Impact of the Covid-19 pandemic on inpatient health care in Switzerland 2020-2021-A descriptive retrospective study using admission data of all Swiss hospitals.

Background: As part of the Covid-19-restrictions in Switzerland, a federal ban on non-urgent examinations and treatments was applied to all hospitals during six weeks in spring 2020 ("spring lockdown"). The aim of this study was to comprehensively investigate the consequences of the Covid-19 pandemic on Swiss inpatient admissions based on data of all hospitals, focusing on selected procedures of different medical urgency.

Methods: The study includes all acute care inpatient cases (including Covid-19 cases, excluding cases in psychiatry and rehabilitation) according to the Swiss Medical Statistics of Hospitals.

Real-world treatment patterns and medical costs of prostate cancer patients in Switzerland - A claims data analysis.

Background: Prostate cancer (PC) is the most prevalent cancer in men in Switzerland. However, evidence on the real-world health care use of PC patients is scarce. The aim of this study is to describe health care utilization, treatment patterns, and medical costs in PC patients over a period of five years (2014-2018).

What drives health care spending in Switzerland? Findings from a decomposition by disease, health service, sex, and age.

Background: High and increasing spending dominates the public discussion on healthcare in Switzerland. However, the drivers of the spending increase are poorly understood. This study decomposes health care spending by diseases and other perspectives and estimates the contribution of single cost drivers to overall healthcare spending growth in Switzerland between 2012 and 2017.

Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1.

An immunosuppressive microenvironment causes poor tumor T cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumors is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identified complement receptor C5aR1 as a druggable target, which when inhibited improved radiotherapy, even in tumors displaying immunosuppressive features and poor CD8+ T cell infiltration.

Factors associated with the choice of supplementary hospital insurance in Switzerland - an analysis of the Swiss Health Survey.

Background: Switzerland has universal coverage via mandatory health insurance that covers a generous basket of health services. In addition to the basic coverage, the insured can buy supplementary insurance for the inpatient sector. Supplementary hospital insurance in Switzerland provides additional services during inpatient stays.

The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis.

The accurate repair of DNA double-strand breaks (DSBs), highly toxic DNA lesions, is crucial for genome integrity and is tightly regulated during the cell cycle. In mitosis, cells inactivate DSB repair in favor of a tethering mechanism that stabilizes broken chromosomes until they are repaired in the subsequent cell cycle phases. How this is achieved mechanistically is not yet understood, but the adaptor protein TOPBP1 is critically implicated in this process.

The CIP2A-TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer.

BRCA1/2-mutated cancer cells adapt to the genome instability caused by their deficiency in homologous recombination (HR). Identification of these adaptive mechanisms may provide therapeutic strategies to target tumors caused by the loss of these genes. In the present study, we report genome-scale CRISPR-Cas9 synthetic lethality screens in isogenic pairs of BRCA1- and BRCA2-deficient cells and identify CIP2A as an essential gene in BRCA1- and BRCA2-mutated cells.

Decomposition of outpatient health care spending by disease - a novel approach using insurance claims data.

Background: Decomposing health care spending by disease, type of care, age, and sex can lead to a better understanding of the drivers of health care spending. But the lack of diagnostic coding in outpatient care often precludes a decomposition by disease. Yet, health insurance claims data hold a variety of diagnostic clues that may be used to identify diseases.

Mechanisms of genome stability maintenance during cell division.

During mitosis, chromosomes undergo extensive structural changes resulting in the formation of compact cylindrical bodies and in the termination of the bulk of DNA-dependent metabolic activities. Therefore, DNA lesions that interfere with processes such as DNA replication and transcription in interphase are not expected to pose a major threat to genome stability in mitosis. There are, however, a few exceptions.

Epigenetic Silencing of Immune-Checkpoint Receptors in Bone Marrow- Infiltrating T Cells in Acute Myeloid Leukemia.

Background: Immune-checkpoint (IC) inhibitors have revolutionized the treatment of multiple solid tumors and defined lymphomas, but they are largely ineffective in acute myeloid leukemia (AML). The reason why especially PD1/PD-L1 blocking agents are not efficacious is not well-understood but it may be due to the contribution of different IC ligand/receptor interactions that determine the function of T cells in AML.

Methods: To analyze the interactions of IC ligands and receptors in AML, we performed a comprehensive transcriptomic analysis of FACS-purified leukemia stem/progenitor cells and paired bone marrow (BM)-infiltrating CD4 and CD8 T cells from 30 patients with AML.

Factors related to the change in Swiss inpatient costs by disease: a 6-factor decomposition.

