Search

The blue bottle genus Physalia is one of the well-known siphonophore belonging to the Cnidaria, Hydrozoa. Physalia is also known as a ferocious predator, occasionally stinging and fatally wounding humans, but key details of its life cycle and reproductive biology are unclear. Physalia have separate sexes, and sexual reproduction occurs through the release of complex structures called gonodendra that contain many gonophores that will release either eggs or sperm. It is not known how mature the gonophores are when the gonodendra are released. In this study, we aim to characterize germ cell maturation by conducting histological, cytological, and gene expression analyses of the gonodendron of Physalia utriculus from Japan. We found a layered structure of the gonophore, consistent with other studies; however, gametes were not found even in gonophores that were within the released gonodendra. Moreover, haploid cells were not detected by flow cytometry. Analysis of the expression of putative germ cell marker and meiosis related genes showed high expression in the gonophore. These results strongly suggest that germ cells do not mature until after gonodendra are released. These findings provide valuable insights into the reproductive ecology and life cycle of Physalia., (© 2024. The Author(s).)

Objective: Treatment with immune checkpoint inhibitors (ICIs) has shown clinical benefit for a wide range of cancer types. The neutrophil-to-lymphocyte ratio (NLR) reportedly correlates with survival time or progression-free survival in patients treated with ICIs. However, NLR has not yet been assessed in patients with brain metastases (BMs) receiving stereotactic radiosurgery (SRS) combined with concurrent ICIs. The authors investigated the predictive impact of NLR on the survival data of patients with BMs who received SRS with concurrent ICIs., Methods: The clinical records of patients who had undergone SRS with concurrent ICIs for BMs between January 2015 and August 2023 were retrospectively analyzed. NLR was calculated using the data obtained from the last examination prior to SRS. The optimal NLR cutoff value was identified by receiver operating characteristic (ROC) curve analysis for time-to-event data (overall survival [OS] ≤ 18 months). OS and intracranial disease progression-free survival (IC-PFS) rates were compared between the two NLR groups., Results: Of the 185 eligible patients included, 132 were male. The median (IQR) patient age was 69 (61-75) years. The primary cancers were lung, genitourinary, skin, breast, gastrointestinal, and others in 132, 23, 22, 2, 2, and 4 patients, respectively. The post-SRS median OS and IC-PFS times for the entire cohort were 18.4 (95% CI 14.0-23.1) months and 9.2 (95% CI 6.9-10.8) months, respectively. ROC curve analysis identified the optimal NLR cutoff value for 18-month OS to be 5.0 (area under the curve 0.64, Youden index 0.31). Kaplan-Meier analysis revealed that patients with high NLR (> 5) had a significantly shorter OS (median survival time 10.9 months for 48 patients vs 22.2 months for 137 patients, HR 2.0, 95% CI 1.3-3.0, p < 0.001). Similarly, a significant difference in median IC-PFS was noted: 4.8 months with high NLR versus 10.7 months with low NLR (HR 1.7, 95% CI 1.2-2.5, p = 0.003)., Conclusions: The authors found elevated pre-SRS NLR (> 5) to be associated with shorter OS and IC-PFS after SRS with concurrent ICIs for BMs. NLR is a simple, cost-effective, and widely accessible biomarker, which can thus be used for managing patients with BMs receiving SRS concurrently with ICIs. Further investigation in other large datasets is, however, required to validate these findings.

The objectives of this study were to conduct a survey of failure-of-passive-transfer (FPT) in eastern Hokkaido Japan, to evaluate the association between herd-level FPT and death and culling or treatment, and to test the effectiveness of monitoring using herd-level FPT. A total of 4,411 Holstein and Holstein-Wagyu crossbreds calves born from Holstein dams during the year beginning April 2, 2019 on 39 dairy farms were included in the study to investigate death-and-culling and the treatment rate during the first month of life, as well as rearing management up to 3 weeks of age. A subset of Holsteins (n=381) was included in the study for passive transfer and farms were diagnosed as having FPT if more than 20% of newborn calves had serum IgG levels below 10 g/L at the herd level. The prevalence of FPT (

In social insects, interactions among colony members trigger caste differentiation with morphological modifications. During caste differentiation in termites, body parts and caste-specific morphologies are modified during postembryonic development under endocrine controls such as juvenile hormone (JH) and ecdysone. In addition to endocrine factors, developmental toolkit genes such as Hox- and appendage-patterning genes also contribute to the caste-specific body part modifications. These toolkits are thought to provide spatial information for specific morphogenesis. During social evolution, the complex crosstalks between physiological and developmental mechanisms should be established, leading to the sophisticated caste systems. This article reviews recent studies on these mechanisms underlying the termite caste differentiation and addresses implications for the evolution of caste systems in termites., Competing Interests: Declaration of Competing Interest The authors declare there are no conflicts of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Timing the acquisition of a beneficial microbe relative to the evolutionary history of its host can shed light on the adaptive impact of a partnership. Here, we investigated the onset and molecular evolution of an obligate symbiosis between Cassidinae leaf beetles and Candidatus Stammera capleta, a γ-proteobacterium. Residing extracellularly within foregut symbiotic organs, Stammera upgrades the digestive physiology of its host by supplementing plant cell wall-degrading enzymes. We observe that Stammera is a shared symbiont across tortoise and hispine beetles that collectively comprise the Cassidinae subfamily, despite differences in their folivorous habits. In contrast to its transcriptional profile during vertical transmission, Stammera elevates the expression of genes encoding digestive enzymes while in the foregut symbiotic organs, matching the nutritional requirements of its host. Despite the widespread distribution of Stammera across Cassidinae beetles, symbiont acquisition during the Paleocene (∼62 mya) did not coincide with the origin of the subfamily. Early diverging lineages lack the symbiont and the specialized organs that house it. Reconstructing the ancestral state of host-beneficial factors revealed that Stammera encoded three digestive enzymes at the onset of symbiosis, including polygalacturonase-a pectinase that is universally shared. Although non-symbiotic cassidines encode polygalacturonase endogenously, their repertoire of plant cell wall-degrading enzymes is more limited compared with symbiotic beetles supplemented with digestive enzymes from Stammera. Highlighting the potential impact of a symbiotic condition and an upgraded metabolic potential, Stammera-harboring beetles exploit a greater variety of plants and are more speciose compared with non-symbiotic members of the Cassidinae., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Stimulated Raman scattering (SRS) microscopy is a powerful vibrational imaging technique with high chemical specificity. However, the insufficient tuning range or speed of light sources limits the spectral range of SRS imaging and, hence, the ability to identify molecular species. Here, we present a widely tunable fiber optical parametric oscillator with a tuning range of 1470 cm -1 , which can be synchronized with a Ti:sapphire laser. By using the synchronized light sources, we develop an SRS imaging system that covers the fingerprint and C-H stretching regions, without balanced detection. We validate its broadband imaging capability by visualizing a mixed polymer sample in multiple vibrational modes. We also demonstrate SRS imaging of HeLa cells, showing the applicability of our SRS microscope to biological samples., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

Cassidine leaf beetles are associated with genome-reduced symbiotic bacteria Stammera involved in pectin digestion. Stammera cells appear to be harbored in paired symbiotic organs located at the foregut-midgut junction either intracellularly or extracellularly, whereas the symbiont is extracellular in the ovary-accessory glands of adult females and during caplet transmission in eggs. However, using fluorescence and electron microscopy, an intracellular symbiotic configuration of Stammera was observed in Notosacantha species. Detailed inspection of other cassidine species revealed fragmented cell membrane and cytoplasm of the symbiotic organs, wherein Stammera cells are in an intermediate status between intracellularity and extracellularity. We also identified a mitochondria-rich region adjacent to the symbiont-filled region and well-developed muscle fibers surrounding the whole symbiotic organ. Based on these observations, we discuss why the Stammera genome has been reduced so drastically and how symbiont-derived pectinases are produced and supplied to the host's alimentary tract for plant cell wall digestion., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors.)

