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.

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.

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.

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.

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.

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.

hnRNP K supports the maintenance of RORγ circadian rhythm through ERK signaling.

Retinoic acid-related orphan receptor γ (RORγ) maintains the circadian rhythms of its downstream genes. However, the mechanism behind the transcriptional activation of RORγ itself remains unclear. Here, we demonstrate that transcription of RORγ is activated by heterogeneous nuclear ribonucleoprotein K (hnRNP K) via the poly(C) motif within its proximal promoter.

COVID-19 in a Role I Evacuation: A Case Series.

Since December 2019, the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) became an emerging infectious disease pathogen that led to a global pandemic with over 43 million cases reported worldwide and more than 1.1 million global deaths (as of 26 Oct 2020, from https://coronavirus.jhu.

Validation of Psychometric Properties of the Itch Numeric Rating Scale for Pruritus Associated With Prurigo Nodularis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: There is an unmet need for psychometrically sound instruments to measure pruritus associated with prurigo nodularis (PN).

Objective: To evaluate the psychometric properties of the itch numeric rating scale (itch NRS), both the Worst Itch Numeric Rating Scale (WI-NRS) and the Average Itch Numeric Rating Scale (AI-NRS).

Design, Setting, And Participants: This secondary analysis is based on a secondary end point of a phase 2 randomized clinical trial of serlopitant for treatment of pruritus associated with PN.

hnRNP K Supports High-Amplitude D Site-Binding Protein mRNA ( mRNA) Oscillation To Sustain Circadian Rhythms.

Circadian gene expression is defined by the gene-specific phase and amplitude of daily oscillations in mRNA and protein levels. D site-binding protein mRNA ( mRNA) shows high-amplitude oscillation; however, the underlying mechanism remains elusive. Here, we demonstrate that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator that activates transcription via the poly(C) motif within its proximal promoter.

Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition.

DNA, when folded into nanostructures with a specific shape, is capable of spacing and arranging binding sites into a complex geometric pattern with nanometre precision. Here we demonstrate a designer DNA nanostructure that can act as a template to display multiple binding motifs with precise spatial pattern-recognition properties, and that this approach can confer exceptional sensing and potent viral inhibitory capabilities. A star-shaped DNA architecture, carrying five molecular beacon-like motifs, was constructed to display ten dengue envelope protein domain III (ED3)-targeting aptamers into a two-dimensional pattern precisely matching the spatial arrangement of ED3 clusters on the dengue (DENV) viral surface.

Defect evaluation by infant photographs in a multicenter pharmaceutical clinical trial.

Object: The NT-04 clinical trial of investigational medication NT100 had a limited, though geographically diverse, study population. To enhance potential birth defect identification, photographic dysmorphology exam of infants was performed along with review of prenatal and postnatal medical records.

Methods: Standardized photographic views were developed: full body (prone and supine), face, both profiles, dorsal and ventral hands and feet, genitalia, and birthmarks/skin lesions.

Comparative genomic analysis of four multidrug-resistant isolates of Acinetobacter baumannii from Georgia.

Objectives: This study reports the draft genomes of four newly isolated multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) isolates (0830, 0365, 4022, and 2846) from western Georgia to identify putative antimicrobial resistance genes (ARGs) and to determine the clonal subtypes of local clinical isolates.

Methods: An Illumina MiSeq sequencer was used to perform whole-genome sequencing (WGS).

Phase 2 trial of a neurokinin-1 receptor antagonist for the treatment of chronic itch in patients with epidermolysis bullosa: A randomized clinical trial.

Background: Chronic pruritus causes major morbidity in epidermolysis bullosa (EB). The substance P-neurokinin 1 receptor (SP-NK1) pathway is a promising target for treating EB-related pruritus.

Objective: To evaluate the safety and efficacy of the oral NK1 receptor antagonist serlopitant in treating moderate-severe pruritus in EB.

The NK1 receptor antagonist serlopitant for treatment of chronic pruritus.

: Pruritus is a common symptom associated with several potential underlying causes, including both dermatologic and systemic diseases; it can also occur without an identifiable cause. Current treatment options are limited and most patients experience impaired quality of life. Serlopitant is a neurokinin 1 (NK) receptor antagonist under development for the treatment of pruritus associated with various dermatologic conditions and chronic pruritus of unknown origin.

The Poly(C) Motif in the Proximal Promoter Region of the D Site-Binding Protein Gene () Drives Its High-Amplitude Oscillation.

The D site-binding protein (Dbp) supports the rhythmic transcription of downstream genes, in part by displaying high-amplitude cycling of its own transcripts compared to other circadian-clock genes. However, the underlying mechanism remains elusive. Here, we demonstrated that the poly(C) motif within the proximal promoter, in addition to an E-box element, provoked transcriptional activation.

Serlopitant reduced pruritus in patients with prurigo nodularis in a phase 2, randomized, placebo-controlled trial.

Background: Anecdotal evidence suggests that neurokinin 1 receptor antagonism reduces pruritus intensity in chronic pruritic conditions such as prurigo nodularis (PN).

Objective: This study assessed safety and efficacy of the neurokinin 1 receptor antagonist serlopitant for treatment of pruritus in PN.

Methods: In this randomized, double-blind, placebo-controlled study, 128 patients with chronic, treatment-refractory PN for more than 6 weeks received serlopitant, 5 mg, or placebo orally once daily for 8 weeks.