Publications by authors named "Wernen Kuepper"

Background: Prehospital management of severely burned patients is extremely challenging. It should include adequate analgesia, decision-making on the necessity of prehospital endotracheal intubation and the administration of crystalloid fluids. Guidelines recommend immediate transport to specialised burn centres when certain criteria are met.

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Adequate fluid therapy is crucial to maintain organ function after burn trauma. Major burns lead to a systemic response with fluid loss and cardiac dysfunction. To guide fluid therapy, measurement of cardiac pre- and afterload is helpful.

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Article Synopsis
  • Autologous split thickness skin grafting is commonly used for treating deep dermal and full thickness burns, but the Meek micrografting technique offers a solution for patients with limited donor sites and larger burn areas.
  • A study reviewing 73 patients treated with Meek micrografting from 2013 to 2022 found a mean graft take rate of 75.8%, with allograft pre-treatment and longer waiting times positively affecting the success of the grafts.
  • Despite older age being a negative predictor for graft success, the overall results indicate that Meek micrografting is a safe and effective option for extensive burn treatment.
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Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two frequently co-occurring neurodevelopmental conditions that share certain symptomatology, including social difficulties. This presents practitioners with challenging (differential) diagnostic considerations, particularly in clinically more complex cases with co-occurring ASD and ADHD. Therefore, the primary aim of the current study was to apply a data-driven machine learning approach (support vector machine) to determine whether and which items from the best-practice clinical instruments for diagnosing ASD (ADOS, ADI-R) would best differentiate between four groups of individuals referred to specialized ASD clinics (i.

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Purpose: To evaluate the effect of different surface wear patterns on the discoloration tendency of two different prefabricated composite veneers and lithium disilicate ceramic veneers.

Materials And Methods: Discoloration tendency of two prefabricated composite resin veneers (Visalys Veneer Chairside (VIS) and Componeer (COM)) were compared to lithium disilicate veneers (IPS) in vitro. For each material, n = 60 samples were allocated to different test groups, and therefore each n = 10 specimens per group went through different wear tests.

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Background:  Free adipocutaneous anterolateral thigh (ALT) flaps have evolved as workhorse flaps to reconstruct complex, multicompound defects. While coverage is safely achieved, flaps may remain bulky. As a standard of care, flaps are refined with liposuction, partial excision, or combination of both.

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The design of high-affinity, RNA-binding ligands has proven very challenging. This is due to the unique structural properties of RNA, often characterized by polar surfaces and high flexibility. In addition, the frequent lack of well-defined binding pockets complicates the development of small molecule binders.

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With a view to developing multimetallic molecular catalysts that mimic the oxygen-evolving catalyst (OEC) in Nature's photosystem II, the synthesis of various dicubanoid manganese clusters is described and their catalytic activity investigated for water oxidation in basic, aqueous solution. Pyridinemethanol-based ligands are known to support polynuclear and cubanoid structures in manganese coordination chemistry. The chelators 2,6-pyridinedimethanol (H L ) and 6-methyl-2-pyridinemethanol (HL ) were chosen to yield polynuclear manganese complexes; namely, the tetranuclear defective dicubanes [Mn Mn (HL ) (OAc) (OMe) ] and [Mn Mn (HL ) (OAc) ] (OAc) ⋅2 H O, as well as the octanuclear-dicubanoid [Mn Mn (L ) (O) (OAc) (HOMe/OH ) ]⋅3MeOH⋅MeCN.

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Novel therapies for the treatment of acute myeloid leukemia (AML) are urgently needed, because current treatments do not cure most patients with AML. We report a domain-focused, kinome-wide CRISPR-Cas9 screening that identified protein kinase targets for the treatment of AML, which led to the identification of Rio-kinase 2 (RIOK2) as a potential novel target. Loss of RIOK2 led to a decrease in protein synthesis and to ribosomal instability followed by apoptosis in leukemic cells, but not in fibroblasts.

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Biomolecular assemblies composed of proteins and oligonucleotides play a central role in biological processes. While in nature, oligonucleotides and proteins usually assemble via non-covalent interactions, synthetic conjugates have been developed which covalently link both modalities. The resulting peptide-oligonucleotide conjugates have facilitated novel biological applications as well as the design of functional supramolecular systems and materials.

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Background: Autism spectrum disorder (ASD) is a chronic neurodevelopmental condition with a prevalence rate above 1%, characterized by deficits in social communication and interaction; restrictive, repetitive patterns of behavior, interests, or activities; and a preference for sameness and routines. The majority of adult ASD patients suffer from comorbid conditions such as depression and anxiety. Therapy options for adult ASD patients are lacking, with presently no available evidence-based interventions in Germany.