Background: We aimed to evaluate patient-reported outcomes (PROs) of stereotactic radiosurgery (SRS) for TN in terms of treatment efficacy and toxicity., Methods: We retrospectively analyzed patients who underwent Gamma Knife SRS for idiopathic or classic TN between January 2013 and February 2022. Questionnaires regarding pain relief, treatment toxicity, and post-SRS treatment were sent between late 2022 and early 2023, and the responses received were analyzed. The Faces Pain Scale (FPS, 0: best, 5: worst) was used for quantitative evaluation., Results: Responses were received from 51 patients (76%). The mean pre-SRS FPS score was 4.1 (standard deviation (SD) 1.1). Forty-three patients (83%) reported initial pain relief and the best post-SRS FPS score was 1.1 (SD 1.5) (P < 0.001). At a median follow-up of 50 months, the FPS score was still 1.1 (SD 1.6) (P < 0.001). Analysis of factors contributing to durable pain relief showed neurovascular compression to be associated with FPS score improvement (Odds ratio 5.7, 95% CI 1.1-29.7, P = 0.038). Facial dysesthesia had a mean pre-SRS FPS score of 1.7 (SD 2.0) and a mean score of 1.4 (SD 1.7) at the last follow-up (P = 0.32). Eight patients (15%) received post-SRS interventions and 21 (40%) no longer required pharmacotherapy without post-SRS intervention. Forty-four patients (85%) reported being satisfied with SRS., Conclusions: We analyzed PROs of SRS for TN using the FPS and showed SRS to be a safe and effective treatment modality achieving long lasting pain relief., (Copyright © 2024 Elsevier Inc. All rights reserved.)

G-protein-coupled receptor class 5 member D (GPRC5D) is detected in malignant plasma cells in approximately 90% of patients diagnosed with multiple myeloma (MM). Here, we constructed BsAb5003, a novel humanized bispecific monoclonal antibody targeting CD3 and GPRC5D, and evaluated its therapeutic impact on MM. BsAb5003 induced specific cytotoxicity of GPRC5D-positive MM cells with concomitant T cell activation and cytokine release. The efficacy of BsAb5003 was associated with GPRC5D expression levels in MM cell lines. Flow cytometry analysis of bone marrow mononuclear cells (BMMNCs) from 49 MM patients revealed that GPRC5D was expressed in a wide population of MM patients, including heavily treated and high-risk patients. In ex vivo assays using BMMNCs, BsAb5003 induced potent efficacy against CD138 + MM cells in both newly diagnosed and relapsed/refractory patient samples in a GPRC5D expression-dependent manner. BsAb5003 significantly enhanced T cell activation and cytokine production in combination with immunomodulatory drugs (IMiDs) against MM cell lines. BsAb5003 also demonstrated significant inhibition of in vivo tumor growth by recruiting T cells. Taken together, these results suggest that T cell-redirecting bispecific antibody targeting GPRC5D as monotherapy and combination therapy with IMiDs could be a highly potent and effective treatment approach for a wide population of MM patients., (© 2024. The Author(s).)

The Omni Legend 32 PET/CT system features silicon photomultiplier (SiPM)-based detectors with bismuth germanium oxide crystals and a 32-cm axial field of view (FOV). The present study aimed to determine the performance characteristics of the Omni Legend 32 PET/CT system according to National Electrical Manufacturers Association (NEMA) NU 2-2018 standards. Methods: The PET component of this system comprises 22 detector modules; each module contains 24 detector blocks with 72 bismuth germanium oxide crystals with a volume of 4.1 × 4.1 × 30 mm coupled to 18 SiPM devices with a 6 × 6 mm area, resulting in an axial FOV of 32 cm. The spatial resolution, sensitivity, count rate performance, and image quality delivered by PET were evaluated using the NEMA NU 2-2018 standard. PET images of 2 patients were evaluated to get a visual first impression of the Omni Legend 32 PET/CT system together with Precision DL. Results: The average spatial resolution at 1, 10, and 20 cm from the central axis was 4.3, 5.3, and 6.2 mm, respectively, for filtered backprojection and 3.7, 4.3, and 5.1 mm, respectively, for ordered-subset expectation maximization. The NEMA sensitivity was 47.30 and 47.05 cps/kBq at the axial center of the FOV and at a 10-cm radial offset, respectively. The scatter fraction, count rate accuracy, and peak noise-equivalent count rates were 35.4%, 1.7%, and 501.7 kcps, respectively, at 15.7 kBq/mL. Contrast recovery for the NEMA body phantom from the smallest to the largest sphere ranged from 61.3% to 93.0%, with a background variability of 5.4%-11.7% and a lung error of 5.1% for Q.Clear (β-value, 50). Good patient image quality was obtained with the Omni Legend 32. Conclusion: The Omni Legend 32 has class-leading sensitivity and count rates within the category of whole-body PET systems while maintaining spatial resolution broadly comparable to that of other current SiPM-based PET/CT systems. This combination of properties results in a very good image quality., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Benthic annelids belonging to the family Syllidae (Annelida, Errantia, Phyllodocida) exhibit a unique reproduction mode called "schizogamy" or "stolonization", in which the posterior body part filled with gametes detaches from the original body, as a reproductive unit (stolon) that autonomously swims and spawns. In this study, morphological and histological observations on the developmental processes during stolonization were carried out in Megasyllis nipponica. Results suggest that the stolon formation started with maturation of gonads, followed by the formation of a head ganglion in the anteriormost segment of the developing stolon. Then, the detailed stolon-specific structures such as stolon eyes and notochaetae were formed. Furthermore, expression profiles of genes involved in the anterior-posterior identity (Hox genes), head determination, germ-line, and hormone regulation were compared between anterior and posterior body parts during the stolonization process. The results reveal that, in the posterior body part, genes for gonadal development were up-regulated, followed by hormone-related genes and head-determination genes. Unexpectedly, Hox genes known to identify body parts along the anterior-posterior axis showed no significant temporal expression changes. These findings suggest that during stolonization, gonad development induces the head formation of a stolon, without up-regulation of anterior Hox genes., (© 2023. The Author(s).)

Background: In social insects, interactions among colony members trigger caste differentiation with morphological modifications. In termite caste differentiation, caste-specific morphologies (such as mandibles in soldiers, genital organs in reproductives or wings in alates) are well developed during post-embryonic development under endocrine controls (e.g., juvenile hormone and ecdysone). Since body part-specific morphogenesis in caste differentiation is hormonally regulated by global factors circulated throughout the body, positional information should be required for the caste-specific and also body part-specific morphogenesis. To identify factors providing the positional information, expression and functional analyses of eight Hox genes were carried out during the three types of caste differentiation (i.e., soldier, neotenic and alate differentiation) in a termite, Hodotermopsis sjostedti., Results: Spatio-temporal patterns of Hox gene expression during caste differentiation were elucidated by real-time qPCR, showing the caste-specific upregulations of Hox genes during the differentiation processes. Among eight Hox genes, Deformed (Dfd) was upregulated specifically in mandibles in soldier differentiation, abdominal-A (abd-A) and Abdominal-B (Abd-B) were upregulated in the abdomen in neotenic differentiation, while Sex-comb reduced (Scr) and Antennapedia (Antp) were upregulated during alate differentiation. Furthermore, RNAi knockdown of Dfd in soldier differentiation and of abd-A and Abd-B in neotenic differentiation distorted the modifications of caste-specific morphologies., Conclusions: Gene expression and functional analyses in this study revealed that, in the caste differentiation in termites, upregulation of Hox genes provide positional identities of body segments, resulting in the caste-specific morphogenesis. The acquisition of such developmental modifications would have enabled the evolution of sophisticated caste systems in termites., (© 2023. The Author(s).)

