Characteristics of suitable cases for treatment with nemolizumab based on clinical findings and cutaneous adverse events.

Nemolizumab is an effective treatment for pruritus in atopic dermatitis, but it has a relatively high incidence of cutaneous adverse events (cAEs). To optimize the use of nemolizumab, we investigated the relationship between baseline severity in specific body areas and the frequency of cAEs. Our findings revealed that cases who discontinued treatment with nemolizumab had more severe erythema and edema/papulation on the trunk than those who continued nemolizumab.

Glucose-induced endocytic degradation of the maltose transporter MalP is mediated through ubiquitination by the HECT-ubiquitin ligase HulA and its adaptor CreD in Aspergillus oryzae.

In the filamentous fungus Aspergillus oryzae, large amounts of amylolytic enzymes are inducibly produced by isomaltose, which is converted from maltose incorporated via the maltose transporter MalP. In contrast, the preferred sugar glucose strongly represses the expression of both amylolytic and malP genes through carbon catabolite repression. Simultaneously, the addition of glucose triggers the endocytic degradation of MalP on the plasma membrane.

Heart rate variability and tension-type headache: A population-based cross-sectional study.

Background: The relationship between tension-type headache (TTH) and autonomic functions is poorly understood, although TTH is one of the most prevalent disorders in the general population. The aim of this study was to investigate the direct and indirect effects of TTH on the autonomic functions measured by heart rate variability (HRV).

Methods: This population-based cross-sectional study was carried out in the general population of Ulaanbaatar between July and September in 2020.

An AsCas12f-based compact genome-editing tool derived by deep mutational scanning and structural analysis.

SpCas9 and AsCas12a are widely utilized as genome-editing tools in human cells. However, their relatively large size poses a limitation for delivery by cargo-size-limited adeno-associated virus (AAV) vectors. The type V-F Cas12f from Acidibacillus sulfuroxidans is exceptionally compact (422 amino acids) and has been harnessed as a compact genome-editing tool.

Quality of life in the general population of Mongolia: Normative data on WHOQOL-BREF.

No data on the quality of life (QOL) of the general population are available for Mongolia. This study aimed to determine normative data on the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF) in the general population of Mongolia. This nationwide, population-based, cross-sectional study was conducted in 48 sampling centers across Mongolia in 2020.

Structural alterations in the amygdala and impaired social incentive learning in a mouse model of a genetic variant associated with neurodevelopmental disorders.

Copy number variants (CNVs) are robustly associated with psychiatric disorders and their dimensions and changes in brain structures and behavior. However, as CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations in the brains of 22q11.

PAM-flexible Cas9-mediated base editing of a hemophilia B mutation in induced pluripotent stem cells.

Background: Base editing via CRISPR-Cas9 has garnered attention as a method for correcting disease-specific mutations without causing double-strand breaks, thereby avoiding large deletions and translocations in the host chromosome. However, its reliance on the protospacer adjacent motif (PAM) can limit its use. We aimed to restore a disease mutation in a patient with severe hemophilia B using base editing with SpCas9-NG, a modified Cas9 with the board PAM flexibility.

The Brain Overwork Scale: A Population-Based Cross-Sectional Study on the Psychometric Properties of a New 10-Item Scale to Assess Mental Distress in Mongolia.

Identifying mental distress is a complex task, particularly when individuals experience physical symptoms. Traditional self-report questionnaires that detect psychiatric symptoms using emotional words may not work for these individuals. Consequently, there is a need for a screening tool that can identify both the physical and mental symptoms of mental distress in individuals without a clinical diagnosis.

Successful liver transduction by re-administration of different adeno-associated virus vector serotypes in mice.

Background: Intravenous administration of adeno-associated virus (AAV) vectors is a promising gene therapy approach for monogenic diseases. However, re-administration of the same AAV serotype is impossible because of the induction of anti-AAV neutralizing antibodies (NAbs). Here, we examined the feasibility of re-administrating AAV vector serotypes different from the initial AAV vector serotype.

[Application of genome editing technology in gene therapy].

Genome editing has been attracting increasing attention as a new treatment for several refractory diseases since the CRISPR-Cas discovery has facilitated easy modification of target chromosomal DNA. The concept of treating refractory diseases by genome editing has been achieved in various animal models, and genome editing has been applied to human clinical trials for β-thalassemia, sickle cell disease, mucopolysaccharidosis, transthyretin amyloidosis, HIV infection, and CAR-T therapy. The genome editing technology targets the germline in industrial applications in animals and plants and is directed at the chromosomal DNA of the somatic cells in human therapeutic applications.

The seroprevalence of neutralizing antibodies against the adeno-associated virus capsids in Japanese hemophiliacs.

Adeno-associated virus (AAV) vectors are promising modalities of gene therapy to address unmet medical needs. However, anti-AAV neutralizing antibodies (NAbs) hamper the vector-mediated therapeutic effect. Therefore, NAb prevalence in the target population is vital in designing clinical trials with AAV vectors.

Mesoscopic-scale grain formation in HfO-based ferroelectric thin films and its impact on electrical characteristics.

Ferroelectric memory devices are expected for low-power and high-speed memory applications. HfO-based ferroelectric is attracting attention for its CMOS-compatibility and high scalability. Mesoscopic-scale grains, of which size is almost comparable to device size, are formed in HfO-based ferroelectric poly-crystalline thin films, which largely influences electrical characteristics in memory devices.

Suppression of Glucocorticoid Response in Stressed Mice Using 50 Hz Electric Field According to Immobilization Degree and Posture.

Various studies on immobilized BALB/c mice to evaluate changes in hormone levels associated with stress responses have advanced the characterization of multiple aspects of the biological actions of extremely low-frequency (ELF) electric fields (EFs). In this study, we aimed to investigate the effect of mouse posture on its stress responses and evaluate the importance of adjusting the stress degree in the model. Mice were immobilized inside centrifuge tubes and exposed to an ELF EF generated between parallel plate electrodes.

Impact of extrapulmonary comorbidities on physical activity in chronic obstructive pulmonary disease in Japan: A cross-sectional study.

Physical activity, which can be affected by airflow limitation and extrapulmonary comorbidities, has been reported to be reduced in patients with chronic obstructive pulmonary disease, and reduced physical activity is associated with higher risks of exacerbation and mortality. The aim of the present study is to elucidate the comprehensive effect of extrapulmonary comorbidities on physical activity in Japanese patients with chronic obstructive pulmonary disease, of which evidence is lacking. We conducted a cross-sectional study with a series of tests, including lung function, physical activity, symptom scores, and parameters for comorbidities.

Selective covalent targeting of SARS-CoV-2 main protease by enantiopure chlorofluoroacetamide.

The coronavirus disease 2019 (COVID-19) pandemic has necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main protease (M) is a promising target for COVID-19 treatment. Here, we report an irreversible SARS-CoV-2 M inhibitor possessing chlorofluoroacetamide (CFA) as a warhead for the covalent modification of M.

Tbx1, a gene encoded in 22q11.2 copy number variant, is a link between alterations in fimbria myelination and cognitive speed in mice.

Copy number variants (CNVs) have provided a reliable entry point to identify the structural correlates of atypical cognitive development. Hemizygous deletion of human chromosome 22q11.2 is associated with impaired cognitive function; however, the mechanisms by which the CNVs contribute to cognitive deficits via diverse structural alterations in the brain remain unclear.