Association Between Local Skin Reactions and Efficacy with 5-Fluorouracil 4% Cream in Actinic Keratosis: A Post-Hoc Analysis of Two Randomised Clinical Trials.

Introduction: Topical 5-fluorouracil (5-FU), 5% or 4% cream, is recommended among first-line treatments for actinic keratosis (AK). Local skin reactions (LSRs) are an expected and transient response to treatment with 5-FU but can lead to treatment discontinuation when severe. This analysis aimed to investigate whether the severity of LSRs during the treatment was associated with lesion clearance assessed 4 weeks after completing treatment.

Protective effects of Euphorbia heterophylla against testicular degeneration in streptozotocin-induced diabetic rats in relation to phytochemical profile.

Background: Diabetes mellitus (DM) poses a major risk to human health due to an array of implications, one of which is a detrimental effect on the testicular and reproductive functions. Euphorbia heterophylla is widely recognized for its medicinal properties worldwide.

Methods And Findings: The objective of this study was to profile E.

Iron metabolism in a mouse model of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains the most prevalent type of primary liver cancer worldwide. p53 is one of the most frequently mutated tumor-suppressor genes in HCC and its deficiency in hepatocytes triggers tumor formation in mice. To investigate iron metabolism during liver carcinogenesis, we employed a model of chronic carbon tetrachloride injections in liver-specific p53-deficient mice to induce liver fibrosis, cirrhosis and subsequent carcinogenesis.

The mechanism of amyloid fibril growth from Φ-value analysis.

Amyloid fibrils are highly stable misfolded protein assemblies that play an important role in several neurodegenerative and systemic diseases. Although structural information of the amyloid state is now abundant, mechanistic details about the misfolding process remain elusive. Inspired by the Φ-value analysis of protein folding, we combined experiments and molecular simulations to resolve amino-acid contacts and determine the structure of the transition-state ensemble-the rate-limiting step-for fibril elongation of PI3K-SH3 amyloid fibrils.

Cortical changes associated with an anterior cruciate ligament injury may retrograde skilled kicking in football: preliminary EEG findings.

Anterior cruciate ligament injuries (ACLi) impact football players substantially leading to performance declines and premature career endings. Emerging evidence suggests that ACLi should be viewed not merely as peripheral injuries but as complex conditions with neurophysiological aspects. The objective of the present study was to compare kicking performance and associated cortical activity between injured and healthy players.

The current landscape of artificial intelligence in oral and maxillofacial surgery- a narrative review.

Objective: This narrative review aims to explore the current applications and future prospects of AI within the subfields of oral and maxillofacial surgery (OMS), emphasizing its potential benefits and anticipated challenges.

Methods: A detailed review of the literature was conducted to evaluate the role of AI in oral and maxillofacial surgery. All domains within OMS were reviewed with a focus on diagnostic, therapeutic and prognostic interventions.

Challenging the Astral mass analyzer to quantify up to 5,300 proteins per single cell at unseen accuracy to uncover cellular heterogeneity.

Despite significant advancements in sample preparation, instrumentation and data analysis, single-cell proteomics is currently limited by proteomic depth and quantitative performance. Here we demonstrate highly improved depth of proteome coverage as well as accuracy and precision for quantification of ultra-low input amounts. Using a tailored library, we identify up to 7,400 protein groups from as little as 250 pg of HeLa cell peptides at a throughput of 50 samples per day.

Response of negative ion beamlet width and axis deflection to RF field in beam extraction region.

Beam-divergence characteristics of single negative ion beamlet have been experimentally investigated with a superimposition of a controlled perturbation of a radio frequency wave (RF) field in a filament-arc discharge negative ion source. Oscillations of a negative-ion beamlet width and axis responding to the RF perturbation were observed, which may be a cause of the larger beam divergence angle of the RF negative ion source for ITER. It is pointed out that the oscillation of the beamlet width depends on the perveance and on an RF frequency such that the oscillation is suppressed at perveance-matched conditions and at low RF frequency.

