Patient Factors Influence Minimal Clinically Important Difference for the SNOT-22 in Medically Treated Chronic Rhinosinusitis.

Background: The present study explores the effect of sociodemographics and comorbidities on the calculated minimal clinically important difference (MCID) for 22-item Sinonasal Outcome Test (SNOT-22) scores in patients with medically treated chronic rhinosinusitis (CRS). The importance of delineating a threshold to indicate clinically meaningful changes perceived by a patient is well acknowledged, yet the influence of patient-specific factors on MCID has not been fully elucidated.

Methods: Patients with CRS (n = 221) presenting to a tertiary care practice reported their change in disease burden with anchor questions following CRS-directed medical treatment.

I'm Getting a Migraine: A Comparative Evaluation of Patient and Clinician Interpretations of Migraine Symptoms.

Patients and providers vary in how they describe common otolaryngology-related complaints. These differences can lead to miscommunication and frustration that may affect patient outcomes and satisfaction. The aim of this cross-sectional survey-based study was to explore the differences in migraine symptom selection by otolaryngology patients and clinicians.

Protein interactions in human pathogens revealed through deep learning.

Identification of bacterial protein-protein interactions and predicting the structures of these complexes could aid in the understanding of pathogenicity mechanisms and developing treatments for infectious diseases. Here we developed RoseTTAFold2-Lite, a rapid deep learning model that leverages residue-residue coevolution and protein structure prediction to systematically identify and structurally characterize protein-protein interactions at the proteome-wide scale. Using this pipeline, we searched through 78 million pairs of proteins across 19 human bacterial pathogens and identified 1,923 confidently predicted complexes involving essential genes and 256 involving virulence factors.

Computational design of serine hydrolases.

Enzymes that proceed through multistep reaction mechanisms often utilize complex, polar active sites positioned with sub-angstrom precision to mediate distinct chemical steps, which makes their de novo construction extremely challenging. We sought to overcome this challenge using the classic catalytic triad and oxyanion hole of serine hydrolases as a model system. We used RFdiffusion to generate proteins housing catalytic sites of increasing complexity and varying geometry, and a newly developed ensemble generation method called ChemNet to assess active site geometry and preorganization at each step of the reaction.

A pseudotyped adenovirus serotype 5 vector with serotype 49 fiber knob is an effective vector for vaccine and gene therapy applications.

Adenoviruses (Ads) have demonstrated significant success as replication-deficient (RD) viral vectored vaccines, as well as broad potential across gene therapy and cancer therapy. Ad vectors transduce human cells via direct interactions between the viral fiber knob and cell surface receptors, with secondary cellular integrin interactions. Ad receptor usage is diverse across the extensive phylogeny.

Cytomegalovirus-induced peroxynitrite promotes virus entry and contributes to pathogenesis in a murine model of infection.

Unlabelled: There are no licensed vaccines for human cytomegalovirus (HCMV), and current antiviral drugs that target viral proteins are toxic and prone to resistance. Targeting host pathways essential for virus replication provides an alternate strategy that may reduce opportunities for drug resistance to occur. Oxidative stress is triggered by numerous viruses including HCMV.

University of Washington Quality of Life subdomain outcomes after treatment of sinonasal malignancy: A prospective, multicenter study.

Purpose: Sinonasal malignancies (SNMs) adversely impact patients' quality of life (QOL) and are frequently identified at an advanced stage. Because these tumors are rare, there are few studies that examine the specific QOL areas that are impacted. This knowledge would help improve the care of these patients.

A targeted single mutation in influenza A virus universal epitope transforms immunogenicity and protective immunity via CD4 T cell activation.

CD4 T cells are central to adaptive immunity. Their role in cross-protection in viral infections such as influenza and severe acute respiratory syndrome (SARS) is well documented; however, molecular rules governing T cell receptor (TCR) engagement of peptide-human leukocyte antigen (pHLA) class II are less understood. Here, we exploit an aspect of HLA class II presentation, the peptide-flanking residues (PFRs), to "tune" CD4 T cell responses within an in vivo model system of influenza.

Rapid and accurate prediction of protein homo-oligomer symmetry with Seq2Symm.

The majority of proteins must form higher-order assemblies to perform their biological functions. Despite the importance of protein quaternary structure, there are few machine learning models that can accurately and rapidly predict the symmetry of assemblies involving multiple copies of the same protein chain. Here, we address this gap by training several classes of protein foundation models, including ESM-MSA, ESM2, and RoseTTAFold2, to predict homo-oligomer symmetry.

Essential and virulence-related protein interactions of pathogens revealed through deep learning.

Identification of bacterial protein-protein interactions and predicting the structures of the complexes could aid in the understanding of pathogenicity mechanisms and developing treatments for infectious diseases. Here, we developed a deep learning-based pipeline that leverages residue-residue coevolution and protein structure prediction to systematically identify and structurally characterize protein-protein interactions at the proteome-wide scale. Using this pipeline, we searched through 78 million pairs of proteins across 19 human bacterial pathogens and identified 1923 confidently predicted complexes involving essential genes and 256 involving virulence factors.

Lymphoedema specialists embedded into community nurse and wound services: impacts and outcomes.

