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Abstract Background Mongolian grasslands, including the Gobi Desert, have been exposed to drought conditions with few rains. In such harsh environments, plants with highly resistant abilities against drought stress survive over long periods. We hypothesized that these plants could harbor novel and valuable genes for enhancing drought stress resistance. Results In this study, we identified Chloris virgata, a Mongolian grassland plant with strong drought resistance. RNA-seq-based transcriptome analysis was performed to uncover genes associated with drought stress resistance in C. virgata. De novo transcriptome assembly revealed 25,469 protein-coding transcripts and 1,219 upregulated genes after 3- and 6-hr drought stress treatments. Analysis by homology search and Gene Ontology (GO) enrichment indicated that abscisic acid (ABA)- and drought stress-related GO terms were enriched. Among the highly induced genes, ten candidate cDNAs were selected and overexpressed in Arabidopsis. When subjected to drought stress, three of these genes conferred strong drought resistance in the transgenic plants. We named these genes Mongolian Grassland plant Drought-stress resistance genes 1, 2, and 3 (MGD1, MGD2, and MGD3). Gene expression analyses in the transformants suggested that MGD1, MGD2, and MGD3 may activate drought stress-related signalling pathways. Conclusion This study highlighted the drought resistance of C. virgata and identified three novel genes that enhance drought stress resistance.

Abstract Background Sarcoglycanopathies (SGPs) are limb-girdle muscular dystrophies (LGMDs) that can be classified into four types, LGMDR3, LGMDR4, LGMDR5, and LGMDR6, caused by mutations in the genes, SGCA, SGCB, SGCG, and SGCD, respectively. SGPs are relatively rare in Japan. This study aims to profile the genetic variants that cause SGPs in Japanese patients. Methods Clinical course and pathological findings were retrospectively reviewed in Japanese patients with SGP. Genetic analyses were performed using a combination of targeted resequencing with a hereditary muscle disease panel, whole genome sequencing, multiplex ligation-dependent probe amplification, and long-read sequencing. The structures of transcripts with aberrant splicing were also determined by RT-PCR, RNA-seq, and in silico prediction. Results We identified biallelic variants in SGC genes in 53 families, including three families with LGMDR6, which had not been identified in Japan so far. SGCA was the most common causative gene, accounting for 56% of cases, followed by SGCG, SGCB, and SGCD, at 17%, 21%, and 6%, respectively. Missense variants in SGCA were very frequent at 78.3%, while they were relatively rare in SGCB, SGCG, and SGCD at 11.1%, 18.2%, and 16.6%, respectively. We also analyzed the haplotypes of alleles carrying three variants found in multiple cases: c.229C > T in SGCA, c.325C > T in SGCB, and exon 6 deletion in SGCG; two distinct haplotypes were found for c.229C > T in SGCA, while each of the latter two variants was on single haplotypes. Conclusions We present genetic profiles of Japanese patients with SGPs. Haplotype analysis indicated common ancestors of frequent variants. Our findings will support genetic diagnosis and gene therapy.

Background: Heart failure should be diagnosed as early as possible. Although deep learning models can predict one or more echocardiographic findings from electrocardiograms (ECGs), such analyses are not comprehensive. Objectives: This study aimed to develop a deep learning model for comprehensive prediction of echocardiographic findings from ECGs. Methods: We obtained 229,439 paired ECG and echocardiography data sets from 8 centers. Six centers contributed to model development and 2 to external validation. We identified 12 echocardiographic findings related to left-sided cardiac abnormalities, valvular heart diseases, and right-sided cardiac abnormalities. These findings were predicted using convolutional neural networks, and a composite label was analyzed using logistic regression. A positive composite label indicated positivity in any of the 12 findings. Results: For the composite findings label, the area under the receiver-operating characteristic curve was 0.80 (95% CI: 0.80-0.81) on hold-out validation and 0.78 (95% CI: 0.78-0.79) on external validation. The composite findings label applying logistic regression had an area under the receiver-operating characteristic curve of 0.80 (95% CI: 0.80-0.81) with accuracy of 73.8% (95% CI: 73.2-74.4), sensitivity of 81.1% (95% CI: 80.5-81.8), and specificity of 60.7% (95% CI: 59.6-61.8). Conclusions: We have developed convolutional neural network models that predict a wide range of echocardiographic findings, including left-sided cardiac abnormalities, valvular heart diseases, and right-sided cardiac abnormalities from ECGs and created a model to predict a composite findings label by logistic regression analysis. This model has potential to serve as an adjunct for early diagnosis and treatment of previously undetected cardiac disease.

This study proposes a wearable motion classification system by employing commercially available conductive threads and everyday garments. The unique feature of the proposed system is an embroidery bending sensor that does not necessitate tight-fitting with the body, which contrasts with traditional motion sensing systems. Therefore, integration can be simplified by allowing motion classification onto loose-fitting everyday garments. The sensor that exhibits a change in resistance to bending deformation is realized by applying multiple zigzag stitch to the fabric. In addition, a significant resistance change is realized during the phase transition of motions (e.g., stance and swing phase). Therefore, motion can be categorized without making joint angle measurements. We fabricated a prototype by attaching the sensors to a commercially available work jacket and pants by sewing them onto the fabric. Ten participants were requested to perform ten various activities (e.g., walking, jogging, ascending and descending stairs). The findings demonstrated that the sensor can measure the degree of joint flexion, the flexion cycle, and the timing of flexion during the wearer’s activities. Moreover, motion classification was performed by training a one-dimensional convolutional neural network (1D-CNN) model with the sensor signals. The model successfully learned the differences in signal amplitude and frequency as distinguishing features of each activity, resulting in an average classification accuracy of 99.02% across the ten types of activities.

Abstract Insulin receptor substrate (IRS)-1 and IRS-2 are major molecules that transduce signals from insulin and insulin-like growth factor-I receptors. The physiological functions of these proteins have been intensively investigated in mice, while little is known in other animals. Our previous study showed that the disruption of IRS-2 impairs body growth but not glucose tolerance or insulin sensitivity in rats, which led us to hypothesize that IRS-1 plays more pivotal roles in insulin functions than IRS-2. Here, we created IRS-1 knockout (KO) rats to elucidate the physiological roles of IRS-1 in rats. The body weight of IRS-1 KO rats at birth was lower than that of wild-type (WT) littermates, and postnatal growth of IRS-1 KO rats was severely impaired. Compared with WT rats, IRS-1 KO rats displayed insulin resistance but maintained euglycemia because of compensatory hyperinsulinemia. In addition, despite the increased activity of insulin-stimulated IRS-2-associated phosphatidylinositol-3 kinase (PI3K), insulin-induced phosphorylation of the kinases downstream of PI3K was suppressed in the liver and skeletal muscle of IRS-1 KO rats. Taken together, these results indicate that in rats, IRS-1 is essential for normal growth and the glucose-lowering effects of insulin. IRS-1 appears to be more important than IRS-2 for insulin functions in rats.

Strain engineering is a crucial approach in the engineering field to optimize various physical properties of materials by applying mechanical strain loading. However, it is extremely challenging to find out the best conditions of strain with unprecedented physical properties in the vast strain space consisting of six components. Here, we developed a technical framework that enables efficient exploration of physical properties in the vast strain space based on machine learning (i.e., artificial neural networks), active learning, and high-throughput first-principles calculation. We demonstrated the active learning technique to successfully and efficiently construct an accurate machine learning model for ferroelectric PbTiO3 with minimal first-principles datasets (only 3.7% of the vast strain-space). Our machine learning model can accurately predict the nonlinear mechanical deformation and electromechanical response in the three components of normal strain loading. We also carried out strain optimization of piezoelectric response using the machine learning model and found that a large piezoelectric response is five times larger than without strain loading. We showed that the physical property explorer framework constructed in this study makes it possible to optimize strain for various material properties in a vast strain space by calculating only a small number of data points. These results suggest paving the way for constructing nonlinear piezoelectric constitutive equations for novel piezoelectric devices via strain engineering.

In recent years, infection cases of H5 subtype highly pathogenic avian influenza viruses (HPAIVs) in wild mammals have increased globally. To obtain recent epidemiological information regarding influenza A virus (IAV) infection in raccoons (Procyon lotor), the prevalence of anti-IAV antibodies in sera was analyzed among raccoons captured in Tokachi District, Hokkaido, Japan, from 2019 to 2023. Screening of serum samples using enzyme-linked immunosorbent assay and agar gel precipitation test detected anti-IAV antibodies in 5 of 114 (4.4 %) raccoons. All positive sera were from raccoons captured from 2022 to 2023. The hemagglutination inhibition test revealed that all five serum samples contained anti-H5 subtype HPAIV antibodies, and one also contained anti-H1 subtype antibodies. The neuraminidase inhibition test revealed that all five sera contained anti-N1 subtype antibodies, and one also contained anti-N8 subtype antibodies. In the virus neutralization test, these five sera showed stronger neutralization activity against the H5 subtype clade 2.3.4.4b HPAIV strain recently circulating worldwide compared to the old H5 HPAIV strain isolated in Japan in 2007. These findings suggested that raccoons could be involved in the circulation of H5 HPAIVs in nature.

Orthorubulavirus parotitis, known as the mumps virus (MuV), can cause severe complications, including deafness and reduced fertility in humans. Developing preventive strategies against MuV infections is essential to mitigate these risks. We previously established an effective method for producing a milk-derived sialylglycopeptide (MSGP) concentrate from glycomacropeptide (GMP) in bovine milk using protease treatment. This MSGP concentrate was rich in short glycans containing α2–3 linked sialic acids, resembling the MuV binding receptors, which may contribute to inhibiting MuV infection. Our findings revealed that the MSGP concentrate significantly reduced MuV infection compared to the GMP concentrate. The hemagglutination inhibition of the MSGP concentrate was 2–8 times higher than that of the GMP concentrate, suggesting that the MSGP concentrate inhibits MuV infection by preventing receptor binding. These results highlight the potential of the MSGP concentrate as a food-derived functional material for preventing MuV infections.

Introduction: Diagnosis of diaphragmatic disease using dynamic chest radiography (DCR), a novel imaging testing modality has been previously reported in adults; however, there have been no prior reports of its use in pediatric patients. Herein, we report the novel case of a 14-year-old girl diagnosed with diaphragmatic eventration (DE) using DCR with extremely low-dose pulsed X-rays. Case series: A 14-year-old girl with pectus excavatum was referred to our hospital for surgery. Pre-operative chest radiography revealed that the right diaphragm was higher than the left however, this difference was judged to be within the normal range. Computed tomography (CT) revealed a Haller index of 3.00. Although the patient had no symptoms, she complained of an unsatisfactory appearance, which was considered an indication for surgery. The Nuss procedure was performed under artificial pneumothorax, and DE was not suspected. Six months after surgery, we performed DCR instead of chest radiographs to evaluate the position of the bar and the patient's respiratory status. Utilizing the captured images, we further measured and analyzed the diaphragm movement. DCR revealed a clear impairment of diaphragmic movement on the affected side, and the patient was subsequently diagnosed with DE. However, as she was asymptomatic, we decided to follow up conservatively. Conclusion: This is the first report of DCR in a pediatric patient. DCR appears to be a useful tool for the diagnosis of diaphragmatic eventration in children.

Iodine, being an important resource, must be recovered and reused. Iodine is not only attracted to the hydrophobic silicone membrane but also easily vaporized. In this study, we explored the use of five types of silicone hollow fiber membrane modules (SFMMs) for separating iodine in the gaseous phase. In the SFMM, iodine gas and the recovery solution (sodium sulfite and sodium carbonate at a concentration of 10 mM each) were flowed outside and inside the silicone hollow fiber, respectively, in a co-current-flow manner. At an iodine gas flow rate of 0.2 L/min (8.4 × 10−3 mmol-I2/L), the capture efficiency of iodine into the SFMM was approximately 100% for all five SFMMs. With increasing feed gas flow rates, the capture efficiency of iodine decreased, reducing to approximately 50% at 0.8 L/min. However, the recovery efficiency of iodine in the recovery solution was 60–30% at 0.2–0.8 L/min. This decrease in capture efficiency with increasing flow rates was because iodine could not spread and diffuse successfully in the SFMM, resulting in a low recovery efficiency of iodine. Thus, we next improved the structure of the SFMM by placing a perforated pipe in the center of the module. The perforated pipe effectively directs the iodine feed gas from the holes in the pipe to the hollow fiber membrane bundle wrapped around the pipe. With the improved SFMM, the capture efficiency markedly increased to approximately 100% in the range of the flow rates tested in our experiments. The recovery efficiency also increased to ≥70%. These data illustrate the potential application of the improved SFMM for recovering iodine in the gaseous phase.

Background/Objectives: The effects of ageing on the diaphragm are unclear. This study examined the association between ageing and diaphragm thickness, thickening fraction (TF), and diaphragm excursion (DE) as assessed by ultrasonography after adjusting for other factors. The relationship between these parameters and maximal inspiratory pressure (MIP) was also investigated. Methods: From 2022 to 2024, ambulatory and communicative adult volunteers and outpatients were recruited from four Japanese medical institutions. Each participant’s background factors (including height, weight, and underlying diseases) and pulmonary function test results were assessed. Diaphragm thickness, TF, and DE were evaluated using ultrasonography. Results: The study involved 230 individuals with a mean age of 55.5 years (older adults (65 years and over), n = 117; non-older adults, n = 113). In older adults, the diaphragm was thicker (2.1 vs. 1.7 mm, p < 0.001), and TF was lower (88.7% vs. 116.0%, p < 0.001), with no significant difference in DE. Multivariate linear regression analysis adjusted for sex, height, body mass index, and underlying diseases showed positive associations between age and diaphragm thickness (p = 0.001), but not with TF or DE. MIP was positively associated with DE (p < 0.001) but not with thickness or TF. Age was negatively associated with MIP, regardless of diaphragm thickness, TF, and DE (all p < 0.001). Conclusions: As the diaphragm thickens with age, neither thickness nor TF is associated with MIP; only DE is related to MIP. Additionally, ageing is negatively associated with MIP, independent of diaphragm thickness, TF, and DE. Diaphragm function should be assessed using DE rather than thickness or TF.

Background: Mongolian grasslands, including the Gobi Desert, have been exposed to drought conditions with few rains. In such harsh environments, plants with highly resistant abilities against drought stress survive over long periods. We hypothesized that these plants could harbor novel and valuable genes for enhancing drought stress resistance. Results: In this study, we identified Chloris virgata, a Mongolian grassland plant with strong drought resistance. RNA-seq-based transcriptome analysis was performed to uncover genes associated with drought stress resistance in C. virgata. De novo transcriptome assembly revealed 25,469 protein-coding transcripts and 1,219 upregulated genes after 3- and 6-hr drought stress treatments. Analysis by homology search and Gene Ontology (GO) enrichment indicated that abscisic acid (ABA)- and drought stress-related GO terms were enriched. Among the highly induced genes, ten candidate cDNAs were selected and overexpressed in Arabidopsis. When subjected to drought stress, three of these genes conferred strong drought resistance in the transgenic plants. We named these genes Mongolian Grassland plant Drought-stress resistance genes 1, 2, and 3 (MGD1, MGD2, and MGD3). Gene expression analyses in the transformants suggested that MGD1, MGD2, and MGD3 may activate drought stress-related signalling pathways. Conclusion: This study highlighted the drought resistance of C. virgata and identified three novel genes that enhance drought stress resistance. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to introduce and evaluate a novel software-based system, BioTrace, designed for real-time monitoring of thermal ablation tissue damage during image-guided radiofrequency ablation for hepatocellular carcinoma (HCC). Methods: BioTrace utilizes a proprietary algorithm to analyze the temporo-spatial behavior of thermal gas bubble activity during ablation, as seen in conventional B-mode ultrasound imaging. Its predictive accuracy was assessed by comparing the ablation zones it predicted with those annotated by radiologists using contrast-enhanced computed tomography (CECT) 24 hours post-treatment, considered the gold standard. The study included 20 liver tumors. Results: The median tumor measurement along the major axis was 1.2 cm. The median Dice coefficient, Sensitivity, and Precision between BioTrace and CECT were 0.90, 0.91, and 0.91, respectively. The intraclass correlation showed excellent agreement in volume size between BioTrace and CECT findings (0.98). Conclusion: BioTrace effectively generates an ablation damage prediction map based on real-time ultrasound imaging, accurately predicting the ablation zone as confirmed by 24-hour post-procedural CECT. This system has the potential to enhance the safety and efficacy of ablation procedures in clinical settings. [ABSTRACT FROM AUTHOR]

Background: The Beck Depression Inventory-II (BDI-II) is a widely used patient-reported outcome (PRO) tool designed to screen for depressive symptoms and assess their severity. In recent years, with advancements in digital technology, the BDI-II has been adapted for use as an electronic PRO (ePRO) tool. However, to the best of our knowledge, the reliability of the smartphone version of the BDI-II has not been thoroughly investigated. This study aimed to assess the equivalence of the traditional paper and smartphone versions of the BDI-II. Methods: This study employed a randomized crossover design with adults (n = 100) from the Gunma Prefecture, Japan. Participants completed both the paper and smartphone versions of the BDI-II at 1-week intervals. The equivalence between the two versions was evaluated using the intraclass correlation coefficient (ICCagreement). Additionally, Cronbach's alpha and McDonald's omega were calculated for both versions. Results: The mean age of the participants was 19.78 years (SD = 0.94, 10% male). The ICCagreement between the paper and smartphone versions of the BDI-II was 0.81 (95% CI 0.74–0.87). Cronbach's alpha was 0.88 (95% CI 0.84–0.91) for the paper version and 0.88 (95% CI 0.84–0.91) for the smartphone version. McDonald's omega was 0.88 (95% CI 0.81–0.95) for the paper version and 0.89 (95% CI 0.85–0.93) for the smartphone version. Conclusions: The BDI-II is suitable for use in its smartphone version, and the smartphone version of the BDI-II is a valuable addition to the mental healthcare professional's toolkit. [ABSTRACT FROM AUTHOR]

Simple Summary: Biliary tract cancers (BTCs) present a challenging prognosis. However, advancements in chemotherapy, particularly the use of targeted therapies for specific gene mutations, have led to improved patient outcomes. This retrospective single-center study evaluated 44 patients who received gemcitabine and cisplatin, combined with durvalumab (GCD) chemotherapy, from January 2023 to March 2024, with a median follow-up of 10 months. This study assessed overall survival (OS), progression-free survival (PFS), response rates, and adverse events (AEs). Results indicate an overall response rate of 23% and a disease control rate of 82%. Median OS and PFS were 15.3 and 8.0 months, respectively. Patients receiving primary chemotherapy exhibited prolonged survival, while bile duct drainage was associated with improved outcomes. Notably, Grade 3 or higher AEs occurred in 54.5% of patients. Overall, GCD chemotherapy demonstrates significant potential for BTC treatment, underscoring the importance of bile duct management in enhancing patient outcomes. Background: Biliary tract cancers (BTCs), including gallbladder and bile duct cancers, have a poor prognosis. Recent advances in chemotherapy, such as using targeted drugs for specific gene mutations, have improved outcomes. Gemcitabine plus cisplatin chemotherapy has been the standard of care for the primary treatment of BTCs, but secondary treatment had not been established until recently. In recent years, durvalumab plus gemcitabine and cisplatin (GCD) chemotherapy is emerging as a promising regimen, although more evidence is needed for its effectiveness. Methods: This retrospective single-center study involved 44 patients receiving GCD treatment between January 2023 and March 2024 with a median follow-up of 10 months. Outcomes focused on overall survival (OS), progression-free survival (PFS), response rates, and adverse events (AEs). Results: The overall response rate (ORR) was 23%, and the disease control rate (DCR) was 82%. The overall median OS and PFS were 15.3 and 8.0 months, respectively, with patients receiving primary chemotherapy experiencing longer survival compared to a control group. Patients who did not undergo bile duct drainage had statistically different better OS and PFS. Grade 3 or higher AEs occurred in 54.5% of patients, with neutropenia and biliary infections being common. Conclusions: GCD chemotherapy shows potential as an effective treatment for BTCs. The favorable treatment outcome was the response rate, particularly in primary therapy or those cases with no metastasis. Bile duct management is crucial for improving patient outcomes. GCD chemotherapy has a high response rate, PFS, and OS compared to other forms of chemotherapy. [ABSTRACT FROM AUTHOR]

Background/Objectives: The effects of ageing on the diaphragm are unclear. This study examined the association between ageing and diaphragm thickness, thickening fraction (TF), and diaphragm excursion (DE) as assessed by ultrasonography after adjusting for other factors. The relationship between these parameters and maximal inspiratory pressure (MIP) was also investigated. Methods: From 2022 to 2024, ambulatory and communicative adult volunteers and outpatients were recruited from four Japanese medical institutions. Each participant's background factors (including height, weight, and underlying diseases) and pulmonary function test results were assessed. Diaphragm thickness, TF, and DE were evaluated using ultrasonography. Results: The study involved 230 individuals with a mean age of 55.5 years (older adults (65 years and over), n = 117; non-older adults, n = 113). In older adults, the diaphragm was thicker (2.1 vs. 1.7 mm, p < 0.001), and TF was lower (88.7% vs. 116.0%, p < 0.001), with no significant difference in DE. Multivariate linear regression analysis adjusted for sex, height, body mass index, and underlying diseases showed positive associations between age and diaphragm thickness (p = 0.001), but not with TF or DE. MIP was positively associated with DE (p < 0.001) but not with thickness or TF. Age was negatively associated with MIP, regardless of diaphragm thickness, TF, and DE (all p < 0.001). Conclusions: As the diaphragm thickens with age, neither thickness nor TF is associated with MIP; only DE is related to MIP. Additionally, ageing is negatively associated with MIP, independent of diaphragm thickness, TF, and DE. Diaphragm function should be assessed using DE rather than thickness or TF. [ABSTRACT FROM AUTHOR]

A colorimetric chemosensor array based on an indicator displacement assay has achieved not only visualization of differences in hormone structures but also quantitative detection of sex hormones in their mixtures. Furthermore, the chemosensor array has allowed the detection of a steroid hormone in diluted human saliva. [ABSTRACT FROM AUTHOR]

BICSTaR (BICtegravir Single Tablet Regimen) is an ongoing, observational cohort study assessing the virologic effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in treatment-experienced (TE) and treatment-naïve (TN) people with HIV across 14 countries over 24 months. We present 12-month outcomes from participants in the BICSTaR Japan cohort. Retrospective and prospective data were pooled from people with HIV aged ≥20 years receiving B/F/TAF within routine clinical care in Japan. Outcomes included virologic effectiveness (primary endpoint; HIV-1 RNA <50 copies/mL), CD4 count, CD4/CD8 ratio, drug-related adverse events (DRAEs), persistence, and patient-reported outcomes (prospective TN cohort only). Overall, 200 participants were enrolled and included in the 12-month analysis population (150 retrospective, 50 prospective; 116 TN and 84 TE). Most participants were male at birth (99%); median age was 34 years in TN and 45 years in TE participants. At 12 months, virologic effectiveness was high: 92% (90/98) of TN and 95% (72/76) of TE participants had HIV-1 RNA <50 copies/mL (missing = excluded analysis). Median (quartile [Q]1, Q3) CD4 cell count increased by +202.0 (126.0, 311.0) cells/μL in TN (p<0.001) and +11.0 (−60.0, 87.0) cells/μL in TE (p = 0.380) participants. Through 12 months, DRAEs were reported by 13% (25/200) of all participants (16% [18/116] TN, 8% [7/84] TE); diarrhea, weight gain, and headache were the most common. Most DRAEs were mild in severity and no severe DRAEs were reported. One TN participant (<1%; 1/116) and two TE participants (2%; 2/84) discontinued B/F/TAF due to DRAEs (macrocytic anemia, vertigo, diarrhea, and headache). Treatment persistence at 12 months exceeded 98% in both TN and TE participants. In prospective TN participants, improvements in bothersome symptom count and quality-of-life measures were observed. B/F/TAF demonstrated high levels of virologic effectiveness and tolerability in people with HIV treated as part of routine clinical care in Japan. [ABSTRACT FROM AUTHOR]

Background: Sarcoglycanopathies (SGPs) are limb-girdle muscular dystrophies (LGMDs) that can be classified into four types, LGMDR3, LGMDR4, LGMDR5, and LGMDR6, caused by mutations in the genes, SGCA, SGCB, SGCG, and SGCD, respectively. SGPs are relatively rare in Japan. This study aims to profile the genetic variants that cause SGPs in Japanese patients. Methods: Clinical course and pathological findings were retrospectively reviewed in Japanese patients with SGP. Genetic analyses were performed using a combination of targeted resequencing with a hereditary muscle disease panel, whole genome sequencing, multiplex ligation-dependent probe amplification, and long-read sequencing. The structures of transcripts with aberrant splicing were also determined by RT-PCR, RNA-seq, and in silico prediction. Results: We identified biallelic variants in SGC genes in 53 families, including three families with LGMDR6, which had not been identified in Japan so far. SGCA was the most common causative gene, accounting for 56% of cases, followed by SGCG, SGCB, and SGCD, at 17%, 21%, and 6%, respectively. Missense variants in SGCA were very frequent at 78.3%, while they were relatively rare in SGCB, SGCG, and SGCD at 11.1%, 18.2%, and 16.6%, respectively. We also analyzed the haplotypes of alleles carrying three variants found in multiple cases: c.229C > T in SGCA, c.325C > T in SGCB, and exon 6 deletion in SGCG; two distinct haplotypes were found for c.229C > T in SGCA, while each of the latter two variants was on single haplotypes. Conclusions: We present genetic profiles of Japanese patients with SGPs. Haplotype analysis indicated common ancestors of frequent variants. Our findings will support genetic diagnosis and gene therapy. [ABSTRACT FROM AUTHOR]

International consensus guidance and Japanese clinical guidelines for myasthenia gravis (MG) recommend achieving minimal manifestations or better status (MM-or-better) as the severity component of the treatment goal. However, the subjective nature of determining MM can result in ambiguity regarding this category in clinical practice and clinical trials. This study analyzed severity metrics in a large number of MG patients to propose criteria for MM-or-better. We utilized data obtained from 3800 MG patients who participated in nationwide cross-sectional surveys in Japan. Among these, 2784 patients with generalized MG were divided into two groups based on MG Foundation of America postintervention status: MM-or-better status (n = 1432); and improved-or-worse (I-or-worse) status (n = 1352). We compared severity metrics (MG-activities of daily living scale [MG-ADL], quantitative MG score [QMG], and MG composite scale [MGC]) between groups and calculated cutoff values to separate the two groups. Using these cutoffs, patients subjectively assigned as MM-or-better were classified into strict MM-or-better (below a cutoff) or optimistic MM-or-better (above a cutoff) groups, and clinical characteristics were then compared. Cutoff values for strict MM-or-better were MG-ADL ≤2, QMG ≤7, and MGC ≤4 (sensitivity 82.0%, 88.7%, and 87.4%; specificity 85.0%, 70.0%, and 77.9%; and accuracy 91.2%, 88.7%, and 90.7%, respectively). Mean values of the revised 15-item MG quality of life scale were significantly lower in the strict MM-or-better group than in the optimistic MM-or-better group. Quantitative criteria for MM-or-better appear likely to be useful in the context of rigorous clinical trials and also as reference information in clinical settings. [ABSTRACT FROM AUTHOR]

The O -glycan composition of jellyfish (JF) mucin (qniumucin: Q-mucin) extracted from three Cubozoan species was studied after the optimization of the purification protocol. Application of a stepwise gradient of ionic strength to anion exchange chromatography (AEXC) was effective for isolating Q-mucin from coexisting impurities. In the three species, the amino acid sequence of the tandem repeat (TR) region in Q-mucin in all three Cubozoans seemed to remain the same as that in all Scyphozoans, although their glycan chains seemed to exhibit clear diversity. In particular, the amounts of acidic moieties on the glycan chains of Q-mucin from the Cubozoans markedly varied even in these genetically close species. In two of the three Cubozoan species, the fraction of disaccharides was large, showing a sharp contrast to that of the glycans of Q-mucin in Scyphozoans. This study also indicates that the simple sequence of TR commonly inherited in all Cubozoan and Scyphozoan JF species after the long term of evolution over 500 M years. According to this research, the glycans and the TR of mucin-type glycoproteins (MTGPs), forming a hierarchical structure, appear to complement each other in the evolutionary changes because the time required for their hereditary conversion is considerably different. The cooperation of these mechanisms is a strategy to achieve the contradictory functions of biosystems, namely species conservation and diversity acquisition. [ABSTRACT FROM AUTHOR]