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Aneurysmal subarachnoid hemorrhage (aSAH) is a critical condition with high in-hospital mortality rates. Delayed cerebral ischemia (DCI), a secondary complication associated with aSAH, can also contribute to morbidity and mortality. Although draining the hematoma from the subarachnoid space has been considered effective in preventing DCI, the placement of a drainage system could increase the risk of bacterial meningitis and ventriculitis. This study aimed to examine the association between meningitis following aSAH and the occurrence of DCI, focusing on the role of cerebral vasospasm. Patients who underwent endovascular coiling or surgical clipping for aSAH from April 2001 to March 2022 were included in this study, while those who did not undergo postoperative drainage were excluded. The patient's clinical characteristics, treatment modalities, and outcomes were then analyzed, after which logistic regression was used to assess the odds ratios (OR) for DCI. A total of 810 patients with aSAH were included in this study. Meningitis following aSAH was identified as an independent factor associated with DCI (odds ratio 5.0 [95% confidence intervals (CI) 2.3-11]). Other significant factors were female sex (odds ratio 1.5 [95% CI 0.89-2.5]) and surgical clipping (odds ratio 2.1 [95% CI 1.3-3.4]). This study demonstrated a significant association between meningitis following aSAH and the development of DCI, suggesting that the inflammatory environment associated with meningitis may contribute to cerebral vasospasm. Early recognition and treatment of meningitis in patients with aSAH could reduce the risk of DCI and improve patient outcomes.

Abstract Based on the D5-brane realization of Wilson line operators in anti-symmetric representations, we propose brane expansion formulas for I N,k , the Schur index of N $$ \mathcal{N} $$ = 4 U(N) SYM decorated by line operators in the anti-symmetric representation of rank k. For the large N index I ∞,k we propose a double-sum expansion, and for finite N index I N,k we propose a quadruple-sum expansion. Objects causing finite k and finite N corrections are disk D3-branes ending on the D5-brane.

Background: Patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) sometimes show unexpected liver, peritoneal, and para-aortic lymph node metastases intraoperatively. Despite radical pancreatectomy, a nonnegligible number of patients relapse within 6 months after surgery. The aim of this study was to identify the preoperative predictors of occult metastases (OM), defined as intraoperative distant metastases or within 6 months after pancreatectomy. Materials and methods: This study included patients with R and BR PDAC who underwent curative-intent pancreatectomy or staging laparoscopy between 2006 and 2021. Multivariate logistic regression and Cox hazard analyses were performed to identify the preoperative predictors of OM and to assess the impact of these factors on prognosis after pancreatectomy. Results: Of the 279 patients, OM was observed intraoperatively in 47 and postoperatively in 34. In the OM group, there were no differences in prognosis between patients who had intraoperative metastases and recurrence within 6 months (median survival time [MST], 18.1 vs. 12.9 months), and between patients who underwent pancreatectomy and those who did not (MST, 13.9 vs. 18.1 months). Preoperative tumor size ≥22 mm (odds ratio [OR], 2.03; 95 % confidence interval [CI], 1.16–3.53; p = 0.013) and preoperative CA19–9 level ≥ 118.8 U/mL (OR, 2.64; 95 % CI, 1.22–5.73; p = 0.014) were significant predictors of OM. Additionally, positive OM predictors were strong independent prognostic factors for overall survival after pancreatectomy (hazard ratio, 2.47; 95 % CI, 1.54–3.98; p

Abstract Monovalent Omicron XBB.1.5 mRNA vaccines were newly developed and approved by the FDA in Autumn 2023 for preventing COVID‐19. However, clinical efficacy for these vaccines is currently lacking. We previously established the quantification of antigen‐specific antibody sequence (QASAS) method to assess the response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination at the mRNA level using B‐cell receptor (BCR) repertoire assay and the coronavirus antibody database (CoV‐AbDab). Here, we used this method to evaluate the immunogenicity of monovalent XBB.1.5 vaccines. We analyzed repeated blood samples of healthy volunteers before and after monovalent XBB.1.5 vaccination (BNT162b2 XBB.1.5 or mRNA‐1273.815) for the BCR repertoire to assess BCR/antibody sequences that matched SARS‐CoV‐2‐specific sequences in the database. The number of matched unique sequences and their total reads quickly increased 1 week after vaccination. Matched sequences included those bound to the Omicron strain and Omicron XBB sublineage. The antibody sequences that can bind to the Omicron strain and XBB sublineage revealed that the monovalent XBB.1.5 vaccines showed a stronger response than previous vaccines or SARS‐CoV‐2 infection before the emergence of XBB sublineage. The QASAS method was able to demonstrate the immunogenic effect of monovalent XBB.1.5 vaccines for the 2023–2024 COVID‐19 vaccination campaign.

