Small molecule biomarker discovery: Proposed workflow for LC-MS-based clinical research projects.

Mass spectrometry focusing on small endogenous molecules has become an integral part of biomarker discovery in the pursuit of an in-depth understanding of the pathophysiology of various diseases, ultimately enabling the application of personalized medicine. While LC-MS methods allow researchers to gather vast amounts of data from hundreds or thousands of samples, the successful execution of a study as part of clinical research also requires knowledge transfer with clinicians, involvement of data scientists, and interactions with various stakeholders. The initial planning phase of a clinical research project involves specifying the scope and design, and engaging relevant experts from different fields.

Work-Related Dermatoses of the Feet in Professional Dancers: A Pilot Study.

Objective: The feet of professional dancers are exposed to high work-related stresses. To date, data from the professional dance sector concerning this matter are lacking. The aim of this exploratory project was to analyze and evaluate skin health in the foot area with regard to the prevalence of dermatoses, their locations, as well as gender-specific and load-specific differences.

Functional regeneration of dilated cardiomyopathy by transcatheter bilateral pulmonary artery banding: first-in-human case series.

Background: Dilated cardiomyopathy (DCM) is a leading cause of heart transplantation (HTx) in children. Surgical pulmonary artery banding (PAB) is used worldwide to achieve functional heart regeneration and remodelling.

Case Summary: We report for the first-time successful bilateral transcatheter implantation of bilateral pulmonary artery flow restrictors in a case series of three infants with severe DCM based on left-ventricular non-compaction morphology associated with Barth syndrome in one and a non-classified syndrome in another.

time course of organ uptake and blood-brain-barrier permeation of poly(L-lactide) and poly(perfluorodecyl acrylate) nanoparticles with different surface properties in unharmed and brain-traumatized rats.

Background: Traumatic brain injury (TBI) has a dramatic impact on mortality and quality of life and the development of effective treatment strategies is of great socio-economic relevance. A growing interest exists in using polymeric nanoparticles (NPs) as carriers across the blood-brain barrier (BBB) for potentially effective drugs in TBI. However, the effect of NP material and type of surfactant on their distribution within organs, the amount of the administrated dose that reaches the brain parenchyma in areas with intact and opened BBB after trauma, and a possible elicited inflammatory response are still to be clarified.

Molecular Basis of the Electron Bifurcation Mechanism in the [FeFe]-Hydrogenase Complex HydABC.

Electron bifurcation is a fundamental energy coupling mechanism widespread in microorganisms that thrive under anoxic conditions. These organisms employ hydrogen to reduce CO, but the molecular mechanisms have remained enigmatic. The key enzyme responsible for powering these thermodynamically challenging reactions is the electron-bifurcating [FeFe]-hydrogenase HydABC that reduces low-potential ferredoxins (Fd) by oxidizing hydrogen gas (H).

Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor.

The ephrin type-A receptor 2 (EPHA2) kinase belongs to the largest family of receptor tyrosine kinases. There are several indications of an involvement of EPHA2 in the development of infectious diseases and cancer. Despite pharmacological potential, EPHA2 is an under-examined target protein.

Evaluating natural medicinal resources and their exposure to global change.

Medicinal plants and their bioactive molecules are integral components of nature and have supported the health of human societies for millennia. However, the prevailing view of medicinal biodiversity solely as an ecosystem-decoupled natural resource of commercial value prevents people from fully benefiting from the capacity of nature to provide medicines and from assessing the vulnerability of this capacity to the global environmental crisis. Emerging scientific and technological developments and traditional knowledge allow for appreciating medicinal plant resources from a planetary health perspective.

Photo/mechanical and physical implant surface decontamination approaches in conjunction with surgical peri-implantitis treatment: A systematic review.

Aim: To evaluate the efficacy of adjunctive/alternative photo/mechanical and physical implant-surface decontamination approaches compared to standard instrumentation in conjunction with surgical peri-implantitis treatment.

