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Abstract Cerebral malaria (CM), the most lethal complication of Plasmodium falciparum severe malaria (SM), remains fatal for 15–25% of affected children despite the availability of treatment. P. falciparum infects and multiplies in erythrocytes, contributing to anemia, parasite sequestration, and inflammation. An unbiased proteomic assessment of infected erythrocytes and plasma samples from 24 Beninese children was performed to study the complex mechanisms underlying CM. A significant down-regulation of proteins from the ubiquitin–proteasome pathway and an up-regulation of the erythroid precursor marker transferrin receptor protein 1 (TFRC) were associated with infected erythrocytes from CM patients. At the plasma level, the samples clustered according to clinical presentation. Significantly, increased levels of the 20S proteasome components were associated with SM. Targeted quantification assays confirmed these findings on a larger cohort (n = 340). These findings suggest that parasites causing CM preferentially infect reticulocytes or erythroblasts and alter their maturation. Importantly, the host plasma proteome serves as a specific signature of SM and presents a remarkable opportunity for developing innovative diagnostic and prognostic biomarkers.

Purpose Methods Results Conclusion Level of Evidence While restricted kinematic alignment (rKA) total knee arthroplasty (TKA) with cemented implants has been shown to provide a similar survivorship rate to mechanical alignment (MA) in the short term, no studies have reported on the long‐term survivorship and function.One hundred four consecutive cemented cruciate retaining TKAs implanted using computer navigation and following the rKA principles proposed by Vendittoli were reviewed at a minimum of 10 years after surgery. Implant revisions, reoperations and clinical outcomes were assessed using knee injury and osteoarthritis outcome score (KOOS), forgotten joint score (FJS), patients' satisfaction and joint perception questionnaires. Radiographs were analyzed to identify signs of osteolysis and implant loosening.Implant survivorship was 99.0% at a mean follow‐up of 11.3 years (range: 10.3–12.9) with one early revision for instability. Patients perceived their TKA as natural or artificial without limitation in 50.0% of cases, and 95.3% were satisfied or very satisfied with their TKA. The mean FJS was 67.6 (range: 0–100). The mean KOOS were as follows: pain 84.7 (range: 38–100), symptoms 85.5 (range: 46–100), function in daily activities 82.6 (range: 40–100), function in sport and recreation 35.2 (range: 0–100) and quality of life 79.1 (range: 0–100). No radiological evidence of implant aseptic loosening or osteolysis was identified.Cemented TKA implanted with the rKA alignment protocol demonstrated excellent long‐term implant survivorship and is a safe alternative to MA to improve patient function and satisfaction.IV, continuous case series with no comparison group. [ABSTRACT FROM AUTHOR]

Seamless study designs have the potential to accelerate clinical development. The use of innovative seamless designs has been increasing in the oncology area; however, while the concept of seamless designs becomes more popular and accepted, many challenges remain in both the design and conduct of these trials. This may be especially true when seamless designs are used in late phase development supporting regulatory decision-making. The Innovative Design Scientific Working Group (IDSWG) Oncology team conducted a survey to understand the current use of seamless study designs for registration purposes in oncology clinical development. The survey was designed to provide insights into the benefits and to identify the roadblocks. A total of 16 questions were included in the survey that was distributed using the ASA Biopharmaceutical Section and IDSWG email listings from August to September 2022. A total of 51 responses were received, with 39 (76%) respondents indicating that their organizations had seamless oncology studies in planning or implementation for registration purposes. Detailed survey results are presented in the manuscript. Overall, while seamless designs offer advantages in terms of timeline reduction and cost saving, they also present challenges related to additional complexity and the need for efficient surrogate clinical endpoints in oncology drug development. [ABSTRACT FROM AUTHOR]

Phase-field modeling offers a powerful tool for investigating the electrical control of the domain structure in ferroelectrics. However, its broad application is constrained by demanding computational requirements, limiting its utility in inverse design scenarios. Here, we introduce a machine-learning surrogate to accelerate 3D phase-field modeling of tip-induced electrical switching. By dynamically handling the boundary conditions, the surrogate achieves accurate reproduction of switching trajectories under various tip locations and applied voltages. With stable predictions throughout entire morphological evolution pathways and a relative error inferior to 10% compared to direct solvers, the model efficiently emulates intricate switching sequences. By successfully replicating the boundary conditions, the presented framework strides towards a holistic surrogate for the ferroelectric phase field. With up to 2500-fold speed-ups over classical methods, our approach opens the path for the tractable design of the domain structure and the resolution of realistic inverse problems. [ABSTRACT FROM AUTHOR]

Microbiome research is now demonstrating a growing number of bacterial strains and genes that affect our health1. Although CRISPR-derived tools have shown great success in editing disease-driving genes in human cells2, we currently lack the tools to achieve comparable success for bacterial targets in situ. Here we engineer a phage-derived particle to deliver a base editor and modify Escherichia coli colonizing the mouse gut. Editing of a β-lactamase gene in a model E. coli strain resulted in a median editing efficiency of 93% of the target bacterial population with a single dose. Edited bacteria were stably maintained in the mouse gut for at least 42 days following treatment. This was achieved using a non-replicative DNA vector, preventing maintenance and dissemination of the payload. We then leveraged this approach to edit several genes of therapeutic relevance in E. coli and Klebsiella pneumoniae strains in vitro and demonstrate in situ editing of a gene involved in the production of curli in a pathogenic E. coli strain. Our work demonstrates the feasibility of modifying bacteria directly in the gut, offering a new avenue to investigate the function of bacterial genes and opening the door to the design of new microbiome-targeted therapies.Edited bacteria were stably maintained in mouse gut for at least 42 days following the delivery of a base editor using an engineered phage-derived particle to modify Escherichia coli colonizing the gut. [ABSTRACT FROM AUTHOR]

This article is an editorial written by Pascal‐André Vendittoli, Gautier Beckers, Vincent Massé, Philip Winnock de Grave, Muthu Ganapathi, and Samuel J. MacDessi. It discusses the use of boundaries in personalized knee arthroplasty and the lack of evidence for unrestricted kinematic alignment (uKA). The authors argue that the current scientific literature does not support the idea of reproducing all patients' anatomy without boundaries during total knee arthroplasty (TKA). They emphasize the importance of recognizing physical diversity while also acknowledging that certain physical traits may be linked to health challenges and diseases. The article explores the variability in knee anatomy among individuals and discusses the need to define what is considered normal, abnormal, and pathological. The authors propose the use of restricted kinematic alignment (rKA) protocols that set boundaries for TKA in patients with deviant knee anatomy. They suggest that further research is needed to determine the optimal bony resections and soft-tissue balance in personalized TKA surgery. The authors also emphasize that personalized TKA involves more than just restoring joint surface orientations and that a comprehensive approach is necessary for successful TKA. They state that they have no conflicts of interest and that no IRB approval was required for this editorial. [Extracted from the article]

Based on potential field data, anomalies derived from the EIGEN6C4 satellite model were used to interpret various structural features of the coastal plain, Southwest Cameroon volcanic line, northwestern margin of Congo Craton (CC) and southern extension of Pan-African belt. Since building a global comprehension of unknown phenomena about Earth's materials is of high relevance given the tectonic complexities of the investigated area, some edge enhancement techniques were applied to the gravimetric data. After generating the Bouguer anomalies, a cosine filter was used to provide the residual data set that should characterize the gravity effect arising from superficial density sources, and finally, some amplitude and phase-based edge detection methods were used to interpret the computed Bouguer and residual data. The results of this research work have demonstrated that the enhanced horizontal gradient amplitude and fast sigmoid edge detector (FSED) filters could detect density boundaries more successfully than the other filters tested. The structural map generated by FSED revealed that the delineated lineaments are oriented NW–SE, NE–SW, N–S and NNE–SSW. In addition, important tectonic features such as Central Cameroon, Kribi–Campo and Sanaga shear zones are indicative of the effectiveness of this methodological approach and the CC limit was better highlighted in this research work. In general, the lineament map enhances the knowledge of the structural setting of the Douala Kribi–Campo sedimentary basin as well as unexposed fracture zones that may have caused seismic events in recent years. [ABSTRACT FROM AUTHOR]

The main aim of the study is to perform a high-precision mapping of geological features (lineaments and faults) using advanced gravity processing methods. The main techniques used for gravity data processing are the tilt angle of horizontal gradient (TAHG), the improved logistic filter (ILF), the fast sigmoid edge detector filter (FSF), and an edge detection filter based on the arcsine function (ASF). Before applying these edge detection filters to major geological units of North Cameroon, their effectiveness and performance have been assessed on synthetic gravity data and on random noise incorporated synthetic data. In addition, the Euler deconvolution has been used to estimate the position and depth of anomalous gravity sources in the study region. Using these edge detection techniques, a precise mapping of structural lineaments in the region has been established. It appears that the main structural features are trending along the N-S, NNE-SSW and NE-SW directions. The deepest density anomalies in the region are identified in the NW–SE direction, which coincides well with the extension of the Central and West African rift system in the study area. The advanced edge detection techniques and the Euler deconvolution method have both identified a network of superficial lineaments around longitude 13oN and latitude 8oN, and located between 0 and 4 km depth. The NW–SE trending crustal features outlined in the northeast of the region indicate that the area would have been the target of a uniform tectonic activity. This study is crucial to improve the knowledge of the configuration of fractures network, and to a better exploitation of groundwater resources available in the region. [ABSTRACT FROM AUTHOR]

Purpose: Despite systemic thrombolysis, a few patients with high-risk pulmonary embolism (PE) remain hemodynamically unstable. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a considerable lifesaving therapy but systemic thrombolysis before cannulation could carry a high risk of hemorrhage and alter the prognosis. Methods: Between June 2012 and June 2023, we retrospectively analyzed from three intensive care units in Sorbonne University, ECMO-related complications and 90-day mortality for high-risk PE patients who received ECMO without previous systemic thrombolysis compared to those cannulated after systemic thrombolysis failure. Hospital discharge survivors were assessed for long-term health-related quality of life and echocardiographic evaluations. Results: 72 high-risk PE patients [median age 48 (37–61) years, Simplified Acute Physiology Score II (SAPS II) 74 (60–85)] were placed on VA-ECMO for 5 (5–7) days. 31 (43%) patients underwent pre-ECMO thrombolysis (thrombolysis ECMO group, T +) compared to 41 patients (57%, no thrombolysis ECMO group, T−). There was more pre-ECMO cardiac arrest in the thrombolysis ECMO group (94% vs. 67%, p = 0.02). Ninety-day survival was not different between groups (39% vs 46%, log-rank test, p = 0.31). There was no difference in severe hemorrhages (61% vs 59%, p = 1). Twenty-five over 28 patients attended follow-up at a median time of 69 (52–95) months. Long-term quality of life was acceptable and none of them experienced chronic thromboembolic pulmonary hypertension. Conclusions: Ninety-day survival and bleeding events rates did not differ in patients treated with VA-ECMO after systemic thrombolysis compared to those who were not. Recent systemic thrombolysis, as a single parameter, should not be considered as a contraindication for VA-ECMO in high-risk PE. [ABSTRACT FROM AUTHOR]

Fungicide resistance to crop protection products is a critical sustainability issue in modern agriculture that requires constant monitoring of the field situation considering different environmental conditions and agricultural practices. Regulation strategies based on resistance risk ranking of both pathogen and active compound, underpinned by fast and broad field monitoring, shall result in recommendations for suitable practices with the aim to stabilize or even to restore the sensitivity situation. Alternating and mixing various products according to their modes of action belong to the most common and the most efficient mitigation methods. Though, these resistance management measures can be implemented best when precise knowledge of both the molecular target and the cell biology of the pathogen as well as of the resistance mechanism is acknowledged. To this end, we have investigated the molecular target and cellular effects of fluopicolide, one of the most effective Oomyceticides in the market. By combining data of genomic analysis of resistant field isolates of Plasmopara viticola and Phytophthora infestans with UV-mutagenized strains of P. infestans, we identified the enzyme vacuolar H+-ATPase as the target protein. Biochemical assays confirmed that fluopicolide inhibits specifically Oomycetes targets and has no residual activity on true fungi or insect orthologs. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Our study aims to uncover glycaemic phenotype heterogeneity in type 1 diabetes. Methods: In the Study of the French-speaking Society of Type 1 Diabetes (SFDT1), we characterised glycaemic heterogeneity thanks to a set of complementary metrics: HbA1c, time in range (TIR), time below range (TBR), CV, Gold score and glycaemia risk index (GRI). Applying the Discriminative Dimensionality Reduction with Trees (DDRTree) algorithm, we created a phenotypic tree, i.e. a 2D visual mapping. We also carried out a clustering analysis for comparison. Results: We included 618 participants with type 1 diabetes (52.9% men, mean age 40.6 years [SD 14.1]). Our phenotypic tree identified seven glycaemic phenotypes. The 2D phenotypic tree comprised a main branch in the proximal region and glycaemic phenotypes in the distal areas. Dimension 1, the horizontal dimension, was positively associated with GRI (coefficient [95% CI]) (0.54 [0.52, 0.57]), HbA1c (0.39 [0.35, 0.42]), CV (0.24 [0.19, 0.28]) and TBR (0.11 [0.06, 0.15]), and negatively with TIR (−0.52 [−0.54, −0.49]). The vertical dimension was positively associated with TBR (0.41 [0.38, 0.44]), CV (0.40 [0.37, 0.43]), TIR (0.16 [0.12, 0.20]), Gold score (0.10 [0.06, 0.15]) and GRI (0.06 [0.02, 0.11]), and negatively with HbA1c (−0.21 [−0.25, −0.17]). Notably, socioeconomic factors, cardiovascular risk indicators, retinopathy and treatment strategy were significant determinants of glycaemic phenotype diversity. The phenotypic tree enabled more granularity than traditional clustering in revealing clinically relevant subgroups of people with type 1 diabetes. Conclusions/interpretation: Our study advances the current understanding of the complex glycaemic profile in people with type 1 diabetes and suggests that strategies based on isolated glycaemic metrics might not capture the complexity of the glycaemic phenotypes in real life. Relying on these phenotypes could improve patient stratification in type 1 diabetes care and personalise disease management. [ABSTRACT FROM AUTHOR]

Intrinsic and extrinsic factors, including lifestyle and sun exposure, can contribute to cell senescence, which impairs skin homeostasis, that may in turn lead to skin aging. Senescent cells have a specific secretome, called the senescence-associated secretory phenotype (SASP) that includes MMPs, CXCLs and S100A8/9. Reducing the SASP with senotherapeutics is a promising strategy to reduce skin aging. Here we evaluated the effect of a formula containing niacinamide and hyaluronic acid, which are known to limit senescence and skin aging. We conducted three different studies. (1) Ex vivo explants treated with the formula had more collagen and glycosaminoglycan. (2) In a clinical trial with forty-four women, two months of treatment improved fine lines, wrinkles, luminosity, smoothness, homogeneity, and plumpness. (3) In a third study on thirty women, we treated one arm for two months and took skin biopsies to study gene expression. 101 mRNAs and 13 miRNAs were differentially expressed. We observed a likely senomorphic effect, as there was a decrease in many SASP genes including MMP12 and CXCL9 and a significant downregulation of autocrine signaling genes: S100A8 and S100A9. These pharmaco-clinical results are the first to demonstrate the senomorphic properties of an effective anti-aging formula in skin. [ABSTRACT FROM AUTHOR]

Here, we introduce the Tabulae Paralytica—a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord1. The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.The Tabulae Paralytica, a compilation of four molecular atlases of spinal cord injury, provides a window into the pathobiology of spinal cord injury, establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine. [ABSTRACT FROM AUTHOR]

In the production of cast aluminum automotive parts, cores made of sand and binders are often used to create the complex features that cannot be formed by the mold, such as internal passages. Core binders can be grouped into two different categories: organic and inorganic, depending on the binder system used. Conventional organic binders use petroleum-based materials that are sources of harmful gases. In contrast, inorganic binders such as sodium silicates (water glass) are environmentally friendly. The fabrication of inorganic cores requires a drying step that involves thermal dehydration (using hot box and hot air injection) and chemical reactions (polymerization) to give the sand core the necessary strength to withstand the constraints developed during core storage and the casting process. This drying step increases the duration of the process and affects the production line. This study evaluated different thin layer drying models to understand the drying behavior of sand cores in the inorganic process that uses both hot air and warm box. The Page model was found to best describe the drying kinetics based on experimental measurements on a rectangular core. The sorption properties of the core were determined by characterizing the desorption isotherms at three different temperatures. The energy required to remove water from the core was estimated and it is found that the highest energy reached a theoretical maximum at a box temperature of around 135 °C. [ABSTRACT FROM AUTHOR]

Diet composition impacts metabolic health and is now recognized to shape the immune system, especially in the intestinal tract. Nutritional imbalance and increased caloric intake are induced by high-fat diet (HFD) in which lipids are enriched at the expense of dietary fibers. Such nutritional challenge alters glucose homeostasis as well as intestinal immunity. Here, we observed that short-term HFD induced dysbiosis, glucose intolerance and decreased intestinal RORγt+ CD4 T cells, including peripherally-induced Tregs and IL17-producing (Th17) T cells. However, supplementation of HFD-fed male mice with the fermentable dietary fiber fructooligosaccharides (FOS) was sufficient to maintain RORγt+ CD4 T cell subsets and microbial species known to induce them, alongside having a beneficial impact on glucose tolerance. FOS-mediated normalization of Th17 cells and amelioration of glucose handling required the cDC2 dendritic cell subset in HFD-fed animals, while IL-17 neutralization limited FOS impact on glucose tolerance. Overall, we uncover a pivotal role of cDC2 in the control of the immune and metabolic effects of FOS in the context of HFD feeding. Dietary fibers have beneficial effects on both metabolism and immunity. Here the authors demonstrate that type 2 dendritic cells mediate fibers benefits on Th17 cells homeostasis and glucose metabolism in the context of high-fat diet feeding. [ABSTRACT FROM AUTHOR]

Purpose: To assess efficacy and safety of prostatic artery embolization (PAE) in patients with advanced prostate cancer (PCa). Materials and Methods: In this prospective single-center, single-arm, pilot study, 9 men with advanced PCa underwent PAE. PAE was performed with the use of 250–400 µm Embozene microspheres (Boston Scientific, Natick, Massachusetts, USA). International Prostate Symptoms Score (IPSS), urinary peak flow (Qmax) and post-void residual urine volume (PVR) was assessed at 12 weeks and up to 12 months. Changes in total prostate volume (TPV) and tumor responses by PSA, changes in tumor volume and evaluation of tumor regression by multiparametric magnetic resonance imaging were assessed at 12 weeks after PAE. Results: IPSS reduction in median 6 points (0–19) and a significant decrease in PVR from median 70 (20–600) mL to 10 (0–280) mL could be achieved within 12 weeks after PAE. Median TPV and tumor volumes (TV) increased slightly from 19.7 (6.4–110.8) mL to 23.4 (2.4–66.3) mL and 6.4 (4.6–18.3) mL to 8.1 (2.4–25.6) mL at a median of 12 weeks after the procedure. Significant tumor necrosis (≥ 50%) was found in one patient. Eight patients showed > 50% of viable tumor on post-PAE MRI according to MRI. Only one Clavien-Dindo Grade 1 adverse event related to PAE occurred. Conclusions: PAE with the use of 250–400 µm microspheres is feasible, safe and effective in some patients with advanced PCa regarding functional outcomes. A cytoreductive effect might be achieved in individual patients but must be further assessed. Trials registration: NCT03457805. [ABSTRACT FROM AUTHOR]

This paper analyzes whether repealing net neutrality (NN) improves or decreases the capacity of a regulator to make internet service providers (ISPs) extend broadband coverage through universal service obligations (USOs). We model a two-sided market where a monopolistic ISP links content providers (CPs) to end users with a broadband network of a given bandwidth. A regulator determines whether to subject the ISP to NN or to allow it to supply paid priority (P) services to CPs. She can also impose a broadband USO to the ISP: She can mandate the broadband market coverage. We show that the greater is the network bandwidth, the more likely is the repeal of NN to increase ISP profits and social welfare. Regulation can still be necessary, however, as there are bandwidth ranges for which the ISP would benefit from a repeal of NN while such a repeal is detrimental to society. [ABSTRACT FROM AUTHOR]

Purpose: The integration of palliative care (PC) into oncological management is recommended well before the end of life. It improves quality of life and symptom control and reduces the aggressiveness of end-of-life care. However, its appropriate timing is still debated. Entry into an early-phase clinical trial (ECT) represents hopes for the patient when standard treatments have failed. It is an opportune moment to integrate PC to preserve the patient’s general health status. The objective of this study was to evaluate the motives for acceptance or refusal of early PC management in patients included in an ECT. Methods: Patients eligible to enter an ECT were identified and concomitant PC was proposed. All patients received exploratory interviews conducted by a researcher. Their contents were analyzed in a double-blind thematic analysis with a self-determination model. Results: Motives for acceptance (PC acceptors: n = 27) were both intrinsic (e.g., pain relief, psychological support, anticipation of the future) and extrinsic (e.g., trust in the medical profession, for a relative, to support the advance of research). Motives for refusal (PC refusers: n = 3) were solely intrinsic (e.g., PC associated with death, negative representation of psychological support, no need for additional care, claim of independence). Conclusions: The motives of acceptors and refusers are not internalized in the same way and call for different autonomy needs. Acceptors and refusers are influenced by opposite representations of PC and a different perception of mixed management. [ABSTRACT FROM AUTHOR]

In the 1990s there was a great deal of interest in the study of the role of endogenous market structure under oligopoly in the characterization of emission taxes. This interest was instrumental in providing policy guidance on the design of emission taxes based on market characteristics. However, the literature has been silent on offering policy recommendations on the design of emission taxes under endogenous market structure in the presence of new firm acquisitions. We build a model where new firms enter the market where some are acquired by an incumbent multi-plant firm, altering the initial market structure. In this framework, we characterize the second-best emission tax and examine the role of the resulting market structure, in particular the role of acquiring more/fewer of the new firms, in the optimal design of emission tax. We argue that, under certain conditions, the acquisition of new firms may lead to higher taxation consistent with the Pigouvian rule or even exceed marginal damages. Our contribution is at the intersection of emission tax design and M &A (new firm acquisition) literature. [ABSTRACT FROM AUTHOR]

Quantum bits (qubits) are prone to several types of error as the result of uncontrolled interactions with their environment. Common strategies to correct these errors are based on architectures of qubits involving daunting hardware overheads1. One possible solution is to build qubits that are inherently protected against certain types of error, so the overhead required to correct the remaining errors is greatly reduced2–7. However, this strategy relies on one condition: any quantum manipulations of the qubit must not break the protection that has been so carefully engineered5,8. A type of qubit known as a cat qubit is encoded in the manifold of metastable states of a quantum dynamical system, and thereby acquires continuous and autonomous protection against bit-flips. Here, in a superconducting-circuit experiment, we implemented a cat qubit with bit-flip times exceeding 10 s. This is an improvement of four orders of magnitude over previously published cat-qubit implementations. We prepared and imaged quantum superposition states, and measured phase-flip times greater than 490 ns. Most importantly, we controlled the phase of these quantum superpositions without breaking the bit-flip protection. This experiment demonstrates the compatibility of quantum control and inherent bit-flip protection at an unprecedented level, showing the viability of these dynamical qubits for future quantum technologies.A type of qubit that has inherent resistance to bit-flip errors has been manipulated with a bit-flip time of more than 10 s without losing that error protection. [ABSTRACT FROM AUTHOR]

Key message: The HaOr5 resistance gene is located in a large genomic insertion containing putative resistance genes and provides resistance to O. cumana, preventing successful connection to the sunflower root vascular system. Orobanche cumana (sunflower broomrape) is a parasitic plant that is part of the Orobanchaceae family and specifically infests sunflower crops. This weed is an obligate parasitic plant that does not carry out photosynthetic activity or develop roots and is fully dependent on its host for its development. It produces thousands of dust-like seeds per plant. It possesses a high spreading ability and has been shown to quickly overcome resistance genes successively introduced by selection in cultivated sunflower varieties. The first part of its life cycle occurs underground. The connection to the sunflower vascular system is essential for parasitic plant survival and development. The HaOr5 gene provides resistance to sunflower broomrape race E by preventing the connection of O. cumana to the root vascular system. We mapped a single position of the HaOr5 gene by quantitative trait locus mapping using two segregating populations. The same location of the HaOr5 gene was identified by genome-wide association. Using a large population of thousands of F2 plants, we restricted the location of the HaOr5 gene to a genomic region of 193 kb. By sequencing the whole genome of the resistant line harboring the major resistance gene HaOr5, we identified a large insertion of a complex genomic region containing a cluster of putative resistance genes. [ABSTRACT FROM AUTHOR]

A purification method is developed to determine 90Sr in radioactive waste. A separation based on Sr-resin® with a pretreatment using TRU-resin® provides satisfactory Sr recovery yields before the 90Sr measurement by liquid scintillation counting (LSC) regardless the analyzed samples with low or high activity level. The selectivity of the procedure is checked by measuring the 90Y ingrowth after different days of separation without waiting for secular equilibrium. In order to obtain a REACH compliant method without scintillation cocktails, a plastic scintillation resin selective for Sr is implemented on the basis of the developed protocol. The optimized method is applied successfully to representative nuclear waste including samples with high Pu content (effluents, concretes and sludges). [ABSTRACT FROM AUTHOR]

Objectives: Acute encephalopathy (AE) has been described as a severe complication of COVID-19. Inflammation has been suggested as a pathogenic mechanism, with high-dose glucocorticoids (GC) showing a beneficial effect. Here, we retrospectively analyzed the clinical and radiological features in a group of COVID-19 AE patients who received GC treatment (GT) and in a non-treated (NT) group. Method: Thirty-six patients with COVID-19 AE (mean age 72.6 ± 11 years; 86.11% men) were evaluated for GC treatment. Twelve patients (mean age 73.6 ± 4.5 years; 66.67% men) received GC, whereas 24 patients who showed signs of spontaneous remission were not treated with GC (mean age 70.1 ± 8.6 years; 95.83% men). Differences in clinical characteristics and correlations with imaging features were explored. Results: The GT group showed signs of vulnerability, with a longer hospitalization (p = 0.009) and AE duration (p = 0.012) and a higher hypertensive arteriopathy (HTNA) score (p = 0.022), when compared to NT group. At hospital discharge, the two groups were comparable in terms of clinical outcome (modified Rankin scale; p = 0.666) or mortality (p = 0.607). In our whole group analyses, AE severity was positively correlated with periventricular white matter hyperintensities (p = 0.011), deep enlarged perivascular spaces (p = 0.039) and HTNA score (p = 0.014). Conclusion: This study suggests that, despite signs of radiological vulnerability and AE severity, patients treated by high-dose GC showed similar outcome at discharge, with respect to NT patients. Imaging features of cerebral small vessel disease correlated with AE severity, supporting the hypothesis that brain structural vulnerability can impact AE in COVID-19. [ABSTRACT FROM AUTHOR]

Background: Tourniquet use during total knee arthroplasty (TKA) remains controversial. The purpose of this study is to determine the impact of tourniquet use only during cementation compared with its use throughout the entire surgery concerning early outcomes in functional recovery, pain, quadriceps function, and rehabilitation. Methods: Between November 2019 and March 2020, 118 patients were enrolled in this study, with 59 patients undergoing TKA with a tourniquet during the entire surgery (group 1) and 59 patients with a tourniquet only during cementation (group 2). Twenty-eight patients were unable to complete follow-up leaving fifty in group 1 and forty in group 2. Primary endpoints were surgical time, postoperative knee and thigh pain, and functional recovery. Secondary endpoints were 6-month clinical scores and blood loss. Results: Patients in group 1 had statistically significantly increased knee pain on postoperative day 3 (p = 0.004), and thigh pain on postoperative day 1 (p < 0.001), 2 (p < 0.001), and 3 (p = 0.027), and longer time intervals to achieve straight leg raise maneuver (p = 0.006) compared to group 2. However, it did not affect overall narcotic consumption, knee pain (day 1–2), functional recovery, ROM, ability to do the first walk, Oxford knee score, length of stay, and complication rate. There was no statistically significant difference in terms of 6-month postoperative knee score, surgical time, and blood loss between the two groups. Conclusion: Tourniquet use diminishes quadriceps function and increases postoperative thigh pain and, to a lesser extent, knee pain. We, therefore, recommend the use of a tourniquet only during cementing. Level of evidence: 1; prospective randomized study. [ABSTRACT FROM AUTHOR]

Introduction: Sleeve gastrectomy is the most commonly performed bariatric operation globally. The main complication is GERD. In the medium term, it can increase the incidence of Barrett's esophagus (BE), which is a risk factor for esophageal adenocarcinoma. Following conventional sleeve gastrectomy, BE is noted in up to 16% of patients postoperatively. Recently, Nissen sleeve gastrectomy (NSG) has been shown to reduce the frequency of postoperative GERD compared to conventional sleeve gastrectomy. This study aims to evaluate the impact of NSG on the incidence and remission of BE in the long term. Material and Method: This bicentric retrospective study included 692 patients who received NSG from September 2013 to July 2021. All patients underwent preoperative upper GI endoscopy and were then scheduled to receive upper GI endoscopy between 1 and 2 years and then between 3 and 5 years postoperatively. BE was systematically confirmed by biopsies. Results: Seventy-four patients had endoscopic suspicion of BE, which was confirmed on 54/692 patients by histology. The BE lesions consisted of 18.5% intestinal metaplasia and 75.9% fundal metaplasia. Among these 54 patients, 38 underwent endoscopic investigation within 2 years postoperatively. The biopsies showed healed BE in 25/38 patients (64.1%). At 5 years, two patients had proven BE. Concerning the incidence of BE post NSG: 234 performed the follow-up endoscopy within 2 years. The incidence of de novo BE is nil. Conclusion: The NSG is associated with healing of known BE in approximately two-thirds of patients at 2-year follow-up. This is consistent with the GERD improvement that has been shown with NSG. [ABSTRACT FROM AUTHOR]

In radiochemical analysis of decommissioning waste, reference materials are not commercially available and consequently intercomparison exercises are needed for method validations. This paper reports the results from an intercomparison exercise focusing on analyses of α-emitter radionuclides in spent ion exchange resin. The exercise and statistical analysis of the submitted results were carried out based on ISO 13528 standard according to which the assigned values were calculated from the participant's results and the performances were assessed using z-scores, which showed excellent performance for all 241Am analyses, good performance for 238Pu analyses, tolerable performance for 239,240Pu analyses, and questionable 243,244Cm analyses. [ABSTRACT FROM AUTHOR]

Inflammation is a mediator of a number of chronic pathologies. We synthesized the diethyl (9Z,12Z)-octadeca-9,12-dien-1-ylphosphonate, called NKS3, which decreased lipopolysaccharide (LPS)-induced mRNA upregulation of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) not only in primary intraperitoneal and lung alveolar macrophages, but also in freshly isolated mice lung slices. The in-silico studies suggested that NKS3, being CD36 agonist, will bind to GPR120. Co-immunoprecipitation and proximity ligation assays demonstrated that NKS3 induced protein–protein interaction of CD36 with GPR120in RAW 264.7 macrophage cell line. Furthermore, NKS3, via GPR120, decreased LPS-induced activation of TAB1/TAK1/JNK pathway and the LPS-induced mRNA expression of inflammatory markers in RAW 264.7 cells. In the acute lung injury model, NKS3 decreased lung fibrosis and inflammatory cytokines (IL-1β, IL-6 and TNF-α) and nitric oxide (NO) production in broncho-alveolar lavage fluid. NKS3 exerted a protective effect on LPS-induced remodeling of kidney and liver, and reduced circulating IL-1β, IL-6 and TNF-α concentrations. In a septic shock model, NKS3 gavage decreased significantly the LPS-induced mortality in mice. In the last, NKS3 decreased neuroinflammation in diet-induced obese mice. Altogether, these results suggest that NKS3 is a novel anti-inflammatory agent that could be used, in the future, for the treatment of inflammation-associated pathologies. [ABSTRACT FROM AUTHOR]

Given an undirected graph, are there k matchings whose union covers all of its nodes, that is, a matching-k-cover? When k = 1 , the problem is equivalent to the existence of a perfect matching for which Tutte's celebrated matching theorem (J. Lon. Math. Soc., 1947) provides a 'good' characterization. We prove here, when k is greater than one, a 'good' characterization à la Kőnig: for k ≥ 2 , there existkmatchings covering every node if and only if for every stable setS, we have | S | ≤ k · | N (S) | . Moreover, somewhat surprisingly, we use only techniques from bipartite matching in the proof, through a simple, polynomial algorithm. A different approach to matching-k-covers has been previously suggested by Wang et al. (Math. Prog., 2014), relying on general matching and using matroid union for matching-matroids, or the Edmonds-Gallai structure theorem. Our approach provides a simpler polynomial algorithm together with an elegant certificate of non-existence when appropriate. Further results, generalizations and interconnections between several problems are then deduced as consequences of the new minimax theorem, with surprisingly simple proofs (again using only the level of difficulty of bipartite matchings). One of the equivalent formulations leads to a solution of weighted minimization for non-negative edge-weights, while the edge-cardinality maximization of matching-2-covers turns out to be already NP-hard. We have arrived at this problem as the line graph special case of a model arising for manufacturing integrated circuits with the technology called 'Directed Self Assembly'. [ABSTRACT FROM AUTHOR]

Nanoscale morphological features of branched processes of glial cells may be of decisive importance for neuron–astrocyte interactions in health and disease. The paper presents the results of a correlation analysis of images of thin processes of astrocytes in nervous tissue of the mouse brain, which were obtained by scanning probe microscopy (SPM) and transmission electron microscopy (TEM) with high spatial resolution. Samples were prepared and imaged using a unique hardware combination of ultramicrotomy and SPM. Astrocyte details with a thickness of several tens of nanometers were identifiable in the images, making it possible to reconstruct the three-dimensional structure of astrocytic processes by integrating a series of sequential images of ultrathin sections of nervous tissue in the future. [ABSTRACT FROM AUTHOR]

Purpose: To provide EuroQoL EQ-5D-5L French population norms based on a sample of 15,000 responders. Methods: Based on the National Health and Wellness Survey, an international, annual, selfadministered Internet-based survey, this study extracted data from France for 2018 involving a sample of 15,000 respondents stratified by age and gender. Responses to the EQ-5D-5L questionnaire and the Visual Analog Scale (VAS) score, together with sociodemographic, health behavior, and disease status variables were collected. VAS, value indexes, the level sum score, and the distribution of levels per dimension were described. Multivariate regression analyses were performed to identify covariates with a statistically significant effect on the five dimensions and the three scores. Results: The mean [standard deviation (SD)] VAS was 73.4 (22.2) for the entire sample (male 74.8 vs female 72.2, p < 0.0001). The Mean SD value index was 0.905 (0.158) (male 0.915 vs female 0.895, p < 0.0001). The mean SD level sum score was 7.6 (3.0) (7.4 for males vs. 7.9 for females p < 0.0001). Health state 11,111 (no problem in any dimension) represented 25.1% of all responses. "No problem" responses' proportions were Self Care (91.3%), Usual Activities (74.2%), Mobility (72.4%), Anxiety/Depression (52.6%) and Pain/Discomfort (37.7%). Multivariate regressions revealed a significant relationship for health states, value indexes, and VAS with age, income, employment, marital status, smoking and alcohol consumption, obesity, and the presence of one or more health problems. Conclusion: Based on a large sample, this study is the first to report EQ-5D-5L population norms for France. [ABSTRACT FROM AUTHOR]

GABAA receptors, members of the pentameric ligand-gated ion channel superfamily, are widely expressed in the central nervous system and mediate a broad range of pharmaco-toxicological effects including bidirectional changes to seizure threshold. Thus, detection of GABAA receptor-mediated seizure liabilities is a big, partly unmet need in early preclinical drug development. This is in part due to the plethora of allosteric binding sites that are present on different subtypes of GABAA receptors and the critical lack of screening methods that detect interactions with any of these sites. To improve in silico screening methods, we assembled an inventory of allosteric binding sites based on structural data. Pharmacophore models representing several of the binding sites were constructed. These models from the NeuroDeRisk IL Profiler were used for in silico screening of a compiled collection of drugs with known GABAA receptor interactions to generate testable hypotheses. Amoxapine was one of the hits identified and subjected to an array of in vitro assays to examine molecular and cellular effects on neuronal excitability and in vivo locomotor pattern changes in zebrafish larvae. An additional level of analysis for our compound collection is provided by pharmacovigilance alerts using FAERS data. Inspired by the Adverse Outcome Pathway framework, we postulate several candidate pathways leading from specific binding sites to acute seizure induction. The whole workflow can be utilized for any compound collection and should inform about GABAA receptor-mediated seizure risks more comprehensively compared to standard displacement screens, as it rests chiefly on functional data. [ABSTRACT FROM AUTHOR]

Hip fracture is a common injury and represents a major health problem with an increasing incidence. In older adults, opioids such as oxycodone are often preferred to other analgesics such as tramadol because of a lower risk of delirium. Different parameters, such as inhibition of cytochrome P450 (CYP450) 2D6 and/or 3A4, can potentially lead to pharmacokinetic variations of oxycodone representing a risk of adverse drugs effects or lack of drug response. There is a risk of drug–drug interactions involving CYP450 in older adults due to the high prevalence of polypharmacy. This study sought to identify patient characteristics that influence oxycodone administration. A single-center observational study included 355 patients with a hip fracture hospitalized in a geriatric postoperative unit. Composite endpoint based on form, duration, and timing to intake separated patients into three groups: "no oxycodone", "low oxycodone ", and "high oxycodone ". CYP450 interactions were studied based on a composite variable defining the most involved CYP450 pathways between CYP2D6 and CYP3A4. CYP450 interactions with CYP2D6 pathway involved were associated with the risk of "high oxycodone" [odds ratio adjusted on age and the type of hip fracture (OR*) 4.52, 95% confidence interval (CI) 1.39–16.83, p = 0.02)], as well as serum albumin levels (OR* 1.09, 95% CI 1.02–1.17, p = 0.01). Cognitive impairment was negatively associated with the risk of "high oxycodone" (OR* 0.38, 95% CI 0.18–0.77, p = 0.02). This study showed an association between CYP2D6 interactions and higher oxycodone consumption indirectly reflecting the existence of uncontrolled postoperative pain. [ABSTRACT FROM AUTHOR]

To improve our understanding of how deformable objects are transported in flows, it is necessary to develop new experimental tools capable of accurately measuring the evolution of their deformations. We present a reconstruction process for sheet-like objects utilizing Thin-Plate Splines (TPS), providing access to the object's 3D position and deformation over time. We tested the technique on a simple configuration: a thin-heavy-flexible disc within a vortical flow driven by impellers in a cubic tank. The vortical flow field is characterized using Particle Image Velocimetry (PIV) and is seen to be well approximated as a Lamb–Oseen vortex within the volume of reconstruction. The disc is imaged using three cameras, which are calibrated using the pinhole model. The reconstruction process uses shape-from-silhouette to define an initial 3D reconstruction, which is subsequently refined by minimizing a cost function based on physical and visual criteria. This process is shown to be generalizable to other thin geometries, offering a starting point toward studying the dynamics of more complex sheet-like objects, such as plastic pollutants and vegetation. [ABSTRACT FROM AUTHOR]

Introduction: Revisional bariatric surgery (RBS) is a challenging type of procedure for the surgeons due to its specific morbidity and efficiency. The RBS has a higher prevalence nowadays and this study may help to improve scarce data upon this specific topic. Methods: Data from 252 patients undergoing RBS after laparoscopic adjustable gastric banding (LAGB) or laparoscopic sleeve gastrectomy (LSG) between 2005 and 2019, were analyzed at 2 years of follow up. A subgroup analysis of third procedure was also performed. Results: Overall morbidity occurred in 35 patients (37%) in the LSG group and 40 patients (25%) in the LAGB group (p = 0.045). At 2 years of RBS, mean weight was 92.8 ± 26.7 kg, BMI was 33.1 ± 8.56 kg/m2 for patients who had RBS after LSG. When RBS was performed after LAGB, mean weight at 2 years was 90.1 ± 20.7 kg and BMI was 32.5 ± 6.45 kg/m2. TWL for RBS performed after LSG was 12.7 ± 16.4% versus 25.5 ± 10.3% after LAGB (p < 0.001). Conclusion: RBS after LSG seems to lead to higher overall morbidity whereas RBS after LAGB lead to more perioperative issues. [ABSTRACT FROM AUTHOR]

Background: Venovenous extracorporeal membrane oxygenation (VV ECMO) is frequently associated with deep sedation and neuromuscular blockades, that may lead to diaphragm dysfunction. However, the prevalence, risk factors, and evolution of diaphragm dysfunction in patients with VV ECMO are unknown. We hypothesized that the prevalence of diaphragm dysfunction is high and that diaphragm activity influences diaphragm function changes. Methods: Patients with acute respiratory distress syndrome (ARDS) requiring VV ECMO were included in two centers. Diaphragm function was serially assessed by measuring the tracheal pressure in response to phrenic nerve stimulation (Ptr,stim) from ECMO initiation (Day 1) until ECMO weaning. Diaphragm activity was estimated from the percentage of spontaneous breathing ventilation and by measuring the diaphragm thickening fraction (TFdi) with ultrasound. Results: Sixty-three patients were included after a median of 4 days (3–6) of invasive mechanical ventilation. Diaphragm dysfunction, defined by Ptr, stim ≤ 11 cmH2O, was present in 39 patients (62%) on Day 1 of ECMO. Diaphragm function did not change over the study period and was not influenced by the percentage of spontaneous breathing ventilation or the TFdi during the 1 week. Among the 63 patients enrolled in the study, 24 (38%) were still alive at the end of the study period (60 days). Conclusions: Sixty-two percent of patients undergoing ECMO for ARDS related to SARS CoV-2 infection had a diaphragm dysfunction on Day 1 of ECMO initiation. Diaphragm function remains stable over time and was not associated with the percentage of time with spontaneous breathing. ClinicalTrials.gov Identifier NCT04613752 (date of registration February 15, 2021). [ABSTRACT FROM AUTHOR]

The role of force application in immune cell recognition is now well established, the force being transmitted between the actin cytoskeleton to the anchoring ligands through receptors such as integrins. In this chain, the mechanics of the cytoskeleton to receptor link, though clearly crucial, remains poorly understood. To probe this link, we combine mechanical extraction of membrane tubes from T cells using optical tweezers, and fitting of the resulting force curves with a viscoelastic model taking into account the cell and relevant molecules. We solicit this link using four different antibodies against various membrane bound receptors: antiCD3 to target the T Cell Receptor (TCR) complex, antiCD45 for the long sugar CD45, and two clones of antiCD11 targeting open or closed conformation of LFA1 integrins. Upon disruption of the cytoskeleton, the stiffness of the link changes for two of the receptors, exposing the existence of a receptor to cytoskeleton link—namely TCR-complex and open LFA1, and does not change for the other two where a weaker link was expected. Our integrated approach allows us to probe, for the first time, the mechanics of the intracellular receptor–cytoskeleton link in immune cells. [ABSTRACT FROM AUTHOR]

Background: Early recognition and treatment of bacteremia can be lifesaving. Fever is a well-known marker of bacteremia, but the predictive value of temperature has not been fully explored. Objective: To describe temperature as a predictor of bacteremia and other infections. Design: Retrospective review of electronic health record data. Setting: A single healthcare system comprising 13 hospitals in the United States. Patients: Adult medical patients admitted in 2017 or 2018 without malignancy or immunosuppression. Main Measures: Maximum temperature, bacteremia, influenza and skin and soft tissue (SSTI) infections based on blood cultures and ICD-10 coding. Key Results: Of 97,174 patients, 1,518 (1.6%) had bacteremia, 1,392 (1.4%) had influenza, and 3,280 (3.3%) had an SSTI. There was no identifiable temperature threshold that provided adequate sensitivity and specificity for bacteremia. Only 45% of patients with bacteremia had a maximum temperature ≥ 100.4˚F (38˚C). Temperature showed a U-shaped relationship with bacteremia with highest risk above 103˚F (39.4˚C). Positive likelihood ratios for influenza and SSTI also increased with temperature but showed a threshold effect at ≥ 101.0 ˚F (38.3˚C). The effect of temperature was similar but blunted for patients aged ≥ 65 years, who frequently lacked fever despite bacteremia. Conclusions: The majority of bacteremic patients had maximum temperatures below 100.4 ˚F (38.0˚C) and positive likelihood ratios for bacteremia increased with high temperatures above the traditional definition of fever. Efforts to predict bacteremia should incorporate temperature as a continuous variable. [ABSTRACT FROM AUTHOR]

Background: Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS). Methods: Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results. Results: Forty-seven patients (median age 41 [30–47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p < 0.0001). The rate of biopsy-related treatments modifications was 13%, leading to patients' recovery in only 4% patients. Conclusions: In clinically suspected myocarditis unweanable from MCS, myocardial biopsy increased the rate of definite myocarditis but was associated with a low rate of treatment modification and a significant proportion of adverse events. We believe the benefit/risk ratio of myocardial biopsy should be more carefully weighted in these frail and selected patients than suggested by actual guidelines. Further prospective studies are now needed to determine its value in patients under MCS. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune, inflammatory and fibrotic disease with limited treatment options. Developing new therapies is therefore crucial to address patient needs. To this end, we focused on galectin-3 (Gal-3), a lectin known to be associated with several pathological processes seen in SSc. Using RNA sequencing of whole-blood samples in a cross-sectional cohort of 249 patients with SSc, Gal-3 and its interactants defined a strong transcriptomic fingerprint associated with disease severity, pulmonary and cardiac malfunctions, neutrophilia and lymphopenia. We developed new Gal-3 neutralizing monoclonal antibodies (mAb), which were then evaluated in a mouse model of hypochlorous acid (HOCl)-induced SSc. We show that two of these antibodies, D11 and E07, reduced pathological skin thickening, lung and skin collagen deposition, pulmonary macrophage content, and plasma interleukin-5 and -6 levels. Moreover, E07 changed the transcriptional profiles of HOCl-treated mice, resulting in a gene expression pattern that resembled that of control mice. Similarly, pathological pathways engaged in patients with SSc were counteracted by E07 in mice. Collectively, these findings demonstrate the translational potential of Gal-3 blockade as a therapeutic option for SSc. Galectin-3 (Gal-3) has been proposed to have a pathogenic role in systemic sclerosis (SSc). Here, the authors identify a Gal-3-based transcriptomic signature associated with SSc severity in patients and demonstrate that Gal-3 blockade reduces the severity of SSc skin and lung lesions in murine models. [ABSTRACT FROM AUTHOR]

In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour1,2. The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Here, using mouse models of food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus and central amygdala. Allergen avoidance requires immunoglobulin E (IgE) antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote avoidance requires cysteinyl leukotrienes and growth and differentiation factor 15. Finally, a comparison of C57BL/6 and BALB/c mouse strains revealed a strong effect of the genetic background on the avoidance behaviour. These findings thus point to antigen-specific behavioural modifications that probably evolved to promote niche selection to avoid unfavourable environments.A study using mouse models of food allergy shows that allergic sensitization drives antigen-specific avoidance behaviour mediated by immunoglobulin E antibodies and mast cells. [ABSTRACT FROM AUTHOR]

The development of artificial intelligence–based imaging techniques for prostate cancer (PCa) detection and diagnosis requires a reliable ground truth, which is generally based on histopathology from radical prostatectomy specimens. This study proposes a comprehensive protocol for the annotation of prostatectomy pathology slides. To evaluate the reliability of the protocol, interobserver variability was assessed between five pathologists, who annotated ten radical prostatectomy specimens consisting of 74 whole mount pathology slides. Interobserver variability was assessed for both the localization and grading of PCa. The results indicate excellent overall agreement on the localization of PCa (Gleason pattern ≥ 3) and clinically significant PCa (Gleason pattern ≥ 4), with Dice similarity coefficients (DSC) of 0.91 and 0.88, respectively. On a per-slide level, agreement for primary and secondary Gleason pattern was almost perfect and substantial, with Fleiss Kappa of.819 (95% CI.659–.980) and.726 (95% CI.573–.878), respectively. Agreement on International Society of Urological Pathology Grade Group was evaluated for the index lesions and showed agreement in 70% of cases, with a mean DSC of 0.92 for all index lesions. These findings show that a standardized protocol for prostatectomy pathology annotation provides reliable data on PCa localization and grading, with relatively high levels of interobserver agreement. More complicated tissue characterization, such as the presence of cribriform growth and intraductal carcinoma, remains a source of interobserver variability and should be treated with care when used in ground truth datasets. [ABSTRACT FROM AUTHOR]

Introduction: Absolute quantification of individual metabolites in complex biological samples is crucial in targeted metabolomic profiling. Objectives: An inter-laboratory test was performed to evaluate the impact of the NMR software, peak-area determination method (integration vs. deconvolution) and operator on quantification trueness and precision. Methods: A synthetic urine containing 32 compounds was prepared. One site prepared the urine and calibration samples, and performed NMR acquisition. NMR spectra were acquired with two pulse sequences including water suppression used in routine analyses. The pre-processed spectra were sent to the other sites where each operator quantified the metabolites using internal referencing or external calibration, and his/her favourite in-house, open-access or commercial NMR tool. Results: For 1D NMR measurements with solvent presaturation during the recovery delay (zgpr), 20 metabolites were successfully quantified by all processing strategies. Some metabolites could not be quantified by some methods. For internal referencing with TSP, only one half of the metabolites were quantified with a trueness below 5%. With peak integration and external calibration, about 90% of the metabolites were quantified with a trueness below 5%. The NMRProcFlow integration module allowed the quantification of several additional metabolites. The number of quantified metabolites and quantification trueness improved for some metabolites with deconvolution tools. Trueness and precision were not significantly different between zgpr- and NOESYpr-based spectra for about 70% of the variables. Conclusion: External calibration performed better than TSP internal referencing. Inter-laboratory tests are useful when choosing to better rationalize the choice of quantification tools for NMR-based metabolomic profiling and confirm the value of spectra deconvolution tools. [ABSTRACT FROM AUTHOR]

Elicitors are stressors of biotic nature responsible for the adaptation of plants to cope with environmental stresses. Brassicae species (as white mustard) produce glucosinolates (GSs) that modify soil microbial communities and suppress soil-borne plant diseases. This research aimed to evaluate the glucosinolates levels in white mustard after elicitation with salicylic acid (SA), hydrogen peroxide (H2O2), chitosan (QN), and a commercial oligosaccharide (Xh), as well as the impact on the biofumigant activity of elicited plant residues mixed with fresh manure against soil-borne populations of Fusarium oxysporum. White mustard plants were treated with SA, H2O2, QN, and Xh. White mustard residues of the QN treatment (100 mg/mL) were further evaluated either in combination or not with fresh cow manure for biofumigant activity against F. oxysporum. Spectrophotometric and GC–MS techniques, respectively, determined GSs in white mustard plant organs. Significant increases in GSs in all plant organs except roots were found. The best treatment was chitosan 100 mg/mL, showing increases in leaves, flowers, and seeds. These plants treated with chitosan and mixed with fresh cow manure used in the biofumigation of soils displayed a reduction from 1600 CFU/g of soil to 50 CFU/g of soil F. oxysporum native population. Results suggested that controlled elicitation might increase the amount of GSs on white mustard, especially in the aerial parts; thus, elicited white mustard can be valorized as a potent biofumigant when mixed with fresh cow manure; thus, these green amendments might be a sustainable alternative in agriculture to help in crop management. [ABSTRACT FROM AUTHOR]

Hyperuniformity is the study of stationary point processes with a sub-Poisson variance in a large window. In other words, counting the points of a hyperuniform point process that fall in a given large region yields a small-variance Monte Carlo estimation of the volume. Hyperuniform point processes have received a lot of attention in statistical physics, both for the investigation of natural organized structures and the synthesis of materials. Unfortunately, rigorously proving that a point process is hyperuniform is usually difficult. A common practice in statistical physics and chemistry is to use a few samples to estimate a spectral measure called the structure factor. Its decay around zero provides a diagnostic of hyperuniformity. Different applied fields use however different estimators, and important algorithmic choices proceed from each field’s lore. This paper provides a systematic survey and derivation of known or otherwise natural estimators of the structure factor. We also leverage the consistency of these estimators to contribute the first asymptotically valid statistical test of hyperuniformity. We benchmark all estimators and hyperuniformity diagnostics on a set of examples. In an effort to make investigations of the structure factor and hyperuniformity systematic and reproducible, we further provide the Python toolbox structure_factor, containing all the estimators and tools that we discuss. [ABSTRACT FROM AUTHOR]