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Purpose: To measure surface roughness before and after wear-tests of two different prefabricated composite veneers and compare them to ceramic veneers and human dental enamel.

Materials And Methods: Roughness (Ra-values) of two prefabricated composite veneers (Visalys Veneer Chairside (VIS) and Componeer (COM)) were compared to lithium disilicate Veneers (e.max CAD) and dental enamel (DENT) in vitro.

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Microbial bioproduction of the aromatic acid anthranilate (-aminobenzoate) has the potential to replace its current, environmentally demanding production process. The host organism employed for such a process needs to fulfil certain demands to achieve industrially relevant product levels. As anthranilate is toxic for microorganisms, the use of particularly robust production hosts can overcome issues from product inhibition.

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Despite the successes achieved with molecular targeted inhibition of the oncogenic driver Bcr-Abl in chronic myeloid leukemia (CML), the majority of patients still require lifelong tyrosine kinase inhibitor (TKI) therapy. This is primarily caused by resisting leukemic stem cells (LSCs), which prevent achievement of treatment-free remission in all patients. Here we describe the ITIM (immunoreceptor tyrosine-based inhibition motif)-containing Fc gamma receptor IIb (FcγRIIb, CD32b) for being critical in LSC resistance and show that targeting FcγRIIb downstream signaling, by using a Food and Drug Administration-approved BTK inhibitor, provides a successful therapeutic approach.

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Background: Remote Central Australia has a large Indigenous population and a significant burden of cardiovascular disease. Stress echocardiography has been previously validated as a useful investigation for long-term prognostication. However, there are no prior studies assessing its utility in remote or Indigenous populations.

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Challenging histopathological diagnostics in cancer include microsatellite instability-high (MSI-H) colorectal cancer (CRC), which occurs in 15% of early-stage CRC and is caused by a deficiency in the mismatch repair system. The diagnosis of MSI-H cannot be reliably achieved by visual inspection of a hematoxylin and eosin stained thin section alone, but additionally requires subsequent molecular analysis. Time- and sample-intensive immunohistochemistry with subsequent fragment length analysis is used.

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Intra-abdominal compartment syndrome (ACS) is a devastating complication in burn patients with a high mortality. Apart from high-volume resuscitation as known risk factor, also mechanical ventilation seems to influence the development of ACS. The TIRIFIC trial is a retrospective, matched-pair analysis.

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Protein complex formation depends on the interplay between preorganization and flexibility of the binding epitopes involved. The design of epitope mimetics typically focuses on stabilizing a particular bioactive conformation, often without considering conformational dynamics, which limits the potential of peptidomimetics against challenging targets such as transcription factors. We developed a peptide-derived inhibitor of the NF-Y transcription factor by first constraining the conformation of an epitope through hydrocarbon stapling and then fine-tuning its flexibility.

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Background: Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous disorder of the peripheral nervous system. Biallelic variants in have been associated with autosomal-recessive hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC). We identified heterozygous de novo variants in in three unrelated patients with intermediate CMT.

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Background: Expression of Bcr-Abl in hematopoietic stem cells is sufficient to cause chronic myeloid leukemia (CML) and tyrosine kinase inhibitors (TKI) induce molecular remission in the majority of CML patients. However, the disease driving stem cell population is not fully targeted by TKI therapy, and leukemic stem cells (LSC) capable of re-inducing the disease can persist. Single-cell RNA-sequencing technology recently identified an enriched inflammatory gene signature with TNFα and TGFβ being activated in TKI persisting quiescent LSC.

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Purpose: To investigate the pressure generated by different retraction materials using a novel gingival sulcus model.

Materials And Methods: A gingival sulcus model was made using a polymer frame filled with silicon. A pressure sensor and a sulcus-fluid simulation were embedded into the silicon chamber to evaluate the pressure generated by different retraction materials.

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Fluid management is one of the anticipated risk factors for intra-abdominal compartment syndrome (ACS). Since fluid requirements depend on the burned total body surface area (TBSA), an independent analysis is necessary to adapt resuscitation protocols and prevent this life-threatening complication. A retrospective multicenter study with matched-pair analysis was conducted in four German burn centers, including 38 burn patients with ACS who underwent decompressive laparotomy.

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Tyrosine kinase inhibitor (TKI) therapy effectively blocks oncogenic Bcr-Abl signaling and induces molecular remission in the majority of CML patients. However, the disease-driving stem cell population is not fully targeted by TKI therapy in the majority of patients, and leukemic stem cells (LSCs) capable of re-inducing the disease can persist. In TKI-resistant CML, STAT3 inhibition was previously shown to reduce malignant cell survival.

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