Falls in older adults remain a major clinical concern. Although the Enhanced Paper Grip Test (EPGT), provides an objective measure of lower limb strength and has shown promise in controlled settings, its use in routine podiatric practice has not been described. To audit the implementation of the EPGT in routine private podiatric practice and to explore whether EPGT measures are associated with self-reported recent falls in older adults. The EPGT was introduced on a trial basis in three independent private UK podiatry clinics for six months. People (aged ≥60 y) were tested when the treating podiatrist considered the assessment clinically appropriate. Anonymised routine clinical data were extracted retrospectively at the end of the audit period, including EPGT outcomes, age, sex, and self-reported history of an unexplained fall in the previous twelve months. Seventy-eight participants (mean age 72 ± 7 years) were assessed; 17 reported a fall. Median EPGT force was statistically significantly lower in fallers (11.9 N) than in non-fallers (21.4 N), U= 283,z = -3.554,p < .0005. Differences remained significant after adjustment for age and sex and were robust to outlier exclusion. Hallux-related pathology was not associated with EPGT outcomes. In this pragmatic private practice audit, the EPGT could be incorporated into routine podiatric assessment and lower EPGT values were associated with self-reported recent falls. These findings support the EPGT as a potentially useful adjunct to falls risk screening that could be offered as part of routine podiatry care. Prospective studies are needed before predictive use or clinical thresholds can be established.
The vertically aligned carbon nanotube (VACNT) array, characterized by a vertical arrangement of carbon nanotubes at the bottom and a chaotic crown-like structure at the top, is commonly employed in optical ultrasound emitters due to its high light absorptance and anisotropic thermal conductivity. However, the excessively dense carbon nanotubes at the bottom hinder the incorporation of elastic materials, which necessitates regulation of its morphological structure. To validate the proposed hypothesis, a series of VACNT arrays were synthesized using the chemical vapor deposition technique, which enabled precise control over the morphological properties of the arrays by adjusting the growth duration. Experimental results reveal that an 8 µm thick sample achieves the optimal performance balance, yielding a peak sound pressure of approximately 9.6 MPa, a -6 dB bandwidth of 21.2 MHz, and an energy conversion efficiency of 0.39% under 20mJ laser excitation. Microscopic structural analysis reveals that at this thickness, the carbon nanotube array achieves a vertically aligned yet relatively sparse configuration at its base, which effectively facilitates efficient directional heat transfer while ensuring sufficient infiltration of the elastomer. These findings provide critical insights into the design, fabrication, and performance optimization of high-efficiency VACNT-based photoacoustic transmitters.
In the current study, N-doped apple tree branch-based biochar-supported Co/CoO catalyst (Co/CoO@NBCs) was prepared using an impregnation-pyrolysis synergistic strategy, which addressed the issues of easy aggregation, poor stability, and low specific surface area of the Co/CoO catalyst. The characterization results show that Co/CoO@NBCs has a large specific surface area (1871.02 m2/g), a developed pore structure (0.99 cm3/g), and Co exists in the form of Co atoms and CoO. Under conditions of 0.25 mM peroxymonosulfate (PMS), 10 mg of catalyst, and room temperature, the degradation rate of norfloxacin (NOR, 30 mg/L) reached equilibrium within 70 min, with a removal rate of 99.06%. Besides the strong alkali condition (pH = 11) and the presence of HCO3-, the removal rate of NOR by Co/CoO@NBCs in other pH ranges and in anionic environments can still exceed 73%. Furthermore, analysis of the degradation mechanism shows that the active sites of Co0 and Co2+ can activate PMS to produce reactive oxygen species, with O2-• and 1O2 serving as the main active substances involved in NOR degradation. Additionally, tests with real water systems and cycling experiments further demonstrate that Co/CoO@NBCs have practical application potential. This work offers new insights into designing heterogeneous catalysts with multiple active sites for wastewater treatment.
