UNLABELLED: Cyanobacteria are ubiquitous aquatic organisms with a remarkable evolutionary history reaching as far as 1.9 Ga. They play a vital role in ecosystems yet also raise concerns due to their association with harmful algal blooms. Understanding the historical patterns and drivers behind these blooms is crucial for effective ecosystem management. Lake-sediment cores are valuable natural environmental archives, recording the histories of such blooms. Among others, phycocyanin, a pigment specific to cyanobacteria, emerges as a promising biomarker for reconstructing past cyanobacterial bloom events. However, due to the physicochemical properties of phycocyanin, there is no validated method available to extract and measure this pigment from complex sediment matrix. This study explores the applicability of hyperspectral imaging (HSI), a non-destructive technique, as a novel approach for high resolution in-situ detection and quantification of phycocyanin in lake sediments. Our experiments show that phycocyanin can be detected by HSI with an absorption trough at 620 nm (relative absorption band depth, RABD620). We established a semi-quantitative calibration of the spectral index RABD620 by conducting spiking experiments with phycocyanin standard (known phycocyanin mass) on organic-rich and mineral-rich sediments of varying water contents. We also assessed potential interference from chlorophyll a, another photosynthetic pigment, ensuring the reliability of hyperspectral phycocyanin measurements. Our findings demonstrate a significant correlation (R2 ranging from 0.37 to 0.997) between the RABD620 index and associated phycocyanin amounts in organic-rich and minerogenic sediments. This indicates the potential of the spectral index to directly measure in-situ biomarker concentrations on split sediment cores. Although confounding factors such as water and chlorophyll a content can influence the spectral signal, this method offers a rapid and non-destructive approach for studying historical cyanobacterial blooms in sedimentary records. This opens promising grounds for various applications, including ecosystem-health assessment and environmental change monitoring. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10933-024-00350-y.

• Keywords
• Algal blooms, Cyanobacteria, Environmental change, Paleolimnology, Pigments,
• Publication type
• Journal Article MeSH

UNLABELLED: This study investigates the underlying mechanisms driving the formation of the largest known burial site of the Northern European Mesolithic, Yuzhniy Oleniy Ostrov (YOO). Radiogenic strontium isotope analysis (87Sr/86Sr) was used to identify group dynamics within the cemetery and examine the site's place within local and supra-regional networks. The analysis of 57 humans and 31 animals was supported by the creation of an environmental baseline which identified four key geological zones and defines the strontium characteristics of Lake Onega. Only two individuals had strontium values indicating time spent outside of Lake Onega's northern shores, where the majority of the burial population is likely to have resided. These results suggest that the YOO cemetery predominantly served as a burial place for those with semi-permanent residence in this area, with no significant evidence for gender-based relocation patterns indicative of patri- or matrilocal residency. However, materials seem to have travelled towards Lake Onega even over great distances and the presence of the two outlier individuals suggests these exchanges also involved long-distance travel of people. Our results align with an increasing number of studies that suggest a high degree of residential stability for Late Mesolithic foraging groups relying primarily on aquatic resources, yet simultaneously places the Lake Onega community within a wider Mesolithic communication network. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12520-024-02129-8.

• Keywords
• Bioarchaeology, Geology, Hunter-gatherer-fishers, Mesolithic, Mobility, Strontium,
• Publication type
• Journal Article MeSH

Plasma flows with enhanced dynamic pressure, known as magnetosheath jets, are often found downstream of collisionless shocks. As they propagate through the magnetosheath, they interact with the surrounding plasma, shaping its properties, and potentially becoming geoeffective upon reaching the magnetopause. In recent years (since 2016), new research has produced vital results that have significantly enhanced our understanding on many aspects of jets. In this review, we summarise and discuss these findings. Spacecraft and ground-based observations, as well as global and local simulations, have contributed greatly to our understanding of the causes and effects of magnetosheath jets. First, we discuss recent findings on jet occurrence and formation, including in other planetary environments. New insights into jet properties and evolution are then examined using observations and simulations. Finally, we review the impact of jets upon interaction with the magnetopause and subsequent consequences for the magnetosphere-ionosphere system. We conclude with an outlook and assessment on future challenges. This includes an overview on future space missions that may prove crucial in tackling the outstanding open questions on jets in the terrestrial magnetosheath as well as other planetary and shock environments.

• Keywords
• Bow shock, Foreshock, Magnetopause, Magnetosheath, Magnetosheath jets, Solar wind,
• Publication type
• Journal Article MeSH
• Review MeSH

Reversed-phase ultrahigh-performance liquid chromatography-mass spectrometry (RP-UHPLC/MS) method is optimized for the quantitation of a large number of lipid species in biological samples, primarily in human plasma and serum. The method uses a C18 bridged ethylene hybrid (BEH) column (150 × 2.1 mm; 1.7 μm) for the separation of lipids from 23 subclasses with a total run time of 25 min. Lipid species separation allows the resolution of isobaric and isomeric lipid forms. A triple quadrupole mass spectrometer is used for targeted lipidomic analysis using multiple reaction monitoring (MRM) in the positive ion mode. Data are evaluated by Skyline software, and the concentrations of analytes are determined using internal standards per each individual lipid class.

