搜索结果：commercial

Online scheduling platforms are increasingly chosen by patients for scheduling outpatient appointments. Due to payment for listing or platform decisions on listing visibility, they can amplify access inequalities. Especially in Germany's dual insurance system, the beneficiary difference in waiting times for private health insurance (PHI) patients compared to statutory health insurance (SHI) patients for specialist appointments might increase. The objective of this study was to quantify differences in waiting times for the first available specialist outpatient appointments for SHI versus PHI profiles on a large commercial online scheduling platform (Doctolib) in Berlin and to assess whether practices offering equal appointment options for both insurance types are deprioritized by the platform. We performed a cross-sectional, internet-based audit between January 6, 2025, and February 26, 2025. Two standardized simulated patient profiles (SHI and PHI) were used to query 1867 platform listings; practices with at least 1 bookable slot for both profiles were documented (n=492). The primary outcome was the waiting time in days for the earliest available appointment. Paired 1-tailed t tests and Wilcoxon signed-rank tests were used to compare within-provider waiting times, while exploratory subgroup analyses examined specialty-specific differences. Sensitivity analyses excluded the top 5% of the longest waits. Effect sizes (Hedges g) were computed. Across 492 practices, mean waiting times were 50.4 (SD 52.2) days for SHI and 22.6 (SD 36.8) days for PHI, yielding a mean difference of 27.8 days (95% CI 23.6-31.9 d; t491=13.05; P<.001; Hedges g=0.59). After excluding the top 5% of waiting times (n=44), the difference remained significant (&#x394;=23.1 d; 95% CI 20.0-26.2 d; t447=14.77; P<.001). Providers that offered earlier PHI appointments showed substantially longer SHI waiting times (61.8 vs 37.5 d; P<.001) and substantially shorter PHI waits (12.0 vs 38.2 d; P<.001). Platform ranking was correlated with earlier PHI availability (Spearman rank correlation r=0.574; P<.001). On this commercial online scheduling platform in Berlin, SHI patients experienced substantially longer waits for the first available specialist appointments than PHI patients across multiple specialties. Potential mechanisms that could amplify pre-existing insurance-based access inequities are discussed. Transparency about the platform's ranking criteria should be considered to promote equitable access.

Highly efficient thermal interface materials (TIMs) play an essential role for integrated devices and systems of high energy density such as AI and power semiconductor chips. Conventional polymer-based composite TIMs that have low thermal conductivity and large contact thermal resistance do not meet heat dissipation needs of rapidly developing modern high-power electronics. In this work, we report an indium/vertical graphite (InVGr) composite material, which exhibits thermal conductivity as high as 220.2 W/m&#xb7;K. Moreover, by employing low-melting-point InBiSn liquid metal (LM) for contact surface optimization, the contact thermal resistance was reduced to 0.09 cm2&#xb7;K/W under a pressure of 100 psi. Practical heat dissipation experiments demonstrate that with the LM/InVGr/LM composite, the heat source temperature was drastically decreased from 113.3 &#xb0;C (when using commercial silicone pad SF 600G, 8 W/m&#xb7;K) to 55.5 &#xb0;C. Equivalent heat transfer coefficient analysis demonstrates that the cooling efficiency of LM/InVGr/LM outperforms those of commercial silicone pads and carbon fiber pads. These findings confirm that the surface-modified InVGr serves as a novel solution for the effective thermal management of state-of-the-art high-power electronic devices.

Microcystis aeruginosa is a freshwater cyanobacterium known for its role in the formation of harmful algal blooms. However, less well characterized are the host-phage interactions that occur in these toxic blooms. Here, we describe the relationship between a microcystin-producing strain of M. aeruginosa, NIES-298, and a lytic bacteriophage Ma-LMM01. In this study, we explored how host pre-acclimation to different temperature conditions influenced sensitivity to subsequent infection by Ma-LMM01. We focused on 19&#xb0;C, a cooler temperature often associated with microcystin-producing blooms in spring/early summer, and 26&#xb0;C, a warmer temperature often associated with non-microcystin-producing blooms of late summer. M. aeruginosa cultures pre-acclimated to 26&#xb0;C were completely lysed whether infection occurred at 26&#xb0;C or 19&#xb0;C. In contrast, 19&#xb0;C-acclimated M. aeruginosa grew and resisted infection regardless of infection temperature. We next formulated a mathematical model to investigate the key parameters driving these temperature dynamics. Our modeling suggested both 19&#xb0;C- and 26&#xb0;C-acclimated hosts contain resistant subpopulations of comparable abundance but with different degrees of resistance. Specifically, we found the 19&#xb0;C-acclimated host subpopulation was substantially more resistant to phage infection than the 26&#xb0;C-acclimated host subpopulation, which was only partially resistant. Overall, our observations demonstrate that M. aeruginosa NIES-298 acclimation to 19&#xb0;C played a role in the development of resistance to cyanophage Ma-LMM01. These findings suggest new directions to explore the link between physiological changes and infection outcomes for microcystin-producing cyanobacteria in changing environments.IMPORTANCEHarmful cyanobacterial blooms frequently develop in aquatic systems, causing significant ecological and commercial impact, motivating research into factors influencing bloom formation, persistence, and toxicity. Prior studies identified several contributors to the "life cycle" of a toxic bloom, including abiotic influences, community structure, and host-viral interactions. This paper explores two of these factors, temperature and viral-host interactions, on the growth and survival of Microcystis aeruginosa NIES-298. We report the first observation that the acclimation temperature of M. aeruginosa influences phage susceptibility, and through mathematical modeling, explore resistant subpopulation dynamics. We observed that cells acclimated to cold temperatures, such as those experienced in spring/early summer, were resistant to phage, while those acclimated to warmer temperatures, such as those experienced in late summer, were not. This work contributes to the fields of freshwater ecology and microbial physiology by advancing our understanding of the interplay between host-phage interactions and abiotic influences in toxic algal bloom formation.

Five carbonyl thiacalixarene derivatives (5, 6, 7, 9, and 10) were synthesized via the reactions of mono-substituted thiacalixarenes (2, 3, 4, and 8) with ethyl bromoacetate, 2-chloro-N-(p-tolyl)acetamide, or 2-chloro-N-(p-tolyl)ethanethioamide. The chemical structure of the synthesized compounds was confirmed by IR and NMR spectroscopy. The metal ion recognition abilities of these thiacalixarene derivatives were investigated through liquid-liquid extraction of various metal picrates (Na+, K+, Cs+, Ag+, Pb2 +, Cd2 +, Co2 +, Ni2 +, Cu2 +, and Hg2 +) from water to dichloromethane. Compounds 5 and 6 exhibited poor to moderate extraction efficiencies, likely due to the limited number of carbonyl groups. In contrast, compounds 7, 9, and 10 showed moderate to high extraction capacities, with thiacalixarene 9 demonstrating the highest extraction of Cs+ (93.4%) and strong extraction of other metal ions, highlighting the effect of carbonyl-to-thionyl conversion on metal-ligand interactions. The insecticidal activities of the synthesized thiacalixarene derivatives in combination with the commercial insecticide chlorfenapyr were evaluated against the second and fourth larval instars of Spodoptera littoralis. Mortality was recorded 72 h post-treatment, and LC50 values were determined. These results indicate that calixarene derivatives can enhance pesticide efficiency and offer a promising strategy for designing next-generation agrochemical agents.

Venturicidin A (1) constitutes a glycosylated macrolide endowed with potent antifungal activity; however, the discrete contributions of its post-polyketide synthase modifications to bioactivity have remained elusive. Here we systematically deconvolute the structure-activity relationships of venturicidin A&#xa0;(1), its glycosylated congener venturicidin B&#xa0;(2), and the aglycon derivative venturicidin X&#xa0;(3). The latter was generated through targeted disruption of the glycosyltransferase-encoding gene&#xa0;vtdG.&#xa0;Across a panel of eight phytopathogenic fungal species, the glycosylated congeners exhibit markedly superior antifungal activity relative to the aglycon, with 1 outperforming the commercial fungicide carbendazim against&#xa0;Alternaria alstroemeriae&#xa0;CGMCC 3.1640. Mechanistically, glycosylation critically dictates the extent of plasma membrane disruption and mitochondrial impairment, whereas the carbamoyl moiety contributes negligibly to these phenotypes. Collectively, these findings establish the glycosyl moiety as&#xa0;an indispensable structural determinant of antifungal potency, furnishing a strategic blueprint for the rational optimization of venturicidin analogues.

The kinetics of chemical aging in most commercial plastics have remained long debated, since the nature of dense polymeric solids inhibits the in situ experimental investigation of complex degradation paths, while traditional computational techniques fail to reach the time scales associated with slow-progressing degradative reactions. In this work, a novel mechanistic framework is introduced in which the infrequent reaction events that govern the long-time-scale evolution of the chemistry of any amorphous solid are described as successive elementary transitions of the atomistic configuration between local minima on its energy landscape. For each elementary reaction event, the corresponding transition state is identified, allowing the estimation of the free-energy barrier and, thereby, of the transition rate constant by means of transition state theory. The result is a network of states populated by the stationary states that are visited by the system along chemical paths. We demonstrate the applicability of the presented approach for the study of complex reaction schemes by applying it to the study of the autoxidation of glassy polystyrene. The introduction of an appropriately trained reactive force field, ReaxFF-lg/CHOpox, tailored for the accurate description of the reactions propagating polymer oxidation, i.e., peroxy radical and hydroperoxide formation, in the glassy state, allows the large-scale sampling of potential reaction paths in situ. From the created network of states, we extracted the energetics and rates of the elementary reactions in the glassy state. For both reactions, the broad distribution of free-energy barriers, spanning over many orders of magnitude, is indicative of the significant impact that the local dense environment has on reaction kinetics and highlights the importance of studying solid-state reactions in situ.

NeedDuring deep brain stimulation (DBS) surgery, the base ring of the burr hole is the main structure that anchors the DBS lead. A discrepancy between the burr hole size and ring base renders the ring unstable which in turn compromises lead stability. Burr hole size mismatch is often seen in resource-poor countries where advanced perforators, that make exact size holes are not available.Technical SolutionWe describe a simple, cost-effective technique, the screw-lock method. When there is a mismatch, titanium self-tapping screws are inserted through the holding holes of the base ring into the skull with immediate and stable fixation.Proof of ConceptThis technique not only immediately secures the base ring to the skull but also prevents accidental displacement of the DBS lead.Next StepsThe titanium screws can be included in the burr hole ring set in commercially available products. A new type of expandable burr hole rings can be designed to fit any size of burr hole.ConclusionThis is an effective method to stabilize the burr hole base ring and the DBS lead.

Sphaerulina musiva, a fungal pathogen causing leaf spot and canker disease of poplar trees (Populus spp.), was recently introduced to the Pacific Northwest, where it threatens commercially valuable plantations and native riparian ecosystems. Vascular tissue was collected from the stems of 410 symptomatic and asymptomatic trees in an S. musiva-infested Populus trichocarpa plantation. Resident fungal endophyte communities were characterized with ITS amplicon sequencing. Canker expression and S. musiva presence corresponded with reduced fungal diversity across multiple indices. Fungal endophyte communities of symptomatic tissues were frequently dominated by S. musiva and thus compositionally distinct from those of asymptomatic tissues. Asymptomatic-tissue communities from healthy and diseased stems did not differ in composition or diversity, indicating disease-associated low-diversity mycobiome states are local to the cankered site. The relative abundance of S. musiva was positively correlated with stem cankering. S. musiva was negatively correlated with key non-pathogenic fungal endophytes, which were themselves strongly inter-correlated. Our results illustrate S. musiva's ability to exploit the vascular microhabitat of susceptible Populus trichocarpa stems and dominate resident fungal assemblies at the site of infection. Plant-associated microbial communities can both mediate and be modified by pathogen infection. Thus, understanding disease outcomes of complex plant pathosystems requires characterization of pathogen-phytobiome interactions. Efforts to characterize these interactions have yielded microecological insights with applied relevance for disease management in herbaceous leaf- and root-associated pathosystems. However, pathogen-phytobiome interactions in the vascular tissues of hardwood stems remain largely unexplored. Our findings illuminate the ecological organization of the Populus trichocarpa stem mycobiome under S. musiva disease pressure and advance understanding of microfungal community dynamics in the Septoria stem canker pathosystem. Additionally, we identify potentially interactive fungal taxa that may disproportionately shape mycobiome structure and disease dynamics in Populus trichocarpa stems.

