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Myrtus communis is a Mediterranean shrub cultivated in Israel for traditional, ceremonial use only, with more than 98 % of the crop biomass, equivalent to 26–27 tons per ha per annum, considered agricultural waste. Therefore, potentially profitable use for this excess is being highly sought. As Myrtus is also known for its unique terpene and terpenoid content, this work evaluated the impact of essential oil (EO) extracted from several M. communis cultivars on storage insects, nematodes, fungi, and pathogens. In addition, the allelopathic effect of M. communis litter on the germination success of wheat seeds was evaluated. The EO extracts demonstrated an insecticidal effect on several storage insects in fumigation experiment and a potentially inhibiting effect on wheat development in allelopathy experiments. No significant impact of M. communis EOs on the examined fungi, pathogens, and nematodes was recorded. Additional uses of the M. communis biomass suggest supplying additional income to the farmer through the circular agriculture approach. In addition, the use of this local crop can contribute to sustainable intensification by increasing farming efficiency, providing nature-based substitutes for chemical pesticides, and possibly, improving the future design of agriculture through the integration of Myrtus in monoculture crops.

The phaseout of methyl bromide and the ban on, or withdrawal of, other toxic soil fumigants and non-fumigant nematicides belonging to the organophosphate and carbamate groups are leading to changes in nematode-control strategies. Sustainable nematode-control methods are available and preferred, but not always effective enough, especially for cash crops in intensive agriculture. A few non-fumigant nematicides, which have a relatively high control efficacy with a low toxicity to non-target organisms, have been released to the market or are in the process of being registered for use. Fluensulfone, fluopyram, and fluazaindolizine are the three main and most promising next-generation nematicides. In this paper, several aspects of these non-fumigant nematicides are reviewed, along with a brief history and problems of old-generation nematicides.

Abstract Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled. Whole-exome sequencing identified two novel homozygous variants, c.488G > T (p.W163L) and c.2135G > A (p.W712*), within the myogenesis regulating glycosidase (MYORG) gene. Cerebellar ataxia (n = 5) and pyramidal signs (n = 4) were predominant symptoms, with significant clinical heterogeneity noted even within the same family. An autopsy of one patient revealed extensive brainstem calcifications, sparing the cerebral cortex, and marked by calcifications predominantly in capillaries and arterioles. The pathological study suggested morphological alterations characterized by shortened foot processes within astrocytes in regions with pronounced calcification and decreased immunoreactivity of AQP4. The morphology of astrocytes in regions without calcification remains preserved. Neuronal loss and gliosis were observed in the basal ganglia, thalamus, brainstem, cerebellum, and dentate nucleus. Notably, olivary hypertrophy, a previously undescribed feature in MYORG-PFBC, was discovered. Neuroimaging showed reduced blood flow in the cerebellum, highlighting the extent of cerebellar involvement. Among perivascular cells constituting the blood-brain barrier (BBB) and neurovascular unit, MYORG is most highly expressed in astrocytes. Astrocytes are integral components of the BBB, and their dysfunction can precipitate BBB disruption, potentially leading to brain calcification and subsequent neuronal loss. This study presents two novel homozygous variants in the MYORG gene and highlights the pivotal role of astrocytes in the development of brain calcifications, providing insights into the pathophysiological mechanisms underlying PFBC associated with MYORG variants.

Abstract Background Having no or few confidants is found to be associated with more severe mental health problems and a higher prevalence of depression in adults, but research examining this association in adolescents is scarce. Social relationships may be particularly critical during adolescence, as it is an important developmental period during which vulnerability to mental health problems increases. The present study examined the relationship between having no or few confidants and anxiety/depressive symptoms in adolescents. Methods Cross-sectional self-report survey targeting 7–12th grade students (age range: 12–18) was conducted in public junior and senior high schools in Mie and Kochi, Japan. Data from 17,829 students (49.7% boys) were analyzed. Associations between anxiety/depressive symptoms (12-item General Health Questionnaire; score range: 0–12) and the number of confidants (None, 1–3, or ≥ 4) were examined using multilevel regression analyses. The analyses were stratified by gender and school level (junior/senior high), and adjusted for experiences of being physically abused and bullied and the interactions of these experiences with the number of confidants. Results Having no or 1–3 confidants was associated with more anxiety/depressive symptoms, compared to having ≥ 4 confidants (p

It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse.

Abstract We present expressions for correlation functions of scalar field theories in perturbation theory using quantum A ∞ algebras. Our expressions are highly explicit and can be used for theories both in Euclidean space and in Minkowski space including quantum mechanics. Correlation functions at a given order of perturbation theory can be calculated algebraically without using canonical quantization or the path integral, and we demonstrate it explicitly for φ 3 theory. We show that the Schwinger-Dyson equations are satisfied as an immediate consequence of the form of the expressions based on quantum A ∞ algebras.

Abstract Inflammatory responses are known to suppress neural regeneration in patients receiving stem cell-based regenerative therapy for spinal cord injury (SCI). Consequently, pathways involved in neurogenesis and immunomodulation, such as the hepatocyte growth factor (HGF)/MET signaling cascade, have garnered significant attention. Notably, various studies, including our own, have highlighted the enhanced recovery of locomotor functions achieved in SCI animal models by combining HGF pretreatment and human induced stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation. However, these studies implicitly hypothesized that the functionality of HGF in SCI would be time consistent and did not elucidate its dynamics. In the present article, we investigated the time-course of the effect of HGF on SCI, aiming to uncover a more precise mechanism for HGF administration, which is indispensable for developing crystallizing protocols for combination therapy. To this end, we performed a detailed investigation of the temporal variation of HGF using the RNA-seq data we obtained in our most recent study. Leveraging the time-series design of the data, which we did not fully exploit previously, we identified three components in the effects of HGF that operate at different times: early effects, continuous effects, and delayed effects. Our findings suggested a concept where the three components together contribute to the acceleration of neurogenesis and immunomodulation, which reinforce the legitimacy of empirically fine-tuned protocols for HGF administration and advocate the novel possibility that the time-inconsistent effects of HGF progressively augment the efficacy of combined therapy.

Abstract Background and Objectives The GAA repeat expansion within the fibroblast growth factor 14 (FGF14) gene has been found to be associated with late‐onset cerebellar ataxia. This study aimed to investigate the genetic causes of cerebellar ataxia in patients in Japan. Methods We collected a case series of 940 index patients who presented with chronic cerebellar ataxia and remained genetically undiagnosed after our preliminary genetic screening. To investigate the FGF14 repeat locus, we employed an integrated diagnostic strategy that involved fluorescence amplicon length analysis polymerase chain reaction (PCR), repeat‐primed PCR, and long‐read sequencing. Results Pathogenic FGF14 GAA repeat expansions were detected in 12 patients from 11 unrelated families. The median size of the pathogenic GAA repeat was 309 repeats (range: 270–316 repeats). In these patients, the mean age of onset was 66.9 ± 9.6 years, with episodic symptoms observed in 56% of patients and parkinsonism in 30% of patients. We also detected FGF14 repeat expansions in a patient with a phenotype of multiple system atrophy, including cerebellar ataxia, parkinsonism, autonomic ataxia, and bilateral vocal cord paralysis. Brain magnetic resonance imaging (MRI) showed normal to mild cerebellar atrophy, and a follow‐up study conducted after a mean period of 6 years did not reveal any significant progression. Discussion This study highlights the importance of FGF14 GAA repeat analysis in patients with late‐onset cerebellar ataxia, particularly when they exhibit episodic symptoms, or their brain MRI shows no apparent cerebellar atrophy. Our findings contribute to a better understanding of the clinical variability of GAA‐FGF14‐related diseases.

In order to use plant biomass as biochar for storing carbon in soils, the relationship between the chemical composition of plants and biochar yield obtained by thermogravimetric (TG) analysis was studied. The extractive content of herbaceous plants such as dokudami (Houttuynia cordata), halcyon (Erigeron philadelphicus), and mugwort (Artemisia Spp.) was higher than that of Japanese cypress (Chamaecyparis obtusa), and the yields at 250 and 300 °C tended to decrease with increasing extractive content of plants. This indicated the possibility that thermal decomposition of herbaceous plants can be conducted at low temperatures (below 350 °C). In addition, the content of crystalline carbohydrates (remaining upon treatment with 5% sulfuric acid) of herbaceous plants was lower than that of Japanese cypress, and the yield at 400 °C tended to decrease with increasing crystalline carbohydrate content of plants. This indicated the possibility that herbaceous plants can be used to obtain biochar with higher yield at 400 °C than woody plants. Therefore, herbaceous plants are considered to be feasible resources as raw materials for biochar production for storing carbon in soils.

In order to use plant biomass as biochar for storing carbon in soils, the relationship between the chemical composition of plants and biochar yield obtained by thermogravimetric (TG) analysis was studied. The extractive content of herbaceous plants such as dokudami (Houttuynia cordata), halcyon (Erigeron philadelphicus), and mugwort (Artemisia Spp.) was higher than that of Japanese cypress (Chamaecyparis obtusa), and the yields at 250 and 300 °C tended to decrease with increasing extractive content of plants. This indicated the possibility that thermal decomposition of herbaceous plants can be conducted at low temperatures (below 350 °C). In addition, the content of crystalline carbohydrates (remaining upon treatment with 5% sulfuric acid) of herbaceous plants was lower than that of Japanese cypress, and the yield at 400 °C tended to decrease with increasing crystalline carbohydrate content of plants. This indicated the possibility that herbaceous plants can be used to obtain biochar with higher yield at 400 °C than woody plants. Therefore, herbaceous plants are considered to be feasible resources as raw materials for biochar production for storing carbon in soils.

Background: Infectious mononucleosis (IM) caused by Epstein-Barr virus typically presents with fever, pharyngitis, and lymphadenopathy, and most patients recover within a few weeks. However, bilateral peritonsillar abscess is a rare but serious complication of IM that can lead to airway compromise and descending mediastinitis. Due to its rarity and similarity in clinical presentation of IM, it may be challenging to diagnose bilateral peritonsillar abscess during the course of IM. Case report: A 21-year-old healthy male who initially presented with fever, sore throat, and abdominal discomfort for ten days was diagnosed with IM based on clinical and laboratory findings. Despite initial treatment, the patient returned to the emergency department three times within one week due to persistent symptoms, and on the third visit, he had difficulty opening his mouth and had worsening odynophagia. Contrast-enhanced computed tomography revealed bilateral peritonsillar abscess, and an emergent incision of the right tonsil was performed. Bacterial culture revealed multiple oral organisms. He was diagnosed with bilateral peritonsillar abscess associated with IM and was discharged without complications. Why should an emergency physician be aware of this?: This case highlights two important clinical issues: the potential for patients with IM to develop bilateral peritonsillar abscess and the significance of trismus and exacerbation of odynophagia as a clue for identifying this complication. The rarity of this complication may result in delayed diagnosis and treatment, leading to serious complications. Prompt diagnosis and treatment are crucial for preventing potentially life-threatening consequences.

Abstract Background Floods and torrential rains are natural disasters caused by climate change. Unfortunately, such events are more frequent and are increasingly severe in recent times. The 2018 Japan Floods in western Japan were one of the largest such disasters. This study aimed to evaluate the effect of the 2018 Japan Floods on healthcare costs and service utilization. Methods This retrospective cohort study included all patients whose receipts accrued between July 2017 and June 2019 in Hiroshima, Okayama, and Ehime prefectures using the National Database of Health Insurance Claims. We used Generalized Estimating Equations (GEEs) to investigate yearly healthcare costs during the pre-and post-disaster periods, quarterly high-cost patients (top 10%), and service utilization (outpatient care, inpatient care, and dispensing pharmacy) during the post-disaster period. After the GEEs, we estimated the average marginal effects as the attributable disaster effect. Results The total number of participants was 5,534,276. Victims accounted for 0.65% of the total number of participants (n = 36,032). Although there was no significant difference in pre-disaster healthcare costs (p = 0.63), post-disaster costs were $3,382 (95% CI: 3,254–3,510) for victims and $3,027 (95% CI: 3,015–3,038) for non-victims (p

Summary: The emergence of single-cell RNA sequencing (RNA-seq) has radically changed the observation of cellular diversity. Although annotations of RNA-seq data require preserved properties among cells of an identity, annotations using conventional methods have not been able to capture universal characters of a cell type. Analysis of expression levels cannot be accurately annotated for cells because differences in transcription do not necessarily explain biological characteristics in terms of cellular functions and because the data themselves do not inform about the correct mapping between cell types and genes. Hence, in this study, we developed a new representation of cellular identities that can be compared over different datasets while preserving nontrivial biological semantics. To generalize the notion of cell types, we developed a new framework to manage cellular identities in terms of set theory. We provided further insights into cells by installing mathematical descriptions of cell biology. We also performed experiments that could correspond to practical applications in annotations of RNA-seq data.

Abstract Background Subarachnoid hemorrhage (SAH) is a fatal disease, with early brain injury (EBI) occurring within 72 h of SAH injury contributes to its poor prognosis. EBI is a complicated phenomenon involving multiple mechanisms. Although neuroinflammation has been shown to be important prognosis factor of EBI, whether neuroinflammation spreads throughout the cerebrum and the extent of its depth in the cerebral cortex remain unknown. Knowing how inflammation spreads throughout the cerebrum is also important to determine if anti-inflammatory agents are a future therapeutic strategy for EBI. Methods In this study, we induced SAH in mice by injecting hematoma into prechiasmatic cistern and created models of mild to severe SAH. In sections of the mouse cerebrum, we investigated neuroinflammation and neuronal cell death in the cortex distal to the hematoma injection site, from anterior to posterior region 24 h after SAH injury. Results Neuroinflammation caused by SAH spread to all layers of the cerebral cortex from the anterior to the posterior part of the cerebrum via the invasion of activated microglia, and neuronal cell death increased in correlation with neuroinflammation. This trend increased with the severity of the disease. Conclusions Neuroinflammation caused by SAH had spread throughout the cerebrum, causing neuronal cell death. Considering that the cerebral cortex is responsible for long-term memory and movement, suppressing neuroinflammation in all layers of the cerebral cortex may improve the prognosis of patients with SAH.

