Structural and functional characterization of integrin α5-targeting antibodies for anti-angiogenic therapy.

Integrins are a large family of heterodimeric receptors important for cell adhesion and signaling. Integrin α5β1, also known as the fibronectin receptor, is a key mediator of angiogenesis and its dysregulation is associated with tumor proliferation, progression, and metastasis. Despite numerous efforts, α5β1-targeting therapeutics have been unsuccessful in large part due to efficacy and off-target effects.

Improvement in Patient-reported Symptoms and Satisfaction with Tildrakizumab in a Real-world Study in Patients with Moderate-to-severe Plaque Psoriasis.

Objective: Tildrakizumab, an anti-interleukin-23 p19 monoclonal antibody, is approved for the treatment of adults with moderate-to-severe plaque psoriasis. Limited evidence is available regarding the effects of tildrakizumab on patient-reported symptoms and satisfaction. This report describes the secondary endpoints of patient-reported symptoms and treatment satisfaction over 64 weeks in patients with moderate-to-severe plaque psoriasis treated with tildrakizumab in a Phase IV, real-world study.

An experimental study of the sensorized strain wave gear RT1-T and its capabilities for torque control in robotic joints.

The idea of sensorizing a strain wave gear to measure the transmitted torque has been reported since the 1980s. The strain in the elastic flex spline is typically measured by strain gages attached to it. The resulting voltages relate to the transmitted torque in the gear.

Tildrakizumab Real-World Effectiveness and Safety Over 64 Weeks in Patients With Moderate-to-Severe Plaque Psoriasis.

Background: Tildrakizumab is a humanized anti-interleukin-23 p19 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis. This report describes real-world effectiveness and safety of tildrakizumab through 64 weeks of treatment.

Methods: In this Phase 4, multicenter, uncontrolled, open-label trial (NCT03718299), adults with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at weeks 0 and 4 and every 12 weeks thereafter through week 52.

Development and validation of a stakeholder-driven, self-contained electronic informed consent platform for trio-based genomic research studies.

Increasingly long and complex informed consents have yielded studies demonstrating comparatively low participant and with traditional face-to-face approaches. In parallel, interest in electronic consents for clinical and research genomics has steadily increased, yet limited data are available for trio-based genomic discovery studies. We describe the design, development, implementation, and validation of an electronic iConsent application for trio-based genomic research deployed to support genomic studies of cerebral palsy.

Long-term quality of life outcomes from a phase 4 study of tildrakizumab in patients with moderate-to-severe plaque psoriasis in a real-world setting.

Background: Tildrakizumab is an anti-interleukin-23 p19 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis. This report describes final primary results of a 64-week real-world study of the effect of tildrakizumab on patients' health-related quality of life (HRQoL).

Materials And Methods: In this open-label phase 4 study (NCT03718299), patients with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at week 0, week 4, and every 12 weeks thereafter through week 52.

Candida parapsilosis: A systematic review to inform the World Health Organization fungal priority pathogens list.

Candida parapsilosis is globally distributed and recognised for causing an increasing proportion of invasive Candida infections. It is associated with high crude mortality in all age groups. It has been particularly associated with nosocomial outbreaks, particularly in association with the use of invasive medical devices such as central venous catheters.

Features and global impact of invasive fungal infections caused by Pneumocystis jirovecii: A systematic review to inform the World Health Organization fungal priority pathogens list.

This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%.

Eumycetoma causative agents: A systematic review to inform the World Health Organization priority list of fungal pathogens.

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic review aimed to evaluate the epidemiology and impact of eumycetoma. PubMed and Web of Science were searched to identify studies published between 1 January 2011 and 19 February 2021.

Histoplasmosis: A systematic review to inform the World Health Organization of a fungal priority pathogens list.

Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%-44%) in people living with HIV, with mortality rates ranging from 21% to 53%.

A novel SARS-CoV-2 Beta RBD DNA vaccine directly targeted to antigen-presenting cells induces strong humoral and T cell responses.

Throughout the COVID-19 pandemic, several variants of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have evolved, affecting the efficacy of the approved COVID-19 vaccines. To address the need for vaccines that induce strong and persistent cross-reactive neutralizing antibodies and T cell responses, we developed a prophylactic SARS-CoV-2 vaccine candidate based on our easily and rapidly adaptable plasmid DNA vaccine platform. The vaccine candidate, referred to here as VB2129, encodes a protein homodimer consisting of the receptor binding domain (RBD) from lineage B.

TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions.

Highly conserved transport protein particle (TRAPP) complexes regulate subcellular trafficking pathways. Accurate protein trafficking has been increasingly recognized to be critically important for normal development, particularly in the nervous system. Variants in most TRAPP complex subunits have been found to lead to neurodevelopmental disorders with diverse but overlapping phenotypes.

Electrophilic Agonists Modulate the Transient Receptor Potential Ankyrin-1 Channels Mediated by Insulin and Glucagon-like Peptide-1 Secretion for Glucose Homeostasis.

This pre-clinical study investigated the transient receptor potential ankyrin-1 (TRPA1) channels on modulating targets for glucose homeostasis using agonists: the electrophilic agonists, cinnamaldehyde (CIN) and allyl isothiocyanate (AITC), and the non-electrophilic agonist, carvacrol (CRV). A glucose tolerance test was performed on rats. CIN and AITC (5, 10 and 20 mg/kg) or CRV (25, 100, 300, and 600 mg/kg) were administered intraperitoneally (i.

