Immunogenicity of the 9-valent human papillomavirus vaccine: Post hoc analysis from five phase 3 studies.

Post hoc analyses of 9-valent human papillomavirus (9vHPV) vaccine immunogenicity were conducted in five Phase 3 studies that enrolled males. Month 7 antibody geometric mean titers (GMTs) after three 9vHPV vaccine doses were analyzed in 10,024 males/females aged 16-26 years from studies 001 (NCT00543543), 002 (NCT00943722), 003 (NCT01651949), and 020 (NCT02114385). Covariates considered were age, gender, sexual orientation, region of residence, and race.

Nucleic acid joining enzymes: biological functions and synthetic applications beyond DNA.

DNA-joining by ligase and polymerase enzymes has provided the foundational tools for generating recombinant DNA and enabled the assembly of gene and genome-sized synthetic products. Xenobiotic nucleic acid (XNA) analogues of DNA and RNA with alternatives to the canonical bases, so-called 'unnatural' nucleobase pairs (UBP-XNAs), represent the next frontier of nucleic acid technologies, with applications as novel therapeutics and in engineering semi-synthetic biological organisms. To realise the full potential of UBP-XNAs, researchers require a suite of compatible enzymes for processing nucleic acids on a par with those already available for manipulating canonical DNA.

Combining computational modeling and experimental library screening to affinity-mature VEEV-neutralizing antibody F5.

Engineered monoclonal antibodies have proven to be highly effective therapeutics in recent viral outbreaks. However, despite technical advancements, an ability to rapidly adapt or increase antibody affinity and by extension, therapeutic efficacy, has yet to be fully realized. We endeavored to stand-up such a pipeline using molecular modeling combined with experimental library screening to increase the affinity of F5, a monoclonal antibody with potent neutralizing activity against Venezuelan Equine Encephalitis Virus (VEEV), to recombinant VEEV (IAB) E1E2 antigen.

Digital phenotyping of social functioning and employment in people with schizophrenia: Pilot data from an international sample.

Aim: Individuals living with schizophrenia experience significant impairments in social functioning. As a major clinical outcome, social functioning requires appropriate measurement tools that can capture its dynamic nature. Digital phenotyping, using smartphone technology to collect high volume ecologically valid data, can potentially capture these facets.

Impact of the WHO safe childbirth checklist on birth attendant behavior and maternal-newborn outcomes: A systematic review and meta-analysis.

Background: The intrapartum period is critical for reducing maternal and perinatal morbidity and mortality. The WHO's Safe Childbirth Checklist (SCC) was designed as a reminder of the most critical, evidence-based practices (EBPs) to improve quality care and reduce preventable complications and deaths.

Objective: To assess the impact of SCC on birth attendant behavior and maternal and newborn health outcomes.

Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.

The TGF-β family ligand Nodal is an essential regulator of embryonic development, orchestrating key processes such as germ layer specification and body axis formation through activation of SMAD2/3-mediated signaling. Significantly, this activation requires the co-receptor Cripto-1. However, despite their essential roles in embryogenesis, the molecular mechanism through which Cripto-1 enables Nodal to activate the SMAD2/3 pathway has remained elusive.

EXPRESS: The Time Course of Cognitive Effort During Disrupted Speech.

Listeners often find themselves in scenarios where speech is disrupted, misperceived, or otherwise difficult to recognize. In these situations, many individuals report exerting additional effort to understand speech, even when repairing speech may be difficult or impossible. This investigation aimed to characterize cognitive effort across time during both sentence listening and a post-sentence retention interval by observing the pupillary response of participants with normal to borderline normal hearing in response to two interrupted speech conditions: sentences interrupted by gaps of silence or bursts of noise.

The multifaceted role of XCL1 in health and disease.

The chemokine XC motif chemokine ligand 1 (XCL1) is an unusually specialized member of a conserved family of around 50 small, secreted proteins that are best known for their ability to stimulate the directional migration of cells. All chemokines adopt a very similar folded structure that binds a specific G protein-coupled receptor (GPCR), and most chemokines bind extracellular matrix glycosaminoglycans, often in a dimeric or oligomeric form. Owing in part to the lack of a disulfide bond that is conserved in all other chemokines, XCL1 interconverts between two distinct structures with distinct functions.

