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Improved infrastructure and support needed for paediatric clinical trials in Sweden

Aim: There is a lack of authorised medicines for paediatric patients and improved drug development is necessary. The aim of this study was to evaluate the need for infrastructure and support for paediatric clinical trials in Sweden. Methods: A web-based survey was sent to doctors and nurses involved in the care of neonates, children and adolescents assessing the current situation and future needs

Immune checkpoint inhibitors of the PD-1/PD-L1-axis in non-small cell lung cancer : promise, controversies and ambiguities in the novel treatment paradigm

Immune checkpoint inhibitors (ICIs) have received much attention not least for melanoma since the award of the Nobel prize in 2018. Here, we review the current state of knowledge about the use of these monoclonal antibodies (mAbs) in non-small cell lung cancer (NSCLC). These drugs have generally been conditionally approved on limited early data and there are few long-term follow-up data from rando

Computational investigation of curvature effects on jet impingement heat transfer at internally cooled turbine vane leading edge regions

This study is carried out by using numerical simulations to investigate the effect of target surface curvature and the nozzle-to-target surface distance on the flow structure and heat transfer characteristics in a pin-finned double-wall cooling structure. The flow is directly impinging on the target surface and is disturbed by the pin fins, and then released from the film holes after passing the d

National priority assistive product list development in low resource countries : lessons learned from Tajikistan

Introduction: Developing a national assistive products list is an important part of an assistive technology policy and requires knowledge of total population need, and product costs and benefits; information is not always readily available in low-income countries. Our experience in Tajikistan of developing a national assistive products list provides guidance for others. Methods: Two hundred people

Sustainable and equitable provision of wheelchairs in low- and middle-income countries : an economic assessment of the models for wheelchair provision in Tajikistan

Introduction: Reaching universal coverage of assistive technologies remains a challenge in many low- and middle-income countries. Tajikistan has recently adopted several policies and national strategies to strengthen the rights of people with disabilities and improve the provision of assistive products. However, Tajikistan faces a number of challenges, including ensuring sustainable funding for th

The Role of Melanocyte Lineage Genes in Melanoma

Malignant melanoma accounts for the highest number of deaths among all skin cancer types, and its incidence has increased dramatically over the past decades. Despite the tremendous therapeutic advances, treatment resistant cells emerge in the vast heterogeneity of melanoma, driving tumor relapse and poor patient outcome. The aims of the studies conducted in this thesis were to contribute to the kn

von Willebrand factor D and EGF domains is an evolutionarily conserved and required feature of blastemas capable of multitissue appendage regeneration

Regenerative ability varies tremendously across species. A common feature of regeneration of appendages such as limbs, fins, antlers, and tails is the formation of a blastema-a transient structure that houses a pool of progenitor cells that can regenerate the missing tissue. We have identified the expression of von Willebrand factor D and EGF domains (vwde) as a common feature of blastemas capable

Studies of Thai blood group and platelet polymorphism. Implications for malaria susceptibility.

The objectives of the thesis were to seek a better understanding of polymorphic RBC surface molecules in the Thai, and to investigate the role of certain blood groups in malarial invasion. MALDI-TOF MS was employed in Study I as an efficient method for genotyping to establish the common blood group and platelet antigen genotypes of 396 blood donors. Investigation of outliers identified variation a

Transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution

Regeneration of complex multi-tissue structures, such as limbs, requires the coordinated effort of multiple cell types. In axolotl limb regeneration, the wound epidermis and blastema have been extensively studied via histology, grafting, and bulk-tissue RNA-sequencing. However, defining the contributions of these tissues is hindered due to limited information regarding the molecular identity of th

The Role of Co-stimulatory/Co-inhibitory Signals in Graft-vs.-Host Disease

Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapeutic approach for various hematologic and immunologic ailments. Despite the beneficial impact of allo-HCT, its adverse effects cause severe health concerns. After transplantation, recognition of host cells as foreign entities by donor T cells induces graft-vs.-host disease (GVHD). Activation, proliferation and tr

Identification of regenerative roadblocks via repeat deployment of limb regeneration in axolotls

Axolotl salamanders are powerful models for understanding how regeneration of complex body parts can be achieved, whereas mammals are severely limited in this ability. Factors that promote normal axolotl regeneration can be examined in mammals to determine if they exhibit altered activity in this context. Furthermore, factors prohibiting axolotl regeneration can offer key insight into the mechanis

Host-Derived CD70 Suppresses Murine Graft-versus-Host Disease by Limiting Donor T Cell Expansion and Effector Function

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to TCR signaling, costimulatory pathways are involved in T cell activation. CD27 is a TNFR family member expr

A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors

Mammals have extremely limited regenerative capabilities; however, axolotls are profoundly regenerative and can replace entire limbs. The mechanisms underlying limb regeneration remain poorly understood, partly because the enormous and incompletely sequenced genomes of axolotls have hindered the study of genes facilitating regeneration. We assembled and annotated a de novo transcriptome using RNA-

Granzyme B Contributes to the Optimal Graft-Versus-Tumor Effect Mediated by Conventional CD4+ T Cells

Granzyme B (GzmB) is a key cytotoxic molecule utilized by T cells to kill pathogen-infected cells or transformed tumor cells. Previous studies using allogeneic hematopoietic cell transplantation (allo-HCT) murine models showed that GzmB is required for CD8+ T cells to cause graft-versus-host disease (GVHD). However, our recent study demonstrated that GzmB-mediated damage of CD8+ T cells diminished

The BGOOD experimental setup at ELSA

The BGOOD experiment at the ELSA facility in Bonn has been commissioned within the framework of an international collaboration. The experiment pursues a systematic investigation of non-strange and strange meson photoproduction, in particular t-channel processes at low momentum transfer. The setup uniquely combines a central almost 4 π acceptance BGO crystal calorimeter with a large aperture forwar