Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma.

The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, during the last decade. These treatment modalities re-enable the patient's own immune system to combat malignant cells and offer the potential for sustained remissions and cure for various diseases.Age profoundly affects the physiological function of the immune system.

Identification and validation of WDR5 WIN-site ligands via DNA-encoded chemical library screening.

WD repeat-containing protein 5 (WDR5) is a scaffolding protein involved in critical protein-protein interactions and a promising target for therapeutic development. Novel small-molecule ligands targeting WDR5 were identified using the DELopen platform, a free-access DNA-encoded chemical library (DEL) for academic research. Through off-DNA structure-activity relationship studies and photoaffinity labeling, two promising initial leads, DBL-6-13 and DBL-6-33, were identified as new binders of WDR5.

The crucial involvement of gamma-Mangostin and CYP1B1 in the mechanism underlying the toxicity caused by cigarette smoke extract: In silico and in vitro insights.

Cigarette smoke extracts (CSE) contain harmful substances that significantly contribute to respiratory conditions. Previous studies have primarily focused on the presence of carcinogens in CSE. However, it should be noted that other compounds may also synergistically contribute to a greater impact.

SurfDock is a surface-informed diffusion generative model for reliable and accurate protein-ligand complex prediction.

Accurately predicting protein-ligand interactions is crucial for understanding cellular processes. We introduce SurfDock, a deep-learning method that addresses this challenge by integrating protein sequence, three-dimensional structural graphs and surface-level features into an equivariant architecture. SurfDock employs a generative diffusion model on a non-Euclidean manifold, optimizing molecular translations, rotations and torsions to generate reliable binding poses.

Vital lessons from struggling partnerships and potential partnerships: an international study with leaders across the health sector.

Background: Inter-organizational partnerships and collaborations, used here interchangeably, have growing prominence across the health sector. Successful partnerships have received extensive study. However, especially for partnerships including nonprofit partners, limited attention has been given to negative factors that contribute to struggling partnerships, including failed partnerships, and/or impede potential partnerships, including unexplored and undeveloped potential partnerships.

IMPDH inhibitors upregulate PD-L1 in cancer cells without impairing immune checkpoint inhibitor efficacy.

Tumor cells are characterized by rapid proliferation. In order to provide purines for DNA and RNA synthesis, inosine 5'-monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo guanosine biosynthesis, is highly expressed in tumor cells. In this study we investigated whether IMPDH was involved in cancer immunoregulation.

Isorhapontigenin alleviates acetaminophen-induced liver injury by promoting fatty acid oxidation.

Acetaminophen (APAP) is a widely used analgesic and antipyretic medicine. It is frequently employed to alleviate pain and mitigate fever-related symptoms, but it can cause liver injury or even liver failure when overdosed. Isorhapontigenin, a compound derived from Chinese herbs and grapes, has been demonstrated to exhibit antioxidant and anti-inflammatory effects.

OncoSexome: the landscape of sex-based differences in oncologic diseases.

The NIH policy on sex as biological variable (SABV) emphasized the importance of sex-based differences in precision oncology. Over 50% of clinically actionable oncology genes are sex-biased, indicating differences in drug efficacy. Research has identified sex differences in non-reproductive cancers, highlighting the need for comprehensive sex-based cancer data.

Predicting Pancreatic Cancer in New-Onset Diabetes Cohort Using a Novel Model With Integrated Clinical and Genetic Indicators: A Large-Scale Prospective Cohort Study.

Introduction: Individuals who develop new-onset diabetes have been identified as a high-risk cohort for pancreatic cancer (PC), exhibiting an incidence rate nearly 8 times higher than the general population. Hence, the targeted screening of this specific cohort presents a promising opportunity for early pancreatic cancer detection. We aimed to develop and validate a novel model capable of identifying high-risk individuals among those with new-onset diabetes.

Accuracy and efficiency of drilling trajectories with augmented reality versus conventional navigation randomized crossover trial.

Conventional navigation systems (CNS) in surgery require strong spatial cognitive abilities and hand-eye coordination. Augmented Reality Navigation Systems (ARNS) provide 3D guidance and may overcome these challenges, but their accuracy and efficiency compared to CNS have not been systematically evaluated. In this randomized crossover study with 36 participants from different professional backgrounds (surgeons, students, engineers), drilling accuracy, time and perceived workload were evaluated using ARNS and CNS.

Carrier-free immobilized enzyme for ligand fishing of carbonic anhydrase inhibitors in Salvia miltiorrhiza.

The traditional method for natural products discovering could be time-consuming and labor-intensive, thus ligand fishing has attracted a lot of attention as a fast-screening method. Nevertheless, ligand fishing often relied on immobilized enzyme with solid carriers, which can be expensive and complicated to prepare. In this study, a carrier-free enzyme immobilization technology, cross-linked enzyme aggregates (CLEAs), was introduced by preparing carbonic anhydrase cross-linked enzyme aggregates (CA-CLEAs), aiming to develop a method for ligand fishing that is simpler, faster and more cost-effective.

Sorcin can trigger pancreatic cancer-associated new-onset diabetes through the secretion of inflammatory cytokines such as serpin E1 and CCL5.

