Data-driven insights to inform splice-altering variant assessment.

Disease-causing genetic variants often disrupt mRNA splicing, an intricate process that is incompletely understood. Thus, accurate inference of which genetic variants will affect splicing and what their functional consequences will be is challenging, particularly for variants outside of the essential splice sites. Here, we describe a set of data-driven heuristics that inform the interpretation of human splice-altering variants (SAVs) based on the analysis of annotated exons, experimentally validated SAVs, and the currently understood principles of splicing biology.

A Comparative Pilot Study of Computer-Based Evaluation Software Versus Traditional Evaluation in Preclinical Operative Procedures.

Objectives: The aim of the paper is to assess the effectiveness of a computer-based evaluation software for preclinical preparations and restorations when compared to traditional faculty grading/evaluation.

Methods: Forty-four Class I (#30-O) and Class II (#30-MO) preparations and Class II amalgam restorations (#31-MO) were generated in preclinical setting by first-year dental students. Calibrated faculty evaluated the preparations and restorations using a validated rubric from preclinical operative class.

Design, development, and evaluation of gene therapeutics specific to KSHV-associated diseases.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and two human lymphoproliferative diseases: primary effusion lymphoma and AIDS-related multicentric Castleman's disease. KSHV-encoded latency-associated nuclear antigen (LANA) is expressed in KSHV-infected cancer cells and is responsible for maintaining viral genomes in infected cells. Thus, LANA is an attractive target for therapeutic intervention for KSHV-associated diseases.

Crystalline Organic Compounds as Effective Nuclei in Contact Efflorescence of Ammonium Sulfate.

Contact nucleation is believed to play a role in liquid-to-solid phase transitions in the atmosphere including ice nucleation and salt efflorescence. Here contact efflorescence of optically levitated ammonium sulfate droplets by collisions with organic particles is probed using a long working-distance optical trap. Two highly viscous water-soluble organic compounds (-(+)-raffinose and citric acid), and two insoluble highly surface-active organic compounds (stearic acid and -pinonic acid) were probed for their ability to induce efflorescence upon contact.

Evaluation of [F]AlF NOTA-5G, an Aluminum [F]fluoride Labeled Peptide Targeting the Cell Surface Receptor Integrin Alpha(v)beta(6) for PET Imaging.

Purpose: Peptide-based probes targeting integrin αβ have shown promise in clinical trials for cancer imaging based on the high over-expression of this epithelial-specific cell surface receptor in many cancerous tissues. Recently, the αβ-targeting gallium-68 labeled DOTA-5G peptide, [Ga]Ga DOTA-5G, demonstrated diagnostic value in patients with metastatic pancreatic cancer. To facilitate adoption at sites without access to gallium-68 and take advantage of the characteristics of fluorine-18 through convenient [F]fluoride chelation chemistry, this study evaluated the fluorine-18 labeled analog, [F]AlF NOTA-5G, in vitro and in vivo in a tumor mouse model, and compared it to [Ga]Ga DOTA-5G.

Use of Neuromuscular Electrical Stimulation to Elicit Muscle Contractions Does Not Impair the Hyperemic Response Compared to Volitional Contractions.

Purpose: Electrical stimulation-induced muscle contractions in individuals with paralyzed muscles are often associated with early-onset fatigue. We examined whether electrical stimulation of the quadriceps muscle results in vasoconstriction and a reduction in blood flow, which may contribute to this early-onset fatigue.

Methods: Seventeen young individuals completed 40 electrical stimulation isometric contractions (stimulation frequency of 75 Hz, pulse duration of 400 μs, on-off ratio 6.

Caffeine in the Perioperative Setting.

There are emerging roles for caffeine in the perioperative setting, and anesthesiologists should be familiar with the ways in which caffeine may be able to improve postoperative recovery for adults.

Genetic and epigenetic characterization of sarcoma stem cells across subtypes identifies EZH2 as a therapeutic target.

High-grade soft tissue sarcomas (STS) are a heterogeneous and aggressive set of cancers. Failure to respond anthracycline chemotherapy, standard first-line treatment, is associated with poor outcomes. We investigated the contribution of STS cancer stem cells (STS-CSCs) to doxorubicin resistance.

Formation of β-UO from UCl Salt Compositions under Oxygen Exposure.

Complementary X-ray absorption fine structure (XAFS) and Raman spectroscopy studies were conducted on various UCl concentrations in alkali chloride salt compositions. The samples were 5 mol % UCl in LiCl (S1), 5 mol % UCl in KCl (S2), 5 mol % UCl in LiCl-KCl eutectic (S4), 50 mol % UCl in KCl (S5), and 20 mol % UCl in KCl (S6) molar concentrations. Samples were heated to 800 °C and allowed to cool to room temperature with measurements performed at selected temperatures; the highest temperatures showed the most stability and will be primarily referenced for conclusions.

