A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.

Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.

Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.

A national survey of career development according to gender and subspecialties among cardiologists in Japan.

Background: Training opportunities, work satisfaction, and the factors that influence them according to gender and subspecialties are understudied among Japanese cardiologists.

Methods: We investigated the career development of Japanese cardiologists with an e-mail questionnaire. Feelings of inequality in training opportunities, work dissatisfaction, and reasons were assessed by examining the cardiologists' gender and invasiveness of subspecialties.

Clinical practice guidelines for management of disseminated intravascular coagulation in Japan 2024. Part 3: solid cancers and vascular abnormalities.

This study discusses disseminated intravascular coagulation (DIC) associated with solid cancers and various vascular abnormalities, both of which generally exhibit chronic DIC patterns. Solid cancers are among the most significant underlying diseases that induce DIC. However, the severity, bleeding tendency, and progression of DIC vary considerably depending on the type and stage of the cancer, making generalization difficult.

Investigation of Teicoplanin Trough Concentrations and Safety Following High-Dose Loading in a Pediatric Population.

Background: Therapeutic drug monitoring-informed teicoplanin dosage adjustments are recommended for safe and effective use. The authors' group previously reported that only half of children reached the recommended blood concentration range at the standard teicoplanin loading dose. It has been suggested that higher loading doses are necessary; however, the usefulness and safety of high-dose loading in pediatric patients in clinical practice are unknown.

Health Literacy and Internet Use Among Japanese Older Adults: A Gender-Stratified Cross-Sectional Analysis of the Moderating Effects of Neighborhood Relationships.

: Internet use positively impacts mental health in older adults, with health literacy (HL) playing a key role. While social networks may complement individual HL, the role of neighborhood relationships in this association, particularly by gender, remains unclear. This study examined how the association between HL and Internet use among older adults was modified by neighborhood relationships.

Large Polarization Change Induced by Spin Crossover-Driven Fe(II) Ion Shuttling within a Tripodal Ligand.

The integration of spin crossover (SCO) magnetic switching and electric polarization properties can engender intriguing correlated magnetic and electric phenomena. However, achieving substantial SCO-induced polarization change through rational molecular design remains a formidable challenge. Herein, we present a polar Fe(II) compound that exhibits substantial polarization change in response to a thermally regulated low-spin ↔ high-spin transition.

Anion photoelectron velocity-map imaging using a tunable laser at a 100 kHz repetition rate.

We present velocity-map imaging (VMI) of photoelectrons detached from anions using an optical parametric amplifier operating at a repetition rate as high as 100 kHz. The light source generates femtosecond (fs) laser pulses tunable from near-infrared to ultraviolet (310-2600 nm), which interact synchronously with mass-selected anion bunches. We demonstrate this technique by measuring two-dimensional projections of photoelectrons ejected from silver trimer anions, Ag3-, across a photon energy range from 2.

Early Clinical Results for a New Self-Organizing Hybrid Fabric in Congenital Cardiac Surgery.

Background: We have developed a new hybrid warp-knit fabric for induction of in situ tissue regeneration that has shown appropriate antideterioration properties and expandability in preclinical studies. This study was performed to assess the clinical efficacy and safety of this fabric in the early postoperative period after congenital cardiac surgery.

Methods: The fabric comprises biodegradable (complete degradation period, 2-3 years) and nonbiodegradable yarns coated with cross-linked gelatin.

Traction-assisted endoscopic ultrasound-guided fine-needle biopsy using the clip-with-thread method for small gastric subepithelial lesions: Randomized controlled trial (with video).

Objectives: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is the gold standard for diagnosing gastric subepithelial lesions (SELs), but diagnosing lesions smaller than 20 mm remains challenging. We developed traction-assisted EUS-FNB (TA-EUS-FNB) using the clip-with-thread method to enhance diagnostic accuracy by stabilizing the lesion and providing counter-traction for easier needle access. This study evaluates the effectiveness of TA-EUS-FNB in diagnosing small gastric SELs.

Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA.

The impact of clinical stage on the effectiveness of osimertinib for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) remains unexamined. We investigated osimertinib therapeutic efficacy variation between stage IVA or lower and stage IVB EGFR mutation-positive lung cancers, focusing on differences in pretreatment co-occurring genetic alterations in circulating tumor DNA. This was a secondary analysis of the ELUCIDATOR study, a multicenter prospective observational study in Japan that assessed the mechanisms underlying resistance to osimertinib as a first-line treatment for advanced NSCLC with EGFR mutations.

Prognostic impact of subcutaneous fat quality and sarcopenia on the survival outcomes in patients with colorectal cancer.

Purpose: This study aimed to evaluate the relationship between the quantity and quality of subcutaneous fat and prognosis following colorectal cancer resection.

Method: We conducted a retrospective analysis of the clinical data of 399 patients who underwent curative resection for stage 2 or 3 colorectal cancer between January 2013 and March 2019. This study examined the correlation between sarcopenia and various fat parameters, including fat area and density, and assessed their impact on the prognosis.

Primary intraosseous squamous cell carcinoma with pagetoid spread arising in periapical odontogenic epithelium of the maxilla.

To date, pagetoid spread-the proliferation of pagetoid cells in intraepidermal lesions, as observed in secondary extramammary Paget's disease-has not been reported in squamous epithelium derived from the extension of head and neck carcinomas. Herein, we report a case of pagetoid squamous cell proliferation associated with a primary intraosseous carcinoma (PIOC) arising in the periapical lesion of the maxilla, a finding not reported previously. A 60-year-old man presented with prostate adenocarcinoma and bilateral pubic bone, ilium bone, and sacral bone metastases.

Influence of irrigation with oxygen plasma treated metal contaminated water on plant growth.

This study aimed to evaluate the effects of plasma treated metal contaminated water, used for irrigation, on plant growth. Zinc (Zn) is a commonly used metal that can enter the environment through industrial processes. It may be released as particles into the atmosphere or discharged as wastewater into waterways or the ground.

Utilization of telemedicine in conjunction with wearable devices for patients with chronic musculoskeletal pain: a randomized controlled clinical trial.

The present randomized controlled trial aimed to investigate the effects of home-based telemedicine with wearable devices and usual care on pain-related outcomes in patients with chronic musculoskeletal pain, compared to usual care alone. The patients with chronic musculoskeletal pain were randomly allocated to the usual care group or the telemedicine group, which participated in telemedicine with wearable devices, the objective data from which were recorded, in conjunction with usual care for six months. The primary outcome measure was the Numeric Rating Scale (NRS) for pain.

The impact of air pollution control measures and the COVID-19 pandemic on photosynthesis in urban trees.

Phytotoxic air pollutants such as atmospheric nitrogen dioxide (NO) are among the major stresses affecting tree photosynthesis in urban areas. We clarified the relationship between NO concentrations and photosynthetic function for three major urban trees, Prunus × yedoensis, Rhododendron pulchrum, and Ginkgo biloba, planted in Kyoto and surrounding cities, combining our published data and new data collected from 2020 to 2023. High NO increased long-term water use efficiency for all species.

Mitochondrial diseases: from molecular mechanisms to therapeutic advances.

Mitochondria are essential for cellular function and viability, serving as central hubs of metabolism and signaling. They possess various metabolic and quality control mechanisms crucial for maintaining normal cellular activities. Mitochondrial genetic disorders can arise from a wide range of mutations in either mitochondrial or nuclear DNA, which encode mitochondrial proteins or other contents.

Analysis and Categorization of Various Types of Vocal Distortion in Rock, Metal, Pop Styles, and Throat Singing Observed by High-Speed Digital Imaging.

Introduction: Vocal distortion, also known as a scream or growl, is used worldwide as an essential technique in singing, especially in rock and metal, and as an ethnic voice in Mongolian singing. However, the production mechanism of vocal distortion is not yet clearly understood owing to limited research on the behavior of the larynx, which is the source of the distorted voice.

Objectives: This study used high-speed digital imaging (HSDI) to observe the larynx of professional singers with exceptional singing skills and determine the laryngeal dynamics in the voice production of various vocal distortions.

Workload and emotional exhaustion among older assistant care workers in Japan: Buffering effect of work resources.

Aim: Based on the Job Demands-Resources model, this study aimed to assess the predictive effect of workload on emotional exhaustion and test the buffering effect of three types of work resources (workplace cohesion, work control, and workplace support) on the relationship between workload and emotional exhaustion among older Japanese assistant care workers.

Methods: We analyzed data from a national survey on the work features and work-related outcomes of 1601 older assistant care workers working in geriatric health services facilities in Japan. Demographic characteristics, workload, work resources, and emotional exhaustion were analyzed.

Generation of a transgenic chicken line with reporters for limb bud mesenchyme and apical ectodermal ridge cells.

Cell type-specific reporter transgenic chicken lines are invaluable tools in developmental biology, allowing the visualization of dynamics and differentiation states of target cell types in living embryos. Here, we report the establishment of a new transgenic chicken line in which limb mesenchyme and apical ectodermal ridge (AER) cells are labeled with different fluorescent proteins in the embryos. The processes for generating the reporter line involved using tissue-specific promoters, the Tol2 transposon-mediated genomic integration, and clonal culture system of primordial germ cells.

Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers.

Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination of hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as a liver biopsy, which makes it impractical to access the dynamics of cccDNA in patients. Although HBV RNA and HBV core-related antigens (HBcrAg) have been proposed as surrogate markers for evaluating cccDNA activity, they do not necessarily estimate the amount of cccDNA.

Decomposition of friction coefficients to analyze hydration effects on a C60(OH)n.

To analyze hydration effects on macromolecular diffusion, the friction coefficients of macromolecules were examined using molecular dynamics simulations with an all-atom model. In the present study, a method was introduced to decompose the molecular friction coefficient into the contributions for each site on the macromolecule. The method was applied to several fullerenols in ambient water.

Prevalence and Clinical Outcomes of Discordant Lesions Between Fractional Flow Reserve and Nonhyperemic Pressure Ratios in Clinical Practice: The J-PRIDE Registry.

Background: Limited large-scale, real-world data exist on the prevalence and clinical impact of discordance between fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs).

Methods: The J-PRIDE registry (Clinical Outcomes of Japanese Patients With Coronary Artery Disease Assessed by Resting Indices and Fractional Flow Reserve: A Prospective Multicenter Registry) prospectively enrolled 4304 lesions in 3200 patients from 20 Japanese centers. The lesions were classified into FFR+/NHPR-, FFR-/NHPR+, FFR+/NHPR+, or FFR-/NHPR groups according to cutoff values of 0.

Evaluation of physical activity with the International Physical Activity Questionnaire among outpatients with type 2 diabetes mellitus in Japan.

Objective: This study aimed to investigate the amount of physical activity, including daily movement, and the factors related to the amount of physical activity undertaken by patients with type 2 diabetes mellitus at an outpatient clinic.

Patients And Methods: A self-administered questionnaire was distributed to 111 patients, aged 20 years or older, with type 2 diabetes mellitus, who visited a diabetes outpatient clinic. The amount of physical activity was investigated using the International Physical Activity Questionnaire-Long Version.