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This paper compares the results of a theoretical approach, finite element analysis (FEA) and mechanical tests of monolithic TA6V Dode-Thin lattice core sandwich structures manufactured by powder bed laser beam melting process. An analytical approach to evaluate the mechanical properties of one Dode-Thin strut is briefly presented. The strut is then replaced by an equivalent beam whose cross-section is a solid circle. Various finite element (FE) models are used to calculate the effective mechanical properties of a defect-free structure and compared to the analytical results of beam theory. Besides the calculations, different experimental tests and measurements are carried out to measure the stiffness of the sandwich beams. These experiments show that both theoretical and numerical predictions significantly overestimate the stiffnesses. The discrepancies between the models and the as-built components are mainly due to geometrical imperfections and internal defects (porosity) caused by the AM process. Optical observations and X-ray computed tomography (CT) are then performed to determine the actual cross-sectional properties of the struts. Finally, this study provides the engineer with a simple method to replace a Dode-Thin strut with an equivalent beam of solid circular cross-section, and to define the equivalent 3D-orthotropic material with homogenized mechanical properties. Another contribution of this work is the insight into the as-built physical parameters to improve the correlation between models and experimental data. [ABSTRACT FROM AUTHOR]

We consider the additive version of the matrix denoising problem, where a random symmetric matrix S of size n has to be inferred from the observation of Y = S + Z , with Z an independent random matrix modeling a noise. For prior distributions of S and Z that are invariant under conjugation by orthogonal matrices we determine, using results from first and second order free probability theory, the Bayes-optimal (in terms of the mean square error) polynomial estimators of degree at most D, asymptotically in n, and show that as D increases they converge towards the estimator introduced by Bun et al. (IEEE Trans Inf Theory 62:7475, 2016). We conjecture that this optimality holds beyond strictly orthogonally invariant priors, and provide partial evidences of this universality phenomenon when S is an arbitrary Wishart matrix and Z is drawn from the Gaussian Orthogonal Ensemble, a case motivated by the related extensive rank matrix factorization problem. [ABSTRACT FROM AUTHOR]

As the most frequent cause of acquired myopathy, toxic myopathies are characterised by clinicopathological features that vary depending on the mode of action of the drugs or toxins involved. Although a large number of substances can induce myotoxicity, the main culprits are statins, alcohol, and corticosteroids. A rigorous, well-organised diagnostic approach is necessary to obtain a rapid diagnosis. For early diagnosis and management, it is important for clinicians to be aware that most toxic myopathies are potentially reversible, and the goal of treatment should be to avoid serious muscle damage. [ABSTRACT FROM AUTHOR]

Mechanical contacts in dry conditions are often characterized by an interfacial layer called “third body”, which generally originates from the degradations of the surfaces, but which can exhibit strongly different material properties. This layer is a direct consequence of past wear, but also exerts a control on the rate at which surfaces in contact will keep getting worn. A comprehensive understanding of mechanical contacts therefore relies on a theory describing the interplay between this sheared layer and the moving surfaces which confine it. In this paper, we make a step towards such a theory by quantitatively investigating the link between the flow regime of the third body and the mechanical loading it applies to the surfaces. For that purpose, a previously developed local model of solid flow based on the Multibody Meshfree Approach is employed, in order to simulate characteristic flow regimes identified in experiments. Typical stress concentration patterns endured by the surfaces are then described and quantified, and a simple damage model is used to demonstrate how such a model could lead to wear prediction. We demonstrate that agglomerated flow regimes are prone to enhance large and deep damaging of surfaces, while granular third body flows have a more limited and shallow damaging effect. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common genetically inherited myopathies in adults. It is characterized by incomplete penetrance and variable expressivity. Typically, FSHD patients display asymmetric weakness of facial, scapular, and humeral muscles that may progress to other muscle groups, particularly the abdominal and lower limb muscles. Early-onset patients display more severe muscle weakness and atrophy, resulting in a higher frequency of associated skeletal abnormalities. In these patients, multisystem involvement, including respiratory, ocular, and auditory, is more frequent and severe and may include the central nervous system. Adult-onset FSHD patients may also display some degree of multisystem involvement which mainly remains subclinical. In 95% of cases, FSHD patients carry a pathogenic contraction of the D4Z4 repeat units (RUs) in the subtelomeric region of chromosome 4 (4q35), which leads to the expression of DUX4 retrogene, toxic for muscles (FSHD1). Five percent of patients display the same clinical phenotype in association with a mutation in the SMCHD1 gene located in chromosome 18, inducing epigenetic modifications of the 4q D4Z4 repeated region and expression of DUX4 retrogene. This review highlights the complexities and challenges of diagnosing and managing FSHD, underscoring the importance of standardized approaches for optimal patient outcomes. It emphasizes the critical role of multidisciplinary care in addressing the diverse manifestations of FSHD across different age groups, from skeletal abnormalities in early-onset cases to the often-subclinical multisystem involvement in adults. With no current cure, the focus on alleviating symptoms and slowing disease progression through coordinated care is paramount. [ABSTRACT FROM AUTHOR]

The practical implementation of many quantum algorithms known today is limited by the coherence time of the executing quantum hardware and quantum sampling noise. Here we present a machine learning algorithm, NISQRC, for qubit-based quantum systems that enables inference on temporal data over durations unconstrained by decoherence. NISQRC leverages mid-circuit measurements and deterministic reset operations to reduce circuit executions, while still maintaining an appropriate length persistent temporal memory in the quantum system, confirmed through the proposed Volterra Series analysis. This enables NISQRC to overcome not only limitations imposed by finite coherence, but also information scrambling in monitored circuits and sampling noise, problems that persist even in hypothetical fault-tolerant quantum computers that have yet to be realized. To validate our approach, we consider the channel equalization task to recover test signal symbols that are subject to a distorting channel. Through simulations and experiments on a 7-qubit quantum processor we demonstrate that NISQRC can recover arbitrarily long test signals, not limited by coherence time. Inherent limitations on continuously measured quantum systems calls into question whether they could even in principle be used for online learning. Here, the authors experimentally demonstrate a quantum machine learning framework for inference on streaming data of arbitrary length, and provide a theory with criteria for the utility of their algorithm for inference on streaming data. [ABSTRACT FROM AUTHOR]