Allosteric modulation of NF1 GAP: Differential distributions of catalytically competent populations in loss-of-function and gain-of-function mutants.

Neurofibromin (NF1), a Ras GTPase-activating protein (GAP), catalyzes Ras-mediated GTP hydrolysis and thereby negatively regulates the Ras/MAPK pathway. NF1 mutations can cause neurofibromatosis type 1 manifesting tumors, and neurodevelopmental disorders. Exactly how the missense mutations in the GAP-related domain of NF1 (NF1) allosterically impact NF1 GAP to promote these distinct pathologies is unclear.

Human recombinant tyrosinase destabilization caused by the double mutation R217Q/R402Q.

Oculocutaneous albinism is an autosomal recessive inherited disorder associated with mutations in the TYR gene. A single missense change in the tyrosinase (Tyr) could result in partial or complete loss of catalytic activity. The effect of two genetic mutations in the same Tyr as the molecule is less studied.

α-N-Methyltransferase regiospecificity is mediated by proximal, redundant enzyme-substrate interactions.

N-Methylation of the peptide backbone confers pharmacologically beneficial characteristics to peptides that include greater membrane permeability and resistance to proteolytic degradation. The borosin family of ribosomally synthesized and post-translationally modified peptides offer a post-translational route to install amide backbone α-N-methylations. Previous work has elucidated the substrate scope and engineering potential of two examples of type I borosins, which feature autocatalytic precursors that encode N-methyltransferases that methylate their own C-termini in trans.

LEA_4 motifs function alone and in conjunction with synergistic cosolutes to protect a labile enzyme during desiccation.

Organisms from all kingdoms of life depend on Late Embryogenesis Abundant (LEA) proteins to survive desiccation. LEA proteins are divided into broad families distinguished by the presence of family-specific motif sequences. The LEA_4 family, characterized by 11-residue motifs, plays a crucial role in the desiccation tolerance of numerous species.

Predictors and Moderators of Panic Disorder: Cognitive Behavioral Therapy vs. Acceptance and Commitment Therapy.

Background: Understanding variables that influence therapy outcomes can improve the results of interventions and reduce socio-health costs. The current study examined possible predictors and moderators of outcome (age, gender, duration of panic disorder, motivation to change, conscientiousness, and experiential avoidance) in Cognitive Behavioral Therapy (CBT) and Acceptance and Commitment Therapy (ACT).

Method: Eighty participants with a diagnosis of panic disorder, 56 women and 24 men, with an average age of 38 years, received 12 group sessions of CBT or ACT.

Multifaceted pulmonary manifestations of amyloidosis: state-of-the-art update.

Introduction: Amyloidosis, a polymeric deposition disease classified according to protein subtype, may have varied pulmonary manifestations. Its anatomic-radiologic phenotypes include nodular, cystic, alveolar-septal, and tracheobronchial forms. Clinical presentation may range from asymptomatic parenchymal nodules to respiratory failure from diffuse parenchymal infiltration or diaphragmatic deposition.

The weight of multiple hits: how TBI and infectious encephalitis co-modulate adverse outcomes.

Background: Chronic neurologic deficits from traumatic brain injury (TBI) and subsequent infectious encephalitis are poorly characterized.

Methods: Using TriNetX database we queried patients 18 years or older with a confirmed diagnosis of encephalitis between 2016 and 2024. Patient cohorts included those with a diagnosis of TBI at least one month before encephalitis ( = 1,038), those with a diagnosis of a TBI anytime before encephalitis ( = 1,886), and those with encephalitis but no TBI, ( = 45,210;  = 45,215).

A novel transgenic reporter of extracellular acidification in zebrafish elucidates skeletal muscle T-tubule pH regulation.

Disruption of extracellular pH and proton-sensing can profoundly impact cellular and protein functions, leading to developmental defects. To visualize changes in extracellular pH in the developing embryo, we generated a zebrafish transgenic line that ubiquitously expresses the ratiometric pH-sensitive fluorescent protein pHluorin2, tethered to the extracellular face of the plasma membrane using a glycosylphosphatidylinositol (GPI) anchor. Monitoring of pHluorin2 with ratiometric fluorescence revealed dynamic and discrete domains of extracellular acidification over the first 72 h of embryonic development.

Orbital and Ocular Venous Congestion: A Rare Manifestation of Hypervascular Paget Disease of the Bone.

A 73-year-old male with a history of incidentally diagnosed Paget disease of bone affecting the skull and left orbit 2 years prior presented with 3 months of vision loss, proptosis, and periorbital swelling of the OS. Examination showed best-corrected Snellen visual acuity of 20/150 in the affected eye, intact motility, 7 mm of relative proptosis, significant dilated and tortuous "corkscrew" conjunctival vessels, serous choroidal and retinal detachments, optic nerve hyperemia, and venous tortuosity and dilation. Although the bony lesions in the left orbit were stable from 1 year prior on imaging, the diagnostic angiogram demonstrated osseous blush and hypervascularity of the lesion.

Toward a Consistent Framework for Describing the Free Vibration Modes of the Brain.

Frequency-domain analysis of brain tissue motion has received increased focus in recent years as an approach to describing the response of the brain to impact or vibration sources in the built environment. While researchers in many experimental and numerical studies have sought to identify natural resonant frequencies of the brain, limited description of the associated vibration modes limits comparison of results between studies. We performed a modal analysis to extract the natural frequencies and associated mode shapes of a finite element model of the head.

Evaluating the Combined Neurotoxicity of Amyloid Beta and Tau Oligomers in Alzheimer's Disease: A Novel Cellular-Level Criterion.

A criterion characterizing the combined neurotoxicity of amyloid beta and tau oligomers is suggested. A mathematical model that makes it possible to calculate a value of this criterion during senile plaque and NFT formation is proposed. Computations show that for physiologically relevant parameter values, the value of the criterion increases approximately linearly as time increases.

Multicentric Mucinous Adenocarcinoma of Bilateral Eyelids.

A 59-year-old female patient presented with a purple, fluid-filled lesion on her left upper eyelid that contained a solid component. Excisional biopsy revealed a diagnosis of mucinous adenocarcinoma. Extensive oncological workup was negative for a distant primary tumor or metastasis and confirmed a diagnosis of primary mucinous adenocarcinoma.

HEalth-Related Quality of Life-Intervention in Survivors of Breast and Other Cancers Experiencing Cancer-Related Fatigue and Associated Cognitive Symptoms Using TraditionAL Chinese Medicine: The 'HERBAL' Trial.

Introduction: As pharmacological strategies remain limited for relieving fatigue and associated cognitive symptoms, integrative modalities such as traditional Chinese medicine (TCM) could be explored as therapeutic strategies in cancer survivors. Here, we evaluate and report the efficacy and safety of a TCM concoction, modified Xiang Bei Yang Rong Tang (XBYRT), on quality of life (QOL), cancer-related fatigue (CRF), and cognitive symptoms, compared to placebo.

Methods: In a single-centered, randomized, double-blinded, placebo-controlled pilot trial conducted from 2019 to 2022, fatigued cancer survivors ≥21 years old were recruited to receive the XBYRT intervention or placebo (5% diluted) once daily for the duration of 8 weeks.

Correction: Single glucose molecule transport process revealed by force tracing and molecular dynamics simulations.

Correction for 'Single glucose molecule transport process revealed by force tracing and molecular dynamics simulations' by Yangang Pan , , 2018, , 517-524, https://doi.org/10.1039/C8NH00056E.

Molecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases.

Introduction: Mitochondrial dysfunction stands as a pivotal feature in neurodegenerative disorders, spurring the quest for targeted therapeutic interventions. This review examines Ubiquitin-Specific Protease 30 (USP30) as a master regulator of mitophagy with therapeutic promise in Alzheimer's disease (AD) and Parkinson's disease (PD). USP30's orchestration of mitophagy pathways, encompassing PINK1-dependent and PINK1-independent mechanisms, forms the crux of this exploration.

Chemical and temporal manipulation of early steps in protein assembly tunes the structure and intermolecular interactions of protein-based materials.

The Drosophila intrinsically disordered protein Ultrabithorax (Ubx) undergoes a series of phase transitions, beginning with noncovalent interactions between apparently randomly organized monomers, and evolving over time to form increasingly ordered coacervates. This assembly process ends when specific dityrosine covalent bonds lock the monomers in place, forming macroscale materials. Inspired by this hierarchical, multistep assembly process, we analyzed the impact of protein concentration, assembly time, and subphase composition on the early, noncovalent stages of Ubx assembly, which are extremely sensitive to their environment.