Super-resolution vibrational microscopy is promising to increase the degree of multiplexing of nanometer-scale biological imaging because of the narrower spectral linewidth of molecular vibration compared to fluorescence. However, current techniques of super-resolution vibrational microscopy suffer from various limitations including the need for cell fixation, high power loading, or complicated detection schemes. Here, we present reversible saturable optical Raman transitions (RESORT) microscopy, which overcomes these limitations by using photoswitchable stimulated Raman scattering (SRS). We first describe a bright photoswitchable Raman probe (DAE620) and validate its signal activation and depletion characteristics when exposed to low-power (microwatt level) continuous-wave laser light. By harnessing the SRS signal depletion of DAE620 through a donut-shaped beam, we demonstrate super-resolution vibrational imaging of mammalian cells with excellent chemical specificity and spatial resolution beyond the optical diffraction limit. Our results indicate RESORT microscopy to be an effective tool with high potential for multiplexed super-resolution imaging of live cells.

Objective: Stereotactic radiosurgery (SRS) is the mainstay treatment for brain metastases (BMs) from lung cancer. In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic lung cancer and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for lung cancer BMs prolongs overall survival (OS), improves intracranial disease control, and raises safety concerns., Methods: Patients who underwent SRS for lung cancer BMs at Aizawa Hospital between January 2015 and December 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The two treatment groups, which had a similar likelihood of receiving concurrent ICIs, were generated by propensity score matching (PSM; match ratio 1:1) based on 11 potential prognostic covariates. Patient survival and intracranial disease control were compared between the groups with and without concurrent ICIs (ICI + SRS vs SRS) by time-dependent analyses, taking into account competing events., Results: Five hundred eighty-five patients with lung cancer BM (494 with non-small cell lung cancer and 91 with small cell lung cancer) were eligible. Of those patients, 93 (16%) received concurrent ICIs. Two groups, each with 89 patients (ICI + SRS group and SRS group), were generated by PSM. The 1-year survival rates of the ICI + SRS and SRS groups after the initial SRS were 65% and 50% and the median survival times were 16.9 and 12.0 months, respectively (HR 0.62, 95% CI 0.44-0.87, p = 0.006). The 2-year cumulative neurological mortality rates were 12% and 16%, respectively (HR 0.55, 95% CI 0.28-1.10, p = 0.091). The 1-year intracranial progression-free survival rates were 35% and 26% (HR 0.73, 95% CI 0.53-0.99, p = 0.047). The 2-year local failure rates were 12% and 18% (HR 0.72, 95% CI 0.32-1.61, p = 0.43) and the 2-year distant recurrence rates were 51% and 60% (HR 0.82, 95% CI 0.55-1.23, p = 0.34). Severe adverse radiation events (Common Terminology Criteria for Adverse Events [CTCAE] grade 4) occurred in 1 patient in each group, and CTCAE grade 3 toxicities were observed in 3 patients in the ICI + SRS group and in 5 in the SRS group (OR 1.53, 95% CI 0.35-7.7, p = 0.75)., Conclusions: The present study found that SRS with concurrent ICIs for patients with lung cancer BMs was associated with longer survival and durable intracranial disease control, with no apparent increase in treatment-related adverse events.

Background: Arthropods gradually change their forms through repeated molting events during postembryonic development. Anamorphosis, i.e., segment addition during postembryonic development, is seen in some arthropod lineages. In all millipede species (Myriapoda, Diplopoda), for example, postembryonic processes go through anamorphosis. Jean-Henri Fabre proposed 168 years ago the "law of anamorphosis", that is, "new rings appear between the penultimate ring and the telson" and "all apodous rings in a given stadium become podous rings in the next stadium", but the developmental process at the anamorphic molt remains largely unknown. In this study, therefore, by observing the morphological and histological changes at the time of molting, the detailed processes of leg- and ring-addition during anamorphosis were characterized in a millipede, Niponia nodulosa (Polydesmida, Cryptodesmidae)., Results: In the preparatory period, a few days before molting, scanning electron microscopy, confocal laser scanning microscopy, and histological observations revealed that two pairs of wrinkled leg primordia were present under the cuticle of each apodous ring. In the rigidation period, just prior to molt, observations of external morphology showed that a transparent protrusion was observed on the median line of the ventral surface on each apodous ring. Confocal laser scanning microscopy and histological observations revealed that the transparent protrusion covered by an arthrodial membrane contained a leg bundle consisting of two pairs of legs. On the other hand, ring primordia were observed anterior to the telson just before molts., Conclusions: Preceding the anamorphic molt in which two pairs of legs are added on an apodous ring, a transparent protrusion containing the leg pairs (a leg bundle) appears on each apodous ring. The morphogenetic process of the rapid protrusion of leg bundles, that is enabled by thin and elastic cuticle, suggested that millipedes have acquired a resting period and unique morphogenesis to efficiently add new legs and rings., (© 2023. The Author(s).)

In this article, we theoretically designed and simulated a silicon core fiber for the simultaneous detection of temperature and refractive index. We first discussed the parameters of the silicon core fiber for near single-mode operation. Second, we designed and simulated a silicon core-based fiber Bragg grating and applied it for simultaneous sensing of temperature and environmental refractive index. The sensitivities for the temperature and refractive index were 80.5 pm/°C and 208.76 dB/RIU, respectively, within a temperature range of 0 to 50 °C and a refractive index range of 1.0 to 1.4. The proposed fiber sensor head can provide a method with simple structure and high sensitivity for various sensing targets.

Wearable devices for the quantification of walking have recently been adopted for gait rehabilitation. To apply this method in subacute rehabilitation settings, this approach must be effective in these populations and implemented as a feasible method in terms of adherence and safety, especially the risk of falling. This study aimed to investigate the feasibility and efficacy of an activity monitoring approach in subacute rehabilitation using a commercially available pedometer validated with slow walking. This randomized controlled study with blinded assessors recruited 29 patients admitted to a rehabilitation ward. The participants were randomly assigned to either the feedback (intervention) or the no-feedback (control) group. Participants in both groups received at least 120 min of therapy sessions every day for 6 or 7 days per week while wearing pedometers on their unaffected ankles from the day they were permitted to walk independently till discharge. Only participants in the feedback group received weekly encouragement and the next goals. The primary outcome was the change in the 6-minute walking distance (Δ6MD). Feasibility (percentage of pedometer data acquisition days in the total observational period and the number of falls) and other efficacy outcomes (step counts, gait speed, 30-seconds chair stand test, Berg Balance Scale, and Timed Up and Go Test) were also evaluated. Regarding feasibility outcomes, the data acquisition rate was 94.1% and the number of falls during the observation period was one in the feedback group. Regarding efficacy outcomes, Δ6MD was not significantly greater in the feedback group [mean (standard deviation): 79.1 (51.7) m] than in the no-feedback group [86.1 (65.4) m] ( p  = 0.774) and the other five secondary outcomes showed no between-group difference. Considering the large number of steps per day in both groups [6,912 (4,751) and 5,600 (5,108) steps in the feedback and no-feedback group, respectively], the effect of the intended intervention might have been masked by the effect of simply wearing pedometers in the control group. This study revealed that the activity monitoring approach using an ankle-worn pedometer was practical in terms of adherence and safety. Further clinical trials are required to elucidate ways to effectively use wearable devices in subacute rehabilitation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Otaka, Oguchi, Yagihashi, Hoshino, Munakata, Hayakawa and Otaka.)