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

Play is thought to serve different purposes at different times during ontogeny. The nature and frequency of play are expected to change accordingly over the developmental trajectory and with socio-ecological context. Orangutans offer the opportunity to disentangle the ontogenetic trajectories of solitary and social play with their extended immature phase, and socio-ecological variation among populations and species. We evaluated the frequency of play in 39 immature individuals across two populations (Pongo pygmaeus wurmbii, at Tuanan, Borneo, and P. abelii at Suaq, Sumatra), age (0–11 years), sex, and social context, using more than 11 500 h of full-day focal observation data. We found independent age trajectories of different play types, with solitary object and solitary locomotor peaking before social play. Social play partners changed during ontogeny, and male immatures were more likely to engage in non-mother social play than females. Overall, social play was more frequent at Suaq than Tuanan, linked to the more frequent availability of partners. Furthermore, per time in association with conspecifics, Tuanan immatures were as likely to engage in social play as their peers at Suaq, suggesting similar intrinsic motivation. Increasing fruit availability correlated with both longer associations and increased social play frequency in the less sociable population of Tuanan, but not at Suaq. Our findings on orangutans support evidence from other species that different play types follow different developmental trajectories, vary with sex, social opportunities, and ecological context. Although drawing functional inferences is challenging, the distinct developmental trajectories reflecting adult sociability and behavioral repertoires may indicate that play serves several, non-mutually exclusive functions during ontogeny. [ABSTRACT FROM AUTHOR]

Evolutionary transitions in individuality are events in the history of life leading to the emergence of new levels of individuality. Recent studies have described an ecological scaffolding scenario of such transitions focused on the evolutionary consequences of an externally imposed renewing meta-population structure with limited dispersal. One difficulty for such a scenario has been explaining the stability of collective-level traits when scaffolding conditions no longer apply. Here, we show that the stability of scaffolded traits can rely on evolutionary hysteresis: even if the environment is reverted to an ancestral state, collectives do not return to ancestral phenotypes. We describe this phenomenon using a stochastic meta-population model and adaptive dynamics. Further, we show that ecological scaffolding may be limited to Goldilocks zones of the environment. We conjecture that Goldilocks zones—even if they might be rare—could act as initiators of evolutionary transitions and help to explain the near ubiquity of collective-level individuality. The stability of newly emerged collective-level traits during an evolutionary transition in individuality under the ecological-scaffolding scenario is not fully explained. Here, the authors use a stochastic meta-population model and adaptive dynamics to show that evolutionary hysteresis supports this stability. [ABSTRACT FROM AUTHOR]

The interferometric control of dissipation in a two-port system is a fruitful concept enabling the enhancement or cancellation of the input amplitudes as a function of their relative phases. Here, beyond the canonical configuration of Coherent Perfect Absorption (CPA), we apply this concept to two simultaneously excited strongly-coupled nanoscale electromechanical resonators submitted to independently controlled phase-shifted excitations. Both subsystems are read simultaneously by optical means allowing us to completely reconstruct the signature of coherent annihilation or amplification on both quadrature. We evidence that the mechanical modes amplitude can be enhanced or inhibited with respect to the case of single port excitation while phase experiences strong variations with the excitation imbalance and phase difference. Meanwhile, phase singularities with opposite topological charges are observed for mechanical normal modes. Close to the phase singularity, we demonstrate that the input of a weak phase modulation induces a large, pure phase modulation of the normal mode. These experimental demonstrations are fully modelled via the mechanical dynamical equations of our system. The interferometric control may open avenues for low-power amplitude controlled phase modulation schemes and vice-versa for potential switches and logical gates. Coherent perfect absorption allows to entirely dissipate the energy impinging on both single and multimode systems, but it typically does not allow for a control of the phase quadratures. Here, the authors implement coherent interferometric control of the phase quadratures in two strongly-coupled electromechanical nanoresonators. [ABSTRACT FROM AUTHOR]

Background: Targeting of angiogenesis has become a major therapeutic approach for the treatment of various advanced cancers. There are many unresolved questions on the toxicity of anti-angiogenic tyrosine kinase inhibitors (TKIs). Objective: We performed a meta-analysis to assess the toxicity prevalence of the different anti-angiogenic TKIs among cancer patients and in subpopulations of interest including patients with renal cell carcinoma. Patients and Methods: We searched the MEDLINE and Cochrane Library databases to November 2023. Clinical trials were eligible if they set out to report the grade ≥3 toxicities related to one of the seven currently approved anti-angiogenic TKIs as monotherapies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was applied with PROSPERO (CRD42023411946). Results: The 421 eligible studies included a total of 56,895 cancer patients treated with anti-angiogenic TKI monotherapy. Twenty-four different cancer types were identified, mainly renal cell carcinoma (41.9% of the patients). The anti-angiogenic TKI was sorafenib (34.5% of the patients), sunitinib (30.5%), regorafenib (10.7%), pazopanib (9.4%), cabozantinib (7.7%), axitinib (4.3%), and lenvatinib (2.9%). The pooled prevalence of grade 3 and 4 toxicities was 56.1% (95% confidence interval 53.5–58.6), with marked between-study heterogeneity (I2 = 96.8%). Toxicity profiles varied considerably depending on the type of TKI, the cancer type, and the specific patient characteristics. In particular, Asian patients and elderly people had higher prevalences of severe toxicities, with pazopanib being the best-tolerated drug. For patients treated with sunitinib, particularly those with metastatic RCC, there was no significant difference in terms of toxicity according to the regimen schedule. Conclusions: This meta-analysis highlights the toxicity profiles of anti-angiogenic TKI monotherapies, and thus enables high-level recommendations for the choice of anti-angiogenic TKIs on the basis of the patient's age, ethnicity, comorbidities, and comedications, for personalized treatment. [ABSTRACT FROM AUTHOR]

Motor neuron disorders comprise a clinically and pathologically heterogeneous group of neurologic diseases characterized by progressive degeneration of motor neurons (including both sporadic and hereditary diseases), affecting the upper motor neurons, lower motor neurons, or both. Hereditary motor neuron disorders themselves represent a vast and heterogeneous group, with numerous clinical and genetic overlaps that can be a source of error. This narrative review aims at providing an overview of the main types of inherited motor neuron disorders by recounting the stages in their historical descriptions. For practical purposes, this review of the literature sets out their various clinical characteristics and updates the list of all the genes involved in the various forms of inherited motor neuron disorders, including spinal muscular atrophy, familial amyotrophic lateral sclerosis, hereditary spastic paraplegia, distal hereditary motor neuropathies/neuronopathies, Kennedy's disease, riboflavin transporter deficiencies, VCPopathy and the neurogenic scapuloperoneal syndrome. [ABSTRACT FROM AUTHOR]

Objective: X-linked myopathy with excessive autophagy (XMEA) linked to the VMA21 gene leads to autophagy failure with progressive vacuolation and atrophy of skeletal muscles. Current knowledge of this rare disease is limited. Our objective was to define the clinical, radiological, and natural history of XMEA. Methods: We conducted a retrospective study collecting clinical, genetic, muscle imaging, and biopsy data of XMEA patients followed in France and reviewed the literature for additional cases. Results: Eighteen males had genetically confirmed XMEA in France, carrying four different VMA21 variants. Mean age at disease onset was 9.4 ± 9.9 (range 1–40) years. In 14/18 patients (77.8%), onset occurred during childhood (< 15 years); however in four patients, the disease started in adulthood. Patients had anterior and medial compartment thigh muscle weakness, distal contractures (56.3%), elevated CK levels (1287.9 ± 757.8 U/l) and autophagic vacuoles with sarcolemmal features on muscle histopathology. Muscle MRI (n = 10) showed a characteristic pattern of lower limb muscle involvement. In 11 patients, outcome measures were available for an average follow-up period of 10.6 ± 9.8 years and six of them show disease progression. Mean change of functional outcomes was 0.5 ± 1.2 points for Brooke and 2.2 ± 2.5 points for Vignos score, 7/16 patients (43.8%) needed a walking aid and 3/16 (18.8%) were wheelchair-bound (median age of 40 years old, range 39–48). The variant c.164-7 T > G was associated with a later onset of symptoms. Respiratory insufficiency was common (57.1%) but cardiac involvement rare (12.5%). Interpretation: XMEA has variable age of onset, but a characteristic clinical, histopathological, and muscle imaging presentation, guiding the diagnosis. Although slowly, motor disability progresses with time, and relevant genotype–phenotype correlations will help design future clinical trials. [ABSTRACT FROM AUTHOR]

SrTiO3-based conducting interfaces, which exhibit coexistence of gate-tunable 2D superconductivity and strong Rashba spin-orbit coupling (RSOC), are candidates to host topological superconductive phases. Yet, superconductivity is usually in the dirty limit, which tends to suppress nonconventional pairing and therefore challenges these expectations. Here we report on LaAlO3/SrTiO3 (LAO/STO) interfaces with large mobility and mean free paths comparable to the superconducting coherence length, approaching the clean limit for superconductivity. We further show that the carrier density, mobility, and formation of the superconducting condensate are controlled by the fine-tuning of La/Al chemical ratio in the LAO film. We find a region in the superconducting phase diagram where the critical temperature is not suppressed below the Lifshitz transition, at odds with previous experimental investigations. These findings point out the relevance of achieving a clean-limit regime to enhance the observation of unconventional pairing mechanisms in these systems. SrTiO3-based oxide interfaces, which exhibit coexistence of gate-tunable two-dimensional superconductivity and Rashba spin-orbit coupling, are candidates to host topological superconductive phases. By controlling the chemical ratio in LaAlO3, the authors demonstrate tuning of carrier densities, mobilities and the formation of superconductivity, showing that, approaching to clean limit, significant enhancement below the Lifshitz transition is observed, at odds with previous experimental investigations. [ABSTRACT FROM AUTHOR]

CNES (French Space Agency) is in charge of the development of the X-ray Integral Field Unit (X-IFU) instrument for Athena, the high resolution X-ray spectrometer of the ESA Athena X-ray Observatory. X-IFU will deliver spectra from 0.2 to 12 keV with a spectral resolution in the range of 2.5 eV up to 7 keV on a 5′′ pixels, with a field of view > 4′ equivalent diameter. The main sensor array detection chain is a key part of the instrument, being by far the main contributor to its performance. It involves major partners: NASA GFSC, NIST, SRON, VTT, APC, and IRAP. The cryo-harness interconnecting the Focal Plane Assembly cold interface to the Warm Front End Electronics is under CNES responsibility. The different technical solutions are the loom technology and the shielded twisted pair technology. Characterizations have been performed on breadboards to assess the crosstalk performances for each solution. The results of these analysis are a driver to perform the trade-off between the available cryo-harness technologies. [ABSTRACT FROM AUTHOR]

Although many studies link mineral deposit formation to rifting and hydrothermal processes, we present a study that focuses on the relationship between crustal necking and mineral deposit formation. Necking corresponds to the timing, location, and process of rift localization and abrupt crustal and lithospheric thinning. Although necking is well identified and described from present-day rifted margins and has been modeled numerically, little is known about the necking process and its possible link to ore deposit formation. We present observations from the Mont-Blanc fossil detachment system, one of the few exposed examples of a necking detachment fault. We show that fluids flowed along the fault zone and leached metals (mainly Pb and Zn). This process was associated with the hydrothermal breakdown of feldspar and biotite at temperatures of 200 °C and salinities ranging from 5 to 20 eq. wt% with a H2O-NaCl (-KCl) composition. The resulting metal-rich fluids reacted with mainly carbonate-rich units to form Pb-Zn ore deposits in basement and sedimentary cover rocks. A direct link can, therefore, be demonstrated between fluid and reaction-assisted breakdown of silicates, metal transfer and trapping along detachment faults, and the overlying sedimentary rocks during necking. Similar ore deposits can be found throughout the inner External Crystalline Massif of the Western Alps, interpreted as the former necking domain of the Alpine Tethys. This leads to the suggestion that necking and Pb-Zn deposit formation may be closely linked, a hypothesis, if correct, that has the potential to predict additional Pb-Zn-Ba-F resources in rifts, rifted margins, and reactivated fossil rifted margins forming collisional mountain belts. [ABSTRACT FROM AUTHOR]

Certification through auditing allows to ensure that critical embedded systems are secure. This entails reviewing their critical components and checking for dangerous execution paths. This latter task requires the use of specialized tools which allow to explore and replay executions but are also difficult to use effectively within the context of the audit, where time and knowledge of the code are limited. Fault analysis is especially tricky as the attacker may actively influence execution, rendering some common methods unusable and increasing the number of possible execution paths exponentially. In this work, we present a new method which mitigates these issues by reducing the number of fault injection points considered to only the most relevant ones relatively to some security properties. We use fast and robust static analysis to detect injection points and assert their impactfulness. A more precise dynamic/symbolic method is then employed to validate attack paths. This way the insight required to find attacks is reduced and dynamic methods can better scale to realistically sized programs. Our method is implemented into a toolchain based on Frama-C and KLEE and validated on WooKey, a case study proposed by the National Cybersecurity Agency of France. [ABSTRACT FROM AUTHOR]

The application of nonlinear vibration absorbers in a variety of dynamic systems is attracting significant attention. The so-called nonlinear energy sink (NES) has the ability to provide high vibration attenuation in a broad frequency with robustness. However, the effectiveness of this device can be limited with the increase of excitation, as it may induce high amplitude (i.e., detach zone) oscillation and leading to sudden failure. To address these limitations, this work proposes an investigation into an electromagnetic-enhanced nonlinear energy sink (NES-EH) aiming to combine hybrid vibration control and energy harvesting. The device comprises the conventional NES, with a cubic stiffness spring, coupled with a magnet-coil assembly. The electro-magneto-mechanical coupling provides nonlinear damping dynamics allowing mitigation of the detached zone and an efficient conversion of the absorbed energy into electrical power. Two different assemblies, varying the relative static position of the magnet coil, are considered to explore alternative nonlinear damping models. The harmonic balance method is used to build analytical solutions to characterize the dynamics of coupled systems. After a numerical validation of the analytical approach, a complete characterization of the system dynamics is performed regarding frequency-response and slow invariant manifold (SIM) curves. Parametric analysis and optimization procedure are employed to design the NES-EH parameters. The performance of the designed absorber is compared with the classical NES solution, and their robustness is also investigated. [ABSTRACT FROM AUTHOR]