Materials And Methods: Randomized controlled clinical trials (RCTs) and controlled clinical trials investigating the efficacy of adjunctive or alternative photo/mechanical/physical measures for implant surface decontamination in conjunction with surgical peri-implantitis treatment without (PICOS 1) or with (PICOS 2) additional decontamination methods performed in test and control groups with changing inflammation parameters were covered. Changes in bleeding scores (i.

Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update.

Purpose: To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients.

Methods: The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients.

Sodium butyrate and voluntary exercise through activating VEGF-A downstream signaling pathway improve heart angiogenesis in type 2 diabetes.

Background: Inadequate angiogenesis in patients with type 2 diabetic heart could result in deprived collateral formation. Herein, we aimed to investigate the effects of sodium butyrate (NaB) along with voluntary exercise simultaneously on the mechanisms acting on cardiac angiogenesis.

Materials And Methods: Animals were divided into the following five groups: control (Con), diabetic rats (Dia), diabetic rats treated with NaB (200 mg/kg, i.

Epidemiology of carpal fractures: is it only about the scaphoid?

Because of their low incidence, studies about carpal fractures are rare. The aim of the present study was to analyze epidemiology and treatment of fractured carpal bones. We retrospectively analyzed data of 178 patients admitted to our emergency room with carpal fractures over 6 years.

Additional benefit of systemic antibiotics in subgingival instrumentation of stage III and IV periodontitis with Aggregatibacter actinomycetemcomitans: A retrospective analysis.

Aim: To evaluate subgingival instrumentation (SI) in periodontitis stage III and IV, grade B and C with systemic antibiotics (AB) only after detection of Aggregatibacter actinomycetemcomitans.

Materials And Methods: Patients of the Department of Periodontology of Goethe University Frankfurt/Germany were screened for microbiological testing between 2008 and 2018. All patients with aggressive and generalized severe chronic periodontitis were tested.

Treatment of Infants and Children With SARS-CoV-2 Monoclonal Antibodies: A European Case Series.

Background: Although severe COVID-19 in children is rare, those with certain pre-existing health conditions are more prone to severe disease. Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are potent antiviral agents that reduce adverse clinical outcomes in adults, but are commonly not approved for use in pediatric patients.

Methods: We retrospectively evaluated mAb treatment in children <12 years of age or <40kg with SARS-CoV-2 infection between January 1, 2021, and March 7, 2022, in 12 tertiary care centers in 3 European countries.

Real-world Comparative Effectiveness of Ustekinumab vs Anti-TNF in Crohn's Disease With Propensity Score Adjustment: Induction Phase Results From the Prospective, Observational RUN-CD Study.

Background: In addition to randomized controlled trials (RCTs), real-world studies on the effectiveness of ustekinumab (UST) in Crohn's disease (CD) are required inasmuch as RCTs are usually confined to selected patients, which may not represent everyday clinical practice. Within the framework of the prospective real-world RUN-CD registry, a total of approximately 900 CD patients from 44 inflammatory bowel disease centers from all over Germany starting a new therapy with UST or other biologics were screened for a real-world evidence (RWE) comparison of CD patients with UST vs antitumor necrosis factor (TNF).

Methods: A total of 618 CD patients with a nonrandomized biological therapy were qualified for this induction phase effectiveness RUN-CD study of UST vs anti-TNF.

Discovery of Potent and Exquisitely Selective Inhibitors of Kinase CK1 with Tunable Isoform Selectivity.

Casein kinases 1 (CK1) are key signaling molecules that have emerged recently as attractive therapeutic targets in particular for the treatment of hematological malignancies. Herein, we report the identification of a new class of potent and highly selective inhibitors of CK1α, δ and ϵ. Based on their optimal in vitro and in vivo profiles and their exclusive selectivity, MU1250, MU1500 and MU1742 were selected as quality chemical probes for those CK1 isoforms.

