Toward expert-level medical question answering with large language models.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval.

FLAIR: A Phase II, Open Label, Randomized Study of Osimertinib Plus Bevacizumab Versus Osimertinib in Recurrent or Metastatic Treatment-Naïve NSCLC Patients Harboring EGFR 21L858R Mutation.

Introduction: Osimertinib, the 3rd generation EGFR-TKI, has emerged as standard first-line treatment for patients with advanced EGFR mutated nonsmall cell lung cancer (NSCLC). Patients with exon 21 L858R mutation showed lower efficacy with EGFR-TKIs than those with 19Del mutation, even with osimertinib, it remains an unmet medical need to further improve the efficacy in L858R population. We present the rationale and design for FLAIR (NCT04988607), which will investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib monotherapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation.

Prognostic Value of Murray Law-Based QFR (μQFR)-Guided Virtual PCI in Patients With Physiological Ischemia.

Background: Quantitative flow ratio (QFR)-based virtual percutaneous coronary intervention (PCI) is associated with improved post-PCI physiological results. Murray law-based QFR (μQFR) is a new method for physiological assessment that has higher feasibility and efficiency. The purpose of this study was to investigate the performance of μQFR-guided virtual PCI in improving post-PCI outcomes.

Three-Year Clinical Impact of Murray Law-Based Quantitative Flow Ratio and OCT- or FFR-Guidance in Angiographically Intermediate Coronary Lesions.

Background: The FORZA trial (FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty) prospectively compared the use of fractional flow reserve (FFR) or optical coherence tomography (OCT) for treatment decisions and percutaneous coronary intervention (PCI) optimization in patients with angiographically intermediate coronary lesions. Murray law-based quantitative-flow-ratio (μQFR) is a novel noninvasive method for the computation of FFR. In the present study, we evaluated the clinical impact of μQFR, FFR, or OCT guidance in FORZA trial lesions at 3-year follow-up.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

Background: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown.

Methods: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy.

Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC (CTONG1804): a multicenter open-label phase II study.

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive (N) and nivolumab-chemotherapy (N/C) combinations based on PD-L1 expression. Eligible patients exhibited resectable clinical stage IIA-IIIB (AJCC 8th edition) NSCLC without EGFR/ALK alterations. Patients received either mono-nivolumab (N) or nivolumab + nab-paclitaxel+ carboplatin (N/C) for three cycles based on PD-L1 expression.

Tumor vaccine based on extracellular vesicles derived from γδ-T cells exerts dual antitumor activities.

γδ-T cells are innate-like T cells with dual antitumor activities. They can directly eradicate tumor cells and function as immunostimulatory cells to promote antitumor immunity. Previous studies have demonstrated that small extracellular vesicles (EVs) derived from γδ-T cells (γδ-T-EVs) inherited the dual antitumor activities from their parental cells.

Large language models encode clinical knowledge.

Large language models (LLMs) have demonstrated impressive capabilities, but the bar for clinical applications is high. Attempts to assess the clinical knowledge of models typically rely on automated evaluations based on limited benchmarks. Here, to address these limitations, we present MultiMedQA, a benchmark combining six existing medical question answering datasets spanning professional medicine, research and consumer queries and a new dataset of medical questions searched online, HealthSearchQA.

Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards.

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex.

Cardiovascular Risk Stratification by Automatic Coronary Artery Calcium Scoring on Pretreatment Chest Computed Tomography in Diffuse Large B-Cell Lymphoma Receiving Anthracycline-Based Chemotherapy: A Multicenter Study.

Background: Balancing the cardiovascular risk and benefit of anthracycline-based chemotherapy in patients with diffuse large B-cell lymphoma is an important clinical issue. We aimed to evaluate whether the pretreatment coronary artery calcium score (CACS) can stratify the risk of cancer therapy-related cardiac dysfunction (CTRCD) and major adverse cardiovascular events (MACEs) in patients with diffuse large B-cell lymphoma receiving anthracycline-based chemotherapy.

Methods: The patients with diffuse large B-cell lymphoma from 4 hospitals were retrospectively enrolled.

Subsequent treatments beyond progression on osimertinib in EGFR-mutated NSCLC and leptomeningeal metastases.

Background: Despite the reported efficacy of osimertinib, central nervous system (CNS) progression is still frequent in EGFR-mutated NSCLC. This study aimed to reveal site-specific resistant mechanisms to osimertinib and investigate subsequent treatments for leptomeningeal metastases (LM).

Methods: EGFR-mutated NSCLC with LM who progressed on osimertinib were included.

Precise druggability of the PTH type 1 receptor.