We reported the main results of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 4, a nationwide surveillance of therapy (NET) in Japan from January 2015 to December 2019. JR-NET 4 registered consecutive patients who underwent NETs by Japan Society of Neuroendovascular Therapy (JSNET)-certified specialists. The primary endpoint was functional independence (mRS score of 0-2) at 30 days post-NET, with secondary endpoints focusing on technical success and major adverse events within 30 days. A total of 63,230 patients and 60,354 NET procedures from 166 participating centers were analyzed. During the study period, NET cases have consistently increased, with an increase in the proportion of elderly patients. A significant trend shift was observed in the distribution of NET procedures, with endovascular treatment for acute ischemic stroke that showed a dramatic increase in 5 years. This trend aligns with key randomized clinical trials from 2015 that presented the efficacy of this treatment. Clinical outcomes at 30 days posttreatment revealed that endovascular treatment for acute ischemic stroke and other NETs maintained safety and effectiveness despite varying prevalence of functional independence between target diseases. The study also observed a steady increase in emergency treatment cases, reflecting the increase in acute ischemic stroke, a time-sensitive medical condition. This comprehensive surveillance highlights the trend of NET practices in Japan, driven by clinical evidence and advancements in treatment devices. Although these findings were specific to Japan, they offer valuable insights into the broader trends in NETs and acute stroke care.

Ovarian cancer is classified as type 1 or 2, representing low- and high-grade serous carcinoma (LGSC and HGSC), respectively. LGSC arises from serous borderline tumor (SBT) in a stepwise manner, while HGSC develops from serous tubal intraepithelial carcinoma (STIC). Rarely, HGSC develops from SBT and LGSC. Herein, we describe the case of a patient with HGSC who presented with SBT and LGSC, and in whom we analyzed the molecular mechanisms of carcinogenesis. We performed primary debulking surgery, resulting in a suboptimal simple total hysterectomy and bilateral salpingo-oophorectomy due to strong adhesions. The diagnosis was stage IIIC HGSC, pT3bcN0cM0, but the tumor contained SBT and LGSC lesions. After surgery, TC (Paclitaxel + Carbopratin) + bevacizumab therapy was administered as adjuvant chemotherapy followed by bevacizumab as maintenance therapy. The tumor was chemo-resistant and caused ileus, and bevacizumab therapy was conducted only twice. Next-Generation Sequencing revealed KRAS (p.G12V) and NF2 (p.W184*) mutations in all lesions. Interestingly, the TP53 mutation was not detected in every lesion, and immunohistochemistry showed those lesions with wild-type p53. MDM2 was amplified in the HGSC lesions. DNA methylation analysis did not show differentially methylated regions. This case suggests that SBT and LGSC may transform into HGSC via p53 dysfunction due to MDM2 amplification.

The progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations but how these alterations arise is poorly understood. Here we perform haplotype-specific analysis of chromosomal copy-number evolution in the progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data of BE with dysplasia and microscopic EAC foci. We identify distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss. While abnormal mitosis, including whole-genome duplication, underlies chromosomal copy-number changes, segmental alterations display signatures of successive breakage-fusion-bridge cycles and chromothripsis of unstable dicentric chromosomes. Our analysis elucidates how multigenerational chromosomal instability generates copy-number variation in BE cells, precipitates complex alterations including DNA amplifications, and promotes their independent clonal expansion and transformation. In particular, we suggest sloping copy-number variation as a signature of ongoing chromosomal instability that precedes copy-number complexity. These findings suggest copy-number heterogeneity in advanced cancers originates from chromosomal instability in precancerous cells and such instability may be identified from the presence of sloping copy-number variation in bulk sequencing data.

BackgroundThe demand for more accurate and early diagnosis of mild cognitive impairment (MCI) patients due to Alzheimer’s disease (AD) has increased after disease-modifying drugs were launched. Among these needs, there is a requirement for tools that can easily assess the ability to recall memories, which changes early in the disease.ObjectivesWe established Self Assessment Memory Scale (SAMS) method before, which includes 8-picture recall test and 16-word recognition test. We adopted this method to software that can be operated on a tablet computer so that participants can perform the method independently. The purpose of this study was to validate this method.DesignCross sectional research.SettingSome of the participants were recruited from hospitals for patients diagnosed with AD or MCI. The others were recruited from three regional cohorts of healthy older adults.ParticipantsThe total number of participants was 304 (20 of whom had AD or MCI), and the mean age was 71.2 years. 64% of the participants were women.MeasurementsWe used the logical memory subtest of the WMS-R as the standard for memory evaluation and assessed the relationship between this score and the SAMS score calculated by the software.ResultsThe 2nd SAMS score were higher than the 1st SAMS score in some participants, on the other hand, the intraclass correlation coefficient was good. Since the number of false recognition in the 16-word recognition test was higher in participants with lower LM II scores, we developed a new score to reflect the ratio of false recognition, SAMS-R, and we observed it has good correlation with LM II. The mean SAMS-R score decreased gradually after the age of 65 years, indicating that age-related changes in memory recall can be detected. The ROC curve analysis was conducted to evaluate the detectability to determine whether if the WMS-R LM II score is above or below 10, showing that the AUC was greater than 0.9.ConclusionSAMS-R, which can be performed on a tablet literally by himself/herself independently, shows a high correlation with the WMS-R Logical Memory II score, and has the advantage of being performed in a short time without the need for a clinical psychologist or other personnel.

Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a severe and deadly adverse event following ERCP. The ideal method for predicting PEP risk before ERCP has yet to be identified. We aimed to establish a simple PEP risk score model (SuPER model: Support for PEP Reduction) that can be applied before ERCP. Methods: This multicenter study enrolled 2074 patients who underwent ERCP. Among them, 1037 patients each were randomly assigned to the development and validation cohorts. In the development cohort, the risk score model for predicting PEP was established via logistic regression analysis. In the validation cohort, the performance of the model was assessed. Results: In the development cohort, five PEP risk factors that could be identified before ERCP were extracted and assigned weights according to their respective regression coefficients: –2 points for pancreatic calcification, 1 point for female sex, and 2 points for intraductal papillary mucinous neoplasm, a native papilla of Vater, or the pancreatic duct procedures (treated as ‘planned pancreatic duct procedures’ for calculating the score before ERCP). The PEP occurrence rate was 0% among low-risk patients (≤0 points), 5.5% among moderate-risk patients (1–3 points), and 20.2% among high-risk patients (4–7 points). In the validation cohort, the C statistic of the risk score model was 0.71 (95% CI 0.64–0.78), which was considered acceptable. The PEP risk classification (low, moderate, and high) was a significant predictive factor for PEP that was independent of intraprocedural PEP risk factors (precut sphincterotomy and inadvertent pancreatic duct cannulation) (OR 4.2, 95% CI 2.8–6.3; p

BackgroundKnee osteoarthritis (KOA) is the most common form of arthritis in adults and a leading cause of years lived with disability, representing a significant burden on healthcare worldwide.ObjectiveDescribe the structure and educational elements of the Knee-SCHOOL, a brief patient-centered multidisciplinary educational program for patients with KOA.DesignObservational prospective study.SettingAcademically affiliated rehabilitation outpatient center in Brazil.MethodsThe program consisted of three in-person educational sessions (4.5 hr each) for 55 community dwelling adults, aged ≥50 years, with primary KOA-related pain. Study measures included demographic data (age, sex, and educational level), pain duration (years), pain intensity (visual analogue scale), affected knee (right, left, or both knees), comorbidities (presence of hypertension, diabetes, and hypercholesterolemia), Body Mass Index (BMI), Bristol Stool Scale, Adapted Healthy Eating Index (AHEI), bioelectrical impedance, daytime sleepiness, and the impact of the KOA on pain, symptoms, activities of daily living, recreation, and quality of life. Participants attended educational sessions delivered by a multidisciplinary team (two physicians, two nurses, two physical therapists, one occupational therapist, one dietitian, one psychologist, one social worker, and one physical educator) addressing several aspects of KOA. They also participated in supervised exercise practice and a home exercise program.ResultsFifty-five subjects completed the study. The mean age was 67.73 (± 7.73) years; most were females (70.9%), 92.7% had bilateral KOA, with mean pain duration of 12.41 (± 10.17) years. The mean BMI was 32.52 (± 5.99), 65.5% were obese, and 96.4% reported an inadequate diet. KOA had a more negative impact on sports, recreation and quality of life. Daytime sleepiness was uncommon. The mean pain intensity, measured with visual analogue scale, score reduced from 5.52 (± 2.11) at baseline to 4.04 (± 2.38) after the program (week 2). The effect size was 0.7 (95% CI 0.32 to 1.07). All participants received the program well, with no drop-out rates or reported adverse events.ConclusionThe Knee-SCHOOL utilized a multidisciplinary educational approach and an exercise practice addressing multiple aspects of KOA pain. While more studies are needed to assess the longitudinal impact of the program, it was promising in managing pain.

