Long-term effect and safety of mesenchymal stromal cell therapy for radiation-induced hyposalivation in head and neck cancer survivors: A randomised, phase-2, trial.

Background: The long-term effect of adipose-derived mesenchymal stromal cells (ASCs) to restore radiation-induced salivary gland hypofunction in previous head and neck cancer patients have not been validated in larger settings.

Methods: The study was the 12-months follow-up of a randomised trial, including patients with hyposalivation. Patients were randomised to receive allogeneic ASCs or placebo in the submandibular glands.

Organizing to address overtreatment in cancer care near the end of life: Evidence from Denmark.

Objectives: The purpose of this study is to investigate how organizational factors influence the ethical and economic problems of overtreatment of cancer patients.

Methods: The study applies a sequential mixed-method approach. First, our logistic regression model assesses how patient characteristics and hospital department variables influence the use of late cancer treatment (LCT), primarily chemotherapy, in stage IV non-small cell lung cancer cases using Danish registry data.

"I have to charge my social battery": Perspectives from autistic young adults on Quality of Life.

In this study we have asked a group of autistic young adults to describe what is important for their quality of life. The 14 participants (aged 21-29 years) were recruited from a 10-year follow-up study of autistic people. During interviews, our participants described the importance of having relationships with family, friends and pets.

Long-Term Outcome Following Treatment With Allogeneic Mesenchymal Stem/Stromal Cells for Radiation-Induced Hyposalivation and Xerostomia.

Background: Adipose-derived mesenchymal stem/stromal cells (ASCs) are proposed as a new xerostomia treatment. The study evaluated the long-term safety and effectiveness of allogeneic ASCs in radiation-induced xerostomia among patients with previous oropharyngeal cancer.

Methods: This study constitutes 3-year follow-up on the original 10 patients who received allogeneic ASCs injections to the submandibular and parotid glands as part of the MESRIX-II trial.

A novel SARS-CoV-2 Beta RBD DNA vaccine directly targeted to antigen-presenting cells induces strong humoral and T cell responses.

Throughout the COVID-19 pandemic, several variants of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have evolved, affecting the efficacy of the approved COVID-19 vaccines. To address the need for vaccines that induce strong and persistent cross-reactive neutralizing antibodies and T cell responses, we developed a prophylactic SARS-CoV-2 vaccine candidate based on our easily and rapidly adaptable plasmid DNA vaccine platform. The vaccine candidate, referred to here as VB2129, encodes a protein homodimer consisting of the receptor binding domain (RBD) from lineage B.

Identification of the novel HLA allele HLA-DRB1*03:201 by next-generation sequencing.

HLA-DRB1*03:201 differs from HLA-DRB1*03:01 in exon 3 at codon 178 resulting in a proline to serine substitution.

Regulating diagnosis-Molecular and regulatory sub-stratifications of lung cancer treatment.

The sociology of diagnosis has shown that diagnosis not only serves to label the underlying cause of disease but also to provide access to services and resources. Elaborating on this double-affordance of diagnosis, this article examines how precision medicine reconfigures diagnosis as a label and as a process in regulatory and clinical settings. Reporting from an ethnographic case study of the introduction of immunotherapy for lung cancer, the paper unfolds the uncertainties involved in dissecting diagnosis into layers and examines the efforts and negotiations it takes to enable these layers to work both as clinical entities and regulative entities with the purpose of delineating access to treatment.

Good conduct in a context of rationing: A case study of how frontline professionals deal with distributive dilemmas of novel gene therapies.

Classical dilemmas of how to distribute limited resources have been rekindled by the rise of advanced, high-cost therapies. Building on a case study of a novel gene therapy in neuropaediatric care, this article explores the dilemmas that explicit priority setting can create for frontline professionals and develops a typology of professionals' responses to these dilemmas. Despite political attempts to centralise priority setting and spare health professionals from having to consider treatment costs at the 'bedside', this study shows that concern for economic efficiency and budget control nonetheless need to be handled and balanced against other accountabilities in the daily work of frontline professionals.

Exploring life with autism: Quality of Life, daily functioning and compensatory strategies from childhood to emerging adulthood: A qualitative study protocol.

Introduction: This study aims to investigate self-perceived quality of life, daily functioning, and the use of compensatory strategies in emerging adults with autism.

Methods And Analysis: Participants will be recruited from the Lillehammer Neurodevelopmental 10-year follow-up study (LINEUP), with the aim of 15 individual in-depth interviews. Subsequently, two focus groups with clinicians will be invited to reflect on the themes found in the individual interviews.

Prioritized Brain Circulation During Ergometer Cycling with Apnea and Face Immersion in Ice-Cold Water: A Case Report.

Background: Successful cardiopulmonary resuscitation after drowning or avalanche is often attributed to hypothermia-induced decrease in metabolism, which adapts the oxygen demand to the amount supplied under cardiac compression. Four decades ago, we speculated if oxygen-sparing mechanisms like those found in marine mammals, may improve cerebral oxygenation during acute airway blockade in humans. We investigated hemodynamic changes during steady state ergometer cycling with intermittent periods of apnea and face immersion (AFI) in ice-cold water.

Detection of the novel HLA allele, HLA-DQA1*01:65, identified in a Danish donor.

HLA-DQA1*01:65 differs from HLA-DQA1*01:03 in exon 1 at amino acid -7 a valine to methionine substitution.

Strategies of stratification: Regulating market access in the era of personalized medicine.

Personalized medicine raises the stakes of pharmaceutical market regulation. Drawing on pragmatist valuation studies and science and technology studies literature on personalized medicine and pharmaceutical markets, this article demonstrates how complex negotiations about the value of a pharmaceutical can constitute a market in various ways, while also shaping the concerned patient populations. Tracing the path of a pharmacogenetic treatment, Spinraza, from its approval by the European Medicines Agency to its adoption in the publicly funded Danish healthcare system, we show how the market was formatted through particular stratifications of the patient population.

