CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.

Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).

Development and Validation of an AI-Based Multimodal Model for Pathological Staging of Gastric Cancer Using CT and Endoscopic Images.

Rationale And Objectives: Accurate preoperative pathological staging of gastric cancer is crucial for optimal treatment selection and improved patient outcomes. Traditional imaging methods such as CT and endoscopy have limitations in staging accuracy.

Methods: This retrospective study included 691 gastric cancer patients treated from March 2017 to March 2024.

Global Fatty Degeneration Index on Preoperative Magnetic Resonance Imaging Predicts Early Postoperative Shoulder Stiffness at 3 Months After Primary Rotator Cuff Repair.

Purpose: To determine whether the fatty infiltration of rotator cuff muscles, as measured by magnetic resonance imaging (MRI) preoperatively and assessed using the Goutallier fatty degeneration index (GFDI), can predict early postoperative shoulder stiffness (POSS) after rotator cuff repair (RCR).

Methods: This retrospective longitudinal cohort study included patients who underwent primary RCR, had available medical records, and underwent MRI before RCR between November 2012 and July 2022. Patients were excluded on the basis of the following criteria: (1) preoperative shoulder stiffness, (2) additional procedures (e.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.

Feasibility of Sub-milliSievert Low-dose Computed Tomography with Deep Learning Image Reconstruction in Evaluating Pulmonary Subsolid Nodules: A Prospective Intra-individual Comparison Study.

Rationale And Objectives: To comprehensively assess the feasibility of low-dose computed tomography (LDCT) using deep learning image reconstruction (DLIR) for evaluating pulmonary subsolid nodules, which are challenging due to their susceptibility to noise.

Materials And Methods: Patients undergoing both standard-dose CT (SDCT) and LDCT between March and June 2023 were prospectively enrolled. LDCT images were reconstructed with high-strength DLIR (DLIR-H), medium-strength DLIR (DLIR-M), adaptive statistical iterative reconstruction-V level 50% (ASIR-V-50%), and filtered back projection (FBP); SDCT with FBP as the reference standard.

Non-Markovian Dynamic Models Identify Non-Canonical KRAS-VHL Encounter Complex Conformations for Novel PROTAC Design.

Targeted protein degradation (TPD) is emerging as a promising therapeutic approach for cancer and other diseases, with an increasing number of programs demonstrating its efficacy in human clinical trials. One notable method for TPD is Proteolysis Targeting Chimeras (PROTACs) that selectively degrade a protein of interest (POI) through E3-ligase induced ubiquitination followed by proteasomal degradation. PROTACs utilize a warhead-linker-ligand architecture to bring the POI (bound to the warhead) and the E3 ligase (bound to the ligand) into proximity.

Development of a Novel Label-Free Subunit HILIC-MS Method for Domain-Specific Free Thiol Identification and Quantitation in Therapeutic Monoclonal Antibodies.

Cysteine residues are crucial for the formation of conserved disulfide bonds in therapeutic monoclonal antibodies (mAbs), which are essential for their folding and structural stability. The presence of free thiols in mAbs can indicate incomplete disulfide bond formation, potentially impacting the molecule's conformational stability. Free thiol quantitation has been achieved using labeling-based strategies such as maleimide and haloalkyl derivatives at both intact and peptide levels.

Decision Fusion Model for Predicting Microvascular Invasion in Hepatocellular Carcinoma Based on Multi-MR Habitat Imaging and Machine-Learning Classifiers.

Rationale And Objectives: Accurate prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is crucial for guiding treatment. This study evaluates and compares the performance of clinicoradiologic, traditional radiomics, deep-learning radiomics, feature fusion, and decision fusion models based on multi-region MR habitat imaging using six machine-learning classifiers.

Materials And Methods: We retrospectively included 300 HCC patients.

Colocalization of Cancer-Associated Biomarkers on Single Extracellular Vesicles for Early Detection of Cancer.

Detection of cancer early, when it is most treatable, remains a significant challenge because of the lack of diagnostic methods sufficiently sensitive to detect nascent tumors. Early-stage tumors are small relative to their tissue of origin, heterogeneous, and infrequently manifest in clinical symptoms. The detection of early-stage tumors is challenging given the lack of tumor-specific indicators (ie, protein biomarkers, circulating tumor DNA) to enable detection using a noninvasive diagnostic assay.

Surface Microstructure Study on Corona Discharge-Treated Polyethylene Using Positron Annihilation Spectroscopy.

The microstructure and chemical properties of the corona discharge process could provide an effective method for predicting the performance of high-voltage cable insulation materials. In this work, the depth profile of the microstructure and chemical characteristics of corona discharge-treated PE were extensively investigated using Doppler broadening of position annihilation spectroscopy accompanied with positron annihilation lifetime spectroscopy, attenuated total reflectance Fourier transform infrared spectra, Raman spectra and contact angle measurement. By increasing corona discharge duration, the oxygen-containing polar groups, including hydroxyl, carbonyl and ester groups, strongly contribute to the deterioration of hydrophobicity and the enhancement of hydrophilicity.

Development of a breastfeeding co-parenting intervention program for couples with primiparas: a program development process study.

Background: The exclusive breastfeeding rates is low in some countries. Low breastfeeding rates results in higher healthcare expenses and adverse health outcomes for individuals and society. Co-parenting is effective in promoting breastfeeding as it involves shared responsibility and collaboration between parents in raising children.

Entangling gates on degenerate spin qubits dressed by a global field.

Semiconductor spin qubits represent a promising platform for future large-scale quantum computers owing to their excellent qubit performance, as well as the ability to leverage the mature semiconductor manufacturing industry for scaling up. Individual qubit control, however, commonly relies on spectral selectivity, where individual microwave signals of distinct frequencies are used to address each qubit. As quantum processors scale up, this approach will suffer from frequency crowding, control signal interference and unfeasible bandwidth requirements.

A fully automatic tool for development of population pharmacokinetic models.

Population pharmacokinetic (PK) models are widely used to inform drug development by pharmaceutical companies and facilitate drug evaluation by regulatory agencies. Developing a population PK model is a multi-step, challenging, and time-consuming process involving iterative manual model fitting and evaluation. A tool for fully automatic model development (AMD) of common population PK models is presented here.

The ISR downstream target ATF4 represses long-term memory in a cell type-specific manner.

The integrated stress response (ISR), a pivotal protein homeostasis network, plays a critical role in the formation of long-term memory (LTM). The precise mechanism by which the ISR controls LTM is not well understood. Here, we report insights into how the ISR modulates the mnemonic process by using targeted deletion of the activating transcription factor 4 (ATF4), a key downstream effector of the ISR, in various neuronal and non-neuronal cell types.

Affinity-Resolved Size Exclusion Chromatography Coupled to Mass Spectrometry: A Novel Tool to Study the Attribute-and-Function Relationship in Therapeutic Monoclonal Antibodies.

Assessment of critical quality attributes (CQAs) is an important aspect during the development of therapeutic monoclonal antibodies (mAbs). Attributes that affect either the target binding or Fc receptor engagement may have direct impacts on the drug safety and efficacy and thus are considered as CQAs. Native size exclusion chromatography (SEC)-based competitive binding assay has recently been reported and demonstrated significant benefits compared to conventional approaches for CQA identification, owing to its faster turn-around and higher multiplexity.

Discovery of Potent, Orally Bioavailable Sphingosine-1-Phosphate Transporter (Spns2) Inhibitors.

Targeting the S1P pathway has resulted in the development of S1P1 receptor modulators for the treatment of multiple sclerosis and ulcerative colitis. We hypothesize that targeting an upstream node of the S1P pathway may provide an improved adverse event profile. In this report, we performed a structure-activity relationship study focusing on the benzoxazole scaffold in , which lead to the discovery of () as a potent inhibitor of S1P release from HeLa cells (IC: 51 ± 3 nM).

Validation Study of the Newly Proposed Refined Diagnostic Criteria for Malignant Phyllodes Tumor With 136 Borderline and Malignant Phyllodes Tumor Cases.

The World Health Organization (WHO) diagnostic criteria for malignant phyllodes tumor (MPT) may miss a significant number of MPTs with metastatic potential. New refined diagnostic criteria (Refined Criteria) for MPT were recently proposed. The aim of this study is to validate the Refined Criteria.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

Background: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS.

Methods: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m) and cisplatin (75 mg/m).

ZBTB11 Depletion Targets Metabolic Vulnerabilities in K-Ras Inhibitor Resistant PDAC.

Over 95% of pancreatic ductal adenocarcinomas (PDAC) harbor oncogenic mutations in K-Ras. Upon treatment with K-Ras inhibitors, PDAC cancer cells undergo metabolic reprogramming towards an oxidative phosphorylation-dependent, drug-resistant state. However, direct inhibition of complex I is poorly tolerated in patients due to on-target induction of peripheral neuropathy.