Environmental enrichment affects immunity and reduces disease severity in pigs after co-infection, with stronger effects when applied from birth than from weaning.

We investigated whether environmental enrichment applied at different life stages of pigs affects the susceptibility to and severity of disease by studying immune cell functions around weaning and during nursery, the effects of infection in models and using a co-infection model of (PRRSV) followed by an infection. Pigs were either conventionally housed (CCH) or enriched housed throughout life, with enrichment consisting of extra space, rooting materials and co-mingling with another litter before weaning (EEH), or they were switched from conventional to enriched housing at weaning (CEH). Sixty days after birth, ten pigs per treatment were infected with PRRSV followed by an infection eight days later.

Visual Electroencephalography Assessment in the Diagnosis and Prognosis of Cognitive Disorders.

Purpose: Electroencephalography (EEG) is a noninvasive diagnostic tool that can be of diagnostic value in patients with cognitive disorders. In recent years, increasing emphasis has been on quantitative EEG analysis, which is not easily accessible in clinical practice. The aim of this study was to assess the diagnostic and prognostic value of visual EEG assessment to distinguish different causes of cognitive disorders.

Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness.

Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 T cells to uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced cell death (AICD); (2) acute, triggering expansion; (3) chronic, causing dysfunction.

A double-blind, randomised, placebo-controlled trial comparing intrathecal bupivacaine with bupivacaine plus morphine to reduce delirium in patients with hip fractures-Salmon-Mind trial study protocol.

Background: Surgical treatment of proximal femur fractures is complicated by postoperative delirium in about one-third of patients. Pain and opioid consumption are modifiable factors that may influence the incidence of delirium. An intrathecal injection of morphine may lead to a reduction in postoperative pain and reduced systemic opioid consumption.

An adverse tumor-protective effect of IDO1 inhibition.

By restoring tryptophan, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors aim to reactivate anti-tumor T cells. However, a phase III trial assessing their clinical benefit failed, prompting us to revisit the role of IDO1 in tumor cells under T cell attack. We show here that IDO1 inhibition leads to an adverse protection of melanoma cells to T cell-derived interferon-gamma (IFNγ).

MeVa2.1.dOVA and MeVa2.2.dOVA: two novel BRAFV600E-driven mouse melanoma cell lines to study tumor immune resistance.

While immunotherapy has become standard-of-care for cutaneous melanoma patients, primary and acquired resistance prevent long-term benefits for about half of the late-stage patients. Pre-clinical models are essential to increase our understanding of the resistance mechanisms of melanomas, aiming to improve the efficacy of immunotherapy. Here, we present two novel syngeneic transplantable murine melanoma cell lines derived from the same primary tumor induced on BrafV600E Pten-/- mice: MeVa2.

Feeding behavior in relation to ovarian cyclicity in cows with no or a short dry period.

The objective of this study was to investigate relations between feeding behavior (FB) variables focusing on intake of the basal ration during 3 wk prepartum until 3 wk postpartum, and postpartum onset of luteal activity (OLA) in dairy cows subjected to no (0-d) or a short (30-d) dry period (DP). Feeding behavior of the basal ration intake (concentrate intake excluded) was continuously recorded by computerized feeders for 123 dairy cows and analyzed from 3 wk prepartum to 3 wk postpartum. Cows were subjected to a DP length: 0-d DP (n = 81), or 30-d DP (n = 42).

RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells.

Tumor escape mechanisms for immunotherapy include deficiencies in antigen presentation, diminishing adaptive CD8 T cell antitumor activity. Although innate natural killer (NK) cells are triggered by loss of MHC class I, their response is often inadequate. To increase tumor susceptibility to both innate and adaptive immune elimination, we performed parallel genome-wide CRISPR-Cas9 knockout screens under NK and CD8 T cell pressure.

Reliability and validity of the standardized elevated arm stress test in the diagnosis of neurogenic thoracic outlet syndrome.

Objective: We developed a standardized elevated arm stress test (sEAST) meter to standardize patients' posture and measure additional grip and fatigue parameters. In the present prospective cohort study, we aimed to determine the reliability and validity of the sEAST in the diagnosis of neurogenic thoracic outlet syndrome (NTOS).

Methods: Patients evaluated for NTOS between October 2018 and February 2020 were included and performed the sEAST.

Reliability and validity of the elevated arm stress test in the diagnosis of neurogenic thoracic outlet syndrome.

Objectives: The objective of this retrospective analysis of prospectively collected data was to assess the test-retest reliability and validity of the elevated arm stress test (EAST) as measured by the duration in a cohort of patients with suspected neurogenic thoracic outlet syndrome (NTOS).

Methods: Patients evaluated for NTOS between January 2017 and September 2018 were identified. Test-retest reliability by the intraclass correlation coefficient was determined for duration of the EAST.

