Divergent transcriptional states and kinetics of circulating tumor-infiltrating lymphocyte repertoires with highly homologous T-cell receptor sequences in a patient during immunotherapy.

Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy.

Anise and Fennel Essential Oils and Their Combination as Natural and Safe Housefly Repellents.

Essential oils (EOs) are effective repellents and eco-friendly alternatives. We tested single and combination EOs of fennel and anise for repellency and stability against houseflies. All treatments were stored at 27 °C for up to 360 days.

How Can We Improve the Survival of Patients with Colorectal Liver Metastases Using Thermal Ablation?

Thermal ablation has been widely used for patients with small colorectal liver metastases (CRLMs), even for resectable cases; however, solid evidence has been scarce. Some propensity-score matching studies using patients with balanced baseline characteristics have confirmed less invasiveness and the comparable survival benefits of thermal ablation to liver resection. A more recent pivotal randomized controlled trial comparing thermal ablation and liver resection was presented during the American Society of Clinical Oncology 2024 meeting.

Insufficient Sleep Syndrome in Childhood.

Sleep disorders in children have a negative impact on mental and physical development, and a lack of sleep is one of the most important problems in infancy. At the age when naps are commonly accepted, the judgment of whether the amount of sleep is adequate has been based on the total amount of sleep per day. In other words, the idea is that even if the amount of sleep at night is insufficient, it is not considered insufficient if it is compensated for by taking a long nap or sleeping late on weekend mornings.

Pertuzumab Retreatment for Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced/Metastatic Breast Cancer (PRECIOUS Study): Final Overall Survival Analysis.

In the primary analysis of the open-label phase III PRECIOUS study, pertuzumab retreatment combined with trastuzumab plus chemotherapy of physician's choice (PTC) significantly improved investigator-assessed progression-free survival (PFS) compared with trastuzumab plus physician's choice chemotherapy (TC) in patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced/metastatic breast cancer (LA/mBC). Here, we report final overall survival (OS) at the median follow-up of 25.8 months.

Overexpression of the RNA-binding protein NrdA affects global gene expression and secondary metabolism in species.

RNA-binding protein Nrd1 plays a role in RNA polymerase II transcription termination. In this study, we showed that the orthologous NrdA is important in global mRNA expression and secondary metabolism in species. We constructed an conditional expression strain using the Tet-On system in mut.

Impacts of Racket Handle Design on Table Tennis Topspin Forehand Rally Performance Among Beginner Players.

Physical inactivity is a major global public health concern, and table tennis offers a low-impact, engaging way to promote physical activity across various age groups. However, many beginners struggle to maintain effective participation due to their lower skill levels. Therefore, the development and reinforcement of stable grip techniques is crucial because it will help beginners achieve sustainable improvements in performance.

Injectable Chitosan Hydrogel Particles as Nasal Packing Materials After Endoscopic Sinus Surgery for Treatment of Chronic Sinusitis.

After endoscopic sinus surgery (ESS), nasal packing is often used to stop bleeding and promote wound healing. Because maintaining a moist environment is important to enhance wound healing, hydrogel-based wound dressings are effective to promote wound healing. Chitosan is used in the medical field because of its high hemostatic and wound healing properties.

Microdifferential Pressure Measurement Device for Cellular Microenvironments.

Mechanical forces influence cellular proliferation, differentiation, tissue morphogenesis, and functional expression within the body. To comprehend the impact of these forces on living organisms, their quantification is essential. This study introduces a novel microdifferential pressure measurement device tailored for cellular-scale pressure assessments.

Potent HIV‑1 protease inhibitors containing oxabicyclo octanol-derived P2-ligands: Design, synthesis, and X‑ray structural studies of inhibitor-HIV-1 protease complexes.

We describe here the design, synthesis, and X-ray structural studies of a new class of HIV-1 protease inhibitors containing 8-oxabicyclo[3.2.1]octanol-derived P2 ligands.

Global expansion of microphysiological systems (MPS) and Japan's initiatives: Innovation in pharmaceutical development and path to regulatory acceptance.

Microphysiological systems (MPS) are gaining global attention as potential game-changers in pharmaceutical development. Since 2013, MPS suppliers from university laboratories in the United States and Europe have competed to develop these devices. After the development phase, the focus shifted to the accumulation of applications using MPS for pharmaceutical companies and end users.

Personalized Dosing of Linezolid to Reduce the Risk of Thrombocytopenia: A Systematic Review and Meta-Analysis.

Background: Linezolid-induced thrombocytopenia (LIT) occurs in a dose-dependent manner. There is no consensus regarding personalized dosing of linezolid in the real world. This study investigated the usefulness of personalized dosing for the potential mitigation of LIT compared with standard dosing.

Immune evasion through mitochondrial transfer in the tumour microenvironment.

Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses. However, detailed mechanisms of such processes remain unclear.

Clinical and genetic spectrum of patients with IRF2BPL syndrome.

Interferon regulatory factor 2 binding protein-like (IRF2BPL) is a single-exon gene that is ubiquitously expressed in various tissues, including the brain. IRF2BPL encodes a transcription factor with two zinc-finger domains that potentially downregulate WNT signaling in the nervous system. Pathogenic IRF2BPL variants have been reported to cause developmental delay, seizures, myoclonus epilepsies, autistic spectrum disorder, and other neurodevelopmental disorders.

Nail growth arrest under low body temperature during hibernation.

Growth and differentiation are reduced or stopped during hibernation, an energy conserving strategy in harsh seasons by lowered metabolism and body temperature. However, few studies evaluated this in a same individual using a non-invasive method. In this study, we applied a non-invasive tracking method of the nail growth throughout the hibernation period in the same hibernating animals, the Syrian hamster (Mesocricetus auratus).

Preparation of a Stable Indomethacin Supersaturated Solution Using Hydrophobically Modified Hydroxypropylmethylcellulose and α-Cyclodextrin.

In the present study, the stability of a supersaturated solution of indomethacin (IM) was evaluated in hydrophobically modified hydroxypropylmethylcellulose (HM-HPMC) solutions, with and without parent cyclodextrins (CDs). A highly supersaturated state of IM was maintained in the HM-HPMC solution and was further stabilized by the addition of α-CD and β-CD. Notably, the highest level of supersaturation was achieved in HM-HPMC/α-CD solution, which maintained a high concentration of IM for up to 120 h.

High spatial resolution gene expression profiling and characterization of neuroblasts migrating in the peri-injured cortex using photo-isolation chemistry.

In the ventricular-subventricular-zone (V-SVZ) of the postnatal mammalian brain, immature neurons (neuroblasts) are generated from neural stem cells throughout their lifetime. These V-SVZ-derived neuroblasts normally migrate to the olfactory bulb through the rostral migratory stream, differentiate into interneurons, and are integrated into the preexisting olfactory circuit. When the brain is injured, some neuroblasts initiate migration toward the lesion and attempt to repair the damaged neuronal circuitry, but their low regeneration efficiency prevents functional recovery.

Update on the treatment navigation for functional cure of chronic hepatitis B: expert consensus 2.0.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements.

Serial assessment of coronary artery inflammation using cardiac CT in anthracycline chemotherapy for breast cancer.

Objectives: There is limited evidence of the pericoronary fat attenuation index (FAI) as an imaging marker to assess cancer therapy-related cardiovascular toxicity. We aimed to measure FAI in four consecutive coronary CT angiography (CTA) scans before and 3, 6, and 12 months after anthracycline treatment in patients with breast cancer to determine trends in dynamic changes in FAI after treatment.

Methods: We performed a post hoc analysis of a prospective study (between August 2019 and July 2020) in which anthracycline-induced myocardial injury was evaluated using cardiac CT.

Myeloablative conditioning in cord blood transplantation for acute myeloid leukemia patients is efficacious only until age 55.

Umbilical cord blood transplantation (CBT) is accepted as an effective treatment for acute myeloid leukemia (AML), and reduced-intensity conditioning (RIC), rather than myeloablative conditioning (MAC) regimens allowed elderly patients to be treated safely. However, appropriate intensities of conditioning regimens are still unclear, especially for middle-aged patients. To compare outcomes after RIC and MAC regimens, we analyzed AML patients aged 16 years or older in the Japanese registry database, who underwent single cord unit CBT between 2010-2019.

Increased Non-Relapse Mortality in Older People With Allogeneic Hematopoietic Stem Cell Transplantation Using Fludarabine and Myeloablative Dose of Busulfan-Based Regimen.

Fludarabine and myeloablative busulfan (FluBu4) in allogeneic hematopoietic stem cell transplantation (HSCT) for older people have not been adequately examined. This retrospective study analyzed data from a large-scale, nationwide database in Japan. Adult patients (> 15 years old, y/o) who received their first HSCT with FluBu4 for hematological malignancies were included.

Magnitude of opportunistic infections and associated factors among HIV-infected individuals attending care and treatment clinics in Dar es Salaam, Tanzania: a hospital-based cross-sectional study.

Objectives: This study aims to assess the magnitude of opportunistic infection (OI) and to identify factors associated with OIs among people living with HIV (PLHIV) on antiretroviral treatment (ART), attending HIV care and treatment clinics.

Design: A hospital-based cross-sectional study.

Setting: The study was conducted at Muhimbili National Hospital, Mwananyamala and Temeke Regional Referral Hospitals, in Dar es Salaam, Tanzania.

Clinical significance of the estimation of pulmonary-right ventricular uncoupling in patients with transthyretin amyloid cardiomyopathy.

Aims: There are few data on the prognostic impact of pulmonary-right ventricular (RV) uncoupling in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM).

Methods And Results: Among the 174 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from 2002 to 2021, 143 patients who met the current Japanese guideline and had sufficient information for two-dimensional speckle tracking echocardiography were retrospectively analysed. During a median follow-up of 1209 days, 39 cardiac deaths occurred.

An orally available P1'-5-fluorinated M inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier.

We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.