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Purpose: QSM provides insight into healthy brain aging and neuropathologies such as multiple sclerosis (MS), traumatic brain injuries, brain tumors, and neurodegenerative diseases. Phase data for QSM are usually acquired from 3D gradient‐echo (3D GRE) scans with long acquisition times that are detrimental to patient comfort and susceptible to patient motion. This is particularly true for scans requiring whole‐brain coverage and submillimeter resolutions. In this work, we use a multishot 3D echo plannar imaging (3D EPI) sequence with shot‐selective 2D CAIPIRIHANA to acquire high‐resolution, whole‐brain data for QSM with minimal distortion and blurring. Methods: To test clinical viability, the 3D EPI sequence was used to image a cohort of MS patients at 1‐mm isotropic resolution at 3 T. Additionally, 3D EPI data of healthy subjects were acquired at 1‐mm, 0.78‐mm, and 0.65‐mm isotropic resolution with varying echo train lengths (ETLs) and compared with a reference 3D GRE acquisition. Results: The appearance of the susceptibility maps and the susceptibility values for segmented regions of interest were comparable between 3D EPI and 3D GRE acquisitions for both healthy and MS participants. Additionally, all lesions visible in the MS patients on the 3D GRE susceptibility maps were also visible on the 3D EPI susceptibility maps. The interplay among acquisition time, resolution, echo train length, and the effect of distortion on the calculated susceptibility maps was investigated. Conclusion: We demonstrate that the 3D EPI sequence is capable of rapidly acquiring submillimeter resolutions and providing high‐quality, clinically relevant susceptibility maps. [ABSTRACT FROM AUTHOR]

An environmental proxy routinely used in paleoecological studies of peatlands is testate amoebae, which are used to infer successional and hydrological shifts through time. However, since many species of protists globally remain undescribed, important ecological information about community assemblages and their interaction with environmental conditions in both the past and present has potential gaps. During the analysis of testate amoeba assemblages from peat cores across the Hudson and James Bay region of Canada, a testate amoeba that has not been formally described was discovered with high abundance in subfossil assemblages (up to 50%). We describe this new species, Pyxidicula muskegii sp. nov., using morphometric measurements of tests from these peat core records and demonstrate its environmental preferences using modern samples collected from the same region. The hemispheric shape and irregular areolar surface pattern on the test, along with its preference for lawns in both fens and bogs, support that P. muskegii is a new species. This species is also found in much lower relative abundance in modern samples (<3%) than in paleo-peat core records. This difference in modern and paleo-assemblage suggests that there is a taphonomic bias in their relative abundance with depth, which we attribute to their organic test that is less prone to decomposition. Therefore, it is critical to include rare taxa within future transfer function models to incorporate their environmental tolerances and improve model predictions. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) and chronic kidney disease (CKD) place significant challenges on the healthcare system, and their co‐existence is associated with shared adverse outcomes. The multinational CaReMe project was initiated to provide contemporary, real‐world epidemiological data on cardiovascular and reno‐metabolic diseases. Utilizing data from the German CaReMe cohort, we characterize a multicentric HF population and describe in‐hospital outcomes stratified for co‐morbid CKD. Methods and results: This retrospective, observational study analysed administrative data from inpatient cases hospitalized in 87 German Helios hospitals between 1 January 2016 and 31 August 2022. The first hospitalization of patients aged ≥18 years with a primary discharge diagnosis of HF, based on ICD‐10 codes, were considered the index cases, and subsequent hospitalizations were considered as readmissions. Baseline characteristics and outcomes were stratified for co‐morbid CKD using ICD‐10‐encoding from the index cases. Cox regression was utilized for readmission endpoints and in‐hospital mortality. In total, 174 829 index cases (mean age 79 ± 15 years, 49.9% female) were included; of these, 55.0% had coexisting CKD. Patients with CKD were older, suffered from worse HF‐related symptoms, had a higher co‐morbidity burden, and in‐hospital mortality was increased at index and during follow‐up. Prevalent CKD was associated with higher rehospitalization rates and was an independent predictor for in‐hospital death. Conclusions: Within this HF inpatient cohort from a multicentric German database, CKD was diagnosed in more than half of the patients and was associated with increased in‐hospital mortality at baseline and during follow‐up. Rehospitalizations were observed earlier and more frequently in patients with HF and co‐morbid CKD. [ABSTRACT FROM AUTHOR]

It is normally supposed that populations of the same species should evolve shared mechanisms of adaptation to common stressors due to evolutionary constraint. Here, we describe a system of within-species local adaptation to coastal habitats, Brassica fruticulosa, and detail surprising strategic variability in adaptive responses to high salinity. These different adaptive responses in neighboring populations are evidenced by transcriptomes, diverse physiological outputs, and distinct genomic selective landscapes. In response to high salinity Northern Catalonian populations restrict root-to-shoot Na+ transport, favoring K+ uptake. Contrastingly, Central Catalonian populations accumulate Na+ in leaves and compensate for the osmotic imbalance with compatible solutes such as proline. Despite contrasting responses, both metapopulations were salinity tolerant relative to all inland accessions. To characterize the genomic basis of these divergent adaptive strategies in an otherwise non-saline-tolerant species, we generate a long-read-based genome and population sequencing of 18 populations (nine inland, nine coastal) across the B. fruticulosa species range. Results of genomic and transcriptomic approaches support the physiological observations of distinct underlying mechanisms of adaptation to high salinity and reveal potential genetic targets of these two very recently evolved salinity adaptations. We therefore provide a model of within-species salinity adaptation and reveal cryptic variation in neighboring plant populations in the mechanisms of adaptation to an important natural stressor highly relevant to agriculture. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment of bladder cancer is still a challenge. New treatment options are required for patients not responding to established chemotherapy (e.g., cisplatin) due to primary or acquired chemoresistance. Bladder cancer cells are known for disturbed epigenetics contributing to resistance. This study aimed to investigate the combination of cisplatin, the class I histone deacetylase inhibitor (HDACi) entinostat, and bromodomain inhibitors (BETis) in two urothelial grade 3 bladder carcinoma cell pairs J82, cisplatin-resistant J82 cisR, T24, and cisplatin-resistant T24 LTT. Our results indicate that treatment of bladder cancer cells with entinostat and a BETi prior to cisplatin can completely reverse cisplatin resistance. This is of particular interest since entinostat and OTX015 (one of the used BETi) are already in clinical trials in other cancers. Thus, this study encourages further preclinical and eventually clinical trials with epigenetic inhibitors in combination with cisplatin to re-establish cisplatin efficacy in bladder cancer. Background/Objectives. Cisplatin is part of the first-line treatment of advanced urothelial carcinoma. Cisplatin resistance is a major problem but may be overcome by combination treatments such as targeting epigenetic aberrances. Here, we investigated the effect of the class I HDACi entinostat and bromodomain inhibitors (BETis) on the potency of cisplatin in two pairs of sensitive and cisplatin-resistant bladder cancer cell lines. Cisplatin-resistant J82cisR and T24 LTT were 3.8- and 24-fold more resistant to cisplatin compared to the native cell lines J82 and T24. In addition, a hybrid compound (compound 20) comprising structural features of an HDACi and a BETi was investigated. Results. We found complete (J82cisR) or partial (T24 LTT) reversal of chemoresistance upon combination of entinostat, JQ1, and cisplatin. The same was found for the BETis JQ35 and OTX015, both in clinical trials, and for compound 20. The combinations were highly synergistic (Chou Talalay analysis) and increased caspase-mediated apoptosis accompanied by enhanced expression of p21, Bim, and FOXO1. Notably, the combinations were at least 4-fold less toxic in non-cancer cell lines HBLAK and HEK293. Conclusions. The triple combination of entinostat, a BETi, and cisplatin is highly synergistic, reverses cisplatin resistance, and may thus serve as a novel therapeutic approach for bladder cancer. [ABSTRACT FROM AUTHOR]