Ubiquitin ligase STUB1 destabilizes IFNγ-receptor complex to suppress tumor IFNγ signaling.

The cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about regulation of its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators of IFNγ-R1 cell surface abundance, we identify STUB1 as an E3 ubiquitin ligase for IFNγ-R1 in complex with its signal-relaying kinase JAK1.

Predictive Immune-Checkpoint Blockade Classifiers Identify Tumors Responding to Inhibition of PD-1 and/or CTLA-4.

Purpose: Combining anti-PD-1 + anti-CTLA-4 immune-checkpoint blockade (ICB) shows improved patient benefit, but it is associated with severe immune-related adverse events and exceedingly high cost. Therefore, there is a dire need to predict which patients respond to monotherapy and which require combination ICB treatment.

Experimental Design: In patient-derived melanoma xenografts (PDX), human tumor microenvironment (TME) cells were swiftly replaced by murine cells upon transplantation.

Cooperative Targeting of Immunotherapy-Resistant Melanoma and Lung Cancer by an AXL-Targeting Antibody-Drug Conjugate and Immune Checkpoint Blockade.

Although immune checkpoint blockade (ICB) has shown remarkable clinical benefit in a subset of patients with melanoma and lung cancer, most patients experience no durable benefit. The receptor tyrosine kinase AXL is commonly implicated in therapy resistance and may serve as a marker for therapy-refractory tumors, for example in melanoma, as we previously demonstrated. Here, we show that enapotamab vedotin (EnaV), an antibody-drug conjugate targeting AXL, effectively targets tumors that display insensitivity to immunotherapy or tumor-specific T cells in several melanoma and lung cancer models.

Measurement of drug concentration and bacterial contamination after diluting morphine for intrathecal administration: an experimental study.

Background: Low concentrations of morphine are required for safe dosing for intrathecal injections. Sometimes, manual dilution of morphine is performed to achieve these low concentrations, but risks dilution errors and bacterial contamination. The primary goal was to compare the concentrations of morphine and bupivacaine between four groups of syringes.

Reversal of pre-existing NGFR-driven tumor and immune therapy resistance.

Melanomas can switch to a dedifferentiated cell state upon exposure to cytotoxic T cells. However, it is unclear whether such tumor cells pre-exist in patients and whether they can be resensitized to immunotherapy. Here, we chronically expose (patient-derived) melanoma cell lines to differentiation antigen-specific cytotoxic T cells and observe strong enrichment of a pre-existing NGFR population.

Global Public Health Surveillance Using Media Reports: Redesigning GPHIN.

Global public health surveillance relies on reporting structures and transmission of trustworthy health reports. But in practice, these processes may not always be fast enough, or are hindered by procedural, technical, or political barriers. GPHIN, the Global Public Health Intelligence Network, was designed in the late 1990s to scour mainstream news for health events, as that travels faster and more freely.

Irreversible electroporation of locally advanced pancreatic cancer transiently alleviates immune suppression and creates a window for antitumor T cell activation.

: Local tumor ablation through irreversible electroporation (IRE) may offer a novel therapeutic option for locally advanced pancreatic cancer (LAPC). It may also serve as a means of vaccination. To obtain evidence of the induction of systemic antitumor immunity following local IRE-mediated ablation, we performed an explorative immune monitoring study.

Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold.

New opportunities are needed to increase immune checkpoint blockade (ICB) benefit. Whereas the interferon (IFN)γ pathway harbors both ICB resistance factors and therapeutic opportunities, this has not been systematically investigated for IFNγ-independent signaling routes. A genome-wide CRISPR/Cas9 screen to sensitize IFNγ receptor-deficient tumor cells to CD8 T cell elimination uncovered several hits mapping to the tumor necrosis factor (TNF) pathway.

A randomized trial provided new evidence on the accuracy and efficiency of traditional vs. electronically annotated abstraction approaches in systematic reviews.

Objectives: Data Abstraction Assistant (DAA) is a software for linking items abstracted into a data collection form for a systematic review to their locations in a study report. We conducted a randomized cross-over trial that compared DAA-facilitated single-data abstraction plus verification ("DAA verification"), single data abstraction plus verification ("regular verification"), and independent dual data abstraction plus adjudication ("independent abstraction").

Study Design And Setting: This study is an online randomized cross-over trial with 26 pairs of data abstractors.

Data and systems for medication-related text classification and concept normalization from Twitter: insights from the Social Media Mining for Health (SMM4H)-2017 shared task.

Objective: We executed the Social Media Mining for Health (SMM4H) 2017 shared tasks to enable the community-driven development and large-scale evaluation of automatic text processing methods for the classification and normalization of health-related text from social media. An additional objective was to publicly release manually annotated data.

Materials And Methods: We organized 3 independent subtasks: automatic classification of self-reports of 1) adverse drug reactions (ADRs) and 2) medication consumption, from medication-mentioning tweets, and 3) normalization of ADR expressions.