Temporal Trends in Knowledge of Human Papillomavirus and Associated Oropharyngeal Cancer Following Expanded Vaccination Eligibility.

Objective: Human papillomavirus (HPV) is a significant driver of elevated risk for oropharyngeal squamous cell carcinoma (OPSCC). In 2018, HPV vaccination eligibility was expanded to men and women aged 27 to 45. We evaluated changes in awareness of HPV, its association with OPSCC, and HPV vaccination among all US adults between 2018 and 2020, focusing on those aged 27 to 45.

A LANA peptide inhibits tumor growth by inducing CHD4 protein cleavage and triggers cell death.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection, and viral genes are poised to be transcribed in the latent chromatin. In the poised chromatins, KSHV latency-associated nuclear antigen (LANA) interacts with cellular chromodomain-helicase-DNA-binding protein 4 (CHD4) and inhibits viral promoter activation. CHD4 is known to regulate cell differentiation by preventing enhancers from activating promoters.

Persistent Opioid Use Following Artificial Urinary Sphincter Placement: A Large Claims Database Analysis.

Objective: To assess risk of persistent opioid use and emergency department (ED) and office/outpatient visits following post-operative prescriptions of common opioids in patients following artificial urinary sphincter (AUS) implantation using a nationwide claims database.

Methods: The TriNetX US Collaborative Network, which encompasses over 115 million patients from 66 healthcare organizations was used to identify males who underwent first-time AUS placement between 2010-2024. Patients with history of opioid dependence/abuse, opioid use within 6 months prior to AUS placement, or surgery within 9 months post-operation were excluded.

CT-Guided Online Adaptive Hypofractionated Radiotherapy for Primary Bladder Cancer: A Report of Two Cases.

Trimodality treatment for bladder cancer, consisting of maximal transurethral resection of the tumor followed by concurrent chemoradiotherapy, is an attractive management option with curative and organ-sparing intent. However, such treatment can be associated with acute toxicities related to the large treatment margins required due to daily variation in bladder filling, with resultant bladder, bowel, and rectal toxicity. Adaptive radiation, which accounts for inter-fraction variations in bladder size, allows the confident delivery of radiation to bladder cancer with smaller margins, with the potential to reduce toxicities without the associated risk of compromising the target coverage.

Over-the-Counter Hearing Aids: A Nationwide Survey Study to Understand Perspectives in Primary Care.

Objectives: The expansion of over-the-counter (OTC) hearing aids has raised inquiries regarding primary care physicians' (PCP) knowledge, perspective, and perceived roles. We aimed to understand PCP perspectives on OTC hearing aids via nationwide online surveys.

Methods: RedCap survey was distributed to PCPs via online forums and public mailing lists.

Characterizing the Adoption and Experiences of Users of Artificial Intelligence-Generated Health Information in the United States: Cross-Sectional Questionnaire Study.

Background: OpenAI's ChatGPT is a source of advanced online health information (OHI) that may be integrated into individuals' health information-seeking routines. However, concerns have been raised about its factual accuracy and impact on health outcomes. To forecast implications for medical practice and public health, more information is needed on who uses the tool, how often, and for what.

IgG4 porta-hepatis pseudotumor mimicking a hilar cholangiocarcinoma.

A 60-year-old female with a BRCA2 mutation and a history of breast cancer presented with diffuse abdominal pain and elevated liver enzymes. Imaging revealed a porta-hepatis mass, prompting consideration of hilar cholangiocarcinoma or breast cancer metastasis. Further investigation including biopsy and F-fluorodeoxyglucose positron emission tomography/computed tomography findings were inconsistent with malignancy, leading to investigation of non-neoplastic causes.

External Auditory Canal Exostosis and the California Surfer Population: A Cross-Sectional Study.

Objectives: California has the most surfers in the United States and a high prevalence of external auditory canal exostoses (EACEs) among them. We aimed to characterize their EACE knowledge, use of earplugs, and barriers toward earplug use.

Methods: A RedCap survey was distributed to online surfing forums and surfers at California beaches.

TrachGPT: Appraisal of tracheostomy care recommendations from an artificial intelligent Chatbot.

Objective: Safe home tracheostomy care requires engagement and troubleshooting by patients, who may turn to online, AI-generated information sources. This study assessed the quality of ChatGPT responses to such queries.

Methods: In this cross-sectional study, ChatGPT was prompted with 10 hypothetical tracheostomy care questions in three domains (complication management, self-care advice, and lifestyle adjustment).