The Ongoing Evolution of Abdominal Aortic Surgery.

Abdominal aortic surgery has witnessed significant paradigm shifts in recent years with the introduction of structured screening programs, as well as the evolution of endovascular aortic aneurysm repair (EVAR), which has allowed physicians to promptly identify and successfully treat an increasing number of patients, even including those previously considered unfit for open repair [...

COVI-Prim international: Similarities and discrepancies in the way general practices from seven different countries coped with the COVID-19 pandemic.

Objectives: General practitioners (GPs) are frequently patients' first point of contact with the healthcare system and play an important role in identifying, managing and monitoring cases. This study investigated the experiences of GPs from seven different countries in the early phases of the COVID-19 pandemic.

Design: International cross-sectional online survey.

Genomic Classifiers in Personalized Prostate Cancer Radiation Therapy Approaches: A Systematic Review and Future Perspectives Based on International Consensus.

Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk stratification after surgery, but less data exist for patients treated with definitive radiation therapy (RT) or RT in oligo-/metastatic disease stages. To guide future perspectives of GCs for RT, we conducted (1) a systematic review on the evidence of GCs for patients treated with RT and (2) a survey of experts using the Delphi method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research.

Site-Specific Labeling of RNAs with Modified and F-Labeled Nucleotides by Chemo-Enzymatic Synthesis.

More than 170 post-transcriptional modifications of RNAs have currently been identified. Detailed biophysical investigations of these modifications have been limited since large RNAs containing these post-transcriptional modifications are difficult to produce. Further, adequate readout of spectroscopic fingerprints are important, necessitating additional labeling procedures beyond the naturally occurring RNA modifications.

Subannular repair for functional mitral regurgitation with reduced systolic ventricle function: rationale and design of REFORM-MR registry.

Background: Functional mitral regurgitation (FMR) is one of the most common heart valve diseases that is a sequel of left ventricular remodelling. Although mitral valve annuloplasty is a standard treatment of FMR, the recurrence of FMR is a major drawback and occurs in 10-50% of patients. The REFORM-MR registry aims to investigate the effectiveness of standardized papillary muscle relocation and ring annuloplasty and to identify the risk factors associated with recurrent FMR.

Imaging biomarkers to stratify lymph node metastases in abdominal CT - Is radiomics superior to dual-energy material decomposition?

Purpose: To assess the potential of radiomic features in comparison to dual-energy CT (DECT) material decomposition to objectively stratify abdominal lymph node metastases.

Materials And Methods: In this retrospective study, we included 81 patients (m, 57; median age, 65 (interquartile range, 58.7-73.

Subsiding of Periodontitis in the Permanent Dentition in Individuals with Papillon-Lefèvre Syndrome through Specific Periodontal Treatment: A Systematic Review.

Papillon-Lefèvre syndrome (PLS) is a rare hereditary disease characterized by palmoplantar hyperkeratosis (PPK) and periodontitis in the primary and permanent dentition, usually resulting in edentulism in youth. Subsiding of PLS-associated periodontitis through specific therapy has occasionally been reported. We aimed to systematically assess periodontal treatment strategies that may decelerate disease progression.

Serum Beta-D-Glucan in the Diagnosis of Invasive Fungal Disease in Neonates, Children and Adolescents: A Critical Analysis of Current Data.

β-D-glucan (BDG) is a cell wall component of many pathogenic fungi. The detection of BDG as an assay is clinically broadly used as a diagnostic tool. However, the current data on BDG in paediatrics are limited, prompting specific considerations about when BDG can be used in neonates and children.

Branch point strength controls species-specific alternative splicing and regulates LTP.

Regulation and functionality of species-specific alternative splicing has remained enigmatic to the present date. Calcium/calmodulin-dependent protein kinase IIβ (CaMKIIβ) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific splice isoforms, which show altered kinetic properties and changes in substrate specificity.