Semimetallic state transition in Two-Dimensional carbon nitride covalent networks and enhanced electrocatalytic activity for nitrate to ammonia conversion.

Single-atom catalysts (SACs), due to their maximum atomic utilization rate, show tremendous potential for application in the electrocatalytic synthesis of ammonia from nitrate. Yet, the development of superior supports that preserve the high selectivity, activity, and stability of SACs remains an imperative challenge. In this work, based on first-principles calculations and tight-binding (TB) model analysis, a new two-dimensional (2D) carbon nitride monolayer, C7N6, is proposed. The C7N6 structure exhibits a strong covalent network, with dynamical, thermal, and mechanical stability. Surprisingly, the structural transition from C9N4 to C7N6 corresponds to a semimetallic state transition. Further symmetry analysis unveils that the Dirac states in C7N6 are protected by space-time inversion symmetry, and the physical origin of the Dirac cone was confirmed using the TB model. Additionally, a non-zero Z2 invariant and significant topological edge states demonstrate its topologically nontrivial nature. Considering the excellent structural and topological properties of C7N6, a three-step screening strategy is designed to identify eligible SACs for electrochemical nitrate reduction reaction (NO3RR), and Ti@C7N6 is identified as possessing the best activity, with the last proton-electron coupling step *NH2→*NH3 being the potential-determining step (PDS), for which the limiting potential is 0.48 V. Moreover, a free energy diagram shows that the *NOH reaction pathway is energetically preferred on Ti@C7N6, and ab initio molecular dynamics (AIMD) calculations at 500 K confirm its good thermal stability. Our study not only provides excellent CN-based support material but also offers theoretical guidance for constructing highly active and selective SACs for nitrate reduction.

Strong mechanical anisotropy and an anisotropic Dirac state in 2D C5N3.

Two-dimensional (2D) carbon nitride materials have emerged as a versatile platform for the design of high-performance nanoelectronics, but strong anisotropy in 2D carbon nitrides has rarely been reported. In this work, a 2D carbon nitride with strong anisotropy composed of tetra-, penta-, and hexa-rings (named as TPH-C5N3) is proposed. This TPH-C5N3 exhibits both dynamical and mechanical stability. Furthermore, it also showcases remarkable thermal stability, reaching up to 2300 K, as evidenced by AIMD simulations conducted in an NVT environment utilizing the Nosé-Hoover thermostat. Significantly, TPH-C5N3 demonstrates high anisotropic ratios in its mechanical properties, positioning it as the frontrunner in the current carbon nitride systems. In addition, a Dirac cone with an anisotropic ratio of 55.8% and Fermi velocity of 7.26 × 105 m s-1 is revealed in TPH-C5N3. The nontrivial topological properties of TPH-C5N3 are demonstrated by a non-zero Z2 invariant and topologically protected edge states. Our study offers theoretical insights into an anisotropic 2D carbon nitride material, laying the groundwork for its design and synthesis.

Evaluating population-level interventions to reduce inappropriate antibiotic use in healthcare and community settings: A systematic review protocol.

BACKGROUND: Inappropriate antibiotic use contributes significantly to the global challenge of antimicrobial resistance. While government-initiated population-level interventions are fundamental in addressing this issue, their full potential remains to be explored. This systematic review aims to assess the effectiveness of such interventions in reducing inappropriate antibiotic use among antibiotic providers and users in healthcare and community settings. METHODS: We will conduct a systematic literature search across multiple databases and grey literature sources. We will include studies which evaluate the effectiveness of population-level interventions to reduce inappropriate antibiotic use in healthcare and community settings in both high-income and low- and middle-income countries. This includes government-initiated measures targeting antibiotic use through education, restriction, incentivization, coercion, training, persuasion, context modification, behavior modeling, or barrier reduction. Two reviewers will independently perform screening to select eligible studies, followed by data extraction. The outcomes of interest are various measures of antibiotic prescription and consumption, such as Defined Daily Dose (DDD) or number of prescriptions per year. We anticipate including a broad range of study designs and outcome measures. Therefore, we will narratively synthesize results using the categories of the population-level policy interventions of the Behavior Change Wheel Framework. We will organize outcome data by economic contexts, target populations, and implementation settings. DISCUSSION: This review will strengthen the evidence base for the use of population-level interventions to address inappropriate antibiotic use. Drawing lessons from global experiences, the findings will provide valuable guidance to health policymakers, public health authorities, and researchers on tailoring interventions to specific economic contexts, populations, and settings, thereby enhancing their capacity to drive substantial improvement in appropriate antibiotic use.