Background: Lymphoedema is a progressive condition causing significant alterations to life, exerting pressures on unscheduled care from complications including cellulitis and wounds. An on the ground education programme (OGEP) was implemented to raise knowledge, competence and confidence in lymphoedema management in community clinical services. The aim of this study was to explore the impact and outcomes of the OGEP intervention.

Mucosal T-cell responses to chronic viral infections: Implications for vaccine design.

Mucosal surfaces that line the respiratory, gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment. Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses. Numerous pathogenic viruses, including herpesviruses and retroviruses, exploit this environment to establish chronic infection.

Generalized biomolecular modeling and design with RoseTTAFold All-Atom.

Deep-learning methods have revolutionized protein structure prediction and design but are presently limited to protein-only systems. We describe RoseTTAFold All-Atom (RFAA), which combines a residue-based representation of amino acids and DNA bases with an atomic representation of all other groups to model assemblies that contain proteins, nucleic acids, small molecules, metals, and covalent modifications, given their sequences and chemical structures. By fine-tuning on denoising tasks, we developed RFdiffusion All-Atom (RFdiffusionAA), which builds protein structures around small molecules.

How Do Patients and Otolaryngologists Define Dizziness?

Objective: To assess for differences in how patients and otolaryngologists define the term dizziness.

Methods: Between June 2020 and December 2022, otolaryngology clinicians and consecutive patients at 5 academic otolaryngology institutions across the United States were asked to define the term "dizziness" by completing a semantics-based questionnaire containing 20 common descriptors of the term within 5 symptom domains (imbalance-related, lightheadedness-related, motion-related, vision-related, and pain-related). The primary outcome was differences between patient and clinician perceptions of dizzy-related symptoms.

SNOT-22 subdomain outcomes following treatment for sinonasal malignancy: A prospective, multicenter study.

Background: Patients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22-item Sinonasal Outcomes Test (SNOT-22) has been shown to improve with treatment. This study aims to characterize SNOT-22 subdomain outcomes in SNM.

Impact of an educational intervention on hand hygiene practice among nursing students, with a focus on hand drying efficacy.

Background: Hand hygiene and its significance for reducing the spread of infection is well evidenced and has been brought into sharp focus following the COVID-19 pandemic. Although a crucial clinical skill in ensuring safe healthcare, little is known regarding nursing students' effectiveness of hand hygiene practice.

Aim: The aim of this study was to evaluate the impact of an educational intervention on hand hygiene practice, designed by the research team for first year pre-registration nursing students.

Cognition and saccadic eye movement performance are impaired in chronic rhinosinusitis.

Background: Patients with chronic rhinosinusitis (CRS) can experience cognitive dysfunction. The literature on this topic mostly reflects patient-reported measurements. Our goal was to assess cognitive function in patients with CRS using objective measures, including saccadic eye movements-a behavioral response reflecting cognitive and sensory information integration that is often compromised in conditions with impaired cognition.

CompARE: study protocol for a phase III randomised controlled platform trial comparing alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer.

Background: Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival.

Methods: CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention.

Acquisition of suppressive function by conventional T cells limits antitumor immunity upon T depletion.

Regulatory T (T) cells contribute to immune homeostasis but suppress immune responses to cancer. Strategies to disrupt T cell-mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for treatment failure are poorly understood. By modeling T cell-targeted immunotherapy in mice, we find that CD4 Foxp3 conventional T (T) cells acquire suppressive function upon depletion of Foxp3 T cells, limiting therapeutic efficacy.

Impact and outcomes after lymphaticovenous anastomosis for 150 cases of lymphoedema followed up over 24 months.

Background: Lymphoedema is a chronic condition affecting daily activities of life, causing significant alterations and adjustments. Since 2015, lymphaticovenous anastomosis (LVA) has been available on the National Health Service for people with lymphoedema in Wales, United Kingdom. This study aimed to explore the impact and outcomes after LVA over a 24-month follow-up.

Inhibitory IL-10-producing CD4 T cells are T-bet-dependent and facilitate cytomegalovirus persistence via coexpression of arginase-1.

Inhibitory CD4 T cells have been linked with suboptimal immune responses against cancer and pathogen chronicity. However, the mechanisms that underpin the development of these regulatory cells, especially in the context of ongoing antigen exposure, have remained obscure. To address this knowledge gap, we undertook a comprehensive functional, phenotypic, and transcriptomic analysis of interleukin (IL)-10-producing CD4 T cells induced by chronic infection with murine cytomegalovirus (MCMV).

Are you congested? A comparison of definitions between otolaryngologists and their patients.

Objective: To assess for differences of intended meaning in the description of congestion-related symptoms among otolaryngology patients and clinicians.

Materials And Methods: Between June 2020 and October 2022, a questionnaire consisting of 16 common descriptors of congestion-related symptoms within four domains (obstructive-related, pressure-related, mucus-related, and other symptoms) was completed by patients and otolaryngologists at five tertiary otolaryngology practices. The primary outcome was to assess differences in patient and clinician perceptions of congestion-related symptoms.

Automatic summarization of endoscopic skull base surgical videos through object detection and hidden Markov modeling.

Endoscopic endonasal surgery is a medical procedure that utilizes an endoscopic video camera to view and manipulate a surgical site accessed through the nose. Despite these surgeries being video recorded, these videos are seldom reviewed or even saved in patient files due to the size and length of the video file. Editing to a manageable size may necessitate viewing 3 h or more of surgical video and manually splicing together the desired segments.