Decades of research have uncovered the complex signaling network downstream of the opioid receptors and suggested how this signaling could be modulated to improve opioid therapy. In our study, we have found that heat shock protein 90 (Hsp90) regulates downstream opioid signaling oppositely in the brain vs the spinal cord. In the spinal cord, we have found that Hsp90 inhibition enables antinociceptive signaling and disables pronociceptive signaling to enhance opioid pain relief and reduce side effects. We have now extended this study to analyze the contribution of protein kinase C (PKC) to the opioid signaling cascade. We used the Hsp90 inhibitor 17-AAG along with a PKC activator or inhibitor (Go6983) delivered into the spinal cords of male and female CD-1 mice to show that pan-PKC signaling contributes to the enhanced opioid antinociception observed in tail flick and postsurgical pain models. We used Western blot and immunohistochemistry to observe increased pan-PKC phosphorylation across calcitonin gene-related peptide (CGRP) and IB4 nociceptors in the spinal dorsal horn. We then used selective siRNA to identify PKCβ as the active isoform and further found PKCβ to be selectively activated in CGRP neurons by Hsp90 inhibition and morphine combined. Finally, we used cell-type-selective Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to knock down PKCβ in CGRP neurons and showed that this specific isoform in these specific cells was necessary for enhanced opioid antinociception after Hsp90 inhibition.Together, these studies further uncover the novel Hsp90-regulated opioid signaling cascade and suggest how Hsp90 inhibitors could be used to improve opioid therapy by increasing analgesic efficacy and decreasing side effects.
This review examines the use of polymer solutions for in-situ subsurface remediation, with a focus on their rheological behavior and implications for contaminant removal. The in-situ remediation of subsurface contamination is often constrained by aquifer heterogeneity, preferential flow, and limited reagent contact with trapped contaminants. Polymer solutions, particularly shear-thinning biopolymers such as xanthan gum (XG), have emerged as promising tools to overcome these challenges. Originally adapted from enhanced oil recovery applications, their unique rheological properties allow high injectivity near the well while promoting mobility control farther into the formation. This enables more stable displacement fronts, suppression of viscous fingering, and enhanced crossflow into low-permeability zones, thereby improving Non-Aqueous Phase Liquids (NAPLs) recovery while also enhancing contaminant removal and amendment delivery in low-permeability regions of heterogeneous media. Beyond direct displacement, polymers may act as carriers for a wide range of remedial amendments, including oxidants, reducers, electron donors, surfactants, and nanoparticles, improving their placement, persistence, and effectiveness. Yield-stress and densified formulations further expand applications by blocking preferential pathways or counteracting buoyancy forces in gravity-dominated systems. Field demonstrations confirm these benefits: Polymer-amended oxidants and electron donors have produced larger swept volumes, more homogeneous propagation, and longer remanence than water-based solutions, with electrical resistivity tomography and coring providing direct evidence of improved distribution and contact. Industrial-scale applications have also shown that formulation and injectivity must be carefully balanced to avoid excessive pressures, fracturing, or reagent incompatibility. Continued integration of laboratory rheology, numerical models, and field validation will be essential to fully realize polymers as multifunctional technologies for contaminant displacement, amendment delivery, and unwanted flow blocking. With growing field evidence, polymer solutions are poised to become central to the design of predictable, durable, and site-specific remediation strategies.
Perovskite solar cells (PSCs) offer exceptional tunability of optoelectronic properties, enabling wide-band-gap absorbers that are highly attractive for semitransparent devices in building-integrated photovoltaics (BIPV). However, challenges associated with stability, scalability, and materials' cost continue to limit their practical deployment, highlighting the pivotal role of hole transport materials (HTMs) in achieving high efficiency and durable device operation. Herein, we report the rational design and synthesis of three novel small-molecule HTMs based on phenothiazine-triarylamine cores, prepared via concise synthetic routes with moderate-to-high yields. The electron-rich, nonplanar phenothiazine scaffold enables suppressed aggregation and favorable energy-level alignment, rendering these materials particularly suitable for wide-band-gap and semitransparent PSCs. When implemented in FAPbBr3-based semitransparent devices, two candidates (SM1 and SM2) achieve power conversion efficiencies comparable to those of the state-of-the-art poly(triarylamine) (PTAA) (PCE = 6.26% and 6.09% for SM1 and SM2, respectively, vs 6.39% for PTAA). Notably, their enhanced optical transparency leads to comparable light-utilization efficiency (LUE) (4.05 and 3.99 for SM1 and SM2, respectively, vs 4.07 for PTAA), with outstanding and superior bifaciality factors (84% and 82% for SM1 and SM2, respectively, vs 81% for PTAA), providing a distinct advantage beyond conventional opaque-PV efficiency metrics. These findings position phenothiazine-based HTMs as promising, cost-effective alternatives to PTAA for scalable semitransparent perovskite solar cells.
Lacto-N-biose I (LNB), a core structural unit of human milk oligosaccharides, was usually fermented by microbial cell factories because its biosynthesis involved the supplies of ATP and UDP-sugars. Here we designed an in vitro ATP- and UDP-sugar-free enzymatic pathway for the biosynthesis of LNB from lactose and N-acetylglucosamine (GlcNAc). Thermoclostridium caenicola cellobiose phosphorylase was discovered to have a very high promiscuous activity of lactose phosphorylase. Its lactose phosphorylase activity was enhanced greatly by directed evolution, yielding the variant M2 (N654A/Y501A) having 1.56-fold higher lactose activity and doubled lactose/cellobiose specificity. The coenzyme-free three-enzyme molecular machine containing lactose phosphorylase M2, lacto-N-biose phosphorylase and polyphosphate glucokinase produced up to 115 g/L LNB from lactose and GlcNAc and exhibited the highest volumetric productivity of 14.4 g/L/h. This coenzyme-free multienzyme molecular machine could provide a cost-competitive platform for in vitro biomanufacturing of LNB.
Purpose: Stroke is one of the leading global causes of disability, with motor deficits, particularly in the upper limb, being among the most common and debilitating consequences. Occupational therapists are crucial members of the multidisciplinary team, working to enhance patients' participation in daily activities by addressing motor impairments through interventions such as Functional Electrical Stimulation (FES). However, an evidence-practice gap exists in the application of FES. This study aimed to explore occupational therapists' perceptions of using FES in adult stroke rehabilitation in Gauteng, South Africa. Materials and Methods: This study employed a descriptive qualitative research design. Twelve occupational therapists participated in semi-structured interviews conducted via an online platform. The research population included clinicians working in the neurorehabilitation field in Gauteng, South Africa from both public and private healthcare sectors. An inductive thematic analysis was used to analyse the data. Results: Three themes emerged from this qualitative study, namely, 'A Tug of War', 'The Lost Leading the Lost' and 'A Puzzle of Practicality'. These themes unravel the perceptions of occupational therapists and explore the factors that influence the use of FES in stroke rehabilitation. Conclusion: Many identified perceptions and factors challenge the use of FES in adult stroke rehabilitation. Addressing these challenges is essential for improving evidence-based practices in occupational therapy, especially for motor impairments after stroke. Training on FES needs to be enhanced at an undergraduate and postgraduate level for improved application of the technology.Open-loop FES currently does not align with the complex movement patterns required for occupation-based intervention and is therefore best suited as a preparatory modality.Policy, protocol, and guideline development is needed for a unified approach to FES use in stroke rehabilitation.The commercial availability and access to closed-loop FES systems should be explored by rehabilitation technology manufacturers and sales representatives.
Gas-driven element redistribution, characterized by the preferential enrichment of one element at the surface relative to the bulk, is frequently observed in multicomponent alloys. Using L10-ordered PtNi as a model system, we reveal that gas pressure plays a critical role in governing adsorption-driven surface composition during annealing in reducing gases: low pressure favors Pt surface segregation, while high pressure facilitates Ni surface enrichment. In this study, we developed a high-pressure nitriding (HPN) strategy that modulates the surface structure and composition of PtNi catalysts. The resulting HPN-PtNi exhibits enhanced performance and durability in membrane electrode assemblies for heavy-duty fuel cell applications, maintaining a high current density of 1.19 A cm-2 at 0.7 V after 90,000 voltage cycles. Through a combination of experimental and theoretical analyses, we reveal that the HPN process forms additional stabilizing Ni-N bonds and induces elemental redistribution with Ni surface enrichment and a Ni-deficient Pt subsurface. These modifications alter the atomic coordination environment of the ordered PtNi phase. This work presents a generalizable strategy to design robust and high-performing Pt-based catalysts by controlling gas-pressure-driven elemental redistribution and dopant incorporation.
The aim of this study was to investigate the effects of ultrasound-assisted tumbling (100, 300, 500, and 700 W) with different treatment times (30, 60, 90, 120, 150, and 180 min) on the quality, myofibrillar protein structure, and protein oxidation of beef (knuckles, 48 h postmortem). Differences in physicochemical properties were assessed, including tumbling yield, protein content in the brine, cooking loss, color, texture, and moisture distribution. Additionally, protein structural and oxidative characteristics were analyzed by measuring carbonyl groups, sulfhydryl groups, and secondary structural conformations. Results indicated that ultrasound-assisted treatment increased both tumbling yield and brine protein content (P < 0.05). Compared with single tumbling (conventional tumbling without ultrasound treatment), ultrasound-assisted tumbling increased the L* value and myofibrillar fragmentation index, while reducing the a* value, hardness, and shear force (P < 0.05). Magnetic resonance imaging, low-field nuclear magnetic resonance, and cooking loss results confirmed that the ultrasound process raised the bound water content and enhanced water-holding capacity of beef (P < 0.05). Moreover, increased ultrasonic power elevated protein carbonyl content and reduced total sulfhydryl content, thus promoting protein oxidation. Conformational analyses revealed that ultrasound treatment reduced protein α-helix content while elevating β-sheet content. In summary, ultrasound-assisted tumbling improved cured beef quality by regulating water migration and modifying protein and myofibrillar structures.
The Arabidopsis enolase2 (AtENO2) gene produces both the glycolytic enzyme enolase and an N-terminal truncated isoform, termed the transcriptional repressor Arabidopsis cMyc-Binding Protein 1 (AtMBP-1), through alternative translation. Maintaining AtENO2 homeostasis via feedback repression by AtMBP-1 is essential for its biological functions; however, the underlying regulatory mechanism remains unclear. Cadmium (Cd), a toxic soil pollutant, strongly inhibits plant growth and development. Interestingly, Cd induces enolase accumulation in plants, and AtMBP-1 binds to metal-responsive elements (MREs) that confer a Cd response in Arabidopsis. Here, we demonstrate that AtMBP-1-mediated repression via an MRE in the AtENO2 promoter maintains the AtENO2 expression balance, which is required for Arabidopsis Cd resistance. Knockdown of AtENO2 via antisense RNA increased Cd sensitivity, which was accompanied by altered intermediates of the tryptophan pathway (notably those involved in auxin biosynthesis), elevated Cd accumulation in the shoots and roots, and increased lipid peroxidation. We further showed that AtENO2 utilizes its 5'-UTR as a Cd-responsive alternative promoter, driving a predominant short transcript that is efficiently translated into the AtENO2 protein. Accordingly, Cd stress increased AtENO2 protein accumulation. An MRE located within the 5'-UTR promoter was functional: CRISPR/Cas9-mediated deletion of a 50 bp MRE-containing fragment in vivo increased AtENO2 abundance and significantly enhanced Arabidopsis growth under Cd stress. AtMBP-1 binds to this MRE to repress AtENO2 promoter activity, thereby forming an autoregulatory loop that fine-tunes AtENO2 levels and prevents its overaccumulation during prolonged Cd stress. Our findings reveal a previously unknown mechanism underlying AtENO2 function in plant adaptation to heavy metal stress.
Non-small-cell lung cancer (NSCLC) mortality remains high because mutation-specific therapies target only small patient subsets and inevitably encounter drug resistance. In this regard, multipathway-assisted mesenchymal stem cell-derived nanovesicles (stemsomes) offer a promising universal platform for overcoming the unmet needs of lung cancer therapeutics, particularly for patients lacking identifiable oncogenic drivers. This study introduces a novel strategy in which dexamethasone, a compound conventionally used as an anti-inflammatory drug, is repurposed to enhance the tumor-targeting capabilities of stemsomes. Nanoparticles engineered by fusing these dexamethasone-primed stemsomes with liposomes exhibit markedly improved therapeutic effects. According to transcriptomic and siRNA-mediated knockdown experiments, this enhanced targeting of tumor cells is driven by the dexamethasone-induced upregulation of key cell adhesion proteins, specifically ephrin type-A receptor 2 and neurogenic locus notch homolog protein 3. Furthermore, a comprehensive map of potential adhesion interactions and computational simulations suggest a multivalent interaction network between the surfaces of dexamethasone-primed stemsomes and NSCLC H1975 cells. These findings indicate the discovery of a highly translational and mutation-independent strategy that represents a promising novel mechanism for engineering vesicle surfaces for NSCLC therapy.
It has long been known that Pro35S-driven sense transgenes have a high propensity to undergo post-transcriptional gene silencing (S-PTGS). However, what exactly conditions S-PTGS initiation and amplification to make it systemic remains unknown. Through genetic screens, we show that antagonistic chromatin-related mutations enhancing and reducing transgene expression, result in enhanced and reduced S-PTGS amplification capacities, respectively, without affecting the initiation rate. Analysis of a large set of independent transgenic plants confirm a direct relationship between transgene expression and its capacity to amplify S-PTGS. Combining an inducible or a tissue-specifically expressed GUS transgene with a Pro35S:GUS transgene locus prone to amplify S-PTGS but unable to spontaneously initiate it induces systemic S-PTGS, indicating that transient and/or local passing of a discrete threshold is sufficient to initiate S-PTGS. Together, these results call for the existence of distinct thresholds related to transiently produced aberrant RNA and permanently produced target mRNA levels, which condition S-PTGS initiation and amplification, respectively. We show that this model also applies to endogenous genes for which RNA Quality Control (RQC) acts as a first layer of protection against S-PTGS, and DCL2's obscuration by DCL4 as a second layer, allowing RQC to dysfunction locally without translating into the drama of systemic S-PTGS.
Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is a key negative regulator of T cell activation, acting with C-terminal Src kinase (Csk) to suppress early T cell receptor (TCR) signaling and maintain immune tolerance. Given that the autoimmune disease-associated R620W variant alters T cell responses, we investigated the effects of PTPN22 on T cell activation. We identified a role for PTPN22 in modulating cytoskeletal dynamics at the immunological synapse in Jurkat cells through its interaction with proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1), a cytoskeletal adaptor protein that recruits actin nucleation-promoting factors, including WASp, to the TCR. PTPN22 deficiency or inhibition disrupted Arp2/3-dependent actin remodeling, leading to excessive central F-actin foci, PSTPIP1 mislocalization, and enhanced Ca2+ signaling, especially under low-affinity stimulation of the TCR. Super-resolution DNA-PAINT analysis revealed that loss of PTPN22 promoted aberrant PSTPIP1-TCR nanoscale colocalization and increased TCR clustering. These findings uncover a PTPN22-PSTPIP1 signaling axis that is critical for regulating cytoskeletal remodeling and receptor organization, providing insights into T cell hyperactivation that may be relevant to autoimmune disease.
The exercise is medicine (EIM) initiative, promoted as routine care for cancer populations, is inadequately integrated into oncology practice. While barriers to and facilitators of physical activity (PA) promotion are well documented, oncology nurses' perspectives on EIM remain underexplored. This mixed-methods study examined oncology nurses' current PA promotion practice and perspectives on implementing the EIM initiative in China. A total of 155 oncology nurses across Hong Kong and Shenzhen in China participated in an online survey (including a 3-min EIM introductory video) assessing current PA promotion practices, personal PA habits, and attitudes toward PA and EIM, among which 14 were subsequently interviewed. The results revealed infrequent PA discussions with patients and relatively low confidence in PA promotion. After watching an EIM introductory video, participants' attitudes toward PA promotion improved slightly, with most expressing average interest and preparedness to integrate EIM in practice. Qualitative analysis revealed 5 key themes influencing EIM implementation: confidence in PA promotion, perceived priority of promoting PA in practice, perceived appropriateness of promoting PA for patients, organizational infrastructure (trainings, guidelines, collaborations, resources), and societal support. Oncology EIM implementation requires systematic organizational support, necessitating a multifaceted approach encompassing competency development, standardized procedural guidelines, cross-sector collaborations, and strategic resource allocation. Integrating EIM in oncology care requires enhanced organizational support, including training, guidelines, collaboration and resources. Implementation assessment and research are essential to ensure successful and sustainable integration and to evaluate applicability, effectiveness, and sustainability of EIM in real-world oncology settings.
Accurate classification of sea turtle species is crucial for ecological monitoring and conservation, yet traditional visual classification methods remain limited by underwater imaging challenges such as occlusions, poor lighting, and background noise. To address these limitations, we propose an enhanced deep learning-based classification framework that integrates both color and structural features to improve the robustness of species recognition in complex marine environments. Building upon the ResNet-50 backbone, we introduce a four-channel input tensor comprising RGB data and Sobel-filtered edge maps, capturing both semantic and morphological information. Two novel fusion modules, LiteAFNet and AlphaBlendNet, are designed to integrate these features effectively. LiteAFNet leverages a lightweight attention mechanism to highlight discriminative regions, while AlphaBlendNet adaptively balances RGB and edge cues based on spatial context. Experimental results demonstrate significant improvements in classification performance across all evaluation metrics. Specifically, AlphaBlendNet achieves the highest precision (0.84), recall (0.88), F1-score (0.86), and mean average precision (mAP) of 87.2%, outperforming both the baseline fusion and LiteAFNet configurations. These results indicate that integrating color histograms with structural edge features enhances the model's ability to distinguish between species with similar visual traits. This framework offers a scalable, accurate, and automated solution for underwater species classification and holds potential for broader application in marine biodiversity monitoring.
Oxytocin modulates social information processing by altering excitatory-inhibitory balance at the microcircuit level, but how such local modulation gives rise to selective processing at the level of distributed brain systems remains unclear. Here, we investigated the effects of oxytocin on large-scale neurodynamics across cortico-limbic network in the mouse brain using multisite local field potential recordings. Oxytocin selectively enhanced neural responses to infant calls in the auditory cortex (AC) and medial prefrontal cortex (mPFC). These enhancements occurred while baseline activity was reduced, indicating increased signal-to-noise ratio rather than a global increase in excitability. During auditory steady-state responses (ASSRs), oxytocin increased prefrontal phase coherence without altering ASSR power. During rest, oxytocin induced a transient, broadband reduction in spontaneous spectral power across regions. Despite this reduction in activity, analyses of interregional interactions revealed a selective increase in low-theta phase coupling and directional connectivity of AC→mPFC. Session-level analyses showed that stronger bottom-up AC→mPFC coupling was associated with lower prefrontal power, consistent with a gating or disinhibitory network regime favoring sensory-to-prefrontal information transfer. Multivariate analyses showed that oxytocin/saline conditions were reliably discriminable using supervised classification models, with specific contributions from spectral power, phase-locking, and Granger-causal connectivity features. Conversely, unsupervised dimensionality reduction did not identify a distinct low-dimensional manifold separating conditions, although a modest shift in the centroid of neural state space was observed. Together, these results indicate that oxytocin reduces background neural activity while selectively enhancing sensory-prefrontal network interactions, providing a systems-level account linking local inhibitory modulation to selective processing of socially salient infant cues.
Cyanobacteria are photoautotrophic microorganisms that fix CO2 through oxygenic photosynthesis during the day and rely on heterotrophic metabolism at night. In nature, the availability of inorganic carbon (Ci) is often limited, posing a major constraint on photosynthetic efficiency. To overcome this, cyanobacteria have evolved a sophisticated CO2-concentrating mechanism (CCM) that enhances the catalytic performance of the primary carboxylating enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO). The CCM functions by elevating intracellular CO2 concentrations around RubisCO to suppress its oxygenase activity and enhance CO2 fixation efficiency. Central to this system is the carboxysome, a proteinaceous microcompartment that encapsulates RubisCO and carbonic anhydrase, facilitating efficient conversion of bicarbonate (HCO3 -) to CO2 and its subsequent fixation. This is complemented by multiple Ci transporters that mediate active uptake of CO2 and HCO3 -. Five major transport systems have been characterized: two specialized NDH-1 complexes for CO2 transport and its conversion into HCO3 -, and SbtA, BicA, and BCT1 for HCO3 - uptake. Recent structural studies on CCM uptake systems have revealed key mechanisms of HCO3 - transport, CO2 hydration and transport coupling. These insights provided a deeper understanding of how these systems enhance Ci acquisition and maintain photosynthetic efficiency across diverse environmental conditions and various CO2 regimes. Moreover, the CCM is tightly regulated at both transcriptional and post-translational levels to balance energy usage and carbon demand. This review outlines our current insights into the molecular architecture, transport dynamics, and regulatory networks of the cyanobacterial CCM, emphasizing its critical role in photosynthesis and its potential as a model for bioengineering enhanced CO2 fixation or for engineering synthetic bacterial microcompartments.
The transition toward value-based care in the United States has introduced episode-based payment models that increasingly tie physician reimbursement to longitudinal costs and standardized outcomes. The Centers for Medicare & Medicaid Services (CMS) Ambulatory Specialty Model (ASM), targeting chronic low back pain (cLBP), represents a pivotal extension of this framework into interventional pain management. While intended to reduce low-value utilization, such models risk redefining clinical success in ways that may not align with the heterogeneous and biopsychosocial nature of chronic pain. This perspective examines the potential for outcome-driven reimbursement to incentivize risk selection, marginalize clinically meaningful but non-durable functional gains, and exacerbate existing health disparities. Based on available literature, we propose a "Value Plus" framework incorporating enhanced risk adjustment and patient-centered composite outcomes to better align economic incentives with the realities of chronic pain care. In conclusion, in the field of interventional pain management, withdrawal of multiple conflicting models (ASM, WISER, etc.), and addition of a payment model including a value plus framework would better align incentives with the realities of delivering care to chronic pain patients.
In computational pathology, Hematoxylin and Eosin (H&E) staining offers a cost-effective solution for tissue analysis, while Immunohistochemistry (IHC) delivers specific biomarker expression at substantially higher cost and operational complexity. Existing H&E-to-IHC translation methods predominantly operate at the pixel level, often overlooking the preservation of high-level semantic features required by modern multi-instance learning frameworks. To bridge this gap, we present FeatStainDiff, a diffusion-based model that performs direct feature-level transformation between staining modalities. Our framework incorporates two novel components: a Contrastive Semantic Bridging mechanism that ensures diagnostic semantics are preserved during cross-modal translation, and a Frequency-domain Mixture of Experts module that adaptively handles distribution shifts through spectral processing. This design enables the generation of high-fidelity and pathologically consistent IHC features directly from H&E inputs. Through extensive evaluation on two virtual staining datasets and two whole-slide image classification benchmarks, we demonstrate that FeatStainDiff consistently surpasses existing approaches. The method achieves significant improvements in feature similarity metrics, while downstream classification tasks benefit from markedly enhanced performance. FeatStainDiff provides an effective and practical pathway for computational biomarker prediction, with promising potential to expand access to specialized staining analysis in resource-limited clinical environments. Code will be made publicly available upon publication.