The correlation between LAG-3 expression and the efficacy of chemoimmunotherapy in advanced biliary tract cancer.

In our previous phase II T1219 trial for advanced biliary tract cancer (ABTC), the combination of nivolumab with modified gemcitabine and S-1 exhibited promising efficacy, while the programmed-death-ligand-1 (PD-L1) expression did not predict chemoimmunotherapy efficacy. Lymphocyte-activation-gene-3 (LAG-3), a negative immune checkpoint, is frequently co-expressed with PD-L1. This study assessed the predictive value of LAG-3 expression in ABTC patients who received chemoimmunotherapy.

Anti-PD1-/PDL1-induced chronic intestinal pseudo-obstruction: three cases treated with vedolizumab after corticosteroid failure with mixed results.

Immune checkpoint inhibitors (ICI), i.e., anti-PD1/PDL1 and anti-CTLA-4, have reshaped the prognosis of many cancers.

TDO2 + cancer-associated fibroblasts mediate cutaneous squamous cell carcinoma immune escape via impeding infiltration of CD8 + T cells.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, originating from the malignant proliferation of squamous epithelial cells. However, its pathogenesis remains unclear. To further explore the mechanisms underlying cSCC, we analyzed the data from one single-cell RNA sequencing study and discovered a significant upregulation of tryptophan 2,3-dioxygenase (TDO2) in the cancer-associated fibroblasts (CAFs).

Ga-DOTA-FAPI-04 and F-FDG PET/CT: a head-to-head comparison for peritoneal carcinomatosis diagnostic accuracy.

Purpose: The study aimed to compare the diagnostic accuracy of Ga-DOTA-FAPI-04 (Ga-FAPI) and F-FDG PET/CT for peritoneal carcinomatosis (PC) in patients with various types of cancer.

Methods: The study enrolled 113 patients with suspected peritoneal malignancy, each of whom underwent Ga-FAPI and F-FDG PET/CT scans. Lesions in all patients were confirmed through pathology or radiological follow-up.

Preoperative magnetic resonance evaluation of Struma Ovarii and its importance for the surgical modality: a retrospective study from two institutions.

Objectives: To improve preoperative diagnostic accuracy of struma ovarii by retrospectively reviewing magnetic resonance (MR) findings. It is beneficial to choose the most appropriate surgical modality for the patient.

Methods: We retrospectively reviewed the clinical course and MR characteristics of 52 patients who were diagnosed postoperatively with struma ovarii, pathologically, from two institutions.

Prognostic relevance of CD163 immune cells in patients with metastatic breast cancer.

Metastatic breast cancer (MBC) is generally considered an incurable disease and even though new treatments are available, the median survival is approximately three years. The introduction of immune therapies for MBC highlights the importance of the immune system in cancer progression and treatment. CD163 anti-inflammatory myeloid cells, including tumor associated macrophages (TAMs), are known to be of relevance in early breast cancer but their role in MBC is not yet established.

Sex differences in immunotherapy outcomes and tumor-infiltrating immune cell profiles in patients with advanced renal cell carcinoma.

Sex differences in the outcomes of advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) and the profiles of tumor-infiltrating immune cells (TIICs) remain unclear. We retrospectively evaluated data from 563 patients with RCC receiving systemic therapy, including first-line dual ICI combinations (i.e.

Timing is everything: the age-related impact of plyometric training on lower limb explosive strength in male adolescents and its general effectiveness in female adolescents.

Objective: This study investigates the impact of plyometric training on age-related lower limb explosive strength in male adolescents and its effectiveness in female adolescents.

Methods: A thorough search was conducted across five databases from their inception until September 20, 2024. Study quality was assessed using the Cochrane Risk Assessment Tool, and data analysis was performed with Stata 15 software.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the leading cause of dementia worldwide. The recent announcement that lecanemab, a monoclonal antibody targeting amyloid-b, can slow down cognitive decline in AD is a great step forward in the battle against the disease. However, the modest success achieved in the clinical trial speak to the need for developing additional pharmaceutical approaches to target other key features of AD.

Basic Science and Pathogenesis.

Background: Applying single-cell RNA sequencing (scRNA-seq) to the study of neurodegenerative disease has propelled the field towards a more refined cellular understanding of Alzheimer's disease (AD); however, directly linking protein pathology to transcriptomic changes has not been possible at scale. Recently, a high-throughput method was developed to generate high-quality scRNA-seq data while retaining cytoplasmic proteins. Tau is a cytoplasmic protein and when hyperphosphorylated is integrally involved in AD progression.

Basic Science and Pathogenesis.

Background: In 43-63% of symptomatic Alzheimer's disease (AD) patients, there is an observed accumulation of misfolded alpha-synuclein (αSyn). Two primary αSyn subtypes have been identified based on the underlying spreading pattern of this pathology: caudo-rostral and amygdala-predominant. Interactions between pathological TDP-43, Tau, and αSyn can aggravate their spread and aggregation.

Basic Science and Pathogenesis.

Background: Glial cells exhibit distinct transcriptional responses to β-amyloid pathology in Alzheimer's disease (AD). While sophisticated single-cell based methods have revealed heterogeneous glial subpopulations in the human AD brain, the histological localization of these multicellular responses to AD pathology has not been fully characterized due to the loss of spatial information. Here, we combined spatial transcriptomics (ST) with immunohistochemistry to explore the molecular mechanisms in the neuritic plaque niche.

Basic Science and Pathogenesis.

Background: Heterogeneity in the progression of clinical dementia poses a significant challenge, impeding the effectiveness of current therapies for Alzheimer's disease (AD). To decipher the molecular mechanisms governing heterogeneity in AD progression that remains a critical knowledge gap precluding rational therapeutic design, we investigated the biochemical and biophysical properties of tau present in the inferior temporal gyrus (ITG) and prefrontal cortex (PFC) brain regions of AD patients who had varying disease progression rates. To explore gene expression changes in the ITG which are associated with tau pathology and cognitive decline, we used RNA sequencing for molecular characterization of patients displaying tau and clinical heterogeneity.

Basic Science and Pathogenesis.

Background: A recent case report described an individual who was a homozygous carrier of the APOE3 Christchurch (APOE3ch) mutation and resistant to autosomal dominant Alzheimer's Disease (AD) caused by a PSEN1-E280A mutation. Whether APOE3ch contributed to the protective effect remains unclear.

Method: We generated a humanized APOE3ch knock-in mouse and crossed it to an amyloid-β (Aβ) plaque-depositing model.

Basic Science and Pathogenesis.

Background: Pathological tau plays critical roles in many neurodegenerative diseases (NDD), including Alzheimer's disease (AD). However, the mechanisms underlying the initial tau pathogenesis are largely unknown. Extensive tau pathology has been observed in the brains with chronic traumatic encephalopathy (CTE), suggesting repeated traumatic brain injury (rTBI) correlates with tau pathogenesis.

Basic Science and Pathogenesis.

Background: Psychosis occurs in 30-40% of individuals with AD. New insights into disease mechanisms may lead to novel pharmacological targets and treatments. Previous studies have focused on bulk tissue analysis with limited results.

Basic Science and Pathogenesis.

Background: Brain arteriolosclerosis (B-ASC) is a pathologic hallmark characterized by dysmorphic brain arteriolar wall thickening. B-ASC is a common finding at autopsy in aged persons - some degree of B-ASC is seen in >80% of brains beyond age 80 years - and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC.

Basic Science and Pathogenesis.

Background: The brain is shielded from the peripheral circulation by central nervous system (CNS) barriers, comprising the well-known blood-brain barrier (BBB) and the less recognized blood-cerebrospinal fluid (CSF) barrier located within the brain ventricles. The gut microbiota represents a diverse and dynamic population of microorganisms that can influence the health of the host, including the development of neurological disorders like Alzheimer's disease (AD). However, the intricate mechanisms governing the interplay between the gut and brain remain elusive, and the means by which gut-derived signals traverse the CNS barriers remain unclear.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the most common tauopathy and characterized by the progressive accumulation of Aß and tau. Tau is expressed in two major isoforms containing either 3 or 4 c-terminal repeats labeled as 3R and 4R tau. While these two isoforms occur in roughly equimolar ratios in AD, most research focus and mouse models of tau center only the 4Rtau protein and not 3Rtau.

Basic Science and Pathogenesis.

Background: Senescence is a cellular response to stress or damage leading to a state of irreversible growth arrest. As we age, the number of senescent cells increases and directly contributes to age-related conditions including cancer and neurodegenerative diseases. As a result, there is a growing interest to therapeutically target senescence either with drugs eliminating senescent cells (senolytics) or with strategies to modulate their secretory phenotype among others.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is associated with synaptic and memory dysfunction. A pathological hallmark of the disease is reactive astrogliosis, with reactive astrocytes surrounding amyloid plaques in the brain. Astrocytes have also been shown to be actively involved in disease progression, nevertheless, mechanistic information about their role in synaptic transmission during AD pathology is lacking.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD), characterized by significant brain volume reduction, is influenced by genetic predispositions related to brain volumetric phenotypes. While genome-wide association studies (GWASs) have linked brain imaging-derived phenotypes (IDPs) with AD, existing polygenic risk scores (PRSs) based models inadequately capture this relationship. We develop BrainNetScore, a network-based model enhancing AD risk prediction by integrating genetic associations between multiple brain IDPs and AD incidence.

Basic Science and Pathogenesis.

Background: Despite significant advancements in the development of blood biomarkers for AD, challenges persist due to the complex interplay of genetic and environmental risk factors in AD pathogenesis. Epigenetic processes, including non-coding RNAs and especially microRNAs (miRs), have emerged as important players in the molecular mechanisms underlying neurodegenerative diseases. MiRs have the ability to fine-tune gene expression and proteostasis, and microRNAome profiling in liquid biopsies is gaining increasing interest since changes in miR levels can indicate the presence of multiple pathologies.

Basic Science and Pathogenesis.

Background: Huntington's disease (HD) is an autosomal dominant condition causing severe neurodegeneration in the striatum and the entorhinal cortex (EC). An epigenome wide association study of DNA methylation in HD by our group, identified potential hypomethylation at the PTGDS gene in the striatum. We aimed to validate this result through pyrosequencing, examining the locus in fine detail, and to assess the signal specificity by profiling multiple neurodegenerative diseases.

Basic Science and Pathogenesis.

Background: The recent approval of two anti-amyloid antibodies, Aducanamab and Lecanamab, have set the stage for the next generation of anti-amyloid treatments. Despite the capability of these treatments to lower Aβ brain levels, there is thus far limited clinical efficacy on cognitive outcomes. Because eligibility for treatment includes individuals with MCI or mild dementia, that often harbor mixed pathologies, the cognitive impact of other brain pathologies may be important.