Dual Roles of miR-10a-5p and miR-10b-5p as Tumor Suppressors and Oncogenes in Diverse Cancers.

Cancer is a complex genetic disorder characterized by abnormalities in both coding and regulatory non-coding RNAs. microRNAs (miRNAs) are key regulatory non-coding RNAs that modulate cancer development, functioning as both tumor suppressors and oncogenes. miRNAs play critical roles in cancer progression, influencing key processes such as initiation, promotion, and metastasis.

Validation of a Cancer-Focused Information Seeking Experience (ISEE) Scale.

Background: Searching for health information is critical for maintaining one's health and reducing risk of disease, including cancer. However, some people are more likely to experience challenges in finding and comprehending health information; therefore, it is important to measure health information-seeking behavior. In order to add to prior research conducted with the scale, this study provides the first formal evaluation of the validity and reliability of the four-item, cancer-focused Information Seeking Experience (ISEE) scale in a cross-sectional, nationally representative health survey of U.

Prognostic Testing for Prostate Cancer-A Cost-Effectiveness Analysis Comparing a Prostatype P-Score Biomarker Approach to Standard Clinical Practice.

Background: The Prostatype score (P-score) is a prognostic biomarker that integrates a three-gene (IGFBP3, F3, and VGLL3) signature derived from prostate biopsy samples, with key clinical parameters, including prostate-specific antigen (PSA) levels, Gleason grade, and tumor stage at diagnosis. The test has demonstrated superior predictive accuracy for prostate cancer outcomes compared with traditional risk categorization systems such as D'Amico. Notably, it reclassifies a higher proportion of patients into the low-risk category, making them eligible for active surveillance.

Substrate adaptors are flexible tethering modules that enhance substrate methylation by the arginine methyltransferase PRMT5.

Protein arginine methyltransferase (PRMT) 5 is an essential arginine methyltransferase responsible for the majority of cellular symmetric dimethyl-arginine (SDMA) marks. PRMT5 uses substrate adaptors such as pICln, RIOK1, and COPR5, to recruit and methylate a wide range of substrates. Although the substrate adaptors play important roles in substrate recognition, how they direct PRMT5 activity towards specific substrates remains incompletely understood.

Developing a simplified measure to predict the risk of autism spectrum disorders: Abbreviating the M-CHAT-R using a machine learning approach in China.

Background: Early screening for autism spectrum disorder (ASD) is crucial, yet current assessment tools in Chinese primary child care are limited in efficacy.

Objective: This study aims to employ machine learning algorithms to identify key indicators from the 20-item Modified Checklist for Autism in Toddlers, revised (M-CHAT-R) combining with ASD-related sociodemographic and environmental factors, to distinguish ASD from typically developing children.

Methods: Data from our prior validation study of the Chinese M-CHAT-R (August 2016-March 2017, n = 6,049 toddlers) were reviewed.

Tissue concepts: Supervised foundation models in computational pathology.

Due to the increasing workload of pathologists, the need for automation to support diagnostic tasks and quantitative biomarker evaluation is becoming more and more apparent. Foundation models have the potential to improve generalizability within and across centers and serve as starting points for data efficient development of specialized yet robust AI models. However, the training of foundation models themselves is usually very expensive in terms of data, computation, and time.

Learning the language of antibody hypervariability.

Protein language models (PLMs) have demonstrated impressive success in modeling proteins. However, general-purpose "foundational" PLMs have limited performance in modeling antibodies due to the latter's hypervariable regions, which do not conform to the evolutionary conservation principles that such models rely on. In this study, we propose a transfer learning framework called Antibody Mutagenesis-Augmented Processing (AbMAP), which fine-tunes foundational models for antibody-sequence inputs by supervising on antibody structure and binding specificity examples.

Mechanism-guided engineering of a minimal biological particle for genome editing.

The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.

Evaluation of Larger Side-Group Functionalities and the Side/End-Group Interplay in Ritonavir-Like Inhibitors of CYP3A4.

A new series of 13 ritonavir-like inhibitors of human drug-metabolizing CYP3A4 was rationally designed to study the R side-group and R end-group interplay when the R side-group is represented by phenyl. Spectral, functional, and structural characterization showed no improvement in the binding affinity and inhibitory potency of R/R-phenyl inhibitors upon elongation and/or fluorination of R-Boc (tert-butyloxycarbonyl) or its replacement with benzenesulfonyl. When R is pyridine, the impact of R-phenyl-to-indole/naphthalene substitution was multidirectional and highly dependent on side-group stereo configuration.

Electrocardiographic markers predict hemodynamic parameters in adults with uncorrected secundum atrial septal defect.

Background: Precapillary pulmonary hypertension (PH) as complication in atrial septal defect (ASD) is closely related to right heart hemodynamics, such as right atrial pressure (RAP) and pulmonary vascular resistance (PVR). Right heart catheterization (RHC) as the gold standard for their measurement is invasive and not widely available in Indonesia. Electrocardiography (ECG) was proposed to be alternative in this matter.

The utility of parent's and teacher's concerns for the screening of speech sound disorders: A study on French-speaking preschool children.

Speech sound disorders (SSD) are associated with difficulties in communication, social participation, literacy, and learning. An early identification process is therefore necessary. Our study was aimed at determining the utility and accuracy of parent's and teacher's concerns in screening for SSD.

Pregnancy & cardiovascular disease: the PREG-CVD-HH registry.

