Textbook Neoadjuvant Experience: Defining a Novel Composite Outcomes Measure for Patients with Pancreatic Cancer Undergoing Neoadjuvant Therapy.

Background: Neoadjuvant therapy (NT) is increasingly utilized for patients with pancreatic ductal adenocarcinoma (PDAC). Disease progression, toxicity, and failure to undergo surgical resection are common during NT, yet little research has focused on efforts to optimize care delivery. We sought to define and validate a novel composite outcomes metric that characterizes the successful delivery of NT.

Calpain 2 regulates IL-1α secretion and inhibits tumor development via modulating calpain 1 expression in the tumor microenvironment.

Tumor-promoting inflammation significantly impacts cancer progression, and targeting inflammatory cytokines has emerged as a promising therapeutic approach in clinical trials. Interleukin (IL)-1α, a member of the IL-1 cytokine family, plays a crucial role in both inflammation and carcinogenesis. How IL-1α is secreted in the tumor microenvironment has been poorly understood, and we previously showed that calpain 1 cleaves pro-IL-1α for mature IL-1α secretion, which exacerbates hepatocellular carcinoma by recruiting myeloid-derived suppressor cells.

Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures.

Cerebellar Purkinje cells (PCs) exhibit a unique interplay of high metabolic rates, specific chromatin architecture, and extensive transcriptional activity, making them particularly vulnerable to DNA damage. This necessitates an efficient DNA damage response (DDR) to prevent cerebellar degeneration, often initiated by PC dysfunction or loss. A notable example is the genome instability syndrome, ataxia-telangiectasia (A-T), marked by progressive PC depletion and cerebellar deterioration.

Influence of Preoperative Physical Function Scores on Outcomes After Single-level Cervical Disc Replacement.

Study Design: Retrospective study.

Objective: We aim to determine the influence of preoperative Patient-Reported Outcome Measurement Information System Physical Function (PROMIS-PF) scores on perioperative and postoperative outcomes, the latter determined through patient-reported outcome measures (PROMs) and the degree of achievement rates of minimum clinically important difference (MCID) following single-level cervical disc replacement (CDR).

Background: Several studies have examined the relationship between preoperative PROMIS-PF as a prognostic factor for postoperative outcomes.

Correlation between IL-17 and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a protracted, persistent gastrointestinal disease that is distinguished by recurring, persistent inflammation of the digestive tract. IBD, including Crohn's disease and ulcerative colitis, is characterized by persistent inflammation due to immune dysregulation. Interleukin -17 (IL-17) contributes significantly to the pathophysiology of IBD, as highlighted in the context of the provided research.

Downregulation of proinflammatory cytokines and dynamic expression of TGF-β1 molecules induced by anti-IL-17 mAb in murine schistosomiasis mansoni.

Hepato-intestinal schistosomiasis is characterized by severe pathological changes at advanced chronic stages, including granulomatous lesions and liver fibrosis. The objective of our research was to assess the dynamic expression of profibrotic molecules, the transforming growth factor beta 1 (TGF-β1), and proinflammatory cytokines immunomodulation induced by interleukin 17 (IL-17) neutralization in murine Schistosomiasis mansoni. The study included 56 specific pathogen-free male C57BL/6 mice, divided into 3 main groups: GI uninfected normal controls, GII S.

Regioselective N1-ribosylation of hydantoin: synthesis and properties of the first contracted uridine analog.

Modified nucleosides are vital in mRNA vaccines. We developed a contracted uridine analog, N1-hydantoinyl-ribose, HR, using steric shields to invert the regioselectivity of the classic Vorbrüggen reaction. We report synthetic routes and explore HR features such as acidity, stability, base pairing/stacking, and crystal/solution conformation compared to uridine.

Left superior cervical ganglia lymph node mimicry and its role in rat ventricular arrhythmias following myocardial infarction.

Aim: Sympathetic overactivation may lead to severe ventricular arrhythmias (VAs) post-myocardial infarction (MI). The superior cervical ganglion (SCG) is an extracardiac sympathetic ganglion which regulates cardiac autonomic tone. We aimed to investigate the characteristics and functional significance of SCG on neuro-cardiac communication post-MI.

Retrospective analysis of clinical and molecular characteristics as prognostic factors in adult T-cell lymphoblastic lymphoma.

Objective: To analyze the clinical characteristics and molecular biomarkers of adult T-cell lymphoblastic lymphoma (T-LBL) to identify prognostic factors, and to evaluate the efficacy of different chemotherapy regimens, providing a basis for optimizing treatment strategies for T-LBL.

Methods: A total of 89 Patients aged 18-72 years with T-LBL, confirmed via histopathological examination of lymph nodes, extranodal tissues, or bone marrow, were retrospectively included. Clinical data, treatment details, and mutational profiles were collected.

Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is a lethal endocrine malignancy. It has been shown that tumor-associated macrophages (TAMs) contribute to the aggressiveness of ATC. However, stimulatory factors that could facilitate the induction and infiltration of TAMs in the ATC tumor microenvironment (TME) are not fully elucidated.

Brainstem infarct from cervical vertebral artery dissection presenting as a transient Parinaud syndrome.

Purpose: To report a case of transient diplopia and upgaze paresis in the setting of acute dorsal midbrain infarcts from a cervical vertebral artery dissection in an otherwise healthy man.

Observations: A 33-year old man presented to the ophthalmology urgent clinic with a 1 h history of blurred and double vision, asthenopia, and a mild focal left posterior headache. Ocular motility examination revealed a profound upgaze palsy and convergence-retraction horizontal jerk nystagmus in attempted upgaze that gradually improved over the course of 1 h.

A microphysiological system of sterile injury demonstrates neutrophil reverse migration via macrophage-derived extracellular vesicle crosstalk.

Persistent neutrophilic inflammation can lead to tissue damage and chronic inflammation, contributing to non-healing wounds. The resolution phase of neutrophilic inflammation is critical to preventing tissue damage, as observed in diseases characterized by influx of neutrophils such as atherosclerosis and non-healing wounds. Animal models have provided insight into resolution of neutrophilic inflammation via efferocytosis and reverse migration (rM); however, species-specific differences and complexity of innate immune responses make translation to humans challenging.

Protein CREATE enables closed-loop design of synthetic protein binders.

Proteins have proven to be useful agents in a variety of fields, from serving as potent therapeutics to enabling complex catalysis for chemical manufacture. However, they remain difficult to design and are instead typically selected for using extensive screens or directed evolution. Recent developments in protein large language models have enabled fast generation of diverse protein sequences in unexplored regions of protein space predicted to fold into varied structures, bind relevant targets, and catalyze novel reactions.

BLOC1S1 control of vacuolar organelle fidelity modulates T 2 cell immunity and allergy susceptibility.

The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4 T cells, may further advance our understanding of regulatory events linked to mitochondrial and/or endolysosomal function in adaptive immunity.

Immune Checkpoint Molecules as Biomarkers of Staphylococcus aureus Bone Infection and Clinical Outcome.

Staphylococcus aureus prosthetic joint infections (PJIs) are broadly considered incurable, and clinical diagnostics that guide conservative vs. aggressive surgical treatments do not exist. Multi-omics studies in a humanized NSG-SGM3 BLT mouse model demonstrate human T cells: 1) are remarkably heterogenous in gene expression and numbers, and 2) exist as a mixed population of activated, progenitor-exhausted, and terminally-exhausted Th1/Th17 cells with increased expression of immune checkpoint proteins (LAG3, TIM-3).

A PI3Kδ-Foxo1-FasL signaling amplification loop rewires CD4 T helper cell signaling, differentiation and epigenetic remodeling.

While inputs regulating CD4 T helper cell (Th) differentiation are well-defined, the integration of downstream signaling with transcriptional and epigenetic programs that define Th-lineage identity remain unresolved. PI3K signaling is a critical regulator of T cell function; activating mutations affecting PI3Kδ result in an immunodeficiency with multiple T cell defects. Using mice expressing activated-PI3Kδ, we found aberrant expression of proinflammatory Th1-signature genes under Th2-inducing conditions, both and .

Fit for purpose testing and independent GMP validation of the monocyte activation test.

The present study describes the "fit for purpose" testing and the independent product-specific GMP validation of the monocyte activation test (MAT) to detect pyrogenic and pro-inflammatory contaminants, MAT Method A, Quantitative Test (European Pharmacopoeia, Ph. Eur. chapter 2.

Respiratory Protective Effects of Perilla Leave Varieties () Against Fine Particulate Matter (PM)-induced Damage in Human Nasal Cells.

Fine particulate matter (PM2.5) is known to exacerbate chronic respiratory disorders, primarily by inducing inflammatory responses and mucus overproduction. Perilla leaves are reported to have significant health benefits, such as antioxidant, antibacterial, and antiallergic properties, attributed to phenolic compounds that vary depending on genetic diversity.

The Potential of the Probiotic Isolate SS18-50 to Prevent Colitis in Mice.

The objective of this study was to investigate the effect of the () SS18-50 (an isolate with favorable probiotic properties following space traveling) on dextran sulfate sodium (DSS)-induced colitis in mice. Male ICR mice were randomly assigned to one of six groups: a control group, a model group, and four intervention groups comprising the isolate (SS18-50-L and SS18-50-H) and the wild type (GS18-L and GS18-H) strains. The model group and the intervention groups were administered a 3.

Sea Hare Hydrolysate Reduces PD-L1 Levels in Cancer Cells and Mitigates Rheumatoid Arthritis Ina Collagen-Induced Arthritis Mouse Model.

Our previous study highlighted the anticancer potential of sea hare hydrolysate (SHH), particularly its role in regulating macrophage polarization and inducing pyroptotic death in lung cancer cells through the inhibition of signal transducer and activator of transcription 3 (STAT3). These findings prompted us to investigate additional features of immune-oncology (I-O) agents or adjuvants, such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition and their association with rheumatoid arthritis (RA) risk, to explore the potential of SHH as an I-O agent or adjuvant. In this study, we investigated the effects of SHH on PD-L1 levels in various cancer cell types and assessed its effectiveness in treating RA, a common side effect of I-O agents.

Nutritional, Antibacterial and Thrombolytic Prospects of Freshwater Protein Hydrolysate and Its Anti-Inflammatory Potential in LPS-Induced RAW 264.7 Macrophage Cells.

Chronic inflammation and heme-iron overload can result from bacterial hemolysis. Along with the synthetic drugs, numerous traditional and functional food approaches are equally trialed to eradicate the problem. As a prospective new source of dietary protein hydrolysates, freshwater mollusks () have recently drawn huge interest from researchers.

The Role of Pharmacotherapy for Smoking Cessation and Pregnancy.

Tobacco and nicotine use is widely recognized as harmful to both the user and those exposed to the substances. Pregnant individuals face additional risks, with potential adverse outcomes for the fetus and newborn. A combination of behavioral and pharmacological interventions is recommended for smoking cessation; however, in pregnancy, there are additional considerations with the use of pharmacotherapy.

Efficacy, safety, and multi-omics analysis of pembrolizumab combined with nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: A single-arm phase 2 study.

Objective: Based on the findings of the KEYNOTE-048 study, pembrolizumab in combination with platinum and fluorouracil is the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The efficacy and safety of pembrolizumab combined with nab-paclitaxel and platinum in such patients remain unexplored.

Methods: This single-arm phase 2 study enrolled patients with R/M HNSCC who received pembrolizumab (200 mg), nab-paclitaxel (260 mg/m²), and either cisplatin (75 mg/m²) or carboplatin [area under the curve (AUC) 5] every 21 d for up to six cycles, followed by pembrolizumab maintenance therapy.

Prophylactic administration of PEPITEM in experimental autoimmune encephalomyelitis delays disease onset, inhibits leukocyte infiltration, and alleviates severity.

Background: Multiple sclerosis (MS) is a chronic, immune-mediated neurological disorder in which the immune system mistakenly attacks the myelin sheath, affecting the communication between the brain and the rest of the body.

Objective: This study investigated the prophylactic use of peptide inhibitor of trans-endothelial migration (PEPITEM), a novel peptide, in alleviating experimental autoimmune encephalomyelitis (EAE), a mouse model for Multiple Sclerosis (MS).

Methods: Female C57BL/6 female mice were assigned to the control, untreated EAE, or PEPITEM group.

Infant action understanding: the roles of active training and motor development.

Introduction: This study examined the potential interplay between motor development and intervention in support of action understanding.

Methods: Eighty nine-month-old infants completed a tool-use training session and goal imitation paradigm that assessed action understanding in counterbalanced order. A metric of motor development was obtained using the Early Motor Questionnaire.