Access Program for Unapproved and Off-Label Drug Use in Pediatric BRAF V600E-Mutated Brain Tumors in Japan.

Programs allowing access to investigational drugs and off-label drug use for serious diseases have often been applied to pediatric cancers. A clinical study conducted under the Japanese "Patient-Proposed Healthcare Services" evaluated the efficacy and safety of dabrafenib plus trametinib in children with BRAF V600 mutant glioma (jRCTs071210071). This study successfully provided unapproved and off-label medications to four enrolled patients, two with low-grade glioma and two with high-grade glioma (median age: 10.

Sentinel Lymph Node Detection Using SPECT and Gamma Probe in Low-Risk Endometrial Cancer: Efficacy and Factors Associated With Detection Failure.

Introduction: This study examined factors that affected sentinel lymph node (SLN) identification of patients with endometrial cancer having a preoperative estimation of low recurrent risk.

Methods: This study included 97 patients with endometrial cancer who attempted to identify SLN using a uterine cervical injection of technetium-99 m phytate under laparoscopic or robotic-assisted surgery at our institute. A preoperative single photon emission computed tomography (SPECT) and intraoperative gamma probe were used to detect hot nodes.

Nonocclusive Ablation Technique Using a Novel Cryoballoon for Failed Left Superior Pulmonary Vein Isolation Despite Complete Occlusion.

Background: An indicator of successful cryoballoon (CB)-assisted pulmonary vein (PV) isolation is complete PV occlusion. However, CBs may exhibit a weaker freezing effect on the equatorial plane. This study investigates the predictors of failed left superior PV (LSPV) isolation despite complete occlusion with novel CBs.

Effect of Cholic Acid Salt and Its Mixed Micelles on the Morphology of Giant Unilamellar Vesicles (GUV).

Bile salts, present in the gastrointestinal tract as biosurfactants, play a crucial role in emulsifying and solubilizing fat-soluble nutrients and drugs, thereby facilitating their absorption. However, the cellular permeation of bile acid-mixed micelles solubilized with lipophilic substances remains inadequately explored. To comprehend the cell permeation behavior of bile salts and their mixed micelles, giant unilamellar vesicles (GUVs) were employed as a cell-mimetic system, prepared with dioleylphosphatidylcholine (DOPC).

High Altitude Pulmonary Edema Associated with Climbing Mount Fuji: A Case Report.

A 51-year-old man presented to the emergency department with rapidly progressive dyspnea that developed while climbing Mount Fuji. He had climbed Mount Fuji twice without experiencing similar symptoms. On arrival, his oxygen saturation was 91% on 10 L/min of oxygen with a non-rebreather mask.

A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan.

Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy of treatments for metastatic or unresectable EMPD remains poor, development of a novel therapeutic approach is strongly desired. However, the lack of EMPD models has hampered investigation of EMPD.

Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.

A master regulatory loop that activates genes in a temporally coordinated manner in muscle cells of ascidian embryos.

Ascidian larval muscle cells present a classic example of autonomous development. A regulatory mechanism for these cells has been extensively investigated, and the regulatory gene circuit has been documented from maternal factors to a muscle-specific gene. In the present study, we comprehensively identified genes expressed specifically in ascidian muscle cells, and found that all of them are under control of a positive regulatory loop of Tbx6-r.

Hierarchical chirality observed from chiral supramolecular assembling of racemic and enantiopure helicene derivatives on silica nanohelix surfaces.

Cast films of racemic helicene derivatives adsorbed onto the surface of nanometric silica helices with controlled handedness exhibited distinct CD signals, whereas no CD signal was observed in the absence of silica nanohelices. These CD signals originate from the helical supramolecular assemblies formed by the racemic mixture of helicenes, with no evidence of enantiospecific adsorption. Interestingly, when enantiomerically pure forms of these helicenes were drop-cast onto the silica helices, different CD spectra were observed depending on the combination of the helicenes' handedness with that of the silica nanohelices.

Bone marrow niches orchestrate stem-cell hierarchy and immune tolerance.

Stem cells reside in specialized microenvironments, termed niches, at several different locations in tissues. The differential functions of heterogeneous stem cells and niches are important given the increasing clinical applications of stem-cell transplantation and immunotherapy. Whether hierarchical structures among stem cells at distinct niches exist and further control aspects of immune tolerance is unknown.

Centrophilic retrotransposon integration via CENH3 chromatin in Arabidopsis.

In organisms ranging from vertebrates to plants, major components of centromeres are rapidly evolving repeat sequences, such as tandem repeats (TRs) and transposable elements (TEs), which harbour centromere-specific histone H3 (CENH3). Complete centromere structures recently determined in human and Arabidopsis suggest frequent integration and purging of retrotransposons within the TR regions of centromeres. Despite the high impact of 'centrophilic' retrotransposons on the paradox of rapid centromere evolution, the mechanisms involved in centromere targeting remain poorly understood in any organism.

Prevalence and clinicopathological features of microsatellite instability-high metastatic or recurrent gastric and esophagogastric junction cancer: WJOG13320GPS.

Background: Microsatellite instability (MSI)-high tumors represent a distinct, small-fraction subtype in esophagogastric junction cancer or gastric cancer (GC), yet their clinical significance remains poorly understood. This study aimed to investigate the prevalence and clinicopathological features of chemotherapy-naïve metastatic or recurrent MSI-high GC as a prescreening study for a phase II trial of nivolumab plus ipilimumab.

Methods: Key inclusion criteria included metastatic or recurrent adenocarcinoma of GC, ECOG performance status of 0 or 1, and no prior systemic therapy for metastatic or recurrent disease.

BET inhibitor JQ1 induces apoptosis of ovarian and endometrial endometrioid carcinoma cells by downregulating .

Although ovarian endometrioid carcinoma (OEC), frequently associated with endometrial endometrioid carcinoma (EEC), is often diagnosed at an early stage, the prognosis remains poor. The development of new, effective drugs to target these cancers is highly desirable. The bromodomain and extra-terminal domain (BET) family proteins serve a role in regulating transcription by recognizing histone acetylation, which is implicated in several types of cancer.

B-Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma Mimicking Fibrosing Mediastinitis: A Case Report and Diagnostic Insight.

BACKGROUND Fibrosing mediastinitis (FM) is a rare, fibroproliferative disorder within the mediastinum. It is extremely rare for hematologic malignancies to develop as FM. CASE REPORT A 32-year-old Japanese man with a 1-month history of headache and 2-week history of facial swelling underwent chest computed tomography (CT); a diffuse mass-like lesion was revealed in the anterior mediastinum with severe stenosis of vital mediastinal organs.

Effect of feeding spent coffee grounds on the methane production in bovine rumen.

The environmental impact of methane, a greenhouse gas emitted from ruminants, is a pressing issue and methods to control methane emissions from ruminants are being investigated worldwide. In this study, we investigated the effects of the administration of spent coffee grounds (SCG) on methane production in the rumen in two cows. In the control condition (days 1 and 2), the cows were fed a basic diet twice daily (roughage and concentrate), and in the SCG condition (days 1 and 2) sequentially, the cows were fed the same basic diet and administered SCG into the rumen twice daily.

Effect of commercial prescription diets containing prebiotics on clinical signs and fecal microbiome in dogs with intestinal disease.

Diet has emerged as a key modulator of the gut microbiota, offering a potential strategy for disease prevention and management. This study investigated the effects of the Prescription Diet Gastrointestinal Biome (GB) on 7 healthy dogs and 16 dogs with chronic gastrointestinal diseases (GI dogs). Our investigation monitored changes in body weight and the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) in 16 GI dogs fed a GB diet.

Association between antinuclear antibodies status and preterm birth in Japanese pregnant women: a prospective cohort study from Adjunct Study of the Japan Environment and Children's Study.

Background: Antinuclear antibodies (ANA) are important biomarkers for the diagnosis of autoimmune diseases; however, the general population also tests positive at a low frequency, especially in women. Although the effects of various autoimmune diseases on pregnancy outcomes have been studied, the association of ANA with pregnancy outcomes in healthy individuals is unclear. Preterm birth (PTB), a major cause of neonatal death or long-term health problems, is a complex condition with a multifactorial etiology, and the underlying mechanism remains unclear.

TIM3 on natural killer cells regulates antibody-dependent cellular cytotoxicity in HER2-positive gastric cancer.

Therapies targeting HER2 are the standard treatment for HER2-positive gastric cancer (GC). Trastuzumab, a monoclonal antibody against HER2, exerts anti-tumor activity through cell growth regulation and antibody-dependent cellular cytotoxicity (ADCC). ADCC is induced by the binding of trastuzumab to Fcγ receptor III (CD16) in natural killer (NK) cells.

Tumor infiltration of inactive CD8 + T cells was associated with poor prognosis in Gastric Cancer.

Background: Gastric cancer (GC) shows limited response to immune checkpoint inhibitors due to its complex tumor immune microenvironment (TIME). This study explores the functions of various immune cells in the complex TIME in GC.

Methods: We assessed CD8 + T-cell infiltration of GC tissues by immunohistochemistry, and performed single-cell RNA sequencing (scRNA-seq) of tumor and normal tissues from 34 patients with GC.

Alternating Administration of Osimertinib for Leptomeningitis and Docetaxel Plus Ramucirumab for Lung Adenocarcinoma Resistant to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Case Report.

Traditionally, leptomeningitis (LM) has been considered untreatable and terminal, but the development of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has significantly improved the prognosis of patients with EGFR mutations. However, non-LM lesions occasionally progress or recur, even when the LM is successfully controlled with EGFR-TKIs, and treatment of such cases remains unclear. We herein report a patient with advanced non-small-cell lung cancer (NSCLC) who was treated with an EGFR-TKI for LM and cytotoxic chemotherapy for EGFR-TKI-resistant pulmonary lesions.

One interesting and elusive two-coupled oscillator problem.

Chronobiology experiments often reveal intriguing non-linear phenomena, which require mathematical models and computer simulations for their interpretation. One example is shown here, where the two circadian oscillators located in the eyes of the mollusk were isolated and measured . By maintaining one eye under control conditions and manipulating the period of the second eye, Page and Nalovic (1992) obtained a diversity of results, including synchronized and desynchronized eyes, associated to weak coupling and period differences.

Revealing an origin of temperature-dependent structural change in intrinsically disordered protein.

Intrinsically disordered proteins (IDPs) show structural changes stimulated by changes in external conditions. This study aims to reveal the temperature dependence of the structure and dynamics of the intrinsically disordered region of Hef, one of the typical IDPs, using an integrative approach. Small-angle X-ray scattering (SAXS) and circular dichroism (CD) studies revealed that the radius of gyration and ellipticity at 222 nm remained constant up to 313-323 K, followed by a decline above this temperature range.

Treatment of Tenosynovial Giant Cell Tumor of the Cervical Spine with Postoperative Anti-RANKL Antibody (Denosumab) Administration.

Tenosynovial giant cell tumor (TGCT) is a fibrous histiocytic tumor originating in the synovial membrane. While cervical TGCT may not be considered a common diagnosis preoperatively because it is relatively rare, it has a high recurrence rate and should be considered. Total resection is preferable, but it can be challenging due to the risk of damaging the vertebral artery.

Loss of SMARCA4 induces sarcomatogenesis through epithelial-mesenchymal transition in ovarian carcinosarcoma.

Ovarian carcinosarcoma (OCS) is a rare and aggressive tumor, and the development of its sarcomatous component is believed to be due to epithelial-mesenchymal transition (EMT). The SWIch/sucrose nonfermentable chromatin remodeling factor (CRF) is closely related to EMT; however, the relationship between CRF and EMT in OCS remains unclear. In this study, we analyzed the protein expression of CRFs, including ARID1A and SMARCA4, and their downstream mRNA expression in 28 OCS cases, two fallopian tube CS cases, and one peritoneal CS case.