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Abstract: There is a scarcity of data on the tumor B-cell receptor (BCR) repertoire and lymphoid microenvironment in primary mediastinal B-cell lymphoma (PMBL). We applied 5ʹ rapid amplification of complimentary DNA ends (5′RACE) to tumor RNA samples from 137 patients with PMBL with available gene expression profiling and next-generation sequencing data. We obtained 5′RACE results for 75 of the 137 (54.7%) patients with the following clinical characteristics: median age (range), 33 years (18-64); female, 53.3%; performance status score 0 to 1, 86.7%; stage I to II, 57.3%; first-line treatment with anti-CD20 plus doxorubicin-based chemotherapy, 100%. Among the 60 biopsies that expressed a productive BCR, we highlighted a strong somatic hypermutation profile, defined as 81.1% and >78.6% of all complementarity-determining region 3 sequences for IgVH and IgVL, respectively. When compared with other patients, this subgroup had similar clinical characteristics but a greater median allele frequency for all somatic variants, a decreased BCR diversity, and greater expression of PDL1/PDL2 and MS4A1 genes, suggesting greater tumoral infiltration. We confirmed this poorer prognosis in a multivariate model and in an independent validation cohort in which 6 of 37 (16%) PMBL patients exhibited HCD (PFS: HR, 12; OS: HR, 17).

Abstract: Activated protein C (APC) is a pleiotropic plasma protease with diverse functions derived from its anticoagulant, anti-inflammatory, and cytoprotective activities. The selective uncoupling and/or modulation of these APC activities by antibodies may have therapeutic benefit in diseases such as traumatic bleeding, hemophilia, sepsis, and ischemia. TPP-26870 is an antibody that targets a nonactive site of APC for the selective modulation of APC activities. To optimize the potency of TPP-26870, variants with single amino acid mutation in the complementarity-determining regions (CDRs) were screened, and 21 variants with improved affinity constant were identified. Interestingly, the affinity maturation of TPP-26870 did not merely generate a panel of variants with higher potency in functional assays. Functional data demonstrated that the pleiotropic functions of APC were very sensitive to epitope-CDR interactions. Single amino acid mutations within the CDRs of TPP-26870 were sufficient to elicit divergent antagonistic and agonistic effects on the various APC functional activities. These include prolonged in vitro APC plasma half-life, increased inhibition of anticoagulant activity, and agonistic enhancement of histone H3 cleavage, while having less impact on protease-activated receptor 1 cleavage, compared with TPP-26870. This study illustrates that APC is highly sensitive to non–active site targeting that can lead to unpredictable changes in its activity profile of this pleiotropic enzyme. Furthermore, this study demonstrates the ability to modify APC functions to advance the potential development of APC-targeted antibodies as therapeutics for the treatment of diseases including trauma bleeding, hemophilia, ischemia, and sepsis.

Background: Tendon transfers of the latissimus dorsi transfer (LDT) or the lower trapezius transfer (LTT) are treatment options for irreparable posterosuperior irreparable rotator cuff tears (PSIRCT). There is still no consensus on which type of tendon transfer is superior in the treatment of PSIRCT. Due to the differences in the anatomy and biomechanics, we hypothesize that there are different clinical situations in which either LDT or LTT should be preferred. The aim of this study was to evaluate the clinical and radiological outcomes of LDT and LTT in patients with PSIRCT to establish a clinical algorithm for the treatment decision. Materials and methods: This is a retrospective, single-center observational study. Included were patients who underwent arthroscopically assisted LDT (aaLDT) or arthroscopically assisted LTT (aaLTT) for PSIRCT. In all patients, range of motion (ROM), external rotation strength, visual analog scale of pain and subjective shoulder value were determined pre- and postoperatively. Constant–Murley score was evaluated at the final follow-up. The complication rate, failure of the tendon transfer, and revision rate were analyzed. Results: In total, 29 aaLDT (age 64 years, median follow-up time 45 months) and 8 aaLTT (age 54 years, median follow-up time 34 months) were included. Active ROM, visual analog scale and subjective shoulder value was significantly improved in both cohorts. At follow-up, the median Constant–Murley score was 73 (aaLDT) and 77 (aaLTT), respectively. The failure rate, including revision surgery, was 14% (aaLDT) and 13% (aaLTT), respectively. Low functional findings preoperatively were correlated to a lower functional outcome at follow-up in both groups. Painful loss of anterior elevation and loss of external rotation had no significant impact on functional outcomes in aaLDT. Conclusion: Following the treatment algorithm based on the clinical examination, clinical outcome parameters, active ROM and pain could be significantly improved. A good preoperative function was associated with a good clinical outcome in both transfers. A low failure and revision rate supports the good decision-making of the algorithm presented.

Background: Several bacterial species belonging to the Gammaproteobacteria possess intrinsic class A β-lactamase genes that may represent a source of further dissemination and acquisition to other Gram-negative species. Here we characterised KSA-1 class A β-lactamase, the gene of which was identified within the chromosome of an environmental Enterobacterales species, namely Kosakonia sacchari, which was also recently identified as the progenitor of an MCR-like colistin-resistance determinant. Methods: In silico analysis using the GenBank database identified a class A β-lactamase gene within the chromosome of K. sacchari SP1 (GenBank accession no. WP_017456759). The corresponding protein KSA-1 shared 63% amino acid identity with the intrinsic CKO-1 from Citrobacter koseri and 53% with TEM-1. Using the K. sacchari DSM 100203 reference strain as a template, blaKSA-1 was amplified, cloned into the plasmid pUCp24 and expressed in Escherchia coli TOP10. Minimal inhibitory concentrations and kinetic parameters were obtained from the purified enzyme. Results: K. sacchari strain SP1 conferred resistance to amino-, carboxy- and ureido-penicillins only. Once produced within E. coli, KSA-1 showed a typical clavulanic acid-inhibited extended spectrum β-lactamase associated with a peculiar temocillin resistance profile. Kinetic assays were performed using a purified extract of KSA-1 and demonstrated a high hydrolysis rate for benzylpenicillin and piperacillin, as well as weakly extended spectrum cephalosporins. Determination of inhibitory constants showed 50% inhibitory concentration values of 2.2, 3 and 1.8 nM for clavulanic acid, tazobactam and avibactam, respectively. Analysis of sequences surrounding the blaKSA-1 gene did not reveal any mobile element that could have been involved in the acquisition of this β-lactamase gene in that species. Conclusion: KSA-1 is a class A extended spectrum β-lactamase distantly related to known extended spectrum or broad-spectrum Ambler class A β-lactamases, which is highly resistant to temocillin. The blaKSA-1 gene could be considered as intrinsic within the species.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical antimicrobial resistance threat and a WHO-prioritized pathogen. With intrinsic resistance to multiple antibiotics and the emergence of pan-resistant isolates, CRAB infections are challenging to treat, often relying on polymyxins, tigecycline, aminoglycosides, or combinations, though co-resistance is rising globally. Phage therapy is considered as a potential treatment for multidrug-resistant A. baumannii. This study focused on isolating and characterizing phages active against CRAB strains from healthcare-associated infections in Dakar, Senegal. Methods: A lytic phage, Acinetobacter vAbaIN10, was isolated from wastewater collected at the Aristide Le Dantec Hospital in Dakar, Senegal. Isolation, host range, efficiency of plating, temperature and pH stability, lysis kinetics, one-step growth test, sequencing, and genomic analysis were performed. Results: Phage vAbaIN10 belongs to the class Caudoviricetes and the genus Friunavirus. Its genome is 40,279 bp in size. Phage vAbaIN10 is stable across a wide pH range (3–9) and temperature range (25°C–60°C). The phage's lytic activity was evaluated at different multiplicities of infection (MOI): MOI 10, 1, and 10⁻¹. All MOIs significantly reduced the growth of host bacteria. The one-step growth curve showed that vAbaIN10 had a latency period of 25 min and a burst size of approximately 4.78 × 10³ phages per infected bacterial cell. No tRNA, mtRNA, clustered regularly interspaced short palindromic repeat, virulence factors, or antibiotic resistance genes were found in the genome. Conclusions: The biological and genomic characteristics of vAbaIN10 meet the requirements for its potential use in phage therapy.