Diagnosis of Lyme borreliosis (LB) is mainly based on clinical symptoms, patient's history, and serological testing. Despite a lack of standardization, polymerase chain reaction (PCR) has gained importance for the detection of Borrelia DNA. So far, extensive studies comparing different protocols used in molecular diagnostic or research setting are missing. Here, we describe a European-wide comparison of commercial and in-house PCR protocols using a standardized DNA panel including all relevant Borrelia burgdorferi sensu lato (Bbsl) species to explore variation in PCR results in different laboratories. A DNA testing panel composed of 90 DNA samples from 14 Bbsl strains in six different dilutions, plus six specificity controls, was sent blinded to 34 laboratories (33 European plus one in the US). The results from a total of 57 different amplification protocols were collected and compared regarding their detection limits, specificity, and sensitivity over all Bbsl strains for each dilution included in the DNA panel. While the detection limits showed vast differences (>105 genome equivalents (GE)) between different amplification protocols, none of the most commonly used PCR targets (ospA, 16S rRNA, flagellin, 5S-23S intergenic spacer) significantly outperformed other PCR targets. Interestingly, large differences in detection limits were found not only between different protocols, but also when the same protocol was used on different Bbsl species (>105 GE) and even on different strains of the same Bbsl species (>104 GE). Specificity also varied between different protocols, with many protocols recognizing relapsing fever Borreliae. A standardization of PCR methods used for confirmation of LB diagnosis is urgently needed.

Simultaneously achieving high power density and longevity in cost-effective proton-exchange membrane fuel cells (PEMFCs) is imperative for their commercialization, yet it poses a significant challenge to the fuel cell catalyst, particularly under light-duty vehicle (LDV) or heavy-duty vehicle (HDV) conditions. Here, we present a versatile phosphorus (P)-driven strategy to enhance the activity and durability of platinum-manganese (Pt3Mn) alloys, in which P acts as a pivotal bridging element between Pt3Mn nanoparticles and the carbon support as well as an activator for Pt3Mn surfaces. Importantly, goblet-like P-Pt3Mn enables outstanding peak power densities of 4.11 W cm-2 in H2/O2 and 2.05 W cm-2 in H2/air under HDV condition, as verified by a third-party platform and stack-level validation. Meanwhile, P-Pt3Mn exhibits an exceptional accelerated stress test (AST) stability for 30&#x202f;000 cycles (2.1% mass activity decline), significantly exceeding the U.S. Department of Energy (DOE) target. For commercial visibility, we demonstrate that the P-Pt3Mn-based fuel cell can be operated stably at a high current density of 3.0 A cm-2 beyond 1000 h. Detailed mechanistic and theoretical investigations reveal the excellent performance of P-Pt3Mn from the surface enrichment of P on Pt3Mn alloys and the formation of interfacial Pt-P-C coordination, which effectively promotes *OH desorption and mass transport as well as inhibits nanoparticle agglomeration. These groundbreaking results firmly establish P-Pt3Mn as the most efficient and durable fuel cell catalyst for practical PEMFC applications in urban transportation.

Mechanical unloading leads to bone loss and cardiovascular deconditioning, accompanied by elevated sclerostin expression. Genetic Sost knockout or pharmacologic sclerostin antibody treatment was reported to counteract bone loss during mechanical unloading in mice. However, severe cardiovascular events were reported in postmenopausal osteoporotic patients treated with commercially available sclerostin antibody targeting loop2. It is desirable to develop a precise sclerostin inhibition strategy to counteract unloading-induced bone loss, without increasing cardiovascular risk. In a previously published rodent studies under normal loading condition, it was found that sclerostin loop3 participated in the inhibitory effect of sclerostin on bone formation, while the preventive action of sclerostin against cardiovascular events was independent of sclerostin loop3. Nevertheless, whether and how sclerostin loop3 contributes to bone formation reduction and bone loss under mechanical unloading condition remains unclear. In this study under mechanical unloading condition, either sclerostin loop3-specific deficiency in Sost loop3-/ - mice or sclerostin loop3-specific inhibition by our tailor-made aptamer Apc001 counteracted unloading-induced bone loss without increasing arterial stiffness, whereas either Sost knockout or romosozumab treatment significantly increased unloading-induced arterial stiffness in mice. These findings indicated sclerostin loop3 as a therapeutic target with cardiovascular safety against unloading-induced bone loss. Mechanistically, we identified that sclerostin loop3 bound to LRP4 in osteoblasts under mechanical unloading condition. Osteoblast-specific Lrp4 knockout counteracted unloading-induced bone formation reduction and bone loss in OB. Lrp4 -/- mice. Further, blocking the interaction of sclerostin loop3 with LRP4 via mutation of the interaction residues (Lrp4m) or pharmacologic inhibition with LRP4 peptide tool (LRP4-Pep) dramatically attenuated binding of sclerostin to LRP6, counteracted decrease of Wnt/&#x3b2;-catenin signaling activity and osteogenic potential in osteoblasts under mechanical unloading condition in vitro. Consistently, Lrp4m counteracted unloading-induced bone formation reduction and bone loss in mice in vivo. In Lrp4m/OB-Lrp4 mice, osteoblast-conditional correction of Lrp4m to wild-type Lrp4 attenuated the counteractive effect of Lrp4m on unloading-induced bone loss. Pharmacologically, osteoblasts-targeted LRP4-Pep counteracted bone formation reduction and bone loss during mechanical unloading in wild-type mice. Sclerostin loop3-mediated anchoring of sclerostin to LRP4 facilitated its binding to LRP6 in osteoblasts, contributing to bone formation reduction and bone loss under mechanical unloading condition. Specifically blocking the interaction of sclerostin loop3 with LRP4 in osteoblasts would offer a precise strategy with cardiovascular safety for treatment of unloading-induced bone loss.

Infected foot wounds often exhibit markedly prolonged healing due to local ischemia, multidrug-resistant pathogens, and chronic inflammation, representing a major clinical challenge. This work reports a piezoelectric heterojunction-based smart textile dressing, in which the heterostructure was constructed via atomic layer deposition (ALD) to achieve precise band-structure engineering. By tailoring the number of ZnO deposition cycles on BaTiO3, the optimized BaTiO3-10ZnO heterojunction (10 ALD cycles) exhibits the most favorable band alignment and a 2.95-fold boost in ROS generation efficiency compared with pristine BaTiO3. The composite is covalently immobilized onto textile fibers via amine-aldehyde condensation, yielding an intelligent textile platform. In a rat plantar infection model, the dressing, activated by walking-triggered mechanical pressure, achieves the most prominent therapeutic outcome, outperforming other ALD-cycle variants and commercial Ag+ dressings. Systematic histological and transcriptomic analyses further unveil its multipronged antibacterial mechanisms, including bacterial membrane disruption, metabolic interference, and oxidative-stress induction. This work offers an innovative strategy for self-powered antimicrobial systems and demonstrates great potential for chronic wound management.

