Workforce diversity in dermatology is crucial for equitable, high-quality care, given the impact of skin tone, culture, and socio-economic status on skin conditions. Although this has been studied in other countries, data on the demographic makeup of Dutch dermatologists is lacking. This study aims to assess workforce diversity in Dutch dermatology over time. We conducted a nationwide repeated cross-sectional study using pseudonymized microdata from Statistics Netherlands, including sex, migration background, and parental socio-economic indicators. Descriptive statistics were used to track demographic trends between 2005 and 2023, and multivariable logistic regression analyses were performed to evaluate which variables influenced the odds that registered physicians in the 2023 national healthcare professional register (BIG register) had to be a dermatologist. Female representation rose from 35.4% in 2005 to 61.7% in 2023. In 2023, 84.4% of dermatologists had no migration background or a European migration background. Dermatologists with Turkish, Moroccan, Surinamese, or Caribbean Dutch origins were underrepresented. Despite a net increase of 289 dermatologists, only 56 of this net increase consisted of dermatologists with a non-European background. Multivariable regression analysis showed that being female (OR 1.609 [1.143-2.266]), having parents in the top 20% assets bracket (OR 2.251 [1.272-3.984]), or having physician parents (OR 1.326 [1.011-1.740]) were associated with higher odds of being a registered dermatologist among the younger generation of physicians. The findings highlight a persistent lack of ethnic and socio-economic diversity in the Dutch dermatology workforce, despite broader demographic shifts in the general population and medical student cohorts. The underrepresentation of dermatologists with a migration background may have implications for equitable patient care, particularly in the context of cultural and linguistic barriers, as well as differences in disease presentation across skin tones. Further research is warranted to explore the potential impact of workforce diversity on patient outcomes.
Animals that filter-feed on environmental microbes must rapidly discriminate among captured bacteria to maintain beneficial associations while avoiding inappropriate immune activation. In innate immunity, this discrimination is executed through transcription factors (TFs), whose activation and nuclear translocation initiate effector gene expression and shape the nature of the host response. In sponges, bacteria are first physically captured by choanocytes, but the timing and cellular context in which TF-mediated immune discrimination becomes evident remains unclear. Here, we investigate the earliest detectable regulatory responses associated with discrimination between symbiotic and non-symbiotic bacteria in the marine sponge Amphimedon queenslandica. Using a feeding-based design to model post-metamorphic microbiome restructuring, we exposed juvenile sponges that already harbour vertically inherited symbionts to native (symbiont) or foreign (non-symbiont) bacterial communities and assessed early cellular processing and transcriptional responses to bacterial uptake. Symbiotic bacteria were rapidly transported across the epithelium and induced a strong, transient activation of conserved innate immune TFs, including IRF, NF-κB, and STAT, together with associated signalling pathways. IRF and NF-κB translocated to the nuclei of amoebocytes that had engulfed symbionts, indicating that discrimination becomes evident shortly after uptake and precedes downstream effector responses. In contrast, foreign bacteria were internalized more slowly, failed to induce coordinated immune TF activation or nuclear translocation, and instead elicited a xenobiotic-dominated transcriptional program. Together, these findings identify TF activation as an early regulatory checkpoint in sponge-microbe interactions and reveal key mechanisms that underpin the initial stages of symbiont discrimination.
Intrinsically disordered regions (IDRs) of transcription factors are frequent sites for post-translational modifications (PTMs), which mediate regulation through diverse mechanisms including protein-protein interactions. In the fusion oncoprotein PAX3-FOXO1, which drives alveolar rhabdomyosarcoma, a lysine-rich region of the FOXO1 IDR is subject to acetylation resulting in stabilization and enhanced transcriptional activity. Here, we leveraged 13C direct-detect nuclear magnetic resonance (NMR) spectroscopy to characterize acetylation in this system and identified a novel acetylation site corresponding to lysine 233 in endogenous FOXO1. In previous structural characterization of the endogenous FOXO1 DNA binding domain, local structure appears to prevent this site from becoming acetylated, suggesting that it becomes exposed in the context of the fusion protein. In addition, we demonstrate that the first bromodomain of the bromodomain and extraterminal domain-containing protein BRD4 binds to the acetylated region of interest and that this interaction is inhibited through the bromodomain and extraterminal domain inhibitor JQ1. These findings confer molecular mechanistic detail to previous observations that BRD4 and PAX3-FOXO1 colocalize at superenhancers in ARMS, adding to the growing body of literature exploring how BRD4 contacts cancer-relevant transcription factors in ways potentially relevant to the use of bromodomain and extraterminal domain inhibitors in cancer treatment.
Boron neutron capture therapy (BNCT) is a targeted radiotherapeutic modality that employs boron-10 (10B) to capture thermal neutrons, thereby releasing high-linear energy transfer α-particles and lithium ions that selectively eradicate tumor cells while sparing the surrounding normal tissues. Immune checkpoint inhibitors (ICIs), including inhibitors of PD-1/PD-L1 and CTLA-4, enhance antitumor immunity by alleviating immunosuppression within the tumor microenvironment. As immunotherapy continues to expand across multiple tumor types and becomes integral to systemic cancer treatment, attention has increasingly focused on combining systemic immunomodulation with localized therapies. BNCT functions primarily as a local therapeutic approach, whereas ICIs elicit systemic immune activation. Whether the two modalities can produce synergistic therapeutic effects remains an important question.In this narrative review, we summarize current mechanistic insights, preclinical and clinical developments, and ongoing challenges associated with the combination of BNCT and ICIs, highlighting the potential of this strategy to achieve durable, synergistic antitumor responses.
Revision surgery for occlusal correction in facial trauma is a highly specialized and technically demanding aspect of reconstructive surgery. While contemporary practices in primary fracture management have reduced the incidence of posttraumatic malocclusion, circumstances such as delayed treatment, insufficient fracture reduction, overlooked injuries, and complex comminution continue to create challenging cases in which revision becomes inevitable. Effective secondary correction of occlusion involves a deep understanding of both trauma principles and orthognathic concepts, rigorous diagnostic steps and precise surgical technique.
Approximately half of all methane (CH4) emissions come from freshwaters, where they are regulated by the microbial 'CH4 filter' whose efficiency describes the fraction of CH4 produced that is subsequently oxidized back to CO2 (methanotrophy) before emission. How the CH4 filter efficiency responds to natural warming over centuries or millennia remains unknown. Here we address this question using a natural experiment comprising high-latitude, geothermally warmed streams in five regions spanning the Northern Hemisphere. CH4 production becomes more efficient with warming, linked to increased abundance of methanogens and underpinned by community shifts. In contrast, while CH4 oxidation activity increases, its process-level efficiency does not, and methanotrophs shift towards less efficient taxa. Consequently, the system-level CH4 filter efficiency remains fixed, and CH4 emissions increase. If this fixed CH4 filter efficiency under warming is common to freshwaters worldwide (wetlands, lakes and rivers), then an upward trajectory for CH4 emissions through future climate change appears inevitable.
Maladaptive learned fear responses to stress underlie several debilitating neuropsychiatric disorders. Here, we identify a brain-to-spleen neural pathway that mediates learned fear through coordinated neuroimmune interactions. Using a chronic acquired olfactory stress (CAOS) model, we demonstrate that sustained enhancement of the piriform cortex (Pir) excitability contributes to the transformation of stress-associated olfactory inputs into learned fear-avoidance behavior. Through comprehensive neural tracing approaches, we mapped a functional tetrasynaptic circuit (Pir→ventral hippocampus CA1 subregion [vCA1]→CeM→DVC→spleen) regulating T helper 17 (Th17) cell-dependent fear responses. Single-nucleus RNA sequencing revealed that olfactomedin 3-expressing glutamatergic neurons in the Pir integrate olfactory stress inputs to activate this pathway. Importantly, targeted disruption of this circuit through either conditional knockdown of Olfm3 within Pir→vCA1 projecting glutamatergic neurons or chemogenetic inhibition of these projections eliminated CAOS-induced splenic Th17 cell expansion and fear avoidance. These findings provide fundamental insights into how learned fear becomes maladaptive by identifying a complete neural circuit linking olfactory perception to peripheral immunity.
Hexagonal boron nitride (hBN) is a widely studied van der Waals material that supports highly confined phonon polaritons-hybrid light-matter quasiparticles arising from the coupling of infrared photons with optical phonons. While prior works-primarily using scattering-type near-field optical microscopy (s-SNOM)-have explored the effect of hBN layer number on the wavelength and propagation characteristics of phonon polaritons, the direct spectroscopic investigation of their resonance energy as a function of layer number has remained largely unaddressed. In this study, we present the first systematic spectroscopic analysis of layer-dependent phonon polariton resonance frequencies in hBN, using photo-induced force microscopy (PiFM). By probing hBN with layer numbers ranging from approximately 10 to 60, we uncover clear and opposing trends in the resonance behavior of the two principal Reststrahlen bands. Specifically, we observe that the in-plane phonon polariton resonance exhibits a blue shift with increasing layer number, while the out-of-plane resonance shows a red shift. Additionally, the peak intensity in the out-of-plane band increases with layer number, whereas the in-plane resonance becomes weaker and broader. These findings reveal critical insights into the optical response of hBN across different layer regimes and underscore the importance of layer number as a tuning parameter in nanophotonic applications.
Deep infiltrating endometriosis (DIE) is a rare and severe subtype of endometriosis that can cause marked distortion of pelvic anatomy. Diagnosis becomes particularly challenging when it presents as an acute abdomen with significantly elevated tumor marker levels. In this study, we describe a rare and deceptive presentation of acute abdomen caused by severe DIE that closely mimicked ovarian carcinoma. A 42-year-old woman (gravida 1, para 1) was admitted with sudden-onset severe diffuse abdominal pain lasting 5 hours. Preoperative findings-including cancer antigen 125 and carbohydrate antigen 19-9 were both elevated to approximately 20-fold above the upper limit of normal, along with imaging results-strongly suggested a ruptured malignant ovarian tumor. Intraoperatively, the lesions were indistinguishable from advanced ovarian cancer, and a definitive diagnosis of deep infiltrating endometriosis (American Society for Reproductive Medicine score 178, Stage IV) was confirmed only through postoperative histopathological examination. Her postoperative recovery was unremarkable, with rapid symptomatic relief, and no recurrence was observed during follow-up. This case highlights that deep infiltrating endometriosis should be considered in patients presenting with acute abdomen, even when clinical and biochemical features strongly suggest pelvic malignancy. Furthermore, the emergency surgery for definitive diagnosis and radical resection also achieved excellent therapeutic outcomes.
Wireless sensor networks (WSNs) deployed for seismic monitoring must sustain long-term operation under strict energy constraints, where premature node failure degrades spatial coverage and detection reliability. This paper presents a safety-constrained reinforcement learning framework for transmission scheduling in energy-harvesting seismic WSNs. The proposed approach integrates Proximal Policy Optimisation (PPO) with action masking and a runtime guard-layer safety filter that enforces battery-preservation and load-balancing constraints without retraining. The guard layer intercepts policy actions and substitutes safe alternatives when constraint violations are detected, using a scoring function that combines battery headroom with network-wide load equity. Experiments across three network scales (10, 15, and 30 nodes) with solar energy harvesting demonstrate that the guard-enhanced PPO achieves 99.46% transmission success at 30 nodes while maintaining 66.47% node survival-a 58.3% improvement in survival over the highest-reward baseline (Closest) at the cost of only a 6.2% reduction in cumulative reward. Crucially, the guard-enhanced policy outperforms the unconstrained PPO baseline simultaneously on cumulative reward (+11.4%), transmission success (+0.8 pp), and node survival (+15.4%), demonstrating that hard safety constraints, when properly aligned with the system's energy model, provide both performance and safety gains rather than a fundamental trade-off. Sensitivity analysis across event rates (pevent=0.5 and 0.9) confirms that the guard layer's advantage persists under both moderate and extreme monitoring conditions. Analysis across scales reveals distinct operational regimes: at 10 nodes, heuristic baselines are near-optimal; at 30 nodes, learned policies dominate, and safety filtering becomes critical for sustained operation.
This study aims to demonstrate the feasibility of controlling particle size through a mathematical model in the design of industrially applicable ultrasonic spray nozzles by utilizing the vibrational characteristics of piezoelectric ceramics. A piezoelectric ceramic composition with a low sintering temperature and excellent thermal stability (Curie temperature above 300 °C) was developed and used as a ceramic vibrator. Furthermore, the resonance frequency and nozzle displacement were calculated using the COMSOL program and applied to a mathematical model to design an ultrasonic nozzle capable of producing a spray particle diameter of approximately 30 μm. The designed ultrasonic nozzle was fabricated, and its spray characteristics were analyzed. The consistency of the spray characteristics was examined by comparing them with the mathematical model based on changes in ultrasonic nozzle length, resonance frequency, and fluid viscosity. When the ultrasonic nozzle horn length was 22 mm, the resonance frequency was found to be 42.1 kHz, and at a flow rate of 65 mL/min. the average spray particle size was approximately 30-40 μm, indicating fine and uniform particles. In addition, it can be seen that as the length of the nozzle horn increases, the resonance frequency decreases, reducing the supply energy delivered to the liquid, and the particle size increases as shown in the mathematical analysis. The theoretical separation energy required to atomize pure water at a flow rate of 65 mL/min. is 2100 J, which was found to be greater than all energy loss occurring during the atomization process. However, it can be seen that as the length of the ultrasonic nozzle increases, the maximum atomization volume increases, and as viscosity increases, the energy required to separate a single atomized particle becomes greater.
Photodissociation of diazines following UV excitation provides a prototypical system for examining unimolecular reaction dynamics on vibrationally excited ground-state potential energy surfaces. In this work, we present a comprehensive theoretical study of the isomerization and dissociation dynamics of the isomers of diazines (C4H4N2), with particular emphasis on pyrazine, after rapid internal conversion to the ground electronic state. A unified ground-state potential energy surface is constructed using CCSD(T)/CBS energies, and microcanonical rate constants and product branching ratios are evaluated using Rice-Ramsperger-Kassel-Marcus theory in combination with microcanonical variational transition-state theory. The results reveal a strong energy dependence of the photodissociation dynamics arising from the interplay between isomerization and competing fragmentation pathways. At lower excitation energies (248 nm), rapid isomerization funnels population into pyrimidine, and dissociation proceeds predominantly through pyrimidine-centered channels. At intermediate energies (193 nm), direct dissociation of pyrazine becomes competitive, with concerted three-body fragmentation producing acetylene and hydrogen cyanide accounting for approximately 36% of the total product yield. At higher energies (157 nm), the dynamics approach a statistical limit dominated by concerted three-body dissociation. These results demonstrate that product branching in diazine photodissociation is governed by a coupled isomerization-dissociation network and cannot be inferred from isolated reaction pathways.
In the field of biomolecular condensates and synthetic systems, it is an open question whether liquid droplets can undergo self-sustained oscillations of formation and dissolution. To unravel the minimal physicochemical prerequisite for such droplet oscillations, we present a simple model composed of only two independent chemical components with their diffusive and chemical fluxes governed by nonequilibrium thermodynamics. There is turnover of fuel that maintains a chemical reaction away from equilibrium, leading to active droplets. We find that a single active droplet undergoes a saddle-node bifurcation in the droplet volume upon increasing the fueling strength. Strikingly, the active droplet becomes excitable upon adding a further chemical reaction. For sufficient fueling, the system undergoes self-sustained oscillations.
Zinc (Zn) is essential for rice but becomes toxic under excess supply, yet the processes governing Zn uptake, long-distance transport, and organ allocation remain unclear. Here we combine Zn stable isotopes (δ66Zn), transport efficiencies (φ), and expression of OsZIP4 and OsZIP1 (ZIP-family influx/efflux transporters), and OsHMA2 (a heavy metal ATPase mediating xylem loading) to quantify Zn homeostasis across a Zn gradient at tillering and maturity. Under sufficient Zn, whole-plant δ66Zn was lighter than the nutrient, indicating net uptake favoring light isotopes. Under high Zn, whole-plant δ66Zn shifted heavier, consistent with preferential exclusion/export of light Zn and supported by strong OsZIP1 induction. Shoots were consistently lighter than roots across treatments and stages, evidencing persistent kinetic fractionation during xylem loading. Development further modulated bulk flux independently of isotopic selectivity: at tillering, high Zn sharply reduced root-to-stem transport efficiency (φ2/φ1) while the Zn isotope fractionation factor between root and plant sap (ε2) changed little, indicating restricted translocation and enhanced root detoxification; at maturity, φ2/φ1 remained high with pronounced OsHMA2 upregulation, sustaining long-distance Zn delivery. Meanwhile, Zn excess rerouted Zn away from grains and toward vegetative pools, coinciding with strong OsZIP4 suppression in leaves. These patterns reveal a stage-dependent switch from "restricted transport and root detoxification" at tillering to "maintained transport but altered allocation" at maturity under Zn excess.
Differentiation of skeletal muscle is associated with increased mitochondrial biogenesis and reliance of oxidative phosphorylation (OXPHOS). The terminal enzyme complex in the electron transport chain, cytochrome c oxidase (COX), requires copper for its assembly and activity, and copper delivery to mitochondria is essential for OXPHOS. However, when mitochondrial copper becomes essential during skeletal myoblast differentiation is not known. Here, we show that genetic deficiency of the mitochondrial copper and phosphate carrier SLC25A3 induced prior to myoblast differentiation leads to the formation of smaller myotubes, but SLC25A3 deficiency induced in mature myotubes leads to cell death and detachment. Both phenotypes are recapitulated upon genetic knockdown of COX17, a critical assembly protein for both COX copper cofactors, or by chemical inhibition of COX. Importantly, myotube death caused by SLC25A3 deficiency is rescued by copper supplementation or expression of an SLC25A3 variant that transports copper but not phosphate. Taken together these data support a model wherein copper transport by SLC25A3 and copper delivery to COX is critical for survival in mature myotubes.
In China, K-12 teachers are expected to innovate in their classrooms increasingly due to the shift of education toward creativity, problem-solving, and adaptable teaching methods. But, not much is known about how principal instructional leadership helps teachers to behave innovatively and under what school conditions it becomes stronger. Based on the theories of Social Cognitive Theory and Social Exchange Theory, this study analyzed the mediation effect of psychological safety between principal instructional leadership and teacher innovative behavior, and the strengthening effect of collective teacher efficacy on the principal instructional leadership to psychological safety to innovative behavior path. The data gathered from the respondents were analyzed by partial least square structural equation modeling (PLS-SEM) in SmartPLS software from in-service teachers in grades K-12 across Nanjing, Wuhan, Xi'an and Hangzhou. The results indicated that the principal's instructional leadership had a positive relationship with the innovative behavior of teachers, and it was a strong influence on the psychological safety of teachers. Psychological safety, in turn, was a critical process which fostered teachers' generation, promotion, and implementation of new instructional ideas through instructional leadership. Results also reveal that collective teacher efficacy amplified the link between psychological safety and teacher innovative behavior, meaning that teachers are more likely to turn a safe climate into innovation when they feel confident in their ability to work together to enhance teaching and learning. Based on the study, the researcher learns that PS is an important mediating process, and the collective teacher efficacy is an important contextual amplifier in the teaching work of Chinese K-12 schools, which enriches the research on teaching practice and innovation.
Multimodal sensors can collect multiple signals and have great potential in robotics and other technical fields. However, such sensors often encounter challenges of signal crosstalk and insufficient real-time performance, particularly in the detection of pressure and temperature, which significantly affect measurement accuracy. To address this issue, a multimodal PCSC sensor was developed. This sensor reduces signal crosstalk by separating force and temperature signals. It uses the pressure-resistance variation of carbon quantum dots (CQDs) to detect force and the thermochromic properties of spiropyran (SP) to detect temperature. When pressure and temperature act on the sensor simultaneously, the resistance increases with pressure and stabilizes when the pressure becomes constant. The response time is 0.4 s. As the temperature rises, the resistance decreases, and the color becomes deeper. Both resistance and color stabilize within 7.5 s. To improve temperature sensing accuracy, a lightweight ResNet-Transformer network (LRTNet) was proposed. This algorithm combines ResNet's ability to extract features and Transformer's ability to model sequences. It efficiently fuses color and resistance signals for temperature detection. Tests on a robotic manipulator for dual recognition of temperature and force showed that LRTNet achieved a runtime of 152.08 ms and a temperature sensing accuracy of 95%. LRTNet improved overall performance by at least 11% compared to traditional algorithms. The sensor and algorithm improved the performance and reliability of multimodal sensors.
Ionic liquids (ILs) exhibiting temperature-responsive phase separation offer promising opportunities for microscale extraction when combined with optical tweezers. Here, we induce local phase separation to generate a single IL-rich microdroplet under optical trapping and investigate the dynamics of molecular extraction into, and release from, the droplet using microspectroscopic analysis. At the high laser power, the microdroplet grows and becomes concentrated, thereby promoting molecular extraction. Upon reducing the laser power, the droplet shrinks while maintaining a high IL concentration. During this process, a dense domain forms around the shrinking droplet, accelerating molecular release from the droplet. Furthermore, we find that the local microenvironment experienced by the extracted molecules is governed by the concentration balance between the IL and the solute molecules. These findings elucidate the key factors controlling molecular extraction and release in an optically manipulated IL microdroplet and provide insights into the design of a new single-droplet-based approach for microanalysis.
Drawing on interpreting research and intervention studies, this article proposes that the interplay between attentional control (AC) and language task schemas (TSs) effectively explains how language experience may enhance AC, and highlights the progressive adaptation of AC via control functions demanded in TSs. Specifically, being heavily taxed in interpreting, AC helps build and adjust interpreting TSs via control functions, and then becomes strengthened in these functions, transitioning from more reactive to more proactive control. The scope of AC adaptation depends on control demands embedded in language TSs, as evidenced by comparing significant and null results in interpreter advantage research (of both professional training and intervention programs). This interplay and the adaptive scope also apply to general bilingual processing, consistent with the Adaptive Control Hypothesis and supported by null results of intervention studies involving in older adults' L2 learning. Future research should adopt a developmental perspective alongside more granular task analyses.
A scaling framework unifying the markedly different and independently studied cylindrical and spherical shock convergence is presented. For ionizing argon, we show that the focal temperature becomes invariant to shock symmetry and initial shock conditions when scaled by the prefocus shock Mach number, after accounting for pressure effects. The resulting collapsed focal temperature-Mach number relation is governed by the thermodynamics of argon, up to an equilibrium temperature of 35 000 K. Such a scaling enables both predictive estimation of focal temperatures over a wide range of initial conditions and, conversely, determination of the parameters required to achieve a target temperature in a given medium.