Efficacy and safety of filgotinib as induction and maintenance therapy for Crohn's disease (DIVERSITY): a phase 3, double-blind, randomised, placebo-controlled trial.

Background: There is a need for efficacious therapies for patients with Crohn's disease that are better tolerated and more durable than available treatments. We aimed to evaluate the efficacy and safety of filgotinib, an oral Janus kinase 1 preferential inhibitor, for treating Crohn's disease.

Methods: This phase 3, double-blind, randomised, placebo-controlled trial was conducted in 371 centres in 39 countries.

Additively manufactured, long, serpentine submillimeter channels by combining binder jet printing and liquid-phase sintering.

Metallic microfluidic devices made from powder-bed additive manufacturing systems have received increasing attention, but their feasible channel geometry and complexity are often limited by lack of an effective approach to removing trapped powder particles within the channels or conduits of the sintered parts. Here, we present an innovative approach to fabricating long serpentine, high-aspect-ratio submillimeter channels made of stainless steel 316L (SS) by binder jet printing (BJP) and liquid-phase sintering. We leverage the unique nature of the BJP process, that is printing and consolidation steps are decoupled, enabling us to join two or more parts during the sintering step.

Revolutionizing Combat Casualty Care: The Power of Digital Twins in Optimizing Casualty Care Through Passive Data Collection.

The potential impact of large-scale combat operations and multidomain operations against peer adversaries poses significant challenges to the Military Health System including large volumes of critically ill and injured casualties, prolonged care times in austere care contexts, limited movement, contested logistics, and denied communications. These challenges contribute to the probability of higher casualty mortality and risk that casualty care hinders commanders' forward momentum or opportunities for overmatch on the battlefield. Novel technical solutions and associated concepts of operation that fundamentally change the delivery of casualty care are necessary to achieve desired medical outcomes that include maximizing Warfighter battle-readiness, minimizing return-to-duty time, optimizing medical evacuation that clears casualties from the battlefield while minimizing casualty morbidity and mortality, and minimizing resource consumption across the care continuum.

An Ex-Vivo Study Comparing the Accuracy of the E-Connect S+ and Morita Tri Auto ZX2+ Endodontic Handpieces in Root Canal Length Determination.

Introduction: This ex vivo study evaluated the accuracy of the Electronic Apex Locator (EAL) and Automatic Apical Stop (AAS) functions of the E-Connect S+ and Morita Tri Auto ZX2+ cordless apex locators in determining patency length.

Methods: Sixty-four human teeth with a single root were randomly allocated into E-connect or Morita groups (n = 32). The canals were accessed and preflared, after which a size 15 K-file was inserted into the canal to the major foramen and recorded as the actual length (AL).

A tough bioadhesive hydrogel supports sutureless sealing of the dural membrane in porcine and ex vivo human tissue.

Complete sequestration of central nervous system tissue and cerebrospinal fluid by the dural membrane is fundamental to maintaining homeostasis and proper organ function, making reconstruction of this layer an essential step during neurosurgery. Primary closure of the dura by suture repair is the current standard, despite facing technical, microenvironmental, and anatomic challenges. Here, we apply a mechanically tough hydrogel paired with a bioadhesive for intraoperative sealing of the dural membrane in rodent, porcine, and human central nervous system tissue.

Augmented-reality-assisted intraoral scanning: A proof-of-concept study.

Purpose: The aims of the present study were (a) to compare the scanning time and image count to complete optical scans of a typodont between augmented-reality-assisted intraoral scanning (ARIOS) and intraoral scanning (IOS); (b) to compare the accuracy of the digital casts derived from ARIOS and IOS; (c) to compare participant-related outcomes between ARIOS and IOS.

Materials And Methods: A multi-session within-subject experiment was conducted to compare ARIOS and IOS. Thirty-one dental students participated in the study.

Instant tough adhesion of polymer networks.