Summary: Background: The excision of oropharyngeal carcinoma of more than 50% of the soft palate followed by static reconstruction may result in functional deficits, including velopharyngeal insufficiency, swallowing, and speech difficulties. We describe a functional soft palate reconstruction technique aimed at restoring aeromechanical and acoustic functions, enabling swallowing without nasal regurgitation and speech with low nasalance. Material and Methods: We developed a new operative technique, using muscle transfer and a free flap to create a dynamic reconstruction. To prove the distinct nerve innervation of the two digastric bellies and the feasibility of the technique, we first performed an anatomical study, and then implemented the technique in our clinic. The surgical technique included transfer of the anterior and posterior bellies of the digastric muscle in association with a folded radial forearm free flap. A retrospective analysis of patients who underwent this soft palate functional reconstruction after cancer resection between 2007 and 2017 was performed, and a subjective analysis of nasalance and swallowing was done to evaluate the functional outcomes. Results: Eight patients (six males, two females) with a mean age of 56 years (range 43–69) who were affected by oropharynx carcinoma (stage T1-3) infiltrating the soft palate were included. Analysis of the reconstruction showed that seven of the eight patients had satisfactory swallowing function, and all patients were able to speak in an understandable manner with minimal nasalance. Conclusions: Our surgical approach provided a functional reconstruction with outcomes close to normality, making it a suitable technique for patients with large soft palate defects.

The work focuses on particle trajectories from a railway braking device. We have developed an experimental method based on Particle Image Velocimetry analysis to evaluate the dispersion of the particulate matter. The motion of a train is simulated with an airflow imposed in a wind tunnel and a reduced-scale braking bench is embedded in the test section. The particle motion can be observed using a laser sheet in the rubbing contact plane. Images are recorded with cameras synchronized with braking bench measurements such as braking pressure, disc and pad temperature, sliding speed. The results demonstrate some correlation with particle counters and the stages of braking events regarding the concentration. They highlight opposing effects of the flow induced by the disc and by the wind tunnel. The particle motions are initially dominated by the disc induced airflow until they leave the boundary layer. The induced airflow becomes dominant.

Summary: Background: In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period. Methods: Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time. Findings: A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn’s disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 105 person-years, respectively. The incidence of CD increased from 5.1/105 in 1988–1990 to 7.9/105 in 2015–2017 (annual percent change (APC): +1.9%, p

This study introduces an innovative approach of incorporating in-situ vibrations into Directed Energy Deposition (DED) process, utilizing aluminium 5356 wire, a welding arc heat source, and an electromagnetic vibration system. The findings underscore the method's efficacy in mitigating defects of aluminium 5356 alloy fabricated part. Specifically, the anisotropic distribution of residual stress was reduced by 60%, leading to improved structural integrity. Moreover, the application of in-situ vibrations resulted in a marked reduction in surface waviness, thereby enhancing surface quality and increasing the building efficiency factor by 14% (from 78.5% to 92.25%). Gas porosity was substantially decreased, with a reduction from 1.5 ± 0.04% in as-built parts (AB) to 0.34 ± 0.07% in vibration-assisted (VA) parts. A notable 25% reduction in grain size was observed. The synergistic effect of vibrations and lower interpass temperatures effectively influenced the solidification kinetics, reducing microstructural anisotropy by eliminating characteristic columnar growth and promoting the formation of equiaxed grains. Tensile tests confirmed elimination of anisotropy in strength, with the ultimate tensile strength deviation between the x and z directions of less than 0.4% for VA samples, compared to 7.9% for AB samples. Analysis of secondary phases confirmed a homogenisation effect, evidenced by a lower segregation rate and more finely dispersed peaks of magnesium and iron-enriched precipitates in the VA samples compared to the AB ones (3.57 ± 3.42 μm2 vs. 11.28 ± 12.49 μm2). These results highlight the substantial potential of vibration-assisted DED in improving the properties of manufactured parts.

Objectives: Acinetobacter baumannii is classified by the centre for Disease Control and Prevention (CDC) as an ''urgent threat'' due to its ability to acquire and develop resistance to multiple classes of antibiotics. As a result, it is one of the most concerning pathogens in healthcare settings, with increasing incidence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) associated with high morbidity and mortality rates. Therefore, there are ongoing efforts to find novel treatment options, one of which is cefiderocol. We aim to review available evidence on cefiderocol use for severe nosocomial pneumonia due to carbapenem-resistant Acinetobacter baumannii. Methods: A comprehensive review was conducted from 2017 to 2023, covering articles from databases such as Pubmed, Scopus, and Embase, along with conference proceedings from ECCMID 2023. The primary focus was on severe nosocomial pneumonia due A. baumannii and cefiderocol. Discussion: Cefiderocol, targeting periplasmic space Penicillin-Binding Proteins (PBPs) via siderophore transport pathways, exhibits promise against multi-drug resistant Gram-negative bacilli. Its effectiveness in treating CRAB pneumonia remains debated. The CREDIBLE trial reported higher mortality with cefiderocol compared to the best available treatment, while other cohort studies showed contrasting outcomes. Patient variations and pharmacokinetic factors may underlie these discrepancies. The recommended cefiderocol dosage regimen may fall short of desired pharmacokinetic targets, especially in critically ill patients and lung infections. Pulmonary factors hindering cefiderocol's entry into bacteria through iron transporters are overlooked in clinical breakpoints. Optimized dosing or combination regimens may enhance infection site exposure and outcomes. Conclusions: Further research is needed to determine the optimal cefiderocol dosage and administration (mono vs. dual therapy, continuous vs. intermittent infusion), in severe Acinetobacter baumannii nosocomial pneumonia.

Summary: Among lyssaviruses, West Caucasian bat virus (WCBV) and Lleida bat lyssavirus (LLEBV) raise concern as their divergence from rabies virus leads to the inefficacy of available prophylactic agents. Both viruses were described in the bat Miniopterus schreibersii. We investigated the European distribution of WCBV and LLEBV by screening sera from Miniopterus schreibersii across eight countries, finding widespread serological evidence and positivity up to 70%. We evaluated the intramuscular lethality of wild type isolates in Syrian hamsters. WCBV induced 100% lethality and a clinical disease compatible with furious rabies. All animals infected with LLEBV remained healthy for 40 days, despite one individual testing positive in the brain. We confirmed LLEBV’s intramuscular a-pathogenicity using mice. Infected hamsters developed antibodies by day seven, regardless the virus and the clinical outcome. This study highlights the widespread circulation of WCBV and LLEBV in Europe and suggests differences in neuro-invasiveness and/or pathogenesis that are crucial for risk assessment.

In this paper, a new boundary element method and generalized Newton method for the resolution of quasi-static contact problems with friction in 2D is presented. The time discretization of the model and the mixed duality-fixed point formulation combined with augmented lagrangian approach are considered. This leads at each time step, to a system of static contact problem with Coulomb friction, where the study is carried out by the dual–primal active set method. After proving the well-posedness of the regularized dual problem and convergence to the solutions of the static problem, the generalized Newton method based on active set strategy method and fixed point method are constructed. An error estimate for the Galerkin discretization is established and some numerical examples are presented.

A gentle bio-inspired approach to the biosilicification occurring in diatom frustule is proposed to develop, at room temperature and without addition of a co-solvent, self-supported hybrid organic/inorganic films with pH-sensitive properties. It was found that chitosan (CS) biopolymer, a polysaccharide possessing numerous amine groups (–NH2) is capable of mimicking the action of the silaffins proteins of diatom frustule in the polycondensation process of the TetraEthoxyOrthoSilicate (TEOS) silica precursor to form a cohesive self-supported hybrid film under soft conditions in aqueous media. Thanks to its good film-forming property, hybrid chitosan/silica (CS/SiO2) films have been elaborated varying the amount of TEOS to study their optical and mechanical properties. It is shown that increasing the amount of TEOS up to 90 wt% improves the transparency, strength and stability of the films due to the interpenetration of the chitosan and silicaq networks. The incorporation of sustainable pH-sensitive alizarin dye during the elaboration of the films does not affect their mechanical properties whatever the composition. Moreover, these colored hybrid materials show good pH-sensitiveness under basic environment. Therefore, thanks to their antimicrobial properties and their pH-sensitivity, such self-supported films could be designed for applications such as smart sustainable food packaging and food degradation indicator.

Summary: Background: Systemic mastocytosis (SM) diagnosis requires the presence of 3 minor criteria or 1 major and 1 minor criterion according to the WHO 2016 classification. The aim of this study was to characterize patients with 1 or 2 minor SM criteria including KIT 816 mutation and/or aberrant expression of CD2 and/or CD25 on bone marrow (BM) mast cells (MCs), but without MC activation syndrome (MCAS) criteria. Methods: We included eligible patients from two countries diagnosed between 2011 and 2021. These patients are reported herein as monoclonal MC with clinical significance (MMCS). MMCS patients were compared with 432 patients with indolent SM (ISM) and 51 with BM mastocytosis (BMM) from the CEREMAST database. Findings: Overall, 51 patients with MMCS were included. MMCS patients with (n = 29) or without (n = 22) KIT 816 mutation did not differ significantly with regard to the prevalence of anaphylaxis and basal tryptase level. Anaphylaxis, often in the context of hymenoptera venom allergy, was more frequent in MMCS than in ISM (78% vs 35%, respectively; p

Background: Several methods for measuring IMR derived from angiography have been developed. AngioIMR is a novel method for the assessment of angiography-derived IMR with no requirement for a wire and hyperemia. The prognostic value of AngioIMR is unknown in STEMI patients. We aimed to provide the prognostic value of AngioIMR in patients with ST-elevation myocardial infarction (STEMI). Methods: This study included patients with STEMI who underwent invasive coronary angiography and primary percutaneous coronary intervention (PPCI). AngioIMR was calculated using computational flow and pressure simulation immediately after PPCI. The presence of significant coronary microvascular dysfunction was defined as AngioIMR > 40. The primary outcome was a composite of all cause death or hospitalization for heart failure (MACE). Results: A total of 178 patients were included (65.0 ± 12.8 years on average, 74 % male gender). An AngioIMR > 40 was found in 72 patients. During a median follow-up of 2.9 (2.3–6.9) years, a primary endpoint was observed in 56 patients. By Kaplan-Meier analysis, the risk of MACE was significantly higher in patients with AngioIMR > 40 (log-rank P < 0.01). An Angio IMR > 40 was significantly associated with the occurrence of the primary endpoint in univariate (70 % vs 27 %; hazard ratio 4.519; 95 % CI: 2.550–8.009; p

Summary: Background: Confidence in pregnancy outcome data for women with bipolar disorder is compromised by small cohort sizes. However, comprehensive national data have been published over the last decade, but no quantitative synthesis has been established to determine the factors associated with complications in these women. Our goal is to summarise the evidence of population-based data on obstetric complications and neonatal outcomes in women with bipolar disorder compared to women without bipolar disorder. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a comprehensive search was conducted of PubMed/MEDLINE, Embase, PsycINFO, Web of Science, and Google Scholar from inception to September 26th, 2024. Thirty-six outcomes were extracted from eligible articles for consideration. The study protocol was registered on PROSPERO (CRD42023369031). Findings: Fourteen population-based retrospective cohort studies from six high-income countries (Australia, Canada, Hong-Kong, Sweden, Taiwan, and USA) involving 47,954 women with bipolar disorder and their newborns compared to 11,896,577 women without bipolar disorder, published between 2005 and 2024, were identified. During pregnancy, women with bipolar disorders seemed to exhibit an increased risk of gestational diabetes OR = 1.46, (95% Confidence Interval [1.06–2.03]; I2 = 87%), gestational hypertension OR = 1.19 (95% CI [1.02–1.40]; I2 = 41%), antepartum haemorrhage OR = 2.02 (95% CI [1.30–3.13]; I2 = 67%), and pre-eclampsia or eclampsia OR = 1.20 (95% CI [1.05–1.36]; I2 = 67%). At delivery, women with bipolar disorder were observed to face a higher risk of caesarean section OR = 1.35 (95% CI [1.26–1.45]; I2 = 56%), and postpartum haemorrhage OR = 1.39 (95% CI [1.20–1.62]; I2 = 0%). Their newborns also appear to be at high risks of very prematurity OR = 1.84 (95% CI [1.32–2.57]; I2 = 74%), infant death OR = 1.77 (95% CI [1.01–3.13]; I2 = 41%), low birth weight OR = 1.54 (95% CI [1.19–1.99]; I2 = 70%), preterm birth OR = 1.49 (95% CI [1.29–1.72]; I2 = 87%), small for gestational age OR = 1.28 (95% CI [1.14–1.45]; I2 = 57%), and congenital malformations OR = 1.29 (95% CI [1.09–1.53]; I2 = 42%). According to the AMSTAR 2 tool, these results correspond to moderate-quality evidence. Interpretation: Despite substantial heterogeneity observed, our findings suggest the presence of a broad spectrum of complications that may affect both pregnant women with bipolar disorder and their newborns. These results can serve as a basis for the development of guidelines for the prevention and management of these complications. We need additional data from other countries, particularly from low-to-moderate income countries. Funding: The ‘Jeunes Espoirs de la Psychiatrie’ (Young Hopes of Psychiatry) doctoral programme is supported by the Fondamental Foundation and sponsored by the Bettencourt Schueller Foundation.

Summary: During infection, dengue virus (DENV) and Zika virus (ZIKV), two (ortho)flaviviruses of public health concern worldwide, induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmission electron microscopy-based quantitative analysis to demonstrate that both DENV and ZIKV alter endoplasmic reticulum-mitochondria contact sites (ERMC). This correlated at the molecular level with an impairment of ERMC tethering protein complexes located at the surface of both organelles. Furthermore, virus infection modulated the mitochondrial oxygen consumption rate. Consistently, metabolomic and mitoproteomic analyses revealed a decrease in the abundance of several metabolites of the Krebs cycle and changes in the stoichiometry of the electron transport chain. Most importantly, ERMC destabilization by protein knockdown increased virus replication while dampening ZIKV-induced apoptosis. Overall, our results support the notion that flaviviruses hijack ERMCs to generate a cytoplasmic environment beneficial for sustained and efficient replication.

The exposure of the general population to artificial light at night has dramatically increased in recent decades. Current standards for domestic lighting are based on acute exposure to light and consider blue wavelengths to be responsible for phototoxicity. However, meta-analyses pointed out the role of lifelong light exposure in the onset of age-related macular degeneration, suggesting a cumulative effect of light exposure. Here, we investigate the retinal phototoxicity of a repeated exposure to light emitting diodes of different spectral compositions in 6-week-old albino rats. Rats were exposed twice a day for 15 days to retinal doses that were safe in acute exposure (0.1 and 0.2 J/cm² for blue and white lights, 0.2 J/cm² for green light and 0.05 J/cm² for red light). We show that rats repeatedly exposed to blue and white lights display irreversible retinal damage, characterized by a degradation of the global retinal structure, a significant photoreceptor loss, and an increase of stress and inflammation markers. We highlight the role of green wavelengths in the phototoxicity of white light and show the protective effect of the addition of red light to mitigate the phototoxicity of blue light. All of this points out the need to rethink the current phototoxicity standards by taking into account the cumulative effect of the exposure to light and the role of the different parts of the emission spectrum.

Summary: Over the last decade, Hippo signaling has emerged as a major tumor-suppressing pathway. Its dysregulation is associated with abnormal expression of YAP1 and TEAD-family genes. Recent works have highlighted the role of YAP1/TEAD activity in several cancers and its potential therapeutic implications. Therefore, identifying patients with a dysregulated Hippo pathway is key to enhancing treatment impact. Although recent studies have derived RNA-seq-based signatures, there remains a need for a reproducible and cost-effective method to measure the pathway activation. In recent years, deep learning applied to histology slides have emerged as an effective way to predict molecular information from a data modality available in clinical routine. Here, we trained models to predict YAP1/TEAD activity from H&E-stained histology slides in multiple cancers. The robustness of our approach was assessed in seven independent validation cohorts. Finally, we showed that histological markers of disease aggressiveness were associated with dysfunctional Hippo signaling.

Background: Rates of venous thromboembolism (VTE) recurrence and bleeding remain high in patients with cancer who are prescribed anticoagulants (ACs) such as low-molecular-weight heparin (LMWH) after an initial VTE event. Objectives: To identify patient characteristics associated with VTE recurrence and bleeding in patients receiving LMWH for cancer-associated VTE and to explore secondary AC management and clinical outcomes in these patients. Methods: An observational study was conducted using nationwide French data for adults with active cancer who were hospitalized with VTE in 2013-2018 and were reimbursed for LMWH ≤ 30 days after hospital discharge. The main outcomes were VTE recurrence and bleeding. For both outcomes, the proportions of patients who experienced the outcome were calculated for different patient characteristics. AC switching following VTE recurrence and bleeding was tracked using Anatomical Therapeutic Chemical codes. Results: A total of 31,771 patients received LMWH, of whom 1925 (6.1%) experienced VTE recurrence and 1804 (5.7%) bleeding. Most recurrent VTE and bleeding events occurred within 6 months after the initial VTE event. The proportion of patients with VTE recurrence and bleeding varied between cancer types. Most patients who experienced VTE recurrence or bleeding continued to receive LMWH. Eleven percent of patients with VTE recurrence experienced a further recurrent VTE event within 3 months. Conclusion: More than 10% of patients who received LMWH for cancer-associated VTE experienced VTE recurrence or bleeding. AC management options in this patient population should be prospectively assessed in clinical trials.

Nitrous oxide (N2O) emissions from soil are partly controlled by aeration and gas transfer in soil, and thus by soil structure. The intensity of N2O emissions is usually expressed according to the water filled pore space (WFPS), calculated using the soil bulk density. These factors, even if they describe the soil structure and the water proportion in the porous network, do not inform about porous network characteristics among scales and their connectivity. The aim of this work was therefore to determine (1) to what extent the soil structure of an agricultural soil controlled N2O emissions during a snap-shot campaign and (2) which metric of gas transfer or soil structure was the most appropriate to describe the N2O emission variability at field scale. N2O emissions were measured with a mobile chamber on a maize crop after fertilization with several soil management practices resulting in four soil states (strip-till versus tillage, compacted soil versus uncompacted) with contrasting soil structure. Soil cylinders and bulk soil were sampled from 24 plots exhibiting a strong gradient in N2O emissions. Classical soil physical and chemical properties were measured, including soil bulk density and water filled pore space. Soil structure also was characterized quantitatively by X-ray tomography at meso and macro scales, and indirectly by gas transfer parameters. Clear differences were observed between low and high emission plots in terms of soil structure, soil temperature and nitrate concentration. However, soil structure appeared more strongly connected to N2O emissions, and some thresholds on soil structural indicators were relevant to disentangle high and low N2O fluxes. Some structural indicators at both scales (e.g. porosity, surface density) and gas transfer parameters (relative gas diffusivity, air permeability) were good descriptors of the observed N2O fluxes. Nevertheless, the gas transfer parameters can be easily measured over a short period of time, whereas the soil structure indicators determined from 3D images require an acquisition and a processing phase that can be time consuming. A good compromise to evaluate the field N2O flux potential from an easy measure would be to evaluate the relative gas diffusivity, which directly controls the diffusion of oxygen in soil and thereby the microbial processes of N2O production.

Background: Cortical high-frequency activation immediately before death has been reported, raising questions about an enhanced conscious state at this critical time. Here, we analyzed an electroencephalogram (EEG) from a comatose patient during the dying process with a standard bedside monitor and spectral parameterization techniques. Methods: We report neurophysiologic features of a dying patient without major cortical injury. Sixty minutes of frontal EEG activity was recorded using the Sedline™ monitor. Quantitative metrics of the frequency spectrum, the non-oscillatory 1/f characteristic, and signal complexity with Lemple-Ziv-Welch and permutation entropy were calculated. In addition to comparing the EEG trajectories over time, we provide a comparison to EEG records obtained from other studies with well-known vigilance states (sleep, anesthesia, and wake). Results: Although we observed changes in high-frequency activation during the dying process, larger alterations of the aperiodic EEG components were also noted. These changes differed dramatically when compared to EEG records representative of wake, slow-wave sleep, or anesthesia. Although still fundamentally unique, the neuronal activity present in the dying brain is more similar to REM sleep than any other state we tested. Conclusion: Even in patients with coma, temporal dynamics in quantitative EEG features (including the aperiodic components) can be observed in the final hour before death.

Summary: Background: Drug use disorder (DUD) poses a major public health crisis globally, necessitating immediate attention to global trends and future projections to develop effective health policies and interventions. Thus, we aimed to estimate the global trends in DUD mortality rates from 1990 to 2021 and future projections of DUD deaths until 2040 across 73 countries. Methods: In this time-series analysis and modelling study, we investigated the global trends in DUD mortality rates from 1990 to 2021 using the WHO Mortality Database and forecasted future trends through 2040. Global trend analysis was analysed using a locally weighted scatter plot smoother (LOESS) curve, and future projections were calculated based on a Bayesian age-period-cohort analysis. In addition, we performed a decomposition analysis to identify the variations in DUD deaths, specifically examining factors such as population growth, ageing, and epidemiological changes. Findings: Of the 73 countries included in the analysis of DUD mortality, 45 were high-income countries (HICs), and 28 were low to middle-income countries (LMICs). The LOESS estimates of the global DUD mortality rate were 1.84 deaths per 1,000,000 people (95% CI, −0.44 to 4.12) in 1990 and 13.09 deaths per 1,000,000 people (95% CI, 10.74–15.43) in 2021. Notably, HICs showed a significant increase in DUD mortality from 1.43 deaths per 1,000,000 people (95% CI, −1.55 to 4.42) in 1990 to 17.19 deaths per 1,000,000 people (95% CI, 13.84–20.53) in 2021. A significant increase in DUD mortality was observed among individuals aged 25–64 and males. Our analysis also identified associations between DUD mortality rates and several log-transformed parameters, including Human Development Index (β, 14.92; p

Elevational gradients are often used to reveal how soil microorganisms will respond to climate change. However, inconsistent microbial distribution patterns across different elevational transects have raised doubts about their practical applicability. We hypothesized that variations in bedrock, which influence soil physical and chemical properties, would explain these inconsistencies. We therefore investigated soil microbial communities (bacterial and fungal) along two adjacent elevational transects with different bedrocks (granite vs. slate) in a subtropical forest. Our findings reveal that soil microbial communities are shaped by complex interactions between bedrock type and environmental factors along elevational gradients. Bacterial biomass was higher on slate, whereas fungal biomass was higher on granite. On granite, both bacterial and fungal biomass increased with elevation, whereas divergent patterns were observed on slate, likely due to the distinct soil properties or combinations of properties influencing microbial biomass on each bedrock. Bedrock and elevation strongly influenced microbial beta-diversity, with beta-diversity on granite driven primarily by soil total phosphorus and moisture, and on slate by soil organic carbon and pH. In contrast, alpha-diversity was impacted less by bedrock and elevation, but its relationship with environmental factors varied markedly between bedrock types. Overall, our results highlight the critical influence of bedrock in determining soil microbial community structure along elevational gradients and their potential responses to climate change.

Introduction and Objectives: Patients increasingly use social media to share and access health-related information and experiences. This study employed social media listening to gain patient-centric insights into metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD). Materials and Method: Publicly available social media data was collected between November 4th, 2020, and November 4th, 2022, about MASLD from eight countries: Brazil, China, France, Germany, Japan, South Korea, Spain, and the United Kingdom. The analysis involved capturing patient conversations on their journey stages (causes-risk factors, symptoms, diagnosis, and treatment), unmet needs, and impact on patient's quality of life (QoL) from various social media platforms to gain insights associated with MASLD. Results: A total of 1600 patient-centric posts were analyzed. The patient journey was the most prevalent topic (92 %) mentioned, followed by comorbidities (38 %) and interactions with HCPs (26 %, health care professionals). Key causes discussed included unhealthy diet (39 %) and overweight/obese (32 %), while the most mentioned symptoms were fatigue (20 %) and pain or abdominal discomfort (20 %). Ultrasound (n=170/553, 31 %) was the most used diagnosis, followed by blood tests (n=130/553, 24 %) and liver function tests (n=91/553, 16 %). Lifestyle management techniques were mainly the standard of care, followed by treatment (n=270/1061, 25 %) and follow-ups with HCPs (n=133/1061, 13 %). Over half (54 %) of the QoL discussion (n=104/192) focused on patients’ comorbidities, and 27 % on disease severity, indicating that having MASLD in moderate to severe form with comorbidities significantly affects patients’ quality of life. An emotional analysis revealed that patients were worried and frustrated about their condition but were also hopeful and determined to improve their health. Nearly 38 % of the posts mentioned that patients were emotionally affected by negative feelings, especially those with multiple comorbidities. Lack of access to knowledgeable HCPs and treatment options were the most frequently discussed unmet needs. Conclusions: This analysis of NAFLD patient experiences introduces a unique approach for deriving insights into patients' experiences and their impact on QoL. These insights have the potential to complement conventional methods and foster patient-centric research.

Introduction: In a phase 1 study, bintrafusp alfa was found to have an encouraging clinical activity in patients with previously treated advanced NSCLC. This study evaluated the safety and efficacy of bintrafusp alfa with chemotherapy in patients with stage IV NSCLC regardless of the programmed death-ligand 1 (PD-L1) expression status. Methods: In this open-label, phase 1b/2 study (NCT03840915), eligible patients were assigned to one of four cohorts. Patients with previously untreated metastatic NSCLC (cohorts A, B, and C) received bintrafusp alfa with chemotherapy as first-line treatment, whereas patients whose disease progressed on previous treatment with programmed cell death protein 1 or PD-L1 inhibitors (cohort D) received bintrafusp alfa with chemotherapy as second-line treatment. The primary objective of this study was to evaluate the safety and tolerability of bintrafusp alfa with chemotherapy. Results: Four serious and one nonserious treatment-emergent adverse events were considered dose-limiting toxicities, none of which were assessed as related to bintrafusp alfa by the investigator. Any-grade bintrafusp alfa-related adverse events occurred in 20.7% of patients in cohorts A+B+C and in 16.7% of patients in cohort D. Keratoacanthoma was the most common transforming growth factor-β inhibition-mediated skin lesion (cohorts A+B+C: 12.1% and cohort D: 8.3%). In cohorts A+B+C, the overall response rate was 48.3%, and in patients with PD-L1 tumor proportion score of more than or equal to 50.0%, it was 71.4%. On the basis of an interim analysis, the data were considered mature, and no further analysis has been planned. Conclusion: Bintrafusp alfa with chemotherapy was found to have a manageable safety profile and encouraging clinical activity in patients with stage IV NSCLC.

Background: Noise exposure during surgery is a known occupational hazard, impacting staff hearing and surgical outcomes. Despite guidelines such as the Australian Work Health and Safety Act, noise safety remains largely neglected in orthopaedic surgery. Anecdotally, the introduction of robotic-assisted arthroplasty has contributed to increased noise production. This research article aims to investigate the role of robots in noise levels during arthroplasty. Methods: In this prospective observational study, we collected noise exposure data during total knee arthroplasty with and without robotic assistance. Noise levels were measured using a smartphone placed in the surgeon’s breast pocket. Patient demographics and surgical details were collected for subgroup analysis. Mean (LAeq), time-weighted average, and peak noise levels, as well as dose equivalent were calculated to quantify the exposure. Results: A total of 65 knee arthroplasty sound recordings were included with a mean noise level of 82.0 dB (standard deviation [SD]: 3.9). Robotic-assisted surgeries exhibited significantly higher levels than using the conventional technique: 82.4 (SD: 3.2) vs 78.4 dB (SD: 3.8) (

Objective: This study created and evaluated the face validity of a novel, low-cost, three-dimensional printed pediatric laparoscopic trainer and compared it to a standard laparoscopic trainer (LT). Design: We developed the Space Child Laparoscopic Trainer (SCLT) using fused deposition modeling technology with a Bambulab P1S 3D printer.The cost per unit was five euros and the assembly time was 10 min. The printing time was 543 min for 434 g of polylactic acid filament (PLA). A smartphone was used as the camera.The performance of experienced surgeons and surgical residents was evaluated on SCLT and LT using the Objective Structured Assessment of Technical Skill score (OSATS) and time spent. Two fundamental laparoscopic tasks, peg transfer and precision cutting, were randomly performed by each trainer. Participant satisfaction was assessed using a questionnaire. This study assessed the learning speed of surgical residents using the SCLT compared to a standard LT through a non-inferiority test. The test results were compared with those of a control group of experienced senior surgeons. Setting: A medical training program was set up for first-year surgery residents from different French cities (Rouen, Caen, Amiens, and Lille) at the Medical Training Center of Rouen, in collaboration with the University Hospital of Rouen. Participants: Ten pediatric surgeons with at least ten years of experience in laparoscopic surgery, 51 first-year surgical residents, and six external evaluators with at least five years of laparoscopic experience. Results: In total, 200 exercises were performed by 50 residents. The estimated learning speed was +0.139 (95 % confidence interval [CI]: +0.053–+0.252, p = 0.01) for LT and +0.153 (95%CI: +0.035–+0.243, p = 0.004) for SCLT. The estimated learning speed ratio for the SCLT compared to that for the LT was 1.10 (95%CI: 0.35–3.46, p = 0.09 for non-inferiority to 0.50). Conclusions: The results demonstrated a similar performance between the SCLT and standard LT for resident training in pediatric surgery. The widespread dissemination of this tool to residents and surgeons, especially in developing countries, may allow easier access to laparoscopic training.

Fault detection are essential in machine condition monitoring to ensure reliable and efficient operations. This article introduces a methodology to achieve this goal, using tacholess method. Techniques such as the Hilbert transform, adaptive observer, generalized demodulation transform (GDT), and Vold-Kalman filtering (VKF) are combined. The novelty introduced in this article lies in the use of the adaptive observer and the incorporation of the estimated speed to make the generalized Vold-Kalman filter adaptive as a function of motor current. Experimental evaluations were carried out, simulating artificial defect, corresponds to a scenario where the rotor has multiple impacts per revolution, often associated with issues such as misalignment or imbalance. These experimental findings demonstrate the performance of the proposed method, with an adaptive filter showing improved signal extraction across a range of operating situations. A diagnostic protocol has been developed, using statistical analysis, to guarantee the applicability of the method under all operating conditions.

In the context of climate change, there is a need to identify the most vulnerable ''hotspots'' to the various risks that should attract the most attention from analysts and decision-makers. In this paper, we focus on territories’ exposure to the main consequences of climate change, considering both intensity and the level of physical exposure to main climate change hazards. We propose a composite indicator that can be computed globally but at the sub-national level, covering 47,138 administrative units in the World (all land but Antarctica). It should be helpful as a first step to assess risks for countries characterized by high geoclimatic diversity but also transboundary risks. It would help identify the most vulnerable subnational administrative units and serve as one tool for adaptation planning.

Background: Non-pharmaceutical approaches can help manage preoperative anxiety, but few studies have evaluated psychoeducational programmes, especially for cancer surgery. We assessed the feasibility of the COHErence Cardiaque (COHEC) programme where cardiac coherence and medical hypnosis are combined to manage preoperative anxiety in patients undergoing breast or gynaecological cancer surgical interventions (BGCSI). Methods: Patients undergoing BGCSI were enrolled and followed a daily home programme with cardiac coherence and medical hypnosis sessions, starting 7 days before the procedure. The primary endpoint was optimal patient adherence (i.e. completion of ≥14 sessions). Secondary endpoints were anxiety levels, measured using the Visual Analogue Scale (VAS) and the Amsterdam Preoperative Anxiety and Information Scale (APAIS), satisfaction (EVAN-G), and quality of postoperative recovery (QoR-15). Results: In total, 53 patients [mean age: 55 (34–82) yr] were included; 83.7% had breast cancer and 15.1% had gynaecological cancer. Optimal adherence was achieved by 64.2% (95% confidence interval: 49.8–76.9%) of the intention-to-treat population. Among the 43 patients who completed at least one session, exploratory analysis showed that anxiety on the day before (P=0.02) and the morning of the intervention (P=0.04) was decreased in patients with severe anxiety at baseline (VAS ≥70). The median VAS satisfaction score for the programme was 10 (4–10). Overall, 94% of patients were willing to include the COHEC programme in their daily routine. Conclusions: The implementation of a psychoeducational programme combining cardiac coherence and medical hypnosis is feasible and might potentially help patients undergoing BGCSI to manage preoperative anxiety. A randomised trial is underway to assess the efficacy of the COHEC programme. Clinical trial registration: NCT03981731.

A global rise in population and environmental degradation pose challenges to agricultural productivity worldwide, compelling the need for new strategies to tackle abiotic stress, pathogens, and other pests. Despite increasing crop yields, the Green Revolution has not achieved sustainable agriculture, largely due to indiscriminate use of chemical pesticides. Extensive use of synthetic pesticides elicits a persistent impact on the ecosystem, besides affecting the health of humans, animals, and other non-target beings. These considerations have mandated the need for alternative approaches such as the utilization of bio-pesticides, comprising biochemical pesticides, microbial pesticides, and plant-incorporated protectants, to preserve agriculture output, enhance plant growth, and compensate for the reduced use of synthetic pesticides. Bio-pesticides derived from microbial sources (viruses, bacteria, and fungi) are gaining much prominence due to their sustainability, non-toxic nature, and specific action against target species. Moreover, they are also non-pathogenic and have been shown to promote the growth of agricultural crops. Therefore, they are rendered as promising choices in integrated pest management where less dependency on chemical agents is desired. Up until now, several microbial biocontrol agents have been recognized, mass-produced, and effectively formulated for commercial availability as bio-pesticides. Additionally, a few have achieved dominant positions in the market. This review highlights the sources, mode of action, and formulation of microbial bio-pesticides and provides an insight into their associated merits in the agricultural sector. It also emphasizes the commercialization and global market potential of microbial bio-control agents, paving the way for sustainable agriculture.

Background: Mixta calida, previously known as Pantoea calida, is an environmental bacterium rarely associated with human pathologies. Rare case reports mention sepsis, meningitis and implantable defibrillator infection. Case presentation: A 67-year-old female with multiple comorbidities was referred to the emergency room for a comminuted fracture of both right tibial plateaus secondary to a fall and for which she benefited from an external fixator. After removal of the fixator, failure of osteosynthesis and placement of a new fixator, a skin necrosis appeared and a propeller distal anteromedial thigh perforator flap was performed. After 6 weeks, she presented a necrosis of the flap and an osteitis. The bone biopsy was positive with pure M. calida. The patient underwent an above-knee amputation, but 6 weeks later the wound was dehiscent and again positive with pure M. calida. Conclusions: Serious infections due to M. calida are uncommon but can occur in immunocompromised patients. This case illustrates the first reported osteitis and skin necrosis due to M. calida.

Bromobenzoquinones and 2,4,6-tribromophenol belong to disinfection or chlorination by-products than can be formed in bromide-rich waters during chlorination or chloramination. Due to their high toxicities, sensitive and cost-effective analytical methods are necessary to detect and quantify them in various environmental matrices. A determination method of 2,5-dibromo-1,4-benzoquinone, 2,6-dibromo-3,5-dimethyl-1,4-benzoquinone, 2,6-dibromo-3-chloro-5-methyl-1,4-benzoquinone, 2,3,5,6-tetrabromo-1,4-benzoquinone and, 2,4,6-tribromophenol was developed using solid-phase extraction and electron capture detector-gas chromatography separation and detection (SPE-GC-ECD). Preservation of the four bromobenzoquinones with ascorbic acid allow to stabilize them into their bromohydroquinone analogues and to quench residual chlorine. Efficiency of different sorbents was tested and extraction and elution parameters were optimized by use of an experimental design. The recovery rates of each of the five compounds studied were between 59 and 101.4 %. The limits of detection (LODs) of the SPE-GC-ECD method were between 7 and 22 ng L−1. Applying this analytical procedure to real industrial chlorinated discharges in seawater, we report for the first time the presence of 2,6-dibromo-3- chloro-5-methyl-1,4-benzoquinone (up to 47 ng L−1), 2,6-dibromo-3,5-dimethyl-1,4-benzoquinone (35 ng L−1) and 2,4,6-tribromophenol (up to 42 ng L−1) in such effluents.

Summary: Prion diseases, or transmissible spongiform encephalopathies (TSEs), are neurodegenerative disorders caused by the accumulation of misfolded conformers (PrPSc) of the cellular prion protein (PrPC). During the pathogenesis, the PrPSc seeds disseminate in the central nervous system and convert PrPC leading to the formation of insoluble assemblies. As for conventional infectious diseases, variations in the clinical manifestation define a specific prion strain which correspond to different PrPSc structures. In this work, we implemented the recent developments on PrPSc structural diversity and tissue response to prion replication into a stochastic reaction-diffusion model using an application of the Gillespie algorithm. We showed that this combination of non-linearities can lead prion propagation to behave as a complex system, providing an alternative to the current paradigm to explain strain-specific phenotypes, tissue tropisms, and strain co-propagation while also clarifying the role of the connectome in the neuro-invasion process.

Summary: Background: Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years. Prolonged follow-up of responders after treatment cessation shows sustained response and a low risk of relapse in the months following cessation. To date, the optimal duration of anti-PD-1 therapy for metastatic melanoma remains unestablished. The objective of this work was to evaluate the optimal duration of ICI administration. Methods: We emulated target trials using the cloning, weighting and censoring approach. Each emulation trial aimed to compare the effect of discontinuing versus continuing ICIs at a specific timepoint, among patients still under treatment and with disease control at that time. Patients were from MelBase between 2015 and 2021. Findings: 435 participants in the MelBase cohort were eligible and were included in the 6-month discontinuation emulated trial. The results showed significantly lower OS when treatment was discontinued, than when treatment was prolonged for at least three months. The 48-month survival difference was 37.8% (95% confidence interval [CI] 19.8–60.5), and the corresponding restricted mean survival time difference was 8.3 months (95% CI: 4.1–12.7). Neither the 12-month nor the 18-month discontinuation emulated trials showed evidence of benefit of either discontinuing or continuing ICIs at either of these timepoints. The 24-month discontinuation emulated trial results were more in favor of discontinuing than continuing treatment at that time point, with an absolute 48-month survival rate that was 10.5% higher (95% CI 4.4–18.1). Interpretation: These results suggest that a one-year course of immunotherapy is both necessary and sufficient for patients with advanced melanoma. Prolonged treatment beyond 2 years does not appear to be beneficial in terms of survival and could even be detrimental. Funding: This work was supported by a grant from Bristol Myers Squibb, Merck Sharp Dhome, Pierre Fabre, Novartis, Sun Pharm, Regeneron, Sanofi, Nektar, Therapeutics and Oncyte.

Heating, ventilation, and air conditioning (HVAC) system limit electrical vehicles (EVs) range as it induces important power consumption particularly in cold climate condition. In the present pilot study, the hypotheses are that EVs range could be improved by reducing HVAC setpoint consign and that despite the resulting lower cabin temperature, the thermal comfort could be at least maintained by proper activation of the heating elements near the occupant. Furthermore, one supplemental expectation is that associated thermal comfort and thermal sensation should be correlated between human participants' perception and thermal manikin's prediction. The objective of the present pilot study, involving a panel of six participants and the use of a thermal manikin, is to assess the comfort and energy efficiency of a strategy consisting in reducing the HVAC setpoint and compensating the ambient temperature reduction through heating seat (HS) and heating steering-wheel (HSW) activation. An EV exposed to an external temperature of -7 °C and two vehicle thermal conditioning strategies were compared: the configuration A consisted in activating only the HVAC in auto mode with setpoint 21; whereas in the configuration B, the HVAC was set in auto mode with setpoint 19 and HS and HSW were also activated. For both configurations, ambient temperature and EV power consumption was measured. Moreover, thermal sensation and comfort were assessed through human participants subjective evaluation and thermal manikin estimation. After 1 h, the energy consumption is reduced in configuration B compared to configuration A by 16,9 ± 1,5 %. Despite a lower temperature in configuration B, the global thermal perception perceived by participants and manikin is not impaired. The configuration B must be considered as a suitable strategy to reduce total energy consumption of EV maintaining users' thermal comfort. Overall, thermal manikin estimation correlated well with participants subjective thermal perception.

Compressed earth bricks (CEBs) are increasingly used as a sustainable building material, but their hygroscopic nature makes them susceptible to moisture-related degradation. Monitoring moisture content in CEBs is crucial for ensuring structural integrity and durability, yet existing methods are often destructive or limited in application. This study presents a non-destructive approach for assessing moisture content in CEBs using electrical resistivity measurements, adapted from geophysical surveying techniques. The research employed a modified Syscal Junior Switch-48 resistivity meter with 4-electrode and 16-electrode configurations to measure electrical resistance in CEB samples under controlled relative humidity conditions ranging from 20 % to 100 %. Clear logarithmic correlations were established between moisture content (1.86–9.48 %) and electrical resistivity. The measured electrical resistivity varied from 12.4Ωm at 9.48 % moisture content to 3350Ωm at 1.86 % moisture content, demonstrating the method's sensitivity across a wide range of moisture levels. The 50 mA measurement mode demonstrated capability to assess moisture levels down to 1.86 %, while the standard 1250 mA mode was effective above 2.9 % moisture content. Numerical modeling using finite element analysis was conducted to determine geometric factors and true resistivity values. The 16-electrode multiplexed measurements showed good agreement with the experimental trend, enabling potential internal moisture mapping. This application of resistivity measurements represents a significant advance in non-destructive monitoring of earthen construction materials.

Summary: Background: Following mild traumatic brain injury (mTBI), elevated concentrations of brain-specific blood proteins glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) may be indicative of intracranial lesions normally detected by head CT scans. We sought to validate the performance of this combination of biomarkers at predetermined cutoff values with an automated immunoassay to predict which patients did not have intracranial lesions. Methods: This prospective, observational study was conducted in France and Spain at 16 emergency departments. Adult patients with mTBI were eligible if they had a head CT scan and gave a 10-ml blood sample within 12 h of injury. GFAP and UCH-L1 serum concentrations were measured and analysed, in less than an hour time, according to predefined cutoff values of 22 pg/ml and 327 pg/ml, respectively. Serum concentrations of S100B protein were concomitantly determined in a subset of patients. The primary outcome measures were the sensitivity and negative predictive value (NPV) of the combined GFAP–UCH-L1 test to rule out intracranial lesions on head CT scans. ClinicalTrials.gov (NCT04032509). Findings: Between August 2019 and June 2021, 1508 patients were recruited, and 1438 were included in the main analysis. Median age was 69 years (IQR 44–83). Most patients (74%) presented 3 h after trauma. 179 (12.4%) patients were positive for intracranial lesions by CT. The sensitivity of the combined test was 98.3% (95% CI 95.0–99.7) and the specificity 24.9 (95% CI 22.6–27.4), with a NPV of 99.1% (95% CI 97.1–99.8). Three patients with a positive CT scan had negative biomarker test results. S100B had a sensitivity of 83.0% (95% CI 76.2–88.2) and a NPV of 94.2% (95% CI 91.6–96.0). Patients with higher biomarker values more frequently had poorer recovery at 3 months after injury. Interpretation: Testing for GFAP and UCH-L1, using validated cutoffs obtained with a new, fast automated immunoassay platform, accurately predicted the absence of intracranial lesions on head CT following mTBI. Funding: This study is co-funded by the European Institute of Innovation and Technology (EIT) Health, a body of the European Union (Grant nº19474). Biomarkers tests were funded by bioMérieux.

Zika virus (ZIKV) is a major public health problem worldwide. After several reported outbreaks, the current extent of infections caused by this orthoflavivirus in the Sahel remains to be explored. We investigated the prevalence of neutralizing antibodies against ZIKV in the general population, in HIV-infected individuals and in livestock in Chad using a seroneutralization assay that ensures high specificity level. In this retrospective serological serosurveillance investigation, we estimated the neutralizing seroprevalence to be approximately 26 % (18/69) in healthy Chadian participants and 17 % (16/94) in HIV-infected individuals, with no statistical difference between these two subgroups or genders. In addition, we found an overall ZIKV prevalence of 14 % (8/59) in small ruminants (sheep and goats) living in the Lake Chad Basin area, demonstrating virus circulation in animals. Our pilot study shows for the first-time evidence of ZIKV circulation in humans and in livestock in Chad in close interaction with humans, and highlights the main challenges associated with this virus in Sahelian areas.

It is necessary to ensure security and community safety around High Voltage Transmission Poles (HVTP). Legislation requires a safety perimeter around HVTP and the High Voltage Lines (HVL) where no building and tree can be located. However, surveying thousands of kilometers of circuit is an expensive and challenging task that is currently performed by human inspection. Therefore, the use of automatic detection methods enables to facilitate the inspection is necessary to reduce time and cost. Convolutional Neural Network (CNN) is proposed in this work to detect, from Google Earth images, buildings and trees within the safety perimeter of HVTP. A dedicated 3 class (House, forest and HVTP) dataset of approximately 1 million tiles with a resolution of 0.09 m/pixel is created. Tiles size for trees and building classes is 64 × 64 pixels while for the HVTP 128 × 128 pixels is used. Three CNN models are built and optimized to classify each of these classes. Models validation shows that, except for houses where the accuracy is only 84 %, the other two classes have an accuracy of over 89 %. Moreover, by analyzing the classified HVTP, type can be identified. Finally, buildings and trees within the safety perimeter around the HVTP can be identified and displayed on the image demonstrating the usefulness of the tool.

The northeastern Sunda Strait is a narrow strait separating Java and Sumatra islands. Currently, it forms a seaway between the Java Sea and the Indian Ocean. The geological setting of the region is extremely dynamic, but how the Plio-Pleistocene interplay between sea level oscillations, magmatism, and tectonics, which lead to the current setting, has not been completely understood. We analysed an important set of legacy shallow seismic data from this area to decipher these intricate relationships. Our results indicate that the tectonic extension partly dismantled the Indonesian arc since the Middle Miocene. However, volcanic products formed a barrier between the Sunda Shelf and the Indian Ocean during the Late Pliocene to the Middle Pleistocene. Marine flooding started during the Middle Pleistocene but bypassed the barrier by flooding the NW edge of Java Island. During the Late Pleistocene, high amplitudes and longer periods of the glacial-interglacial cycles ultimately connected the Java Sea with the Indian Ocean. Still, it was only during the Holocene that important erosion made this seaway efficient in transporting seawater between the two reservoirs.

Lupus nephritis (LN) diagnosis and follow-up requires noninvasive biomarkers. Therefore, the added value of coupling the urinary soluble (s)CD163/creatinuria ratio with serological markers was evaluated in a real-world clinical practice. To this end, a monocentric and retrospective study was conducted in 139 SLE patients with biopsy-proven nephritis having an active LN (LN-A, n = 63 with a positive SLEDAI-renal score) or inactive (n = 76), as well as 98 non-renal SLE patients. The urinary sCD163/creatinuria ratio outperformed serological markers for predicting LN-A (AUC>0.972; p 0.750 versus non-LN patients, and AUC>0.640 versus LN-IR patients) best predicted LN-A, and higher levels were retrieved in class III/IV proliferative LN-A. In multivariate logistic regression analysis, the urinary sCD163/creatinuria ratio remained the only statistically significant biomarker to predict LN-A (p

Studies of free-ranging wildlife often involve individual tracking by sequentially recording animals’ positions over a continuous and extended period. Automatic, programmable, operational continuously, and user-friendly thanks to the development of intuitive software, GPS (Global Positioning System) enable the acquisition of large quantities of data, day and night, regardless of field and weather conditions, while allowing for levels of spatial and temporal resolution in the location data never before achieved in wildlife tracking studies. However, GPS collars deployment on wild fauna does not directly translate into scientific outcomes. This article delves into the hidden aspects of telemetry programs, offering a reflective account of our transdisciplinary experience (between researchers and wildlife managers) in GPS tracking of urban wild boar. The described protocol and its discussion aim to outline the necessary conditions to benefit from GPS programs. The program first requires a common construction of the protocol, which meets the objectives of each partner. Second, raw data collection and transformation into information involve four steps. Finally, both technical and human-related dimensions are to be anticipated and considered for further analyses. • Transdisciplinary research requires a common construction of the protocol in line with the research question. • Technical constraints and negotiations between partners need to be considered. • Multiple steps are required to leverage the scientific advantages of the monitoring.

Background: The results of the OlympiA study led to the approval of a PARP inhibitor (olaparib) as adjuvant treatment for early breast cancer (eBC) at high risk of relapse in patients with a germline BRCA1/2 mutation (gBRCAm). However, the proportion of patients in routine practice who meet the “high-risk” criteria applied in the OlympiA study, and for whom gBRCAm testing would now be mandatory, remains unknown. Patients and methods: In this population-based study, we use unique data from the French specialized Côte d'Or Breast and Gynecological Cancer Registry, to assess the real-life proportion, and long-term prognosis of patients treated for eBC between 2005 and 2015 with standard treatment, and at “high risk” of relapse according to the OlympiA trial criteria. Results: We included 3483 patients treated for HER2-negative eBC (N = 380 with ER-, and N = 3103 with ER + tumor). We found N = 62 (1.8 %) patients with gBRCA1/2 mutations. A total of 494 patients (14.2 %) were classified as “high risk” according to the Olympia criteria; 55 % with ER-tumors, and 9.1 % with ER + tumors, respectively. Despite more intensive systemic treatments in “high risk” patients, 10-year overall survival was much worse in these “high risk” patients compared to the others: 60.1 % vs 83.8 % in ER-tumors, and 55.4 % vs 84.1 % in ER + tumors. Our estimates of net survival show an even greater difference. Conclusion: This study provides real-life insights into the prevalence and prognosis of patients with high-risk eBC, in a context where the approval of adjuvant olaparib requires careful reorganization of care, so as not to overlook a patient with gBRCAm who could benefit from adjuvant olaparib.

The data presented in this paper include the original and processed MRI images acquired with a 1.5 T whole-body MRI scanner, describing the growth kinetics, spatialization and appearance of internal defaults of individual tubers of potato plants (Rosanna cultivar of Solanum tuberosum) grown in pots in a semi-controlled environment and exposed to two water regimes. The 2 conditions were a well-watered regime, in which soil moisture was maintained at 70 % of field capacity, and a variable water deficit regime, in which soil moisture was reduced to 20 % of field capacity several times during tuber growth, followed each time by a few-day period of rehydration to 70 % of field capacity. These data are supplemented by physiological, biochemical and gene expression data obtained from the leaves and tubers of additional potato plants grown under the same conditions. All these data contribute to highlight the long-term effects of water stress on plant functioning with a particular focus on the growth kinetics, spatialization and quality of potato tubers. The dataset presented here is related to the research article entitled “Growth kinetics, spatialization and quality of potato tubers monitored in situ by MRI - long-term effects of water stress”. It is made publicly available to enable extended analyzes. It is a useful resource for biologists, agronomists and breeders interested in the potato crop, as well as for researchers interested in developing new imaging methods. All data can be used to improve databases on development and quality of tubers and to feed and validate mathematical models.