Cellular liquid biopsy provides unique chances for disease monitoring, preclinical model generation and therapy adjustment in rare salivary gland cancer patients.

While cell-free liquid biopsy (cfLB) approaches provide simple and inexpensive disease monitoring, cell-based liquid biopsy (cLB) may enable additional molecular genetic assessment of systemic disease heterogeneity and preclinical model development. We investigated 71 blood samples of 62 patients with various advanced cancer types and subjected enriched circulating tumor cells (CTCs) to organoid culture conditions. CTC-derived tumoroid models were characterized by DNA/RNA sequencing and immunohistochemistry, as well as functional drug testing.

TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1.

Viruses are able to efficiently penetrate cells, multiply, and eventually kill infected cells, release tumor antigens, and activate the immune system. Therefore, viruses are highly attractive novel agents for cancer therapy. Clinical trials with first generations of oncolytic viruses (OVs) are very promising but show significant need for optimization.

Ex vivo expansion of lung cancer-derived disseminated cancer cells from lymph nodes identifies cells associated with metastatic progression.

The cellular basis of the apparent aggressiveness in lung cancer is poorly understood but likely associated with functional or molecular features of disseminated cancer cells (DCCs). DCCs from epithelial cancers are mostly detected by antibodies directed against histogenetic markers such as cytokeratin or EpCAM. It has been argued that marker-negative metastatic founder cells might escape detection.

The Application, Challenges, and Advancement Toward Regulatory Acceptance of Digital Toxicologic Pathology: Results of the 7th ESTP International Expert Workshop (September 20-21, 2019).

With advancements in whole slide imaging technology and improved understanding of the features of pathologist workstations required for digital slide evaluation, many institutions are investigating broad digital pathology adoption. The benefits of digital pathology evaluation include remote access to study or diagnostic case materials and integration of analysis and reporting tools. Diagnosis based on whole slide images is established in human medical pathology, and the use of digital pathology in toxicologic pathology is increasing.

Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency.

Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profile rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identify IL6/PI3K-signaling as candidate pathway for DCC activation. Surprisingly, and similar to mammary epithelial cells, DCCs lack membranous IL6 receptor expression and mechanistic dissection reveals IL6 trans-signaling to regulate a stem-like state of mammary epithelial cells via gp130.

Monodisperse versus Polydisperse Ultrasound Contrast Agents: In Vivo Sensitivity and safety in Rat and Pig.

Recent advances in the field of monodisperse microbubble synthesis by flow focusing allow for the production of foam-free, highly concentrated and monodisperse lipid-coated microbubble suspensions. It has been found that in vitro, such monodisperse ultrasound contrast agents (UCAs) improve the sensitivity of contrast-enhanced ultrasound imaging. Here, we present the first in vivo study in the left ventricle of rat and pig with this new monodisperse bubble agent.

Ultrasound Molecular Imaging With BR55, a Predictive Tool of Antiangiogenic Treatment Efficacy in a Chemo-Induced Mammary Tumor Model.

Objectives: The aim of this study was to evaluate the added value of ultrasound molecular imaging of the vascular growth factor receptor 2 (VEGFR2) expression, using the clinical grade contrast agent BR55, for the early evaluation of antiangiogenic treatment efficacy in a chemo-induced rat mammary tumor model.

Materials And Methods: In this preclinical study, chemo-induced rat mammary tumors were obtained after a single injection of N-nitroso-N-methylurea intraperitoneally in 46 prepubescent (age 38 ± 2 days) female rats. All experiments were performed under the authorization of the Direction Générale de la Santé, Geneva, Switzerland.

Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats.

Objectives: The purpose of this study was to compare Gd levels in rat tissues after cumulative exposure to four commercially available macrocyclic gadolinium-based contrast agents (GBCAs).

Methods: Sixty-five male Sprague-Dawley rats were randomized to four exposure groups (n = 15 per group) and one control group (n = 5). Animals in each exposure group received 20 GBCA administrations (four per week of ProHance®, Dotarem®, Clariscan™, or Gadovist® for 5 consecutive weeks) at a dose of 0.

