The effects of diazepam on sleep depend on the photoperiod.

Daylength (i.e., photoperiod) provides essential information for seasonal adaptations of organisms.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Single immunization with genetically attenuated Pf∆mei2 (GA2) parasites by mosquito bite in controlled human malaria infection: a placebo-controlled randomized trial.

Malaria vaccines consisting of metabolically active Plasmodium falciparum (Pf) sporozoites can offer improved protection compared with currently deployed subunit vaccines. In a previous study, we demonstrated the superior protective efficacy of a three-dose regimen of late-arresting genetically attenuated parasites administered by mosquito bite (GA2-MB) compared with early-arresting counterparts (GA1-MB) against a homologous controlled human malaria infection. Encouraged by these results, we explored the potency of a single GA2-MB immunization in a placebo-controlled randomized trial.

Deep learning-based pelvimetry in pelvic MRI volumes for pre-operative difficulty assessment of total mesorectal excision.

Background: Specific pelvic bone dimensions have been identified as predictors of total mesorectal excision (TME) difficulty and outcomes. However, manual measurement of these dimensions (pelvimetry) is labor intensive and thus, anatomic criteria are not included in the pre-operative difficulty assessment. In this work, we propose an automated workflow for pelvimetry based on pre-operative magnetic resonance imaging (MRI) volumes.

Flow-Based Coronary Artery Bypass Graft Patency Metrics: Uncertainty Quantification Simulations to Guide Development.

Purpose: Over time, transit time flow measurement (TTFM) has proven itself as a simple and effective tool for intra-operative evaluation of coronary artery bypass grafts (CABGs). However, metrics used to screen for possible technical error show considerable spread, preventing the definition of sharp cut-off values to distinguish between patent, questionable, and failed grafts. The simulation study presented in this paper aims to quantify this uncertainty for commonly used patency metrics, and to identify the most important physiological parameters influencing it.

Generating unseen diseases patient data using ontology enhanced generative adversarial networks.

Generating realistic synthetic health data (e.g., electronic health records), holds promise for fundamental research, AI model development, and enhancing data privacy safeguards.

Establishing bio-logging data collections as dynamic archives of animal life on Earth.

Rapid growth in bio-logging-the use of animal-borne electronic tags to document the movements, behaviour, physiology and environments of wildlife-offers opportunities to mitigate biodiversity threats and expand digital natural history archives. Here we present a vision to achieve such benefits by accounting for the heterogeneity inherent to bio-logging data and the concerns of those who collect and use them. First, we can enable data integration through standard vocabularies, transfer protocols and aggregation protocols, and drive their wide adoption.

Oligometastatic Esophagogastric Cancer: Does It Exist and How Do We Treat It?

Purpose Of The Review: This narrative review aims to provide an overview of recently completed randomized trials and expert consensus recommendations, and their implications for clinical practice and future trial design in patients with de-novo esophagogastric oligometastatic disease (OMD).

Recent Findings: The IKF-575/RENAISSANCE phase III trial showed no significant overall survival difference between systemic therapy alone and systemic therapy combined with local therapy for patients with gastric or gastroesophageal junction cancer and de-novo OMD, except for patients with retroperitoneal lymph node metastases only. The ESO-Shanghai 13 phase II trial demonstrated superiority of adding local therapy to systemic therapy for progression-free and overall survival in oligometastatic esophageal squamous cell carcinoma.

Comprehensive genomic characterization of early-stage bladder cancer.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Degrowth as a plausible pathway for food systems transformation.

Food systems require urgent transformation towards social and ecological sustainability. Degrowth posits a radical pathway of transformation to reduce ecological impacts while increasing well-being and reducing inequality. Here we highlight that degrowth and food systems-albeit both linked to transformation-are not well integrated.

Perennial disaster patterns in Central Europe since 2000 and implications for hospital preparedness planning - a cross-sectional analysis.

The goal of this analysis is to describe seasonal disaster patterns in Central Europe in order to raise awareness and improve hospital disaster planning and resilience, particularly during peak events. Hospitals are essential pillars of a country's critical infrastructure, vital for sustaining healthcare services and supporting public well-being-a key issue of national security. Disaster planning for hospitals is crucial to ensure their functionality under special circumstances.

A non-metallic PEEK topology optimization reconstruction implant for large mandibular continuity defects, validated using the MANDYBILATOR apparatus.

In cases of large mandibular continuity defects resulting from malignancy resection, the current standard of care involves using patient-specific/custom titanium reconstruction plates along with autogenous grafts (fibula, scapula, or iliac crest segments). However, when grafts are not feasible or desired, only the reconstruction plate is used to bridge the gap. Unfortunately, metal osteosynthesis and reconstruction plates, including titanium, exhibit adverse effects such as stress-shielding and limitations in accurate postoperative irradiation (especially with proton-beam therapy).

Multiscale X-ray scattering elucidates activation and deactivation of oxide-derived copper electrocatalysts for CO reduction.

Electrochemical reduction of carbon dioxide (CO) into sustainable fuels and base chemicals requires precise control over and understanding of activity, selectivity and stability descriptors of the electrocatalyst under operation. Identification of the active phase under working conditions, but also deactivation factors after prolonged operation, are of the utmost importance to further improve electrocatalysts for electrochemical CO conversion. Here, we present a multiscale in situ investigation of activation and deactivation pathways of oxide-derived copper electrocatalysts under CO reduction conditions.

Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction.

Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.

Vascularized human brain organoids: current possibilities and prospects.

Human brain organoids (hBOs) are in vitro, 3D, self-organizing brain tissue structures increasingly used for modeling brain development and disease. Although they traditionally lack vasculature, recent bioengineering developments enable their vascularization, which partly recapitulates neurodevelopmental processes such as neural tube angiogenesis, formation of neurovascular unit (NVU)-like structures, and early barriergenesis. Although vascularized hBOs (vhBOs) are already used to model (defects in) neurovascular development, vascularization efficiency and other outcomes differ substantially between vascularization protocols and overall shortcomings should be considered.

Machine learning based prediction model for bile leak following hepatectomy for liver cancer.

Objective: We sought to develop a machine learning (ML) preoperative model to predict bile leak following hepatectomy for primary and secondary liver cancer.

Methods: An eXtreme Gradient Boosting (XGBoost) model was developed to predict post-hepatectomy bile leak using data from the ACS-NSQIP database. The model was externally validated using data from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) multi-institutional databases.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

This is the first in a series of five papers that detail the role and substantial impact that external quality assessment (EQA) and their providers' services play in ensuring diagnostic (IVD) performance quality. The aim is to give readers and users of EQA services an insight into the processes in EQA, explain to them what happens before EQA samples are delivered and after examination results are submitted to the provider, how they are assessed, what benefits participants can expect, but also who are stakeholders other than participants and what significance do EQA data and assessment results have for them. This first paper presents the history of EQA, insights into legal, financing and ethical matters, information technology used in EQA, structure and lifecycle of EQA programs, frequency and intensity of challenges, and unique requirements of extra-examination and educational EQA programs.

Reliability of the OMERACT Giant cell arteritis Ultrasonography Score (OGUS): results of a patient-based exercise involving experts and non-experts in vascular ultrasonography.

Objective: To test the reliability of the Outcome Measures in Rheumatology Giant cell arteritis (GCA) Ultrasonography Score (OGUS) and other composite scores in a patient-based exercise involving experts and non-experts in vascular ultrasonography.

Methods: Six GCA patients were scanned twice (two rounds separated ≥3 hours) by 12 experts and 12 non-experts. Non-experts received 90 min of theoretical and 240 min of practical training between rounds 1 and 2.

Perspectives of older patients on the preventability of their unplanned emergency department return visit within 30 days in the Netherlands: a multicentre mixed methods study.

Objective: Older adults are prone to unplanned emergency department (ED) return visits (URVs). Knowledge about patient perspectives on the preventability and reasons for these URVs is limited and lacks a representable ED study population. This study aims to determine the proportion of URVs and to explore the preventability and underlying causes as perceived by a wide range of older adults and their caregivers.