. In some cases, surgical intervention is required to improve the cosmetic or functional disturbance of a FD in the maxillofacial region, but it is necessary to confirm symmetry of the maxillofacial region in real time, and a surgical support system is required to compensate. Furthermore, prosthetic intervention is considered when postoperative acquired defects occur or further cosmetic or occlusal function improvement is needed. A comprehensive approach by an oral surgeon and a maxillofacial prosthodontist is necessary for the successful treatment and rehabilitation of such patients. In this article, we describe the case of a craniomaxillofacial FD patient with facial asymmetry and denture incompatibility with improved quality of life measures by integrating surgical treatment using a navigation system and postoperative prosthetic rehabilitation. We also discuss recent diagnostic methods and treatment strategies for craniomaxillofacial FD in the literature.