Vaccination against Rabbit Hemorrhagic Disease Virus 2 (RHDV2) Using a Baculovirus Recombinant Vaccine Provides Durable Immunity in Rabbits.

Rabbit hemorrhagic disease virus 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly once introduced in a rabbit population. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners.

Air channels create a directional light signal to regulate hypocotyl phototropism.

In plants, light direction is perceived by the phototropin photoreceptors, which trigger directional growth responses known as phototropism. The formation of a phototropin activation gradient across a photosensitive organ initiates this response. However, the optical tissue properties that functionally contribute to phototropism remain unclear.

A novel vaccine candidate against rabbit hemorrhagic disease virus 2 (RHDV2) confers protection in domestic rabbits.

Objective: To evaluate efficacy of a novel vaccine against rabbit hemorrhagic disease virus 2 (RHDV2) in domestic rabbits.

Animals: 40 New Zealand White rabbits obtained from a commercial breeder.

Procedures: Rabbits were vaccinated and held at the production facility for the duration of the vaccination phase and transferred to Colorado State University for challenge with RHDV2.

Older patients with EGFR mutation-positive non-small cell lung cancer treated with afatinib in clinical practice: A subset analysis of the non-interventional GIDEON study.

Introduction: Lung cancer is most common in older patients; despite this, older patients are historically under-represented in clinical studies. Here we present data from GIDEON, a study undertaken in Germany in patients with epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) receiving first-line afatinib. GIDEON enrolled a high proportion of patients aged ≥70 years, providing an opportunity to study afatinib use in older patients.

External Validation of a Machine Learning Based Delirium Prediction Software in Clinical Routine.

Background: Various machine learning (ML) models have been developed for the prediction of clinical outcomes, but there is missing evidence on their performance in clinical routine and external validation.

Objectives: Our aim was to deploy and prospectively evaluate an already developed delirium prediction software in clinical routine of an external hospital.

Methods: We compared updated ML models of the software and models re-trained with the external hospital's data.

Marking 2-Years of New Thinking in Clinical Trials: The Estimand Journey.

The ICH E9(R1) addendum on Estimands and Sensitivity Analyses in Clinical Trials has introduced a new estimand framework for the design, conduct, analysis, and interpretation of clinical trials. We share Pharmaceutical Industry experiences of implementing the estimand framework in the first two years since the final guidance became available with key lessons learned and highlight what else needs to be done to continue the journey in embedding the estimand framework in clinical trials. Emerging best practices and points to consider on strategies for implementing a new estimand thinking process are provided.

Electronic Regulation of Nickel Single Atoms by Confined Nickel Nanoparticles for Energy-Efficient CO Electroreduction.

Modulating the electronic structure of atomically dispersed active sites is promising to boost catalytic activity but is challenging to achieve. Here we show a cooperative Ni single-atom-on-nanoparticle catalyst (NiSA/NP) prepared via direct solid-state pyrolysis, where Ni nanoparticles donate electrons to Ni(i)-N-C sites via a network of carbon nanotubes, achieving a high CO current density of 346 mA cm at -0.5 V vs RHE in an alkaline flow cell.

Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial.

Background: Pimasertib is a selective, potent mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor.

Objectives: The aim of this study was to describe the efficacy, safety, and pharmacodynamics of pimasertib at pharmacologically active doses in a cohort of patients with locally advanced/metastatic melanoma from a first-in-human study of pimasertib.

Methods: This was a phase I, open-label, two-part, dose-escalation study.

Supporting Advanced Practice Providers' Professional Advancement: The Implementation of a Professional Advancement Model at an Academic Medical Center.

Organizational commitment to a structured professional advancement model (PAM) is critical for advanced practice provider (APP) development in order to promote and reward excellence, enhance job satisfaction and improve retention and recruitment. A PAM may also serve as a motivational tool for personal and professional growth by developing and promoting a professional, evidence-based collaborative practice environment. A voluntary PAM was implemented at a large Midwestern academic medical center to recognize experienced APPs including certified nurse practitioners, certified nurse-midwives and physician assistants.

Pharmacokinetics and Pharmacodynamics of a Proposed Pegfilgrastim Biosimilar MSB11455 Versus the Reference Pegfilgrastim Neulasta in Healthy Subjects: A Randomized, Double-blind Trial.

Purpose: MSB11455 is a proposed biosimilar to the reference pegfilgrastim (Neulasta®). This pivotal equivalence study (NCT03251248) assessed the pharmacokinetic and pharmacodynamic equivalence of MSB11455 to the reference product.

Methods: This 2-way, 2-sequence, group-sequential, crossover study was conducted in healthy subjects.

Pimasertib Versus Dacarbazine in Patients With Unresectable -Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover.

This study investigated the efficacy and safety of pimasertib (1/2 inhibitor) versus dacarbazine (DTIC) in patients with untreated -mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 -mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg; oral twice-daily) or DTIC (1000 mg/m; intravenously) on Day 1 of each 21-day cycle.

Immunogenicity and safety of a proposed pegfilgrastim biosimilar MSB11455 versus the reference pegfilgrastim Neulasta in healthy subjects: A randomized, double-blind trial.

MSB11455 is a proposed biosimilar to the currently licensed reference pegfilgrastim (Neulasta ). This study was designed primarily to compare the immunogenicity of MSB11455 and Neulasta . As secondary objectives, the safety and tolerability of MSB11455 and Neulasta were also compared.

Phase I trial of pimasertib monotherapy in Japanese patients with solid tumors and those with hepatocellular carcinoma.

Purpose: This study aimed to confirm the recommended phase II dose (RP2D) of pimasertib in Japanese patients.

Methods: This two-part, phase I dose-escalation and expansion study was conducted in Japanese patients (≥ 18 years old) with advanced solid tumors (ST) including hepatocellular carcinoma (HCC). In Part 1, patients with ST (Arm A) and HCC (Arm B) received escalating doses (3 + 3 design) of oral pimasertib [starting at 45 mg twice daily (BID)] in 21-day cycles, until disease progression or unacceptable toxicity.

Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer.

The selective MEK1/2 inhibitor pimasertib has shown anti-tumour activity in a pancreatic tumour model. This phase I/II, two-part trial was conducted in patients with metastatic pancreatic adenocarcinoma (mPaCa) (NCT01016483). In the phase I part, oral pimasertib was given once daily discontinuously (5 days on/2 days off treatment) or twice daily continuously (n = 53) combined with weekly gemcitabine (1,000 mg/m ) in 28-day cycles to identify the recommended phase II dose (RP2D) of pimasertib.

Van der Waals MoS/VO heterostructure junction with tunable rectifier behavior and efficient photoresponse.

Junctions between n-type semiconductors of different electron affinity show rectification if the junction is abrupt enough. With the advent of 2D materials, we are able to realize thin van der Waals (vdW) heterostructures based on a large diversity of materials. In parallel, strongly correlated functional oxides have emerged, having the ability to show reversible insulator-to-metal (IMT) phase transition by collapsing their electronic bandgap under a certain external stimulus.

[Transretinal Biopsy of Intraocular Lymphoma].

Background: Intraocular lymphoma is in most cases a diagnostic challenge. Gold standard is a diagnostic vitrectomy. Vitreous biopsy and transretinal biopsies are therefore employed.

Management of transradial access for coronary angiography.

The transradial approach for percutaneous coronary intervention and angiography has been shown to be a safe and effective alternative to the traditional transfemoral approach. Used extensively throughout Europe for the past 15 years, this technique has recently gained widespread popularity throughout the United States. Lower direct costs, fewer vascular complications, better patient acceptance, and earlier ambulation are some of the direct benefits from using radial access.

Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study.

Background: Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting.

Methods: Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays.

[Intraocular medulloepithelioma - series of 10 cases and review of the literature].

Intraocular medulloepithelioma is an extremely rare unilateral intraocular tumor arising from the nonpigmented ciliary epithelium. Medulloepitheliomas may be classified as benign and malignant and as teratoid and nonteratoid tumors. As a rule a long latency period occurs after first symptoms until the final diagnosis of a medulloepithelioma is made.

Platinum-based chemotherapy plus cetuximab in head and neck cancer.

Background: Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck.

Methods: We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles.

Driver reaction time before and after treatment for lumbar radiculopathy.

Study Design: Prospective observational pilot study. OBJECTIVE.: To investigate the effect of right and left radiculopathy on driver reaction time (DRT), and the effect of selective nerve root block (SNRB) on DRT.

Photodynamic therapy in retinoblastoma: effects of verteporfin on retinoblastoma cell lines.

Purpose: In contrast to the excellent survival rates of the malignant childhood tumor retinoblastoma (RB), morbidity is high in patients with this disease because of the enucleation or loss of retinal areas caused by current bulb-saving therapies. The authors aimed to preclinically assess the effects of photochemotherapy using second-generation photochemotherapeutics as a prerequisite to develop a promising therapeutic alternative. This therapy implies intravenous application of a photosensitizer activated locally by light of the appropriate wavelength.

Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy.

Purpose: To evaluate the efficacy and safety of the epidermal growth factor receptor-directed monoclonal antibody cetuximab administered as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression on platinum therapy.

Patients And Methods: An open-label multicenter study in which patients with disease progression on two to six cycles of platinum therapy received single-agent cetuximab (initial dose 400 mg/m2 followed by subsequent weekly doses of 250 mg/m2) for > or = 6 weeks (single-agent phase). Patients who experienced disease progression could receive salvage therapy with cetuximab plus platinum (combination-therapy phase).

Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Purpose: This was an open, randomized, multicenter, phase I/II study to investigate the safety and tolerability of cetuximab in the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).

Patients And Methods: Treatment comprised cetuximab (initial dose 400 mg/m2 with subsequent weekly doses of 250 mg/m2) in combination with 3-week cycles of either cisplatin (100 mg/m2) or carboplatin (area under the curve, 5), each in combination with a 5-day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1,000 mg/m2/d. The study was divided into two phases: A, the first two cycles (6 weeks) focusing on the safety and tolerability of combination therapy; and B, the remaining time for those benefiting from therapy until disease progression or intolerable toxicity.