Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

In-hospital mortality of patients admitted to the intermediate care unit in hospitals with and without an intensive care unit: a nationwide inpatient database study.

Background: Intermediate care units (IMCUs) provide care for patients who need more intensive treatment than general wards but less than intensive care units (ICUs). Although the concept of an IMCU requires co-location with an ICU, some hospitals have IMCUs but no ICUs, which potentially worsens patient outcomes. This study aimed to examine the annual trends and care processes, and compare the outcomes of patients admitted to IMCUs in hospitals with and without ICUs using a nationwide inpatient database in Japan.

FRET analysis of the unwrapping of nucleosomal DNA containing a sequence characteristic of the + 1 nucleosome.

Sequence-dependent mechanical properties of DNA could play essential roles in nuclear processes by affecting histone-DNA interactions. Previously, we found that the DNA entry site of the first nucleosomes from the transcription start site (+ 1 nucleosome) in budding yeast enriches AA/TT steps, but not the exit site, and the biased presence of AA/TT in the entry site was associated with the transcription levels of yeast genes. Because AA/TT is a rigid dinucleotide step, we considered that AA/TT causes DNA unwrapping.

Association Between Child Varicella Vaccination and Zoster in Household Adults: A Retrospective Japanese Cohort Study.

Aim: Some countries are hesitant to implement routine varicella vaccination for children because of concerns over the exogenous boosting hypothesis, which suggests that vaccinating children may increase herpes zoster cases in adults. However, substantial evidence supporting this hypothesis is lacking. This study assessed the association between a child's varicella vaccination status and herpes zoster occurrence in adults in the same household.

Identification and structure-guided development of triazole urea-based selective antagonists of Arabidopsis karrikin signaling.

The smoke-derived butenolides, karrikins (KARs), regulate many aspects of plant growth and development. However, KARs and a plant hormone, strigolactones (SLs), have high resemblance in signal perception and transduction, making it hard to delineate KARs response due to the shortage of chemical-genetic tools. Here, we identify a triazole urea KK181N1 as an inhibitor of the KARs receptor KAI2.

Fucosterol and Fucoxanthin Enhance Dentin Collagen Stability and Erosion Resistance Through Crosslinking and MMP Inhibition.

Purpose: To evaluate the effects of fucosterol and fucoxanthin on ultimate microtensile strength (µUTS), dentin collagen cross-linking, erosion resistance, and matrix metalloproteinase (MMP) inhibition.

Methods: Dentin beams and slices were prepared from extracted human teeth and treated with concentrations of 50 µg/mL, 100 µg/mL, and 200 µg/mL of fucosterol and fucoxanthin. Fourier-transform infrared spectroscopy (FTIR) was used to analyze collagen cross-linking.

Association between preoperative antifungal therapy and postoperative complications in patients with pulmonary aspergilloma: A national database study in Japan.

Postoperative complications of pulmonary resection in patients with pulmonary aspergilloma are common. Preoperative antifungal therapy is a perioperative management strategy to reduce postoperative complications; however, the benefit of the treatment remains controversial. A retrospective cohort study was conducted using data from the Diagnosis Procedure Combination database (July 2010-March 2021), a national inpatient database in Japan.

Comparison of open and laparoscopic appendectomy according to the trimester of pregnancy: A nationwide observational study.

Objective: To compare the outcomes of open appendectomy (OA) and laparoscopic appendectomy (LA) for acute appendicitis during pregnancy by trimester.

Methods: We conducted a nationwide retrospective cohort study using the Diagnosis Procedure Combination database in Japan. We identified pregnant women diagnosed with appendicitis who underwent OA or LA from 2010 to 2022.

Non-thermal atmospheric pressure plasma-irradiated cysteine protects cardiac ischemia/reperfusion injury by preserving supersulfides.

Ischemic heart disease is the main global cause of death in the world. Abnormal sulfide catabolism, especially hydrogen sulfide accumulation, impedes mitochondrial respiration and worsens the prognosis after ischemic insults, but the substantial therapeutic strategy has not been established. Non-thermal atmospheric pressure plasma irradiation therapy is attracted attention as it exerts beneficial effects by producing various reactive molecular species.

Higher relapse and worse overall survival in recipients with CTLA-4 AA genotype of rs231775 following single-unit cord blood transplantation in adults.

We retrospectively investigated the impact of CTLA-4 polymorphism on outcomes for adult patients who received single-unit cord blood transplantation (CBT) at our institution. CTLA-4 genotyping was performed using real-time polymerase chain reaction with the TaqMan SNP genotyping assay for rs231775. This study included 143 recipient-donor pairs.

Development of Continuous-Flow Reactions for the Synthesis of Anti-Alzheimer Drug Memantine.

Memantine hydrochloride, a non-competitive antagonist of NMDA-type glutamate receptors, is known to suppress the progression of symptoms in Alzheimer's disease. Possessing a characteristic adamantane skeleton as its core structure and an amino group at the bridgehead position, memantine was synthesized starting from acenaphthene. The synthesis involved nucleus hydrogenation of acenaphthene to perhydroacenaphthene, skeletal rearrangement of perhydroacenaphthene, nitration of 1,3-dimethyladamantane, and reduction of the nitro groups to an amino group.

Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial.

The clinical significance of FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) plus anti-EGFR monoclonal antibody using cetuximab for metastatic colorectal cancer (mCRC) remains controversial. We report results from a randomized phase 2 DEEPER trial (UMIN000018217, jRCTs061180022) to test the superiority of modified (m)-FOLFOXIRI plus weekly cetuximab over bevacizumab in patients with RAS wild-type (wt) mCRC. Primary endpoint was depth of response (DpR).

MCGAE: unraveling tumor invasion through integrated multimodal spatial transcriptomics.

Spatially Resolved Transcriptomics (SRT) serves as a cornerstone in biomedical research, revealing the heterogeneity of tissue microenvironments. Integrating multimodal data including gene expression, spatial coordinates, and morphological information poses significant challenges for accurate spatial domain identification. Herein, we present the Multi-view Contrastive Graph Autoencoder (MCGAE), a cutting-edge deep computational framework specifically designed for the intricate analysis of spatial transcriptomics (ST) data.

X-206 exhibits broad-spectrum anti-β-coronavirus activity, covering SARS-CoV-2 variants and drug-resistant isolates.

Coronaviruses such as the Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2, causing MERS, SARS, and Coronavirus disease-19, respectively, are highly pathogenic to humans. Notably, several antiviral drugs against SARS-CoV-2, such as nirmatrelvir and remdesivir, have been approved. However, no approved vaccines or antiviral agents are available for other highly pathogenic β-coronaviruses.

Design of enzyme immobilized zwitterionic copolymer nanogels and its size effect on electrochemical reaction.

For enzyme-based electrochemical devices, an improvement in electron transfer between the enzyme and electrode is important. Thus, we developed a nano-scaled hydrogel that includes an electron mediator and enzyme to realize nano-sized effects that enhance the functions. Three different chain lengths (short, medium, and long) of copolymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and methacrylic acid N-hydroxysuccinimide ester (MNHS; poly(MPC-co-MNHS), PMS) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization.

Enantiomer-Specific Stable Carbon and Nitrogen Isotopic Analyses of Underivatized Individual l- and d-Amino Acids by HPLC + HPLC Separation and Nano-EA/IRMS.

We developed a new method for stable carbon and nitrogen isotopic (δC and δN) analysis of underivatized amino acid (AA) enantiomers simultaneously, based on high-performance liquid chromatography (HPLC) separation and off-line isotopic measurement. l- and d-Enantiomers of each AA were isolated using a ReproSil Chiral-AA column, purified by wet chemical procedure, and analyzed for δC and δN values with a nanomol-scale elemental analyzer/isotope-ratio mass spectrometry (nano-EA/IRMS) system. We successfully achieved the separation of l- and d-enantiomers of 15 proteinogenous AAs, with all l-enantiomers eluting before respective d-enantiomers.

Structural insights into the agonist selectivity of the adenosine A receptor.

Adenosine receptors play pivotal roles in physiological processes. Adenosine A receptor (AR), the most recently identified adenosine receptor, is expressed in various tissues, exhibiting important roles in neuron, heart, and immune cells, and is often overexpressed in tumors, highlighting the therapeutic potential of AR-selective agents. Recently, we identified RNA-derived N-methyladenosine (mA) as an endogenous agonist for AR, suggesting the relationship between RNA-derived modified adenosine and AR.

Cost-Effectiveness Analysis of Adjuvant Pertuzumab and Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer in Japan.

Background And Objective: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer presents considerable treatment challenges owing to its aggressive nature. Global guidelines have endorsed a full year of HER2-targeted therapy for early-stage breast cancer. However, previous cost-effectiveness analyses of dual HER2-targeted therapies have been limited.