Background: Cerebral amyloid angiopathy (CAA) is becoming the most common and serious complications in long-lived hereditary ATTR amyloidosis patients. It is therefore imperative to elucidate the characteristics of ATTR-type CAA and develop useful biomarkers., Methods: We enrolled 34 ATTRv amyloidosis patients with the V30M (p.V50M) variant for analysis with three-dimensional stereotactic surface projection z score imaging of Pittsburgh compound B (PiB)-PET., Results: Eight patients exhibited central nervous system (CNS) symptoms. Seven patients suffered transient focal neurologic episodes, and 2 patients each experienced cerebellar haemorrhages or cognitive decline. The amount of 11 C-PiB accumulation increased as a function of disease duration. 11 C-PiB-PET abnormalities were seen at 8 years from onset and were associated with CNS manifestations from 12 years. The annual increase rate of the standardised uptake value ratio (SUVR) in female patients was significantly higher than in male patients. CNS amyloid deposition started in the upper middle surface of the cerebellar cortex, and then spread out over the entire surface of the cerebellum, Sylvian fissure, and anterior part of the longitudinal fissure of the cerebrum., Conclusions: PiB-PET is a useful biomarker for the early detection and treatment evaluation of ATTR-type CAA. Female gender is associated with more rapid progression of ATTR-type CAA.

[Purpose] The purpose of this study was to identify the optimal visual cues for gait disturbance in patients with Parkinson's disease based on the luminous duration and the individual patient preferences for a wearable visual cue device. [Participants and Methods] Twenty-four patients with Parkinson's disease walked while wearing only a visual cue device in the control condition. They then walked while the device was set to two stimulus conditions: the luminous duration at 10% and 50% of the individual gait cycle. After walking under the two stimulus conditions, the patients were asked for their preferred visual cue condition. The walking results were compared between the two stimulus conditions and the control condition. Gait parameters were compared among the three conditions. The comparisons with preference, non-preference, and control conditions were also made for the same gait parameter. [Results] When compared to the control condition, walking with visual cues in the stimulus conditions reduced stride duration and increased cadence. The preference and non-preference conditions had shorter stride durations than the control condition. Furthermore, the preference condition also resulted in a faster gait speed than the non-preference condition. [Conclusion] This study suggests that a wearable visual cue device with the patient's preferred luminous duration may help manage gait disturbance in patients with Parkinson's disease., Competing Interests: There is no conflict of interest., (2023©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Genetic alterations in human epidermal growth factor receptor type 2 (HER2)/epidermal growth factor receptor (EGFR) are commonly associated with breast and lung cancers and glioblastomas. Cancers with avian erythroblastosis oncogene B (ERBB) deregulation are highly metastatic and can cause primary brain tumors. Currently, no pan-ERBB inhibitor with remarkable brain penetration is available. Here, TAS2940, a novel irreversible pan-ERBB inhibitor with improved brain penetrability, was evaluated for its efficacy against several ERBB aberrant cancer models. The selectivity of TAS2940 was evaluated by enzymatic kinase assays. The inhibitory effects of TAS2940 against ERBB genetic alterations were examined using MCF10A cells expressing various HER2 or EGFR mutations and other generic cell lines harboring deregulated ERBB expression. In vivo efficacy of TAS2940 was examined following oral treatment in subcutaneous or intracranial xenograft cancer models. TAS2940 was highly potent against cells harboring HER2/EGFR alterations. TAS2940 could selectively inhibit phosphorylation of targets and the growth of cancer cells with ERBB aberrations in vitro. TAS2940 also inhibited tumor growth in xenograft mouse models with ERBB aberrations: HER2 amplification, HER2/EGFR exon 20 insertions, and EGFR vIII mutation. TAS2940 was effective in the intracranial xenograft models of HER2/EGFR cancers and improved the survival of these mice. TAS2940 has promising therapeutic effects in preclinical study against cancers harboring HER2/EGFR mutations, especially metastatic and primary brain tumors. Our results highlight potential novel strategies against lung cancers with brain metastases harboring HER2/EGFR exon 20 insertions and glioblastomas with EGFR aberrations., (© 2022 Taiho Pharmaceutical Co., Ltd and The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

We present a method for characterizing the intensity waveform, spectrum, frequency chirp, and spectral phase of picosecond pulses at a moderate repetition rate of ∼100 MHz. The proposed method exploits the intensity modulation at ∼10 GHz, which is slightly offset from the integer multiple of the repetition rate of the pulses. The modulated pulses are split into two, and one is measured by an optical spectrum analyzer, whose output is detected by a lock-in amplifier, while the other is directly detected by a photodiode and its output is used as a reference signal of the lock-in amplifier. In the experiment, we demonstrate the measurement of picosecond Ti:sapphire laser pulses to investigate frequency chirp induced by self-phase modulation. We anticipate that the proposed method will be useful for the characterization of various types of picosecond pulses.

Quantum-enhanced stimulated Raman scattering (QESRS) microscopy is expected to realize molecular vibrational imaging with sub-shot-noise sensitivity, so that weak signals buried in the laser shot noise can be uncovered. Nevertheless, the sensitivity of previous QESRS did not exceed that of state-of-the-art stimulated Raman scattering (SOA-SRS) microscopes mainly because of the low optical power (3 mW) of amplitude squeezed light [Nature594, 201 (2021)10.1038/s41586-021-03528-w]. Here, we present QESRS based on quantum-enhanced balanced detection (QE-BD). This method allows us to operate QESRS in a high-power regime (>30 mW) that is comparable to SOA-SRS microscopes, at the expense of 3 dB sensitivity drawback due to balanced detection. We demonstrate QESRS imaging with 2.89 dB noise reduction compared with classical balanced detection scheme. The present demonstration confirms that QESRS with QE-BD can work in the high-power regime, and paves the way for breaking the sensitivity of SOA-SRS microscopes.

Objective: Stereotactic radiosurgery (SRS) is the mainstay for treating brain metastases (BMs) from renal cell carcinoma (RCC). In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic RCC and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for RCC BM prolongs overall survival (OS) and improves intracranial disease control and whether there are any safety concerns., Methods: Patients who underwent SRS for RCC BMs at the authors' institution between January 2010 and January 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The time-to-event analysis of OS and intracranial progression-free survival (IC-PFS) between the groups with and without ICIs (ICI+SRS and SRS, respectively) was performed using inverse probability of treatment weighting (IPTW) based on propensity scores (PSs) to control for selection bias. Four baseline covariates (Karnofsky Performance Scale score, extracranial metastases, hemoglobin, and number of BMs) were selected to calculate PSs., Results: In total, 57 patients with 147 RCC BMs were eligible. The median OS for all patients was 9.1 months (95% CI 6.0-18.9 months), and the median IC-PFS was 4.4 months (95% CI 3.1-6.8 months). Twelve patients (21%) received concurrent ICIs. The IPTW-adjusted 1-year OS rates in the ICI+SRS and SRS groups were 66% and 38%, respectively (HR 0.30, 95% C 0.13-0.69; p = 0.005), and the IPTW-adjusted 1-year IC-PFS rates were 52% and 16%, respectively (HR 0.30, 95% CI 0.14-0.62; p = 0.001). Severe tumor hemorrhage (Common Terminology Criteria for Adverse Events [CTCAE] grade 4 or 5) occurred immediately after SRS in 2 patients in the SRS group. CTCAE grade 2 or 3 toxicity was observed in 2 patients in the ICI+SRS group and 5 patients in the SRS group., Conclusions: Although the patient number was small and the analysis preliminary, the present study found that SRS with concurrent ICIs for RCC BM patients prolonged survival and provided durable intracranial disease control, with no apparent increase in treatment-related adverse events.

