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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

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.

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 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.

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.

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.