Comparison of L1 and L5 Bands GNSS Signals Acquisition.

Nowadays, civil Global Navigation Satellite System (GNSS) signals are available in both L1 and L5 bands. A receiver does not need to acquire independently the signals in both bands coming from a same satellite, since their carrier Doppler and code delay are closely related. Therefore, the question of which one to acquire first rises naturally.

Non-clinical assessment of safety and gadolinium deposition after cumulative administration of gadobenate dimeglumine (MultiHance) to neonatal and juvenile rats.

To determine the impact of single and cumulative doses of MultiHance on toxicity, pharmacokinetics, tissue gadolinium presence, behavior and neurological function in juvenile rats. Juvenile male and female rats received either physiological saline or MultiHance at 0.6, 1.

Differences in gadolinium retention after repeated injections of macrocyclic MR contrast agents to rats.

Purpose: To compare the levels of gadolinium in the blood, cerebrum, cerebellum, liver, femur, kidneys, and skin after multiple exposure of rats to the macrocyclic gadolinium-based contrast agents (GBCAs) gadoterate, gadobutrol, and gadoteridol.

Materials And Methods: Fifty male Wistar Han rats were randomized to three exposure groups (n = 15 per group) and one control group (n = 5). Animals in the exposure groups received a total of 20 GBCA administrations (four administrations per week for 5 consecutive weeks) at a dose of 0.

Derivation of the Cramér-Rao Bound in the GNSS-Reflectometry Context for Static, Ground-Based Receivers in Scenarios with Coherent Reflection.

The use of the reflected Global Navigation Satellite Systems' (GNSS) signals in Earth observation applications, referred to as GNSS reflectometry (GNSS-R), has been already studied for more than two decades. However, the estimation precision that can be achieved by GNSS-R sensors in some particular scenarios is still not fully understood yet. In an effort to partially fill this gap, in this paper, we compute the Cramér-Rao bound (CRB) for the specific case of static ground-based GNSS-R receivers and scenarios where the coherent component of the reflected signal is dominant.

Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke.

Background: Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model.

Standalone GPS L1 C/A Receiver for Lunar Missions.

Global Navigation Satellite Systems (GNSSs) were originally introduced to provide positioning and timing services for terrestrial Earth users. However, space users increasingly rely on GNSS for spacecraft navigation and other science applications at several different altitudes from the Earth surface, in Low Earth Orbit (LEO), Medium Earth Orbit (MEO), Geostationary Earth Orbit (GEO), and feasibility studies have proved that GNSS signals can even be tracked at Moon altitude. Despite this, space remains a challenging operational environment, particularly on the way from the Earth to the Moon, characterized by weaker signals with wider gain variability, larger dynamic ranges resulting in higher Doppler and Doppler rates and critically low satellite signal availability.

The effects of taurine on vigabatrin, high light intensity and mydriasis induced retinal toxicity in the pigmented rat.

The overall purpose of this study was to establish a model that may be used for examining the effect of Vigabatrin-induced retinal toxicity in pigmented rats, and subsequently examine the possible effects of taurine on the retinal toxicity. In the first part of the study, pigmented Long Evans rats were subjected to combinations of induced mydriasis, low/high light intensities (40/2000 lx) and oral administration of near-MTD (Maximum Tolerated Dose) doses (200 mg/kg/day) of Vigabatrin for up to 6 weeks. The combination of mydriasis and high light intensity applied to Long Evans rats resulted in retinal damage that was increased by the administration of Vigabatrin.

Normalized GNSS interference pattern technique for altimetry.

It is well known that reflected signals from Global Navigation Satellite Systems (GNSS) can be used for altimetry applications, such as monitoring of water levels and determining snow height. Due to the interference of these reflected signals and the motion of satellites in space, the signal-to-noise ratio (SNR) measured at the receiver slowly oscillates. The oscillation rate is proportional to the change in the propagation path difference between the direct and reflected signals, which depends on the satellite elevation angle.

