Affinity-tuned mesothelin CAR T cells demonstrate enhanced targeting specificity and reduced off-tumor toxicity.

The application of chimeric antigen receptor (CAR) T cell therapy in solid tumors is hindered by life-threatening toxicities resulting from on-target, off-tumor killing of nonmalignant cells that express low levels of the target antigen. Mesothelin (MSLN) has been identified as a target antigen for CAR T cell treatment of mesothelioma, lung, ovarian, and other cancers because of its high expression on tumor cells and limited expression on mesothelial cells. However, fatal off-tumor toxicity of high-affinity MSLN-targeting CAR T cells has been reported in multiple clinical trials.

Developing a Predictive Model for Metastatic Potential in Pancreatic Neuroendocrine Tumor.

Context: Pancreatic neuroendocrine tumors (PNETs) exhibit a wide range of behavior from localized disease to aggressive metastasis. A comprehensive transcriptomic profile capable of differentiating between these phenotypes remains elusive.

Objective: Use machine learning to develop predictive models of PNET metastatic potential dependent upon transcriptomic signature.

Low-dose targeted radionuclide therapy synergizes with CAR T cells and enhances tumor response.

Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering -emitting Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2). We hypothesized that the delivery of radiation to tumors could synergize with CAR T therapy, resulting in enhanced antitumor immunity and tumor response.

Enhancement of denitrification by sulfur-based carrier in sequencing batch reactor (SBR) for advanced wastewater treatment.

This study was to enhance the nitrogen removal efficiency in the sequencing batch reactor (SBR) process by adding sulfur-based carriers. The nitrogen removal efficiency of the control group was compared with that of the experimental group through a two-series operation of SBR1 without carrier and SBR2 with the carrier under the condition of no external carbon source. A total nitrogen (T-N) removal efficiency of 6.

Chimeric Antigen Receptor T Cell Therapy Targeting Epithelial Cell Adhesion Molecule in Gastric Cancer: Mechanisms of Tumor Resistance.

Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen that is frequently overexpressed in various carcinomas. We have developed chimeric antigen receptor (CAR) T cells specifically targeting EpCAM for the treatment of gastric cancer. This study sought to unravel the precise mechanisms by which tumors evade immune surveillance and develop resistance to CAR T cell therapy.

A wireless, solar-powered, optoelectronic system for spatial restriction-free long-term optogenetic neuromodulations.

Numerous wireless optogenetic systems have been reported for practical tether-free optogenetics in freely moving animals. However, most devices rely on battery-powered or coil-powered systems requiring periodic battery replacement or bulky, high-cost charging equipment with delicate antenna design. This leads to spatiotemporal constraints, such as limited experimental duration due to battery life or animals' restricted movement within specific areas to maintain wireless power transmission.

Biomarker-Based Assessment Model for Detecting Sepsis: A Retrospective Cohort Study.

The concept of the quick sequential organ failure assessment (qSOFA) simplifies sepsis detection, and the next SOFA should be analyzed subsequently to diagnose sepsis. However, it does not include the concept of suspected infection. Thus, we simply developed a biomarker-based assessment model for detecting sepsis (BADS).

Pneumatic Compression-Assisted Lymphoscintigraphy for Quantitative Evaluation of Breast Cancer-Related Lymphedema.

Objectives: Acquired lymphedema of upper extremity is a chronic pathologic status that frequently occurs after breast cancer treatment. Reliable and quantitative evaluation of lymphedema is crucial for successful management of patients. Although lymphoscintigraphy is the primary investigation for the confirmation and evaluation of lymphedema, the specific protocol of stress intervention is not well established.

Fluorescent-based biodegradable microneedle sensor array for tether-free continuous glucose monitoring with smartphone application.

Continuous glucose monitoring (CGM) allows patients with diabetes to manage critical disease effectively and autonomously and prevent exacerbation. A painless, wireless, compact, and minimally invasive device that can provide CGM is essential for monitoring the health conditions of freely moving patients with diabetes. Here, we propose a glucose-responsive fluorescence-based highly sensitive biodegradable microneedle CGM system.

Outcomes in Patients with Pulmonary Arterial Hypertension Underwent Transcatheter Closure of an Atrial Septal Defect.

Pulmonary arterial hypertension (PAH) related to an atrial septal defect (ASD) poses a challenge to transcatheter closure of an ASD (tcASD). We aimed to determine the predictors for remaining PAH (rPAH) post-tcASD. This retrospective study was conducted at a single tertiary university hospital.

Inducible expression of interleukin-12 augments the efficacy of affinity-tuned chimeric antigen receptors in murine solid tumor models.

The limited number of targetable tumor-specific antigens and the immunosuppressive nature of the microenvironment within solid malignancies represent major barriers to the success of chimeric antigen receptor (CAR)-T cell therapies. Here, using epithelial cell adhesion molecule (EpCAM) as a model antigen, we used alanine scanning of the complementarity-determining region to fine-tune CAR affinity. This allowed us to identify CARs that could spare primary epithelial cells while still effectively targeting EpCAM tumors.

Activation of the JAK/STAT Pathway Leads to BRAF Inhibitor Resistance in BRAFV600E Positive Thyroid Carcinoma.

Unlabelled: A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis.

Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis.

This study aimed to evaluate the predictive performance of pre-existing well-validated hepatocellular carcinoma (HCC) prediction models, established in patients with HBV-related cirrhosis who started potent antiviral therapy (AVT). We retrospectively reviewed the cases of 1339 treatment-naïve patients with HBV-related cirrhosis who started AVT (median period, 56.8 months).

Metastatic pancreatic neuroendocrine tumors feature elevated T cell infiltration.

Pancreatic neuroendocrine tumors (PNETs) are malignancies arising from the islets of Langerhans. Therapeutic options are limited for the over 50% of patients who present with metastatic disease. We aimed to identify mechanisms to remodel the PNET tumor microenvironment (TME) to ultimately enhance susceptibility to immunotherapy.

Effect of Applying a Real-Time Medical Record Input Assistance System With Voice Artificial Intelligence on Triage Task Performance in the Emergency Department: Prospective Interventional Study.

Background: Natural language processing has been established as an important tool when using unstructured text data; however, most studies in the medical field have been limited to a retrospective analysis of text entered manually by humans. Little research has focused on applying natural language processing to the conversion of raw voice data generated in the clinical field into text using speech-to-text algorithms.

Objective: In this study, we investigated the promptness and reliability of a real-time medical record input assistance system with voice artificial intelligence (RMIS-AI) and compared it to the manual method for triage tasks in the emergency department.

Sex-Based Clinicopathologic and Survival Differences Among Patients with Pancreatic Neuroendocrine Tumors.

Introduction: Sex-based differences in survival have emerged among patients with pancreatic neuroendocrine tumors (PNETs). Mechanisms driving these differences remain poorly understood. We aimed to further characterize sex-based clinicopathologic and survival differences among patients with PNETs and correlate divergent mutational signatures in these patients.

A propensity score-adjusted analysis of efficacy of high-flow nasal oxygen during awake tracheal intubation.

Oxygen supplementation is crucial for awake tracheal intubation (ATI) using a flexible bronchoscope in patients with an anticipated difficult airway. However, the modality of optimal oxygen delivery remains unclear. This retrospective study compared high-flow nasal oxygen (HFNO) and conventional low-flow oxygen supply during ATI.

Evaluation of drought propagations with multiple indices in the Yangtze River basin.

This paper explored the drought propagation phenomenon based on meteorological, hydrological, and agricultural aspects in the Yangtze River basin (YRB), China. To evaluate meteorological, hydrological, and agricultural droughts, this paper used three drought indices, standardized precipitation evapotranspiration index (SPEI), standardized runoff index (SRI), and standardized soil moisture index (SSMI), respectively. The community land model (CLM) in the YRB to generate the monthly evapotranspiration, soil moisture, runoff data, which are required for the estimation of drought index, were applied.

Exposure to Polybrominated Diphenyl Ether Flame Retardants Causes Deoxyribonucleic Acid Damage in Human Thyroid Cells In Vitro.

Introduction: The incidence of papillary thyroid cancer (PTC) in the United States has tripled in the past 30 y. Polybrominated diphenyl ethers (PBDEs) are flame retardants that were ubiquitously used over that time period, and exposure to PBDEs has been associated with PTC prevalence. They are potential carcinogens via their induction of reactive oxygen species (ROS) formation and resultant deoxyribonucleic acid (DNA) damage.

Skeletonizing En Bloc Esophagectomy Revisited: Oncologic Outcome in Association with the Presence of Thoracic Duct Lymph Nodes.

Background: Skeletonizing en bloc esophagectomy (SEBE) involves the removal of the esophagus en bloc with locoregional soft tissues and lymph nodes, including the thoracic duct (TD); however, its oncologic benefits remain unclear. We evaluated the impact of SEBE on oncologic outcomes in patients with esophageal squamous cell carcinoma.

Methods: Patients undergoing McKeown esophagectomy without neoadjuvant therapy between 2013 and 2019 were evaluated.

Usefulness of contrast-enhanced multi-detector computed tomography in identifying upper gastrointestinal bleeding: A retrospective study of patients admitted to the emergency department.

Upper gastrointestinal bleeding (UGIB) is a major cause of clinical deterioration worldwide. A large number of patients with UGIB cannot be diagnosed through endoscopy, which is normally the diagnostic method of choice. Therefore, this study aimed to investigate the diagnostic value of multi-detector computed tomography (MDCT) for patients with suspected UGIB.

Image Quality and Lesion Detectability of Lower-Dose Abdominopelvic CT Obtained Using Deep Learning Image Reconstruction.

Objective: To evaluate the image quality and lesion detectability of lower-dose CT (LDCT) of the abdomen and pelvis obtained using a deep learning image reconstruction (DLIR) algorithm compared with those of standard-dose CT (SDCT) images.

Materials And Methods: This retrospective study included 123 patients (mean age ± standard deviation, 63 ± 11 years; male:female, 70:53) who underwent contrast-enhanced abdominopelvic LDCT between May and August 2020 and had prior SDCT obtained using the same CT scanner within a year. LDCT images were reconstructed with hybrid iterative reconstruction (h-IR) and DLIR at medium and high strengths (DLIR-M and DLIR-H), while SDCT images were reconstructed with h-IR.