• Keywords
• High-throughput lipidomics, Mass spectrometry, Plasma, Quantitation, Reversed-phase, Serum, Ultrahigh-performance liquid chromatography,
• MeSH
• Chromatography, Reverse-Phase * methods   MeSH
• Mass Spectrometry methods   MeSH
• Liquid Chromatography-Mass Spectrometry MeSH
• Humans MeSH
• Lipidomics * methods   MeSH
• Lipids * analysis   MeSH
• High-Throughput Screening Assays methods   MeSH
• Software MeSH
• Tandem Mass Spectrometry methods   MeSH
• Chromatography, High Pressure Liquid methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Lipids * MeSH

In esophageal squamous cell carcinoma, genetic activation of NRF2 increases resistance to chemotherapy and radiotherapy, which results in a significantly worse prognosis for patients. Therefore NRF2-activated cancers create an urgent clinical need to identify new therapeutic options. In this context, we previously identified the geldanamycin family of HSP90 inhibitors, which includes 17DMAG, to be synthetic lethal with NRF2 activity. As the first-generation of geldanamycin-derivative drugs were withdrawn from clinical trials due to hepatotoxicity, we designed second-generation compounds with C19-substituted structures in order to inhibit glutathione conjugation-mediated hepatotoxicity. In this study, using a variety of in vitro and in vivo cancer models, we found that C19-substituted 17DMAG compounds maintain their enhanced toxicity profile and synthetic lethal interaction with NRF2-NQO1-activated cancer cells. Importantly, using a xenograft mouse tumor model, we found that C19-substituted 17DMAG displayed significant anticancer efficacy against NRF2-NQO1-activated cancer cells without causing hepatotoxicity. These results clearly demonstrate the improved clinical potential for this new class of HSP90 inhibitor anticancer drugs, and suggest that patients with NRF2-NQO1-activated esophageal carcinoma may benefit from this novel therapeutic approach.

• Keywords
• C19-position substituted geldanamycin derivatives, ESCC, HSP90, NQO1, NRF2-NQO1-activated cancer,
• MeSH
• Benzoquinones * pharmacology   chemistry   MeSH
• NF-E2-Related Factor 2 * metabolism   genetics   MeSH
• Humans MeSH
• Lactams, Macrocyclic * pharmacology   chemistry   MeSH
• Mice, Nude MeSH
• Mice MeSH
• NAD(P)H Dehydrogenase (Quinone) * metabolism   genetics   MeSH
• Cell Line, Tumor MeSH
• Esophageal Neoplasms * drug therapy   metabolism   pathology   MeSH
• HSP90 Heat-Shock Proteins antagonists & inhibitors   metabolism   MeSH
• Antineoplastic Agents * pharmacology   chemistry   MeSH
• Esophageal Squamous Cell Carcinoma * drug therapy   metabolism   MeSH
• Xenograft Model Antitumor Assays MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Benzoquinones * MeSH
• NF-E2-Related Factor 2 * MeSH
• geldanamycin MeSH Browser
• Lactams, Macrocyclic * MeSH
• NAD(P)H Dehydrogenase (Quinone) * MeSH
• NFE2L2 protein, human MeSH Browser
• NQO1 protein, human MeSH Browser
• HSP90 Heat-Shock Proteins MeSH
• Antineoplastic Agents * MeSH

PURPOSE: To evaluate treatment outcomes and toxicity in patients with stage T1-3N0M0 oral cancer treated with surgery followed by high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Retrospective study of 50 patients with stage T1-T3N0 tongue and floor-of-mouth cancer who underwent tumour excision (+ elective neck dissection) followed by postoperative HDR-BT due to the presence of negative prognostic factors (close or positive resection margins, lymphovascular and/or perineural invasion, deep invasion). The plastic tube technique (dose: 18 x 3 Gy b.i.d.) was used. Survival outcomes, toxicity, and prognostic factors were evaluated. RESULTS: At a median follow-up of 81 months (range, 4-121), actuarial 5-year local control (LC), nodal control (NC) and progression-free survival (PFS) rates were 79%, 69%, and 64%. After salvage treatment (surgery + external beam radiotherapy), LC, NC, and PFS increased to 87%, 77%, and 72.3%, respectively. Five-year overall survival and cancer-specific survival (CSS) rates were 73% and 77%. Treatmentrelated toxicity included two cases of mandibular osteoradionecrosis and five cases of small soft tissue necrosis. T stage was significantly correlated with nodal control (p=0.02) and CSS (p=0.04). Tumour grade correlated with DFS (p=0.01). CONCLUSION: Postoperative HDR-BT 18 x 3 Gy b.i.d. seems to be an effective method in patients with T1-3N0M0 oral cancer with negative prognostic factors after tumour resection.

• Keywords
• Brachytherapy, Early oral cancer, Postoperative treatment,
• MeSH
• Brachytherapy * methods   adverse effects   MeSH
• Radiotherapy Dosage MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Mouth Neoplasms * radiotherapy   surgery   pathology   mortality   MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.

• MeSH
• Aortic Valve Stenosis * surgery   complications   MeSH
• Heart Valve Prosthesis Implantation methods   MeSH
• Fractional Flow Reserve, Myocardial * MeSH
• Percutaneous Coronary Intervention * methods   MeSH
• Coronary Artery Bypass * methods   MeSH
• Humans MeSH
• Coronary Artery Disease * surgery   complications   therapy   MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Transcatheter Aortic Valve Replacement * methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Equivalence Trial MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

Bacterial oxygen sensing embodies a fascinating interplay between evolutionary pressures and physiological adaptations to varying oxygen levels. Throughout Earth's history, the composition of the atmosphere has undergone significant changes, from anoxic conditions to the gradual accumulation of oxygen. In response, microbial life has evolved diverse strategies to cope with these shifting oxygen levels, ranging from anaerobic metabolism to oxygen-dependent pathways crucial for energy production and cellular processes typical for eukaryotic, multicellular organisms. Of particular interest is the role of iron in bacterial oxygen sensing systems, which play pivotal roles in adaptation to changing oxygen levels. Only free iron, heme-iron, and non-heme iron directly sense oxygen. These iron-containing proteins, such as heme-containing sensors and iron-sulfur cluster proteins, regulate the expression of genes and activity of enzymes involved in oxidative stress defence, virulence, and biofilm formation, highlighting their significance in bacterial pathogenesis and environmental adaptation. Special attention in the review is paid to the mechanisms of oxygen detection and signal transduction from heme-containing sensing to functional domains in the case of bacterial heme-based oxygen sensors.

• Keywords
• Heme-based sensor, Intramolecular catalytic regulation, Oxygen sensing, Signal transduction,
• MeSH
• Bacteria * metabolism   genetics   MeSH
• Bacterial Proteins metabolism   genetics   MeSH
• Bacterial Physiological Phenomena * MeSH
• Heme * metabolism   MeSH
• Hemeproteins metabolism   MeSH
• Oxygen * metabolism   MeSH
• Gene Expression Regulation, Bacterial MeSH
• Signal Transduction MeSH
• Iron * metabolism   MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Bacterial Proteins MeSH
• Heme * MeSH
• Hemeproteins MeSH
• Oxygen * MeSH
• Iron * MeSH

Degrowth is coming of age, and its analysis of what can be called degrowth spatial politics is advancing rapidly. In this article, we attempt to unravel the history of spatial thought in the degrowth literature to reveal its tendencies, tipping points, and blank spots. We argue that the more recent degrowth spatial literature overly focuses on the big urban scale by reversing what has purportedly been one of the weak spots of degrowth scholarship: its focus and preference for small-scale, relocalization, and decentralized communities. While we see the merit of this shift, first, we try to contextualize it in the broader sustainability discourse, and second, we contend that it has not been without problems and omissions. We see three predicaments stemming from it: first, a deficit of the degrowth spatial literature in recognizing and engaging with unsustainable rural transformations such as rural depopulation and shrinkage, as well as rural dispossession and depeasantisation. Second, a difficulty to account for urban and rural interconnectedness and engage with new epistemological frames that emerge in urban studies, such as planetary urbanization. Third, the urban shift may affect the capacity of degrowth to remain pluriversal, anti-colonial, and grassroots-fueled, or what Chertkovskaya et al. (Towards a political economy of degrowth. Rowman & Littlefield, 2019. https://books.google.com/books?hl=en&lr=&id=PuXaDwAAQBAJ&oi=fnd&pg=PP1&dq=info:c45bQLgYCfYJ:scholar.google.com&ots=5LsDF9Y_Er&sig=buZn4ogpUN4octi3_WFJf1mO9Lg) called nomadic utopianism. Finally, in the concluding part, we set the stepstones for a relational degrowth spatial politics, focusing on a solidary connection of space and place across the urban and rural and in multiple scales. This approach avoids the pitfalls of both degrowth proposals for relocalization and those who put excessive trust in urban transformations alone.

• Keywords
• Degrowth, Depopulation, Planetary urbanization, Post-growth planning, Urban studies, Urbanization, Urban–rural relations, Utopianism,
• Publication type
• Journal Article MeSH

INTRODUCTION AND OBJECTIVES: With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. MATERIALS AND METHODS: This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. RESULTS: Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). CONCLUSIONS: Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. GOV REGISTRATION: NCT04895943.

• Keywords
• Elastography, Intragastric balloon, Liver fibrosis, Non-alcoholic fatty liver disease, Obesity,
• MeSH
• Bariatric Surgery * MeSH
• Time Factors MeSH
• Equipment Design MeSH
• Adult MeSH
• Elasticity Imaging Techniques MeSH
• Weight Loss MeSH
• Liver Cirrhosis * etiology   diagnostic imaging   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Non-alcoholic Fatty Liver Disease * diagnostic imaging   diagnosis   etiology   MeSH
• Obesity * complications   surgery   diagnosis   MeSH
• Pilot Projects MeSH
• Prospective Studies MeSH
• Treatment Outcome MeSH
• Gastric Balloon * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH