Utilizing a domain-specific large language model for LI-RADS v2018 categorization of free-text MRI reports: a feasibility study.

Objective: To develop a domain-specific large language model (LLM) for LI-RADS v2018 categorization of hepatic observations based on free-text descriptions extracted from MRI reports.

Material And Methods: This retrospective study included 291 small liver observations, divided into training (n = 141), validation (n = 30), and test (n = 120) datasets. Of these, 120 were fictitious, and 171 were extracted from 175 MRI reports from a single institution.

Integrated molecular and functional characterization of the intrinsic apoptotic machinery identifies therapeutic vulnerabilities in glioma.

Genomic profiling often fails to predict therapeutic outcomes in cancer. This failure is, in part, due to a myriad of genetic alterations and the plasticity of cancer signaling networks. Functional profiling, which ascertains signaling dynamics, is an alternative method to anticipate drug responses.

[18F]-Fluorodeoxyglucose Uptake as a Marker of Residual Anaplastic and Poorly Differentiated Thyroid Carcinoma Following BRAF-Targeted Therapy.

Background And Purpose: Neoadjuvant BRAF-directed therapy and immunotherapy followed by surgery improves survival in patients with BRAF-mutant anaplastic thyroid carcinoma (ATC), more so in those who have complete ATC pathologic response. This study assesses the ability of FDG-PET to non-invasively detect residual high-risk pathologies including ATC and poorly differentiated thyroid carcinoma (PDTC) in the preoperative setting.

Materials And Methods: This retrospective, single-center study included consecutive BRAF-mutant ATC patients treated with at least 30 days of neoadjuvant BRAF-directed therapy and who underwent FDG-PET/CT within 30 days prior to surgery.

Cerebral Blood Flow Dynamics in Neurogenic Orthostatic Hypotension: A Systematic Review and Meta-Analysis.

Background: Neurogenic orthostatic hypotension (nOH) causes pathological falls in standing blood pressure that may or may not be symptomatic. nOH also raises the risk of poor neurological outcomes irrespective of symptom presence, possibly reflecting subclinical cerebral hypoperfusion. Dynamic changes in cerebral blood flow velocity (CBFv) help infer how blood pressure fluctuations influence CBFv and cerebral autoregulation.

A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease.

Background: Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.

Background: The EF-hand Ca sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75-94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.

Postoperative Opioid Reduction Using a Multimodal Pain Protocol for Outpatient Orthopaedic Sports Medicine Surgery.

Background: Orthopaedic surgery regularly employs opioids for postoperative pain management. Multimodal pain protocols have been shown to reduce opioid prescriptions in orthopaedic surgery.

Purpose: To analyze the impact of a division-level multimodal pain protocol for orthopaedic sports medicine surgery on opioid prescription reduction and pain level postoperatively.

Assessment of In-Office Tympanostomy Tube Insertion Tolerability in Children Under 2 Years.

In-office tympanostomy tube insertion (TTI) is becoming more available in the practice of pediatric otolaryngology. This study evaluated the tolerability of this procedure in young children. Four methods were used to assess tolerability.

A cell atlas foundation model for scalable search of similar human cells.

Single-cell RNA sequencing has profiled hundreds of millions of human cells across organs, diseases, development and perturbations to date. Mining these growing atlases could reveal cell-disease associations, identify cell states in unexpected tissue contexts and relate in vivo biology to in vitro models. These require a common measure of cell similarity across the body and an efficient way to search.

Molecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer.

Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expression. Durvalumab induces an activation of immune and stromal gene expression as well as a reduction of proliferation-related gene expression.

Long-Term Cognitive, Functional, and Patient-Reported Outcomes in Patients With Anti-NMDAR Encephalitis.

Background And Objectives: Anti-NMDA receptor (anti-NMDAR) encephalitis generally manifests in young adults. Although 80%-90% returns to independence, the majority experience persistent cognitive and psychosocial difficulties. Studies have demonstrated that cognitive recovery may continue for years; the temporal trajectory is largely unknown, as are factors influencing cognitive/psychosocial recovery.

Discovery of IRAK1/4/pan-FLT3 Kinase Inhibitors as Treatments for Acute Myeloid Leukemia.

We report the discovery of an imidazopyridine series of IRAK1/4/pan-FLT3 kinase inhibitors. Optimization of this series has produced compound which displays potent and selective inhibition of IRAK1, IRAK4, FLT3, and all mutant forms of FLT3, as well as good in vitro ADME and pharmacokinetic properties. In a mouse xenograft model of AML, produces survival prolongation equal to that of Gilteritinib, the leading marketed FLT3 inhibitor currently used to treat AML.

Reply to 'Experimental measurement of assembly indices are required to determine the threshold for life'.

We clarify misunderstandings of Walker et al. (Walker 2024 21, 20240367 (doi:10.1098/rsif.

Experimentally measured assembly indices are required to determine the threshold for life.

Assembly theory (AT) aims to distinguish living from non-living systems by explaining and quantifying selection and evolution. The theory proposes that the degree of assembly depends on the number of complex objects, with complexity measured using a combination of the object's assembly index (AI) and its abundance. We previously provided experimental evidence supporting AT's predictive power, finding that abiotic systems do not randomly produce organic molecules with an AI greater than approximately 15 in detectable amounts.

The 1978 English boarding school influenza outbreak: where the classic SEIR model fails.

Previous work has failed to fit classic SEIR epidemic models satisfactorily to the prevalence data of the famous English boarding school 1978 influenza A/H1N1 outbreak during the children's pandemic. It is still an open question whether a biologically plausible model can fit the prevalence time series and the attack rate correctly. To construct the final model, we first used an intentionally very flexible and overfitted discrete-time epidemiologic model to learn the epidemiological features from the data.

Health Economic Evaluation of Antimicrobial Stewardship, Procalcitonin Testing, and Rapid Blood Culture Identification in Sepsis Care: A 90-Day Model-Based, Cost-Utility Analysis.

Objective: We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis.

Methods: We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective.