Pharmacological Properties of JTE-151; A Novel Orally Available RORγ Antagonist That Suppresses Th17 Cell-Related Responses and .

Retinoid-related orphan receptor-γ (RORγ) is a nuclear receptor that plays important roles in the development and activation of T helper type-17 (Th17) cells. In this study, we characterized the pharmacological profile of JTE-151 ((4S)-6-[(2-chloro-4-methylphenyl)amino]-4-{4-cyclopropyl-5-[cis-3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3yl}-6-oxohexanoic acid), which is a novel RORγ antagonist identified by our group. JTE-151 dissociated co-activator peptide from the human RORγ-ligand binding domain (LBD) and recruited co-repressor peptide into human RORγ-LBD, and potently inhibited the transcriptional activity of RORγ of human, mouse and rat.

A pituitary gland squeezed upward by intrasellar kissing carotid arteries: Mimicking a pituitary microadenoma.

Background: Intrasellar kissing carotid arteries are a rare variant in which bilateral internal carotid arteries run very near each other at their cavernous sinus portion. We encountered a woman with the pituitary gland mimicking a pituitary microadenoma because the pituitary gland was compressed bilaterally by intrasellar kissing carotid arteries.

Case Description: A 61-year-old woman with a chronic headache underwent magnetic resonance imaging, which revealed a sellar mass measuring 10.

Validity and reliability of the Checklist for Habitual Physical Activity for people 75 years and older in Japan.

Background: Despite health benefits, many older adults struggle to meet physical activity guidelines, leading to stagnant activity levels. While integrating physical activity into daily routines has been proposed as a promising strategy for older adults, fit-for-purpose measurement tools to assess such routines are lacking. The Checklist for Habitual Physical Activity (CHaPA) was developed based on the positive deviance approach and socio-ecological model to assess daily behaviours encouraging physical activity among adults aged 75 and older.

Prospective therapeutic studies of disseminated extranodal large B-cell lymphoma including intravascular large B-cell lymphoma.

This study aimed to establish a standard treatment for disseminated extranodal large B-cell lymphoma, including intravascular large B-cell lymphoma (DEN-LBCL/IVL), and to validate the clinical diagnostic criteria we proposed. Between 2006 and 2016, 22 patients were enrolled in a clinical trial conducted by the Hokuriku Hematology Oncology Study Group. The first cycle of chemotherapy consisted of dose-reduced cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with delayed administration of rituximab.

CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes.

Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency, centromeric instability, and facial anomalies syndrome, characterized by DNA hypomethylation at heterochromatin. It remains unclear why CDCA7-HELLS is the sole nucleosome remodeling complex whose deficiency abrogates the maintenance of DNA methylation. We here identify the unique zinc-finger domain of CDCA7 as an evolutionarily conserved hemimethylation-sensing zinc finger (HMZF) domain.

Endovascular treatment of unruptured aneurysm arising from duplicate origin of the middle cerebral artery - A case report and literature review.

Background: Duplicate origin of the middle cerebral artery (MCA) is a rare variation of MCA, often mislabeled as the fenestration of the M1 segment of MCA.

Case Description: The authors treated an unruptured aneurysm, 8 mm in diameter, associated with a duplicate origin of MCA in a 42-year-old woman who underwent magnetic resonance imaging for transient vertigo. Clipping surgery was inapplicable due to the lack of space to insert clip blades between the neck and two origins of MCA.

Structure of human DPPA3 bound to the UHRF1 PHD finger reveals its functional and structural differences from mouse DPPA3.

DNA methylation maintenance is essential for cell fate inheritance. In differentiated cells, this involves orchestrated actions of DNMT1 and UHRF1. In mice, the high-affinity binding of DPPA3 to the UHRF1 PHD finger regulates UHRF1 chromatin dissociation and cytosolic localization, which is required for oocyte maturation and early embryo development.

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation.

The radical hydroarylation of alkenes is an efficient strategy for accessing linear alkylarenes with high regioselectivity. Herein, we report the electroreductive hydroarylation of electron-deficient alkenes and styrene derivatives using (hetero)aryl halides under mild reaction conditions. Notably, the present hydroarylation proceeded with high efficiency under transition-metal-catalyst-free conditions.

Synthesis of Zwitterionic Phospholipid-Connected Silane Coupling Agents and Their Hybridization with Graphene Oxide.

The hybridization of lipids with graphene is expected to produce a promising, novel biomaterial. However, there are limited examples of the covalent introduction of lipid molecules, especially the immobilization of lipid molecules, onto graphene on a substrate. Therefore, we investigated the hybridization of a silane coupling agent having phospholipid moieties with graphene oxide on substrates prepared by photo-oxidation using chlorine dioxide.

Fatal hemophagocytic lymphohistiocytosis with intravascular large B-cell lymphoma following coronavirus disease 2019 vaccination in a patient with systemic lupus erythematosus: an intertwined case.

Hemophagocytic lymphohistiocytosis (HLH) has been recognized as a rare adverse event following the coronavirus disease 2019 (COVID-19) vaccination. We report a case of neuropsychiatric symptoms and refractory HLH in a woman with systemic lupus erythematosus (SLE) after receiving her COVID-19 vaccine treated with belimumab, later found to have intravascular large B-cell lymphoma (IVLBCL) at autopsy. A 61-year-old woman with SLE was referred to our hospital because of impaired consciousness and fever.

Decreased moment of inertia of the lower limb facilitates a rapid hip internal rotation in a simulated foot impact maneuver. A laboratory-controlled biomechanical study for a precursor mechanism of noncontact anterior cruciate ligament injury.

Background: Anterior cruciate ligament injury frequently occurs in the deceleration with the knee-extended position. In addition, a rapid hip internal rotation is concomitantly observed. However, how the extended knee position induces the hip internal rotation is unclear.

Effect of ferric citrate hydrate on fibroblast growth factor 23 and platelets in non-dialysis-dependent chronic kidney disease and non-chronic kidney disease patients with iron deficiency anemia.

Background: Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA.

Methods: In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.

Secondary fracture and mortality risk with very high fracture risk osteoporosis and proximal femoral fracture.

Introduction: We aimed to investigate secondary fracture and mortality rates, and risk factors in patients with proximal femoral fractures.

Materials And Methods: We conducted a multicenter prospective cohort study on female patients with proximal femoral fractures who underwent surgical treatment between April 2020 and March 2021. Postoperative follow-ups were performed at 6-, 12-, 18-, and 24-month intervals to determine the secondary fracture and mortality rates, and the risk factors and its influence were examined.

Checklist for Habitual Physical Activity (CHaPA) for adults 75 years and older: tool development and content and face validation.

Background: Physical activity significantly contributes to older adults' physical and mental health, suggesting that physical activity could enhance healthy life expectancy. Despite its importance for adults aged 75 and older, activity levels among a large proportion of individuals aged 75 and older in Japan do not meet the recommended levels of physical activity, indicating a need for specific strategies tailored to this age group. This study aimed to develop a screening tool that measures daily activities promoting physical activity among older adults and assessed its content and face validity.

Absorption function loss due to the history of previous ankle sprain explored by unsupervised machine learning.

Background: Ankle sprains are common and cause persistent ankle function reduction. To biomechanically evaluate the ankle function after ankle sprains, the ground reaction force (GRF) measurement during the single-legged landing had been used. However, previous studies focused on discrete features of vertical GRF (vGRF), which largely ignored vGRF waveform features that could better identify the ankle function.

[Image Diagnosis of Trigeminal Neuralgia].

Classic trigeminal neuralgia is mainly caused by arterial compression; most cases involve the superior cerebellar artery, followed by the anterior cerebellar, basilar, and vertebral arteries. The detection of neurovascular conflicts in trigeminal neuralgia requires special magnetic resonance imaging(MRI)modalities, including high-resolution three-dimensional(3D)-T2 sequence, 3D-time of flight angiography, 3D-T1 sequencing with gadolinium injection, and merged images of these sequences. The conflicting sites are not necessarily restricted to the root entry zone of the trigeminal nerve root and can be located more distally, proximal to the Meckel's cavum.

Cryo-electron microscopy reveals the impact of the nucleosome dynamics on transcription activity.

The structural biology of nucleosomes and their complexes with chromatin-associated factors contributes to our understanding of fundamental biological processes in the genome. With the advent of cryo-electron microscopy (cryo-EM), several structures are emerging with histone variants, various species and chromatin-associated proteins that bind to nucleosomes. Cryo-EM enables visualization of the dynamic states of nucleosomes, leading to the accumulation of knowledge on chromatin-templated biology.

CDCA7 is a hemimethylated DNA adaptor for the nucleosome remodeler HELLS.

Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, characterized by hypomethylation at heterochromatin. The unique zinc-finger domain, zf-4CXXC_R1, of CDCA7 is widely conserved across eukaryotes but is absent from species that lack HELLS and DNA methyltransferases, implying its specialized relation with methylated DNA. Here we demonstrate that zf-4CXXC_R1 acts as a hemimethylated DNA sensor.

Discovery and SAR of JTE-151: A Novel RORγ Inhibitor for Clinical Development.

A number of RORγ inhibitors have been reported over the past decade. There were also several examples advancing to human clinical trials, however, none of them has reached the market yet, suggesting that there could be common obstacles for their future development. As was expected from the general homology of nuclear receptor ligands, insufficient selectivity as well as poor physicochemical properties were identified as potential risks for a RORγ program.

Patients of idiopathic normal-pressure hydrocephalus have small dural sac in cervical and upper thoracic levels: A supposed causal association.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder presenting a triad including dementia and ventricular enlargement. The mechanism causing excessive cerebrospinal fluid (CSF) accumulation in the ventricles in iNPH is poorly understood. We hypothesized that the age-related degradation of the spinal shock-absorbing system composed of a spinal dural sac (SDS) and surrounding soft tissue, preventing ventricular enlargement caused by wide CSF pulsation driven by heartbeats, may be involved in the ventricular enlargement observed in iNPH.

Cooperative DNA-binding activities of Chp2 are critical for its function in heterochromatin assembly.

Heterochromatin protein 1 (HP1) is an evolutionarily conserved protein that plays a critical role in heterochromatin assembly. HP1 proteins share a basic structure consisting of an N-terminal chromodomain (CD) and a C-terminal chromoshadow domain (CSD) linked by a disordered hinge region. The CD recognizes histone H3 lysine 9 methylation, a hallmark of heterochromatin, while the CSD forms a dimer to recruit other chromosomal proteins.

Paravertebral Cerebrospinal Fluid Exudation in Young Women with Postdural Puncture Headache: A Hypothetical Interpretation based on Anatomical Study on Intervertebral Foramen.

 Postdural puncture headache (PDPH) is defined as a prolonged orthostatic headache secondary to a lumbar puncture. The mechanism underlying this unpleasant complication and the reasons explaining its higher incidence in the young are not well understood. Here, we speculate on the mechanisms underlying PDPH based on spinal magnetic resonance imaging (MRI) in patients with PDPH and an anatomical study on the size of the intervertebral foramen.

Comparison of the Efficacy of Zoledronate Acid or Denosumab After Switching from Romosozumab in Japanese Postmenopausal Patients.

We aimed to compare the efficacy of switching from romosozumab (RMAb) to denosumab (DMAb) or zoledronic acid (Zol) with respect to changes in bone mineral density (BMD) and bone metabolism. We also aimed to determine predictors of changes in BMD among patients who received sequential therapy from RMAb. One hundred patients who received RMAb therapy were recruited for this study.