Many insects are associated with facultative symbiotic bacteria, and their infection prevalence provides an important clue to understand the biological impact of such microbial associates. Here we surveyed diverse stinkbugs representing 13 families, 69 genera, 97 species and 468 individuals for Spiroplasma infection. Diagnostic PCR detection revealed that 4 families (30.8%), 7 genera (10.1%), 11 species (11.3%) and 21 individuals (4.5%) were Spiroplasma positive. All the 21 stinkbug samples with Spiroplasma infection were subjected to PCR amplification and sequencing of Spiroplasma 's 16S rRNA gene. Molecular phylogenetic analysis uncovered that the stinkbug-associated Spiroplasma symbionts were placed in three distinct clades in the Spiroplasmataceae, highlighting multiple evolutionary origins of the stinkbug- Spiroplasma associations. The Spiroplasma phylogeny did not reflect the host stinkbug phylogeny, indicating the absence of host-symbiont co-speciation. On the other hand, the Spiroplasma symbionts associated with the same stinkbug family tended to be related to each other, suggesting the possibility of certain levels of host-symbiont specificity and/or ecological symbiont sharing. Amplicon sequencing analysis targeting bacterial 16S rRNA gene, FISH visualization of the symbiotic bacteria, and rearing experiments of the host stinkbugs uncovered that the Spiroplasma symbionts are generally much less abundant in comparison with the primary gut symbiotic bacteria, localized to various tissues and organs at relatively low densities, and vertically transmitted to the offspring. On the basis of these results, we conclude that the Spiroplasma symbionts are, in general, facultative bacterial associates of low infection prevalence that are not essential but rather commensalistic for the host stinkbugs, like the Spiroplasma symbionts of fruit flies and aphids, although their impact on the host phenotypes should be evaluated in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kakizawa, Hosokawa, Oguchi, Miyakoshi and Fukatsu.)

Understanding the processes and consequences of the morphological diversity of organisms is one of the major goals of evolutionary biology. Studies on the evolution of developmental mechanisms of morphologies, or evo-devo, have been extensively conducted in many taxa and have revealed many interesting phenomena at the molecular level. However, many other taxa exhibiting intriguing morphological diversity remain unexplored in the field of evo-devo. Although the annelid family Syllidae shows spectacular diversity in morphological development associated with reproduction, its evo-devo study, especially on molecular development, has progressed slowly. In this study, we focused on Megasyllis nipponica as a new model species for evo-devo in syllids and performed transcriptome sequencing to develop a massive genetic resource, which will be useful for future molecular studies. From the transcriptome data, we identified candidate genes that are likely involved in morphogenesis, including genes involved in hormone regulation, sex determination and appendage development. Furthermore, a computational analysis of the transcriptome sequence data indicated the occurrence of DNA methylation in coding regions of the M. nipponica genome. In addition, flow cytometry analysis showed that the genome size of M. nipponica was approximately 524 megabases. These results facilitate the study of morphogenesis in molecular terms and contribute to our understanding of the morphological diversity in syllids.

Insects exclusively feeding on vertebrate blood are usually dependent on symbiotic bacteria for provisioning of B vitamins. Among them, sucking lice are prominent in that their symbiotic bacteria as well as their symbiotic organs exhibit striking diversity. Here we investigated the bacterial diversity associated with the boar louse Haematopinus apri in comparison with the hog louse Haematopinus suis . Amplicon sequencing analysis identified the primary endosymbiont predominantly detected from all populations of H. apri with some minor secondary bacterial associates. Sequencing and phylogenetic analysis of bacterial 16S rRNA gene confirmed that the endosymbionts of the boar louse H. apri , the hog louse H. suis and the cattle louse Haematopinus eurysternus form a distinct clade in the Gammaproteobacteria. The endosymbiont clade of Haematopinus spp. was phylogenetically distinct from the primary endosymbionts of other louse lineages. Fluorescence in situ hybridization visualized the endosymbiont localization within midgut epithelium, ovarial ampulla and posterior oocyte of H. apri , which were substantially the same as the endosymbiont localization previously described in H. suis and H. eurysternus . Mitochondrial haplotype analysis revealed that, although the domestic pig was derived from the wild boar over the past 8,000 years of human history, the populations of H. apri constituted a distinct sister clade to the populations of H. suis . Based on these results, we discussed possible evolutionary trajectories of the boar louse, the hog louse and their endosymbionts in the context of swine domestication. We proposed ' Candidatus Haematopinicola symbiotica' for the distinct clade of the endosymbionts of Haematopinus spp., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nishide, Oguchi, Murakami, Moriyama, Koga and Fukatsu.)

Microorganisms often live in symbiosis with their hosts, and some are considered mutualists, where all species involved benefit from the interaction. How free-living microorganisms have evolved to become mutualists is unclear. Here we report an experimental system in which non-symbiotic Escherichia coli evolves into an insect mutualist. The stinkbug Plautia stali is typically associated with its essential gut symbiont, Pantoea sp., which colonizes a specialized symbiotic organ. When sterilized newborn nymphs were infected with E. coli rather than Pantoea sp., only a few insects survived, in which E. coli exhibited specific localization to the symbiotic organ and vertical transmission to the offspring. Through transgenerational maintenance with P. stali, several hypermutating E. coli lines independently evolved to support the host's high adult emergence and improved body colour; these were called 'mutualistic' E. coli. These mutants exhibited slower bacterial growth, smaller size, loss of flagellar motility and lack of an extracellular matrix. Transcriptomic and genomic analyses of 'mutualistic' E. coli lines revealed independent mutations that disrupted the carbon catabolite repression global transcriptional regulator system. Each mutation reproduced the mutualistic phenotypes when introduced into wild-type E. coli, confirming that single carbon catabolite repression mutations can make E. coli an insect mutualist. These findings provide an experimental system for future work on host-microbe symbioses and may explain why microbial mutualisms are omnipresent in nature., (© 2022. The Author(s).)

We investigated the pathogenic relationship between cerebral microbleeds and lacunar strokes. Two cases of lacunar strokes in the region of the basal ganglia, a 72-year-old man and a 67-year-old man, were studied; both cases showed cerebral microbleeds in the stroke areas. The cerebral microbleeds were surrounded by oedema, and the oedema faded out over time, suggesting the cerebral microbleeds had developed acutely. The cerebral microbleeds were located at the ventrolateral edge of the lacunar infarctions, and the locations appeared to be at or near the sites of occlusion of the lenticulostriatal branches. Although a cerebral microbleed and a lacunar infarction may be two unrelated events on juxtapositioned vessels, or a cerebral microbleed may be haemorrhagic conversion of an infarction, a cerebral microbleed could cause an occlusion of the arterial branch, leading to lacunar infarction of its supplying territories.

We describe two new species of resupinate Sistotrema sensu lato ( Cantharellales ) collected in Japan: S. flavorhizomorphae and S. chloroporum . Both species have urniform basidia with more than four sterigmata and monomitic hyphal system, oil-rich hyphae in subiculum, which is typical for this genus. Sistotrema chloroporum is characterized by poroid hymenophore partly yellowish-green, basidia 4-6-spored, medium-sized basidiospores (4.5-6.5 × 3.5-6 µm), and broadleaf forest habitat. Sistotrema flavorhizomorphae is characterized by hydnoid-irpicoid hymenophore, bright yellowish rhizomorphs, basidia 6-8-spored, small basidiospores (3-3.5 × 2.5-3 µm), and pine forest habitat. Phylogenetic trees inferred from the fungal nrDNA ITS and LSU and the rpb2 sequences supported that both species were distinct and grouped with other ectomycorrhizal Sistotrema and Hydnum species, but their generic boundary was unclear. Mycorrhizae underneath basidiomes of both species were identified and described via molecular techniques. Mycorrhizae of S. chloroporum have similar characteristics to those of other Sistotrema s.l. and Hydnum species, i.e., S. confluens and H. repandum , whereas S. flavorhizomorphae has a distinct morpho-anatomy, for example, a distinct pseudoparenchymatous mantle. Comprehensive characterizations of basidiomes and mycorrhizae improve the taxonomic analysis of mycorrhizal species of Sistotrema s.l., (2022, by The Mycological Society of Japan.)

Quantum-enhanced stimulated Raman scattering (QE-SRS) is a promising technique for highly sensitive molecular vibrational imaging and spectroscopy surpassing the shot noise limit. However, the previous demonstrations of QE-SRS utilized rather weak optical power which hinders from competing with the sensitivity of state-of-the-art SRS microscopy and spectroscopy using relatively high-power optical pulses. Here, we demonstrate SRS spectroscopy with quantum-enhanced balanced detection (QE-BD) scheme, which works even when using high-power optical pulses. We used 4-ps pulses to generate pulsed squeezed vacuum at a wavelength of 844 nm with a squeezing level of -3.28 ± 0.12 dB generated from a periodically-poled stoichiometric LiTaO 3 waveguide. The squeezed vacuum was introduced to an SRS spectrometer employing a high-speed spectral scanner to acquire QE-SRS spectrum in the wavenumber range of 2000-2280 cm -1 within 50 ms. Using SRS pump pulses with an average power of 11.3 mW, we successfully obtained QE-SRS spectrum whose SNR was better than classical SRS with balanced-detection by 2.27 dB.

Caste development in social insects requires the coordination of molting and metamorphosis during postembryonic development. In termites, i.e., hemimetabolous eusocial insects, caste fate is determined during postembryonic development. However, it is not fully understood how the mechanisms of molting/metamorphosis are regulated in the course of differentiation between reproductive and sterile castes. In termites, only reproductives derived from alates are imagos and other sterile castes (including developmentally-terminal soldier caste) are basically juveniles or nymphs. Furthermore, supplementary reproductives that appear when the original queens and kings die or become senescent, exhibit larval features such as winglessness, and are called neotenics. Therefore, the question of whether neotenics are larvae or imagos is still under debate. In this study, by inducing female neotenic differentiation in a damp-wood termite Hodotermopsis sjostedti, morphological investigations together with juvenile hormone (JH) quantification and expression/functional analyses of genes responsible for molting and/or metamorphosis were carried out. JH titer and expression of one of the downstream genes (Kr-h1) were shown to be temporarily lowered, but increased just prior to the molt into neotenics, while consistently lowered in imaginal molt (i.e., alate differentiation). In contrast, ecdysone-related genes (EcR and E93) were upregulated at both neotenic and alate differentiation, suggesting that the heterochronic actions of ecdysone and JH lead the neotenic differentiation. Moreover, expression analyses, supported by reverse genetic experiments, showed that EcR and E93 were specifically upregulated in genital sternites (EcR and E93) and ovaries (E93) and required for the development of imaginal characters. These results suggest that the resultant mosaic phenotype of female neotenics is due to modular responses of different body parts to hormonal actions., (Copyright © 2022. Published by Elsevier Inc.)

Echinoderms constitute an animal phylum characterized by the pentaradial body plan. During the development from bilateral larvae to pentaradial adults, the formation of the multiple of five hydrocoel lobes, i.e., the buddings from the mesodermal coelom, is the firstly emerging pentameral character. The developmental mechanism underlying the hydrocoel-lobe formation should be revealed to understand the evolutionary process of this unique and highly derived body plan of echinoderms, although the morphogenetic mechanisms of hydrocoel lobes are largely uninvestigated. In this study, using the sea cucumber Apostichopus japonicus, in which hydrocoel is easily observable, the developmental process of hydrocoel lobes was described in detail, focusing on cell proliferation and rearrangement. Cell proliferation was not specifically distributed in the growing tips of the hydrocoel lobes, and inhibition of cell proliferation did not affect lobe formation. During lobe formation, the epithelium of the hydrocoel lobes was firstly thickened and then transformed into a simple epithelium, suggesting that tissue expansion via tissue remodeling contributes to the hydrocoel-lobe formation., (© 2022. The Author(s).)

Four new species of annelids, Ctenodrilus japonicus sp. nov., Raphidrilus misakiensis sp. nov., Raphidrilus okinawaensis sp. nov., and Raricirrus anubis sp. nov., are described based on specimens collected from Japanese waters. Ctenodrilus japonicus sp. nov. inhabits the interstitial environment and can be distinguished from the other congeners by the following features: ( i ) total of 16 chaetigers, ( ii ) chaetigers 1-3 with stout hooks, ( iii ) minute body (approximately 1 mm in length), ( iv ) all parapodia with the same number of chaetae (two notochaetae; two neurochaetae), and ( v ) presence of dorsal and ventral papillae. Raphidrilus misakiensis sp. nov. lives under intertidal stones and can be distinguished from other congeners by having pectinate neurochaetae. Raphidrilus okinawaensis sp. nov. inhabits the interstitial environment and can be distinguished from other congeners by: ( i ) absence of annulation on the peristomium and achaetous segment and ( ii ) presence of a heart body in chaetigers 4-5. Raricirrus anubis sp. nov. inhabits whale bones and can be distinguished from other congeners by the following features: ( i ) presence of a heart body in chaetigers 9-14, ( ii ) presence of capillary neurochaetae on chaetiger 1, and ( iii ) presence of simple curved spines. A phylogenetic tree based on partial sequences of cytochrome c oxidase subunit I and 16S rRNA from the new species and other cirratulid worms showed that Raphidrilus is included in Cirratuliformia. This is the first record of Raphidrilus and Raricirrus from Japanese waters., Competing Interests: The authors declare that they have no competing interests., (© 2022 Jimi et al.)

The small biomolecule methionine (Met) is a fundamental amino acid required for a vast range of biological processes such as protein synthesis, cancer metabolism, and epigenetics. However, it is still difficult to visualize the subcellular distribution of small biomolecules including Met in a minimally invasive manner. Here, we demonstrate stimulated Raman scattering (SRS) imaging of cellular uptake of deuterated methionine (d 8 -Met) in live HeLa cells by way of comparison to the previously used alkyne-labeled Met analogue─homopropargylglycine (Hpg). We show that the solutions of d 8 -Met and Hpg have similar SRS signal intensities. Furthermore, by careful image analysis with background subtraction, we succeed in the SRS imaging of cellular uptake of d 8 -Met with a much greater signal intensity than Hpg, possibly reflecting the increased and minimally invasive uptake kinetics of d 8 -Met compared with Hpg. We anticipate that d 8 -Met and other deuterated biomolecules will be useful for investigating metabolic processes with subcellular resolution.

