Iron Deficiency in Inflammatory Bowel Disease Is Associated With Low Levels of Vitamin D Modulating Serum Hepcidin and Intestinal Ceruloplasmin Expression.

Introduction: Iron deficiency and vitamin D deficiency are common comorbidities in inflammatory bowel disease (IBD). Accumulating evidence indicates that active 1,25-dihydroxyvitamin D (1,25(OH)D) may enhance iron absorption by suppressing hepcidin. We investigated the influence of vitamin D on iron metabolism in patients with IBD and on the expression of genes facilitating intestinal epithelial iron absorption.

Cancer therapy in mice using a pure population of CD8 T cell specific to the AH1 tumor rejection antigen.

There is a growing interest in the use of patient-derived T cells for the treatment of various types of malignancies. The expansion of a polyclonal and polyspecific population of tumor-reactive T cells, with a subsequent infusion into the same donor patient, has been implemented, sometimes with positive results. It is not known, however, whether a set of T cells with a single antigen specificity may be sufficient for an effective therapy.

Quality of life after traumatic brain injury: a cross-sectional analysis uncovers age- and sex-related differences over the adult life span.

Traumatic brain injury (TBI) is the leading cause of disability in the working population and becomes increasingly prevalent in the elderly. Thus, TBI is a major global health burden. However, age- and sex-related long-term outcome regarding patient's health-related quality of life (HRQoL) is yet not clarified.

The targeted delivery of interleukin-12 to the carcinoembryonic antigen increases the intratumoral density of NK and CD8 T cell in an immunocompetent mouse model of colorectal cancer.

The recent success achieved by immune checkpoint inhibitors in the field of immuno-oncology has been less evident for the treatment of metastatic colorectal cancer (mCRC) patients. To date, cancer immunotherapy has been efficacious only in few patients bearing high mutational burden (less than 25%) mCRCs. In this Communication, we report the generation of a novel antibody cytokine fusion protein (termed Sm3E-mIL12) targeting the CRC-associated carcinoembryonic antigen (CEA).

Large-scale benchmark study of survival prediction methods using multi-omics data.

Multi-omics data, that is, datasets containing different types of high-dimensional molecular variables, are increasingly often generated for the investigation of various diseases. Nevertheless, questions remain regarding the usefulness of multi-omics data for the prediction of disease outcomes such as survival time. It is also unclear which methods are most appropriate to derive such prediction models.

Decompressive Craniectomy Is Associated With Good Quality of Life Up to 10 Years After Rehabilitation From Traumatic Brain Injury.

Objectives: Traumatic brain injury is the number one cause of death in children and young adults and has become increasingly prevalent in the elderly. Decompressive craniectomy prevents intracranial hypertension but does not clearly improve physical outcome 6 months after traumatic brain injury. However, it has not been analyzed if decompressive craniectomy affects traumatic brain injury patients' quality of life in the long term.

Quality of life up to 10 years after traumatic brain injury: a cross-sectional analysis.

Background: Traumatic brain injury (TBI) is the leading cause of death and disability among children and young adults in industrialized countries, but strikingly little is known how patients cope with the long-term consequences of TBI. Thus, the aim of the current study was to elucidate health-related quality of life (HRQoL) and outcome predictors in chronic TBI adults.

Methods: In this cross-sectional study, 439 former patients were invited to report HRQoL up to 10 years after mild, moderate or severe TBI using the QOLIBRI (Quality of Life after Brain Injury) questionnaire.

Immunotherapy of CT26 murine tumors is characterized by an oligoclonal response of tissue-resident memory T cells against the AH1 rejection antigen.

Mice bearing CT26 tumors can be cured by administration of L19-mIL12 or F8-mTNF, two antibody fusion proteins which selectively deliver their cytokine payload to the tumor. In both settings, cancer cures crucially depended on CD8 T cells and the AH1 peptide (derived from the gp70 protein of the murine leukemia virus) acted as the main tumor-rejection antigen, with ∼50% of CD8 T cells in the neoplastic mass being AH1-specific after therapy. In order to characterize the clonality of the T cell response, its phenotype, and activation status, we isolated CD8 T cells from tumors and secondary lymphoid organs and submitted them to T cell receptor (TCR) and total mRNA sequencing.

Congruence and Discrepancy of Interictal and Ictal EEG With MRI Lesions in Pediatric Epilepsies.

. To evaluate the congruence or discrepancy of the localization of magnetic resonance imaging (MRI) lesions with interictal epileptiform discharges (IEDs) or epileptic seizure patterns (ESPs) in surface EEG in lesional pediatric epilepsy patients. .

Impact of pathologic body composition assessed by CT-based anthropometric measurements in adult patients with multiple trauma: a retrospective analysis.

Purpose: In recent years, there has been mounting evidence on the clinical importance of body composition, particularly obesity and sarcopenia, in various patient populations. However, the relevance of these pathologic conditions remains controversial, especially in the field of traumatology. Computed tomography-based measurements allow clinicians to gain a prompt and thorough assessment of fat and muscle compartments in trauma patients.