IntroductionChemoradiation therapy (CRT) with concurrent high-dose cisplatin (CDDP) is one of the standard treatment options for locally advanced head and neck cancer. Since the indications specific to the older population have not been reported, we conducted a multicenter survey on the indications.MethodsIn April and May 2023, a questionnaire survey was emailed to all institutions belonging to the JCOG-HNCSG, consisting of 37 institutions.ResultsThe major factors influencing the indications for high-dose CDDP were renal function and performance status (PS). The majority agreed that the treatment is administered to patients aged 65–74 years with PS 0–1 and 65–74 years with eGFR ≥60 (ml/ min/1.73m2), and not in patients aged ≥75 years with PS 2, ≥80 years with PS 1, and ≥65 years with eGFR

Introduction Work engagement enhances nurses’ physical and mental health, well-being, job performance and satisfaction. This reduces turnover rates and improves patient care quality, making work engagement a crucial factor in the nursing workplace. However, no systematic review or meta-analysis has explored the effects of randomised controlled trial (RCT) interventions aimed at improving nurses’ work engagement. This study aimed to evaluate the effectiveness of these interventions, providing healthcare organisations with evidence-based recommendations for enhancing work engagement among nurses.Methods and analysis This systematic review and meta-analysis will use the PICO criteria: (P) nurses, (I) psychosocial interventions, (C) no intervention or non-work engagement interventions and (O) work engagement as a primary outcome. Published studies will be searched by September 2025 using databases such as the Cochrane Central Register of Controlled Trials, PubMed (MEDLINE), Embase, CINAHL, PsycINFO, PsycARTICLES and the Japan Medical Abstracts Society. Eligible studies must use RCT designs, assess the impact of interventions on nurses’ work engagement and provide adequate data (sample sizes, means and SDs) to calculate effect sizes with 95% CIs. Publications must be written in English or Japanese as original articles. Two reviewers will independently select studies and assess the risk of bias. The methodological quality of the included studies will be evaluated using the Grading of Recommendation Assessment, Development and Evaluation approach. A meta-analysis will be conducted for statistical synthesis and publication bias will be assessed using Egger’s test and a visual funnel plot. Heterogeneity will be evaluated using Q statistics.Ethics and dissemination This systematic review and meta-analysis are based on existing studies and do not require ethical approval. The findings will be shared through publications in peer-reviewed international journals and presentations at relevant conferences, symposia and seminars.PROSPERO registration number CRD42024510479.

To enhance plant biomass production under low nitrogen conditions, we employed a method to artificially and temporarily accumulate the bacterial second messenger, guanosine tetraphosphate (ppGpp), to modify plastidial or mitochondrial metabolism. Specifically, we fused a chloroplast or mitochondrial transit-peptide to the N-terminus of the bacterial ppGpp synthase YjbM, which was conditionally expressed by an estrogen-inducible promoter in Arabidopsis. The resulting recombinant Arabidopsis plants exhibited estrogen-dependent ppGpp accumulation in chloroplasts or mitochondria and showed reduced fresh weight compared to wild type (WT) plants when grown on agar-solidified plates containing a certain amount of estrogen. This finding aligns with the previous study indicating that plastidial ppGpp levels can influence plant biomass production. When the recombinant plants were grown in the soil with estrogen and low nitrogen-containing water at specific time intervals, they exhibited greater fresh weight than WT plants. These results suggest that the conditional accumulation of ppGpp in not only chloroplasts, but also in mitochondria can lead to improved plant biomass production in soil with low nitrogen applications.