A self-regulated interface enabled by trivalent gadolinium ions toward highly reversible zinc metal anodes.

Aqueous zinc-ion batteries (AZIBs) have become an ideal candidate for large-scale energy storage systems owing to their inherent safety and highly competitive capacity. However, severe dendrite growth and side reactions on the surface of zinc metal anodes lead to quick performance deterioration, seriously impeding the commercialization of AZIBs. In this work, a self-regulated zinc metal/electrolyte interface is constructed to solve these problems by incorporating the trivalent Gd3+ additive with a lower effective reduction potential into the aqueous ZnSO4 electrolyte. It is revealed that the inert Gd3+ ions preferentially adsorb on the active sites of the zinc anode, and the induced electrostatic shielding layer is beneficial to uniform Zn deposition. Meanwhile, the adsorbed Gd3+ ions act as a buffer interface to lower the direct contact of the zinc anode with water molecules, thereby suppressing the interfacial parasitic reaction. These features endow the Zn//Zn battery using 0.2 M Gd3+ ions with 2940 h of cycling life at 5 mA cm-2 and a cumulative plating capacity (CPC) of 6.2 Ah cm-2 at 40 mA cm-2. When assembling with a MnO2 cathode, the full cell using the modified electrolyte exhibits a high capacity of 268.9 mAh/g at 0.2 A/g, as well as improved rate capability and cycle stability. The results suggest the great potential of a rare earth ion additive in reinforcing Zn metal anodes for developing practical AZIBs.

Effectiveness of a comprehensive package based on electronic medication monitors at improving treatment outcomes among tuberculosis patients in Tibet: a multicentre randomised controlled trial.

BACKGROUND: WHO recommends that electronic medication monitors, a form of digital adherence technology, be used as a complement to directly observed treatment (DOT) for tuberculosis, as DOT is inconvenient and costly. However, existing evidence about the effectiveness of these monitors is inconclusive. Therefore, we evaluated the effectiveness of a comprehensive package based on electronic medication monitors among patients with tuberculosis in Tibet Autonomous Region (hereafter Tibet), China. METHODS: This multicentre, randomised controlled trial recruited patients from six counties in Shigatse, Tibet. Eligible participants had drug-susceptible tuberculosis and were aged 15 years or older when starting standard tuberculosis treatment. Tuberculosis doctors recruited patients from the public tuberculosis dispensary in each county and the study statistician randomly assigned them to the intervention or control group based on the predetermined randomised allocation sequence. Intervention patients received an electronic medication monitor box. The box included audio medication-adherence reminders and recorded box-opening data, which were transmitted to a cloud-based server and were accessible to health-care providers to allow remote adherence monitoring. A linked smartphone app enabled text, audio, and video communication between patients and health-care providers. Patients were also provided with a free data plan. Patients selected a treatment supporter (often a family member) who was trained to support patients with using the electronic medication monitor and app. Patients in the control group received usual care plus a deactivated electronic medication monitor, which only recorded and transmitted box-opening data that was not made available to health-care providers. The control group also had no access to the app or trained treatment supporters. The primary outcome was a binary indicator of poor monthly adherence, defined as missing 20% or more of planned doses in the treatment month, measured using electronic medication monitor opening data, and verified by counting used medication blister packages during consultations. We recorded other secondary treatment outcomes based on national tuberculosis reporting data. We analysed the primary outcome based on the intention-to-treat population. This trial is registered at ISRCTN, 52132803. FINDINGS: Between Nov 17, 2018, and April 5, 2021, 278 patients were enrolled into the study. 143 patients were randomly assigned to the intervention group and 135 patients to the control group. Follow-up ended when the final patient completed treatment on Oct 4, 2021. In the intervention group, 87 (10%) of the 854 treatment months showed poor adherence compared with 290 (37%) of the 795 months in the control group. The corresponding adjusted risk difference for the intervention versus control was -29·2 percentage points (95% CI -35·3 to -22·2; p<0·0001). Five of the six secondary treatment outcomes also showed clear improvements, including treatment success, which was found for 133 (94%) of the 142 individuals in the intervention arm and 98 (73%) of the 134 individuals in the control arm, with an adjusted risk difference of 21 percentage points (95% CI 12·4-29·4); p<0·0001. INTERPRETATION: The interventions were effective at improving tuberculosis treatment adherence and outcomes, and the trial suggests that a comprehensive package involving electronic medication monitors might positively affect tuberculosis programmes in high-burden and low-resource settings. FUNDING: TB REACH.