Removal of dissolved organic carbon in the West Pacific hadal zones.

The deep oceans are environments of complex carbon dynamics that have the potential to significantly impact the global carbon cycle. However, the role of hadal zones, particularly hadal trenches (water depth > 6 km), in the oceanic dissolved organic carbon (DOC) cycle is not thoroughly investigated. Here we report distinct DOC signatures in the Japan Trench bottom water.

Recent Advances in the Genetics of Ataxias: An Update on Novel Autosomal Dominant Repeat Expansions.

Purpose Of Review: Autosomal dominant cerebellar ataxias, also known as spinocerebellar ataxias (SCAs), are genetically and clinically diverse neurodegenerative disorders characterized by progressive cerebellar dysfunction. Despite advances in sequencing technologies, a large proportion of patients with SCA still lack a definitive genetic diagnosis. The advent of advanced bioinformatic tools and emerging genomics technologies, such as long-read sequencing, offers an unparalleled opportunity to close the diagnostic gap for hereditary ataxias.

Safety and efficiency of trainees performing bilateral internal thoracic artery coronary bypass grafting using the T-graft technique.

Objectives: Aim of this study was to assess safety and efficiency of multiarterial coronary bypass grafting using bilateral internal thoracic arteries in T-graft technique performed by trainees.

Methods: Patients from January 2005 to February 2023 who had undergone multiarterial coronary bypass grafting using bilateral internal thoracic arteries in T-graft technique were analysed. Patients were divided into two groups based on the primary surgeon: Consultant and Trainees.

Transcriptional activation and coactivator binding by yeast Ino2 and human proto-oncoprotein c-Myc.

Basic helix-loop-helix domains in yeast regulatory proteins Ino2 and Ino4 mediate formation of a heterodimer which binds to and activates expression of phospholipid biosynthetic genes. The human proto-oncoprotein c-Myc (Myc) and its binding partner Max activate genes important for cellular proliferation and contain functional domains structure and position of which strongly resembles Ino2 and Ino4. Since Ino2-Myc and Ino4-Max may be considered as orthologs we performed functional comparisons in yeast.

Personalized Dynamic Prediction Model for Biopsy Timing in Patients With Prostate Cancer During Active Surveillance.

Importance: Active surveillance (AS) for patients with prostate cancer (PC) often includes fixed repeat prostate biopsies that do not account for the varying risk of reclassification to significant disease. Given the invasive nature and potential complications of biopsies, a personalized approach is needed to balance the burden of biopsies with the risk of missing disease progression.

Objective: To develop and externally validate a dynamic model that predicts an individual's risk of PC reclassification during AS.

Colorectal Cancer and Central Obesity.

Importance: The proportion of colorectal cancer (CRC) cases attributable to excess weight, known as population attributable fraction (PAF), has been commonly based on measures of body mass index (BMI). Central obesity metrics, such as waist circumference (WC) and waist to hip ratio (WHR), are potentially better indicators of adiposity and have demonstrated stronger associations with CRC incidence.

Objectives: To examine PAFs of CRC cases that are attributable to high WC and WHR and compare them to those attributable to high BMI.

Biomechanics of flail chest injuries: tidal volume and respiratory work changes in multiple segmental rib fractures.

Background: Flail chest (FC) injuries are segmental osseous injuries of the thorax that typically result from high-energy blunt trauma and regularly occur in multiple trauma (MT) patients. FC injuries are associated with paradoxical chest wall movements and, thus, have a high risk of respiratory insufficiency or even death. An increasing number of studies recommend an early surgical stabilization of FC injuries, but a definite trigger that would indicate surgery has, thus far, not been identified.

Prognostic relevance of CT-defined body composition in patients with acute bleeding undergoing endovascular embolization.

