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.
View Article and Find Full Text PDFMetrics for health-care sustainability are crucial for tracking progress and understanding the advantages of different operations or systems as the health-care sector addresses the climate crisis and other environmental challenges. Measurement of the key metrics of absolute energy use and greenhouse gas emissions now has substantial momentum, but our overall measurement framework generally has serious deficiencies. Because existing metrics are often borrowed from other sectors, many are unconnected to the specifics of health-care provision or existing health system performance indicators, the potential negative effects of health care on public health are largely absent, a consistent and standardised set of health-care sustainability measurement concepts does not yet exist, and current dynamics in health systems such as privatisation are largely ignored.
View Article and Find Full Text PDFPatients with multiple myeloma (MM) are a heterogenous, immunocompromised group with increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations and breakthrough infections (BTIs) on antibody (Ab) levels and cross-protection to variants of concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral and cellular vaccine responses in MM patients stratified according to disease stage/treatment into group (1) monoclonal gammopathy of undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) after SCT with IT, and (4) progressed MM, and in healthy subjects (prospective cohort study).
View Article and Find Full Text PDFTreatment of post-dissection arch and thoracoabdominal aortic aneurysms presents significant therapeutic challenges. True lumen collapse or take off of aortic branches from the false lumen makes endograft alignment difficult, if not impossible. We present herein the first successful case of an extensive thoracoabdominal electro aortic septotomy of the entire dissection membrane from the aortic arch down to the aortic bifurcation during an open redo aortic arch replacement employing the frozen elephant trunk technique.
View Article and Find Full Text PDFThe current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment.
View Article and Find Full Text PDFDisruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet the underlying mechanism has remained enigmatic. Immunostaining of sympathetic axons in optically cleared pineal glands from humans and mice with cardiac disease revealed their substantial denervation compared with controls. Spatial, single-cell, nuclear, and bulk RNA sequencing traced this defect back to the superior cervical ganglia (SCG), which responded to cardiac disease with accumulation of inflammatory macrophages, fibrosis, and the selective loss of pineal gland-innervating neurons.
View Article and Find Full Text PDFAnti-CD19 immunotherapy tafasitamab is used in combination with lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Open-label, phase 1b, First-MIND study assessed safety and preliminary efficacy of tafasitamab + R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) ± lenalidomide as first-line therapy in patients with DLBCL. From December 2019 to August 2020, 83 adults with untreated DLBCL (International Prognostic Index 2-5) were screened and 66 were randomly assigned (33 per arm) to R-CHOP-tafasitamab (arm T) or R-CHOP-tafasitamab-lenalidomide (arm T/L) for 6 cycles.
View Article and Find Full Text PDFBuilding stock management is becoming a global societal and political issue, inter alia because of growing sustainability concerns. Comprehensive and openly accessible building stock data can enable impactful research exploring the most effective policy options. In Europe, efforts from citizen and governments generated numerous relevant datasets but these are fragmented and heterogeneous, thus hindering their usability.
View Article and Find Full Text PDFThe optomotor response (OMR) is central to the locomotory behavior in diverse animal species including insects, fish and mammals. Furthermore, the study of the OMR in larval zebrafish has become a key model system for investigating the neural basis of sensorimotor control. However, a comprehensive understanding of the underlying control algorithms is still outstanding.
View Article and Find Full Text PDFThe analysis of ultralow input samples or even individual cells is essential to answering a multitude of biomedical questions, but current proteomic workflows are limited in their sensitivity and reproducibility. Here, we report a comprehensive workflow that includes improved strategies for all steps, from cell lysis to data analysis. Thanks to convenient-to-handle 1 μL sample volume and standardized 384-well plates, the workflow is easy for even novice users to implement.
View Article and Find Full Text PDFData on women's living conditions and socio-economic development are important for understanding and addressing the pronounced challenges and inequalities faced by women worldwide. While such information is increasingly available at the national level, comparable data at the sub-national level are missing. We here present the LivWell global longitudinal dataset, which includes a set of key indicators on women's socio-economic status, health and well-being, access to basic services and demographic outcomes.