Background: Cardiovascular disease (CVD) remains the leading cause of death in pregnant and peripartal women in western countries. Physiological changes during pregnancy can lead to cardiovascular complications in the mother; women with pre-existing heart disease may not tolerate these changes well, increasing their susceptibility to adverse cardiovascular outcomes during pregnancy. The aim of this study is to characterize pregnancy-induced changes in cardiac function, biomarker concentrations and cardiovascular outcomes in women with CVD during pregnancy at a tertiary care hospital in Germany.

Correlates Between Temporomandibular Disorder Symptom Severity, Psychological Distress, Well-Being, and Oral Health-Related Quality of Life: Insights From Chinese Young Adults.

Background: There is limited understanding of how temporomandibular disorder (TMD) symptoms, psychological distress, and well-being are related to each other and to OHRQoL in Chinese young adults.

Objectives: This study aimed to identify correlations between TMD symptom severity, psychological status, and OHRQoL while also examining factors associated with low OHRQoL.

Methods: Participants, recruited from a major university in the capital city, completed a survey that included demographics, the Chinese versions of the expanded five TMD symptoms (5Ts) screener, Depression, Anxiety, Stress Scales-21 (DASS-21), Ryff's Scales of Psychological Well-being-18 (SPWB-18), and Oral Health Impact Profile for TMDs (OHIP-TMD).

Analysis of time to regulatory approval in an exception from informed consent trial in trauma patients.

Background: The interactive media-based approach to community consultation and public disclosure (CC/PD), a key step when conducting exception from informed consent (EFIC) clinical trials, is intended to be completed in 4 months. This analysis characterizes the process, from initiation of CC/PD activities to institutional review board approval, to better understand the barriers and how these can be mitigated.

Methods: This is a retrospective post hoc analysis of data collected as part of the CC/PD campaigns conducted for a large trial involving up to 90 trauma centers in the United States.

Exploring Evolution to Uncover Insights Into Protein Mutational Stability.

Determining the impact of mutations on the thermodynamic stability of proteins is essential for a wide range of applications such as rational protein design and genetic variant interpretation. Since protein stability is a major driver of evolution, evolutionary data are often used to guide stability predictions. Many state-of-the-art stability predictors extract evolutionary information from multiple sequence alignments of proteins homologous to a query protein, and leverage it to predict the effects of mutations on protein stability.

Impact of Subarachnoid Hemorrhage on Human Glymphatic Function: A Time-Evolution Magnetic Resonance Imaging Study.

Background: Subarachnoid hemorrhage (SAH) is associated with significant mortality and morbidity. The impact of SAH on human glymphatic function remains unknown.

Methods: This prospective, controlled study investigated whether human glymphatic function is altered after SAH, how it differs over time, and possible underlying mechanisms.

Combination Antithrombotic Therapy for Reduction of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease.

Background: Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin.

Preoperative medication management turnkey order set for nonemergent adult cardiac surgery.

Objective: The management of preoperative medications is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Numerous guidelines and expert consensus documents have been published to provide guidance in preoperative medication management.

Enhanced Recovery After Surgery (ERAS) cardiac turnkey order set for perioperative pain management in cardiac surgery: Proceedings from the American Association for Thoracic Surgery (AATS) ERAS Conclave 2023.

Objective: Optimal perioperative pain management is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Several guidelines and expert consensus documents have been published to provide guidance on pain management and opioid reduction in cardiac surgery.

Transcript-specific enrichment enables profiling of rare cell states via single-cell RNA sequencing.

Single-cell genomics technologies have accelerated our understanding of cell-state heterogeneity in diverse contexts. Although single-cell RNA sequencing identifies rare populations that express specific marker transcript combinations, traditional flow sorting requires cell surface markers with high-fidelity antibodies, limiting our ability to interrogate these populations. In addition, many single-cell studies require the isolation of nuclei from tissue, eliminating the ability to enrich learned rare cell states based on extranuclear protein markers.

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.

Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals.

The analysis of circulating tumour DNA (ctDNA) through minimally invasive liquid biopsies is promising for early multi-cancer detection and monitoring minimal residual disease. Most existing methods focus on targeted deep sequencing, but few integrate multiple data modalities. Here, we develop a methodology for ctDNA detection using deep (80x) whole-genome TET-Assisted Pyridine Borane Sequencing (TAPS), a less destructive approach than bisulphite sequencing, which permits the simultaneous analysis of genomic and methylomic data.

Efficacy outcomes of CDK4/6 inhibitors in combination with endocrine therapy treatment in hormone receptor-positive/HER2-negative advanced breast cancer according to PAM50 intrinsic subtype: Primary results of SOLTI-1801 CDK-PREDICT study.

Introduction: The prognostic value of PAM50 intrinsic subtypes (IS), cell cycle, and immune-related gene expression in HR+ /HER2- advanced breast cancer (BC) treated with CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) in a first-line metastatic setting is unclear. This study evaluates these biomarkers in metastatic biopsies from patients diagnosed with HR+ /HER2- advanced BC.

Methods: CDK-PREDICT study is a multicentric, ambispective observational cohort study conducted in six Spanish hospitals.

A Comparison of Peripherally Inserted Central Catheter Materials.

Background: New catheter materials for peripherally inserted central catheters (PICCs) may reduce the risk of device failure due to infectious, thrombotic, and catheter occlusion events. However, data from randomized trials comparing these catheters are lacking.

Methods: We conducted a randomized, controlled, superiority trial in three Australian tertiary hospitals.

Priorities for research on improving health behaviours for optimal mental health of Australian university students: A twin-panel Delphi study.

Issue Addressed: University students are at risk of poor health behaviours which negatively affect mental health and wellbeing. Informing the implementation of appropriate strategies to support Australian university students' health and wellbeing, requires quality evidence. This study aimed to identify research priorities for improving health behaviours to optimise mental health of Australian university students.