Abstract Aim Assessing symptoms and daily functioning in patients with major depressive disorder (MDD) can be challenging, as their limited self‐monitoring abilities may result in behavior observed during structured interviews not accurately reflecting their daily lives. This study aimed to determine if specific occupational behaviors could distinguish individuals with MDD from healthy individuals. Methods Baseline data were collected from medical records and activity programs. Three occupational therapists conducted content analysis to assess occupational performance characteristics. Chi‐squared tests compared the prevalence of these characteristics between patients with MDD and healthy controls. Multivariable logistic regression controlled for potential confounders, with independent variables selected based on clinical relevance and sample size (p

Background: Several previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) and oxytocin are associated with dementia, depression, and mental health. The aim of this study was to measure the serum BDNF and oxytocin levels of community-dwelling older adults and evaluate the relationship between the two biomarkers in the study cohort. Methods: This survey was conducted between November 2016 and September 2017 in Kurokawa-cho, Imari, Saga Prefecture, Japan, and the participants were community-dwelling older adults aged ≥ 65 years old. Their blood samples were collected for the measurement of their serum BDNF and oxytocin levels using enzyme-linked immunosorbent assays. The relationship between serum BDNF and oxytocin levels was analyzed using correlation and multiple regression analyses. Results: A total of 95 participants (25 men and 70 women; mean age: 78.24 ± 3.85 years and 77.96 ± 5.52 years, respectively) were analyzed. The results of the analyses indicated that serum BDNF level was positively associated with serum oxytocin level, even after adjusting for age, sex, and years of education. Conclusion: The results of this study suggest that BDNF and oxytocin may interact in older adults and may be associated with maintaining good mental health among them.

Background Although endovascular therapy (EVT) is effective for large ischemic region strokes, the impact of hyperglycemia remains unclear. Methods and Results We analyzed data from the RESCUE‐Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism‐Japan Large Ischemic Core) trial, which randomized stroke patients with Alberta Stroke Program Early Computed Tomography Score of 3 to 5 to EVT versus medical management. Outcomes were compared among patients with normoglycemia (

Summary: Macroautophagy (autophagy) involves the formation of phagophores that mature into autophagosomes. The impact of inhibiting autophagosome closure remains unclear. Here, we report the generation and analysis of mice with impaired autophagosome closure by targeting the ubiquitin E2 variant-like (UEVL) β strands of the endosomal sorting complex required for transport (ESCRT) I subunit VPS37A. The VPS37A UEVL mutation (Δ43–139) impairs bulk autophagic flux without disrupting ESCRT-I complex assembly and endosomal function. Homozygous mutant mice exhibit signs of autophagy impairment, including p62/SQSTM1 and ubiquitinated protein accumulation, neuronal dysfunction, growth retardation, antioxidant gene upregulation, and tissue abnormalities. However, about half of the mutant neonates survive to adulthood without severe liver injury. LC3 proximity proteomics reveals that the VPS37A UEVL mutation leads to active TANK-binding kinase 1 (TBK1) accumulation on phagophores, resulting in increased p62 phosphorylation and inclusion formation. These findings reveal a previously unappreciated role of LC3-conjugated phagophores in facilitating protein aggregation and sequestration, potentially alleviating proteotoxicity.

Background & Aims: Polystyrene microplastics (PS-MPs) are pervasive in our daily life and can be ingested by the human body through bioaccumulation, causing organ damage, especially liver damage. However, the effect of PS-MPs bioaccumulation on human hepatotoxicity and their metabolism remains unclear. Recent studies have demonstrated that PS-MPs cause lipid and bile acid metabolism disorders. The human hepatobiliary organoids (HBOs) regenerated from chemically induced liver progenitor cells converted by mature hepatocytes and the bile duct provides a bioengineering model for liver disease and hepatic metabolism. Approach & Results: Exposure of HBOs to PS-MPs with a diameter of 1 µm for 48 h causes hepatotoxicity, hepatocyte damage, and changes in bile acid metabolism. PS-MPs could be accumulated into the bile ducts of HBOs, which can be promoted by ursodeoxycholic acid, increasing bile flow and volume by activating the bile transporter of BSEP in a dose-dependent manner along with MRP-2. The accumulation of PS-MPs in the bile duct was able to be inhibited by the bile transporter inhibitor of troglitazone that could inhibit the transporters of BSEP and MRP-2, which increased the hepatotoxicity caused by PS-MPs. Conclusions: This study provides insights into the metabolic pathways of PS-MPs in the liver and suggests potential therapeutic strategies to reduce MP-induced liver damage.