Here we present a new 850-year long coccolithophore record from core SO130-289KL in the northeastern Arabian Sea that spans the Greenland Interstadial 20–Greenland Stadial 20 transition including the timing of the ∼74 ka Youngest Toba Tuff (YTT) supereruption. During the warm interstadial, the coccolithophore assemblage is characterized by Gephyrocapsa oceanica (41%) and Florisphaera profunda (30%) while the succeeding cold stadial is distinguished by the abundance of small placolith species (Emiliania huxleyi + G. ericsonii) (52%). However, the oldest samples of the study interval seem to show a stadial-like coccolithophore assemblage. Spectral analysis revealed an interdecadal cycle imprinted in the coccolithophore record during the interstadial that was also independently reported in other terrestrial and marine proxies. Immediately after the YTT eruption, small placoliths increased by 42% from 5% right below the YTT layer to 47% ∼1 mm above the YTT layer, while G. oceanica and Helicosphaera carteri increased and F. profunda decreased within the ∼1.15 cm layer representing about 8–19 years. Subsequently, the coccolithophore assemblage returned to a composition similar to the warm interstadial period before abruptly changing to a stadial composition characterized by the abundance of small placoliths about 100–130 years after the YTT eruption. Therefore, the YTT eruption had a significant impact on the overall coccolithophore assemblage but appears to have not caused the climate transition from interstadial to stadial conditions, supporting proxy and modeling data. However, the overall mechanism driving the observed changes and cyclicities remains unknown but might be related to rapid atmospheric teleconnections of North Atlantic climate variability to the low latitudes. [ABSTRACT FROM AUTHOR]

The trematodes that cause schistosomiasis in humans require aquatic snails as intermediate hosts. Identifying the genes in snails at which allelic variation controls resistance to infection by schistosomes could lead to novel ways to break the cycle of transmission. We therefore mapped genetic variation within the BS90 population of Biomphalaria glabrata snails that controls their resistance to infection by the SmLE population of Schistosoma mansoni. A marker in the PTC2 genomic region strongly associates with variation in resistance. The S-haplotype, which confers increased susceptibility, appears to be almost completely dominant to the R-haplotype, which confers increased resistance. This result suggests a model in which the parasite must match a molecule on the host side to successfully infect. The genomic region surrounding our marker shows high structural and sequence variability between haplotypes. It is also highly enriched for genes that code for single-pass transmembrane (TM1) genes. Several of the TM1 genes present on the S-haplotype lack orthologs on the R-haplotype, which makes them intriguing candidate genes in a model of dominant susceptibility. These results add to a growing body of work that suggests TM1 genes, especially those in this exceptionally diverse genomic region, may play an important role in snail-schistosome compatibility polymorphisms. Author summary: Schistosomiasis is a parasitic disease of humans that is caused by trematodes in the genus Schistosoma. Schistosomes require aquatic snails as an intermediate host. Infected snails shed parasites into water, which then infect people through their skin. Biomphalaria glabrata host snails show substantial genetic variation for susceptibility to infection by Schistosoma mansoni. Via genome-wide mapping we identified the general location of a gene in the B. glabrata genome at which different alleles control whether snails can be infected or not. The allele that causes susceptibility is dominant to the allele that causes resistance. This uncommon pattern suggests that an invading parasite must match some target on the host side to successfully establish an infection. The mapped snail genomic region contains multiple genes that code for proteins that span cell membranes. These proteins have an extracellular piece that can interact with molecules outside of cells. We hypothesize that these proteins are the targets of molecules produced by the schistosome. If so, then identifying the interacting molecules on the schistosome side, and how they interact with snail proteins, might reveal ways we could genetically modify snails to make them unable to transmit schistosomes to humans. [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic has significantly affected acute ischemic stroke (AIS) care. In this study, we examined the effects of the pandemic on neurosurgical AIS care by means of decompressive surgery (DS). Methods In this retrospective observational study, we compared the characteristics, in-hospital processes, and in-hospital mortality rates among patients hospitalized for AIS during the first four waves of the pandemic (between January 1, 2020 and October 26, 2021) versus the corresponding periods in 2019 (prepandemic). We used administrative data from a nationwide hospital network in Germany. Results Of the 177 included AIS cases with DS, 60 were from 2019 and 117 from the first four pandemic waves. Compared with the prepandemic levels, there were no changes in weekly admissions for DS during the pandemic. The same was true for patient age (range: 51.7–60.4 years), the number of female patients (range: 33.3–57.1%), and the prevalence of comorbidity, as measured by the Elixhauser Comorbidity Index (range: 13.2–20.0 points). Also, no alterations were observed in transfer to the intensive care unit (range: 87.0–100%), duration of in-hospital stay (range: 14.6–22.7 days), and in-hospital mortality rates (range: 11.8–55.6%). Conclusion In Germany, compared with the prepandemic levels, AIS patients undergoing DS during the first four waves of the pandemic showed no changes in demographics, rates of comorbidity, and in-hospital mortality rates. This is in contrast to previous evidence on patients with less critical types of AIS not requiring DS and underlines the uniqueness of the subgroup of AIS patients requiring DS. Our findings suggests that these patients, in contrast to AIS patients in general, were unable to forgo hospitalization during the COVID-19 pandemic. Maintaining the delivery of DS is an essential aspect of AIS care during a pandemic. [ABSTRACT FROM AUTHOR]

The quickly developing drone technology can be used efficiently in the field of pipeline leak detection. The aim of this article is to provide drone mission concepts for detecting releases from pipelines. It provides an overview of the current applications of natural gas pipeline surveys, it considers environmental conditions by plume modelling, it discusses suitable commercially available sensors, and develops concepts for routine monitoring of pipelines and short term missions for localising and identifying a known leakage. Suitable platforms depend on the particular mission and requirements concerning sensors and legislation. As an illustration, a feasibility study during a release experiment is introduced. The main challenge of this study was the variability of wind direction on a time scale of minutes, which produces considerable differences to the plume simulations. Nevertheless, the leakage rates derived from the observations are in the same order of magnitude as the emission rates. Finally the results from the modeling, the release experiment and possible drone scenarios are combined and requirements for future application derived. [ABSTRACT FROM AUTHOR]

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1–18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta‐Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females. [ABSTRACT FROM AUTHOR]

Liquid organic hydrogen carrier (LOHC) systems offer a particularly interesting option for chemical hydrogen storage. In order to characterize and understand the endothermal hydrogen release from the carrier liquid and to evaluate suitable catalyst materials, knowledge of the temperature fields in the dehydrogenation reactor is important. One suitable technique for planar temperature sensing in reacting systems is phosphor thermometry. It is based on the excitation of a luminescent material by a laser pulse and detection of the subsequent phosphorescence signal. We investigated the luminescence of the thermographic phosphor (Sr,Ca)SiAIN3:Eu2+ ("SCASN:Eu2+") dispersed in the H0-DBT / H18-DBT LOHC system in a temperature range from 400 to 600 K. A measurement cell enables repeatable and homogeneous measurement conditions of the hydrogen release reaction. A catalytic plate was put inside the heated LOHC. Temperature fields during the hydrogen release reaction were measured for the first time using the phosphorescence decay time (PDT) and the phosphorescence intensity ratio method (PIR). As expected, a strong cooling at the catalyst surface during the endothermal hydrogen release reaction could be observed, which was quantified to be in the range of 40 K. [ABSTRACT FROM AUTHOR]

Azole-resistant Aspergillus fumigatus (ARAf) fungi have been found inconsistently in the environment in Denmark since 2010. During 2018-2020, nationwide surveillance of clinical A. fumigatus fungi reported environmental TR34/L98H or TR46/Y121F/T289A resistance mutations in 3.6% of isolates, prompting environmental sampling for ARAf and azole fungicides and investigation for selection of ARAf in field and microcosmos experiments. ARAf was ubiquitous (20% of 366 samples; 16% TR34/L98H- and 4% TR46/Y121F/T289A-related mechanisms), constituting 4.2% of 4,538 A. fumigatus isolates. The highest proportions were in flower- and compost-related samples but were not correlated with azole-fungicide application concentrations. Genotyping showed clustering of tandem repeat-related ARAf and overlaps with clinical isolates in Denmark. A. fumigatus fungi grew poorly in the field experiment with no postapplication change in ARAf proportions. However, in microcosmos experiments, a sustained complete (tebuconazole) or partial (prothioconazole) inhibition against wild-type A. fumigatus but not ARAf indicated that, under some conditions, azole fungicides may favor growth of ARAf in soil. [ABSTRACT FROM AUTHOR]

We present a new, annually resolved coccolithophore relative abundance record (1889–1993 CE) from a laminated marine sediment core obtained from the northeastern Arabian Sea to document assemblage variations during the last century. Our analysis revealed that ∼80% of the assemblage is composed of the coccolithophore species Gephyrocapsa oceanica, Emiliania huxleyi, and Florisphaera profunda. Hierarchical clustering of the coccolithophore data delineates time intervals (1889–1909 CE, 1910–1959 CE, 1960–1993 CE) comparable to previously reported interdecadal changes of the El Niño–Southern Oscillation (ENSO)–Indian monsoon variance. We find that F. profunda (Fp%) is positively correlated with central Pacific ENSO (Niño 4 and Niño 3.4). Frequency analyses of Fp% match ENSO quasiperiodicity reported from instrumental data and proxy records and support the existence of previously described ENSO–Indian monsoon teleconnections. Furthermore, the increased variance of Fp% and associated decrease in marine primary productivity starting ∼1960 CE appears to be driven by decreased upward nutrient transport linked to increased surface water stratification due to surface ocean warming. With the predicted increases in frequency and strength of central Pacific El Niño as well as surface ocean warming and upper ocean stratification in the Indian Ocean over the coming century, our results imply further impacts on coccolithophores in the northeastern Arabian Sea that may have cascading effects on the marine food web and global biogeochemical cycles. Plain Language Summary: Coccolithophores are photosynthetic marine plankton with calcium carbonate coverings and form the base of the marine food web. Therefore, documenting the response of coccolithophores to environmental variables over the instrumental period may improve understanding of how they will react to anthropogenic climate change—with important implications for the marine ecosystem. Here, we analyzed coccolithophores preserved in yearly deposited sediments from the Arabian Sea and identified potential drivers of their variations over the last century, a time period highly relevant in societal time frames. Our results show that the coccolithophore assemblage responds in relation to previously described interdecadal changes in the Indian monsoon system and the El Niño–Southern Oscillation (ENSO). We also find a 4–5‐year cycle in the coccolithophore assemblage that matches the ENSO cycle. Atmospheric processes in India related to ENSO may have weakened the Indian monsoon winds, decreased the intensity of surface ocean water mixing and lessened the availability of nutrients. Therefore, nutrient availability is likely the main driver of the changes in the coccolithophore assemblage in our record. Predicted future warming of the oceans might result in further decrease in surface nutrients that may impact coccolithophores and the marine ecosystem. Key Points: A yearly coccolithophore assemblage record from the Arabian Sea documents changes linked to climatic variability in the last centuryChanges in the coccolithophore assemblage composition independently delineate El Niño–Southern Oscillation and Indian monsoon variationsDecreased land–ocean thermal gradients weakened the monsoon and increased water stratification [ABSTRACT FROM AUTHOR]

Simple Summary: While sun exposure and associated tissue changes stemming from ultraviolet radiation are closely associated with the most common forms of skin cancer, far less is known regarding rare types of skin cancer. In this study, for the first time, we used a light microscopy technique to evaluate connective tissue changes in samples from patients with six different types of rare skin cancers, assessing the relationship between these changes, patient age, and whether tumors arose on sun-exposed parts of the body. We found that these tissue changes were most pronounced for patients with specific cancers known to be linked to chronic sun damage and tumors arising on sun-exposed parts of the body. We also noted tumor type-specific trends in terms of sex ratios, sites of tumor presentation, and the relationship between the development of particular tumors and patient immunosuppression. Our results are important and novel as they expand the available data associated with these rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic, and/or therapeutic approaches. (1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes mellitus (T2DM) is a leading cause of chronic kidney disease (CKD) globally. Both conditions substantially worsen patients' prognosis. Current data on German in-hospital CKD cohorts are scarce. The multinational CaReMe study was initiated to evaluate the current epidemiology and healthcare burden of cardiovascular, renal and metabolic diseases. In this substudy, we share real-world data on CKD inpatients stratified for coexisting T2DM derived from a large German hospital network. Methods: This study used administrative data of inpatient cases from 89 Helios hospitals from 01/01/2016 to 28/02/2022. Data were extracted from ICD-10-encoded discharge diagnoses and OPS-encoded procedures. The first case meeting a previously developed CKD definition (defined by ICD-10- and OPS-codes) was considered the index case for a particular patient. Subsequent hospitalizations were analysed for readmission statistics. Patient characteristics and pre-defined endpoints were stratified for T2DM at index case. Results: In total, 48,011 patients with CKD were included in the present analysis (mean age ± standard deviation, 73.8 ± 13.1 years; female, 44%) of whom 47.9% had co-existing T2DM. Patients with T2DM were older (75 ± 10.6 vs 72.7 ± 14.9 years, p < 0.001), but gender distribution was similar to patients without T2DM. The burden of cardiovascular disease was increased in patients with T2DM, and index and follow-up in-hospital mortality rates were higher. Non-T2DM patients were characterised by more advanced CKD at baseline. Patients with T2DM had consistently higher readmission numbers for all events of interest, except for readmissions due to kidney failure/dialysis, which were more common in non-T2DM patients. Conclusion: In this study, we present recent data on hospitalized patients with CKD in Germany. In this CKD cohort, nearly half had T2DM, which substantially affected cardiovascular disease burden, rehospitalization frequency and mortality. Interestingly, non-diabetic patients had more advanced underlying renal disease, which affected renal outcomes. [ABSTRACT FROM AUTHOR]

The marine coccolithophore species Emiliania huxleyi tolerates a broad range of salinity conditions over its near-global distribution, including the relatively stable physiochemical conditions of open-ocean environments and nearshore environments with dynamic and extreme short-term salinity fluctuations. Previous studies show that salinity impacts the physiology and morphology of E. huxleyi, suggesting that salinity stress influences the calcification of this globally important species. However, it remains unclear how rapidly E. huxleyi responds to salinity changes and therefore whether E. huxleyi morphology is sensitive to short-term transient salinity events (such as occur on meteorological timescales) in addition to longer-duration salinity changes. Here, we investigate the real-time growth and calcification response of two E. huxleyi strains isolated from shelf sea environments to the abrupt onset of hyposaline and hypersaline conditions over a time period of 156 h (6.5 d). Morphological responses in the size of the cell covering (coccosphere) and the calcium carbonate plates (coccoliths) that form the coccosphere occurred as rapidly as 24–48 h following the abrupt onset of salinity 25 (hyposaline) and salinity 45 (hypersaline) conditions. Generally, cells tended towards smaller coccospheres (-24 %) with smaller coccoliths (-7 % to -11 %) and reduced calcification under hyposaline conditions, whereas cells growing under hypersaline conditions had either relatively stable coccosphere and coccolith sizes (Mediterranean strain RCC1232) or larger coccospheres (+35 %) with larger coccoliths (+13 %) and increased calcification (Norwegian strain PLYB11). This short-term response is consistent with reported coccolith size trends with salinity over longer durations of low- and high-salinity exposure in culture and under natural-salinity gradients. The coccosphere size response of PLYB11 to salinity stress was greater in magnitude than was observed in RCC1232 but occurred after a longer duration of exposure to the new salinity conditions (96–128 h) compared to RCC1232. In both strains, coccosphere size changes were larger and occurred more rapidly than changes in coccolith size, which tended to occur more gradually over the course of the experiments. Variability in the magnitude and timing of rapid morphological responses to short-term salinity stress between these two strains supports previous suggestions that the response of E. huxleyi to salinity stress is strain specific. At the start of the experiments, the light condition was also switched from a light : dark cycle to continuous light, with the aim of desynchronising cell division. As cell density and mean cell size data sampled every 4 h showed regular periodicity under all salinity conditions, the cell division cycle retained its entrainment to pre-experiment light : dark conditions for the entire experiment duration. Extended acclimation periods to continuous light are therefore advisable for E. huxleyi to ensure successful desynchronisation of the cell division cycle. When working with phased or synchronised populations, data should be compared between samples taken from the same phase of the cell division cycle to avoid artificially distorting the magnitude or even direction of physiological or biogeochemical response to the environmental stressor. [ABSTRACT FROM AUTHOR]

Background: The intensive care unit (ICU) is a scarce resource in all health care systems, necessitating a well-defined utilization. Therefore, benchmarks are essential; and yet, they are limited due to heterogenous definitions of what an ICU is. This study analyzed the case distribution, patient characteristics, and hospital course and outcomes of 6,204,093 patients in the German Helios Hospital Group according to 10 derived ICU definitions. We aimed to set a baseline for the development of a nationwide, uniform ICU definition. Methods: We analyzed ten different ICU definitions: seven derived from the German administrative data set of claims data according to the German Hospital Remuneration Act, three definitions were taken from the Helios Hospital Group's own bed classification. For each ICU definition, the size of the respective ICU population was analyzed. Due to similar patient characteristics for all ten definitions, we selected three indicator definitions to additionally test statistically against IQM. Results: We analyzed a total of 5,980,702 completed hospital cases, out of which 913,402 referred to an ICU criterion (14.7% of all cases). A key finding is the significant variability in ICU population size, depending on definitions. The most restrictive definition of only mechanical ventilation (DOV definition) resulted in 111,966 (1.9%) cases; mechanical ventilation plus typical intensive care procedure codes (IQM definition) resulted in 210,147 (3.5%) cases; defining each single bed individually as ICU or IMC (ICUᴧIMC definition) resulted in 411,681 (6.9%) cases; and defining any coded length of stay at ICU (LOSi definition) resulted in 721,293 (12.1%) cases. Further testing results for indicator definitions are reported. Conclusions: The size of the population, utilization rates, outcomes, and capacity assumptions clearly depend on the definition of ICU. Therefore, the underlying ICU definition should be stated when making any comparisons. From previous studies, we anticipated that 25–30% of all ICU patients should be mechanically ventilated, and therefore, we conclude that the ICUᴧIMC definition is the most plausible approximation. We suggest a mandatory application of a clearly defined ICU term for all hospitals nationwide for improved benchmarking and data analysis. [ABSTRACT FROM AUTHOR]

Aims: Endemic SARS-CoV-2 infections still burden the healthcare system and represent a considerable threat to vulnerable patient cohorts, in particular immunocompromised (IC) patients. This study aimed to analyze the in-hospital outcome of IC patients with severe SARS-CoV-2 infection in Germany. Methods: This retrospective, observational study, analyzed administrative data from inpatient cases (n = 146,324) in 84 German Helios hospitals between 1 January 2022 and 31 December 2022 with regard to in-hospital outcome and health care burden in IC patients during the first 12 months of Omicron dominance. As the primary objective, in-hospital outcomes of patients with COVID-19-related severe acute respiratory infection (SARI) were analyzed by comparing patients with (n = 2037) and without IC diagnoses (n = 14,772). Secondary analyses were conducted on IC patients with (n = 2037) and without COVID-19-related SARI (n = 129,515). A severe in-hospital outcome as a composite endpoint was defined per the WHO definition if one of the following criteria were met: intensive care unit (ICU) treatment, mechanical ventilation (MV), or in-hospital death. Results: In total, 12% of COVID-related SARI cases were IC patients, accounting for 15% of ICU admissions, 15% of MV use, and 16% of deaths, resulting in a higher prevalence of severe in-hospital courses in IC patients developing COVID-19-related SARI compared to non-IC patients (Odds Ratio, OR = 1.4, p < 0.001), based on higher in-hospital mortality (OR = 1.4, p < 0.001), increased need for ICU treatment (OR = 1.3, p < 0.001) and mechanical ventilation (OR = 1.2, p < 0.001). Among IC patients, COVID-19-related SARI profoundly increased the risk for severe courses (OR = 4.0, p < 0.001). Conclusions: Our findings highlight the vulnerability of IC patients to severe COVID-19. The persistently high prevalence of severe outcomes in these patients in the Omicron era emphasizes the necessity for continuous in-hospital risk assessment and monitoring of IC patients. [ABSTRACT FROM AUTHOR]

Aims High-power-short-duration (HPSD) ablation is an effective treatment for atrial fibrillation but poses risks of thermal injuries to the oesophagus and vagus nerve. This study aims to investigate incidence and predictors of thermal injuries, employing machine learning. Methods and results A prospective observational study was conducted at Leipzig Heart Centre, Germany, excluding patients with multiple prior ablations. All patients received Ablation Index-guided HPSD ablation and subsequent oesophagogastroduodenoscopy. A machine learning algorithm categorized ablation points by atrial location and analysed ablation data, including Ablation Index, focusing on the posterior wall. The study is registered in clinicaltrials.gov (NCT05709756). Between February 2021 and August 2023, 238 patients were enrolled, of whom 18 (7.6%; nine oesophagus, eight vagus nerve, one both) developed thermal injuries, including eight oesophageal erythemata, two ulcers, and no fistula. Higher mean force (15.8 ± 3.9 g vs. 13.6 ± 3.9 g, P = 0.022), ablation point quantity (61.50 ± 20.45 vs. 48.16 ± 19.60, P = 0.007), and total and maximum Ablation Index (24 114 ± 8765 vs. 18 894 ± 7863, P = 0.008; 499 ± 95 vs. 473 ± 44, P = 0.04, respectively) at the posterior wall, but not oesophagus location, correlated significantly with thermal injury occurrence. Patients with thermal injuries had significantly lower distances between left atrium and oesophagus (3.0 ± 1.5 mm vs. 4.4 ± 2.1 mm, P = 0.012) and smaller atrial surface areas (24.9 ± 6.5 cm2 vs. 29.5 ± 7.5 cm2, P = 0.032). Conclusion The low thermal lesion's rate (7.6%) during Ablation Index-guided HPSD ablation for atrial fibrillation is noteworthy. Machine learning based ablation data analysis identified several potential predictors of thermal injuries. The correlation between machine learning output and injury development suggests the potential for a clinical tool to enhance procedural safety. [ABSTRACT FROM AUTHOR]

Understanding how anthropogenic activities induce changes in the functional traits of arthropod communities is critical to assessing their ecological consequences. However, we largely lack comprehensive assessments of the long‐term impact of global‐change drivers on the trait composition of arthropod communities across a large number of species and sites. This knowledge gap critically hampers our ability to predict human‐driven impacts on communities and ecosystems.Here, we use a dataset of 1.73 million individuals from 877 species to study how four functionally important traits of carabid beetles and spiders (i.e. body size, duration of activity period, tolerance to drought, and dispersal capacity) have changed at the community level across ~40 years in different types of land use and as a consequence of land use changes (that is, urbanisation and loss of woody vegetation) at the landscape scale in Switzerland.The results show that the mean body size in carabid communities declined in all types of land use, with particularly stronger declines in croplands compared to forests. Furthermore, the length of the activity period and the tolerance to drought of spider communities decreased in most land use types. The average body size of carabid communities in landscapes with increased urbanisation in the last ~40 years tended to decrease. However, the length of the activity period, the tolerance to drought, and the dispersal capacity did not change significantly. Furthermore, urbanisation promoted increases in the average dispersal capacities of spider communities. Additionally, urbanisation favoured spider communities with larger body sizes and longer activity periods. The loss of woody areas at the landscape level was associated with trait shifts to carabid communities with larger body sizes, shorter activity periods, higher drought tolerances and strongly decreased dispersal capacities. Decreases in activity periods and dispersal capacities were also found in spider communities.Our study demonstrates that human‐induced changes in land use alter key functional traits of carabid and spider communities in the long term. The detected trait shifts in arthropod communities likely have important consequences for their functional roles in ecosystems. [ABSTRACT FROM AUTHOR]

Age alters the host's susceptibility to immune induction. Humoral immunity with circulating antibodies, particularly immunoglobulin G (IgG), plays an essential role in immune response. IgG glycosylation in the fragment crystallizable (Fc) region, including sialylation, is important in regulating the effector function by interacting with Fc gamma receptors (FcγRs). Glycosylation is fundamentally changed with age and inflammatory responses. We aimed to explore the regulation of humoral immunity by comparing responses to antigen-induced immune challenges in young and adult mice using a local antigen-induced arthritis mouse model. This study examines the differences in immune response between healthy and immune-challenged states across these groups. Our initial assessment of the arthritis model indicated that adult mice presented more severe knee swelling than their younger counterparts. In contrast, we found that neither histological assessment, bone mineral density, nor the number of osteoclasts differs. Our data revealed an age-associated but not immune challenge increase in total IgG; the only subtype affected by immune challenge was IgG1 and partially IgG3. Interestingly, the sialylation of IgG2b and IgG3 is affected by age and immune challenges but not stimulated further by immune challenges in adult mice. This suggests a shift in IgG towards a pro-inflammatory and potentially pathogenic state with age and inflammation. [ABSTRACT FROM AUTHOR]

Continuous monitoring of physiological signals such as electrocardiogram (ECG) in driving environments has the potential to reduce the need for frequent health check-ups by providing real-time information on cardiovascular health. However, capturing ECG from sensors mounted on steering wheels creates difficulties due to motion artifacts, noise, and dropouts. To address this, we propose a novel method for reliable and accurate detection of heartbeats using sensor fusion with a bidirectional long short-term memory (BiLSTM) model. Our dataset contains reference ECG, steering wheel ECG, photoplethysmogram (PPG), and imaging PPG (iPPG) signals, which are more feasible to capture in driving scenarios. We combine these signals for R-wave detection. We conduct experiments with individual signals and signal fusion techniques to evaluate the performance of detected heartbeat positions. The BiLSTMs model achieves a performance of 62.69% in the driving scenario city. The model can be integrated into the system to detect heartbeat positions for further analysis. [ABSTRACT FROM AUTHOR]

Plant-associated microbes play vital roles in promoting plant growth and health, with plants secreting root exudates into the rhizosphere to attract beneficial microbes. Exudate composition defines the nature of microbial recruitment, with different plant species attracting distinct microbiota to enable optimal adaptation to the soil environment. To more closely examine the relationship between plant genotype and microbial recruitment, we analysed the rhizosphere microbiomes of landrace (Chevallier) and modern (NFC Tipple) barley (Hordeum vulgare) cultivars. Distinct differences were observed between the plant-associated microbiomes of the 2 cultivars, with the plant-growth promoting rhizobacterial genus Pseudomonas substantially more abundant in the Tipple rhizosphere. Striking differences were also observed between the phenotypes of recruited Pseudomonas populations, alongside distinct genotypic clustering by cultivar. Cultivar-driven Pseudomonas selection was driven by root exudate composition, with the greater abundance of hexose sugars secreted from Tipple roots attracting microbes better adapted to growth on these metabolites and vice versa. Cultivar-driven selection also operates at the molecular level, with both gene expression and the abundance of ecologically relevant loci differing between Tipple and Chevallier Pseudomonas isolates. Finally, cultivar-driven selection is important for plant health, with both cultivars showing a distinct preference for microbes selected by their genetic siblings in rhizosphere transplantation assays. Plants secrete root exudates into the rhizosphere to attract beneficial microbes. This study shows that barley genotype exerts multi-level selective pressure on the soil Pseudomonas population, affecting overall abundance, genotype and individual genetic features as well as expression of specific genes. [ABSTRACT FROM AUTHOR]

Kavango Zambezi (KAZA) is the world's largest terrestrial Transfrontier Conservation Area (TFCA), covering vast regions of Angola, Botswana, Namibia, Zambia and Zimbabwe. Elephants and other species traverse KAZA across national borders through both protected and inhabited landscapes along wildlife migration corridors. Zimbabwe's Simangani ward is located within such a corridor. As in most rural areas of KAZA, subsistence farming constitutes the predominant livelihood strategy in Simangani. Research across KAZA has mostly focused either on climate- or wildlife-induced impacts on farming communities. This paper combines findings from in-depth, qualitative fieldwork with quantitative livelihood survey data and provides a detailed assessment from a farming-household perspective of on-farm and off-farm income sources, which are mobilised in order to mitigate grain harvest shortfalls resulting from climatic fluctuations and wildlife depredation. This study concludes that drought and other stressors have a considerably higher impact on food insecurity than unintended conservation impacts. However, it also confirms that the impacts of crop raiding and livestock depredation caused by wildlife do indeed trigger additional food security risk factors for farming households whose livelihoods are already under pressure. [ABSTRACT FROM AUTHOR]

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The global impact of the Youngest Toba Tuff (YTT) supereruption is still heavily debated, ranging from having little effects on climate to significantly affecting modern human evolution. Climate models and proxy records show that the eruption may have caused cooling of the Asian landmass, thus impacting regional climate such as the Indian monsoon system. However, the immediate effect of the eruption on the Indian monsoon has not been indisputably demonstrated in any proxy record. Here, we present a paleo‐primary productivity (PP) record in core SO130‐289KL from the northeastern Arabian Sea based on the coccolithophore species Florisphaera profunda transfer function. Florisphaera profunda decreased from ∼30% before the YTT eruption to ∼8% right after the YTT eruption, which translates to an increase in PP by ∼65% from a long‐term average of ∼200 gC/m2/yr for about 8–19 years after the eruption. The duration was estimated using a new error‐weighted mean age of the YTT eruption (73.9 ± 0.1 ka, 2σ uncertainties) based on recent age estimates from ice cores, radiometric dating, and speleothem records. The elevated PP is most likely linked to the deepening of the surface ocean mixed layer driven by strengthened northeasterly Indian winter monsoon winds. This hypothesis is supported by stable oxygen isotope records from speleothem and ice cores, which show indications of a strengthening of the Indian winter monsoon during times of increased PP. Our results support previous modeling studies and provide unequivocal evidence from a marine record for an Indian monsoon response to the supereruption. Plain Language Summary: The Toba eruption ∼74,000 years ago was one of the largest volcanic eruptions in the last 2.58 million years, however its effects on climate and human evolution remain debated because of conflicting results from modeling and paleoclimate studies. Here, we analyzed a unique marine sediment record from the northeastern Arabian Sea that recorded interannual variations of remains of marine phytoplankton called coccolithophores spanning the time of the eruption. We focus on the fossils of the coccolithophore species Florisphaera profunda, a robust proxy for marine primary productivity (PP). The record shows that PP increased for at least 8 years after the eruption, likely due to high nutrient availability related to a deepened ocean surface mixed layer. This deep mixed layer resulted from strengthened northeasterly winds of the Indian winter monsoon which, in turn, were most probably induced by an air pressure gradient formed from a faster cooling of the continents relative to the oceans after the eruption. Our study thus provides a lens into the impact of a supereruption on regional climate and the marine ecosystem through fast interactions of the ocean and the atmosphere. Key Points: Marine primary productivity record from the northeastern Arabian Sea is a proxy for Indian winter monsoon intensityPrimary productivity increased for at least 8 years after the Youngest Toba Tuff supereruptionPrimary productivity was likely driven by strengthened winter winds resulting from volcanically induced differential land–ocean cooling [ABSTRACT FROM AUTHOR]

The boundaries between tissues with different magnetic susceptibilities generate inhomogeneities in the main magnetic field which change over time due to motion, respiration and system instabilities. The dynamically changing field can be measured from the phase of the fMRI data and corrected. However, methods for doing so need multi‐echo data, time‐consuming reference scans and/or involve error‐prone processing steps, such as phase unwrapping, which are difficult to implement robustly on the MRI host. The improved dynamic distortion correction method we propose is based on the phase of the single‐echo EPI data acquired for fMRI, phase offsets calculated from a triple‐echo, bipolar reference scan of circa 3–10 s duration using a method which avoids the need for phase unwrapping and an additional correction derived from one EPI volume in which the readout direction is reversed. This Reverse‐Encoded First Image and Low resoLution reference scan (REFILL) approach is shown to accurately measure B0 as it changes due to shim, motion and respiration, even with large dynamic changes to the field at 7 T, where it led to a > 20% increase in time‐series signal to noise ratio compared to data corrected with the classic static approach. fMRI results from REFILL‐corrected data were free of stimulus‐correlated distortion artefacts seen when data were corrected with static field mapping. The method is insensitive to shim changes and eddy current differences between the reference scan and the fMRI time series, and employs calculation steps that are simple and robust, allowing most data processing to be performed in real time on the scanner image reconstruction computer. These improvements make it feasible to routinely perform dynamic distortion correction in fMRI. [ABSTRACT FROM AUTHOR]

Objective: With a lack of experimental designs in psychotherapy/counselling process research, evidence is limited regarding which therapeutic style is helpful for which patient and the role of expectations. Therefore, the aim of this experimental study was to manipulate the therapeutic style and clients' expectations towards psychological counselling and investigate their effects on counselling outcome. Method: Eighty healthy participants (74% female, Mage = 31.2 years, SDage = 12.21) received a single counselling session focussing on interpersonal conflicts. We defined two therapeutic styles (relationship‐focussed vs. problem‐focussed) based on the interpersonal circumplex, and participants were led to believe they would receive one of the two styles. In the actual counselling session, they received either the expected or the contrary, resulting in a 2 x 2 design. Primary outcome rated by participants was subjective impairment caused by the conflict 2 weeks after the session; secondary outcomes were satisfaction with the session and perceived working alliance. Results: The successful implementation of the proposed therapeutic styles was confirmed by adherence ratings (U = 25.50, p < 0.001) and ratings of counsellors' behaviour in the circumplex model (p < 0.001) for the friendly and hostile dimensions. Impairment was significantly reduced 2 weeks after the counselling session, but this effect was dependent on neither the therapeutic style, clients' expectations, nor their interaction. Discussion: The study provides the first evidence that a single counselling session appears to be effective in alleviating impairment caused by an interpersonal conflict, independent of the counselling style and client expectations. The novel experimental design provides a basis for further process research in psychological counselling and psychotherapy. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation has become one of the main treatment strategies in patients with premature ventricular complexes (PVC). The successful mapping and ablation can be performed with an ablation catheter without additional diagnostic catheters. Hypothesis: We hypothesize that using a single catheter for PVC ablation may decrease complications, procedure time, and fluoroscopy exposure while maintaining comparable success rates. Methods: Sixty‐nine consecutive patients with PVC were treated with a single catheter approach compared to a historical cohort, in which a conventional setup was used. Propensity score matching was conducted with a 1:1 ratio. Outcome parameters included acute procedural success with elimination of all premature ventricular contractions after catheter ablation, procedural data as well as complication rates. Results: Patients treated with a single catheter approach had shorter total procedure (60 minutes [IQR: 47,5–69,0 minutes] vs. 90 minutes [IQR 60–120 minutes]; p = 0.001) and fluoroscopy times (218 seconds [IQR: 110,5–446 seconds] vs. 310 seconds [IQR 190–640 seconds]; p = 0.012), which consecutively leads to a reduction of radiation exposure signified by a lower dose area product (155 cGycm² [IQR 74.4–334.5 cGycm²] vs. 368.4 cGycm² [IQR: 126–905.4 cGycm²]; p value 0.009). Acute procedural success rates were comparable in both groups (54 [84.3%] in the single catheter approach group and 58 [90.6%] in the conventional group; p: 0.287). Conclusion: A single catheter approach for the treatment of PVC is associated with a reduction of procedure‐ and fluoroscopy time, as well as a lesser radiation exposure, while maintaining equivalent acute success and complication rates compared with a conventionally used catheter setup. [ABSTRACT FROM AUTHOR]

Adeno-associated viruses (AAV) are currently predominant viral transfer tools for gene therapy, and efforts are being made to design faster and more efficient methods and technologies for their manufacturing. The early selection of high-performing filters is essential for developing an ultrafiltration and diafiltration (UF/DF) process, especially when feed material is scarce, and timelines are short. However, few methods and technologies exist to enable process optimization with multiple variations in a single run. In this study, we explored the potential of Ambr® Crossflow for high-throughput, automated screening of different membrane materials, pore sizes and different process conditions for the UF/DF step of AAV8. The best overall performance was obtained with a 100 kDa PES flat sheet cassette. The UF/DF process was further transferred to a larger scale to the Sartoflow® Smart Tangential Flow Filtration (TFF) system using a 100 kDa PES Sartocon® Slice 200 cassette and compared to a 100 kDa PES hollow fiber. Virus recovery, permeate flux and total protein removal values of the flat sheet cassette were similar to those achieved in small-scale devices, and higher than those of the hollow fiber, thus demonstrating similar performance at a larger process scale. The high-throughput, automated method described herein allowed to screen multiple materials and process parameters of a UF/DF process in a time- and resource-efficient way, making it a useful tool to accelerate early-stage downstream process development of AAV. [ABSTRACT FROM AUTHOR]

Camelina is an oil seed crop that is enjoying increasing interest because it has a particularly valuable fatty acid profile, is modest regarding its water and nutrient requirements, and is comparatively resilient to abiotic and biotic stress factors. The regeneration of plants from cells accessible to genetic manipulation is an essential prerequisite for the generation of genetically engineered plants, be it by transgenesis or genome editing. Here, immature embryos were used on the assumption that their incomplete differentiation was associated with totipotency. In culture, regenerative structures appeared adventitiously at the embryos' hypocotyls. For this, the application of auxin- or cytokinin-type growth regulators was essential. The formation of regenerative structures was most efficient when indole-3-acetic acid was added to the induction medium at 1 mg/L, zygotic embryos of the medium walking stick stage were used, and their hypocotyls were stimulated by pricking to a wound response. Histological examinations revealed that the formation of adventitious shoots was initiated by locally activated cell division and proliferation in the epidermis and the outer cortex of the hypocotyl. While the regeneration of plants was established in principle using the experimental line Cam139, the method proved to be similarly applicable to the current cultivar Ligena, and hence it constitutes a vital basis for future genetic engineering approaches. [ABSTRACT FROM AUTHOR]

The marine coccolithophore species Emiliania huxleyi tolerates a broad range of salinity conditions over its near-global distribution, including the relatively stable physiochemical conditions of open ocean environments and nearshore environments with dynamic and extreme short-term salinity fluctuations. Previous studies show that salinity impacts the physiology and morphology of E. huxleyi , suggesting that salinity stress influences the calcification of this globally important species. However, it remains unclear how rapidly E. huxleyi responds to salinity changes and therefore whether E. huxleyi morphology is sensitive to short-term, transient salinity events (such as occur on meteorological timescales) in addition longer duration salinity changes. Here, we investigate the real-time growth and calcification response of two E. huxleyi strains isolated from shelf-sea environments to the abrupt onset of hyposaline and hypersaline conditions over a time periods of 156 h (6.5 days). Morphological responses in the size of the cellular exoskeleton (coccosphere) and the calcium carbonate plates (coccoliths) that form the coccosphere occurred as rapidly as 24–48 h following the abrupt onset of salinity 25 (hyposaline) and salinity 45 (hypersaline) conditions. Generally, cells tended towards smaller coccospheres (-24 %) with smaller coccoliths (-7 to -11 %) and reduced calcification under hyposaline conditions whereas cells growing under hypersaline conditions had either relatively stable coccosphere and coccolith sizes (Mediterranean strain RCC1232) or larger coccospheres (+35 %) with larger coccoliths (+13 %) and increased calcification (Norwegian strain PLYB11). This short-term response is consistent with reported coccolith size trends with salinity over longer durations of low and high salinity exposure in culture and under natural salinity gradients. The coccosphere size response of PLYB11 to salinity stress was greater in magnitude than observed in RCC1232 but occurred after a longer duration of exposure (ca. 96–128 h) to the new salinity conditions compared to RCC1232. In both strains, coccosphere size changes were larger and occurred more rapidly than changes in coccolith size, which tended to occur more gradually over the course of the experiments. Variability in the magnitude and timing of rapid morphological responses to short-term salinity stress between these two strains supports previous suggestions that the response of E. huxleyi to salinity stress is strain specific. At the start of the experiments, the light condition was also switched from a light: dark cycle to continuous light with the aim of desynchronising cell division. As cell density and mean cell size data sampled every 4 h showed regular periodicity under all salinity conditions, the cell division cycle retained its entrainment to pre-experiment light: dark conditions for the entire experiment duration. Extended acclimation periods to continuous light are therefore advisable for E. huxleyi to ensure successful desynchronisation of the cell division cycle. When working with phased or synchronised populations, data should be compared between samples taken from the same phase of the cell division cycle to avoid artificially distorting the magnitude or even direction of physiological or (bio)geochemical response to the environmental stressor. [ABSTRACT FROM AUTHOR]

The marine coccolithophore species Emiliania huxleyi tolerates a broad range of salinity conditions over its near global distribution, including the relatively stable physiochemical conditions of open ocean environments and nearshore environments with dynamic and extreme short-term salinity fluctuations. Previous studies show that salinity impacts the physiology and morphology of E. huxleyi, suggesting that salinity stress influences the calcification of this globally important species. However, it remains unclear how rapidly E. huxleyi responds to salinity changes and therefore whether E. huxleyi morphology is sensitive to short-term, transient salinity events (such as occur on meteorological timescales) in addition longer duration salinity changes. Here, we investigate the real-time growth and calcification response of two E. huxleyistrainsisolated from shelf-sea environments to the abrupt onset of hyposaline and hypersaline conditions over a time periods of 156 h (6.5 days). Morphological responses in the size of the cellular exoskeleton (coccosphere) and the calcium carbonate plates (coccoliths) that form the coccosphere occurred as rapidly as 24-48 h following the abrupt onset of salinity 25 (hyposaline) and salinity 45 (hypersaline) conditions. Generally, cells tended towards smaller coccospheres (-24%) with smaller coccoliths (-7 to -11%) and reduced calcification under hyposaline conditions whereas cells growing under hypersaline conditions had either relatively stable coccosphere and coccolith sizes (Mediterranean strain RCC1232) or larger coccospheres (+35%) with larger coccoliths (+13%) and increased calcification (Norwegian strain PLYB11). This short-term response is consistent with reported coccolith size trends with salinity over longer durations of low and high salinity exposure in culture and under natural salinity gradients. The coccosphere size response of PLYB11 to salinity stress was greater in magnitude than observed in RCC1232 but occurred after a longer duration of exposure (ca. 96-128 h) to the new salinity conditions compared to RCC1232. In both strains, coccosphere size changes were larger and occurred more rapidly than changes in coccolith size, which tended to occur more gradually over the course of the experiments. Variability in the magnitude and timing of rapid morphological responses to short-term salinity stress between these two strains supports previous suggestions that the response of E. huxleyi to salinity stress is strain specific. At the start of the experiments, the light condition was also switched from a light: dark cycle to continuous light with the aim of desynchronising cell division. As cell density and mean cell size data sampled every 4 h showed regular periodicity under all salinity conditions, the cell division cycle retained its entrainment to pre-experiment light: dark conditions for the entire experiment duration. Extended acclimation periods to continuous light are therefore advisable for E. huxleyi to ensure successful desynchronisation of the cell division cycle. When working with phased or synchronised populations, data should be compared between samples taken from the same phase of the cell division cycle to avoid artificially distorting the magnitude or even direction of physiological or (bio)geochemical response to the environmental stressor. [ABSTRACT FROM AUTHOR]

Background: Control and elimination of schistosomiasis is an arduous task, with current strategies proving inadequate to break transmission. Exploration of genetic approaches to interrupt Schistosoma mansoni transmission, the causative agent for human intestinal schistosomiasis in sub-Saharan Africa and South America, has led to genomic research of the snail vector hosts of the genus Biomphalaria. Few complete genomic resources exist, with African Biomphalaria species being particularly underrepresented despite this being where the majority of S. mansoni infections occur. Here we generate and annotate the first genome assembly of Biomphalaria sudanica sensu lato, a species responsible for S. mansoni transmission in lake and marsh habitats of the African Rift Valley. Supported by whole-genome diversity data among five inbred lines, we describe orthologs of immune-relevant gene regions in the South American vector B. glabrata and present a bioinformatic pipeline to identify candidate novel pathogen recognition receptors (PRRs). Results: De novo genome and transcriptome assembly of inbred B. sudanica originating from the shoreline of Lake Victoria (Kisumu, Kenya) resulted in a haploid genome size of ~ 944.2 Mb (6,728 fragments, N50 = 1.067 Mb), comprising 23,598 genes (BUSCO = 93.6% complete). The B. sudanica genome contains orthologues to all described immune genes/regions tied to protection against S. mansoni in B. glabrata, including the polymorphic transmembrane clusters (PTC1 and PTC2), RADres, and other loci. The B. sudanica PTC2 candidate immune genomic region contained many PRR-like genes across a much wider genomic region than has been shown in B. glabrata, as well as a large inversion between species. High levels of intra-species nucleotide diversity were seen in PTC2, as well as in regions linked to PTC1 and RADres orthologues. Immune related and putative PRR gene families were significantly over-represented in the sub-set of B. sudanica genes determined as hyperdiverse, including high extracellular diversity in transmembrane genes, which could be under pathogen-mediated balancing selection. However, no overall expansion in immunity related genes was seen in African compared to South American lineages. Conclusions: The B. sudanica genome and analyses presented here will facilitate future research in vector immune defense mechanisms against pathogens. This genomic/transcriptomic resource provides necessary data for the future development of molecular snail vector control/surveillance tools, facilitating schistosome transmission interruption mechanisms in Africa. [ABSTRACT FROM AUTHOR]

Aim: The microclimate and light conditions on the forest floor are strongly modified by tree canopies. Therefore, we need to better consider the micro‐environment when quantifying trait–environment relationships for forest understorey plants. Here, we quantify relationships between micro‐environmental conditions and plant functional traits at the community level, including intraspecific trait variation, and their relationship with microclimate air temperature, light and soil properties. Location: Deciduous temperate forests across Europe. Time period: 2018. Major taxa studied: Herbaceous vegetation. Methods: We sampled 225 plots across 15 regions along four complementary gradients capturing both macro‐ and microclimatic conditions including latitude, elevation, forest management and distance to forest edges. We related the community‐weighted mean of five plant functional traits (plant height, specific leaf area [SLA], plant carbon [C], plant nitrogen [N] and plant C:N ratio) across 150 vascular plant species to variation in local microclimate air temperature, light and soil properties. We tested the effect of accounting for intraspecific variation in trait–environment relationships and performed variation partitioning to identify major drivers of trait variation. Results: Microclimate temperature, light availability and soil properties were all important predictors of community‐weighted mean functional traits. When light availability and variation in temperature were higher, the herb community often consisted of taller plants with a higher C:N ratio. In more productive environments (e.g. with high soil nitrogen availability), the community was dominated by individuals with resource‐acquisitive traits: high SLA and N but low C:N. Including intraspecific trait variation increased the strength of the trait–micro‐environment relationship, and increased the importance of light availability. Main conclusions: The trait–environment relationships were much stronger when the micro‐environment and intraspecific trait variation were considered. By locally steering light availability and temperature, forest managers can potentially impact the functional signature of the forest herb‐layer community. [ABSTRACT FROM AUTHOR]

Aims Recurrences of ventricular tachycardia (VT) after initial catheter ablation is a significant clinical problem. In this study, we report the efficacy and risks of repeat VT ablation in patients with structural heart disease (SHD) in a tertiary single centre over a 7-year period. Methods and results Two hundred ten consecutive patients referred for repeat VT ablation after previous ablation in our institution were included in the analysis (53% ischaemic cardiomyopathy, 91% males, median age 65 years, mean left ventricular ejection fraction 35%). After performing repeat ablation, the clinical VTs were acutely eliminated in 82% of the patients, but 46% of the cohort presented with VT recurrence during the 25-month follow-up. Repeat ablation led to a 73% reduction of shock burden in the first year and 61% reduction until the end of follow-up. Similarly, VT burden was reduced 55% in the first year and 36% until the end of the study. Fifty-two patients (25%) reached the combined endpoint of ventricular assist device implantation, heart transplantation, or death. Advanced New York Heart Association functional class, anteroseptal substrate, and periprocedural complication after repeat ablation were associated with worse prognosis independently of the type of cardiomyopathy. Conclusion While complete freedom from VT after repeat ablation in SHD was difficult to achieve, ablation led to a significant reduction in VT and shock burden. Besides advanced heart failure characteristics, anteroseptal substrate and periprocedural complications predicted a worse outcome. [ABSTRACT FROM AUTHOR]

Over the last 30 years, the prevalence of osteoarthritis (OA), a disease characterized by a loss of articular cartilage, has more than doubled worldwide. Patients suffer from pain and progressive loss of joint function. Cartilage is an avascular tissue mostly consisting of extracellular matrix with embedded chondrocytes. As such, it does not regenerate naturally, which makes an early onset of OA prevention and treatment a necessity to sustain the patients' quality of life. In recent years, tissue engineering strategies for the regeneration of cartilage lesions have gained more and more momentum. In this study, we aimed to investigate the scaffold-free 3D cartilage tissue formation under simulated microgravity in the NASA-developed rotating wall vessel (RWV) bioreactor. For this purpose, we cultured both primary human chondrocytes as well as cells from the immortalized line C28/I2 for up to 14 days on the RWV and analyzed tissue morphology, development of apoptosis, and expression of cartilage-specific proteins and genes by histological staining, TUNEL-assays, immunohistochemical detection of collagen species, and quantitative real-time PCR, respectively. We observed spheroid formation in both cell types starting on day 3. After 14 days, constructs from C28/I2 cells had diameters of up to 5 mm, while primary chondrocyte spheroids were slightly smaller with 3 mm. Further inspection of the 14-day-old C28/I2 spheroids revealed a characteristic cartilage morphology with collagen-type 1, -type 2, and -type 10 positivity. Interestingly, these tissues were less susceptible to RWV-induced differential gene expression than those formed from primary chondrocytes, which showed significant changes in the regulation of IL6, ACTB, TUBB, VIM, COL1A1, COL10A1, MMP1, MMP3, MMP13, ITGB1, LAMA1, RUNX3, SOX9, and CASP3 gene expression. These diverging findings might reflect the differences between primary and immortalized cells. Taken together, this study shows that simulated microgravity using the RWV bioreactor is suitable to engineer dense 3D cartilage-like tissue without addition of scaffolds or any other artificial materials. Both primary articular cells and the stable chondrocyte cell line C28/I2 formed 3D neocartilage when exposed for 14 days to an RWV. [ABSTRACT FROM AUTHOR]

Most Asian countries exhibit modest income levels and low insurance penetration, while facing rising exposures to natural disasters due to climate change. This paper discusses a strategy for regional collaboration among Asian countries to build resilience through participation in a regional insurance pool. At the core of this strategy is a new type of Climate De-risk Insurance (CDRI) product, where a portion (10–20 %) of the premium is designated for risk assessment and mitigation as compared to conventional loss coverage. CDRI products are offered through commercial insurance companies in participating countries and distributed through a network of dedicated risk management agencies. CDRI insurance needs to be guided by enabling regulation, with greater emphasis on the effectiveness of the use of funds in risk mitigation and claims payments. Moreover, the CDRI development fund can be created in the form of a public-private partnership, as a means of mobilizing financial support for rolling out CDRI insurance. [ABSTRACT FROM AUTHOR]

While many studies on insect diversity report declines, others show stable, fluctuating or increasing trends. For a thorough understanding of insect trends and their effects on ecosystem functioning, it is important to simultaneously assess insect richness, abundance and biomass, and to report trends for multiple taxa.We analysed insect richness, abundance and biomass data for all insects and for eight insect taxa (Buprestidae, Cerambycidae, Carabidae, other Coleoptera, Aculeata, other Hymenoptera, Heteroptera and Lepidoptera) from 42 sites across Switzerland from 2000 to 2007, representing three major habitat types in Switzerland (agricultural, unmanaged [open and forested] and managed forest habitats). As potential drivers of temporal patterns, we evaluated weather‐ and land‐use‐related factors. As predictors, we included temperature and precipitation as well as the vegetation index and the habitat type, respectively.We found a consistent pattern of stable or increasing trends for richness, abundance and biomass of insects in total and the eight taxa over 8 years. Both overall patterns and six out of eight taxa (except for Cerambycidae and Lepidotpera) showed the highest values in agricultural habitats. However, when accounting for elevation, there was no difference in open habitats regardless of whether they were used agriculturally.Habitat types were the most important predictors, followed by weather‐ and vegetation‐related factors. Modelled responses to mean temperature were unimodal, whereas the standard deviation of temperature showed positive and precipitation negative effects. Longer time series are needed to draw robust inferences and to investigate potential negative effects of future warming. [ABSTRACT FROM AUTHOR]

Background: Estimating the risks and impacts of COVID-19 for different health groups at the population level is essential for orienting public health measures. Adopting a population-based approach, we conducted a systematic review to explore: (1) the etiological role of multimorbidity and frailty in developing SARS-CoV-2 infection and COVID-19-related short-term outcomes; and (2) the prognostic role of multimorbidity and frailty in developing short- and long-term outcomes. This review presents the state of the evidence in the early years of the pandemic. It was conducted within the European Union Horizon 2020 program (No: 101018317); Prospero registration: CRD42021249444. Methods: PubMed, Embase, World Health Organisation COVID-19 Global literature on coronavirus disease, and PsycINFO were searched between January 2020 and 7 April 2021 for multimorbidity and 1 February 2022 for frailty. Quantitative peer-reviewed studies published in English with population-representative samples and validated multimorbidity and frailty tools were considered. Results: Overall, 9,701 records were screened by title/abstract and 267 with full text. Finally, 14 studies were retained for multimorbidity (etiological role, n = 2; prognostic, n = 13) and 5 for frailty (etiological role, n = 2; prognostic, n = 4). Only short-term outcomes, mainly mortality, were identified. An elevated likelihood of poorer outcomes was associated with an increasing number of diseases, a higher Charlson Comorbidity Index, different disease combinations, and an increasing frailty level. Discussion: Future studies, which include the effects of recent virus variants, repeated exposure and vaccination, will be useful for comparing the possible evolution of the associations observed in the earlier waves. [ABSTRACT FROM AUTHOR]

Somatostatin-expressing interneurons (SOMIs) in the mouse dentate gyrus (DG) receive feedforward excitation from granule cell (GC) mossy fiber (MF) synapses and provide feedback lateral inhibition onto GC dendrites to support environment representation in the DG network. Although this microcircuitry has been implicated in memory formation, little is known about activity-dependent plastic changes at MF-SOMI synapses and their influence on behavior. Here, we report that the metabotropic glutamate receptor 1α (mGluR1α) is required for the induction of associative long-term potentiation (LTP) at MF-SOMI synapses. Pharmacological block of mGluR1α, but not mGluR5, prevented synaptic weight changes. LTP at MF-SOMI synapses was postsynaptically induced, required increased intracellular Ca2+, involved G-protein-mediated and Ca2+-dependent (extracellular signal-regulated kinase) ERK1/2 pathways, and the activation of NMDA receptors. Specific knockdown of mGluR1α in DG-SOMIs by small hairpin RNA expression prevented MF-SOMI LTP, reduced SOMI recruitment, and impaired object location memory. Thus, postsynaptic mGluR1α-mediated MF-plasticity at SOMI input synapses critically supports DG-dependent mnemonic functions. [ABSTRACT FROM AUTHOR]