A rise in blood glucose is an early warning sign of underlying pancreatic cancer (PC) and may be an indicator of genetic events in PC progression. However, there is still a lack of mechanistic research on pancreatic cancer-associated new-onset diabetes (PCAND). In the present study, we identified a gene SRI, which possesses a SNP with the potential to distinguish PCAND and Type 2 diabetes mellitus (T2DM), by machine learning on the basis of the UK Biobank database.

Metabolic reprogramming in KRAS-mutant cancers: Proven targetable vulnerabilities and potential therapeutic strategies.

Kras (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog), one of the most frequently mutated oncogenes in the human genome, is considered 'untargetable'. Although specific KRAS inhibitors have been developed, their overall impact is limited, highlighting the need for further research on targeting KRAS-mutant cancers. Metabolic abnormalities are key hallmarks of cancer, with KRAS-driven tumors exhibiting traits like glycolysis upregulation, glutamine addiction, lipid droplet accumulation, highly active macropinocytosis, and metabolic reprogramming-associated tumor microenvironment remodeling.

Leveraging Machine Learning to Identify Subgroups of Misclassified Patients in the Emergency Department: Multicenter Proof-of-Concept Study.

Background: Hospitals use triage systems to prioritize the needs of patients within available resources. Misclassification of a patient can lead to either adverse outcomes in a patient who did not receive appropriate care in the case of undertriage or a waste of hospital resources in the case of overtriage. Recent advances in machine learning algorithms allow for the quantification of variables important to under- and overtriage.

Chem(Pro)2: the atlas of chemoproteomic probes labelling human proteins.

Chemoproteomic probes (CPPs) have been widely considered as powerful molecular biological tools that enable the highly efficient discovery of both binding proteins and modes of action for the studied compounds. They have been successfully used to validate targets and identify binders. The design of CPP has been considered extremely challenging, which asks for the generalization using a large number of probe data.

WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc.

The dysfunction of the ubiquitin-proteasome system (UPS) facilitates the malignant progression of hepatocellular carcinoma (HCC). While targeting the UPS for HCC therapy has been proposed, identifying effective targets has been challenging. In this study, we conducted a focused screen of siRNA libraries targeting UPS-related WD40 repeat (WDR) proteins and found that silencing WDR20, a deubiquitinating enzyme activating factor, selectively inhibited the proliferation of HCC cells without affecting normal hepatocytes.

Trans-arterial embolization for treatment of acute lower gastrointestinal bleeding-a multicenter analysis.

Purpose: To assess the technical feasibility, safety, and clinical success rate of trans-arterial embolization (TAE) as an emergency treatment for acute lower gastrointestinal bleeding (LGIB).

Materials And Methods: Consecutive patients who received urgent TAE due to active LGIB at five academic centers in Germany were retrospectively analyzed. LGIB was confirmed and localized using contrast-enhanced computed tomography (CT) or endoscopy.

Opportunistic Screening for Low Bone Mineral Density in Adults with Cystic Fibrosis Using Low-Dose Computed Tomography of the Chest with Artificial Intelligence.

Cystic fibrosis bone disease (CFBD) is a common comorbidity in adult people with cystic fibrosis (pwCF), resulting in an increased risk of bone fractures. This study evaluated the capacity of artificial intelligence (AI)-assisted low-dose chest CT (LDCT) opportunistic screening for detecting low bone mineral density (BMD) in adult pwCF. In this retrospective single-center study, 65 adult pwCF (mean age 30.

In-depth theoretical modeling to explore the mechanism of TPX-0131 overcoming lorlatinib resistance to ALK mutation.

A number of anaplastic lymphoma kinase (ALK) inhibitors have been clinically approved, with lorlatinib, particularly as a third-generation drug, demonstrating efficacy against various drug-resistant ALK single mutations. However, continued clinical use of lorlatinib has led to the emergence of ALK double mutations conferring resistance to lorlatinib, notably ALK. TPX-0131 is a potential fourth-generation ALK inhibitor currently under development.

CT-based body composition analysis and pulmonary fat attenuation volume as biomarkers to predict overall survival in patients with non-specific interstitial pneumonia.

Background: Non-specific interstitial pneumonia (NSIP) is an interstitial lung disease that can result in end-stage fibrosis. We investigated the influence of body composition and pulmonary fat attenuation volume (CTpfav) on overall survival (OS) in NSIP patients.

Methods: In this retrospective single-center study, 71 NSIP patients with a median age of 65 years (interquartile range 21.

The role of Tim-3 blockade in the tumor immune microenvironment beyond T cells.

Numerous preclinical studies have demonstrated the inhibitory function of T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) on T cells as an inhibitory receptor, leading to the clinical development of anti-Tim-3 blocking antibodies. However, recent studies have shown that Tim-3 is expressed not only on T cells but also on multiple cell types in the tumor microenvironment (TME), including dendritic cells (DCs), natural killer (NK) cells, macrophages, and tumor cells. Therefore, Tim-3 blockade in the immune microenvironment not only affect the function of T cells but also influence the functions of other cells.