Background: Methods to improve stratification of small (≤15 mm) lung nodules are needed. We aimed to develop a radiomics model to assist lung cancer diagnosis. Methods: Patients were retrospectively identified using health records from January 2007 to December 2018. The external test set was obtained from the national LIBRA study and a prospective Lung Cancer Screening programme. Radiomics features were extracted from multi-region CT segmentations using TexLab2.0. LASSO regression generated the 5-feature small nodule radiomics-predictive-vector (SN-RPV). K-means clustering was used to split patients into risk groups according to SN-RPV. Model performance was compared to 6 thoracic radiologists. SN-RPV and radiologist risk groups were combined to generate "Safety-Net" and "Early Diagnosis" decision-support tools. Results: In total, 810 patients with 990 nodules were included. The AUC for malignancy prediction was 0.85 (95% CI: 0.82–0.87), 0.78 (95% CI: 0.70–0.85) and 0.78 (95% CI: 0.59–0.92) for the training, test and external test datasets, respectively. The test set accuracy was 73% (95% CI: 65–81%) and resulted in 66.67% improvements in potentially missed [8/12] or delayed [6/9] cancers, compared to the radiologist with performance closest to the mean of six readers. Conclusions: SN-RPV may provide net-benefit in terms of earlier cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background: Heterometallic gold metallacages are of great interest for the incorporation of several cations. Especially in nuclear medicine, those metallacages can serve as a platform for radionuclides relevant for imaging or therapy (e.g. 68Ga or 177Lu). Moreover, the radionuclide 198Au is an attractive beta emitter, for potential application in nuclear medicine. Here, we aim to synthesize a new set of gold metallacages and to study their ability to coordinate to 68Ga, 177Lu and 198Au. Results: New heterometallic gold metallacages of composition [M{Au(Lmorph-κS)}3] (M = La3+, Tb3+, Lu3+ or Y3+) and [Ga{Au(Lmorph-κS)}2]NO3 have been synthesized from 2,6-dipicolinoylbis(N,N-morpholinylthiourea) (H2Lmorph) with [AuCl(THT)] and the target M3+ metal ions in yields ranging from 33 (Lu) to 62% (Tb). The characterization of the compounds bases on ESI–MS, 1H NMR, IR, EA and single-crystal X-ray diffraction techniques (all except the Ga derivative). Selected gold cages derived from H2Lmorph were compared to previously reported gold cages that were derived from 2,6-dipicolinoylbis(N,N-diethylthiourea) (H2Ldiethyl). The tested metallacages show similar IC50 values close to that of auranofin in four different cancer cell lines (MCF-7, PC-3, U383, U343), e.g. 4.5 ± 0.7 µM for [Ga{Au(Ldiethyl)}2]NO3 on PC-3. The radiolabeling experiments thereof show high radiochemical purities with 68Ga and 198Au and low radiochemical purity with 177Lu. Conclusions: The results indicate that these gold metallacages could serve as a novel platform for inclusion of different (radio)nuclides with potential theranostic applications in nuclear medicine. [ABSTRACT FROM AUTHOR]

Background: Dosing regimens of trastuzumab administered by intracerebroventricular (icv) route to patients with HER2-positive brain localizations remain empirical. The objectives of this study were to describe pharmacokinetics (PK) of trastuzumab in human plasma and cerebrospinal fluid (CSF) after simultaneous icv and intravenous (iv) administration using a minimal physiologically-based pharmacokinetic model (mPBPK) and to perform simulations of alternative dosing regimens to achieve therapeutic concentrations in CSF. Methods: Plasma and CSF PK data were collected in two patients with HER2-positive brain localizations. A mPBPK model for mAbs consisting of four compartments (tight and leaky tissues, plasma and lymph) was enriched by an additional compartment for ventricular CSF. The comparison between observed and model-predicted concentrations was evaluated using prediction error (PE). Results: The developed mPBPK model described plasma and CSF trastuzumab concentrations reasonably well with mean PE for plasma and CSF data of 41.8% [interquartile range, IQR = -9.48; 40.6] and 18.3% [-36.7; 60.6], respectively, for patient 1 and 11.4% [-10.8; 28.7] and 22.5% [-27.7; 77.9], respectively, for patient 2. Trastuzumab showed fast clearance from CSF to plasma with Cmin,ss of 0.56 and 0.85 mg/L for 100 and 150 mg q1wk, respectively. Repeated dosing of 100 and 150 mg q3day resulted in Cmin,ss of 10.3 and 15.4 mg/L, respectively. Trastuzumab CSF target concentrations are achieved rapidly and maintained above 60 mg/L from 7 days after a continuous perfusion at 1.0 mg/h. Conclusion: Continuous icv infusion of trastuzumab at 1.0 mg/h could be an alternative dosing regimen to rapidly achieve intraventricular CSF therapeutic concentrations. [ABSTRACT FROM AUTHOR]

Since the Mw 7.9 Gorkha earthquake of April 25, 2015, the seismicity of central and western Nepalese Himalaya has been monitored by an increasing number of permanent seismic stations. These instruments contribute to the location of thousands of aftershocks that occur at the western margin of the segment of the Main Himalayan Thrust (MHT) that ruptured in 2015. They also help to constrain the location of seismic clusters that originated at the periphery of the fault ruptured by the Gorkha earthquake, which may indicate a migration of seismicity along the fault system. We report here a seismic crisis that followed the Lamjung earthquake, a moderate Mw 4.7 event (ML 5.8, MLv 5.3) that occurred on May 18, 2021, about 30 km west of the Gorkha earthquake epicenter at the down-dip end of the locked fault zone. The study of the hypocentral location of the mainshock and its first 117 aftershocks confirms mid-crustal depths and supports the activation of a 30–40° dipping fault plane, possibly associated with the rupture of the updip end of the MHT mid-crustal ramp. The cluster of aftershocks occurs near the upper decollement of the thrust system, probably in its hanging wall, and falls on the immediate northern margin of a region of the fault that has not been ruptured since the 1344 or 1505 CE earthquake. The spatio-temporal distribution of the first 117 aftershocks shows a typical decrease in the associated seismicity rate and possible migration of seismic activity. Since then, the local seismicity has returned to the pre-earthquake rate and careful monitoring has not revealed any large-scale migration of seismicity towards the locked fault segments. [ABSTRACT FROM AUTHOR]

Becker muscular dystrophy (BMD) is one of the most frequent among neuromuscular diseases, affecting approximately 1 in 18,000 male births. It is linked to a genetic mutation on the X chromosome. In contrast to Duchenne muscular dystrophy, for which improved care and management have changed the prognosis and life expectancy of patients, few guidelines have been published for management of BMD. Many clinicians are inexperienced in managing the complications of this disease. In France, a committee of experts from a wide range of disciplines met in 2019 to establish recommendations, with the goal of improving care of patients with BMD. Here, we present the tools to provide diagnosis of BMD as quickly as possible and for differential diagnoses. Then, we describe the multidisciplinary approach essential for optimum management of BMD. We give recommendations for the initial assessment and follow-up of the neurological, respiratory, cardiac, and orthopedic consequences of males who present with BMD. Finally, we describe the optimal therapeutic management of these complications. We also provide guidance on cardiac management for female carriers. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effect of whole-body cryotherapy (WBC), cold-water immersion (CWI) and passive recovery (PAS) on tennis recovery. Methods: Thirteen competitive male tennis players completed three consecutive match-like tennis protocols, followed by recovery (WBC, CWI, PAS) in a crossover design. Five tennis drills and serves were performed using a ball machine to standardize the fatiguing protocol. Maximal voluntary contraction (MVC) peak torque, creatine kinase activity (CK), muscle soreness, ball accuracy and velocity together with voluntary activation, low- and high-frequency torque and EMG activity were recorded before each protocol and 24 h following the third protocol. Results: MVC peak torque (− 7.7 ± 11.3%; p = 0.001) and the high- to low-frequency torque ratio (− 10.0 ± 25.8%; p < 0.05) decreased on Day 1 but returned to baseline on Day 2, Day 3 and Day 4 (p = 0.052, all p > 0.06). The CK activity slightly increased from 161.0 ± 100.2 to 226.0 ± 106.7 UA L−1 on Day 1 (p = 0.001) and stayed at this level (p = 0.016) across days with no differences between recovery interventions. Muscle soreness increased across days with PAS recovery (p = 0.005), while no main effect of time was neither observed with WBC nor CWI (all p > 0.292). The technical performance was maintained across protocols with WBC and PAS, while it increased for CWI on Day 3 vs Day 1 (p = 0.017). Conclusion: Our 1.5-h tennis protocol led to mild muscle damage, though neither the neuromuscular function nor the tennis performance was altered due to accumulated workload induced by consecutive tennis protocols. The muscle soreness resulting from tennis protocols was similarly alleviated by both CWI and WBC. Trial registration: IRB No. 2017-A02255-48, 12/05/2017. [ABSTRACT FROM AUTHOR]

Sensory perception (e.g., vision) relies on a hierarchy of cortical areas, in which neural activity propagates in both directions, to convey information not only about sensory inputs but also about cognitive states, expectations and predictions. At the macroscopic scale, neurophysiological experiments have described the corresponding neural signals as both forward and backward-travelling waves, sometimes with characteristic oscillatory signatures. It remains unclear, however, how such activity patterns relate to specific functional properties of the perceptual apparatus. Here, we present a mathematical framework, inspired by neural network models of predictive coding, to systematically investigate neural dynamics in a hierarchical perceptual system. We show that stability of the system can be systematically derived from the values of hyper-parameters controlling the different signals (related to bottom-up inputs, top-down prediction and error correction). Similarly, it is possible to determine in which direction, and at what speed neural activity propagates in the system. Different neural assemblies (reflecting distinct eigenvectors of the connectivity matrices) can simultaneously and independently display different properties in terms of stability, propagation speed or direction. We also derive continuous-limit versions of the system, both in time and in neural space. Finally, we analyze the possible influence of transmission delays between layers, and reveal the emergence of oscillations. [ABSTRACT FROM AUTHOR]

Background: Guillain–Barre syndrome (GBS) is an acute inflammatory polyradiculoneuropathy rarely observed during pregnancy. Methods: In this retrospective study, we analyzed the characteristics of pregnant women with GBS (pGBS) diagnosed in French University Hospitals in the 2002–2022 period and compared them with a reference group of same-age non-pregnant women with GBS (npGBS) identified in the same institutions & timeframe. Results: We identified 16 pGBS cases. Median age was 31 years (28–36), and GBS developed in the 1st, 2nd, and 3rd trimester in 31%, 31% and 38% of cases respectively. A previous infection was identified in six cases (37%), GBS was demyelinating in nine cases (56%), and four patients (25%) needed respiratory assistance. Fifteen patients (94%) were treated with intravenous immunoglobulins, and neurological recovery was complete in all cases (100%). Unscheduled caesarean section was needed in five cases (31%), and two fetuses (12.5%) died because of cytomegalovirus (CMV) infection (1 case) and HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome (1 case). In comparison with a reference group of 18 npGBS women with a median age of 30 years (27–33), pGBS patients more frequently had CMV infection (31% vs 11%), had a prolonged delay between GBS onset and hospital admission (delay > 7 days: 57% vs 12%), more often needed ICU admission (56% vs 33%) and respiratory assistance (25% vs 11%), and more often presented with treatment-related fluctuations (37% vs 0%). Conclusions: This study shows GBS during pregnancy is a severe maternal condition with significant fetal mortality. [ABSTRACT FROM AUTHOR]

The delivery of genetic cargo remains one of the largest obstacles to the successful translation of experimental therapies, in large part due to the absence of targetable delivery vectors. Enveloped delivery modalities use viral envelope proteins, which determine tropism and induce membrane fusion. Here we develop DIRECTED (Delivery to Intended REcipient Cells Through Envelope Design), a modular platform that consists of separate fusion and targeting components. To achieve high modularity and programmable cell type specificity, we develop multiple strategies to recruit or immobilize antibodies on the viral envelope, including a chimeric antibody binding protein and a SNAP-tag enabling the use of antibodies or other proteins as targeting molecules. Moreover, we show that fusogens from multiple viral families are compatible with DIRECTED and that DIRECTED components can target multiple delivery chassis (e.g., lentivirus and MMLV gag) to specific cell types, including primary human T cells in PBMCs and whole blood. Targetable delivery vectors for genetic cargo are needed. Here the authors report a modular platform with separate fusion and targeting components—Delivery to Intended REcipient Cells Through Envelope Design (DIRECTED)—and show cell type-specific delivery. [ABSTRACT FROM AUTHOR]

RNA-guided systems, which use complementarity between a guide RNA and target nucleic acid sequences for recognition of genetic elements, have a central role in biological processes in both prokaryotes and eukaryotes. For example, the prokaryotic CRISPR–Cas systems provide adaptive immunity for bacteria and archaea against foreign genetic elements. Cas effectors such as Cas9 and Cas12 perform guide-RNA-dependent DNA cleavage1. Although a few eukaryotic RNA-guided systems have been studied, including RNA interference2 and ribosomal RNA modification3, it remains unclear whether eukaryotes have RNA-guided endonucleases. Recently, a new class of prokaryotic RNA-guided systems (termed OMEGA) was reported4,5. The OMEGA effector TnpB is the putative ancestor of Cas12 and has RNA-guided endonuclease activity4,6. TnpB may also be the ancestor of the eukaryotic transposon-encoded Fanzor (Fz) proteins4,7, raising the possibility that eukaryotes are also equipped with CRISPR–Cas or OMEGA-like programmable RNA-guided endonucleases. Here we report the biochemical characterization of Fz, showing that it is an RNA-guided DNA endonuclease. We also show that Fz can be reprogrammed for human genome engineering applications. Finally, we resolve the structure of Spizellomyces punctatus Fz at 2.7 Å using cryogenic electron microscopy, showing the conservation of core regions among Fz, TnpB and Cas12, despite diverse cognate RNA structures. Our results show that Fz is a eukaryotic OMEGA system, demonstrating that RNA-guided endonucleases are present in all three domains of life.Fanzor is shown to be an RNA-guided DNA endonuclease, demonstrating that such endonucleases are found in all domains of life and indicating a potential new tool for genome engineering applications. [ABSTRACT FROM AUTHOR]

Purpose: To review current evidence regarding the management of de novo, oligometastatic, castration-sensitive prostate cancer (PCa). Methods: A literature search was conducted on PubMed/Medline and a narrative synthesis of the evidence was performed in August 2022. Results: Oligometastatic disease is an intermediate state between localized and aggressive metastatic PCa defined by ≤ 3–5 metastatic lesions, although this definition remains controversial. Conventional imaging has limited accuracy in detecting metastatic lesions, and the implementation of molecular imaging could pave the way for a more personalized treatment strategy. However, oncological data supporting this strategy are needed. Radiotherapy to the primary tumor should be considered standard treatment for oligometastatic PCa (omPCa). However, it remains to be seen whether local therapy still has an additional survival benefit in patients with de novo omPCa when treated with the most modern systemic therapy combinations. There is insufficient evidence to recommend cytoreductive radical prostatectomy as local therapy; or stereotactic body radiotherapy as metastasis-directed therapy in patients with omPCa. Current data support the use of intensified systemic therapy with androgen deprivation therapy (ADT) and next-generation hormone therapies (NHT) for patients with de novo omPCa. Docetaxel has not demonstrated benefit in low volume disease. There are insufficient data to support the use of triple therapy (i.e., ADT + NHT + Docetaxel) in low volume disease. Conclusion: The present review discusses current data in de novo, omPCa regarding its definition, the increasing role of molecular imaging, the place of local and metastasis-directed therapies, and the intensification of systemic therapies. [ABSTRACT FROM AUTHOR]

Patient 2 Patient 2 is a 33-year-old male, brother of patient 1, who presented to the emergency department (ED) for worsening fever up to 39.1° Celsius, fatigue, cough and dyspnea. In this case series, three patients likely infected with the Omicron variant presented with mild symptoms and were treated in an outpatient setting (patients 3, 4, 5), while the other two patients were infected with the Delta variant and presented complicated disease courses. One patient was admitted shortly in an ICU due to acute hypoxemic respiratory failure (patient 1) and one patient required repeated hospitalizations for persistent non-severe disease (patient 2). Other treatments, such as antiviral therapies, have been reported in the treatment of XLA patients with COVID-19 with successful outcomes and could also be considered for these patients. [Extracted from the article]

Purpose: Few studies have evaluated patients' characteristics and survival by dialysis modality in Brazil. We evaluated changes in dialysis modality and its survival in the country. Methods: This is a retrospective database of a cohort with incident chronic dialysis patients from Brazil. Patients' characteristics and one-year multivariate survival risk were assessed considering dialysis modality from 2011 to 2016 and 2017 to 2021. Survival analysis was also performed on a reduced sample after adjustment using propensity score matching. Results: Of the 8295 dialysis patients, 5.3% were on peritoneal dialysis (PD) and 94.7% on hemodialysis (HD). PD patients had higher BMI, schooling and the prevalence of elective dialysis starting in the first period than those on HD. In the second period, PD patients were predominantly women, non-white, from the Southeast region, and funded by the public health system, having more frequent elective dialysis starting and predialysis nephrologist follow-ups than those on HD. There was no difference in mortality comparing PD and HD (HR 0.67, 95% CI 0.39–2.42; and HR 1.17, 95% CI 0.63–2.16; first and second period, respectively). This non-significantly different survival between both dialysis methods was also found in the reduced matched sample. Higher age and non-elective dialysis initiation were associated with higher mortality. In the second period, the lack of predialysis nephrologist follow-up and living in the Southeast region increased the mortality risk. Conclusion: Some sociodemographic factors have changed according to dialysis modality over the last decade in Brazil. The one-year survival of the two dialysis methods was comparable. [ABSTRACT FROM AUTHOR]

Functional lung imaging modalities such as hyperpolarized gas MRI ventilation enable visualization and quantification of regional lung ventilation; however, these techniques require specialized equipment and exogenous contrast, limiting clinical adoption. Physiologically-informed techniques to map proton (1H)-MRI ventilation have been proposed. These approaches have demonstrated moderate correlation with hyperpolarized gas MRI. Recently, deep learning (DL) has been used for image synthesis applications, including functional lung image synthesis. Here, we propose a 3D multi-channel convolutional neural network that employs physiologically-informed ventilation mapping and multi-inflation structural 1H-MRI to synthesize 3D ventilation surrogates (PhysVENeT). The dataset comprised paired inspiratory and expiratory 1H-MRI scans and corresponding hyperpolarized gas MRI scans from 170 participants with various pulmonary pathologies. We performed fivefold cross-validation on 150 of these participants and used 20 participants with a previously unseen pathology (post COVID-19) for external validation. Synthetic ventilation surrogates were evaluated using voxel-wise correlation and structural similarity metrics; the proposed PhysVENeT framework significantly outperformed conventional 1H-MRI ventilation mapping and other DL approaches which did not utilize structural imaging and ventilation mapping. PhysVENeT can accurately reflect ventilation defects and exhibits minimal overfitting on external validation data compared to DL approaches that do not integrate physiologically-informed mapping. [ABSTRACT FROM AUTHOR]