We report a method for the synthesis of symmetrical bibenzyls by the reductive dimerization of benzylic halides using sodium dispersion (SD). SD, a reagent consisting of sodium particles dispersed in mineral oil, has recently attracted attention as a safer but more reactive source of sodium than sodium lump. We have found that the reductive dimerization of benzylic halides proceeds within 1 h at room temperature in tetrahydrofuran (THF) solvent using SD as a reducing agent. This method is highly sustainable for the synthesis of symmetrical bibenzyls since it uses sodium, which is abundant on earth. As the SD-derived mineral oil in the crude product can be readily removed, three natural products were synthesized on a gram scale without the need for column chromatography. The utility of this reaction was also exemplified by a decagram-scale reaction using 2-methyltetrahydrofuran, known as a green alternative solvent to THF.

Background: The relationship between patterns of outpatient oral loop diuretic (LD) dose reduction and prognosis in patients with heart failure (HF) remains unclear. Methods: We evaluated 679 patients with HF-prescribed LDs at baseline between September 2015 and August 2019. Dose reduction was defined as a change to a lower LD dose than the previous outpatient dose. Dose intensification was defined as a change to a higher LD dose than the previous outpatient dose. Patients were classified into no-reduction (no LD dose reduction during follow-up) and reduction groups (categorized into successive-reduction [≥2 successive LD dose reductions without intervening LD dose intensification] and single-reduction [LD dose reduction without successive dose reduction] groups). The primary outcomes were all-cause death, HF hospitalization (HFH), and the composite of cardiovascular death (CVD) or HFH. Results: Within a median follow-up of 53.7 (range, 2.6–99.1) months, 156 deaths were recorded: 121 (29 %), 31 (15 %), and three (4 %) patients in the no-reduction (n = 411), single-reduction (n = 195), and successive-reduction (n = 73) groups, respectively. After adjusting for cofounders, the reduction group had a lower risk of primary outcomes than the no reduction group (all-cause death: hazard ratio (HR) = 0.65, 95 % confidence interval (CI) = 0.44–0.96; CVD or HFH: HR=0.69, 95 %CI=0.52–0.93; HFH: HR=0.69, 95 % CI=0.52–0.93). The successive-reduction group had a lower risk of the composite of CVD or HFH (HR=0.26, 95 % CI: 0.10–0.67) and HFH (HR=0.34, 95 % CI=0.13–0.86) than the single-reduction group. Conclusions: Outpatient LD dose reduction patterns can be indicators of good prognosis in HF patients.

Aim: Whether house dust mite (HDM) sublingual immunotherapy (SLIT) is effective for the skin symptoms of adult atopic dermatitis (AD) is unclear.Methods: HDM SLIT was added to conventional AD treatment for 10 HDM-sensitized AD patients with rhinitis for 2 years.Results: Seven out of ten enrolled patients completed the study. Eczema Area and Severity Index score was significantly reduced when comparing before treatment and at 24 months follow-up. CD203c ratio in the basophil activation test using HDM extract, skin prick test with HDM extract and Dermatophagoides pteronyssinus/Dermatophagoides farinae specific-IgG4 tended to improve when comparing before treatment and after treatment.Conclusion: HDM SLIT might be a therapeutic option for AD patients with rhinitis who are sensitized to HDM.

