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The cultivation of grapevines has spanned millennia, leading to thousands of varieties through exchanges, mutations, and crosses between genotypes, as well probably as gene flow from wild populations. These varieties are typically categorized by regional origin and primary use, either for wine production or fruit consumption. France, within the Western European group, hosts many of the world’s renowned wine grape varieties. However, the historical development of cultivated grapevines in France and in the world remains poorly understood. This study applies morphometry on 19,377 charred and waterlogged archaeological grape pips to investigate the evolutionary history of grapevine in France over the last 10,000 years. The study compares seed outlines and lengths, corrected for taphonomic distortions, with a reference collection of 80 wild and 466 modern domestic grapevine accessions. Findings reveal a shift from wild grapevine exploitation to the expansion of domestic varieties around 600–500 BCE, coinciding with Mediterranean cultural influences and the introduction of eastern grape types. The identification of the East-Table group, a group of varieties of eastern origin for fruit consumption, indicates that grapes were also grown for food, especially in Mediterranean regions and near urban areas, alongside wine production. Early French viticulture featured a notable presence of Western European wine-type grapevines. The abundance of pips with wild-like morphology suggests early cultivation involved plants at an initial domestication stage and gene flow between introduced and wild grapevines. As viticulture spread northward, wild and Eastern morphotypes declined, leading to the dominance of Western European wine types in inner France during the Middle Ages. [ABSTRACT FROM AUTHOR]

Accurate predictions concerning a forging process can be obtained by numerical simulation, but only with a thorough knowledge of the main process variables. The material flow behavior and the interface effects are already well studied in the literature, but not the machine behavior, although it is required to estimate blow efficiency and deduce the energy actually transmitted to the workpiece. In this paper, an experimental methodology was applied to determine a spring-mass-damping model and its associated parameters for a screw press. The model and its parameters were identified with press strikes performed without billet. For validation, simulations were performed to predict blows on copper billets. The model's predictions were in good agreement with the experimental measurements for ten consecutive blows on a copper billet. The decrease of process efficiency and the evolution from inelastic blows to elastic blows were correctly depicted by the model. [ABSTRACT FROM AUTHOR]

Purpose: To explore the intensity and variation of workers' worries, pain, psychosocial factors, and margin of manoeuvre before and after a return-to-work program, and identified the psychosocial factors associated with non-return to work at the end of the rehabilitation program. Methods: A pre-post study design was used. A convenience sample of 80 workers starting a return-to-work program and having a compensated musculoskeletal injury that caused an absence of more than three months from their regular work was recruited. Data were collected at baseline and at the end of the rehabilitation program on the nature of the worries and maintenance factors defined in Dugas' generalized anxiety and worry model, using validated questionnaires. The margin of manoeuvre was assessed by the treating occupational therapist. A series of descriptive analyses were performed, as well as Generalized Estimating Equations analyses. Results: Workers' worries were work-related or disability-related 83% of the time at baseline. These worries were essentially based on the situation then occurring at work 90% of the time. For the Generalized Estimating Equations analyses on work status, the final model was significant, explaining 54% of the variance in non-return to work (Pseudo R2 = 0.54; p = 0.0001). Workers were 8.52 times less likely to return to work when the margin of manoeuvre was insufficient, and twice as likely not to return to work in the presence of intense worry. Worries were significantly associated with insufficient margin of manoeuvre. Conclusion: A strong association between workers' lack of margin of manoeuvre at work and their worries about their return to work, and poor work outcomes, supports the importance of the worker-environment interaction in rehabilitation programs. [ABSTRACT FROM AUTHOR]

The planned relocation of communities away from areas of climate-related risk has emerged as a critical strategy to adapt to the impacts of climate change. Empirical examples from around the world show, however, that such relocations often lead to poor outcomes for affected communities. To address this challenge, and contribute to developing guidelines for just and sustainable relocation processes, this paper calls attention to three fundamental tensions in planned relocation processes: (1) conceptualizations of risk and habitability; (2) community consultation and ownership; and (3) siloed policy frameworks and funding mechanisms. Drawing on the collective experience of 29 researchers, policymakers and practitioners from around the world working on planned relocations in the context of a changing climate, we provide strategies for collectively and collaboratively acknowledging and navigating these tensions among actors at all levels, to foster more equitable and sustainable relocation processes and outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Distal radius fractures are the most common upper limb fractures in adults (up to 18% of all fractures in the Emergency Department). Conservative management is possible for the majority, the preferred surgical technique being volar plate fixation. Dorsal bridge plating (DBP) is an alternative method of treatment for complex fractures. DBP acts as an internal fixator and can be used in patients needing early rehabilitation. This systematic review assesses the demographics, functional and radiological outcomes and complications of using DBP in patients with distal radius fractures compared to volar plate fixation. Methods: A literature search of PubMed, Cochrane, EMBASE and Google Scholar was performed according to PRISMA guidelines. Seven hundred and sixty-one articles were found; 11 articles met the inclusion criteria. Cadaveric studies and case studies of less than five patients were excluded. Primary outcome measures were functional and radiological outcomes. Complications were recorded as secondary outcomes. Results: Three hundred and ninety-four patients were included in the study with an average age of 54.8 years (53.9% male and 46.1% female). Weighted mean follow-up was 55.2 weeks; the mean time to plate removal was 17.3 weeks with a mean DASH score of 25.7. The weighted range of movement was 46.9° flexion, 48.8° extension, 68.4° pronation and 67.5° supination. The radiological parameters show satisfactory outcomes with a mean radial height of 10mm, volar tilt of 3.1°, ulnar variance of 0.5mm and radial inclination of 18.8°. The complication rate was 11.4%. Digital stiffness was the most common complication but improved if tenolysis was performed at plate removal. Conclusions: DBP is a good alternative to volar plating for complex distal radius fractures. The functional outcomes showed a slight loss of range of movement, whereas the radiological outcomes were within recommended limits. A significant disadvantage of the plate is the need for further surgical removal. [ABSTRACT FROM AUTHOR]

Microbial toxicity tests play an important role in various scientific and technical fields including the risk assessment of chemical compounds in the environment. There is a large battery of normalized tests available that have been standardized by ISO (International Organization for Standardization) and OECD (Organization for Economic Co-operation and Development) and which are worldwide accepted and applied. The focus of this review is to provide information on microbial toxicity tests, which are used to elucidate effects in other laboratory tests such as biodegradation tests, and for the prediction of effects in natural and technical aqueous compartments in the environment. The various standardized tests as well as not normalized methods are described and their advantages and disadvantages are discussed. In addition, the sensitivity and usefulness of such tests including a short comparison with other ecotoxicological tests is presented. Moreover, the far-reaching influence of microbial toxicity tests on biodegradation tests is also demonstrated. A new concept of the physiological potential of an inoculum (PPI) consisting of microbial toxicity tests whose results are expressed as a chemical resistance potential (CRP) and the biodegradation adaptation potential (BAP) of an inoculum is described that may be helpful to characterize inocula used for biodegradation tests. Key points: • Microbial toxicity tests standardized by ISO and OECD have large differences in sensitivity and applicability. • Standardized microbial toxicity tests in combination with biodegradability tests open a new way to characterize inocula for biodegradation tests. • Standardized microbial toxicity tests together with ecotoxicity tests can form a very effective toolbox for the characterization of toxic effects of chemicals. [ABSTRACT FROM AUTHOR]