There is currently little systematic knowledge about the contribution of different factors to the increase in health care spending in high-income countries such as Switzerland. The aim of this paper is to decompose inpatient care costs in the Swiss canton of Zurich by 100 diseases and 42 age/sex groups and to assess the contribution of six factors to the change in aggregate costs between 2013 and 2017. These six factors are population size, age and sex structure, inpatient treated prevalence, utilization in terms of stays per patient, length of stay per case, and costs per treatment day.

Systemic detectability of dexamethasone and prednisolone after eye drop application in horses.

Background: Equine sport agencies list steroids as prohibited substances for competing horses.

Objectives: The objective of this study was to investigate if the controlled substances dexamethasone and prednisolone are detectable in equine serum and urine samples during and after treatment with eye drops and if this can generate a positive doping test.

Study Design: Prospective cohort study.

Comorbidity-dependent changes in alpha and broadband electroencephalogram power during general anaesthesia for cardiac surgery.

Background: Age and comorbidities are reported to induce neurobiological transformations in the brain. Whilst the influence of ageing on anaesthesia-induced electroencephalogram (EEG) changes has been investigated, the effect of comorbidities has not yet been explored. We hypothesised that certain diseases significantly affect frontal EEG alpha and broadband power in cardiac surgical patients.

How Cells Respond to DNA Breaks in Mitosis.

DNA double-strand breaks (DSBs) are highly toxic lesions that can lead to chromosomal instability if they are not repaired correctly. DSBs are especially dangerous in mitosis when cells go through the complex process of equal chromosome segregation into daughter cells. When cells encounter DSBs in interphase, they are able to arrest the cell cycle until the breaks are repaired before entering mitosis.

Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation.

Induction of DNA double-strand breaks (DSBs) in ribosomal DNA (rDNA) repeats is associated with ATM-dependent repression of ribosomal RNA synthesis and large-scale reorganization of nucleolar architecture, but the signaling events that regulate these responses are largely elusive. Here we show that the nucleolar response to rDNA breaks is dependent on both ATM and ATR activity. We further demonstrate that ATM- and NBS1-dependent recruitment of TOPBP1 in the nucleoli is required for inhibition of ribosomal RNA synthesis and nucleolar segregation in response to rDNA breaks.

Decreasing Frontal Electroencephalogram Alpha Power and Increasing Sensitivity to Volatile Anesthetics Over 3 Surgeries Within 7 Months: A Case Report.

Depth of anesthesia (DoA) monitors are widely used during general anesthesia to guide individualized dosing of hypnotics. Other than age and specific drugs, there are few reports on which comorbidities may influence the brain and the resultant electroencephalogram (EEG) of patients undergoing general anesthesia. We present a case of a patient undergoing 3 cardiac operations within 7 months with severe illness and comorbidity, leading to pronounced physical frailty and significant changes of frontal alpha power in the EEG and increased sensitivity to volatile anesthetics.

Doxycycline reduces MMP-2 activity and inhibits invasion of 12Z epithelial endometriotic cells as well as MMP-2 and -9 activity in primary endometriotic stromal cells in vitro.

Background: Matrix metalloproteinases (MMPs), especially the gelatinases MMP-2 and MMP-9, play a crucial role in the pathogenesis of endometriosis by enabling invasion. Doxycycline is a well-tolerated antibiotic and a potent MMP-inhibitor in subantimicrobial doses.

Methods: Gelatin zymography and activity assays were used to detect latent and active MMP-2 and -9 in cell culture supernatants of immortalized epithelial (12Z) and two isolates of primary endometriotic stromal cells treated with doxycycline.

MDC1 Interacts with TOPBP1 to Maintain Chromosomal Stability during Mitosis.

In mitosis, cells inactivate DNA double-strand break (DSB) repair pathways to preserve genome stability. However, some early signaling events still occur, such as recruitment of the scaffold protein MDC1 to phosphorylated histone H2AX at DSBs. Yet, it remains unclear whether these events are important for maintaining genome stability during mitosis.

NBS1 promotes the endonuclease activity of the MRE11-RAD50 complex by sensing CtIP phosphorylation.

DNA end resection initiates DNA double-strand break repair by homologous recombination. MRE11-RAD50-NBS1 and phosphorylated CtIP perform the first resection step MRE11-catalyzed endonucleolytic DNA cleavage. Human NBS1, more than its homologue Xrs2 in , is crucial for this process, highlighting complex mechanisms that regulate the MRE11 nuclease in higher eukaryotes.

Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.

Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions.