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Abstract Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE−). Blood samples were collected from 30 EE+ and 15 EE− in La Rinconada (Peru, 5100–5300 m a.s.l.), with special attention given to the sampling pre‐analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet‐poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE− and LL (all P

Abstract Characterizing and understanding the processes that shape the structure of ecological networks, which represent who interacts with whom in a community, has many implications in ecology, evolutionary biology and conservation. A highly debated question is whether and how the structure of a bipartite ecological network differs between antagonistic (e.g. herbivory) and mutualistic (e.g. pollination) interaction types. Here, we tackle this question by using a multiscale characterization of network structure, machine learning tools, and a large database of empirical and simulated bipartite networks. Contrary to previous studies focusing on global structural metrics, such as nestedness and modularity, which concluded that antagonistic and mutualistic networks cannot be told apart from only their structure, we find that they can be told apart by combining a meso‐scale characterization of their structure and supervised machine learning. Motif frequencies appear particularly informative, with an over‐representation of densely connected motifs in antagonistic networks and of motifs with asymmetrical specialization in mutualistic networks. These structural properties can be used to predict the type of interaction with relatively good confidence. Beyond this classical mutualism/antagonism dichotomy, we also find significant structural uniqueness linked to specific ecologies (e.g. pollination, parasitism). Our results clarify structural differences between antagonistic and mutualistic networks and suggest the investigation of the structural uniqueness of specific ecologies as a promising approach for characterizing interactions beyond the coarse antagonistic/mutualistic dichotomy.

Abstract A minequake of magnitude ML 4.1 occurred on 18 May 2020 early in the morning at the LKAB underground iron ore mine in Kiruna, Sweden. This is the largest mining‐induced earthquake in Scandinavia. It generated acoustic signals observed at three infrasound arrays at 9.3 (KRIS, Sweden), 155 (IS37, Norway), and 286 km (ARCI, Norway) distance. We perform full‐waveform focal mechanism inversion based on regional seismic data and local infrasound data. These independently highlight that this event was dominated by a shallow‐depth collapse in agreement with in‐mine seismic station data. However, regional infrasound data cannot inform the inversion process without an accurate model of atmospheric winds and temperatures. Yet, our numerical simulations demonstrate a potential of using local and regional infrasound data to constrain an event's focal mechanism and depth.

Key Clinical Message 18F‐FDG PET/CT has clinical relevance in HCL at diagnosis and for the follow‐up of patients treated, especially in case of atypical presentations such as bone involvements (which are probably underestimated) and poor bone marrow infiltration. Abstract Bone lesions are rarely reported in Hairy Cell Leukemia (HCL). We report two BRAFV600E mutated HCL patients presented bone lesions at foreground, poor bone marrow involvement, and the important role 18F‐FDG PET/CT played in their management. We discuss the crucial role that 18F‐FDG PET/CT could play in HCL routine practice.

Abstract Domain of unknown function 239 (DUF239) is a conserved sequence found in the catalytic site of Neprosins which are specific secreted prolyl endopeptidases found in the Nepenthes genus. Neprosins participate in the nitrogen cycle by digesting preys trapped in the pitcher of these carnivorous plants. Apart from that, DUF239s have been poorly documented in plants. We have identified 50 genes containing DUF239‐coding sequences in the Arabidopsis genome that are distributed across six distinct phylogenetic clusters. The chromosomal distribution suggests that several genes are the result of recent duplication events, with up to eight genes found in a strict tandem distribution. In Arabidopsis, most of DUF239‐containing sequences are also associated to a Neprosin‐activating domain (DUF4409) and an amino‐terminal α‐helix which corresponds to the typical domain organization of the Neprosins described in the Nepenthes genus. Analysis of Arabidopsis transcriptomic datasets reveals that 39 genes are exclusively expressed in reproductive organs, mainly during seed development and more specifically in the endosperm (23 genes). The peculiar expression pattern of the DUF239 gene family in Arabidopsis suggests new functions of Neprosin‐like proteins in plants during seed development.

Abstract Objective Patients with drug‐resistant epilepsy (DRE) pose considerable management challenges for patients, their families, and providers. Both the vagus nerve stimulator (VNS) and the ketogenic diet (KD) have been shown to be safe and effective in treating DRE. Nevertheless, information is lacking regarding treatment with combination of both modalities. This study reports the efficacy and tolerability of combining VNS and KD in a pediatric cohort with intractable epilepsy. Methods This is a retrospective review of 33 patients (0‐17 years) with DRE treated with VNS and KD at a single pediatric level IV epilepsy center. We compared seizure reduction rates for each patient at baseline and at every clinic visit for 24 months after adding the second nonpharmacological therapy. The frequency of adverse events on the combined therapy was collected to assess safety and tolerability. Results There were a total of 170 visits for all patients while on the combined therapy. At 88% (95% CI: 83%‐93%) of the visits, patients reported some reduction in seizure frequency. The proportion of patients reporting a greater than 50% seizure reduction over all visits was 62% (95% CI: 55%‐69%). The proportion of a patient's visits with at least a greater than 50% reduction in seizure frequency had a median of 71% (IQR 33%‐100%). Continued improvement was seen over time of combined treatment; for every one‐unit time unit change (one month), there was a 6% increase in the odds of having a reduction in seizure frequency of >50% (OR = 1.06, 95% CI: 1.01‐1.11). Significance This study shows that combining the VNS and KD in patients with drug‐resistant epilepsy is well tolerated and reduces seizure frequency more than either one modality used alone and that the benefits in terms of seizure reduction continue to increase with the length of treatment.

Abstract Background and Aim The molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real‐life use are lacking. Methods This was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives. Results A total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 μmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury–hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44–54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1‐year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P

Abstract Background Exome sequencing (ES) has become the most powerful and cost‐effective molecular tool for deciphering rare diseases with a diagnostic yield approaching 30%–40% in solo‐ES and 50% in trio‐ES. We applied an innovative parental DNA pooling method to reduce the parental sequencing cost while maintaining the diagnostic yield of trio‐ES. Methods We pooled six (Agilent‐CRE‐v2–100X) or five parental DNA (TWIST‐HCE–70X) aiming to detect allelic balance around 8–10% for heterozygous status. The strategies were applied as second‐tier (74 individuals after negative solo‐ES) and first‐tier approaches (324 individuals without previous ES). Results The allelic balance of parental‐pool variants was around 8.97%. Sanger sequencing uncovered false positives in 1.5% of sporadic variants. In the second‐tier approach, we evaluated than two thirds of the Sanger validations performed after solo‐ES (41/59–69%) would have been saved if the parental‐pool segregations had been available from the start. The parental‐pool strategy identified a causative diagnosis in 18/74 individuals (24%) in the second‐tier and in 116/324 individuals (36%) in the first‐tier approaches, including 19 genes newly associated with human disorders. Conclusions Parental‐pooling is an efficient alternative to trio‐ES. It provides rapid segregation and extension to translational research while reducing the cost of parental and Sanger sequencing.