The time that elapsed between the initial introduction and the proliferation of an invasive species is referred to as the lag phase. The identification of the lag phase is critical for generating plans for pest management and for the prevention of biosecurity failure. However, lag phases have been identified mostly through retrospective searches of historical records. The agricultural pest fall armyworm (FAW; Spodoptera frugiperda) is native to the New World. FAW invasion was first reported from West Africa in 2016, then it spread quickly through Africa, Asia, and Oceania. Here, using population genomics approaches, we demonstrate that the FAW invasion involved an undocumented lag phase. Invasive FAW populations have negative signs of genomic Tajima's D, and invasive population-specific genetic variations have particularly decreased Tajima's D, supporting a substantial amount of time for the generation of new mutations in introduced FAW populations. Model-based diffusion approximations support the existence of a period with a cessation of gene flow between native and invasive FAW populations. Taken together, these results provide strong support for the presence of a lag phase during the FAW invasion. These results show the usefulness of using population genomics analyses to identify lag phases in biological invasions. This population genomics analysis show the presence of a lag phase during the fall armyworm invasion and highlight the effectiveness of population genomics in identifying lag phases in biological invasions. [ABSTRACT FROM AUTHOR]

Functional genetics has identified drug targets for metabolic disorders. Opioid use impacts metabolic homeostasis, although mechanisms remain elusive. Here, we explore the OPRD1 gene (encoding delta opioid receptor, DOP) to understand its impact on type 2 diabetes. Large-scale sequencing of OPRD1 and in vitro analysis reveal that loss-of-function variants are associated with higher adiposity and lower hyperglycemia risk, whereas gain-of-function variants are associated with lower adiposity and higher type 2 diabetes risk. These findings align with studies of opium addicts. OPRD1 is expressed in human islets and beta cells, with decreased expression under type 2 diabetes conditions. DOP inhibition by an antagonist enhances insulin secretion from human beta cells and islets. RNA-sequencing identifies pathways regulated by DOP antagonism, including nerve growth factor, circadian clock, and nuclear receptor pathways. Our study highlights DOP as a key player between opioids and metabolic homeostasis, suggesting its potential as a therapeutic target for type 2 diabetes. Opioid use impacts metabolic homeostasis, although the mechanisms remain elusive. Here, the authors explore the OPRD1 gene (encoding the delta opioid receptor, DOP) to understand its impact on type 2 diabetes and highlight DOP as a key player between opioids and metabolic homeostasis. [ABSTRACT FROM AUTHOR]

Background: We conducted a preliminary phase I, dose-escalating, safety, and tolerability trial in the population of patients with acute intracerebral hemorrhage (ICH) by using human allogeneic bone marrow–derived mesenchymal stem/stromal cells. Methods: Eligibility criteria included nontraumatic supratentorial hematoma less than 60 mL and Glasgow Coma Scale score greater than 5. All patients were monitored in the neurosciences intensive care unit for safety and tolerability of mesenchymal stem/stromal cell infusion and adverse events. We also explored the use of cytokines as biomarkers to assess responsiveness to the cell therapy. We screened 140 patients, enrolling 9 who met eligibility criteria into three dose groups: 0.5 million cells/kg, 1 million cells/kg, and 2 million cells/kg. Results: Intravenous administration of allogeneic bone marrow–derived mesenchymal stem/stromal cells to treat patients with acute ICH is feasible and safe. Conclusions: Future larger randomized, placebo-controlled ICH studies are necessary to validate this study and establish the effectiveness of this therapeutic approach in the treatment of patients with ICH. [ABSTRACT FROM AUTHOR]

Deep learning (DL) has shown potential to provide powerful representations of bulk RNA-seq data in cancer research. However, there is no consensus regarding the impact of design choices of DL approaches on the performance of the learned representation, including the model architecture, the training methodology and the various hyperparameters. To address this problem, we evaluate the performance of various design choices of DL representation learning methods using TCGA and DepMap pan-cancer datasets and assess their predictive power for survival and gene essentiality predictions. We demonstrate that baseline methods achieve comparable or superior performance compared to more complex models on survival predictions tasks. DL representation methods, however, are the most efficient to predict the gene essentiality of cell lines. We show that auto-encoders (AE) are consistently improved by techniques such as masking and multi-head training. Our results suggest that the impact of DL representations and of pretraining are highly task- and architecture-dependent, highlighting the need for adopting rigorous evaluation guidelines. These guidelines for robust evaluation are implemented in a pipeline made available to the research community. [ABSTRACT FROM AUTHOR]

TREK-1 is a mechanosensitive channel activated by polyunsaturated fatty acids (PUFAs). Its activation is supposed to be linked to changes in membrane tension following PUFAs insertion. Here, we compared the effect of 11 fatty acids and ML402 on TREK-1 channel activation using the whole cell and the inside-out configurations of the patch-clamp technique. Firstly, TREK-1 activation by PUFAs is variable and related to the variable constitutive activity of TREK-1. We observed no correlation between TREK-1 activation and acyl chain length or number of double bonds suggesting that the bilayer-couple hypothesis cannot explain by itself the activation of TREK-1 by PUFAs. The membrane fluidity measurement is not modified by PUFAs at 10 µM. The spectral shift analysis in TREK-1-enriched microsomes indicates a KD,TREK1 at 44 µM of C22:6 n-3. PUFAs display the same activation and reversible kinetics than the direct activator ML402 and activate TREK-1 in both whole-cell and inside-out configurations of patch-clamp suggesting that the binding site of PUFAs is accessible from both sides of the membrane, as for ML402. Finally, we proposed a two steps mechanism: first, insertion into the membrane, with no fluidity or curvature modifications at 10 µM, and then interaction with TREK-1 channel to open it. [ABSTRACT FROM AUTHOR]

Rationale: The 5-choice serial reaction time task (5-CSRTT) is commonly used to assess attention in rodents. Manipulation of this task by decreasing the light stimulus duration is often used to probe attentional capacity and causes a decrease in accuracy and an increase in omissions. However, although a decrease in response accuracy is commonly interpreted as a decrease in attention, it is more difficult to interpret an increase in omissions in terms of attentional performance. Methods: Here we present a series of experiments in rats that seeks to investigate the origins of these key behavioral measures of attention in the 5-CSRTT. After an initial training in the 5-CSRTT, rats were tested in a variable stimulus duration procedure to increase task difficulty and probe visual attentional capacity under several specific controlled conditions. Conclusions: We found that response accuracy reflects visuospatial sustained attentional processing, as commonly interpreted, while response omission reflects rats' ignorance about the stimulus location, presumably due to failure to pay attention to the curved wall during its presentation. Moreover, when rats lack of relevant information, they choose not to respond instead of responding randomly. Finally, pretreatment with nicotine selectively decreased response omissions, without affecting response accuracy, particularly when the attentional demand was high. Overall, our results indicate that response accuracy and response omission thus correspond to two distinct attentional states. [ABSTRACT FROM AUTHOR]

A variety of 3-hydroxy-isoindolin-1-one derivatives were synthesized using the photodecarboxylative addition of carboxylates to phthalimide derivatives in aqueous media. Subsequent acid-catalyzed dehydration furnished 3-(alkyl and aryl)methyleneisoindolin-1-ones with variable E-diastereoselectivity in good to excellent overall yields. Noteworthy, the parent 3-phenylmethyleneisoindolin-1-one underwent isomerization and oxidative decomposition when exposed to light and air. Selected 3-hydroxy-isoindolin-1-one and 3-(alkyl and aryl)methyleneisoindolin-1-one derivatives showed moderate antibacterial activity that justifies future elaboration and study of these important bioactive scaffolds. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [177Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs). Methods: This study was part of a phase I/II trial of [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.5 GBq), in 40 patients with progressive NETs. Organ absorbed doses were monitored at each cycle using patient-specific dosimetry; the cumulative absorbed-dose limits were set at 23.0 Gy for the kidneys and 1.5 Gy for bone marrow. Absorbed dose coefficients (ADCs) were calculated using both patient-specific and model-based dosimetry for some patients. Results: In all evaluated organs, maximum [177Lu]Lu-satoreotide tetraxetan uptake was observed at the first imaging timepoint (4 h after injection), followed by an exponential decrease. Kidneys were the main route of elimination, with a cumulative excretion of 57–66% within 48 h following the first treatment cycle. At the first treatment cycle, [177Lu]Lu-satoreotide tetraxetan showed a median terminal blood half-life of 127 h and median ADCs of [177Lu]Lu-satoreotide tetraxetan were 5.0 Gy/GBq in tumours, 0.1 Gy/GBq in the bone marrow, 0.9 Gy/GBq in kidneys, 0.2 Gy/GBq in the liver and 0.8 Gy/GBq in the spleen. Using image-based dosimetry, the bone marrow and kidneys received median cumulative absorbed doses of 1.1 and 10.8 Gy, respectively, after three cycles. Conclusion: [177Lu]Lu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy. Trial registration: NCT02592707. Registered October 30, 2015. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown. Objective: To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests. Methods: We analyzed children (≤ 18 y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race). Results: We included 103 children with RIS (67% girls, median age = 14.9 y). Children ≥ 12 y were more likely than children < 12 y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12 y (median 11d vs. 159d, p = 0.03). Conclusions: Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the systemic cytokine signature of critically ill COVID-19 patients in a high mortality setting aiming to identify biomarkers of severity, and to explore their associations with viral loads and clinical characteristics. We studied two COVID-19 critically ill patient cohorts from a referral centre located in Central Europe. The cohorts were recruited during the pre-alpha/alpha (November 2020 to April 2021) and delta (end of 2021) period respectively. We determined both the serum and bronchoalveolar SARS-CoV-2 viral load and identified the variant of concern (VoC) involved. Using a cytokine multiplex assay, we quantified systemic cytokine concentrations and analyzed their relationship with clinical findings, routine laboratory workup and pulmonary function data obtained during the ICU stay. Patients who did not survive had a significantly higher systemic and pulmonary viral load. Patients infected with the pre-alpha VoC showed a significantly lower viral load in comparison to those infected with the alpha- and delta-variants. Levels of systemic CTACK, M-CSF and IL-18 were significantly higher in non-survivors in comparison to survivors. CTACK correlated directly with APACHE II scores. We observed differences in lung compliance and the association between cytokine levels and pulmonary function, dependent on the VoC identified. An intra-cytokine analysis revealed a loss of correlation in the non-survival group in comparison to survivors in both cohorts. Critically ill COVID-19 patients exhibited a distinct systemic cytokine profile based on their survival outcomes. CTACK, M-CSF and IL-18 were identified as mortality-associated analytes independently of the VoC involved. The Intra-cytokine correlation analysis suggested the potential role of a dysregulated systemic network of inflammatory mediators in severe COVID-19 mortality. [ABSTRACT FROM AUTHOR]

In this study, we investigate the nature of Canadian early career (0 to 3 years) nurses' (N = 704; 87.8% female, aged 20 to 52) psychological need fulfillment profiles, accounting for the global and specific level of satisfaction and frustration of their needs for autonomy, relatedness, and competence. Our adoption of a longitudinal design (12 months, three time points with n = 626 at Time 1, 459 at Time 2, and 370 at Time 3) made it possible to test the within-person and within-sample stability of these profiles. To obtain a more in depth understanding of these profiles, we investigated the role of job demands and resources in the prediction of profile membership, and several work-related outcomes of these profiles. Latent transition analysis revealed five profiles differing in global and specific need fulfillment levels. These profiles remained stable over the 12 months, although nurses tended to transition into less fulfilled profiles over time. Nurses' perceptions of job demands and resources shared well-differentiated relations with the profiles, and more fulfilled profiles tended to report more adaptive functioning and well-being at work. [ABSTRACT FROM AUTHOR]

Background: Multiaxial dynamic loading situations occur in many industrial cases and multiaxial dynamic test development is thus a crucial issue. Objective: To meet this challenge, a biaxial compression Hopkinson set-up with four symmetric input bars is designed. Methods: The set-up consists of a vertical single striker, a sliding surface mechanism that transfers the impact energy to four horizontal tension bars, and four horizontal Hopkinson bars whose extremities are dynamically compressed by the previous tension bars. Strain gauges on two positions of each Hopkinson bar enable for force and displacement measurements at the bar-sample interfaces. Results: Simple and biaxial compression tests are carried out on cuboid and cross samples, and the sample material dynamic behavior is deduced from simple compression tests. Conclusions: The displacements are also estimated using digital image correlation, which confirms the previous measurements. The consistency of the global sample behavior identified from a biaxial compression test is checked by processing numerical simulations based on the behavior determined in simple compression. The results show that the experimental device can be used to identify any behavior law in dynamic biaxial compression. [ABSTRACT FROM AUTHOR]

A lack of response to voices, and a great interest for music are part of the behavioral expressions, commonly (self-)reported in Autism Spectrum Disorder (ASD). These atypical interests for vocal and musical sounds could be attributable to different levels of acoustical noise, quantified in the harmonic-to-noise ratio (HNR). No previous study has investigated explicit auditory pleasantness in ASD comparing vocal and non-vocal sounds, in relation to acoustic noise level. The aim of this study is to objectively evaluate auditory pleasantness. 16 adults on the autism spectrum and 16 neuro-typical (NT) matched adults rated the likeability of vocal and non-vocal sounds, with varying harmonic-to-noise ratio levels. A group by category interaction in pleasantness judgements revealed that participants on the autism spectrum judged vocal sounds as less pleasant than non-vocal sounds; an effect not found for NT participants. A category by HNR level interaction revealed that participants of both groups rated sounds with a high HNR as more pleasant for non-vocal sounds. A significant group by HNR interaction revealed that people on the autism spectrum tended to judge as less pleasant sounds with high HNR and more pleasant those with low HNR than NT participants. Acoustical noise level of sounds alone does not appear to explain atypical interest for voices and greater interest in music in ASD. [ABSTRACT FROM AUTHOR]

Personal Protective Equipment (PPE) is used to reduce exposure when working with chemicals. For pesticides, exposure scenarios comprise mixing and loading (M&L) and application. The exposure prediction model recommended by European regulatory agencies for operator risk assessments—the Agricultural Operator Exposure Model (AOEM) – is based on 48 operator exposure studies involving over 500 professional operators from 10 European countries in typical working situations to assess exposure under realistic field conditions. We used the AOEM data to assess the efficiency of exposure reduction resulting from wearing chemical-resistant nitrile gloves and non-certified working coveralls during M&L (tank and backpack sprayer), applications using groundboom and airblast spraying, and outdoor and indoor (greenhouse) applications using handheld sprayers. All studies indicated consistent and high exposure reduction > 90% for gloves and non-certified coveralls across all investigated scenarios. Exceptions were almost exclusively observed when an operator incorrectly used the PPE. The mean exposure reduction from all operators, including those that used PPE incorrectly, was 95.0% for gloves and 96.4% for polyester/cotton working coveralls during M&L, and 91.1% for gloves and 94.9% for non-certified coveralls during all application scenarios. This analysis confirms the essential role of PPE and non-certified working coveralls in reducing operator exposure to pesticides. Outliers indicate that operators need to be properly trained and adhere to label instructions to apply pesticides according to good agricultural practices. [ABSTRACT FROM AUTHOR]

Purpose: To compare the oncological and perioperative outcomes of robot-assisted partial nephrectomy (RPN) and percutaneous thermal ablation (PTA) for treatment of T1 renal cell cancer (RCC) in patients older than 75 years. Materials and methods: Retrospective national multicenter study included all patients older than 75 years treated for a T1 RCC by RPN or PTA between January 2010 and January 2021. Patients' characteristics, tumor data, and perioperative and oncological outcomes were compared. Results: A total of 205 patients for 209 procedures (143 RPN and 66 PTA) were included. In the PTA group, patients were older (80.4 ± 3.7 vs. 79 ± 3.7 years (p = 0.01)); frailer (ASA score (2.43 ± 0.6 vs. 2.17 ± 0.6 (p < 0.01)); and more frequently had a history of kidney surgery (16.7% [11/66] vs. 5.6% [8/143] (p = 0.01)) than in the RPN group. Tumors were larger in the RPN group (2.7 ± 0.7 vs. 3.2 ± 0.9 cm (p < 0.01)). Operation time, length of hospital stay, and increase of creatinine serum level were higher in RPN (respectively 92.1 ± 42.7 vs. 150.7 ± 61.3 min (p < 0.01); 1.7 ± 1.4 vs. 4.2 ± 3.4 days (p < 0.01); 1.9 ± 19.3% vs. 10.1 ± 23.7 (p = 0.03)). Disease-free survival and time to progression were similar (respectively, HR 2.2; 95% CI 0.88–5.5; p = 0.09; HR 2.1; 95% CI 0.86–5.2; p = 0.1). Overall survival was shorter for PTA that disappeared after Cox adjusting model (HR 3.3; 95% CI 0.87–12.72; p = 0.08). Conclusion: Similar oncological outcomes are observed after PTA and RPN for T1 RCC in elderly patients. Clinical relevance statement: Robot-assisted partial nephrectomy and percutaneous thermal ablation have similar oncological outcomes for T1a kidney cancer in patients over 75 years; however, operative time, decrease in renal function, and length of hospital stay were lower with ablation. Key Points: • After adjusting model for age and ASA score, similar oncological outcomes are observed after percutaneous thermal ablation and robot-assisted partial nephrectomy for T1 renal cell cancer in elderly patients. • Operation time, length of hospital stay, and increase of creatinine serum level were higher in the robot-assisted partial nephrectomy group. [ABSTRACT FROM AUTHOR]

Impairment of hand motor function is a frequent consequence after a stroke and strongly determines the ability to regain a self-determined life. An influential research strategy for improving motor deficits is the combined application of behavioral training and non-invasive brain stimulation of the motor cortex (M1). However, a convincing clinical translation of the present stimulation strategies has not been achieved yet. One alternative and innovative approach is to target the functionally relevant brain network-based architecture, e.g., the dynamic interactions within the cortico-cerebellar system during learning. Here, we tested a sequential multifocal stimulation strategy targeting the cortico-cerebellar loop. Anodal transcranial direct current stimulation (tDCS) was applied simultaneously to a hand-based motor training in N = 11 chronic stroke survivors during four training sessions on two consecutive days. The tested conditions were: sequential multifocal (M1-cerebellum (CB)-M1-CB) vs. monofocal control stimulation (M1-sham-M1-sham). Additionally, skill retention was assessed 1 and 10 days after the training phase. Paired-pulse transcranial magnetic stimulation data were recorded to characterize stimulation response determining features. The application of CB-tDCS boosted motor behavior in the early training phase in comparison to the control condition. No faciliatory effects on the late training phase or skill retention were detected. Stimulation response variability was related to the magnitude of baseline motor ability and short intracortical inhibition (SICI). The present findings suggest a learning phase-specific role of the cerebellar cortex during the acquisition of a motor skill in stroke and that personalized stimulation strategies encompassing several nodes of the underlying brain network should be considered. [ABSTRACT FROM AUTHOR]

Background: The incidence, causes and impact of diaphragm thickness evolution in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock are unknown. Our study investigates its evolution during the first week of VA-ECMO and its relationship with sweep gas flow settings. Methods: We conducted a prospective monocentric observational study in a 12-bed ICU in France, enrolling patients on the day of the VA-ECMO implantation. The diaphragm thickness and the diaphragm thickening fraction (as index of contractile activity, dTF; dTF < 20% defined a low contractile activity) were daily measured for one week using ultrasound. Factors associated with diaphragm thickness evolution (categorized as increased, stable, or atrophic based on > 10% modification from baseline to the last measurement), early extubation role (< day4), and patients outcome at 60 days were investigated. Changes in diaphragm thickness, the primary endpoint, was analysed using a mixed-effect linear model (MLM). Results: Of the 29 included patients, seven (23%) presented diaphragm atrophy, 18 remained stable (60%) and 4 exhibited an increase (17%). None of the 13 early-extubated patients experienced diaphragm atrophy, while 7 (46%) presented a decrease when extubated later (p-value = 0.008). Diaphragm thickness changes were not associated with the dTF (p-value = 0.13) but with sweep gas flow (Beta = − 3; Confidence Interval at 95% (CI) [− 4.8; − 1.2]. p-value = 0.001) and pH (Beta = − 2; CI [− 2.9; − 1]. p-value < 0.001) in MLM. The dTF remained low (< 20%) in 20 patients (69%) at the study's end and was associated with sweep gas flow evolution in MLM (Beta = − 2.8; 95% CI [− 5.2; − 0.5], p-value = 0.017). Odds ratio of death at 60 days in case of diaphragm atrophy by day 7 was 8.50 ([1.4–74], p = 0.029). Conclusion: In our study, diaphragm thickness evolution was frequent and not associated with the diaphragm thickening fraction. Diaphragm was preserved from atrophy in case of early extubation with ongoing VA-ECMO assistance. Metabolic disorders resulting from organ failures and sweep gas flow were linked with diaphragm thickness evolution. Preserved diaphragm thickness in VA-ECMO survivors emphasizes the importance of diaphragm-protective strategies, including meticulous sweep gas flow titration. Key points: Question: How does the diaphragm thickness evolves during the first week of VA-ECMO treatment for a cardiogenic shock and is it associated with sweep gas flow settings? Findings: In patient receiving VA-ECMO for a cardiogenic shock, fewer progressive atrophy was described when early extubation was possible and associated with lower death rate at two months. The diaphragm thickness increased with the sweep gas flow and decreased with the acidosis. Diaphragm thickness evolution did not evolve parallel to the diaphragm thickening fraction. Meaning: In VA-ECMO-treated patients, we advocate for diaphragmatic-protective strategies through the careful titration of sweep gas flows, tight pH control, and the promotion of early extubation. [ABSTRACT FROM AUTHOR]

Two-stage anaerobic digestion and trace metals (TM) supplementation are promising techniques to improve biogas production. Fe2+ and Ni2+ can improve process stability since they are part of the cofactors of enzymes and microorganisms' growth. This work attempted to evaluate the effect of Fe2+ and Ni2+ addition on H2-rich biogas production from organic solid waste and the CH4-rich biogas production from the acidogenic effluents (AEs) enriched with TM. The TM concentrations that enhanced the hydrogen yield in the batch were 0.25 mg/L of Ni2+ and 334 mg/L of Fe2+. These concentrations were evaluated in a two-stage system. The substrate for the batch tests and fermentative reactor (first stage) was OSW. The AE generated in the first stage was the substrate to produce CH4-rich biogas in the second stage. In the first stage, the productivity achieved was 1823 ± 160 mL H2/L/day. However, TM supplementation decreased productivity by 65% since the VS removal increased. Megasphaera genus predominated in the first stage. Regarding the methanogenic reactor, the undiluted AE without TM caused the fast decay of the process. Nevertheless, the reactor operated stably after using AE enriched with TM as a substrate, and CH4 yields increased by 42%. The highest productivity achieved in the second stage was 1278 ± 42 mL CH4/L/day, operating with an organic loading rate of 2.8 gVS/L/day. The genera Proteiniphilum, Thermovirga, DMER64, Anaerovorax, and Syntrophomonas predominated in the second stage. In conclusion, AE enriched with TM can be used to recover the stability of anaerobic digesters, increasing methane production. [ABSTRACT FROM AUTHOR]

Purpose: Based on the theoretical framework of the Model of Preventive Behaviours at Work, the aim of this study was to describe the the occupational rehabilitation strategies the literature reports that support workers who have suffered an occupational injury in adopting preventive behaviours. Methods: To conduct this scoping review, we used a systematic methodology in 7 steps : (1) definition of the research question and inclusion/exclusion criteria; (2) scientific and gray literature search; (3) determination of manuscripts' eligibility; (4) extraction and charting of information; (5) quality assessment; (6) interpretation; and (7) knowledge synthesis. Results: We selected 46 manuscripts of various types (e.g. randomized trials, qualitative studies, governmental documents). Manuscripts were mainly of good or high quality according to our quality assessment. The strategies for coaching, engaging, educating and collaborating were mostly reported in the literature to support the development of the six preventive behaviours during occupational rehabilitation. The results also suggest that heterogeneity exists regarding the specificity of the strategies reported in the literature, which may have hindered our ability to provide rich and detailed descriptions. Literature also mainly describes individually oriented behaviours and reports strategies requiring a low level of worker involvement, which represent issues to adress in future researh projects. Conclusion: The strategies described in this article reprensent concrete levers that occupational rehabilitation professionals can use to support workers in the adoption of preventive behaviours at work on return from having suffered an occupational injury. [ABSTRACT FROM AUTHOR]

The emergence of High-Throughput Experimentation (HTE) as a powerful tool for reaction discovery and optimization is changing the way organic chemists are designing their experiments. It is a fantastic way to largely investigate a reaction, in a minimum of time and reagent consumption. However, HTE needs to be accessible to a wide audience for a full implementation in academic and industrial sectors. In that context, developing accessible solid dosing methodologies for submilligram dispensing is necessary. This paper aims at proposing robust mass enhancers solutions for nanomole scale dosing applicable to HTE campaigns. [ABSTRACT FROM AUTHOR]

Psychosocial stress has profound effects on the body, including the immune system and the brain1,2. Although a large number of pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders such as major depressive disorder (MDD)3, the underlying mechanisms are not well understood. Here we show that expression of a circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in the serum of humans with MDD as well as in stress-susceptible mice following chronic social defeat stress (CSDS). In mice, we show that this increase leads to alterations in extracellular space and neurophysiological changes in the nucleus accumbens (NAc), as well as altered social behaviour. Using a combination of mass cytometry and single-cell RNA sequencing, we performed high-dimensional phenotyping of immune cells in circulation and in the brain and demonstrate that peripheral monocytes are strongly affected by stress. In stress-susceptible mice, both circulating monocytes and monocytes that traffic to the brain showed increased Mmp8 expression following chronic social defeat stress. We further demonstrate that circulating MMP8 directly infiltrates the NAc parenchyma and controls the ultrastructure of the extracellular space. Depleting MMP8 prevented stress-induced social avoidance behaviour and alterations in NAc neurophysiology and extracellular space. Collectively, these data establish a mechanism by which peripheral immune factors can affect central nervous system function and behaviour in the context of stress. Targeting specific peripheral immune cell-derived matrix metalloproteinases could constitute novel therapeutic targets for stress-related neuropsychiatric disorders. Serum MMP8 is increased in stress-susceptible mice following chronic stress and leads to brain structure and behavioural changes in mice. [ABSTRACT FROM AUTHOR]

Foxo family transcription factors are critically involved in multiple processes, such as metabolism, quiescence, cell survival and cell differentiation. Although continuous, high activity of Foxo transcription factors extends the life span of some species, the involvement of Foxo proteins in mammalian aging remains to be determined. Here, we show that Foxo1 is down-regulated with age in mouse T cells. This down-regulation of Foxo1 in T cells may contribute to the disruption of naive T-cell homeostasis with age, leading to an increase in the number of memory T cells. Foxo1 down-regulation is also associated with the up-regulation of co-inhibitory receptors by memory T cells and exhaustion in aged mice. Using adoptive transfer experiments, we show that the age-dependent down-regulation of Foxo1 in T cells is mediated by T-cell-extrinsic cues, including type 1 interferons. Taken together, our data suggest that type 1 interferon-induced Foxo1 down-regulation is likely to contribute significantly to T-cell dysfunction in aged mice.Although continuous activity of Foxo transcription factors substantially increase the life span of species such as Hydra vulgaris, these proteins have never been implicated in mammalian aging. In this study, the authors demonstrate that, with age, Foxo1 is down-regulated in mouse T lymphocytes and associated with exhaustion. [ABSTRACT FROM AUTHOR]

Tumor immunosurveillance plays a major role in melanoma, prompting the development of immunotherapy strategies. The gut microbiota composition, influencing peripheral and tumoral immune tonus, earned its credentials among predictors of survival in melanoma. The MIND-DC phase III trial (NCT02993315) randomized (2:1 ratio) 148 patients with stage IIIB/C melanoma to adjuvant treatment with autologous natural dendritic cell (nDC) or placebo (PL). Overall, 144 patients collected serum and stool samples before and after 2 bimonthly injections to perform metabolomics (MB) and metagenomics (MG) as prespecified exploratory analysis. Clinical outcomes are reported separately. Here we show that different microbes were associated with prognosis, with the health-related Faecalibacterium prausnitzii standing out as the main beneficial taxon for no recurrence at 2 years (p = 0.008 at baseline, nDC arm). Therapy coincided with major MB perturbations (acylcarnitines, carboxylic and fatty acids). Despite randomization, nDC arm exhibited MG and MB bias at baseline: relative under-representation of F. prausnitzii, and perturbations of primary biliary acids (BA). F. prausnitzii anticorrelated with BA, medium- and long-chain acylcarnitines. Combined, these MG and MB biomarkers markedly determined prognosis. Altogether, the host-microbial interaction may play a role in localized melanoma. We value systematic MG and MB profiling in randomized trials to avoid baseline differences attributed to host-microbe interactions. MIND-DC was a randomized, placebo-controlled, phase 3 trial of adjuvant blood-derived natural dendritic cell (nDC)-based therapy in patients with stage III melanoma, showing that nDC-induced immune responses did not translate into survival benefit. Here the authors report that, despite randomization, baseline differences in fecal metagenomics and serum metabolomics profiles between treatment arms might have influenced the clinical outcome of the trial. [ABSTRACT FROM AUTHOR]

Background: Adverse drug events (ADEs) are not only a safety and quality of care issue for patients, but also an economic issue with significant costs. Because they often occur during hospital stays, it is necessary to accurately quantify the costs of ADEs. This review aimed to investigate the methods to calculate these costs, and to characterize their nature. Methods: A systematic literature review was conducted to identify methods used to assess the cost of ADEs on Medline, Web of Science and Google Scholar. Original articles published from 2017 to 2022 in English and French were included. Economic evaluations were included if they concerned inpatients. Results: From 127 studies screened, 20 studies were analyzed. There was a high heterogeneity in nature of costs, methods used, values obtained, and time horizon chosen. A small number of studies considered non-medical (10%), indirect (20%) and opportunity costs (5%). Ten different methods for assessing the cost of ADEs have been reported and nine studies did not explain how they obtained their values. Conclusions: There is no consensus in the literature on how to assess the costs of ADEs, due to the heterogeneity of contexts and the choice of different economic perspectives. Our study adds a well-deserved overview of the existing literature that can be a solid lead for future studies and method implementation. Trial registration: PROSPERO registration CRD42023413071. [ABSTRACT FROM AUTHOR]

Robotic-assisted thoracic surgery (RATS) is an effective treatment of non-small cell lung cancer (NSCLC) but the effects of its implementation in university hospital networks has not been described. We analyzed the early clinical outcomes, estimated costs, and revenues associated with three robotic systems implemented in the Paris Public Hospital network. A retrospective study included patients who underwent RATS for NSCLC in 2019 and 2020. Ninety-day morbidity, mortality, hospital costs, and hospital revenues were described. Economic analyses were conducted either from the hospital center or from the French health insurance system perspectives. Cost drivers were tested using univariate and multivariable analyses. Sensitivity analyses were performed to assess uncertainty over in-hospital length of stay (LOS), number of robotic surgeries per year, investment cost, operating room occupancy time, maintenance cost, and commercial discount. The study included 188 patients (65.8 ± 9.3 years; Charlson 4.1 ± 1.4; stage I 76.6%). Median in-hospital LOS was 6 days [5–9.5], 90-day mortality was 1.6%. Mean hospital expenses and revenues were €12,732 ± 4914 and €11,983 ± 5708 per patient, respectively. In multivariable analysis, factors associated with hospital costs were body mass index, DLCO, major complications, and transfer to intensive care unit. Sensitivity analyses showed that in-hospital LOS (€11,802-€15,010) and commercial discounts on the list price (€11,458-€12,732) had an important impact on costs. During the first 2 years following the installation of three robotic systems in Paris Public Hospitals, the clinical outcomes of RATS for NSCLC have been satisfactory. Without commercial discount, hospital expenses would have exceeded hospital revenues. Clinical registration number CNIL, N°2221601, CERC-SFCTCV-2021-07-20–Num17_MOPI_robolution. [ABSTRACT FROM AUTHOR]

Recent work has shown that the Madden–Julian Oscillation (MJO) winds around the Maritime Continent can drive a see-saw in oceanic mass between the Indian and Pacific oceans on intraseasonal time scales. During the boreal winter of 2012–13, this see-saw accounted for about two thirds of an unusually large (~ 30 mas, milliarcseconds) fluctuation in the oceanic excitation of Earth's polar motion about the 90°E meridian. Interestingly, the magnitude of the oceanic influence was nearly at par, but out-of-phase with that of the atmosphere and a factor of ~ 10 larger than effects associated with the hydrological cycle. Here we show that oceanic mass changes and transport anomalies during the 2012–13 boreal winter were indeed most pronounced in the Indo-Pacific basin, and that they possessed a favorable geometry to excite polar motion variations about the 90°E meridian. Phase alignment of the excitation signals from different regions, as well as between mass and motion terms, was a key characteristic of the 2012–13 event, but was far less distinct in other strong see-saw years. Basin-wise, the Indian Ocean acted as a dominant contributor to the 2012–13 polar motion excitation at MJO periods, followed by the Pacific basin. Overall, ocean dynamics in the 10°−65°S latitudinal belt over the Indo-Pacific basin accounted for ~ 93% of the global oceanic excitation function during the 2012–13 winter. The processes figuring most prominently in modulating intraseasonal polar motion were mass rearrangements in the southern Indian Ocean and the south-east Pacific Ocean, the east Australian current, and the Antarctic circumpolar current around the Antarctic landmass. Wind-driven dynamics in the Southern Ocean thus appear to be the main cause for the 2012–13 oceanic excitation signal not attributable to the see-saw. [ABSTRACT FROM AUTHOR]

This document, titled "Re-evaluating the grading of established commercialized meningioma cell line," discusses the classification of meningiomas, which are primary brain tumors. The majority of meningiomas are classified as grade 1, but approximately 20% are more aggressive and classified as grade 2 or 3. The document highlights the importance of genetic profiling in accurately classifying meningiomas and presents a study that analyzed a specific commercial cell line called BEN-MEN-1. The study found genetic mutations in this cell line, including a homozygous loss of CDKN2A, which suggests that it should be reclassified as grade 3 instead of grade 1. The authors emphasize the need for research centers to consider these findings to ensure the accuracy of their results. [Extracted from the article]

The NICO (non-invasive airway management in comatose patients) randomized controlled trial found that withholding intubation in acute poisoned comatose patients with a Glasgow Coma Scale < 9 led to significant clinical improvement in terms of in-hospital death, length of stay in the intensive care unit (ICU), and length of hospital stay compared to routine practice. The trial also conducted an economic evaluation, which showed that withholding intubation was both cost-saving and event-reducing. The study suggests that policymakers should consider utilizing these monetary benefits in critical care. [Extracted from the article]

In the literature, hemp shives have been proposed as adsorbents capable of effectively complexing metals in aqueous solution. However, studies on the localization of metals in these multicell type lignocellulosic materials are scarce and further description of adsorption sites are required for better optimization of adsorbent capacity. In this article, we show the complementarity of two synchrotron-radiation techniques, namely K-edge subtraction micro-tomography and X-ray micro-fluorescence, to visualize the spatial distribution of the copper complexed by hemp shives. Three materials have been studied: a sample washed in water (SHI-W), a sample activated using sodium carbonate (SHI-C), and a sample chemically modified by 1,2,3,4-butanetetracarboxylic acid in order to introduce carboxylic groups (SHI-BTCA). Tomography provides 3D information and only locates areas where copper is present in significant proportions. X-ray fluorescence imaging allows for a lower detection limit, but only provides 2D information. Data analysis confirmed that the Cu distribution is totally different for the three samples, in agreement with the proposed adsorption mechanism: adsorption surface and diffusion for SHI-W and SHI-C and chemisorption and ion-exchange for SHI-BTCA. [ABSTRACT FROM AUTHOR]

In Mali, where the healthcare system is severely underfunded, service delivery is often in such a state of crisis that adaptivity is essential for the continued performance and resilience of staff. The aim of this study is to enhance understanding of the correlates of team-level support for innovation. Specifically, this study investigates the central role played by team-level support for innovation in the relationship between individual-level trust and adaptivity. It also investigates whether innovation support affects the relationship linking team-level participative safety and team-level adaptivity. A single-source, mono-method, multilevel, and cross-sectional study was undertaken in Mali using validated questionnaires with healthcare providers in community healthcare centers. As expected, results indicate that team-level support for innovation positively moderates the relationship between individual-level trust and adaptivity. However, contrary to expectations, results also show that team-level support for innovation negatively moderates the positive relationship between participative safety and team-level adaptivity. This study contributes to extant literature by showing that team-level support for innovation affects adaptivity differently depending on whether it is at the individual- or team-level. While strong team-level support for innovation fosters a positive relationship between trust and individual-level adaptivity, efforts directed at supporting innovation at the team level may have a less positive impact on team adaptivity in a resource-scarce environment. Our results also suggest that managers and leaders in Malian community health centers should instill a climate of participative safety in their teams as well as foster trust behaviors in individuals if individual-level adaptivity is to be encouraged. [ABSTRACT FROM AUTHOR]

Background: Rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily was shown to be better than aspirin 100 mg daily for preventing cardiovascular (CV) death, stroke or myocardial infarction in patients with either stable coronary artery disease (CAD) or peripheral artery disease (PAD). The cost-effectiveness of this regimen in this population is essential for decision-makers to know. Methods: US direct healthcare system costs (in USD) were applied to hospitalized events, procedures and study drugs utilized by all patients. We determined the mean cost per participant for the full duration of the trial (mean follow-up of 23 months) plus quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) over a lifetime using a two-state Markov model with 1-year cycle length. Sensitivity analyses were performed on the price of rivaroxaban and the annual discontinuation rate. Results: The costs of events and procedures were reduced for Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) patients who received rivaroxaban 2.5 mg orally (BID) plus acetylsalicylic acid (ASA) compared with ASA alone. Total costs were higher for the combination group ($7426 versus $4173) after considering acquisition costs of the study drug. Over a lifetime, patients receiving rivaroxaban plus ASA incurred $27,255 more and gained 1.17 QALYs compared with those receiving ASA alone resulting in an ICER of $23,295/QALY. ICERs for PAD only and polyvascular disease subgroups were lower. Conclusion: Rivaroxaban 2.5 mg BID plus ASA compared with ASA alone was cost-effective (high value) in the USA. COMPASS ClinicalTrials.gov identifier: NCT01776424. [ABSTRACT FROM AUTHOR]

Background: Obesity is a multifactorial chronic disease with a high, increasing worldwide prevalence. Genetic causes account for 7% of the cases in children with extreme obesity. Data sources: This narrative review was conducted by searching for papers published in the PubMed/MEDLINE, Embase and SciELO databases and included 161 articles. The search used the following search terms: "obesity", "obesity and genetics", "leptin", "Prader-Willi syndrome", and "melanocortins". The types of studies included were systematic reviews, clinical trials, prospective cohort studies, cross-sectional and prospective studies, narrative reviews, and case reports. Results: The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight. However, several important aspects of the pathophysiology of obesity remain unknown. Genetic causes of obesity can be grouped into syndromic, monogenic, and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years, hyperphagia, or a family history of extreme obesity. A microarray study, an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose. There are three therapeutic levels: lifestyle modifications, pharmacological treatment, and bariatric surgery. Conclusions: Genetic study technologies are in constant development; however, we are still far from having a personalized approach to genetic causes of obesity. A significant proportion of the affected individuals are associated with genetic causes; however, there are still barriers to its approach, as it continues to be underdiagnosed. DAegJsbXdW68Qr_u2JubfX Video Abstract (MP4 1041807 KB) [ABSTRACT FROM AUTHOR]

In the realm of forging processes, the challenge of real-time process control amid inherent variabilities is prominent. To tackle this challenge, this article introduces a Proper Orthogonal Decomposition (POD)-based surrogate model for a one-blow cold upsetting process in copper billets. This model effectively addresses the issue by accurately forecasting energy setpoints, billet geometry changes, and deformation fields following a single forging operation. It utilizes Bézier curves to parametrically capture billet geometries and employs POD for concise deformation field representation. With a substantial database of 36,000 entries from 60 predictive numerical simulations using FORGE® software, the surrogate model is trained using a multilayer perceptron artificial neural network (MLP ANN) featuring 300 neurons across 3 hidden layers using the Keras API within the TensorFlow framework in Python. Model validation against experimental and numerical data underscores its precision in predicting energy setpoints, geometry changes, and deformation fields. This advancement holds the potential for enhancing real-time process control and optimization, facilitating the development of a digital twin for the process. [ABSTRACT FROM AUTHOR]

Purpose: Testicular cancer (TC) predominantly affects young men and early detection enhances survival. However, uncertainty surrounds the impact of population-wide screening. Testicular self-examination (TSE) is a simple detection method but there is a gap in current practices that needs to be assessed. Our goal was to assess the perceptions and knowledge of male subjects in the general population (MP) and general practitioners (GPs) regarding TSE for TC. Methods: Two distinct surveys evaluating knowledge and perceptions of TSE for TC were administered to GPs and MP, aged 15‒45-years. Factors that could favour the realisation of TSE or improve the knowledge of TC were evaluated by multivariable logistic regression. Results: Overall, 1048 GPs (mean (SD) age: 35.1 ± 10.3 years) and 1032 MP (mean (SD) age: 27 ± 8.2 years) answered the survey. Among the GPs, only 93 (8.9%) performed scrotal examination for TC screening. Although the majority (n = 993, 94.8%) were aware of the age of onset of TC, most (n = 768, 73.3%) did not know the overall survival rate from TC. GPs familiar with the guidelines were more likely to explain TSE to their patients (OR = 2.5 [95% CI 1.5‒4.1]; p < 0.01). Among the MP, 800 (77.5%) admitted that they did not know how to perform TSE and 486 (47.1%) did not know the main symptoms associated with TC. MP who had already undergone TC screening were more likely to be familiar with the main symptoms (OR = 2.1 [95% CI 1.6‒2.7]; p < 0.001) and MP who knew someone with TC or who had already undergone TC screening were more likely to be aware of the correct prevalence of TC (OR = 1.9 [95% CI 1.3‒2.7], p < 0.01; and OR = 1.6 [95% CI 1.2‒2.1], p < 0.01; respectively). Conclusion: The knowledge of both GPs and MP regarding TC could be improved. TSE screening and knowing someone close with TC improved the awareness of our subjects. [ABSTRACT FROM AUTHOR]

Aims: Phytomining relies on the use of metal hyperaccumulating plants growing on ultramafic soils. Such soils, naturally enriched with nickel, have drawn the attention of the scientific community for several decades, yet little is known about the effect of this metal on the structure and composition of the rhizosphere and endospheric bacterial communities of hyperaccumulators. This work aimed to investigate the impact of a Ni concentration gradient on soil's physicochemical properties and on the composition of the rhizosphere and endophytic bacterial communities of Odontarrhena chalcidica. Methods: We characterized the bacterial communities associated with O. chalcidica growing in controlled conditions on an ultramafic soil with various levels of nickel contamination obtained by spiking the soil with nickel sulfate. Results: An increase in the available nickel in soil induced changes in the dominant bacterial genera in the communities of the rhizosphere soil and in the root and shoot endosphere. This increase in available nickel also entailed changes in the relative abundance of the predicted functions, for the rhizosphere and root endospheric bacterial communities. In addition, topological features of the bacterial networks seemed to indicate that at an intermediate level of nickel contamination, two coexisting bacterial sub-communities were in competition, one adapted to "low" soil nickel content and the other to higher nickel content, while the bacterial communities were more stable at the lowest and the highest nickel soil contamination levels. Our results revealed shifts in the microbial community's structure and functions, depending of the gradient of soil nickel availability in the soil. [ABSTRACT FROM AUTHOR]

Objective: While the incidence and type of blood malignancies are well documented amid primary Sjögren's syndrome patients (pSS), data focusing on solid neoplasms are more conflicting. We aimed to describe clinical, pathological, and immunological characteristics of pSS patients with cancers, along with the chronological interplay between the two conditions. Methods: Outcomes concerning both pSS and cancer were retrospectively collected from Montpellier University Hospital (tertiary center) between 2019 and 2020. pSS characteristics were compared to a control group of pSS patients without cancer. Results: A total of 165 patients with pSS were included: 55 patients with cancer (52 female, mean age 58.4 ± 10.4 years at pSS diagnosis; mean follow-up 10.5 ± 10.1 years, 12 patients had multiple cancers) and 110 controls without cancer. Characteristics of pSS patients with cancers were different from controls mostly for lymphoma prognosis factors. Among the 70 cancers, we recorded 55 solid neoplasms (whom 27 breast cancers and 8 lung cancers, and 82% of adenocarcinomas), with no evidence of disease at the end of follow-up in 85% of them. Among the 15 recorded blood malignancies, ten were lymphomas with an excellent prognosis. Regarding chronological interplay between cancer and pSS, most cancers (43%) were diagnosed close (± 5 years) to pSS diagnosis. Breast cancers were diagnosed before or close to pSS diagnosis (mean delay − 1.8 ± 13.0 years), at an early stage, with only two relapses (no cancer-related death), while lung cancers were diagnosed late after. Conclusions: The tight chronological interplay between breast cancer and pSS and the intriguing pathological and immunological pattern of pSS in these patients suggest a hypothesis of immune control of cancer. [ABSTRACT FROM AUTHOR]

Introduction: Systemic sclerosis (SSc) is associated with esophageal dysmotility. Autologous hematopoietic cell transplantation (HCT) results in improvement of skin tightness and lung function. Whether esophageal motility improves after HCT is unknown. Methods: Esophageal motility was studied using high-resolution esophageal manometry in 21 SSc patients before and at multiple time points after autologous HCT. Median posttransplant follow-up was 2 years (range, 6 months to 5 years). Results: Prior to HCT, all 21 patients had abnormal motility—10 (48%) had unmeasurable and 11 (52%) had measurable peristalsis. Manometric diagnosis in the former 10 patients was "absent contractility" and in the latter 11 patients "ineffective esophageal motility (IEM)." After HCT, among the 10 patients with absent contractility, 9 continued to have absent contractility and one demonstrated weak measurable peristalsis. Of the 11 patients with IEM, 5 experienced SSc relapse, and 2 out of these 5 patients developed absent contractility. Among the 6 non-relapsed patients, 4 continued to have IEM, and 2 developed normal motility. Conclusions: HCT appears to have no beneficial effect on motility in patients with unmeasurable peristalsis. In patients with measurable peristalsis, HCT appears to stabilize and in some normalize motility, unless relapse occurs. Key Points • In patients with systemic sclerosis, esophageal dysmotility is a significant contributor to morbidity and so far, there has been no data describing the effects of hematopoietic cell transplantation on esophageal motility. • Our work demonstrated that in patients with systemic sclerosis and unmeasurable esophageal peristalsis prehematopoietic cell transplantation, there was no measurable beneficial effect of transplantation on esophageal motility. • In patients with systemic sclerosis and measurable peristalsis prehematopoietic cell transplantation, esophageal motility stabilized, except in relapsed patients. [ABSTRACT FROM AUTHOR]

Purpose: Partial nephrectomy (PN) for large or complex renal tumors can be difficult and associated with a higher risk of recurrence than radical nephrectomy. We aim to evaluate the clinical useful of nephrometry scores for predicting oncological outcomes in a large cohort of patients who underwent PN for renal cell carcinomas. Methods: Our analysis included patients who underwent PN for renal cell carcinoma in 21 French academic centers (2010–2020). RENAL, PADUA, and SPARE scores were calculated based on preoperative imaging. Uni- and multivariate cox models were performed to identify predictors of recurrence-free survival and overall survival. The area under the curve (AUC) was used to identify models with the highest discrimination. Decision curve analyses (DCAs) determined the net benefit associated with their use. Results: A total of 1927 patients were analyzed with a median follow-up of 32 months (14–45). RENAL score (p = 0.01), age (p = 0.002), histological type (p = 0.001), high nuclear grade (p = 0.001), necrotic component (p < 0.001), and positive margins (p = 0.005) were significantly related to recurrence in multivariate analyses. The discriminative performance of the 3 radiological scores was modest (65, 63, and 63%, respectively). All 3 scores showed good calibration, which, however, deteriorated with time. Decision curve analysis of the three models for the prediction of overall and recurrence-free survival was similar for all three scores and of limited clinical relevance. Conclusion: The association between nephrometry scores and oncological outcomes after NP is very weak. The use of these scores for predicting oncological outcomes in routine practice is therefore of limited clinical value. [ABSTRACT FROM AUTHOR]