Abstract Ecological studies have suggested the protective effect of micro-dose lithium in drinking water against suicide, however, the association between body lithium level and suicide is unknown. We aimed to compare body lithium levels between suicide and non-suicide fatalities. This cross-sectional study included 12 suicides and 16 non-suicides who were examined or dissected at the Tokyo Medical Examiner’s Office from March 2018 to June 2021. The aqueous humor lithium concentration was measured twice using inductively coupled plasma mass spectrometry. Analysis of covariance (ANCOVA) was used to compare the lithium concentration between suicides and non-suicides. Mixed-effects model was conducted to account for all lithium concentration data. The aqueous humor lithium concentration did not change after death (t(7) = −0.70, $$\bar v = - 0.02$$ v ¯ = − 0.02 , SE = 0.03, 95% CI = [−0.09, 0.05], P = 0.51, Cohen’s d = 0.01). The aqueous humor lithium concentration was lower in suicides (mean 0.50 μg/L (variance s 2 0.04)) than in non-suicides (mean 0.92 μg/L (s 2 0.07)) (t(26) = 4.47, $$\bar v = 0.42$$ v ¯ = 0.42 , SE = 0.09, 95% CI = [0.22 to 0.61], P

In Japanese hospitals, patients undergoing invasive procedures or surgery are screened for anti-HCV antibodies; however, the majority of possible HCV careers are not referred to hepatologists. In addition to the conventional alert email system, a hepatologist extracted monthly lists of anti-HCV-antibody-positive patients who had been tested two months previously and checked medical records to determine whether the doctors who ordered the tests had properly dealt with the positive results. If the doctors had not yet properly followed up, the hepatologist would send emails to both the doctor and a medical clerk to inform them to conduct an HCV-RNA test and to refer HCV-RNA-positive patients to hepatologists. In total, 130 patients managed in the pre-intervention period and 151 patients managed in the post-intervention period were included in this study. The number of anti-HCV-positive patients whose results were not properly handled showed a significant decrease after the introduction of the double alert system (p = 0.034). Among patients undergoing screening anti-HCV antibody testing, a significant number of patients with probable chronic HCV hepatitis were overlooked by the email alert system and their results were not properly handled. The double alert system was useful for reducing the number of positive anti-HCV antibody patients whose results were not properly handled.

Abstract Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase. Although ABL1-specific tyrosine kinase inhibitors (TKIs) including nilotinib have dramatically improved the prognosis of patients with CML, the TKI efficacy depends on the individual patient. In this work, we found that the patients with different nilotinib responses can be classified by using the estimated parameters of our simple dynamical model with two common laboratory findings. Furthermore, our proposed method identified patients who failed to achieve a treatment goal with high fidelity according to the data collected only at three initial time points during nilotinib therapy. Since our model relies on the general properties of TKI response, our framework would be applicable to CML patients who receive frontline nilotinib or other TKIs.

Background: Extralobar pulmonary sequestration (EPS) is often diagnosed in neonates due to accompanying congenital anomalies. However, even in adulthood, this condition can, in rare cases, be complicated with torsion and may present with pleuritic chest pain at an emergency department in an undiagnosed state. We describe a case with torsion of ELS in a healthy adult female. Case report: A 21-year-old woman presented with acute-onset back pain and pleuritic chest pain at our emergency department and was initially diagnosed with pleurisy based on normal results of investigations. However, she revisited our department due to flare-ups of pain, and a subsequent CT scan revealed an expanding homogeneous opacity in the left lower lobe of the lung. Magnetic resonance imaging (MRI) confirmed the presence of an encapsulated mass with a hypointense signal on T2-weighted imaging and a feeding artery from the aorta to the mass, leading to a preoperative diagnosis of EPS with hemorrhagic infarction. Video-assisted thoracoscopic surgery was performed, and the cause of hemorrhagic infarction was found to be a torsion. The diagnosis was confirmed histologically. Why should an emergency physician be aware of this?: This case highlights the importance of recognizing torsion of EPS as an unusual cause of pleuritic chest pain and emphasizes the need for early diagnosis in order to perform surgery as soon as possible. Changes in CT findings of torsion of EPS over time can help physicians understand this rare condition. MRI may also be useful for the perioperative diagnosis.

Abstract Background Recessive mutations in SLC12A6 have been linked to hereditary motor sensory neuropathy with agenesis of the corpus callosum. Patients with early‐onset peripheral neuropathy associated with SLC12A6 heterozygous variants were reported in 2016. Only five families and three variants have been reported to date, and the spectrum is unclear. Here, we aim to describe the clinical and mutation spectra of SLC12A6‐related Charcot–Marie–Tooth (CMT) disease in Japanese patients. Methods We extracted SLC12A6 variants from our DNA microarray and targeted resequencing data obtained from 2598 patients with clinically suspected CMT who were referred to our genetic laboratory by neurological or neuropediatric departments across Japan. And we summarized the clinical and genetic features of these patients. Results In seven unrelated families, we identified one previously reported and three novel likely pathogenic SLC12A6 heterozygous variants, as well as two variants of uncertain significance. The mean age of onset for these patients was 17.5 ± 16.1 years. Regarding electrophysiology, the median motor nerve conduction velocity was 39.6 ± 9.5 m/sec. For the first time, we observed intellectual disability in three patients. One patient developed epilepsy, and her brain MRI revealed frontal and temporal lobe atrophy without changes in white matter and corpus callosum. Conclusions Screening for the SLC12A6 gene should be considered in patients with CMT, particularly those with central nervous system lesions, such as cognitive impairment and epilepsy, regardless of the CMT subtype.