The HLA-DR4-DQ8 phenotype of the recipient is associated with increased mortality after kidney transplantation.

The importance of the human leukocyte antigen (HLA) system in kidney transplantation is well-known, but it remains unexplored if patient HLA antigens constitute independent risk factors in complications after transplantation. We hypothesized that specific HLA class II phenotypes associated with immune-mediated disease (HLA-IMD) predispose to immunological activity and/or complications after kidney transplantation. Based on the literature we defined HLA-DR2-DQ6; -DR3-DQ2 and -DR4-DQ8 as HLA-IMD phenotypes.

Identification of the novel HLA allele, HLA-DPA1*01:46, identified in a man of Serbian origin.

HLA-DPA1*01:46 differs from HLA-DPA1*01:03 in exon 2 at amino acid 85; Aspartate to Asparagine substitution.

[Donor search for haematopoietic stem cell transplantation].

Allogeneic haematopoietic stem cell transplantation is a clinical example of precision medicine, as one individual donor is selected for one individual patient based on genetic findings in the human leukocyte antigen (HLA) system. Unrelated donor search for Danish patients is based on an international collaboration between global registries hosting more than 37 million potential donors worldwide for patients in need. The implementation of next-generation sequencing technologies has been a revolution in donor registry typing due to more precise, detailed and cheaper HLA analyses, which is discussed in this review.

One last round of chemo? Insights from conversations between oncologists and lung cancer patients about prognosis and treatment decisions.

One more chemo or one too many? The increasing use of expensive cancer treatments close to the patient's death is often explained by oncologists' failure to communicate to patients how close to dying they are, implying that patients are often both ill-prepared and over-treated when they die. This article aims at interrogating the politically charged task of prognosticating. Drawing on an ethnographic study of conversations between oncologists and patients with metastatic lung cancer in a Danish oncology clinic, I show that oncologists utilize, rather than avoid, prognostication in their negotiations with patients about treatment withdrawal.

Adaptor proteins: Flexible and dynamic modulators of immune cell signalling.

To maintain homeostasis, all cells respond to environmental cues via a multitude of surface receptors. In order to act appropriately in their environment, cells are dependent on the transduction of the incoming signal through tightly regulated and interconnected signalling pathways to the cell nucleus. In particular, cells implicated in the immune system greatly depend on such systems to respond in a flexible and dynamic manner to environmental challenges.

DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness.

Tumor hypoxia is associated with resistance to treatment, aggressive growth, metastatic dissemination, and poor clinical outcome in many cancer types. The potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess the extent of hypoxia in tumors has been investigated in several studies in our laboratory. Cervical carcinoma, melanoma, and pancreatic ductal adenocarcinoma (PDAC) xenografts have been used as models of human cancer, and the transfer rate constant () and the extravascular extracellular volume fraction () have been derived from DCE-MRI data by using Tofts standard pharmacokinetic model and a population-based arterial input function.

Antifibrotic therapy to normalize the tumor microenvironment.

Most tumors develop abnormal fibrotic regions consisting of fibroblasts, immune cells, and a dense extracellular matrix (ECM) immersed in a viscous interstitial fluid, and an abundant fibrotic tumor microenvironment (TME) is associated with poor outcome of treatment. It has been hypothesized that the treatment of cancer may be improved by interventions aiming to normalize this TME. The approaches used in attempts to normalize the fibrotic TME can be categorized into three strategies of targeted antifibrotic therapy: targeting of components of the ECM, targeting of the producers of the ECM components-the activated cancer-associated fibroblasts (CAFs), and targeting of the signaling pathways activating CAFs.

Intratumor Heterogeneity in Interstitial Fluid Pressure in Cervical and Pancreatic Carcinoma Xenografts.

Preclinical studies have suggested that interstitial fluid pressure (IFP) is uniformly elevated in the central region of tumors, whereas clinical studies have revealed that IFP may vary among different measurement sites in the tumor center. IFP measurements are technically difficult, and it has been claimed that the intratumor heterogeneity in IFP reported for human tumors is due to technical problems. The main purpose of this study was to determine conclusively whether IFP may be heterogeneously elevated in the central tumor region, and if so, to reveal possible mechanisms and possible consequences.

Next generation sequencing for clinical diagnostics: Five year experience of an academic laboratory.

Clinical laboratories have adopted next generation sequencing (NGS) as a gold standard for the diagnosis of hereditary disorders because of its analytic accuracy, high throughput, and potential for cost-effectiveness. We describe the implementation of a single broad-based NGS sequencing assay to meet the genetic testing needs at the University of Minnesota. A single hybrid capture library preparation was used for each test ordered, data was informatically blinded to clinically-ordered genes, and identified variants were reviewed and classified by genetic counselors and molecular pathologists.

DCE-MRI and Quantitative Histology Reveal Enhanced Vessel Maturation but Impaired Perfusion and Increased Hypoxia in Bevacizumab-Treated Cervical Carcinoma.

Purpose: This study had a dual purpose: to investigate (1) whether bevacizumab can change the microvasculature and oxygenation of cervical carcinomas and (2) whether any changes can be detected with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Methods And Materials: Two patient-derived xenograft models of cervical cancer (BK-12 and HL-16) were included in the study. Immunostained histologic preparations from untreated and bevacizumab-treated tumors were analyzed with respect to microvascular density, vessel pericyte coverage, and tumor hypoxia using CD31, α-SMA, and pimonidazole as markers, respectively.