Preoperative pembrolizumab‑induced hemophagocytic lymphohistiocytosis in a patient with breast cancer: A case report.

Recently, the anti-programmed cell death protein 1 antibody pembrolizumab, a type of immune checkpoint inhibitor (ICI), has been used in preoperative systemic chemotherapy for hormone receptor and human epidermal growth factor 2-negative breast cancer, also known as triple-negative breast cancer (TNBC). Chemotherapy with pembrolizumab has demonstrated clinical activity in terms of pathologic complete response and event-free survival. Despite their efficacy, the current understanding of the full spectrum of side effects associated with relatively new ICIs remains incomplete.

MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX.

Current treatments for hepatitis B virus (HBV), such as interferons and nucleic acid analogs, have limitations due to side effects like depression and the development of drug-resistant mutants, highlighting the need for new therapeutic approaches. In this study, we identified microRNA-3145 (miR-3145) as a host-derived miRNA with antiviral activity that is upregulated in primary hepatocytes during HBV infection. The expression of its precursor, pri-miR-3145, increased in response to the the virus infection, and miR-3145 downregulated the hepatitis B virus S (HBS) antigen and hepatitis B virus X (HBX), thereby inhibiting viral replication.

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.

Comparison of cardiovascular risk prediction models developed using machine learning based on data from a Sri Lankan cohort with World Health Organization risk charts for predicting cardiovascular risk among Sri Lankans: a cohort study.

Introduction: Models derived from non-Sri Lankan cohorts are used for cardiovascular (CV) risk stratification of Sri Lankans.

Objective: To develop a CV risk prediction model using machine learning (ML) based on data from a Sri Lankan cohort followed up for 10 years, and to compare the predictions with WHO risk charts.

Design: Cohort study.

Behavior changes to promote preconception health: a systematic review.

Background: Preconception care is expected to prevent diseases, promote health, and improve pregnancy outcomes. Although a consensus exists on the efficacy of folic acid supplementation and preconception vaccination, evidence regarding comprehensive approaches to preconception care targeting the general population remains lacking. We aimed to identify and examine preconception care programs delivered to reproductive-aged women and men to promote behavioral change.

G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication.

Future pandemic threats may be caused by novel coronaviruses and influenza A viruses. Here we show that when directly added to a cell culture, 12mer guanine RNA (G12) and its phosphorothioate-linked derivatives (G12(S)), rapidly entered cytoplasm and suppressed the propagation of human coronaviruses and influenza A viruses to between 1/100 and nearly 1/1000 of normal virus infectivity without cellular toxicity and induction of innate immunity. Moreover, G12(S) alleviated the weight loss caused by coronavirus infection in mice.

Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology.

Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion.

Expert consensus on sequential surgery after immune-targeted conversion therapy for advanced hepatocellular carcinoma in China.

Hepatocellular carcinoma (HCC) represents a significant global health burden, particularly in the Asia-Pacific region, where it is a leading cause of cancer-related mortality. In China alone, HCC accounts for approximately 367,700 new cases and 316,500 deaths annually; over 50% of patients are diagnosed at an advanced stage, limiting curative treatment options and resulting in poor survival outcomes. Systemic therapies combining immune checkpoint inhibitors (ICIs) with antiangiogenic targeted drugs have shown promise in converting unresectable HCC into resectable cases, potentially transforming clinical outcomes.

A scoping review and thematic analysis of the effects of tropical cyclones on diarrheal diseases.

Background: Tropical cyclones pose significant health risks and can trigger outbreaks of diarrheal diseases in affected populations. Although the effects of individual hazards, such as rainfall and flooding, on diarrheal diseases are well-documented, the complex multihazard nature of tropical cyclones is less thoroughly explored. To date, no dedicated review comprehensively examines the current evidence and research on the association between tropical cyclones and diarrheal diseases.

Proline enhances the hepatic induction of lipogenic gene expression in male hepatic fasn reporter mice.

Hepatic de novo lipogenesis (DNL) is increased by both carbohydrate intake and protein consumption. In hepatic fat synthesis, a key role is played by the induction of the hepatic expression of lipogenic genes, including Fasn, Scd1, and Srebf1. Regarding carbohydrate intake, increased blood glucose and insulin levels promote the expression of hepatic lipogenic genes.

Spontaneous remission of Pneumocystis jirovecii pneumonia followed by severe pulmonary nocardiosis in a patient with HIV infection: A case report.

We describe a rare case of spontaneous remission of Pneumocystis jirovecii pneumonia (PCP) in a 42-year-old patient with human immunodeficiency virus (HIV) infection, followed by severe pulmonary nocardiosis. To our knowledge, this is the first report of spontaneous remission of PCP in a completely untreated patient with HIV infection. The patient, a bisexual Japanese man, presented with fever and anorexia and had a history of non-compliance with antiretroviral therapy (ART) for 13 years.

Predicting depressive symptoms and psychological distress by circulating inflammatory mediators: A 16-month prospective study in Japanese white-collar employees.

Objective: Although increasing evidence suggests that depression/distress involves inflammatory processes, its potential sex differences and the temporal directions for this association remain elusive.

Methods: We examined the temporal association between serum inflammatory mediators and depression/distress as measured by the Center for Epidemiologic Studies Depression Scale (CES-D) and the Kessler Psychological Distress Scale (K6), in non-depressed working men and women (n = 61 and 43, respectively) by a 16-month prospective design.

Results: Fully-adjusted partial correlation analyses revealed that in men, a lower IFN-γ predicted subsequent increases in CES-D and K6 scores, while a higher TNF-α predicted increased K6 scores.

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.

Highly pathogenic avian H5N1 influenza A virus replication in ex vivo cultures of bovine mammary gland and teat tissues.

Since early 2024, highly pathogenic avian influenza H5N1 viruses have been causing outbreaks in dairy cattle in the United States. Here, we compared the replicative capacity of A/dairy cattle/Texas/24-008749-001/2024 (H5N1; Cow-H5N1) isolated from a dairy cow, A/chicken/Ghana/AVL-76321VIR7050-39/2021 (H5N1; Chicken-H5N1) isolated from a chicken, and a human H1N1 2009 pandemic virus in ex vivo explant cultures of mammary gland and teat from lactating cows. We also examined the expression of influenza virus receptors in these organs.

Association of remote work with tobacco and alcohol use: a cross-sectional study in Japan.

Background: Remote work allows one to work free from workplace policy, but it may negatively affect health-related behaviors such as tobacco product use and alcohol drinking. Our study aimed to investigate the association of remote work with tobacco dependence and hazardous alcohol use.

Methods: This nationwide Internet-based survey was conducted in Japan in February 2023.

Association between physical multimorbidity in middle adulthood and mortality: findings from two large cohort studies in Japan.

Background: While previous literature suggests that multimorbidity is linked to a higher risk of mortality, evidence is scarce among individuals in middle adulthood. We aimed to examine the association between physical multimorbidity and all-cause mortality among individuals aged 40-64 years at baseline in Japan.

Methods: Data were obtained from two cohort studies, the Japan Public Health Center-based Prospective Study (JPHC) and the Japan Epidemiology Collaboration on Occupational Health Study (J-ECOH).

Electrocautery ablation therapy for anal intraepithelial carcinoma with high-resolution anoscopy.

Objective: This study investigated the efficacy and safety of electrocautery ablation for high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men (MSM) including people with human immunodeficiency virus, using comprehensive biopsy with high-resolution anoscopy (HRA).

Methods: This single-arm, open-label pilot study included 20 MSM with HSIL who were treated with electrocautery ablation. The participants were recruited from the National Center for Global Health and Medicine and followed up using HRA with a comprehensive biopsy approach at 3- and 6-months post-ablation.

Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice.

The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, we describe a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit.

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in treatment-naïve and treatment-experienced people with HIV: 12-month virologic effectiveness and safety outcomes in the BICSTaR Japan cohort.

BICSTaR (BICtegravir Single Tablet Regimen) is an ongoing, observational cohort study assessing the virologic effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in treatment-experienced (TE) and treatment-naïve (TN) people with HIV across 14 countries over 24 months. We present 12-month outcomes from participants in the BICSTaR Japan cohort. Retrospective and prospective data were pooled from people with HIV aged ≥20 years receiving B/F/TAF within routine clinical care in Japan.

Development of broadly protective influenza B vaccines.

Influenza B viruses pose a significant threat to global public health, leading to severe respiratory infections in humans and, in some cases, death. During the last 50 years, influenza B viruses of two antigenically distinct lineages (termed 'Victoria' and 'Yamagata') have circulated in humans, necessitating two different influenza B vaccine strains. In this study, we devised a novel vaccine strategy involving reciprocal amino acid substitutions at sites where Victoria- and Yamagata-lineage viruses differ, leading to the generation of 'hybrid' vaccine viruses with the potential to protect against both lineages.

Pathology and Treatments of Alzheimer's Disease Based on Considering Changes in Brain Energy Metabolism Due to Type 2 Diabetes.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cognitive dysfunction, memory decline, and behavioral disturbance, and it is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. Although various hypotheses have been proposed to explain the pathogenesis of AD, including the amyloid beta hypothesis, oxidative stress hypothesis, and abnormal phosphorylation of tau proteins, the exact pathogenic mechanisms underlying AD remain largely undefined. Furthermore, effective curative treatments are very limited.

A Unique Case of MBD5 and CCM2 Deletions Leading to a Severe Neurological Phenotype With Prolonged Status Epilepticus.

Heterozygous pathogenic variants in MBD5 (MIM*611472) and CCM2 (MIM*607929) cause autosomal dominant intellectual developmental disorder 1 (MIM#156200) and cerebral cavernous malformations-2 (MIM#603284), respectively. Both conditions may present with seizures, epilepsy, and status epilepticus. However, super-refractory status epilepticus, defined as seizures lasting more than 24 h, has not been described in either condition.

Characterization of Dystrophin Dp71 Expression and Interaction Partners in Embryonic Brain Development: Implications for Duchenne/Becker Muscular Dystrophy.

Duchenne/Becker muscular dystrophy (DMD/BMD) manifests progressive muscular dystrophy and non-progressive central nervous disorder. The neural disorder is possibly caused by abnormalities in the developmental period; however, basic research to understand the mechanisms remains underdeveloped. The responsible gene, Dmd (dystrophin), generates multiple products derived from several gene promoters.