Background Zooplankton plays an important role in the marine ecosystem. A high level of taxonomic expertise is necessary for accurate species identification based on morphological characteristics. As an alternative method to morphological classification, we focused on a molecular approach using 18S and 28S ribosomal RNA (rRNA) gene sequences. This study investigates how the accuracy of species identification by metabarcoding improves when taxonomically verified sequences of dominant zooplankton species are added to the public database. The improvement was tested by using natural zooplankton samples. Methods rRNA gene sequences were obtained from dominant zooplankton species from six sea areas around Japan and registered in the public database for improving the accuracy of taxonomic classifications. Two reference databases with and without newly registered sequences were created. Comparison of detected OTUs associated with single species between the two references was done using field-collected zooplankton samples from the Sea of Okhotsk for metabarcoding analysis to verify whether or not the newly registered sequences improved the accuracy of taxonomic classifications. Results A total of 166 sequences in 96 species based on the 18S marker and 165 sequences in 95 species based on the 28S marker belonging to Arthropoda (mostly Copepoda) and Chaetognatha were registered in the public database. The newly registered sequences were mainly composed of small non-calanoid copepods, such as species belonging to Oithona and Oncaea. Based on the metabarcoding analysis of field samples, a total of 18 out of 92 OTUs were identified at the species level based on newly registered sequences in the data obtained by the 18S marker. Based on the 28S marker, 42 out of 89 OTUs were classified at the species level based on taxonomically verified sequences. Thanks to the newly registered sequences, the number of OTUs associated with a single species based on the 18S marker increased by 16% in total and by 10% per sample. Based on the 28S marker, the number of OTUs associated with a single species increased by 39% in total and by 15% per sample. The improved accuracy of species identification was confirmed by comparing different sequences obtained from the same species. The newly registered sequences had higher similarity values (mean >0.003) than the pre-existing sequences based on both rRNA genes. These OTUs were identified at the species level based on sequences not only present in the Sea of Okhotsk but also in other areas. Discussion The results of the registration of new taxonomically verified sequences and the subsequent comparison of databases based on metabarcoding data of natural zooplankton samples clearly showed an increase in accuracy in species identification. Continuous registration of sequence data covering various environmental conditions is necessary for further improvement of metabarcoding analysis of zooplankton for monitoring marine ecosystems.

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Abstract Background The frequency and intensity of natural disasters are increasing worldwide, which makes our understanding of disaster-related diseases more important than ever. Natural disasters cause mental stress and infectious diarrhea, but the causal relationship between disasters and a potential consequence of these conditions, irritable bowel syndrome (IBS), is unreported. The 2018 Japan Floods, which took place in July 2018 was one of the largest water disasters in Japan’s recorded history. We investigate the change of drug prescriptions for IBS between disaster-suffers and non-sufferers throughout the disaster period to examine the relationship. Methods This is a retrospective cohort study based on the Japanese National Database of Health Insurance Claims and Specific Health Checkups in flood-stricken areas between July 2017 and June 2019. We included subjects older than 15 years of age who had visited a medical institution or been hospitalized in the hardest-hit areas of the disaster. Ramosetron, polycarbophil calcium, and mepenzolate bromide (IBS drugs) approved solely for the treatment of IBS in Japan were analyzed. The monthly rate of prescriptions for IBS drugs was compared between municipality-certified disaster victims and non-victims using a controlled interrupted time series analysis. For those who were not prescribed IBS drugs before the disaster (non-users), the occurrence of an IBS drug prescription after the disaster was evaluated using a multivariable logistic regression analysis adjusted for gender and age. Results Of 5,287,888 people enrolled, 32,499 (0.61%) were certified victims. The prescription rate for IBS drugs among victims increased significantly by 128% immediately after the disaster, while it was stable among non-victims. The trend for the post-disaster prescription rate among victims moved upward significantly when compared to non-victims (0.01% per month; 95% confidence interval (CI) 0.004–0.015; P = 0.001). Among non-users, the occurrence of an IBS drug prescription for victims was 0.71% and was significantly higher than non-victims (0.35%, adjusted odds ratio 2.05; 95% CI 1.81–2.32). Conclusions The 2018 Japan Floods increased the rate of prescriptions for IBS drugs, suggesting that the disaster caused or worsened IBS among victims.

Abstract Background Biallelic POLR3B mutations cause a rare hypomyelinating leukodystrophy. De novo POLR3B heterozygous mutations were recently associated with afferent ataxia, spasticity, variable intellectual disability, and epilepsy, and predominantly demyelinating sensorimotor peripheral neuropathy. Methods We performed whole‐exome sequencing (WES) of DNA samples from 804 Charcot–Marie–Tooth (CMT) cases that could not be genetically diagnosed by DNA‐targeted resequencing microarray using next‐generation sequencers. Using WES data, we analyzed the POLR3B mutations and confirmed their clinical features. Results We identified de novo POLR3B heterozygous missense mutations in two patients. These patients presented with early‐onset demyelinating sensorimotor neuropathy without ataxia, spasticity, or cognitive impairment. Patient 1 showed mild cerebellar atrophy and spinal cord atrophy on magnetic resonance imaging and eventually died of respiratory failure in her 50s. We classified these mutations as pathogenic based on segregation studies, comparison with control database, and in silico analysis. Conclusion Our study is the third report on patients with demyelinating CMT harboring heterozygous POLR3B mutations and verifies the pathogenicity of POLR3B mutations in CMT. Although extremely rare in our large Japanese case series, POLR3B mutations should be added to the CMT‐related gene panel for comprehensive genetic screening, particularly for patients with early‐onset demyelinating CMT.

Abstract Background Japan has established comprehensive education-scholarship programs to supply physicians in rural areas. Their entrants now comprise 16% of all medical students, and graduates must work in rural areas for a designated number of years. These programs are now being adopted outside Japan, but their medium-term outcomes and inter-program differences are unknown. Methods A nationwide prospective cohort study of newly licensed physicians 2014–2018 (n = 2454) of the four major types of the programs—Jichi Medical University (Jichi); regional quota with scholarship; non-quota with scholarship (scholarship alone); and quota without scholarship (quota alone)—and all Japanese physicians in the same postgraduate year (n = 40,293) was conducted with follow-up workplace information from the Physician Census 2018, Ministry of Health, Labour and Welfare. In addition, annual cross-sectional survey for prefectural governments and medical schools 2014–2019 was conducted to obtain information on the results of National Physician License Examination and retention status for contractual workforce. Results Passing rate of the National Physician License Examination was highest in Jichi, followed in descending order by quota with scholarship, the other two programs, and all medical graduates. The retention rate for contractual rural service of Jichi graduates 5 years after graduation (n = 683; 98%) was higher than that of quota with scholarship (2868; 90%; P

Abstract Case control studies have suggested that advanced glycation end products play a key role in the pathophysiology of chronic schizophrenia. However, the longitudinal association between advanced glycation end products and psychotic symptoms among drug-naïve adolescents remains unclear. This study examined whether advanced glycation end products could predict the trajectory of psychotic symptoms in drug-naive adolescents using data from prospective population-based biomarker subsample study of the Tokyo Teen Cohort. A total of 277 community-dwelling adolescents aged 13 years without antipsychotic medication were analyzed. Fingertip advanced glycation end products were measured in adolescents using noninvasive technology that can be used quickly. The trajectory of psychotic symptoms in a 12-month follow-up was assessed by experienced psychiatrists using a semi-structured interview. Of the 277 participants, 13 (4.7%) experienced persistent psychotic symptoms (psychotic symptoms at baseline and follow-up), 65 (23.5%) experienced transient psychotic symptoms (psychotic symptoms at baseline or follow-up), and 199 (71.8%) did not have psychotic symptoms. Multinomial logistic regression analysis adjusted for age and sex revealed that baseline fingertip advanced glycation end products might predict the risk of persistent psychotic symptoms (odds ratio = 1.68; 95% confidence interval, 1.05–2.69; P = 0.03). Altogether, fingertip advanced glycation end products potentially predicted the trajectory of psychotic symptoms among drug-naive adolescents, which indicated its involvement in the pathophysiology of early psychosis. Further studies are required to identify strategies to reduce adolescent advanced glycation end products, which may contribute to preventing the onset of psychosis.

The recessive intronic pentanucleotide repeat AAGGG expansion of replication factor complex subunit 1 (RFC1) is associated with cerebellar ataxia, sensory neuropathy, and vestibular areflexia syndrome. And the clinical spectrum has been continuously expanding. We conducted this study to demonstrate the clinical and genetic features of a large-scale case series of Japanese patients with cerebellar ataxia with RFC1 repeat expansions. We examined 1,289 Japanese patients with cerebellar ataxia and analyzed RFC1 repeat expansions in 840 patients, excluding those with genetic diagnoses or an autosomal dominant inheritance pattern. For individuals where no product was obtained by flanking polymerase chain reaction (PCR), repeat-primed PCR was performed using primers specific for the following four repeat motifs: AAAAG, AAAGG, AAGGG, and ACAGG. RFC1 analysis revealed multitype biallelic pathogenic repeat expansions in 15 patients, including (AAGGG)exp/(AAGGG)exp in seven patients, (ACAGG)exp/(ACAGG)exp in three patients, (AAGGG)exp/(ACAGG)exp in four patients, and (AAGGG)exp/(AAAGG)15(AAGGG)exp in one patient. Clinical analysis showed various combinations of cerebellar ataxia, vestibular dysfunction, neuropathy, cognitive decline, autonomic dysfunction, chronic cough, pyramidal tract disorder, parkinsonism, involuntary movement, and muscle fasciculation. Pathological RFC1 repeat expansions account for 1.8% (15/840) of undiagnosed patients with cerebellar ataxia and sporadic/recessive/unclassified inheritance. Screening of RFC1 repeat expansions should be considered in patients with cerebellar ataxia, irrespective of their subtype and onset age.

Post‐tetanic potentiation (PTP) is a major form of plasticity at hippocampal mossy fiber synapses and is considered an entirely presynaptic phenomenon. The authors show that mossy fiber PTP not only lacks associativity, but rather shows anti‐associative induction properties, implementing a brake on mossy fiber detonation.

Vanadium dioxide (VO2) is a well-known phase-changing material that goes from a semiconducting state to a metallic one at a critical temperature of 68 °C, which is the closest to room temperature (25 °C). The electrical transition is also accompanied by structural and optical changes. The optical transition upon heating-also known as thermochromism-makes VO2 a possible coating for “intelligent” windows. In this work, the relationship between the thermochromic performance of VO2 films and the surface morphology was investigated using Temperature-dependent Atomic Force Microscopy (T-AFM) in conjunction with the X-ray Diffraction technique and Scanning Electron Microscopy. In particular, VO2 films were deposited using the rf sputtering technique on Silicon and glass substrates at a substrate temperature of 300 °C, which is one of the lowest for this technique to grow the thermochromic monoclinic phase of VO2. It was found that upon heating (25–100 °C), there was a decrease in RMS roughness for all films independent from the substrate; the value of RMS roughness, however, varied depending on the substrate. Finally, the thermochromic parameters of the VO2 films were correlated with the surface morphology and appeared to be dependent on the kind of substrate used.

Background: Level of care-need (LOC) is an indicator of elderly person’s disability level and is officially used to determine the care services provided in Japan’s long-term care insurance (LTCI) system. The 2018 Japan Floods, which struck western Japan in July 2018, were the country’s second largest water disaster. This study determined the extent to which the disaster affected the LOC of victims and compared it with that of non-victims. Methods: This is a retrospective cohort study, based on the Japanese long-term care insurance claims from two months before (May 2018) to five months after the disaster (December 2018) in Hiroshima, Okayama, and Ehime prefectures, which were the most severely damaged areas in the country. A code indicating victim status, certified by a residential municipality, was used to distinguish between victims and non-victims. Those aged 64 years or younger, those who had the most severe LOC before the disaster, and those whose LOC increased even before the disaster were excluded. The primary endpoint was the augmentation of pre-disaster LOC after the disaster, which was evaluated using the survival time analysis. Age, gender, and type of care service were used as covariates. Results: Of the total 193,723 participants, 1,407 (0.7%) were certified disaster victims. Five months after the disaster, 135 (9.6%) of victims and 14,817 (7.7%) of non-victims experienced the rise of LOC. The victim group was significantly more likely to experience an augmentation of LOC than the non-victim group (adjusted hazard ratio 1.24; 95% confidence interval 1.06–1.45). Conclusions: Older people who were affected by the disaster needed more care than before and the degree of care-need increase was substantially more than non-victims. The result suggests that natural disasters generate more demand for care services among the older people, and incur more resources and cost for society than before.

Abstract Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members affected by severe or treatment-resistant schizophrenia. A missense variant, chr12:132064747C>T (rs200626129, P2805L), in the E1A-binding protein P400 (EP400) gene completely segregated with schizophrenia in this family. Furthermore, numerous other EP400 mutations were identified in the targeted sequencing of a schizophrenia patient cohort. We also created two lines of Ep400 gene-edited mice, which had anxiety-like behaviours and reduced axon diameters. Our findings suggest that rs200626129 in EP400 is likely to cause schizophrenia in this Japanese family, and may lead to a better understanding and treatment of schizophrenia.

Introduction: Solutions for geographic maldistribution of physicians is challenging around the world, but primary care specialists are expected to resolve this issue. This study compares the geographic distribution of family physicians in Japan and the USA, both of which are developed countries without a major system for physician allocation by the public sector; however, the two countries differ greatly in the maturity of family medicine (ie length of its history as part of the healthcare system and the population of qualified family medicine experts). Methods: This cross-sectional comparative study used publicly available online databases for Japan in 2018 and 2017 in the USA. The municipalities in Japan and counties in the USA were divided into quintile groups according to population density. The number of family physicians per unit population in each group of areas was calculated, and was evaluated with a residual analysis. The geographic distribution of all physicians in Japan was simulated assuming that the proportion of family physicians among all physicians in Japan (0.16%) was increased to match that in the USA (11.8%). Results: Of 320 084 physicians in Japan and 899 244 in the USA, 519 (77.2%) family physicians in Japan and 105 999 (100%) in the USA were included. The distribution of family physicians in Japan was noticeably shifted to areas with the lowest population density. In contrast, family physicians in the USA were distributed equally across areas. The distribution of physicians of other specialties (general internists, pediatricians, surgeons and obstetricians/gynecologists) was shifted heavily to areas with the highest population densities in both countries. The simulation analysis showed the geographic maldistribution of the total number of physicians improved substantially if the proportion of family physicians in Japan is increased to match that in the USA. Conclusion: The distribution of family physicians is more equitable than that of other medical specialists; however, an immature family medicine system can lead to an aggregation of family physicians in rural areas. This aggregation supports equity due to the broader scope of practice required by family physicians in rural areas. In countries where family medicine has not yet matured as a specialty, provided that the equitable aggregation of family physicians in rural areas can be maintained, increasing the number of family physicians as a proportion of the total number of physicians may improve the geographic maldistribution of the total number of physicians.

Abstract Background Copy number variants (CNVs) have been reported to be associated with diseases, traits, and evolution. However, it is hard to determine which gene should have priority as a target for further functional experiments if a CNV is rare or a singleton. In this study, we attempted to overcome this issue by using two approaches: by assessing the influences of gene dosage sensitivity and gene expression sensitivity. Dosage sensitive genes derived from two-round whole-genome duplication in previous studies. In addition, we proposed a cross-sectional omics approach that utilizes open data from GTEx to assess the effect of whole-genome CNVs on gene expression. Methods Affymetrix Genome-Wide SNP Array 6.0 was used to detect CNVs by PennCNV and CNV Workshop. After quality controls for population stratification, family relationship and CNV detection, 287 patients with narcolepsy, 133 patients with essential hypersomnia, 380 patients with panic disorders, 164 patients with autism, 784 patients with Alzheimer disease and 1280 healthy individuals remained for the enrichment analysis. Results Overall, significant enrichment of dosage sensitive genes was found across patients with narcolepsy, panic disorders and autism. Particularly, significant enrichment of dosage-sensitive genes in duplications was observed across all diseases except for Alzheimer disease. For deletions, less or no enrichment of dosage-sensitive genes with deletions was seen in the patients when compared to the healthy individuals. Interestingly, significant enrichments of genes with expression sensitivity in brain were observed in patients with panic disorder and autism. While duplications presented a higher burden, deletions did not cause significant differences when compared to the healthy individuals. When we assess the effect of sensitivity to genome dosage and gene expression at the same time, the highest ratio of enrichment was observed in the group including dosage-sensitive genes and genes with expression sensitivity only in brain. In addition, shared CNV regions among the five neuropsychiatric diseases were also investigated. Conclusions This study contributed the evidence that dosage-sensitive genes are associated with CNVs among neuropsychiatric diseases. In addition, we utilized open data from GTEx to assess the effect of whole-genome CNVs on gene expression. We also investigated shared CNV region among neuropsychiatric diseases.

In the Siemens method, high-purity Si is produced by reducing SiHCl3 source gas with H2 ambient under atmospheric pressure. Since the pyrolysis of SiHCl3, which produces SiCl4 as a byproduct, occurs dominantly in the practical Siemens process, the Si yield is low (~30%). In the present study, we generated hydrogen radicals (H-radicals) at pressures greater than 1 atm using tungsten filaments and transported the H-radicals into a reactor. On the basis of the absorbance at 600 nm of WO3-glass exposed to H-radicals in the reactor, we observed that H-radicals with a density of ~1.1 × 1012 cm−3 were transported approximately 30 cm under 1 atm. When SiCl4 was supplied as a source into the reactor containing H-radicals and allowed to react at 850°C or 900°C, Si was produced more efficiently than in reactions conducted under H2 ambient. Because the H-radicals can effectively reduce SiCl4, which is a byproduct in the Siemens method, their use is expected to increase the Si yield for this method.

Purpose: Wolfram syndrome is a rare genetic disorder characterized by juvenile onset of diabetes mellitus with bilateral optic atrophy. We report a case of adult onset Wolfram syndrome with diabetes mellitus at age 22 and optic atrophy after age 40. The WFS1 gene sequence was analyzed in the patient and her father. Observations: A 46-year-old woman presented with bilateral vision loss. She had developed diabetes mellitus at age 22 and underwent bilateral cataract surgery at age 37. Visual acuity was 20/50 in the right eye and 20/200 in the left eye. The pupillary light reflex was sluggish in both eyes. Fundus examination showed bilateral optic atrophy, but there was no diabetic retinopathy. Cecocentral scotoma of both eyes was observed in Goldmann perimetry. There were no intracranial lesions on magnetic resonance imaging. Audiometry demonstrated high-frequency sensorineural hearing loss. Sequence analysis of the WFS1 gene revealed compound heterozygous mutation: c.908T>C p.L303P and c.1232_1233del, p.S411Cfs*131 in the patient and heterozygous mutation c. 908 T>C, p. L303P in her father. Conclusions and importance: The patient was diagnosed with adult-onset Wolfram syndrome with compound heterozygous mutations of the WFS1 alleles. Wolfram syndrome must be ruled out even in adult-onset diabetic patients with optic atrophy.

The aim of this review is to investigate the diagnostic accuracy or performance of contrast‐enhanced computed tomography (CT) and magnetic resonance imaging (MRI) for acute pelvic inflammatory disease (PID) in an emergency care setting. We searched for studies on the diagnostic test accuracy of contrast‐enhanced CT or MRI for women of reproductive age with acute abdominal pain using MEDLINE, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and ClinicalTrials.gov. The reference standard was gynecological examinations by gynecologists using standard diagnostic criteria with or without laparoscopy or transcervical endometrial biopsy. Two reviewers undertook screening of records, data extraction, and assessment of the risk of bias in each included study using the Quality Assessment of Diagnostic Accuracy Studies‐2 tool. A bivariate model was used for the meta‐analysis. Of 2,619 screened studies, three studies investigating contrast‐enhanced CT and one study investigating MRI were eligible, including a total 635 patients and with a median prevalence of acute PID of 29%. All of the included studies had a high risk of bias for a reference standard and had some applicability concerns. Contrast‐enhanced CT had a pooled sensitivity of 0.79 (95% confidence interval [CI], 0.52–0.93) and specificity of 0.99 (95% CI, 0.94–1.00). Magnetic resonance imaging had a sensitivity of 0.95 (95% CI, 0.76–1.00) and specificity of 0.89 (95% CI, 0.52–1.00). Contrast‐enhanced CT might serve as a practical alternative to gynecological examination in the diagnosis of acute PID in an emergency care setting, however, the evidence was uncertain. The evidence on MRI was also very uncertain.

ObjectiveThe impact of the 2018 Japan Floods on prescriptions of Yokukansan was evaluated.MethodsThis was a retrospective cohort study based on the National Database of Health Insurance Claims which covers all the prescriptions issued in Japan. Participants were patients aged 65 or older who received any medical care at medical institutions located in the three most-severely affected prefectures between 1 year before and after the disaster. We analyzed the number of new prescriptions of Yokukansan and other Kampo drugs among those who had not been prescribed any Kampo for 1 year before the disaster. Kaplan-Meier analysis and a Cox proportional hazards model were used to evaluate the risk of the disaster for a new prescription.ResultsSubjects comprised 1,372,417 people (including 12,787 victims, 0.93%). The hazard ratio (HR) of the disaster for Yokukansan prescriptions was 1.49 [95% confidence intervals (CI): 1.25–1.78], and 1.54 (95% CI: 1.29–1.84) in the crude and age-sex adjusted model, respectively. The HR of the disaster for prescription of other Kampo drugs in the crude and adjusted model was 1.33 (95% CI: 1.27–1.39), and 1.32 (95% CI: 1.27–1.38), respectively. The magnitude of increase of victims prescribed Yokukansan (31.4%) was statistically higher than for those prescribed other Kampo drugs (19.3%) (p < 0.001).ConclusionThe disaster increased prescriptions of both Yokukansan and other Kampo drugs among elderly victims. The increase was more remarkable in Yokukansan than other Kampo drugs. Clinicians and policymakers should be aware of the increased need for Yokukansan in times of natural disaster.

Objective: In order to provide regenerative therapy for millions of patients suffering from corneal blindness globally, we derived corneal endothelial cell substitute (CECSi) cells from induced pluripotent stem cells (iPSCs) to treat corneal edema due to endothelial dysfunction (bullous keratopathy). Methods and results: We developed an efficient xeno-free protocol to produce CECSi cells from both research grade (Ff-MH09s01 and Ff-I01s04) and clinical grade (QHJI01s04) iPSCs. CECSi cells formed a hexagonal confluent monolayer with Na, K-ATPase alpha 1 subunit expression (ATP1A1), tight junctions, N-cadherin adherence junction formation, and nuclear PITX2 expression, which are all characteristics of corneal endothelial cells. CECSi cells can be cryopreserved, and thawed CECSi cell suspensions also expressed N-cadherin and ATP1A1. Residual undifferentiated iPSCs in QHJI01s04-derived CECSi cells was below 0.01%. Frozen stocks of Ff-I01s04- and QHJI01s04-derived CECSi cells were transported, thawed and transplanted into a monkey corneal edema model. CECSi-transplanted eyes significantly reduced corneal edema compared to control group. Conclusion: Our results show a promising approach to provide bullous keratopathy patients with an iPS-cell-based cell therapy to recover useful vision.

Background and Objectives: Adequate initial fixation of the uncemented acetabular component in total hip arthroplasty is necessary to achieve long-term survival. Although screw fixation contributes to improved cup stability, there is currently no consensus on the use of this method. This study aimed to assess the existing randomized controlled trials (RCTs) on the efficacy and safety of cup fixation in total hip arthroplasty without screws. Materials and Methods: We searched the EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases to identify RCTs published before February 2022. Primary outcomes were reoperation, cup migration, and Harris Hip Score. Secondary outcomes were the presence of a radiolucent line in the acetabular region, translation and rotation movement, and polyethylene wear. We conducted meta-analyses using the random-effects models. The revised Cochrane risk-of-bias tool was used to assess the risk of bias for outcomes of interest; the Grading of Recommendations, Assessment, Development, and Evaluation approach was used to summarize the body of evidence. Results: We included six reports from four studies. Total hip arthroplasty without screw fixation to the acetabular cup had little to no effect on reoperation (pooled relative risk, 0.98; 95% confidence interval, 0.14–6.68; I2 = 0%), cup migration (pooled relative risk, 1.72; 95% confidence interval, 0.29–10.33; I2 = 1%), Harris Hip Score (mean difference, 1.19; 95% confidence interval, −1.31–3.70; I2 = 0%), radiolucent line (pooled relative risk, 5.91; 95% confidence interval, 0.32–109.35), translation and rotation of all axes, and polyethylene wear (mean difference, 0.01; 95% confidence interval, −0.01–0.04; I2 = 0%), with very low certainty of evidence on all measures. Conclusions: The efficacy of acetabular cups without screw fixation in total hip arthroplasty remains uncertain, suggesting the need for prudent clinical application. Further large-scale, well-designed studies with low risk of bias are required.

Various genomic variants were linked to inherited peripheral neuropathies (IPNs), including large duplication/deletion and repeat expansion, making genetic diagnosis challenging. This large case series aimed to identify the genetic characteristics of Japanese patients with IPNs. We collected data on 2695 IPN cases throughout Japan, in which PMP22 copy number variation (CNV) was pre-excluded. Genetic analyses were performed using DNA microarrays, next-generation sequencing-based gene panel sequencing, whole-exome sequencing, CNV analysis, and RFC1 repeat expansion analysis. The overall diagnostic rate and the genetic spectrum of patients were summarized. We identified 909 cases with suspected IPNs, pathogenic or likely pathogenic variants. The most common causative genes were MFN2, GJB1, MPZ, and MME. MFN2 was the most common cause for early-onset patients, whereas GJB1 and MPZ were the leading causes of middle-onset and late-onset patients, respectively. Meanwhile, GJB1 and MFN2 were leading causes for demyelinating and axonal subtypes, respectively. Additionally, we identified CNVs in MPZ and GJB1 genes and RFC1 repeat expansions. Comprehensive genetic analyses explicitly demonstrated the genetic basis of our IPN case series. A further understanding of the clinical characteristics of IPN and genetic spectrum would assist in developing efficient genetic testing strategies and facilitate early diagnosis.

Optimal regimens using recent radiotherapy (RT) equipment for bleeding gastric cancer (GC) have not been fully investigated yet. We retrospectively reviewed the clinical data of 20 patients who received RT for bleeding GC in our institution between 2016 and 2021. Three-dimensional conformal RT was performed. The effectiveness of RT was evaluated by the mean serum hemoglobin (Hb) level and the number of transfused red blood cell (RBC) units 1 month before and after RT. The median first radiation dose was a BED of 39.9 Gy. The treatment success rate was 95% and the rebleeding rate was 10.5%. There was a significant increase in the mean Hb level (8.0 ± 1.1 vs. 9.8 ± 1.3 g/dL, p = 0.01), and a significant decrease in the mean number of transfused RBC units (6.8 ± 3.3 vs. 0.6 ± 1.5 units, p < 0.01). Severe toxicity was observed in two patients (anorexia [n = 1] and gastrointestinal [GI] perforation [n = 1]). Reirradiation was attempted in three patients (for hemostasis [n = 2] and for mass reduction [n = 1]). The retreatment success rate for rebleeding was 100%. GI perforation occurred in two patients who had received hemostatic reirradiation. Palliative RT for bleeding GC using recent technology had excellent efficacy. However, it may be associated with a risk of GI perforation.

Abstract We present a new approach to formulating open superstring field theory based on the covering of the supermoduli space of super-Riemann surfaces and explicitly construct a gauge-invariant action in the Neveu-Schwarz sector up to quartic interactions. The cubic interaction takes a form of an integral over an odd modulus of disks with three punctures and the associated ghost is inserted. The quartic interaction takes a form of an integral over one even modulus and two odd moduli, and it can be interpreted as the integral over the region of the supermoduli space of disks with four punctures which is not covered by Feynman diagrams with two cubic vertices and one propagator. As our approach is based on the covering of the supermoduli space, the resulting theory naturally realizes an A ∞ structure, and the two-string product and the three-string product used in defining the cubic and quartic interactions are constructed to satisfy the A ∞ relations to this order.

As an extension of combinatorial molecular layer epitaxy via ablation of perovskite oxides by a pulsed excimer laser, we have developed a laser molecular beam epitaxy (MBE) system for parallel integration of nano-scaled thin films of organic–inorganic hybrid materials. A pulsed infrared (IR) semiconductor laser was adopted for thermal evaporation of organic halide (A-site: CH3NH3I) and inorganic halide (B-site: PbI2) powder targets to deposit repeated A/B bilayer films where the thickness of each layer was controlled on molecular layer scale by programming the evaporation IR laser pulse number, length, or power. The layer thickness was monitored with an in situ quartz crystal microbalance and calibrated against ex situ stylus profilometer measurements. A computer-controlled movable mask system enabled the deposition of combinatorial thin film libraries, where each library contains a vertically homogeneous film with spatially programmable A- and B-layer thicknesses. On the composition gradient film, a hole transport Spiro-OMeTAD layer was spin-coated and dried followed by the vacuum evaporation of Ag electrodes to form the solar cell. The preliminary cell performance was evaluated by measuring I-V characteristics at seven different positions on the 12.5 mm × 12.5 mm combinatorial library sample with seven 2 mm × 4 mm slits under a solar simulator irradiation. The combinatorial solar cell library clearly demonstrated that the energy conversion efficiency sharply changes from nearly zero to 10.2% as a function of the illumination area in the library. The exploration of deposition parameters for obtaining optimum performance could thus be greatly accelerated. Since the thickness ratio of PbI2 and CH3NH3I can be freely chosen along the shadow mask movement, these experiments show the potential of this system for high-throughput screening of optimum chemical composition in the binary film library and application to halide perovskite solar cell.

Weight status and self-weight perception are related to social relationship issues. Studies have suggested links between non-normal weight status or weight perception and youths having fewer confidants, but these relationships are unclear and remain to be studied. This preliminary cross-sectional study examined the effects of weight status and weight perception on the number of confidants in adolescents. Self-report data from 15,279 grade 7-12 students (54.2% boys) were analyzed. The number of confidants (0-3 or ≥ 4) was examined, according to five weight status categories (underweight, low-normal weight, mid-normal weight (reference), high-normal weight, overweight, with Body Mass Index corresponding to ≤ 18.5, ≤ 20.0, ≤ 22.5, ≤ 25.0 and > 25.0 in adults, respectively), and five weight perception categories (too thin, a bit thin, good (reference), a bit fat, too fat). Boys and girls who were overweight and those who perceived themselves to be too fat were significantly more likely to have few confidants. High-normal weight in girls and self-perception of being a bit fat in boys were also associated with having few confidants. In boys, underweight and self-perception of being too thin were additionally associated with having few confidants. Adolescents with non-normal weight status or weight perception may have fewer confidants and require more social support.

Back ground: Theoretical investigations predicting the epidemic curves of seasonal influenza have been demonstrated so far; however, there is little empirical research using ever accumulated epidemic curves. The effects of vaccine coverage and information distribution on influenza epidemics were evaluated. Materials and Methods: Four indices for epidemics (i.e., onset-peak duration, onset-end duration, ratio of the onset-peak duration to onset-end duration and steepness of epidemic curves) were defined, and the correlations between these indices and anti-flu drug prescription dose, vaccine coverage, the volume of media and search trend on influenza through internet were analyzed. Epidemiological data on seasonal influenza epidemics from 2002/2003 to 2013/2014 excluding 2009/2010 season were collected from National Institute of Infectious Diseases of Japan. Results: The onset-peak duration and its ratio to onset-end duration correlated inversely with the volume of anti-flu drug prescription. Onset-peak duration correlated positively with media information volume on influenza. The steepness of the epidemic curve, and anti-flu drug prescription dose inversely correlated with the volume of media information. Pre-epidemic search trend and media volume on influenza correlated with the vaccine coverage in the season. Vaccine coverage had no strong effect on epidemic curve. Conclusion: Education through media has an effect on the epidemic curve of seasonal influenza.

Background and study aims Recently, endoscopic closure of gastrointestinal fistulas using polyglycolic acid (PGA) sheets with fibrin glue (FG) has been attempted. A 70-year-old woman who had undergone pancreaticoduodenectomy for pancreatic cancer suffered from a refractory anastomo-cutaneous fistula at the site of gastro-jejunostomy. We attempted endoscopic closure with filling and shielding using PGA sheets and FG. After introducing a guidewire into the fistula, a small piece of PGA sheet was skewered onto the guidewire and then pushed using a tapered catheter over the guidewire and delivered into the fistula. A total of 10 sheets were delivered via the same procedure. Next, the mucosa around the fistula was ablated, and the orifice of the fistula along with the surrounding mucosa was shielded with a piece of PGA sheet fixed with hemoclips and FG. After this procedure, the leakage disappeared and the fistula was undetectable on contrast radiograms. Endoscopic closure of anastomo-cutaneous fistula with filling and shielding using PGA sheets and FG is an effective, safe, low-invasive treatment, and the filling technique using a guidewire ensures a safe, smooth procedure.

Extra-pair copulation can increase genetic diversity and offspring fitness. However, it may also increase intra-nest variability in avian hosts of brood parasites, which can decrease the discrimination ability of host parents towards the parasite. In New Caledonia, the Fan-tailed Gerygone (Gerygone flavolateralis), which is parasitized by the Shining Bronze-cuckoo (Chalcites lucidus), has two nestling morphs, dark and bright, that can occur in monomorphic and polymorphic broods. Gerygone parents recognize and eject parasite nestlings from their nest, but the presence of polymorphic broods may increase the chances of recognition errors. Using 17 microsatellite markers, we investigated the mating system of the Fan-tailed Gerygone to understand the mechanisms underlying nestling polymorphism. We hypothesised that extra-pair copulations would lead to a higher proportion of polymorphic broods caused by higher genetic variability, thus creating a trade-off between genetic benefits and host defence reliability. Extra-pair paternity occurred in 6 of 36 broods, which resulted in 6 of 69 offspring sired by extra-pair males. Broods with and without mixed paternity were comparably often parasitized. Extra-pair paternity did not influence the proportions of bright, dark and polymorphic broods. Compared to bright siblings in polymorphic broods, dark nestlings tended to have lower heterozygosity, particularly in loci associated with skin coloration. The results also suggested that there is no obstacle for genetic exchange between individuals from forest and savannah, possibly due to dispersal of offspring. We conclude that the Fan-tailed Gerygone is a socially monogamous species with a low rate of extra-pair paternity compared to closely related species. Extra-pair paternity increased offspring genetic variability without measurable associated costs by brood parasitism. The results highlight the importance of studying host mating systems to assess the trade-offs between host defence and offspring fitness in co-evolutionary arms races.

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES) of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ∼45% (17/37) of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy-associated genes in subjects versus controls, confirmed in a second ethnically discrete neuropathy cohort, suggesting that mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HPMVs) and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity.