Search Results (715)

Maintaining a balanced skin microbiota is essential for preserving epidermal barrier integrity and overall skin health. Dysbiosis, particularly the opportunistic overgrowth of Staphylococcus aureus, is associated with barrier dysfunction and inflammatory dermatoses such as atopic dermatitis, psoriasis, and acne. In dysbiotic states, microbial regulatory mechanisms become disrupted, enabling pathogenic strains to proliferate and release proteases that degrade structural components of the skin barrier, increasing epidermal permeability in a manner analogous to ‘leaky gut’ physiopathology. Microbiota dysbiosis has further been proposed as an emerging hallmark of aging, contributing to chronic low-grade inflammation, impaired tissue repair, and progressive barrier decline. Current strategies predominantly target the microbiota itself, leaving the host tissue response to protease-mediated barrier disruption comparatively underaddressed. To fill this gap, an ex vivo human skin model was developed based on topical application of purified S. aureus serine protease SspA to skin explants, enabling controlled investigation of early host–microbiota interaction events. Barrier function, junctional integrity, inflammatory mediators, and proteostasis were assessed through a panel of complementary biomarkers—Lucifer Yellow permeability, claudin-1, desmoglein-1, filaggrin, IL-31, S100A8/A9, PGE2, and protein carbonylation. SspA induced measurable barrier disruption, junctional protein loss, inflammatory mediator upregulation, and proteostasis impairment without overt tissue damage. A biotic culture filtrate of Bifidobacterium adolescentis partially attenuated SspA-induced protein carbonylation. This model provides the scientific community with a controlled, biologically relevant platform for identifying biomarkers of early barrier impairment and evaluating host-targeted interventions aimed at preventing or counteracting protease-driven barrier damage in dysbiosis-associated skin conditions. A better understanding of the early molecular mechanisms through which microbial virulence factors drive barrier disruption and proteostasis decline may further contribute to broader strategies aimed at preserving skin integrity during aging. Full article

Background/Objectives: Ultrasound (US) is a valuable tool in hand surgery because of its portability, low cost, and ability to provide noninvasive, real-time evaluation of soft tissue structures. However, it has not been widely assessed for measuring the scapholunate (SL) interval using dynamic stress views. This study aimed to determine whether ultrasound provides comparable measurements to radiography when evaluating the SL interval in healthy subjects. Methods: We analyzed 29 wrists from 29 individuals. Each wrist underwent dynamic stress maneuvers while the SL interval was measured with both radiography and US. The following views were obtained: neutral rotation, ulnar deviation, clenched fist, and a modified dynamic clenched fist view. The latter was performed by applying pressure on the head of the third metacarpal from distal to proximal. Results: The SL interval could be visualized in the clenched fist and ulnar deviation radiographic views, as well as in the modified dynamic clenched fist US view. Ultrasound in the neutral position produced measurements similar to those of traditional stress radiographs. The most pronounced changes in the SL interval occurred between neutral and dynamic views, whether assessed by radiography or US. There was no significant difference in the magnitude of interval change between the two imaging modalities. Conclusions: Ultrasound with dynamic stress maneuvers provided similar dynamic SL interval changes to stress radiographs in healthy individuals. A modified stress view using a slightly clenched fist and manual pressure on the third metacarpal head may offer hand surgeons a simple, real-time tool to noninvasively evaluate SL instability. Full article

Pelvic xanthogranulomatous inflammation is a rare pathological entity that can closely mimic malignant disease on cross-sectional imaging, often leading to consideration of radical surgical intervention. We report the case of a 59-year-old woman who presented with a large retrovesical pelvic mass initially suspected to be a malignant process. A definitive diagnosis was established only after tissue biopsy and comprehensive histopathological examination, which excluded malignancy and demonstrated xanthogranulomatous histiocytic inflammation. In light of the lesion’s anatomical location and the substantial morbidity associated with surgical resection, a conservative medical strategy was pursued. Treatment with systemic corticosteroids and everolimus led to marked clinical improvement and a substantial radiological response, with reduction in lesion size from 41 × 26 mm to 27 × 17 mm, thereby allowing avoidance of mutilating surgery. This case underscores the critical role of biopsy and expert pathological assessment in guiding clinical decision-making and supports the consideration of non-surgical therapeutic approaches in selected patients with xanthogranulomatous pelvic lesions. Full article

Objectives: To characterize heterozygous pathogenic COCH variants in a French cohort with non-syndromic sensorineural hearing loss (NSHL) and assess genotype–phenotype correlations in autosomal dominant NSHL (DFNA9). Setting: National Reference Center for Genetic Hearing Loss, Necker–Enfants Malades Hospital, Paris, France. Methods: This retrospective observational study included 69 individuals from 20 unrelated families diagnosed with DFNA9 (2005–2025). All individuals underwent clinical and audiological evaluations and genetic testing via targeted COCH Sanger sequencing or next-generation sequencing (NGS) panels. Variants were interpreted according to ACMG guidelines. Audiometric profiles and vestibular data were collected. Results: Seven known pathogenic COCH variants were found in ten families, and ten novel likely pathogenic variants in the others. Variants in vWFA domains were associated with early or late onset, progressive, bilateral and symmetrical hearing loss. Three variants (p.Gln410Arg, p.Ile450Val, p.Cys542Arg) were associated with congenital or prelingual onset, an atypical DFNA9 presentation. Variants in the LCCL domain were associated with later-onset hearing loss and more frequent vestibular dysfunction. Vestibular abnormalities were observed in about half of early-onset cases. Conclusions:COCH-related hearing loss is a rare cause of autosomal dominant NSHL, with only 20 families identified over two decades within the French network. This study expands the mutational spectrum of COCH by reporting ten novel variants and supports a domain-specific genotype–phenotype correlation. These findings improve the understanding of DFNA9 variability and have direct implications for clinical diagnosis, prognosis, and genetic counseling. Full article

This study tackles the middle atmosphere phenomenon known as Mesospheric Inversion Layers (MILs). Reinterpreting Envisat’s GOMOS instrument limb-sounding temperature profiles which we compared to the MSIS-2.0 climatological model, we studied 340,000 resolute temperature profiles, detecting 44,000 (13%) MILs in this dataset. We have shown that MILs are a worldwide phenomenon, concentrated around the tropics and in the Winter Hemisphere’s mid-latitude region (between $30\%$ and $50\%$ of profiles are MILs in those areas). MILs follow a correlation law ($R^2=0.5$ on pure data, $R^2=0.97$ on binned-mean data) between the log-amplitude of its peak and its altitude. Median altitudes are about 70 km worldwide, but the median amplitude reached by equatorial MILs is typically higher (14.5 K compared to the others at 12.5 K). Lastly, equatorial MILs (but not mid-latitude MILs) are correlated with high-difference estimated tide temperature gradient contributions. Results suggest that the MIL is a common phenomenon with statistically consistent characteristics. Seasonal occurrence hinted that there is probably a class of MILs favoured by planetary waves at the edge of the polar vortex, while the equatorial type of inversions seems to occur when the atmospheric tide model flattens the temperature gradient around 70 km. Full article

Soil surface roughness (SSR), referring to surface irregularities, is a key parameter for assessing soil condition and tillage outcomes. Characterizing roughness at fine scales—including clods and depressions—remains challenging for 2.5D digital elevation models (DEMs) collected at the meter scale in the field. This study presents two segmentation methods for high-resolution DEMs from an agricultural site. For clod segmentation, a wavelet-based approach from the literature was used, while a novel histogram-based method was introduced for depressions. Both methods were evaluated on natural soil surfaces with varying roughness levels and a simulated surface, with and without noise, using standard metrics (recall, precision, F1-score, IoU). The best clod segmentation results were achieved on fine seedbeds (95.2% recall, 97.3% precision, 96.2% F1-score), with slightly lower but strong performance on plowed surfaces (84.2% recall, 96.9% precision, 90.1% F1-score). Due to their lower frequency, depressions were primarily assessed visually under field conditions. For the simulated surface (with ground truth), IoU values ranged from 84.2% to 87.9% for clods and around 92% for depressions, demonstrating competitive performance. Additionally, the volume of roughness features was computed and visualized using cumulative distribution functions. These segmentation methods enable monitoring of soil surface conditions, with applications in precision agriculture, surface-water interactions, and meter-scale microwave remote sensing. Full article

Background/Objectives: Glaucoma is a leading cause of irreversible blindness, and lowering intraocular pressure (IOP) is the only proven strategy to slow disease progression. The Preserflo^® Microshunt (PMS) is a minimally invasive subconjunctival drainage device used to treat uncontrolled glaucoma. Given that cataracts and glaucoma often coexist, this study aimed to compare the 12-month efficacy and safety of PMS implanted as a standalone procedure versus combined with phacoemulsification (PCE). Methods: This single-center retrospective case–control study included 104 eyes (26 PMS + PCE; 78 standalone PMS) from patients treated between 2019 and 2023. Controls were matched 3:1 to cases on sex, age, glaucoma severity, baseline IOP, and number of prior glaucoma surgeries. Success at 12 months was defined as absolute (IOP ≤ 21 mmHg without medications) or qualified (IOP ≤ 21 mmHg with the same or fewer medications). Secondary outcomes included changes in IOP, medication burden, and safety profiles. Results: At 12 months, absolute success was achieved in 23.1% of the PMS + PCE group versus 43.6% in the standalone PMS group (p = 0.13). However, the Kaplan–Meier survival probability of absolute success was significantly higher for standalone PMS (75.2% vs. 40.2%, p = 0.0028). Qualified success rates were comparable (53.9% vs. 70.5%, p = 0.30). Both groups showed similar reductions in mean IOP and medication counts. Although safety profiles were comparable, the mean time to first bleb revision (p = 0.031) and first needling (p = 0.015) was significantly shorter in the combined group. Conclusions: Both standalone and combined PMS procedures are effective and safe in achieving sustained IOP reduction. Although standalone implantation appears to be associated with higher medication-free success rates, combined surgery remains a reasonable option for patients with coexisting cataract, despite a tendency toward earlier bleb fibrosis likely related to the inflammatory response induced by PCE. Full article

This paper aims to improve the energy autonomy and the mechanical performances of an on-board drive chain for robotics. The energy autonomy improvement is performed by reducing electrical losses in the inverter. Electrical losses are reduced by decreasing the number of switching cycles per period of the inverter’s power semiconductor switches, while maintaining a low Total Harmonic Distortion (THD). These improvements are expected thanks to a new control strategy called Pre-Calculated Pulse Width Modulation (PC PWM). The principle of this new control strategy is that all the symmetries of an ideal three-phase voltage system are assigned to the real output voltage of the inverter. Then the switching instants of the inverter’s switches are determined off line, by means of Fourier’s analysis, so that the maximum number of successive harmonics is zeroed. This allows the optimal switching sequence to be predefined, thereby reducing unnecessary commutations of the power switches. The performance of the new method (PC PWM) is evaluated through detailed simulation studies and compared with the conventional method called Sinusoidal Pulse Width Modulation (SPWM). The simulation results show that despite the reduction in the number of commutations per period, the performance of the actuation chain has been significantly improved with PC-PWM (new technique). Indeed, for the same mechanical load, the PC-PWM method allows for a lower current, a shorter transient response time and a lower torque ripple than the SPWM method. Full article

Molecular spin-crossover (SCO) compounds constitute prototypical systems exhibiting first-order phase transitions. These transitions involve an abrupt switch between two well-defined states with distinctly different magnetic, optical, and vibrational properties. One state is diamagnetic (low-spin), while the other is paramagnetic (high-spin). Upon heating, the transition occurs at a characteristic temperature, T_up. Upon cooling, it takes place at a lower temperature, T_down < T_up, thereby giving rise to thermal hysteresis. Accordingly, each SCO compound is defined by a distinct pair of transition temperatures, T_up and T_down. The investigation of these molecular solids is of great importance, both for elucidating first-order phase transitions—including the potential emergence of re-entrant phases—and for their broad range of prospective applications. The critical temperatures T_up and T_down are pivotal in defining their practical utility. We present a strategy to modify and tune the transition temperatures of spin-crossover (SCO) compounds to suit different applications. The approach combines a given SCO material with layers of a second SCO system, enabling precise control of the characteristic temperatures of the resulting heterostructure. We illustrate this method with three case studies that span the 100 K–400 K temperature range. All simulations were performed using Monte Carlo methods within the Metropolis algorithm framework. Full article

Excessive sodium intake is a major dietary concern, leading to recommended reductions in several food categories, including cheese. This study aimed to evaluate how cheese composition and texture influence sodium release and perceived saltiness during consumption. Semi-hard cheeses (SHCs) with varying compositions were analyzed for chemical composition, rheological properties, and sensory attributes using quantitative descriptive analysis, temporal sodium release and saltiness intensity. Most compositional factors affected the sensory characteristics of SHCs and the dynamic perception of saltiness. In particular, salt level influenced not only the perceived intensity of saltiness but also bitterness, acidity, overall aromatic intensity, and numerous textural characteristics. The fat content also influenced texture perception and masked taste attributes. Moreover, both sodium release and saltiness perception decreased with increasing fat content. These findings highlight the importance of compositional and textural factors in modulating salt perception and provide useful insights for developing reduced-salt cheeses with acceptable sensory qualities. Full article

Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis, highlighting the need for innovative therapeutic strategies. Chronomodulated chemotherapy yielded improved efficacy and tolerability in several malignancies; however, evidence in breast cancer remains limited. This study investigated the association between the time of day of administration (ToDA) of neoadjuvant chemotherapy (NAC) and clinical outcomes in patients with TNBC treated in a day hospital setting. Methods: This retrospective cohort included patients treated at Saint-Louis Hospital with neoadjuvant dose-dense, dose-intense cyclophosphamide–epirubicin followed by weekly paclitaxel. Infusion start times of each chemotherapy agent were systematically recorded. The primary endpoint was pathological complete response (pCR; Residual Cancer Burden [RCB] = 0). Secondary endpoints included RCB classes, early metabolic response, treatment tolerance, and 36-month event-free survival (EFS). Patients were classified into early or late infusion groups using multiple ToDA cut-offs, and cosine-based analyses were performed. Results: Ninety-four patients (median age 51 years) received NAC between 9:00 and 17:40 which aligns with the day hospital unit’s opening hours. With a median follow-up of 39.9 months, the pCR rate was 48.9%. No significant differences were observed between early and late infusion groups for any endpoint, regardless of ToDA cut-off or analytical approach. Conclusions: This first chronotherapeutic study in patients with early TNBC showed no association between ToDA of NAC administered between 9:00 and 17:40 and histological response or EFS. Although limited by sample size and the restricted infusion time window, our study provides novel data and methodological insights supporting further investigation of chronotherapy in patients with breast cancer. Full article

We report the synthesis of Fe/N/C ORR electrocatalysts by an original collinear CO₂ laser pyrolysis of liquid aerosol droplets in various configurations and compared them to a catalyst synthesized in the classical perpendicular one. While the precursors were always injected at the bottom side of the reactor, two collinear configurations of the laser entry into the reactor are considered: by the Top Side (T.S.) or by the Bottom Side (B.S.). The two corresponding catalysts sets show significant different ORR performances. An in-depth XPS analysis and fitting of the N1s spectra allowed for drawing the ORR performance as a function of FeN_x sites components. An original approach considering the energy delivered to a quantity of precursors in J.g⁻¹, linked to the flame temperature feature, evidenced very different conditions for perpendicular CO₂ laser pyrolysis and each of the two collinear configurations. This mass-weighted energy delivered in the classical perpendicular configuration is too low to allow for the formation of FeN_x sites and the resulting ORR performance is extremely poor, suggesting a marginal role of nitrogen species without interaction with iron atoms. In contrast, the delivered mass-weighted energies are sufficient in both collinear configurations to produce FeN_x sites. The ORR performance for catalysts produced in these both configurations is positively correlated with the amount of energy deposited on the precursors. The ORR performance in the T.S. laser configuration is positively correlated to the amount of FeN_x sites. The best performing catalysts obtained in the B.S. configuration show an opposite variation. These trends, and the ORR performance degradation of B.S. catalysts under prolonged chronoamperometry are discussed in light of the effect of temperature on the formation of the various kind of FeN_x sites. A tentative explanation is given, considering that N1s XPS fitting with a single FeN_x component may hinder the fact that Pyridinic sites components may contain a part of FeN_x sites, as suggested by theoretical calculation from the literature. The best catalysts obtained in this work by collinear configuration show similar performances to those obtained by double stage perpendicular pyrolysis previously reported with an ORR onset potential of ~860 mV. Full article

The dystrophin gene encodes multiple dystrophin isoforms with tissue-specific functions, including several shorter isoforms expressed in the central nervous system and retina. While Duchenne muscular dystrophy (DMD) has historically been characterized as a primary myopathy resulting from loss of the full-length dystrophin Dp427, increasing clinical evidence indicates that dysfunction of shorter dystrophin isoforms contributes to significant extramuscular pathology, including retinal disease. In particular, loss of the Dp71 isoform has been implicated in retinal inflammation, blood–retinal barrier breakdown, and pathological angiogenesis. In this study, we investigated whether low-level residual expression of Dp71 is sufficient to mitigate retinal inflammation in the mdx3Cv mouse model, which displays reduced—but not absent—expression of multiple dystrophin isoforms. Western blot analysis revealed that mdx3Cv retinas express approximately 4% of wild-type Dp71 protein levels. Despite this marked reduction, mdx3Cv mice did not exhibit the inflammatory phenotype previously observed in Dp71-null mice. Retinal VEGF protein levels and VEGF receptor (FLT-1 and KDR) mRNA expression were preserved, while VEGF mRNA levels were modestly reduced. Furthermore, expression of inflammatory markers ICAM-1 and ALOX5AP, leukocyte adhesion to retinal vasculature, Aquaporin-4 expression, and BRB permeability to albumin were all comparable to wild-type littermates. Together, these findings demonstrate that minimal residual expression of Dp71 is sufficient to preserve retinal vascular homeostasis and prevent inflammatory and permeability defects in the mdx3Cv retina. These results further suggest that partial dystrophin restoration—at levels achievable with current exon-skipping or gene-based therapies—may be adequate to prevent or attenuate retinal pathology in DMD, providing a realistic and clinically relevant therapeutic target. Full article

Background: Laser peripheral iridotomy (LPI) is the first-line treatment for eyes with primary angle closure suspect (PACS), but the extent and durability of anterior chamber angle widening over time remain variable. Ultrasound biomicroscopy (UBM) allows detailed quantitative assessment of angle anatomy and underlying mechanisms of residual angle closure. Methods: In this prospective cohort study, 39 eyes of 20 PACS patients underwent UBM examination before LPI and at 1 month and 1 year post-procedure. Angle opening distance at 500 µm from the scleral spur (AOD500) and trabecular–ciliary process distance (TCPD) were measured in four quadrants under standardized light conditions. Paired comparisons and linear regression analyses were performed. Results: Mean AOD500 increased significantly from baseline (90.1 ± 52.5 µm) to 1 month (146.2 ± 58.2 µm, p < 0.001) and remained greater at 1 year (128.4 ± 48.8 µm, p < 0.001), with the largest changes observed in the superior quadrant. TCPD remained unchanged over time. Despite a patent iridotomy, iridotrabecular contact (ITC) persisted in 12.8% of eyes at 1 year. Plateau iris configuration was identified in 35.9% of eyes. Eyes with smaller baseline AOD500 showed a more limited anatomical response to LPI, although interaction testing did not reach statistical significance. Conclusions: LPI induces significant but partially attenuated anterior chamber angle widening at one year in PACS eyes. A substantial subset exhibits persistent angle closure, frequently associated with plateau iris configuration, underscoring the need for continued post-LPI anatomical surveillance and mechanism-based management. Full article

Radiocarbon dating of lead white has progressed considerably in the last decade. Today, the protocol enables the analysis of various types of samples: pure lead white in cosmetics, ancient and modern paint layers containing lead white and oil, and mixtures of lead white and calcite. However, it has also been shown that the presence of a large amount of calcite in lead white paint can alter the radiocarbon result through contamination with dead carbon. To overcome this problem, careful characterization of samples must be carried out prior to dating. Lead white paint layers from the Queen’s apartment at the Palace of Versailles were observed by electronic microscopy and analyzed by Synchrotron X-ray-based diffraction to discriminate the different layers of paint in order to minimize contamination. Chemical analysis and ¹⁴C dating were used to document the implementation of the decorations in Queen Marie-Antoinette’s library. Full article