Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Proximal protection devices for carotid artery stenting - A benchtop assessment of flow reversal performance.

Background And Purpose: Proximal protection devices, such as TransCarotid Artery Revascularization (TCAR, SilkRoad Medical, Sunnyvale), aim to yield better outcomes in carotid artery stenting (CAS) than distal protection devices by preventing plaque embolization to the brain. However, transfemoral catheters may not fully reverse flow from the external carotid artery (ECA) to the internal carotid artery (ICA). We assess a new balloon-sheath device, Femoral Flow Reversal Access for Carotid Artery Stenting (FFRACAS), for this purpose.

The potential role of tumor deposits in the prognosis and TNM staging for colorectal cancer.

Background: Tumor deposits (TDs) can impact proper staging of cancer, which is crucial for discussing prognosis and determining the appropriate treatment plan. Our study aimed to correlate how TDs influence prognosis of resected colorectal cancer (CRC) and how to optimize tumor-node-metastasis (TNM) staging with respect to TDs for clinical decision-making.

Methods: A retrospective analysis was performed on 611 patients with CRC treated in Jiangsu Cancer Hospital from January 1, 2010 to December 31, 2020 among whom 197 had TDs.

Abdominal myosteatosis measured with computed tomography predicts poor outcomes in patients with glioblastoma.

Background: Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM).

Methods: We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.

Aqueous Proteomic and Metabolomic Profiles in Low-Energy vs High-Energy Femtosecond Laser-Assisted Cataract Surgery.

Purpose: To investigate the aqueous proteomics and metabolomics in low-energy and high-energy femtosecond laser-assisted cataract surgery (FLACS).

Methods: In this prospective observational study, 72 patients were randomized to 3 groups: low-energy FLACS, high-energy FLACS, and conventional phacoemulsification (controls). Aqueous was collected after femtosecond laser treatment or at the beginning of surgery (controls).

US-Guided Thermal Ablation for Secondary Hyperparathyroidism: A Prospective Multicenter Study.

Background Interest in microwave ablation (MWA) and radiofrequency ablation (RFA) use for treating secondary hyperparathyroidism (SHPT) is rising; however, ablation outcomes in patients with SHPT are not well characterized. Purpose To assess the response of parathyroid hormone (PTH), calcium, phosphorus, and alkaline phosphatase (ALP) levels to US-guided parathyroid MWA and RFA and the safety of these treatments in participants with SHPT. Materials and Methods This prospective multicenter cohort study, conducted from September 2017 to March 2022, included participants with SHPT.

The Potency of Cytotoxic Mechanisms of Local Anesthetics in Human Chondrocyte Cells.

Local anesthetics are commonly used in various clinical settings for both prevention and symptom relief. Numerous clinical studies have demonstrated that intra-articular injections of local anesthetics achieve high success rates in orthopedic practices. However, several widely used local anesthetics, including bupivacaine, lidocaine, and ropivacaine, have been shown to exhibit toxicity to chondrocytes, with the underlying mechanisms of chondrotoxicity remaining poorly understood.

Deficiency of Endothelial Impairs Pulmonary Vascular Angiogenesis and Predisposes Pulmonary Hypertension.

Background: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.

Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.

Routes to molecular glue degrader discovery.

Molecular glue degraders (MGDs) represent a unique class of targeted protein degradation (TPD) modalities. By facilitating protein-protein interactions between E3 ubiquitin ligases and neo-substrates, MGDs offer a novel approach to target previously undruggable or insufficiently drugged disease-causing proteins. Here, we present an overview of recently reported MGDs, highlighting their diverse mechanisms, and we discuss mechanism-based strategies to discover new MGDs and neo-substrates.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

Radiomics of Periprostatic Fat and Tumor Lesion Based on MRI Predicts the Pathological Upgrading of Prostate Cancer from Biopsy to Radical Prostatectomy.

Rationale And Objectives: To assess the predictive value of MRI-based radiomics of periprostatic fat (PPF) and tumor lesions for predicting Gleason score (GS) upgrading from biopsy to radical prostatectomy (RP) in prostate cancer (PCa).

Methods: A total of 314 patients with pathologically confirmed prostate cancer (PCa) after radical prostatectomy (RP) were included in the study. The patients were randomly assigned to the training cohort (n = 157) and the validating cohort (n = 157) in a 1:1 ratio.

Revolutionizing Epithelial Differentiability Analysis in Small Airway-on-a-Chip Models Using Label-Free Imaging and Computational Techniques.

Organ-on-a-chip (OOC) devices mimic human organs, which can be used for many different applications, including drug development, environmental toxicology, disease models, and physiological assessment. Image data acquisition and analysis from these chips are crucial for advancing research in the field. In this study, we propose a label-free morphology imaging platform compatible with the small airway-on-a-chip system.