Generating strong rapid adhesion between hydrogels has the potential to advance the capabilities of modern medicine and surgery. Current hydrogel adhesion technologies rely primarily on liquid-based diffusion mechanisms and the formation of covalent bonds, requiring prolonged time to generate adhesion. Here, we present a simple and versatile strategy using dry chitosan polymer films to generate instant adhesion between hydrogel-hydrogel and hydrogel-elastomer surfaces.

Ionic Peltier effect in Li-ion electrolytes.

The coupled transport of charge and heat provide fundamental insights into the microscopic thermodynamics and kinetics of materials. We describe a sensitive ac differential resistance bridge that enables measurements of the temperature difference on two sides of a coin cell with a resolution of better than 10 μK. We use this temperature difference metrology to determine the ionic Peltier coefficients of symmetric Li-ion electrochemical cells as a function of Li salt concentration, solvent composition, electrode material, and temperature.

Autonomic Neuropathy as a Predictor of Morbidity and Mortality in People Living With HIV: A Retrospective, Longitudinal Cohort Study.

Background And Objectives: HIV-associated autonomic neuropathy (HIV-AN) is common; however, its clinical effect is unclear. Previously, it was shown that the composite autonomic severity score is associated with markers of morbidity such as the Veterans Affair Cohort Study index. In addition, it is known that cardiovascular autonomic neuropathy due to diabetes is associated with poor cardiovascular outcomes.

Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions.

SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variant (B.

Autonomic Neuropathy is Associated with More Densely Interconnected Cytokine Networks in People with HIV.

Introduction: The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of β-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic neuropathy (HIV-AN) would result in immune hyperresponsiveness which could be depicted using network analyses.

Methods: Forty-two adults with well-controlled HIV underwent autonomic testing to yield the Composite Autonomic Severity Score (CASS).

Phenotyping autonomic neuropathy using principal component analysis.

To identify autonomic neuropathy (AN) phenotypes, we used principal component analysis on data from participants (N = 209) who underwent standardized autonomic testing including quantitative sudomotor axon reflex testing, and heart rate and blood pressure at rest and during tilt, Valsalva, and standardized deep breathing. The analysis identified seven clusters: 1) normal, 2) hyperadrenergic features without AN, 3) mild AN with hyperadrenergic features, 4) moderate AN, 5) mild AN with hypoadrenergic features, 6) borderline AN with hypoadrenergic features, 7) mild balanced deficits across parasympathetic, sympathetic and sudomotor domains. These findings demonstrate a complex relationship between adrenergic and other aspects of autonomic function.

Effects of Different Titanium Surfaces Created by 3D Printing Methods, Particle Sizes, and Acid Etching on Protein Adsorption and Cell Adhesion, Proliferation, and Differentiation.

The surfaces of 3D printed titanium prostheses have major impacts on the clinical performance of the prostheses. To investigate the surface effects of the products generated by 3D printed titanium on osseointegration, six surface types of titanium discs produced by the direct metal laser sintering (DMLS) and electron beam melting (EBM) methods, with two sizes of titanium particles and post-printing acid etching, were used to examine the surface topography and to explore the protein adsorption, pro-inflammatory cytokine gene expressions, and MC3T3-E1 cell adhesion, proliferation, and differentiation. The EBM-printed disc showed a stripy and smooth surface without evidence of the particles used, while the DMLS surface contained many particles.

Prioritizing interventions for preventing COVID-19 outbreaks in military basic training.

Like other congregate living settings, military basic training has been subject to outbreaks of COVID-19. We sought to identify improved strategies for preventing outbreaks in this setting using an agent-based model of a hypothetical cohort of trainees on a U.S.

The effect of photodynamic therapy using Radachlorin on biofilm-forming multidrug-resistant bacteria.

Objectives: This study aimed to test the effect of photodynamic therapy (PDT) on the inhibition and removal of biofilms containing multidrug-resistant Acinetobacter baumannii.

Methods: Using multidrug-resistant A. baumannii strains, an antibiotic susceptibility test was performed using the Gram-negative identification card of the Vitek 2 system (bioMérieux Inc.

Quarantine in a COVID-19 Pandemic: Lessons from a Deployed Role I.

The coronavirus (COVID-19) pandemic has changed the world; and the US military changed with it. Although this virus presents with a wide spectrum of disease progression (no symptoms to acute respiratory distress syndrome leading to death), its impact extends beyond health outcomes. At the time of this study, numerous research and development projects were underway to develop a COVID-19 vaccine or other treatment modalities; however, there were no Federal Drug Administration (FDA) approved vaccines or medical therapeutics that definitively provided a cure.

Interpreting resting heart rate variability in complex populations: the role of autonomic reflexes and comorbidities.

Purpose: Resting heart rate variability (HRV) is an important biomarker linking mental health to cardiovascular outcomes. However, resting HRV is also impaired in autonomic neuropathy, a common and underdiagnosed complication of common medical conditions which is detected by testing autonomic reflexes. We sought to describe the relationship between autonomic reflex abnormalities and resting HRV, taking into consideration medical comorbidities and demographic variables.

Virological and Serological Assessment of US Army Trainees Isolated for Coronavirus Disease 2019.

Background: Laboratory screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key mitigation measure to avoid the spread of infection among recruits starting basic combat training in a congregate setting. Because viral nucleic acid can be detected persistently after recovery, we evaluated other laboratory markers to distinguish recruits who could proceed with training from those who were infected.

Methods: Recruits isolated for coronavirus disease 2019 (COVID-19) were serially tested for SARS-CoV-2 subgenomic ribonucleic acid (sgRNA), and viral load (VL) by reverse-transcriptase polymerase chain reaction (RT-PCR), and for anti- SARS-CoV-2.

Designer DNA nanostructures for viral inhibition.

Emerging viral diseases can substantially threaten national and global public health. Central to our ability to successfully tackle these diseases is the need to quickly detect the causative virus and neutralize it efficiently. Here we present the rational design of DNA nanostructures to inhibit dengue virus infection.

Isoprocurcumenol Supports Keratinocyte Growth and Survival through Epidermal Growth Factor Receptor Activation.

Although proliferation of keratinocytes, a major type of skin cells, is a key factor in maintaining the function of skin, their ability to proliferate tends to diminish with age. To solve such a problem, researchers in medical and skin cosmetic fields have tried to utilize epidermal growth factor (EGF), but achieved limited success. Therefore, a small natural compound that can mimic the activity of EGF is highly desired in both medical and cosmetic fields.

PCA062, a P-cadherin Targeting Antibody-Drug Conjugate, Displays Potent Antitumor Activity Against P-cadherin-expressing Malignancies.

The cell surface glycoprotein P-cadherin is highly expressed in a number of malignancies, including those arising in the epithelium of the bladder, breast, esophagus, lung, and upper aerodigestive system. PCA062 is a P-cadherin specific antibody-drug conjugate that utilizes the clinically validated SMCC-DM1 linker payload to mediate potent cytotoxicity in cell lines expressing high levels of P-cadherin , while displaying no specific activity in P-cadherin-negative cell lines. High cell surface P-cadherin is necessary, but not sufficient, to mediate PCA062 cytotoxicity.

Seeing and doing are not believing: Investigating when and how conceptual knowledge impinges on observation and recall of physical motion.

One standard pedagogical approach in physical science courses engages students in making predictions about physical phenomena that elicit non-normative expectations, then make observations intended to provide counterevidence that sparks conceptual change. This article presents five experiments investigating conditions where observation and recall are impacted by incorrect expectations and how these theory-laden observational errors might be mitigated. Using the context of balancing, Experiments 1-3 examine how the ambiguity of the stimuli may allow observers to selectively attend to information that is consistent with prior beliefs, while discounting incongruent information.