Addition of SHR-1701 to first-line capecitabine and oxaliplatin (XELOX) plus bevacizumab for unresectable metastatic colorectal cancer.

This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β, in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment for unresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologically confirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients received SHR-1701 (30 mg/kg), bevacizumab (7.

Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at F-SynVesT-1 Brain PET Imaging.

Background Synaptic loss is an important factor in Alzheimer disease (AD); however, blood assays that conveniently and rapidly reflect changes in synaptic density are lacking. Purpose To correlate multiple potential synaptic blood markers with synaptic density measured using F-SynVesT-1, a fluorine 18 (F)-labeled radiotracer, brain PET and to explore the independent associations between these markers and synaptic density. Materials and Methods This prospective study included 50 cognitively unimpaired (mean age, 65.

Predicting Preoperative Pathologic Grades of Bladder Cancer Using Intravoxel Incoherent Motion and Amide Proton Transfer-Weighted Imaging.

Rationale And Objectives: To investigate the predictive value of intravoxel incoherent motion (IVIM) combined with amide proton transfer-weighted (APTw) imaging for the preoperative grading of bladder cancer (BC).

Materials And Methods: A total of 69 patients with histopathologically confirmed BC underwent diffusion-weighted imaging (DWI), IVIM, and APTw imaging at 3.0 T MRI.

A Nomogram for the Prediction of Invasiveness in Invasive Pulmonary Adenocarcinoma on the Basis of Multimodal PET/CT Parameters.

Objective: We investigated the value of PET/CT-based multimodal parameters in predicting the degree of differentiation and epidermal growth factor receptor (EGFR) mutations in invasive lung adenocarcinoma (ILA) and assessed the correlation between PET/CT-based multimodal parameters and Ki67.

Methods: We retrospectively collected 113 patients with ILA who underwent PET/CT examination, and differences in PET/CT multimodal parameters between different differentiation groups were analyzed. Binary logistic regression was used to establish a multiparameter model for predicting EGFR mutation, and ROC curve was used to compare the diagnostic efficiency.

Intra-channel bi-epitopic crosslinking unleashes ultrapotent antibodies targeting Na1.7 for pain alleviation.

Crucial for cell activities, ion channels are key drug discovery targets. Although small-molecule and peptide modulators dominate ion channel drug discovery, antibodies are emerging as an alternative modality. However, challenges persist in generating potent antibodies, especially for channels with limited extracellular epitopes.

Exploring Anticancer Potential of Strains: Insights into Cytotoxicity and Apoptotic Mechanisms on HCT 115 Cancer Cells.

Introduction: This study aims to systematically assess the anticancer potential of distinct strains on Human Colorectal Tumor (HCT) 115 cancer cells, with a primary focus on the apoptotic mechanisms involved. strains were isolated from sheep milk and underwent a meticulous microbial isolation process. Previous research indicates that certain probiotic bacteria, including Lactobacillus species, may exhibit anticancer properties through mechanisms such as apoptosis induction.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide.

Total Talus Allograft Transplantation With Subtalar Arthrodesis for Missing Talus: A Report of a Rare Case.

Post-traumatic missing talus is a rare and severe injury that often results in poor functional outcomes, with no consensus on the optimal treatment approach as strategies vary based on injury severity. We present the case of a 44-year-old male who sustained a missing talus following a high-energy motorcycle accident. After initial wound management and application of an external fixator, the patient underwent size-matched, fresh-frozen talus allograft transplantation combined with subtalar fusion.

Multiomic single cell sequencing identifies stemlike nature of mixed phenotype acute leukemia.

Despite recent work linking mixed phenotype acute leukemia (MPAL) to certain genetic lesions, specific driver mutations remain undefined for a significant proportion of patients and no genetic subtype is predictive of clinical outcomes. Moreover, therapeutic strategy for MPAL remains unclear, and prognosis is overall poor. We performed multiomic single cell profiling of 14 newly diagnosed adult MPAL patients to characterize the inter- and intra-tumoral transcriptional, immunophenotypic, and genetic landscapes of MPAL.

Drug-Related Keratitis: A Real-World FDA Adverse Event Reporting System Database Study.

Purpose: This study aimed to assess the drug risk of drug-related keratitis and track the epidemiological characteristics of drug-related keratitis.

Methods: This study analyzed data from the U.S.

Longitudinal refractive errors over 36 months in Hispanic and Black children.

Significance: This study brings awareness of racial/ethnic difference of refractive error characteristics in clinics.

Purpose: This study aimed to assess longitudinal change in refractive errors over a 36-month period in Hispanic and Black children.

Methods: Children (2.

Association of serum 25-hydroxyvitamin D concentrations and myopia in the U.S. Population - Results from the NHANES 2001-2008.

Background: myopia is associated with sight-threatening potential complications, and it becoming increasingly common globally. However, the association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and myopia remains unclear and the evidence is controversial. Thus, this study aimed to investigate the association between serum 25(OH)D concentrations and myopia in the U.

Pharmacokinetics of olverembatinib (HQP1351) in the presence of a strong CYP3A4 inhibitor (itraconazole) or inducer (rifampin) in healthy volunteers.

Olverembatinib (HQP1351) is a BCR-ABL1 tyrosine kinase inhibitor with promising clinical activity. It is approved in China for the treatment of patients with chronic myeloid leukemia harboring drug-resistant mutations, such as T315I. In vitro studies suggested that metabolism of olverembatinib is primarily mediated by cytochrome P450 (CYP3A4).

Generation of dual-attribute iTNK cells from hPSCs for cancer immunotherapy.

Dual-attribute immune cells possess advantageous features of cytotoxic T cells and natural killer (NK) cells and hold promise for advancing immunotherapy. Dual-attribute cell types such as invariant natural killer T cells, induced T-to-NK cells, and cytokine-induced killer cells have demonstrated efficacy and safety in preclinical and clinical studies. However, their limited availability hinders their widespread application.

Antisense Oligonucleotide Therapy for Calmodulinopathy.

Background: Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in , , or , which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)-mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function.

Methods: We tested this hypothesis using human induced pluripotent stem cell-derived cardiomyocyte and mouse models of pathogenic variants.

A Feasibility Study of AI-Assisted Compressed Sensing in Prostate T2-Weighted Imaging.

Rationale And Objectives: To evaluate the image quality and PI-RADS scoring performance of prostate T2-weighted imaging (T2WI) based on AI-assisted compressed sensing (ACS).

Materials And Methods: In this prospective study, adult male urological outpatients or inpatients underwent prostate MRI, including T2WI, diffusion-weighted imaging and apparent diffusion coefficient maps. Three accelerated scanning protocols using parallel imaging (PI) and ACS: T2WI, T2WI and T2WI were evaluated through comparative analysis.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.

Efficacy, immunogenicity, and safety of a monovalent mRNA vaccine, ABO1020, in adults: A randomized, double-blind, placebo-controlled, phase 3 trial.

Background: ABO1020 is a monovalent COVID-19 mRNA vaccine. Results from a phase 1 trial showed ABO1020 was safe and well tolerated, and phase 3 trials to evaluate the efficacy, immunogenicity, and safety of ABO1020 in healthy adults are urgently needed.

Methods: We conducted a multinational, randomized, placebo-controlled, double-blind, phase 3 trial among healthy adults (ClinicalTrials.

Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841).

Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs.

A 5' UTR Language Model for Decoding Untranslated Regions of mRNA and Function Predictions.

The 5' UTR, a regulatory region at the beginning of an mRNA molecule, plays a crucial role in regulating the translation process and impacts the protein expression level. Language models have showcased their effectiveness in decoding the functions of protein and genome sequences. Here, we introduced a language model for 5' UTR, which we refer to as the UTR-LM.