We introduce BICYCL an open-source C++ library that implements arithmetic in the ideal class groups of imaginary quadratic fields, together with a set of cryptographic primitives based on class groups. It is available at under GNU General Public License version 3 or any later version.BICYCL provides significant speed-ups on the implementation of the arithmetic of class groups. Concerning cryptographic applications, BICYCL is orders of magnitude faster than any previous pilot implementation of the CL linearly encryption scheme, making it faster than Paillier’s encryption scheme at any security level. Linearly homomorphic encryption is the core of many multi-party computation protocols, sometimes involving a huge number of encryptions and homomorphic evaluations: class group-based protocols become the best solution in terms of bandwidth and computational efficiency to rely upon. [ABSTRACT FROM AUTHOR]

Nonlinear stability analysis plays a key role in the design and evaluation of dynamical systems. Model-based analysis methods require extensive calibration and computational resources. While data-driven methods might offer a solution to this challenge, they are limited to available data and fail to generalize. Incorporating physical information about the system into data-driven methods can extend the applicability of these methods and improve their accuracy. In this paper, we present a physics-informed forecasting approach to predict bifurcation diagrams in nonlinear systems prone to instabilities using measurements of system dynamics before instabilities occur. The proposed method is a hybrid approach that combines an asymptotic analysis provided by the method of multiple scales and a data-driven forecasting technique. In particular, the approach uses information about the nonlinearities exhibited in the system to obtain the normal form using the method of multiple scales. The coefficients of this generic pre-identified form are then approximated using data from time series in the pre-bifurcation regime. We demonstrate the applicability of the proposed method in identifying post-bifurcation dynamics of nonlinear systems prone to instabilities through the application of the approach to several classes of nonlinear systems. [ABSTRACT FROM AUTHOR]

The intrinsic virulence of extra-intestinal pathogenic Escherichia coli is associated with numerous chromosomal and/or plasmid-borne genes, encoding diverse functions such as adhesins, toxins, and iron capture systems. However, the respective contribution to virulence of those genes seems to depend on the genetic background and is poorly understood. Here, we analyze genomes of 232 strains of sequence type complex STc58 and show that virulence (quantified in a mouse model of sepsis) emerged in a sub-group of STc58 due to the presence of the siderophore-encoding high-pathogenicity island (HPI). When extending our genome-wide association study to 370 Escherichia strains, we show that full virulence is associated with the presence of the aer or sit operons, in addition to the HPI. The prevalence of these operons, their co-occurrence and their genomic location depend on strain phylogeny. Thus, selection of lineage-dependent specific associations of virulence-associated genes argues for strong epistatic interactions shaping the emergence of virulence in E. coli. The virulence of extra-intestinal pathogenic Escherichia coli is associated with multiple different genes in different lineages. Here, Royer et al. show that the emergence of virulence is associated with acquisition of the siderophore-encoding high-pathogenicity island (HPI), and full virulence is associated with the additional presence of the aer or sit operons. [ABSTRACT FROM AUTHOR]

Ochre has been found at many Middle Stone Age sites throughout southern Africa. Much work has been done to document these iron-rich raw materials, their modifications and their implications for past communities’ behaviours, skills and cognition. However, until recently few works focused on the Middle Stone Age Waterberg ochre assemblages. The paper presents the ochre assemblage recovered at Red Balloon rock shelter, a new Middle Stone Age site on the Waterberg Plateau. The site preserves Middle Stone Age occupations dated around 95,000 years ago. Scanning electron microscopy observations, portable X-ray fluorescence spectroscopy and infrared spectroscopy characterization document the presence of four ochre types. The MSA ochre assemblage recovered is mainly composed of specularite and specular hematite similar to the ones of Olieboomspoort and North Brabant. Microscopic observations and infrared analyses of soil sediment and of post-depositional deposits found on the ochre pieces show that this raw material specificity is of anthropic origin and not the result of post-depositional processes. Optical and digital observations of the archaeological assemblage and its comparison with a preliminary exploratory experimental one highlight the use of abrasion and bipolar percussion to process the ochre pieces at the site. The results point to the know-how and skills of the Middle Stone Age populations who inhabited the Waterberg region around 95,000 years ago. This raises the question of whether the specificities of the Waterberg ochre assemblages correspond to populations’ adaptation to the local mountainous mineral resources and the existence of a regional ochre processing tradition. [ABSTRACT FROM AUTHOR]

Optical Mie resonators based on silicon nanostructures allow tuning of light-matter-interaction with advanced design concepts based on complementary metal–oxide–semiconductor (CMOS) compatible nanofabrication. Optically active materials such as transition-metal dichalcogenide (TMD) monolayers can be placed in the near-field region of such Mie resonators. Here, we experimentally demonstrate and verify by numerical simulations coupling between a MoSe2 monolayer and the near-field of dielectric nanoresonators. Through a comparison of dark-field (DF) scattering spectroscopy and photoluminescence excitation experiments (PLE), we show that the MoSe2 absorption can be enhanced via the near-field of a nanoresonator. We demonstrate spectral tuning of the absorption via the geometry of individual Mie resonators. We show that we indeed access the optical near-field of the nanoresonators, by measuring a spectral shift between the typical near-field resonances in PLE compared to the far-field resonances in DF scattering. Our results prove that using MoSe2 as an active probe allows accessing the optical near-field above photonic nanostructures, providing complementary information to sophisticated near-field microscopy equipment. Enhancing and tuning light-matter interactions is crucial for the advancement of future technologies; however, to achieve this, it is essential to find materials that are compatible with CMOS technology. In this study, the authors demonstrate that coupling a MoSe2 monolayer with a silicon-based dielectric nanoresonator can enhance and tune the absorption of the former to near-field resonances. [ABSTRACT FROM AUTHOR]

Purpose: The diagnosis of prostate cancer (PCa) still relies on the performance of both targeted (TB) and systematic biopsies (SB). Micro-ultrasound (mUS)-guided biopsies demonstrated a high sensitivity in detecting clinically significant prostate cancer (csPCa), which could be comparable to that of magnetic resonance imaging (MRI)-TB, but their added value has not been compared to SB yet. Methods: We conducted a systematic review and meta-analysis, based on Medline, EMBASE, Scopus, and Web of Science, in accordance with PRISMA guidelines, to compare mUS-guided biopsies to SB. Results: Based on the literature search of 2957 articles, 15 met the inclusion criteria (2967 patients). Most patients underwent mUS-guided biopsies, followed by MRI-TB and SB. Respectively 5 (n = 670) and 4 (n = 467) studies, providing raw data on SB, were included in a random-effect meta-analysis of the detection rate of csPCa, i.e. Gleason Grade Group (GGG) ≥ 2 or non-csPCa (GGG = 1). Overall, PCa was detected in 56–71% of men, with 31.3–49% having csPCa and 17–25.4% having non-csPCa. Regarding csPCa, mUS-guided biopsies identified 196 and SB 169 cases (Detection Ratio (DR): 1.18, 95% CI 0.83–1.68, I2 = 69%), favoring mUS-guided biopsies; regarding non-csPCa, mUS-guided biopsies identified 62 and SB 115 cases (DR: 0.55, 95% CI 0.41–0.73, I2 = 0%), also favoring mUS-guided biopsies by decreasing unnecessary diagnosis. Conclusion: Micro-ultrasound-guided biopsies compared favorably with SB for the detection of csPCa and detected fewer non-csPCa than SB. Prospective trials are awaited to confirm the interest of adding mUS-guided biopsies to MRI-TB to optimize csPCa detection without increasing overdiagnosis of non-csPCa. [ABSTRACT FROM AUTHOR]

The present paper proposes an experimental study to determine the mechanical properties of an additively manufactured modified Al6061 alloy, where the addition of 2 vol.% of yttrium-stabilized zirconia (YSZ) to Al6061 base powder allows to fully remove cracks during laser beam melting processing. To this end, Vickers tests, tensile tests, Charpy tests and microstructural analyses are used. With respect to the building direction, a quasi-isotropic response is highlighted, on as-built material with properties (engineering yield and ultimate strengths) higher than the wrought 6061 alloy. This improvement can be attributed to the extra-fine microstructure, a large dislocation density and a specific precipitation/solution trapping behavior associated with the Zr addition. Besides, the alloy showed excellent tensile response reproducibility. Thereafter, effect of post-heat treatments is investigated. Classic T6 from wrought alloys practice allowed to precipitate well-known and reported nano-β″-MgxSiy phases, improving the yield and ultimate strengths, but at the expense of significant grain coarsening. The mechanical properties are further increased through an adapted heat treatment, specifically designed for this Al6061 modified alloy. Al3Zr hardening nanoprecipitates are responsible of the improved yield response observed after an annealing for 2 h at 400 °C. The competition between these different hardening precipitation phases (nano-β″/nano-Al3Zr) is finally discussed. [ABSTRACT FROM AUTHOR]

Purpose: The natural history of prostate cancer (PC) almost always evolves to castration-resistant prostate cancer (CRPC) status, sometimes comprising pure or mixed neuroendocrine prostate cancers (NEPC) differentiation. In CRPC, monitoring using only prostate-specific antigen (PSA) is not optimal since neuroendocrine differentiated cells do not secrete PSA. Thus, monitoring with PSA and chromogranin A (CgA) may be useful. This review aims to evaluate evidence for the usefulness of CgA assessments during the monitoring of prostate cancer. Method: This review was based on three recent meta-analysis concerning CgA and prostate cancer. Further data were obtained from PubMed and Embase databases by searches using keywords, including chromogranin A and prostate cancer. Results: CgA levels remain largely unchanged during the early PC evolution. The development of NEPC is characterised by lower PSA secretion and increased CgA secretion. Data supporting the prognostic value of high CgA baseline levels for survival are contrasting and scarce. However, increasing CgA levels early during treatment of metastatic (m)CRPC suggests resistance to treatment and predicts shorter survival, particularly in men with high baseline levels of CgA levels. In men with mCRPC, the first-line chemotherapy may be more appropriate than other agents when baseline CgA levels are high. Also, increasing CgA levels during treatment may indicate disease progression and may warrant a change of therapy. Conclusion: CgA monitoring at baseline and regularly during mCRPC management may be useful for monitoring disease evolution. An increased CgA baseline levels and increasing CgA levels may assist physicians with choosing and modifying therapy. [ABSTRACT FROM AUTHOR]

We explored the resting state functional connectivity correlates of apathy assessed as a multidimensional construct, using behavioral metrics, in behavioral variant frontotemporal dementia (bvFTD). We recorded the behavior of 20 bvFTD patients and 16 healthy controls in a close-to-real-life situation including a free phase (FP—in which actions were self-initiated) and a guided phase (GP—in which initiation of actions was facilitated by external guidance). We investigated the activity time and walking episode features as quantifiers of apathy. We used the means ((FP + GP)/2) and the differences (FP-GP) calculated for these metrics as well as measures by questionnaires to extract apathy dimensions by factor analysis. We assessed two types of fMRI-based resting state connectivity measures (local activity and seed-based connectivity) and explored their relationship with extracted apathy dimensions. Apathy in bvFTD was associated with lower time spent in activity combined with walking episodes of higher frequency, lower acceleration and higher duration. Using these behavioral metrics and apathy measures by questionnaires, we disentangled two dimensions: the global reduction of goal-directed behaviors and the specific deficit of self-initiation. Global apathy was associated with lower resting state activity within prefrontal cortex and lower connectivity of salience network hubs while the decrease in self-initiation was related to increased connectivity of parietal default-mode network hubs. Through a novel dimensional approach, we dissociated the functional connectivity correlates of global apathy and self-initiation deficit. We discussed in particular the role of the modified connectivity of lateral parietal cortex in the volitional process. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy. Methods: From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan–Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes. Results: Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p < 0.001) after adjusting for PSA, pT, grade group, LNI and PSM. Conclusions: Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence. [ABSTRACT FROM AUTHOR]

Introduction: To describe the efficacy of subcutaneous immunoglobulin (SCIg) in patients with myasthenia gravis (MG). Methods: This was a retrospective study conducted in the neuromuscular referral center of Bordeaux (between January 1, 2014 and March 31, 2021) with MG patients treated with SCIg. The main outcome was SCIg efficacy assessed by the before and after SCIg Myasthenia Gravis Foundation of America (MGFA) clinical classification, the duration of hospitalization and the number of days of orotracheal intubation (OTI). Results: Sixteen patients were included in the study (11 females; 5 males). Nine patients were still treated with SCIg at the end of the study (March 31, 2021) and then underwent prospective follow-up. The average age of the patients was 56.1 (19–83) years. The median duration of MG at onset of SCIg was 37.4 months. Eight patients (50%) remained stable (4 in stage MGFA-IV and 4 in MGFA-III). Eight patients (50%) improved: 3 from MGFA-IV to MGFA-III, 1 from MGFA-IV to MGFA-II, 1 from MGFA-IV to MGFA-I, 2 from MGFA-III to MGFA-II and 1 from MGFA-III to MGFA-I (no patient worsened). The duration of disease progression did not appear to affect the response to SCIg therapy. The number of hospital days per month was significantly reduced after SCIg compared to before, and the number of days in intensive care unit and the number of days of OTI were also reduced. Only minor adverse effects were noted, and 80% of patients were in favor of continuing SCIg. Conclusions: SCIg is a well-tolerated and useful treatment in MG, offering interesting perspectives in the management of MG patients. However, further large-scale prospective studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

This correction notice from Nature Communications addresses errors in a previously published article titled "Overcoming the coherence time barrier in quantum machine learning on temporal data." The correction involves adding a missing reference to the bibliography and clarifying two mentions of a specific reference number. The corrected version of the article is authored by Fangjun Hu, Saeed A. Khan, and others. [Extracted from the article]