Class B G protein-coupled receptors (GPCRs) are notoriously difficult to target by small molecules because their large orthosteric peptide-binding pocket embedded deep within the transmembrane domain limits the identification and development of nonpeptide small molecule ligands. Using the parathyroid hormone type 1 receptor (PTHR) as a prototypic class B GPCR target, and a combination of molecular dynamics simulations and elastic network model-based methods, we demonstrate that PTHR druggability can be effectively addressed. Here we found a key mechanical site that modulates the collective dynamics of the receptor and used this ensemble of PTHR conformers to identify selective small molecules with strong negative allosteric and biased properties for PTHR signaling in cell and PTH actions in vivo.

Glomerular disease classification and lesion identification by machine learning.

Background: Classification of glomerular diseases and identification of glomerular lesions require careful morphological examination by experienced nephropathologists, which is labor-intensive, time-consuming, and prone to interobserver variability. In this regard, recent advance in machine learning-based image analysis is promising.

Methods: We combined Mask Region-based Convolutional Neural Networks (Mask R-CNN) with an additional classification step to build a glomerulus detection model using human kidney biopsy samples.

Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study.

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways may delay therapeutic resistance in advanced non-small cell lung cancer (NSCLC). This phase 3 study investigated the efficacy and safety of an erlotinib plus bevacizumab regimen in untreated patients with advanced NSCLC. In total, 311 patients received bevacizumab plus erlotinib (n = 157) or erlotinib only (n = 154).

Thin-Section Chest CT Imaging of COVID-19 Pneumonia: A Comparison Between Patients with Mild and Severe Disease.

Purpose: To compare radiologic characteristics of coronavirus disease 2019 (COVID-19) pneumonia at thin-section CT on admission between patients with mild and severe disease.

Materials And Methods: Seventy patients with COVID-19 pneumonia who were admitted to Zhongnan Hospital of Wuhan University between January 20, 2020 and January 27, 2020 were enrolled. On the basis of the World Health Organization guidelines, 50 patients were categorized with the mild form and 20 with the severe form based on clinical conditions.

Ibrutinib and venetoclax target distinct subpopulations of CLL cells: implication for residual disease eradication.

Ibrutinib inhibits Bruton tyrosine kinase while venetoclax is a specific inhibitor of the anti-apoptotic protein BCL2. Both drugs are highly effective as monotherapy against chronic lymphocytic leukemia (CLL), and clinical trials using the combination therapy have produced remarkable results in terms of rate of complete remission and frequency of undetectable minimal residual disease. However, the laboratory rationale behind the success of the drug combination is still lacking.

, a new species of (Begoniaceae) from Guangdong, China.

A new species of Begonia section Coelocentrum, W.H. Tu, B.

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.

Background: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.

Methods: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao) to the fraction of inspired oxygen (Fio) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone.

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia.

Background: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP.

Methods: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020.

Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.

The mitochondrial complexes are prone to sirtuin (Sirt)3-mediated deacetylation modification, which may determine cellular response to stimuli, such as oxidative stress. In this study, we show that the cytochrome c oxidase (COX)-1, a core catalytic subunit of mitochondrial complex IV, was acetylated and deactivated both in 2,2'-azobis(2-amidinopropane) dihydrochloride-treated NIH/3T3 cells and hydrogen peroxide-treated primary neuronal cells, correlating with apoptotic cell death induction by oxidative stress. Inhibition of Sirt3 by small interfering RNA or the inhibitor nicotinamide induced accumulation of acetylation of COX-1, reduced mitochondrial membrane potential, and increased cell apoptosis.

A safe and potent anti-CD19 CAR T cell therapy.

Anti-CD19 chimeric antigen receptor (CAR) T cell therapies can cause severe cytokine-release syndrome (CRS) and neurotoxicity, impeding their therapeutic application. Here we generated a new anti-CD19 CAR molecule (CD19-BBz(86)) derived from the CD19-BBz prototype bearing co-stimulatory 4-1BB and CD3ζ domains. We found that CD19-BBz(86) CAR T cells produced lower levels of cytokines, expressed higher levels of antiapoptotic molecules and proliferated more slowly than the prototype CD19-BBz CAR T cells, although they retained potent cytolytic activity.

Focal Low and Global High Permeability Predict the Possibility, Risk, and Location of Hemorrhagic Transformation following Intra-Arterial Thrombolysis Therapy in Acute Stroke.

Background And Purpose: The contrast volume transfer coefficient (), which reflects blood-brain barrier permeability, is influenced by circulation and measurement conditions. We hypothesized that focal low BBB permeability values can predict the spatial distribution of hemorrhagic transformation and global high BBB permeability values can predict the likelihood of hemorrhagic transformation.

Materials And Methods: We retrospectively enrolled 106 patients with hemispheric stroke who received intra-arterial thrombolytic treatment.