Associations of the gut microbiome with outcomes in cervical and endometrial cancer patients treated with pembrolizumab: Insights from the phase II PRIMMO trial.

Background: The phase II PRIMMO trial investigated a pembrolizumab-based regimen in patients with recurrent and/or metastatic cervical (CC) or endometrial (EC) carcinoma who had at least one prior line of systemic therapy. Here, exploratory studies of the gut microbiome (GM) are presented.

Methods: The microbial composition of 77 longitudinal fecal samples obtained from 35 patients (CC, n = 15; EC, n = 20) was characterized using 16S rRNA gene sequencing.

Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study.

A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19.

Repurposing Infectious Diseases Vaccines Against Cancer.

Vaccines used to prevent infections have long been known to stimulate immune responses to cancer as illustrated by the approval of the Bacillus Calmette-Guérin (BCG) vaccine to treat bladder cancer since the 1970s. The recent approval of immunotherapies has rejuvenated this research area with reports of anti-tumor responses with existing infectious diseases vaccines used as such, either alone or in combination with immune checkpoint inhibitors. Here, we have reviewed and summarized research activities using approved vaccines to treat cancer.

PRIMMO study protocol: a phase II study combining PD-1 blockade, radiation and immunomodulation to tackle cervical and uterine cancer.

Background: Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13-17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature.

A Phase 2 Study to Assess the Immunomodulatory Capacity of a Lecithin-based Delivery System of Curcumin in Endometrial Cancer.

Curcumin is a botanical with anti-tumor and immunomodulatory properties. We hypothesized that curcumin supplementation might influence inflammatory biomarker levels in endometrial carcinoma (EC). In this open-label, non-randomized phase 2 study (NCT02017353), seven EC patients consumed 2 g/day Curcumin Phytosome (CP) orally for 2 weeks.

ReDO_DB: the repurposing drugs in oncology database.

Repurposing is a drug development strategy that seeks to use existing medications for new indications. In oncology, there is an increased level of activity looking at the use of non-cancer drugs as possible cancer treatments. The Repurposing Drugs in Oncology (ReDO) project has used a literature-based approach to identify licensed non-cancer drugs with published evidence of anticancer activity.

On the use of on-cow accelerometers for the classification of behaviours in dairy barns.

Analysing behaviours can provide insight into the health and overall well-being of dairy cows. Automatic monitoring systems using e.g.

Farm-specific economic value of automatic lameness detection systems in dairy cattle: From concepts to operational simulations.

Although prototypes of automatic lameness detection systems for dairy cattle exist, information about their economic value is lacking. In this paper, a conceptual and operational framework for simulating the farm-specific economic value of automatic lameness detection systems was developed and tested on 4 system types: walkover pressure plates, walkover pressure mats, camera systems, and accelerometers. The conceptual framework maps essential factors that determine economic value (e.

Supporting the Development and Adoption of Automatic Lameness Detection Systems in Dairy Cattle: Effect of System Cost and Performance on Potential Market Shares.

Most automatic lameness detection system prototypes have not yet been commercialized, and are hence not yet adopted in practice. Therefore, the objective of this study was to simulate the effect of detection performance (percentage missed lame cows and percentage false alarms) and system cost on the potential market share of three automatic lameness detection systems relative to visual detection: a system attached to the cow, a walkover system, and a camera system. Simulations were done using a utility model derived from survey responses obtained from dairy farmers in Flanders, Belgium.

Farmers' preferences for automatic lameness-detection systems in dairy cattle.

As lameness is a major health problem in dairy herds, a lot of attention goes to the development of automated lameness-detection systems. Few systems have made it to the market, as most are currently still in development. To get these systems ready for practice, developers need to define which system characteristics are important for the farmers as end users.

Risk factors for development of lameness in gestating sows within the first days after moving to group housing.

Lameness in sows is an important welfare issue that is affected by housing conditions and is thought to be influenced by hierarchical fights within the first days after mixing sows in groups. A longitudinal study in 15 randomly selected herds was performed to investigate the incidence of sow lameness and possible risk factors within the first days of group housing. Each herd was visited just before and again 3-5 days after the sows were moved to group housing.

Daily lying time, motion index and step frequency in dairy cows change throughout lactation.

Lying behaviour in dairy cows has the potential to be used for welfare assessment or problem detection, but knowledge about variation in normal lying behaviour is scarce. Accelerometer data were collected at four Danish farms from 366 Holstein dairy cows in loose-housing systems in 2008 and 2009. Daily lying time decreased steeply during early lactation to a minimum around four weeks after calving, followed by a steady increase towards the end of lactation.

HIV-1 Vpr N-terminal tagging affects alternative splicing of the viral genome.

To facilitate studies on Vpr function in replicating HIV-1, we aimed to tag the protein in an infectious virus. First we showed that N-, but not C-terminal HA/FLAG tagging of Vpr protein preserves Vpr cytopathicity. Cloning the tags into proviral DNA however ablated viral production and replication.