Low-cost hernia simulation models exist, but are commercially sold, use technology such as 3-D printing or have the manufacturing instructions behind pay-walls, rendering them beyond the reach of trainers in low-income countries. This perpetuates dependence on expatriate training missions. We designed an ultra-low-cost hernia training model using only materials readily available in low-resource settings supported by a freely available "You-tube style" how-to-make-it instructional video. A prototype ultra-low-cost model was tested by surgical trainers and trainees in three low-income African countries and the UK. Both trainee and trainer end users were included in the innovation process throughout, amending features according to feedback. Emphasis was placed on anatomical accuracy, providing a platform for trainer instruction and trainee understanding. Test purchases of all necessary materials were made in provincial Sierra Leone. A step-by-step how-to-make-it video and downloadable pattern was created and shared free of charge online. Video link: https://tinyurl.com/2u9nnn6f or Pattern pieces: https://tinyurl.com/ycyhwt52 RESULTS: Test purchase indicated all materials are available in one of the world's poorest countries. The model was well received by trainees in Tanzania, Sierra Leone, Ghana and United Kingdom. Ultra-low-cost mesh hernia trainers have proved an important adjunct to training, but are currently out of reach of trainers in the world's poorest countries. The SWIFTSS model places the necessary information, within reach of anybody with a smart phone.

The monkeypox virus (MPXV) poses a significant and ongoing public health threat, highlighting the urgent need for accessible and accurate diagnostic tools. The viral envelope protein A29L is an immunodominant and highly conserved target for immunoassay development. This study aimed to generate a panel of novel monoclonal antibodies (mAbs) against A29L and to develop both a highly sensitive laboratory-based enzyme-linked immunosorbent assay (ELISA) and a rapid lateral flow immunoassay (LFIA) for specific antigen detection. Following immunization and hybridoma screening, six high-affinity mAbs against A29L were selected and fully characterized. Utilizing this antibody panel, a sandwich ELISA was developed, achieving a notably low detection limit of 31.25 pg/mL, with an excellent linear range. In clinical evaluations using samples from suspected MPXV cases (plasma, vesicular fluid, and swabs), the ELISA demonstrated 95% sensitivity and 100% specificity for plasma samples, performing comparably to gold-standard PCR, and outperforming available commercial kits. Furthermore, the developed LFIA demonstrated sensitivities of 58.3% (7/12) in plasma and 40.0% (4/10) in vesicular fluid samples, with perfect detection in high viral load cases, confirming its strong potential for point-of-care deployment. In conclusion, we present a practical, tiered diagnostic strategy that integrates a highly sensitive confirmatory ELISA with a rapid frontline LFIA. This complementary approach effectively bridges the critical gap between centralized confirmatory testing and decentralized field surveillance, significantly enhancing outbreak response capabilities for MPXV.IMPORTANCEMonkeypox virus has emerged as a global infectious disease threat, creating an urgent need for accurate and accessible diagnostic tools. Currently, the confirmation of an infection necessitates the execution of sophisticated laboratory tests, which can result in delayed results and impede a swift public health response, particularly in settings characterized by limited resources. This study addresses this critical gap by creating a complete diagnostic toolkit. We developed new, highly specific antibodies against the virus and used them to build two complementary tests: a very sensitive lab-based test for definitive confirmation and a simple, rapid paper-strip test that can be used at the point of care, such as in a clinic or field site. This dual approach provides a practical strategy for improving outbreak control, enabling both accurate laboratory diagnosis and immediate on-site screening to quickly identify infected individuals and help stop the chains of transmission.

Efficient delivery of gene editing ribonucleoproteins (RNPs) into the interior of solid tissues remains a key hurdle to the clinical translation of non-viral CRISPR-Cas9 technologies. Here, we report acoustically-actuated peptide nanoemulsions (NPeps) that can be spatiotemporally guided and activated by ultrasound to ballistically deliver RNPs into cells within the bulk of dense 3D cellular structures. Using human kidney organoids as a model, we demonstrate NPep vectors improve the spatial profile of gene editing in the organoid mass relative to commercial lipofection reagents, without disruption of tissue structure or qualitative viability features. This technologic paradigm is poised to advance imaging-guided, deep tissue RNP delivery modalities to expand the clinical diagnostic and therapeutic potential of CRISPR-Cas9 editing strategies.