Survival Among Patients Treated with Total Mesorectal Excision or Selective Watch-and-Wait After Total Neoadjuvant Therapy: A Pooled Analysis of the CAO/ARO/AIO-12 and OPRA Randomized Phase II Trials.

Background: Prospective data comparing watch-and-wait (WW) to mandatory total mesorectal excision (TME) in patients with locally advanced rectal cancer (LARC) remains limited, as randomized control trials assessing these two treatment approaches are considered impractical. This pooled analysis of the CAO/ARO/AIO-12 and OPRA trials analyzes survival outcomes among LARC patients managed with either a selective WW or mandatory TME strategy following total neoadjuvant therapy (TNT).

Patients And Methods: The CAO/ARO/AIO-12 and OPRA trials were multicenter, phase II trials that randomized patients with stage II/III rectal cancer to receive either induction or consolidation chemotherapy as part of TNT.

Genetic Predisposition to Hippocampal Atrophy and Risk of Amnestic Mild Cognitive Impairment and Alzheimer's Dementia.

Background: There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) as well as the rates of cognitive decline.

Methods: Participants were drawn from the population-based HELIAD cohort.

Pre-phase treatment with rituximab and high-dose methotrexate to re-evaluate eligibility for intensive induction treatment of frail patients with central nervous system lymphoma.

Not available.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Phage therapy could be key to conquering persistent bacterial lung infections in children.

Persistent bacterial lung infections in children lead to significant morbidity and mortality due to antibiotic resistance. In this paper, we describe how phage therapy has shown remarkable efficacy in preclinical and clinical studies, demonstrating significant therapeutic benefits through various administration routes. Ongoing trials are evaluating its safety and effectiveness against different pathogens.

From model validation to biomechanical analysis: In silico study of multirooted root analogue implants using 3D finite element analysis.

Objectives: To create a validated 3D finite element model and employ it to examine the biomechanical behaviour of multirooted root analogue implants (RAIs).

Methods: A validated finite element model comprising either an RAI or a threaded implant (TI) and an idealised bone block was developed based on a previously conducted in vitro study. All the experimental boundary conditions and material properties were reproduced.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Exploring the influence of medical staffing and birth volume on observed-to-expected cesarean deliveries: a panel data analysis of integrated obstetric and gynecological departments in Germany.

Introduction: Cesarean deliveries account for approximately one-third of all births in Germany, prompting ongoing discussions on cesarean section rates and their connection to medical staffing and birth volume. In Germany, the majority of departments integrate obstetric and gynecological care within a single department.

Methods: The analysis utilized quality reports from German hospitals spanning 2015 to 2019.

Analyses of Adverse Drug Reactions to Fluoroquinolones in Spontaneous Reports Before and After the Referral and in Clinical Routine Cases.

Introduction: In November 2018, the European Medicines Agency (EMA) restricted the use of fluoroquinolones (used by mouth, injections or inhalation) in the context of a referral due to long-lasting and potentially irreversible adverse drug reactions (ADRs). Fluoroquinolones should no longer be used to treat mild or moderate bacterial infections unless other antibacterials cannot be used.

Objectives: The first aim of our study was to analyze whether in the period before compared with after the referral the characteristics of spontaneous ADR reports related to fluoroquinolones differed and whether specific ADRs were more frequently reported for fluoroquinolones compared with cotrimoxazole.

Trust in scientists and their role in society across 68 countries.

Science is crucial for evidence-based decision-making. Public trust in scientists can help decision makers act on the basis of the best available evidence, especially during crises. However, in recent years the epistemic authority of science has been challenged, causing concerns about low public trust in scientists.

Perceptions of science, science communication, and climate change attitudes in 68 countries - the TISP dataset.

Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries.

Exercise-induced dynamic mitral regurgitation is associated with outcomes in patients with ischaemic cardiomyopathy.