HIV Triggers a cGAS-Dependent, Vpu- and Vpr-Regulated Type I Interferon Response in CD4 T Cells.

Several pattern-recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4 T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response.

Virion encapsidated HIV-1 Vpr induces NFAT to prime non-activated T cells for productive infection.

The majority of T cells encountered by HIV-1 are non-activated and do not readily allow productive infection. HIV-1 Vpr is highly abundant in progeny virions, and induces signalling and HIV-1 LTR transcription. We hence hypothesized that Vpr might be a determinant of non-activated T-cell infection.

Environmental and cow-related factors affect cow locomotion and can cause misclassification in lameness detection systems.

To tackle the high prevalence of lameness, techniques to monitor cow locomotion are being developed in order to detect changes in cows' locomotion due to lameness. Obviously, in such lameness detection systems, alerts should only respond to locomotion changes that are related to lameness. However, other environmental or cow factors can contribute to locomotion changes not related to lameness and hence, might cause false alerts.

Lameness Detection in Dairy Cows: Part 2. Use of Sensors to Automatically Register Changes in Locomotion or Behavior.

Despite the research on opportunities to automatically measure lameness in cattle, lameness detection systems are not widely available commercially and are only used on a few dairy farms. However, farmers need to be aware of the lame cows in their herds in order treat them properly and in a timely fashion. Many papers have focused on the automated measurement of gait or behavioral cow characteristics related to lameness.

Lameness Detection in Dairy Cows: Part 1. How to Distinguish between Non-Lame and Lame Cows Based on Differences in Locomotion or Behavior.

Due to its detrimental effect on cow welfare, health and production, lameness in dairy cows has received quite a lot of attention in the last few decades-not only in terms of prevention and treatment of lameness but also in terms of detection, as early treatment might decrease the number of severely lame cows in the herds as well as decrease the direct and indirect costs associated with lameness cases. Generally, lame cows are detected by the herdsman, hoof trimmer or veterinarian based on abnormal locomotion, abnormal behavior or the presence of hoof lesions during routine trimming. In the scientific literature, several guidelines are proposed to detect lame cows based on visual interpretation of the locomotion of individual cows (i.

Measuring the drinking behaviour of individual pigs housed in group using radio frequency identification (RFID).

Changes in the drinking behaviour of pigs may indicate health, welfare or productivity problems. Automated monitoring and analysis of drinking behaviour could allow problems to be detected, thus improving farm productivity. A high frequency radio frequency identification (HF RFID) system was designed to register the drinking behaviour of individual pigs.

Repurposing Drugs in Oncology (ReDO)-clarithromycin as an anti-cancer agent.

Clarithromycin (CAM) is a well-known macrolide antibiotic available as a generic drug. CAM is traditionally used for many types of bacterial infections, treatment of Lyme disease and eradication of gastric infection with Helicobacter pylori. Extensive preclinical and clinical data demonstrate a potential role for CAM to treat various tumours in combination with conventional treatment.

Long-term clinical outcome of melanoma patients treated with messenger RNA-electroporated dendritic cell therapy following complete resection of metastases.

Purpose: Melanoma patients with a high risk of recurrence may benefit from immunotherapy with mRNA-electroporated autologous monocyte-derived dendritic cells (DCs). Further benefit may be found in combining DC-therapy with interferon alfa-2b.

Patients And Methods: The long-term clinical outcome of AJCC stage III/IV melanoma patients who had no evidence of disease at the time of treatment with autologous mRNA-electroporated DCs in a single-center pilot clinical trial was analyzed.

Review: Quantifying animal feeding behaviour with a focus on pigs.

The study of animal feeding behaviour is of interest to understand feeding, to investigate the effect of treatments and conditions or to predict illness. This paper reviews the different steps to undertake when studying animal feeding behaviour, with illustrations for group-housed pigs. First, one must be aware of the mechanisms that control feeding and the various influences that can change feeding behaviour.

Replication competent virus as an important source of bias in HIV latency models utilizing single round viral constructs.

The central memory T cell (TCM) model forms a unique HIV-1 latency model based on primary cells that closely resemble in vivo TCM. The virus employed in this model is based on an engineered vector incapable of replication after initial infection. We show that despite this strategy, replication competent viral particles are released into the culture medium due to recombination between overlapping sequences of the env deleted HIV genome that is co-transfected with intact env.

Single-step antigen loading and maturation of dendritic cells through mRNA electroporation of a tumor-associated antigen and a TriMix of costimulatory molecules.

Dendritic cells (DC) are key players in several types of cancer vaccines. Large numbers of DC can easily be generated in closed systems from the monocyte fraction of the peripheral blood. They are the professional antigen-presenting cells, and electroporation of mRNA-encoding tumor antigens is a very efficient and a relatively simple way to load the DC with antigen.