Monoallelic expression can govern penetrance of inborn errors of immunity.

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy. Incomplete penetrance is common among IEIs despite their monogenic basis. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele, to phenotypic variability observed in families with IEIs.

Early initiation of intravenous cyclophosphamide and one-year outcome in super-refractory cryptogenic-new onset refractory status epilepticus.

To explore the potential efficacy of early initiation of intravenous cyclophosphamide (IVCPA), we reviewed consecutive four cases of super-refractory cryptogenic-new onset refractory status epilepticus (C-NORSE) between 2015 and 2023. We compared functional outcomes at 3 months and 1 year after the onset between patients who received IVCPA within 20 days (early-treated) and those who received it later (late-treated). All patients (median age: 43 years) had a prodromal fever.

Impact of Fusobacterium nucleatum in the treatment of cancer, including radiotherapy and its future potential in esophageal cancer.

Despite advances in multimodality therapy, including surgery, chemotherapy, radiation therapy and chemoradiation, the fatality rate for esophageal cancer remains high. Specifically, Fusobacterium nucleatum, due to its aggregation capacity, has shown a tendency to form biofilms. The biofilm-forming capabilities of microbial communities are of utmost importance in the context of cancer treatment, as they have been shown to drive significant losses in the efficaciousness of various cancer treatments.

Association between lipid-rich plaques and thrombus formation after excimer laser coronary angioplasty in in-stent restenosis and de novo lesions.

Excimer laser coronary angioplasty (ELCA) in percutaneous coronary intervention (PCI) is safe and effective. However, thrombotic complications after ELCA occasionally occur. This study aimed to evaluate the impact of lipid-rich plaque in both in-stent restenosis (ISR) and de novo lesions on thrombus formation and transient no-reflow after ELCA.

Long-term changes in carotid intima-media thickness according to baseline blood pressure level: J-STARS Echo study.

Background And Aims: We aimed to investigate long-term changes in carotid intima-media thickness (IMT) based on baseline blood pressure (BP) levels in non-cardioembolic stroke patients.

Methods: Patients aged 45-80 years with dyslipidemia who were not on statins before enrollment and had experienced a non-cardioembolic stroke were assigned to either the pravastatin group or the control group in a randomized trial. Patients were classified into three groups according to BP levels: normal BP (N-group: systolic BP [sBP] <140 mmHg and diastolic BP [dBP] <90 mmHg), highly elevated BP (G2 group: sBP ≥160 mmHg or dBP ≥100 mmHg), and mildly elevated BP (G1 group: the remaining patients).

AQUABEAM robotic system use-results survey: Aquablation for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia in the Japanese Population.

Objectives: To evaluate the safety, efficacy, and patient-reported outcomes of Aquablation therapy using the AQUABEAM Robotic System for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) in a Japanese population.

Methods: This post-market use-results survey included 103 Japanese men with BPH who underwent Aquablation across five centers with previously Aquablation naïve physicians. Data were collected at baseline, during the procedure, at discharge, and at 3 and 6 months post-procedure.

Time-course assessment of oral intake function and its impact on end-of-life in older individuals over 90 years with frailty.

Aim: The study investigates end-of-life trajectories, focusing on the degree of oral intake function in older individuals with frailty aged over 90 years.

Methods: This retrospective observational study examined individuals aged 90 years and older who passed away at a long-term chronic care hospital and related facilities in Japan. We assessed their Clinical Frailty Scale (CFS) and Function Oral Intake Scale (FOIS), categorizing them into two groups-"preserved CFS" (CFS score ≤7) and "poor CFS" (CFS score ≥8)-considering evaluations conducted 6 months before death.

Fusobacterium nucleatum in the oral cavity is associated with cerebral small vessel disease in patients with ischemic stroke.

Objectives: Periodontal disease is reportedly associated with an increased risk of stroke. Recent evidence suggests that periodontal disease aggravates cerebral small vessel disease (CSVD), including lacunar stroke. However, the periodontal pathogens associated with CSVD remain unclear.

Real-world experience of tixagevimab/cilgavimab prophylaxis in Japanese patients with immunodeficiency.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe illness and mortality in patients with immunodeficiency. Although vaccination has been recommended, the induction of protective antibodies by immunization, and thus the disease-preventive effect, has proven insufficient in immunodeficient patients, especially in those with predominantly antibody deficiency. A monoclonal antibody combination of tixagevimab and cilgavimab (TIX/CIL) was developed as a pre-exposure prophylaxis (PrEP).

Myelin measurement in amyotrophic lateral sclerosis with synthetic MRI: A potential diagnostic and predictive method.

Background: Myelin damage has recently been highlighted as a major causative factor of amyotrophic lateral sclerosis (ALS). Although myelin damage has been pathologically identified in ALS, it has not been clinically evaluated. This study aimed to quantify myelin volume using synthetic MRI to evaluate myelin damage in patients with ALS, and determine its association with clinical parameters.

Dexamethasone palmitate for children with Epstein-Barr virus associated hemophagocytic lymphohistiocytosis.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a wide range of clinical presentations and is sometimes life-threatening. It is often treated with systemic corticosteroids and etoposide, but no optimal treatment has been identified. Dexamethasone palmitate (DP) contains a combination of dexamethasone and a lipid emulsion and is selectively taken up by activated macrophages.

Evaluation of Bone Density for Primary Implant Stability Using a Newly Designed Drill: An In Vitro Study on Polyurethane Bone Blocks.

Objectives: Bone density is an important factor for long-term implant success. Peri-implant bone density evaluation before implant placement can be useful for treatment planning, such as the selection of proper implant size or drilling protocol in each case. In this study, we aimed to establish an objective intraoperative bone density evaluation method by measuring the drilling torque value using a newly designed density measurement drill.

Prolonged diagnostic journey in delayed-onset adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency typically presents as a severe combined immunodeficiency in early infancy, although its onset may be delayed in some cases. We encountered two patients diagnosed with ADA deficiency in adulthood. In addition to previously reported cases, we aimed to identify and characterize the clinical and immunological features associated with delayed- and late-onset ADA deficiency.

ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice.

Acute kidney injury (AKI), typically caused by ischemia, is a common clinical complication with a poor prognosis. Although proteinuria is an important prognostic indicator of AKI, the underlying causal mechanism remains unclear. In vitro studies suggest that podocytes have high ATP demands to maintain their structure and function, however, analyzing their ATP dynamics in living kidneys has been technically challenging.

Interleukin-33 Deficiency Protects the Skin From Ulcer Formation in an Ischemia-Reperfusion-Induced Decubitus Mouse Model.

Interleukin-33 (IL-33) is an alarmin released upon epithelial tissue damage. It functions as a nuclear factor for regulating gene expression. We hypothesised that IL-33 is involved in the formation of decubitus ulcers through damaged epidermis.

The oral cavity is a potential reservoir of gram-negative antimicrobial-resistant bacteria, which are correlated with ageing and the number of teeth.

Objectives: The suppression of antimicrobial-resistant bacteria (ARB) is an important issue worldwide. In recent years, the presence of various ARB in the oral cavity has been reported, but the details remain unclear. Therefore, we aimed to isolate ARB from the oral cavity and investigate the factors affecting ARB colonization.

Serum uric acid is independently associated with impaired nitroglycerine-induced vasodilation of the brachial artery in women.

Experimental and clinical studies have suggested atherosclerotic effects of uric acid (UA) on vascular smooth muscle cells (VSMCs). Nitroglycerine-induced vasodilation (NID), a control test for flow-mediated vasodilation, can be used as a possible marker of VSMC dysfunction. However, there is little information on the association between UA and NID.

CD1530, selective RARγ agonist, facilitates Achilles tendon healing by modulating the healing environment including less chondrification in a mouse model.

Heterotopic ossification (HO) in Achilles tendon often arises due to endochondral ossification during the healing process following trauma. Retinoic acid receptor γ (RARγ) plays a critical role in this phenomenon. This study aims to elucidate the therapeutic effects of CD1530, an RARγ selective agonist, along with the contributing cells, in Achilles tendon healing, utilizing a cell lineage tracing system.

[Drug developmental strategies based on functional analysis of pain-regulating molecules in astrocytes under chronic pain].

Spinal cord astrocytes are activated in chronic pain models, especially under conditions of prolonged pain. Hence, targeting spinal cord astrocytes for the development of useful analgesics has attracted much attention. In the CNS, connexin43 (Cx43), a membrane protein expressed and functioning exclusively in astrocytes, is well known to be involved in intercellular signaling as a component of gap junction, but also interacts with intracellular molecules via its characteristically long C-terminal region, thereby affecting cellular function.

Long-term clinical and endoscopic outcomes of ustekinumab in pediatric Crohn's disease with anti-tumor necrosis factor failure.

Background And Aim: Only a few studies have reported the long-term effects of ustekinumab on pediatric Crohn's disease. Therefore, this study aimed to describe the long-term clinical and endoscopic outcomes of ustekinumab and its safety profile in pediatric-onset Crohn's disease with anti-tumor necrosis factor failure.

Methods: Medical records of patients with pediatric-onset Crohn's disease in whom anti-tumor necrosis factor therapy failed and ustekinumab treatment was initiated from 2017 to 2022 at a Japanese tertiary children's hospital were retrospectively reviewed.

A Non-targeted Proteomics Newborn Screening Platform for Inborn Errors of Immunity.

Purpose: Newborn screening using dried blood spot (DBS) samples for the targeted measurement of metabolites and nucleic acids has made a substantial contribution to public healthcare by facilitating the detection of neonates with genetic disorders. Here, we investigated the applicability of non-targeted quantitative proteomics analysis to newborn screening for inborn errors of immunity (IEIs).

Methods: DBS samples from 40 healthy newborns and eight healthy adults were subjected to non-targeted proteomics analysis using liquid chromatography-mass spectrometry after removal of the hydrophilic fraction.

Association of physical function with masticatory ability and masticatory habits: a cohort study.

Background: Few studies have evaluated masticatory ability and habits in relation to physical function. This study aimed to investigate the association of physical function with both masticatory ability and masticatory habits.

Methods: In this cohort study, we followed up with 146 community-dwelling older adults aged 65-84 years for 1 year.