Ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution.

Osteosarcoma is the most common primary cancer of the bone, with a peak incidence in children and young adults. Using multi-region whole-genome sequencing, we find that chromothripsis is an ongoing mutational process, occurring subclonally in 74% of osteosarcomas. Chromothripsis generates highly unstable derivative chromosomes, the ongoing evolution of which drives the acquisition of oncogenic mutations, clonal diversification, and intra-tumor heterogeneity across diverse sarcomas and carcinomas.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

To Tweak or Not to Tweak. How Exploiting Flexibilities in Gene Set Analysis Leads to Overoptimism.

Gene set analysis, a popular approach for analyzing high-throughput gene expression data, aims to identify sets of genes that show enriched expression patterns between two conditions. In addition to the multitude of methods available for this task, users are typically left with many options when creating the required input and specifying the internal parameters of the chosen method. This flexibility can lead to uncertainty about the "right" choice, further reinforced by a lack of evidence-based guidance.

Stratified Medicine Paediatrics: Cell free DNA and serial tumour sequencing identifies subtype specific cancer evolution and epigenetic states.

We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature.

Vital lessons from struggling partnerships and potential partnerships: an international study with leaders across the health sector.

Background: Inter-organizational partnerships and collaborations, used here interchangeably, have growing prominence across the health sector. Successful partnerships have received extensive study. However, especially for partnerships including nonprofit partners, limited attention has been given to negative factors that contribute to struggling partnerships, including failed partnerships, and/or impede potential partnerships, including unexplored and undeveloped potential partnerships.

Search for the Exclusive W Boson Hadronic Decays W^{±}→π^{±}γ, W^{±}→K^{±}γ and W^{±}→ρ^{±}γ with the ATLAS Detector.

A search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140  fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13  TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.

Leveraging Machine Learning to Identify Subgroups of Misclassified Patients in the Emergency Department: Multicenter Proof-of-Concept Study.

Background: Hospitals use triage systems to prioritize the needs of patients within available resources. Misclassification of a patient can lead to either adverse outcomes in a patient who did not receive appropriate care in the case of undertriage or a waste of hospital resources in the case of overtriage. Recent advances in machine learning algorithms allow for the quantification of variables important to under- and overtriage.

The Staphylococcus aureus-antagonizing human nasal commensal Staphylococcus lugdunensis depends on siderophore piracy.

Background: Bacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes. Beneficial commensal bacteria can often prevent the invasion and persistence of such pathogens by using molecular strategies that are only superficially understood.

Exploring factors affecting adherence to multiple micronutrient supplementation during pregnancy in Cambodia: A qualitative analysis.

For decades, iron-folic acid (IFA) supplements have been provided to pregnant women in Cambodia through antenatal care (ANC) services. However, mounting evidence suggests that multiple micronutrient supplements (MMS) are superior to IFA supplements in achieving positive pregnancy outcomes. The possibility of transitioning from IFA supplements to MMS in government-run health centres is currently being assessed in Cambodia.

Using PROMIS Methodology to Create Self-Report Measures of Mindfulness and Related Concepts.

Background: Mindfulness meditation is ubiquitous in health care, education, and communities at large. Mindfulness-Based Interventions (MBIs) are the focus of hundreds of NIH-funded trials given the myriad health benefits associated with this practice across multiple populations. Notwithstanding, significant gaps exist in how mindfulness concepts are measured using currently available self-report instruments.

Peace, equanimity and acceptance in the cancer experience: validation of the German version (PEACE-G) and associations with mental health, health-related quality of life and psychological constructs.

Background: Systematic reviews and meta-analyses reveal the importance of an accepting attitude towards cancer for mental health and functional coping. The aim of this study was to examine the psychometric properties of the German translation of the Peace, Equanimity, and Acceptance in the Cancer Experience (PEACE) questionnaire (Mack et al., 2008) and to investigate its associations with mental health, health-related quality of life (HRQoL) and related constructs.

Publisher Correction: Novel immunotherapeutics against LGR5 to target multiple cancer types.

[Image: see text]

Combination of Searches for Higgs Boson Pair Production in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

This Letter presents results from a combination of searches for Higgs boson pair production using 126-140  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV recorded with the ATLAS detector. At 95% confidence level (CL), the upper limit on the production rate is 2.9 times the standard model (SM) prediction, with an expected limit of 2.

Studies of the Energy Dependence of Diboson Polarization Fractions and the Radiation-Amplitude-Zero Effect in WZ Production with the ATLAS Detector.

This Letter presents the first study of the energy dependence of diboson polarization fractions in WZ→ℓνℓ^{'}ℓ^{'}(ℓ,ℓ^{'}=e,μ) production. The dataset used corresponds to an integrated luminosity of 140  fb^{-1} of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the ATLAS detector. Two fiducial regions with an enhanced presence of events featuring two longitudinally polarized bosons are defined.

The gender gap in fair earnings increases with age due to higher age premium for men.

This study explores how gender and age interact in shaping beliefs about fair pay through a factorial survey experiment conducted with German employees. Respondents evaluated hypothetical worker descriptions varying in age, gender, and earnings. While no gender gap in fair earnings was found for the youngest hypothetical workers, a significant gap favoring men emerged with increasing age.

[Effects of a multimodal inpatient treatment for patients with fibromyalgia syndrome at the Rhineland-Palatinate Acute Rheumatology Center].

Introduction: Fibromyalgia syndrome (FMS) is a complex condition that is often refractory to therapy and is associated with impaired quality of life. In some studies, multimodal rheumatological treatment has been shown to be an effective therapy option for patients with systemic-inflammatory and degenerative rheumatic diseases. However, the effects of this therapeutic approach have not been sufficiently investigated in patients with FMS.

Real-life effects of pharmacological osteoporosis treatments on bone mineral density by quantitative computed tomography.

Introduction: Monitoring of bone mineral density (BMD) is used to assess pharmacological osteoporosis therapy. This study examined the real-life effects of antiresorptive and osteoanabolic treatments on volumetric BMD (vBMD) of the spine by quantitative computed tomography (QCT).

Materials And Methods: Patients aged ≥ 50 years with a vBMD < 120 mg/ml had ≥ 2 QCT.

Establishing Medical Intelligence-Leveraging Fast Healthcare Interoperability Resources to Improve Clinical Management: Retrospective Cohort and Clinical Implementation Study.

Background: FHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data.

Objective: This study aimed to design and implement a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making.

Novel immunotherapeutics against LGR5 to target multiple cancer types.

We have developed and validated a highly specific, versatile antibody to the extracellular domain of human LGR5 (α-LGR5). α-LGR5 detects LGR5 overexpression in >90% of colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B-ALL tumour cells and was used to generate an Antibody-Drug Conjugate (α-LGR5-ADC), Bispecific T-cell Engager (α-LGR5-BiTE) and Chimeric Antigen Receptor (α-LGR5-CAR). α-LGR5-ADC was the most effective modality for targeting LGR5 cancer cells in vitro and demonstrated potent anti-tumour efficacy in a murine model of human NALM6 pre-B-ALL driving tumour attrition to less than 1% of control treatment.