Aims: Ischaemic mitral regurgitation (MR) is a dynamic condition influenced by global and regional left ventricular remodelling as well as mitral valvular deformation. Exercise testing plays a substantial role in assessing the haemodynamic relevance of MR and is recommended by current guidelines. We aimed to assess the prevalence, haemodynamic consequences, and prognostic impact of dynamic MR using isometric handgrip exercise.

Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

An immunohistochemical and molecular genetic study of 60 colorectal carcinoma brain metastases in pursuit of predictive biomarkers for cancer therapy.

Colorectal carcinoma brain metastases (n = 60) were studied using next-generation sequencing and immunohistochemistry. RAS and BRAF mutations were detected in 58.2% and 7.

Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies - A stakeholder meeting report.

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs.

Phosphodiesterase 4D inhibition improves the functional and molecular outcome in a mouse and human model of Charcot Marie Tooth disease 1 A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is an inherited peripheral neuropathy caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. It is primarily marked by Schwann cell dedifferentiation and demyelination, leading to motor and sensory deficits. Cyclic adenosine monophosphate (cAMP) is crucial for Schwann cell differentiation and maturation.

Feasibility of very low iodine dose aortoiliac CT angiography using dual-source photon-counting detector CT.

Purpose: To evaluate the feasibility of aortoiliac CT-Angiography (CTA) using dual-source photon-counting detector (PCD)-CT with minimal iodine dose.

Methods: This IRB-approved, single-center prospective study enrolled patients with indications for aortoiliac CTA from December 2022 to March 2023. All scans were performed using a first-generation dual-source PCD-CT.

Fatty-acid amide hydrolase inhibition mitigates Alzheimer's disease progression in mouse models of amyloidosis.

The endocannabinoid N-arachidonoylethanolamine (AEA) is a pro-homeostatic bioactive lipid known for its anti-inflammatory, anti-oxidative, immunomodulatory, and neuroprotective properties, which may contrast/mitigate Alzheimer's disease (AD) pathology. This study explores the therapeutic potential of targeting fatty acid amide hydrolase (FAAH), the major enzyme degrading AEA, in mouse models of amyloidosis (APP/PS1 and Tg2576). Enhancing AEA signaling by genetic deletion of FAAH delayed cognitive deficits in APP/PS1 mice and improved cognitive symptoms in 12-month-old AD-like mice.

Effects of Webcam Access to Preterm Infants in NICUs on Parental Psychological Strain.

Aim: To investigate whether webcam access for parents of infants in neonatal intensive care units influences parental postpartum depression and stress experiences.

Methods: Parents whose infants had a birth weight below 1500 g and who were admitted to one of the four participating tertiary care hospitals were eligible to participate in the study. The study followed the structure of a multi-centre cross-over pragmatic randomised controlled trial.

German evidence- and consensus-based guideline on the management of penile urethritis.

Urethritis is a common condition predominantly caused by sexually transmitted pathogens such as Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium. It is not possible to differentiate with certainty between pathogens on the basis of clinical characteristics alone. However, empirical antibiotic therapy is often initiated in clinical practice.

Resetting of the Human Circadian Melatonin Rhythm by Ambient Hypoxia.

Circadian clocks in the body drive daily cycles in physiology and behavior. A master clock in the brain maintains synchrony with the environmental day-night cycle and uses internal signals to keep clocks in other tissues aligned. Work in cell cultures uncovered cyclic changes in tissue oxygenation that may serve to reset and synchronize circadian clocks.

Borderline Findings in -(2-[F]-Fluoroethyl)-l-Tyrosine PET of Patients with Suspected Glioma Relapse: Role in Clinical Practice.

One of the most common clinical indications for amino acid PET using the tracer -(2-[F]-fluoroethyl)-l-tyrosine (F-FET) is the differentiation of tumor relapse from treatment-related changes in patients with gliomas. A subset of patients may present with an uptake of F-FET close to recommended threshold values. The goal of this study was to investigate the frequency of borderline cases and the role of quantitative F-FET PET parameters in this situation.