Objectives: Body composition assessment includes the parameter skeletal muscle mass, subcutaneous and visceral adipose tissue (SAT and VAT). The purpose of this study was to elucidate associations of body composition parameters with mortality in patients with acute bleeding undergoing transarterial embolization (TAE).

Methods: A mixed cohort of patients from 2018 to 2022 with acute bleeding requiring treatment with a TAE was retrospectively evaluated.

Adoptive NK cell therapy in AML: progress and challenges.

Adoptive cell therapy (ACT) using natural killer (NK) cells has emerged as a promising therapeutic strategy for acute myeloid leukemia (AML), addressing challenges such as chemotherapy resistance and high relapse rates. Over the years, clinical trials and studies have explored various sources of NK cells, including ex vivo expanded NK cell lines, CAR-NK cells, peripheral blood-derived NK cells, and umbilical cord blood-derived NK cells. These therapies have demonstrated varying degrees of therapeutic efficacy, ranging from transient anti-leukemia activity to sustained remission in select patient groups.

Long-term pulse pressure trajectories and risk of incident atrial fibrillation: the Tromsø Study.

Background And Aims: Sex-based differences in the association of long-term trends in pulse pressure with future risk of atrial fibrillation (AF) have been explored using data from the population-based Tromsø Study 1986-2016.

Methods: Women (n = 8331) and men (n = 7638) aged ≥20 years who attended at least two of the three Tromsø Study surveys conducted between 1986 and 2001 (the exposure period) were followed up for incident AF throughout 2016 (the follow-up period). Pulse pressure ≥60 mmHg was considered elevated.

[Evidence for the extent and oncological benefit of lymphadenectomy for pancreatic cancer].

Pancreatic cancer is usually diagnosed at a late stage and is characterized by early systemic metastases, which can also be present in the form of micrometastases that are not primarily visible. Lymphatic metastases in pancreatic cancer are common. The extent of lymph node removal (lymphadenectomy, LAD) in pancreatic cancer is defined in the guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) and according to currently available data has more diagnostic and prognostic relevance than therapeutic relevance; however, within the framework of modern multimodal treatment algorithms, radical surgery is the most relevant of all components of multimodal treatment with LAD playing an important role.

Enhancing NiS performance: Na-doping for advanced photocatalytic and electrocatalytic applications.

Alkali metal doping is a new and promising approach to enhance the photo/electrocatalytic activity of NiS-based catalyst systems. This work investigates the impact of sodium on the structural, electronic, and catalytic properties of NiS. Comprehensive characterization techniques demonstrate that Na-doping causes significant changes in the NiS lattice and surface chemistry translating into a larger bandgap than NiS.

Digital redesign of the radiotherapy course for medical students with a blended learning approach.

Purpose: Due to the need for high-quality teaching, we present a new blended learning concept combining digital modules, interactive seminars, and clinical experience. Furthermore, we evaluated its acceptance among students.

Methods: A new concept for teaching was applied to the radiotherapy module and made available via the Hannover Medical School (MHH) learning management system as part of a blended learning concept with educational films, multimedia learning modules, online seminars, and onsite practical training.

Endovascular management of haemorrhage and vascular lesions in patients with multiple and/or severe injuries: a systematic review and clinical practice guideline update.

Purpose: Our aim was to update evidence-based and consensus-based recommendations for the inhospital endovascular management of haemorrhage and vascular lesions in patients with multiple and/or severe injuries based on current evidence. This guideline topic is part of the 2022 update of the German Guideline on the Treatment of Patients with Multiple and/or Severe Injuries.

Methods: MEDLINE and Embase were systematically searched to June 2021.

Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome- paving the path towards precision medicine: a case report.

Background: Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome characterized by a high familial incidence of various malignancies. It results from pathogenic/likely pathogenic heterozygous constitutional variants of the TP53 gene. Due to impaired DNA damage repair, conventional cytotoxic therapies or radiotherapy should be avoided whenever feasible to mitigate the high incidence of treatment-related secondary malignancies in these patients.