Real-World Effectiveness and Safety of Tildrakizumab in Patients With Moderate-to-Severe Psoriasis: Week 28 Interim Analysis of a Phase 4 Study.

Background: Tildrakizumab is an anti–interleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. This analysis evaluated real-world effectiveness and safety of tildrakizumab for 28 weeks.

Methods: In this Phase 4 study (NCT03718299), adults with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg subcutaneously at week 0, week 4, and every 12 weeks thereafter.

Intrathecal magnesium delivery for Mg++-insensitive NMDA receptor activity due to GRIN1 mutation.

Background: Mutations in the NMDA receptor are known to disrupt glutamatergic signaling crucial for early neurodevelopment, often leading to severe global developmental delay/intellectual disability, epileptic encephalopathy, and cerebral palsy phenotypes. Both seizures and movement disorders can be highly treatment-refractory.

Results: We describe a targeted ABA n-of-1 treatment trial with intrathecal MgSO, rationally designed based on the electrophysiologic properties of this gain of function mutation in the GRIN1 NMDA subunit.

The role of extended coagulation screening in adult cranial neurosurgery.

Introduction: Postoperative hemorrhage after adult cranial neurosurgery is a serious complication with substantial morbidity and mortality.

Research Question: We investigated if an extended preoperative screening and an early treatment of previously undetected coagulopathies may decrease the risk of postoperative hemorrhage.

Methods: A prospective study cohort of patients undergoing elective cranial surgery and receiving the extended coagulatory work-up were compared to a propensity matched historical control cohort.

Quality of life and patient-reported symptoms in a Phase 4, real-world study of tildrakizumab in patients with moderate-to-severe psoriasis: Week 28 interim analysis.

Background: Tildrakizumab is an anti-interleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. Little real-world evidence is available regarding the effects of tildrakizumab on patients' health-related quality of life (HRQoL) and patient-reported symptoms.

Objective: This real-world study of tildrakizumab evaluated changes in HRQoL and clinical symptoms in patients with psoriasis.

Augmenting systems-level implementation of patient-reported outcomes for depression care through the use of structured analysis and design technique.

Background: Health systems increasingly need to implement complex practice changes such as the routine capture of patient-reported outcome (PRO) measures. Yet, health systems have met challenges when trying to bring practice change to scale across systems at large. While implementation science can guide the evaluation of implementation determinants, teams first need tools to systematically understand and compare workflow activities across practice sites.

Guiding the Lean Design of a Hospital's New Laboratory: A Case Study.

Purpose: To present the process used by a clinical laboratory to guide the design of their new facility, part of a major campus expansion at a pediatric hospital.

Objective: The primary objective was to generate information about arrangement and allocation of laboratory space and functional flows in the early phases of the expansion project.

Background: Seattle Children's Hospital has increased the capacity of their primary campus in response to growing demand for specialized services.

Isolated Internal Ophthalmoplegia from Posterior Cerebral Artery Neurovascular Conflict.

We report a rare case of recurrent isolated internal ophthalmoplegia attributed to oculomotor nerve (CN III) compression by the posterior cerebral artery (PCA). A 30-year-old female patient presented with recurrent right-sided headaches, right periorbital pain, and slight anisocoria. Slit-lamp examination revealed normal anterior and posterior segments except for vermiform movements of the right pupil with a temporal hyporeactive flat area.

Real-Time (iOCT) Guided Epiretinal Membrane Surgery Using a Novel Forceps with Laser-Ablated Microstructure Tip Surface.

Purpose: We investigated intraoperative OCT (iOCT)-guided epiretinal membrane (ERM) and internal limiting membrane (ILM) removal using a novel forceps with a laser-ablated tip surface; it was designed to help prevent indentation force, shear stress, or tractional trauma when grasping very fine membranes.

Patients And Methods: This retrospective study included patients who underwent 23- and 25-gauge pars plana vitrectomy (PPV) for vitreoretinal interface disorders. ERM and ILM peeling was performed under guidance with microscope-integrated iOCT using novel ILM forceps with laser-ablated tip surfaces.

Is Resting State Functional MRI Effective Connectivity in Movement Disorders Helpful? A Focused Review Across Lifespan and Disease.

In the evolving modern era of neuromodulation for movement disorders in adults and children, much progress has been made recently characterizing the human motor network (MN) with potentially important treatment implications. Herein is a focused review of relevant resting state fMRI functional and effective connectivity of the human motor network across the lifespan in health and disease. The goal is to examine how the transition from functional connectivity to dynamic effective connectivity may be especially informative of network-targeted movement disorder therapies, with hopeful implications for children.

Effect of substrate properties and phosphorus supply on facilitating the uptake of rare earth elements (REE) in mixed culture cropping systems of Hordeum vulgare, Lupinus albus and Lupinus angustifolius.

This study presents how phosphate (P) availability and intercropping may influence the migration of rare earth elements (REEs) in legume-grass associations. In a replacement model, Hordeum vulgare was intercropped with 11% Lupinus albus and 11% Lupinus angustifolius. They were cultivated on two substrates, A (pH = 7.