Implementation and performance of a GPS/INS tightly coupled assisted PLL architecture using MEMS inertial sensors.

The use of global navigation satellite system receivers for navigation still presents many challenges in urban canyon and indoor environments, where satellite availability is typically reduced and received signals are attenuated. To improve the navigation performance in such environments, several enhancement methods can be implemented. For instance, external aid provided through coupling with other sensors has proven to contribute substantially to enhancing navigation performance and robustness.

Ultrasound molecular imaging of transient acute myocardial ischemia with a clinically translatable P- and E-selectin targeted contrast agent: correlation with the expression of selectins.

Objective: The diagnosis of acute coronary syndrome remains challenging especially in patients without clear symptoms or electrocardiographic and/or biomarker features. A hallmark of ischemia/reperfusion is activation of endothelial cells leading to altered expression of molecular markers, including selectins. In this context, we aimed to validate the value of ultrasound molecular imaging for detecting transient myocardial ischemia by using a clinically translatable dual P- and E-selectin-targeted ultrasound contrast agent (UCA) and microbubble (MB(selectin)).

Molecular profiling of single Sca-1+/CD34+,- cells--the putative murine lung stem cells.

Murine bronchioalveolar stem cells play a key role in pulmonary epithelial maintenance and repair but their molecular profile is poorly described so far. In this study, we used antibodies directed against Sca-1 and CD34, two markers originally ascribed to pulmonary cells harboring regenerative potential, to isolate single putative stem cells from murine lung tissue. The mean detection rate of positive cells was 8 per 10(6) lung cells.

An early reduction in Treg cells correlates with enhanced local inflammation in cutaneous leishmaniasis in CCR6-deficient mice.

Resistance to Leishmania major infection is dependent on the development of a cell-mediated Th1 immune response in resistant C57BL/6 mice whereas Th2-prone BALB/c mice develop non-healing lesions after infection. The chemokine receptor CCR6 is shared by anti-inflammatory regulatory T cells and pro-inflammatory Th17 cells. In a recent study we showed that C57BL/6 mice deficient in CCR6 exhibited enhanced footpad swelling and impaired T helper cell migration indicated by reduced recruitment of total T helper cells into the skin after infection and a reduced delayed type hypersensitivity reaction.

Chronic psychosocial stress promotes systemic immune activation and the development of inflammatory Th cell responses.

Recent studies indicate that chronic psychosocial stress favors the development of generalized immune dysfunction. During stressor exposure neuroendocrine factors affect numbers and functionality of leukocytes. However, the exact mechanisms leading to systemic changes in immune functions during stress are still not clear.

Papillary tumor of the pineal region of a dog.

A 3-year-old, intact, male Beagle dog developed clinical signs of pleurothotonus and altered head position to the right, neck pain, nystagmus, hyperreflexia of the left forelimb, and hyperextension of both forelimbs. Magnetic resonance imaging enabled a tentative diagnosis of thalamic neoplasia with incidental hydromyelia at the level of the second cervical vertebra. The animal was euthanatized due to the poor prognosis, and a necropsy was performed.

Field performance of two rapid screening tests in active surveillance of transmissible spongiform encephalopathies in small ruminants.

Recently, screening tests for monitoring the prevalence of transmissible spongiform encephalopathies specifically in sheep and goats became available. Although most countries require comprehensive test validation prior to approval, little is known about their performance under normal operating conditions. Switzerland was one of the first countries to implement 2 of these tests, an enzyme-linked immunosorbent assay (ELISA) and a Western blot, in a 1-year active surveillance program.

Brain copper elevation and neurological changes in north ronaldsay sheep: a model for neurodegenerative disease?

This study in North Ronaldsay (NR) sheep showed that copper was elevated in both the liver and brain of older animals and that the elevation in these two sites was highly correlated. The accumulation of copper in the liver culminated in chronic active hepatitis. Evidence of tissue damage in the brain was equivocal, but the astrocytes showed strong immunoreactivity for metallothionein.