The antibody-based delivery of interleukin-12 to solid tumors boosts NK and CD8 T cell activity and synergizes with immune checkpoint inhibitors.

We describe the cloning and characterization of a novel fusion protein (termed L19-mIL12), consisting of murine interleukin-12 in single-chain format, sequentially fused to the L19 antibody in tandem diabody format. The fusion protein bound avidly to the cognate antigen (the alternatively spliced EDB domain of fibronectin), retained the activity of the parental cytokine and was able to selectively localize to murine tumors in vivo, as shown by quantitative biodistribution analysis. L19-mIL12 exhibited a potent antitumor activity in immunocompetent mice bearing CT26 carcinomas and WEHI-164 sarcomas, which could be boosted by combination with checkpoint blockade, leading to durable cancer eradication.

Modern Total Knee Arthroplasty (TKA): With Or Without a Tourniquet?

Background: Since arthritis of the knee is one of the most common pathologies in industrialized nations, there has been a growing interest in fast-track total knee arthroplasty (TKA). However, while one of the main concerns is the role of a tourniquet, the available data are inconclusive.

Aim: This study sought to assess the link between postoperative outcomes and use of a tourniquet in TKA.

Antibody-Based Delivery of Cytokine Payloads to Carbonic Anhydrase IX Leads to Cancer Cures in Immunocompetent Tumor-Bearing Mice.

Antibody-cytokine fusion proteins can have the potential to increase the density and activity of subsets of leukocytes within the tumor mass. Here, we describe the design, production, and characterization of four novel antibody-cytokine fusion proteins directed against human carbonic anhydrase IX, a highly validated marker of hypoxia that is overexpressed in clear cell renal cell carcinoma and other malignancies. As immunomodulatory payloads we used TNF, IL2, IFNα2 (corresponding to products that are in clinical use), and IL12 (as this cytokine potently activates T cells and NK cells).

Antibody-mediated delivery of VEGF-C potently reduces chronic skin inflammation.

VEGF-C is an important mediator of lymphangiogenesis and has been shown to alleviate chronic inflammation in a variety of disease models. In this study, we investigated whether targeted delivery of VEGF-C to sites of inflammation and site-specific activation of lymphatic vessels would represent a clinically feasible strategy for treating chronic skin inflammation. To this end, we generated a fusion protein consisting of human VEGF-C fused to the F8 antibody (F8-VEGF-C), which is specific for the alternatively spliced, angiogenesis-marking extradomain A (EDA) of fibronectin.

Asthma features in severe COPD: Identifying treatable traits.

Aim: Biological therapies developed for severe asthma may have a role in COPD patients with asthma features.

Method: We carried out a prospective, consecutive, cross-sectional analysis of 80 patients with severe COPD GOLD IV/D.

Results: We studied 80 patients (48.

Antibody-based Delivery of TNF to the Tumor Neovasculature Potentiates the Therapeutic Activity of a Peptide Anticancer Vaccine.

Purpose: There is a growing interest in the use of tumor antigens for therapeutic vaccination strategies. Unfortunately, in most cases, the use of peptide vaccines in patients does not mediate shrinkage of solid tumor masses. Here, we studied the opportunity to boost peptide vaccination with F8-TNF, an antibody fusion protein that selectively delivers TNF to the tumor extracellular matrix.

Making complex prediction rules applicable for readers: Current practice in random forest literature and recommendations.

Ideally, prediction rules should be published in such a way that readers may apply them, for example, to make predictions for their own data. While this is straightforward for simple prediction rules, such as those based on the logistic regression model, this is much more difficult for complex prediction rules derived by machine learning tools. We conducted a survey of articles reporting prediction rules that were constructed using the random forest algorithm and published in PLOS ONE in 2014-2015 in the field "medical and health sciences", with the aim of identifying issues related to their applicability.

Random forest versus logistic regression: a large-scale benchmark experiment.

Background And Goal: The Random Forest (RF) algorithm for regression and classification has considerably gained popularity since its introduction in 2001. Meanwhile, it has grown to a standard classification approach competing with logistic regression in many innovation-friendly scientific fields.

Results: In this context, we present a large scale benchmarking experiment based on 243 real datasets comparing the prediction performance of the original version of RF with default parameters and LR as binary classification tools.

Sarcoma Eradication by Doxorubicin and Targeted TNF Relies upon CD8 T-cell Recognition of a Retroviral Antigen.

Antibody-cytokine complexes may offer new tools to treat cancer. Here, we show how TNF-linked antibodies, which recognize tumor-selective splice isoforms of fibronectin (F8-TNF), can be exploited to eradicate sarcomas in immunocompetent mice. We treated mice bearing WEHI-164 fibrosarcoma with a combination of F8-TNF and doxorubicin, curing the majority of treated animals (29/37).