View Article and Find Full Text PDFObjective: To present a case series of spontaneous structural failure of bridging stentgrafts (BSGs) after branched endovascular aortic repair (bEVAR), as well as their failure types and their detection. While bEVAR is a safe and effective procedure, one main limitation is the reintervention rate associated with the BSGs. Structural failure of BSGs, defined as fabric disruption, stent fracture with leak or complete separation is a major cause for reinterventions and difficult to detect in computed tomography angiography (CTA).
View Article and Find Full Text PDFLipegfilgrastim is a long-acting glycopegylated granulocyte-colony stimulating factor (G-CSF) approved for the management of chemotherapy-induced neutropenia. In general, there is little information on the use of any G-CSFs specifically in patients with urological malignancies receiving chemotherapy. This report combines information from two prospective non-interventional studies on the prophylactic use of lipegfilgrastim in urological cancer patients receiving chemotherapy in the real-world setting.
View Article and Find Full Text PDFThis position statement is an update to the 2011 consensus statement of the Austrian Society of Cardiology (ÖKG) and the Austrian Society of Cardiac Surgery (ÖGTHG) for transfemoral transcatheter aortic valve implantation.Due to a number of recently published studies, broadening of indications and recommendations of medical societies and our own national developments, the ÖKG and the ÖGHTG wish to combine the 2017 ESC/EACTS guidelines for the management of valvular heart disease with a national position paper and to focus on certain details for the application in Austria. Thus, this position statement serves as a supplement and further interpretation of the international guidelines.
View Article and Find Full Text PDFBackground: Pancreatic cancer (PC) ranks among the deadliest malignancies worldwide. In the MPACT study, first-line nab-paclitaxel plus gemcitabine (nab-P/G) demonstrated activity (median overall survival [OS], 8.7 months) and tolerability in patients with metastatic PC (mPC).
View Article and Find Full Text PDFBackground: Selective Plane Illumination Microscopy (SPIM) is a fluorescence imaging technique that allows volumetric imaging at high spatio-temporal resolution to monitor neural activity in live organisms such as larval zebrafish. A major challenge in the construction of a custom SPIM microscope using a scanned laser beam is the control and synchronization of the various hardware components.
New Method: We present an open-source software, μSPIM Toolset, built around the widely adopted MicroManager platform, that provides control and acquisition functionality for a SPIM.
Background: Health-care services are necessary for sustaining and improving human wellbeing, yet they have an environmental footprint that contributes to environment-related threats to human health. Previous studies have quantified the carbon emissions resulting from health care at a global level. We aimed to provide a global assessment of the wide-ranging environmental impacts of this sector.
View Article and Find Full Text PDFBackground: Several clinical trials in chronic phase (CP) chronic myeloid leukemia (CML) showed that early response to tyrosine kinase inhibitor (TKI) treatment results in an improved long-term survival and progression-free survival. This study assessed whether patients achieving early treatment response (ETR; partial cytogenetic response or BCR-ABL1 mRNA ≤10% at 3 months) in daily practice also have a long-term survival benefit.
Methods: The Retrospective Evaluation of Early response in CML for long-term Treatment outcome (R-EFECT), a multicenter, retrospective chart review, documented patients with newly diagnosed CML-CP starting first-line TKI therapy in routine clinical practice.
An amendment to this paper has been published and can be accessed via the original article.
View Article and Find Full Text PDFBackground: The pretreatment De Ritis ratio [aspartate transaminase (AST)/alanine transaminase (ALT)] has been shown to be an adverse prognostic marker in various cancer entities. However, its relevance to advanced pancreatic ductal adenocarcinoma (PDAC) has not yet been studied. In the present study we investigated the AST/ALT ratio as a possible predictor of treatment response and disease outcome in patients with advanced PDAC treated with first-line gemcitabine/nab-paclitaxel.
View Article and Find Full Text PDFBackground: In the past urine was considered sterile. Through the introduction of next generation sequencing, it has become clear that a urinary microbiome exists. Acute kidney injury (AKI) represents a major threat to kidney transplant recipients.
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