Favorable Outcomes of Patients With High-Risk Uveal Melanoma Treated With a Novel Linear Accelerator-Based Frameless Fractionated Stereotactic Radiosurgery.

Purpose: Uveal melanoma (UM) represents the most prevalent and aggressive intraocular malignancy in adults. This study examined the outcomes of patients diagnosed with high-risk UM who underwent fractionated stereotactic radiosurgery (fSRS) treatment utilizing a novel Linear Accelerator (LINAC)-based frameless technique.

Design: Retrospective, interventional case series.

Diagnostic Efficacy of Ventilation-Perfusion Single Photo Emission Computed Tomography/Computed Tomography for Pulmonary Hypertension due to Fibrinous Mediastinitis.

Rationale And Objectives: Comprehensive data on the use of ventilation-perfusion single-photo emission computed tomography/computed tomography (V/Q SPECT/CT), an established diagnostic tool for chronic thromboembolic pulmonary hypertension, in identifying pulmonary hypertension secondary to fibrinous mediastinitis (PH-FM) is scarce. This study aimed to assess its diagnostic efficacy for PH-FM.

Materials And Methods: Patients with PH due to pulmonary artery stenosis were assessed using V/Q SPECT/CT, computed tomography pulmonary angiography (CTPA), and digital subtraction pulmonary angiography (PAG).

Myeloprotection effects of trilaciclib in Chinese patients with extensive stage small cell lung cancer (ES-SCLC) receiving chemotherapy-a real-world study.

Background: Trilaciclib, an intravenous short acting cyclin-dependent kinase 4/6 inhibitor, has been approved for the prevention of chemotherapy-induced myelosuppression (CIM) in patients with extensive stage small cell lung cancer (ES-SCLC) receiving platinum/etoposide (EP) or topotecan (TPT)-based therapy in United States (US) since February 2021. Trilaciclib use received the priority review and approval in a real-world setting in China. This study thus aimed to collect real-world data and evaluate the protective effect of trilaciclib on CIM in Chinese patients with ES-SCLC.

Predicting Futile Recanalization by Cerebral Collateral Recycle Status in Patients with Endovascular Stroke Treatment: The CHANOA Score.

Rationale And Objectives: The correlation between collateral circulation and futile recanalization (FR) is still controversial, and few studies have explored the influence of comprehensive cerebral collateral circulation on FR after endovascular stroke treatment. Therefore, based on cerebral collateral recycle (CCR) status, we aimed to establish an effective scoring system to identify the probability of FR.

Methods: This was a multicenter retrospective cohort study.

Endothelial FUNDC1 Deficiency Drives Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is associated with endothelial dysfunction. However, the cause of endothelial dysfunction and its impact on PH remain incompletely understood. We aimed to investigate whether the hypoxia-inducible FUNDC1 (FUN14 domain-containing 1)-dependent mitophagy pathway underlies PH pathogenesis and progression.

Engineered platelets as targeted protein degraders and application to breast cancer models.

Clinical application of chimeric molecules for targeted protein degradation has been limited by unfavorable drug-like properties and biosafety concerns arising from nonspecific biodistribution after systemic administration. Here we develop a method to engineer platelets for degradation of either intracellular or extracellular proteins of interest (POIs) in vivo by covalently labeling heat shock protein 90 (HSP90) in platelets with a POI ligand. The degrader platelets (DePLTs) target wound areas and undergo activation.

Engineered extracellular vesicles as nanosponges for lysosomal degradation of PCSK9.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in the degradation of the low-density lipoprotein receptor (LDLR), and PCSK9 inhibition emerges as an attractive strategy for atherosclerosis management. In this study, extracellular vesicles (EVs) were engineered to nanosponges, which could efficiently adsorb and deliver PCSK9 into lysosomes for degradation. Briefly, nanosponges were engineered by modifying EVs with EGF-A/PTGFRN fusion protein (PCSK9 binding domain EGF-A from the mutant LDLR with higher affinity was fused to the C terminus of prostaglandin F2 receptor negative regulator).

Histogram analysis of advanced diffusion-weighted MRI models for evaluating the grade and proliferative activity of meningiomas.

Rationale And Objectives: To explore the value of diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator (MAP) magnetic resonance imaging histogram analysis in evaluating the grade and proliferative activity of meningiomas.

Materials And Methods: A total of 134 meningioma patients were prospectively included and underwent magnetic resonance diffusion imaging. The whole-tumor histogram parameters were extracted from multiple functional maps.

 (Poaceae), a new species from the north-western Qinghai-Tibetan Plateau, China.

A new species from China, Y.C. Zhang, is described and illustrated herein, based on morphological characters and molecular phylogenetic analysis.