Mammalian brains have evolved a neocortex, which has diverged in size and morphology in different species over the course of evolution. In some mammals, a substantial increase in the number of neurons and glial cells resulted in the expansion and folding of the cerebrum, and it is believed that these evolutionary changes contributed to the acquisition of higher cognitive abilities in mammals. However, their underlying molecular and cellular mechanisms remain insufficiently elucidated. A major difficulty in addressing these mechanisms stemmed from the lack of appropriate animal models, as conventional experimental animals such as mice and rats have small brains without structurally obvious folds. Therefore, researchers including us have focused on using ferrets instead of mice and rats. Ferrets are domesticated carnivorous mammals with a gyrencephalic cerebrum, and, notably, they are amenable to genetic manipulations including in utero electroporation to knock out genes in the cerebrum. In this review, we highlight recent research into the mechanisms underlying the development and evolution of cortical folds using ferrets.

BackgroundWe aimed to clarify the association between intraoperative P2Y12 inhibitor administration during EVT and clinical outcomes in patients with anterior circulation TO stroke.MethodsAmong consecutive patients with acute ischemic stroke (AIS) enrolled in the Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolic and Atherothrombotic Stroke with Large Vessel Occlusion Registry from 2016 to 2019, those with anterior circulation TOs who underwent EVT were analyzed. These patients were categorized into the following groups: those who received P2Y12 inhibitors during the perioperative period and those who did not receive P2Y12 inhibitors. The outcomes included good functional outcomes, as indicated by a modified Rankin Scale score of 0–2 at 90 days, and the incidence of symptomatic intracranial hemorrhage (SICH) was compared between the two groups. Multivariate logistic regression models were used to assess the association of outcomes with perioperative P2Y12 inhibitor administration. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the group that did not receive P2Y12 inhibitors as the reference. The perioperative period included the period in which antithrombotic therapy was administered immediately before EVT and during the operative period.ResultsWe enrolled 242 patients with AIS with anterior circulation TOs (42 females [17.4%]; median age, 76 [interquartile range, 69–81] years). Patients who received P2Y12 inhibitors during the perioperative period (n = 131) showed a higher frequency of carotid artery stenting than those who did not receive perioperative P2Y12 inhibitors (n = 111; 86.3% vs. 42.3%, p

Background Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent trabeculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC. Methods and Results We recruited children with left ventricular noncompaction from Japanese multi‐institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated cardiomyopathy, or normal function. In these patients, cardiomyopathy‐associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0–6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate (P=0.0009). Conclusions Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease‐causing genes and phenotype may help identify specific patients with left ventricular noncompaction and mortality‐related cardiac phenotypes.

A patient with GATA2 deficiency developed corticosteroid-responsive sterile granulomatous lung disease despite monocytopenia. The presence of B-lymphopenia, autoimmunity, an elevated level of serum B-cell–activating factor, and pulmonary plasma cell infiltration, which together suggested an underlying mechanism similar to that of combined variable immunodeficiency lung disease.

IntroductionShoulder pain is the third leading cause of musculoskeletal complaints in primary care clinics. Its prevalence varies from 14% to 34%. Among all the structures that can cause shoulder pain, the most vulnerable to injury is the tendon of the supraspinatus muscle. The ideal management protocol is still unknown. To date, little is known in the literature about the use of ultrasound-guided suprascapular nerve block as a treatment for supraspinatus muscle tendinitis. Our objective was to assess the effects of the association of a single ultrasound-guided suprascapular nerve block combined with home-based rotator cuff exercises to reduce pain and improve shoulder functioning in patients with supraspinatus tendinitis.MethodsWe evaluated the effect of a single ultrasound-guided suprascapular nerve block on pain and functioning of people with supraspinatus tendinitis. Diagnosis was performed using the positive Jobe test. Due to large disparity between clinical and radiological findings, only clinical diagnostic criteria were used to select patients. This was a double-blind, randomized, controlled, clinical study in which patients in the intervention group (n = 42) received a single injection of 5 ml of 2% lidocaine, while in the control group (n = 41) patients underwent the same procedure receiving saline solution 0.9%. All patients received face to face instructions by an experienced physiotherapist and a leaflet explaining home-based exercises. Pain and functioning were assessed using the Shoulder Pain and Disability Index (SPADI) questionnaire before the procedure, one week and 12 weeks after the procedure.ResultsPatients in both groups improved significantly since the initial evaluation until the 12th week. Intervention group SPADI (pre, 1 week, 12 weeks): 75.80 ± 18.96, 56.25 ± 31.37, 46.31 ± 31.41 (p