In high-precision optical measurements, squeezed vacuum states are a promising resource for reducing the shot noise. To utilize a squeezed vacuum, it is important to lock the phase of the local oscillator (LO) to the squeezed light. The coherent control sideband (CCSB) scheme has been established for the precise phase locking, while the previous CCSB scheme was designed for the squeezed vacuum generated with an optical parametric oscillator (OPO). Thus the previous CCSB scheme is not applicable to squeezing by a single-pass optical parametric amplifier (OPA), which is attractive for generating broadband squeezed vacuum states. In this study, we propose a variant of CCSB scheme, which is applicable to the squeezing by single-pass OPA. In this scheme, we inject pump light and frequency-shifted signal light into an OPA crystal in the same way as the previous CCSB scheme. The parametric process in the OPA crystal generates a squeezed vacuum, amplifies the signal light, generates an idler light, and causes the pump depletion reflecting the interference of the amplified signal light and the idler light. Through the lock-in detection of the pump depletion, we can phase-lock the injected signal light to the pump light. Then, after the heterodyne detection of the signal and the idler light, we get the error signal of LO and realize the precise phase locking of LO to the squeezed quadrature. We show the feasibility of the proposed scheme by deriving the signal-to-noise ratio (SNR) of the modulated pump signal. We experimentally demonstrate the proposed scheme on pulsed squeezing by a single-pass OPA.

Diverse insects host specific microbial symbionts that play important roles for their growth, survival, and reproduction. They often develop specialized symbiotic organs for harboring the microbial partners. While such intimate associations tend to be stably maintained over evolutionary time, the microbial symbionts may have been lost or replaced occasionally. How symbiont acquisitions, replacements, and losses are linked to the development of the host's symbiotic organs is an important but poorly understood aspect of microbial symbioses. Cassidine leaf beetles are associated with a specific gammaproteobacterial lineage, Stammera , whose reduced genome is streamlined for producing pectin-degrading enzymes to assist the host's digestion of food plants. We investigated the symbiotic system of 24 Japanese cassidine species and found that (i) most species harbored Stammera within paired symbiotic organs located at the foregut-midgut junction, (ii) the host phylogeny was largely congruent with the symbiont phylogeny, indicating stable host-symbiont association over evolutionary time, (iii) meanwhile, the symbiont was not detected in three distinct host lineages, uncovering recurrent losses of the ancient microbial mutualist, (iv) the symbiotic organs were vestigial but present in the symbiont-free lineages, indicating evolutionary persistence of the symbiotic organs even in the absence of the symbiont, and (v) the number of the symbiotic organs was polymorphic among the cassidine species, either two or four, unveiling a dynamic evolution of the host organs for symbiosis. These findings are discussed as to what molecular mechanisms and evolutionary trajectories underpin the recurrent symbiont losses and the morphogenesis of the symbiotic organs in the herbivorous insect group. IMPORTANCE Insects represent the biodiversity of the terrestrial ecosystem, and their prosperity is attributable to their association with symbiotic microorganisms. By sequestering microbial functionality into their bodies, organs, tissues, or cells, diverse insects have successfully exploited otherwise inaccessible ecological niches and resources, including herbivory enabled by utilization of indigestible plant cell wall components. In leaf beetles of the subfamily Cassininae, an ancient symbiont lineage, Stammera , whose genome is extremely reduced and specialized for encoding pectin-degrading enzymes, is hosted in gut-associated symbiotic organs and contributes to the host's food plant digestion. Here, we demonstrate that multiple symbiont losses and recurrent structural switching of the symbiotic organs have occurred in the evolutionary course of cassidine leaf beetles, which sheds light on the evolutionary and developmental dynamics of the insect's symbiotic organs and provides a model system to investigate how microbial symbionts affect the host's development and morphogenesis and vice versa .

Cephalopods have acquired numerous novelties and expanded their habitats to various marine environments as highly agile predators. Among cephalopod novelties, multiple arms are used for complex behaviors, including prey capture. Suckers on arms are innovative features for realizing these arm functions. In addition, tentacles in Decapodiformes (squids and cuttlefishes) are arms specialized in prey capture and tentacular suckers show unique morphologies. However, little is known about the developmental process of sucker formation that should differ between tentacles and other arms. In this study, therefore, sucker formation processes on second arms and tentacles were observed and compared in a bigfin reef squid, Sepioteuthis lessoniana, to reveal the developmental processes forming the unique sucker morphologies, especially in tentacles. Morphological and histological observations of suckers during embryogenesis showed that, in second arms, the sucker-producing area appeared at the most distal part. At the most proximal side of the sucker-producing area, new sucker buds were isolated by invagination of the epithelial tissue. At the proximal arm parts, suckers with functional structures were observed. In tentacles, although the basic sucker formation pattern was similar to that in second arms, sucker formation started at earlier embryonic stages and the number of suckers was drastically increased compared to that in second arms. In addition, although four sucker rows were observed at the tentacular club, that is, the thickest part of a tentacle, our observations suggested that two sets of two sucker rows are compressed to form the four rows. Therefore, the sucker-formation processes are temporally and spatially different between arms and tentacles. In addition, S. lessoniana shows conserved and unique patterns of sucker formation in comparison with previously described species, suggesting that sucker formation patterns were diversified among Decapodiformes lineages., (© 2021 Wiley Periodicals LLC.)

Termites are model social organisms characterized by a polyphenic caste system. Subterranean termites (Rhinotermitidae) are ecologically and economically important species, including acting as destructive pests. Rhinotermitidae occupies an important evolutionary position within the clade representing a transitional taxon between the higher (Termitidae) and lower (other families) termites. Here, we report the genome, transcriptome, and methylome of the Japanese subterranean termite Reticulitermes speratus Our analyses highlight the significance of gene duplication in social evolution in this termite. Gene duplication associated with caste-biased gene expression was prevalent in the R. speratus genome. The duplicated genes comprised diverse categories related to social functions, including lipocalins (chemical communication), cellulases (wood digestion and social interaction), lysozymes (social immunity), geranylgeranyl diphosphate synthase (social defense), and a novel class of termite lineage-specific genes with unknown functions. Paralogous genes were often observed in tandem in the genome, but their expression patterns were highly variable, exhibiting caste biases. Some of the assayed duplicated genes were expressed in caste-specific organs, such as the accessory glands of the queen ovary and the frontal glands of soldier heads. We propose that gene duplication facilitates social evolution through regulatory diversification, leading to caste-biased expression and subfunctionalization and/or neofunctionalization conferring caste-specialized functions., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

We describe a new species of Gerhardtia from Japan based on basidiomata morphology, live culture characteristics, and molecular phylogenetic analyses. Gerhardtia venosolamellata is found on broad-leaf litter, and is characterized by tricholomatoid to marasmioid basidiomata, an off-white to pale salmon-pink pileus surface with faint marginal striae, subdistant lamellae with lateral veins, a tomentose to strigose stipe base with hyphal strands generating arthroconidia measuring 4-7 × 2-3 µm, cyanophilic, elongate-ellipsoid to cylindrical, slightly verrucose or undulate basidiospores measuring 4.5-6 × 2.5-3 µm, and cyanophilic basidia measuring 25-35 × 5-6 µm and containing siderophilous granules. Phylogenetic analyses based on the internal transcribed spacer and large subunit regions of the fungal nrDNA indicates that G. venosolamellata is related to G. sinensis and G. highlandensis , but differs from the former with respect to basidiomata color, basidiospore shape, and habitat. An isotype specimen of G. highlandensis exhibited relatively close lamellae without veins, and slightly larger basidiospores (4.5-6.5 × 2.5-3 µm). Cultured mycelia of G. venosolamellata produced arthroconidia measuring 4.5-8.5 × 2.5-3 µm with both schizolytic and rhexolytic secession on MA and PDA media, and chlamydospores occasionally covered with crystals on MA and MYG media., (2022, by The Mycological Society of Japan.)

Objective: The authors investigated and compared the results of staged stereotactic radiosurgery (S-SRS) alone and those of postoperative cavity SRS (C-SRS) for patients with midsize-to-large brain metastases (BMs)., Methods: Patients with BMs who had undergone S-SRS or C-SRS during the period from 2010 to 2020 were retrospectively identified from an institutional database. The two treatment groups were generated by propensity score matching (PSM; match ratio 2:1) based on 13 potential prognostic covariates: sex, age, Karnofsky Performance Status, type of primary cancer, timing of BM diagnosis, extracranial disease status, driver mutations, molecular target therapy, neurological symptoms, number of BMs, location of BMs treated with S-SRS or C-SRS, maximal tumor or cavity volume, and cumulative intracranial tumor volume. Patient survival and control of intracranial disease were compared between the S-SRS and C-SRS groups using time-dependent analyses taking into account competing events., Results: In total, 110 patients in the S-SRS group and 62 in the C-SRS group were selected by PSM. In the S-SRS group, the median interval between the two radiosurgical sessions was 21 days, and the median total prescription dose was 28 Gy at 50%. In the C-SRS group, the median time from surgery to C-SRS was 16 days, and the median prescription dose delivered to the surgical cavity was 15 Gy at 55%. At the time point of data set fixation, 129 patients had died, 43 were alive, and none had been lost to follow-up. The 2-year survival rates for the S-SRS and C-SRS groups after the initial intervention were 33% and 37% and the median survival times were 14.8 and 17.5 months, respectively (p = 0.33). The 2-year cumulative neurological mortality rates were 11% and 9%, respectively (p = 0.65). The 2-year local failure rates were 32% and 12% (p = 0.036) and the 2-year distant recurrence rates were 55% and 58%, respectively (p = 0.53). The 2-year leptomeningeal disease development rates were 9% and 25%, respectively (p = 0.007)., Conclusions: The present study revealed no significant difference in overall survival or cumulative neurological mortality between the S-SRS and C-SRS groups. The local control failure rate was significantly higher in the S-SRS group, whereas the incidence of leptomeningeal disease development was significantly higher in the C-SRS group.

Background: The diagnosis and therapy of reversible cerebral vasoconstriction syndrome (RCVS) tends to focus on neurological symptoms, but less attention has been paid the occurrence of extracerebral lesion such as the myocardium., Case Presentation: A 40-year-old woman taking iron supplements for iron deficiency anemia due to menorrhagia had suffered from a thunderclap headache and seizure. Brain magnetic resonance imaging revealed high-intensity lesions bilaterally in the cerebellar and cerebral hemispheres. Her symptoms once subsided with steroids and anticonvulsant therapy; however, she experienced a severe headache again while bathing and was transferred to our hospital. Based on the clinical course and imaging data, she was diagnosed as having RCVS triggered by a rapid improvement of anemia. At the same time, she had cardiac involvement revealed by electro and echocardiographs despite without chest symptoms. After the administration of a calcium channel blocker and nitrite, her cerebral and cardiac involvements were rapidly improved., Conclusions: The case presented RCVS with transient myocardial damage. With RCVS, we should always pay attention to the complication of extracerebral lesions., (© 2021. The Author(s).)

Background : Neural connectivity in brain has been known as indicators for neural function and recovery of brain. Although previous studies reported that neural connectivity predicted the recovery of upper limb function after stroke, the relationship between neural connectivity and lower limb function has not been clear. Objectives : To clarify whether functional connectivity (FC) assessed by electroencephalographiy (EEG) with five electrodes placed on motor-related areas could be related to the functional motor recovery of the lower limbs in patients after stroke. Methods : Twenty-four patients with stroke during the recovery phase were recruited. Motor function of the lower limbs was assessed using Fugl-Meyer Assessment lower limb section (FMAL). EEG signals were recorded by five electrodes (C3, C4, FC3, FC4, and FCz) at rest and during ankle movement. Amplitude envelope correlations, as values for FC, were calculated in α (8-12 Hz), β (13-30 Hz), low-β (13-19 Hz), and high-β (20-30 Hz) frequency bands. The predictive regression equation of the FMAL score in the eighth week after stroke (8 W) was created by FCs in the fourth week (4 W). Results : The higher intra-hemispheric FC in both hemispheres in the resting state and during the ankle movement at 4 W was related to a higher lower limb function at 8 W. Additionally, the higher inter-hemispheric FC between M1 on both sides during the ankle movement was related to a higher function recovery. Conclusions : The intra- and inter-hemispheric FC among motor-related areas at 4 W after stroke might be related to the functional recovery of the lower limbs at 8 W.

Introduction: Regorafenib is a multikinase inhibitor approved for the treatment of metastatic colorectal cancer (mCRC). Despite providing a statistically significant survival benefit, a substantial number of patients fail to respond to or continue with treatment, which has resulted in an unmet clinical need for a biomarker of regorafenib efficacy., Methods: The JACCRO CC-12 study was a prospective, multicenter, single-arm phase II trial designed to evaluate the usefulness of [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) as an imaging biomarker of regorafenib in patients with mCRC that progressed after standard chemotherapies. FDG-PET and contrast-enhanced computed tomography (CT) were performed before and after treatment with regorafenib 160 mg once daily 3 weeks on/1 week off. The primary end point was the change in the maximum standardized uptake value in the lesion with the highest uptake at pre-treatment FDG-PET. The secondary end points included overall survival (OS), progression-free survival (PFS), the objective response rate (ORR), safety, and the correlation between FDG-PET and CT., Results: Twenty patients were enrolled from November 2014 to March 2016, 17 of whom were evaluated for metabolic and morphological changes. Metabolic response with FDG-PET was partial response (PR) in one case (5.9%), stable disease (SD) in four (23.5%), and progressive disease (PD) in 12 (70.6%). The metabolic response rate was 5.9%. On CT imaging, no complete response or PR was observed, and the ORR was 0%. Median PFS and OS were 1.7 and 9.8 months, respectively. The median PFS of patients who achieved PR or SD by FDG-PET was 3.7 months, whereas that of those assessed as PD was 1 month (p = 0.13). The median OS of patients who achieved PR or SD by FDG-PET was 13.0 months, whereas that of patients assessed as PD was 10.6 months (p = 0.43). Frequent adverse events were palmar-plantar erythrodysesthesia syndrome, hypertension, loss of appetite, and fatigue., Conclusions: In this study, FDG-PET failed to demonstrate usefulness as an early imaging biomarker of regorafenib in patients with mCRC., (© 2021. The Author(s).)

Although many animals that perform sexual reproduction exhibit sexual dimorphism, individuals with intersex traits between the traits of males and females appear in some species, depending on environmental factors. Ptychognathus ishii , a varunid crab, exhibits distinctive sexual dimorphism in the morphology of its abdomen, chelipeds and setal tufts on the chelipeds. In this study, however, we report for the first time that intersex individuals with intermediate characters between those of males and females were occasionally found in wild populations. Morphological features of intersex individuals are described. Their taxonomic positions are identified based on DNA sequences of part of the mitochondrial cytochrome c oxidase I (COI) gene. It was shown that the intersexuality was induced by entoniscid parasites, because all intersex individuals were parasitized by entoniscid isopods, identified as Entionella sp. The apparent correlation between parasitism and morphological anomalies suggests that the parasitic isopods affect physiological conditions, leading to the feminization of male hosts.