The organization-level and physician-level factors associated with primary care physicians' confidence in pandemic response: A multilevel study in China.

Primary care physicians (PCPs) suffered from heavy workloads and health problems during COVID-19 pandemics, and building their confidence in pandemic response has great potential to improve their well-being and work performance. We identified the organizational factors associated with their confidence in pandemic response and proposed potential management levers to guide primary care response for the pandemic. We conducted a cross-sectional survey with 224 PCPs working in 38 community health centers in China. Guided by self-efficacy theory, organization-level factors (organizational structure and organizational culture) and physician-level factors (job skill variety, perceived organizational support, work-family conflict, and professional fulfillment) were selected, and two-level ordinal logit models were built to examine their association with PCPs' confidence in pandemic response. We found that hierarchical culture (OR = 3.51, P<0.05), perceived organizational support (OR = 2.36, P<0.05), job skill variety (OR = 1.86, P<0.05), and professional fulfillment (OR = 2.26, P<0.05) were positively associated with PCPs' confidence in pandemic response. However, the influence of organization structure and work-family conflict seemed limited. The study not only increases our understanding of the influence of organizational context on PCPs' pandemic response confidence, but also points out potential management levers for front-line primary care managers to enhance primary care pandemic response capacity.

How spin state and oxidation number of transition metal atoms determine molecular adsorption: a first-principles case study for NH3.

Understanding how the electronic state of transition metal atoms can influence molecular adsorption on a substrate is of great importance for many applications. Choosing NH3 as a model molecule, its adsorption behavior on defected SnS2 monolayers is investigated. The number of valence electrons n is controlled by decorating the monolayer with different transition metal atoms, ranging from Sc to Zn. Density-Functional Theory based calculations show that the adsorption energy of NH3 molecules oscillates with n and shows a clear odd-even pattern. There is also a mirror symmetry of the adsorption energies for large and low electron numbers. This unique behavior is mainly governed by the oxidation state of the TM ions. We trace back the observed trends of the adsorption energy to the orbital symmetries and ligand effects which affect the interaction between the 3σ orbitals (NH3) and the 3d orbitals of the transition metals. This result unravels the role which the spin state of TM ions plays in different crystal fields for the adsorption behavior of molecules. This new understanding of the role of the electronic structure on molecular adsorption can be useful for the design of high efficiency nanodevices in areas such as sensing and photocatalysis.

Protection of prior SARS-CoV-2 infection, COVID-19 boosters, and hybrid immunity against Omicron severe illness: A population-based cohort study of five million residents in Canada.

BACKGROUND: Evidence on protection of different patterns of infection- and vaccine-acquired immunity against Omicron-associated severe illness is useful in planning booster vaccination strategies. We examined protection of prior SARS-CoV-2 infection, a third or a fourth COVID-19 vaccine dose, and hybrid immunity against Omicron-associated severe illness. METHODS AND FINDINGS: This population-based cohort study followed five million individuals with at least one SARS-CoV-2 RT-PCR test before November 21, 2021 until an Omicron-associatedhospitalization or death. We used Cox regression models to estimate risks of Omicron-associated hospitalization and a composite severe outcome (hospitalized and death), among individuals with infection- and/or vaccination-acquired immunity. Individuals who were unvaccinated and had no history of a prior infection severed as the reference group. Both adjusted hazard ratios (HR) and corresponding protection (one minus adjusted HR), with 95% confidence intervals (CIs), were reported. Three doses provided 94% (95%CI 93-95) and 93% (95%CI 91-94) protection against Omicron-associated hospitalization at 2-3 and ≥3 months post-vaccination respectively, similar to the protection conferred by three doses and a prior infection (2-3 months: 99%, 95%CI 97-100; ≥3 months: 97%, 95%CI 92-99) and four doses (1 month: 87%, 95%CI 79-92; 1-2 months: 96%, 95%CI 92-98). In individuals ≥65 years old, protection of four doses increased to 95% (95%CI 91-98) at 1-2 months, significantly higher than that of three doses over the follow-up period. Similar results were observed with the composite severe outcome. CONCLUSION: At least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level.

Ultra-high photoelectric conversion efficiency and obvious carrier separation in photovoltaic ZnIn2X4 (X = S, Se, and Te) van der Waals heterostructures.

The need for low-carbon solar electricity production has become increasingly urgent for energy security and climate change mitigation. However, the bandgap and carrier separation critical requirements of high-efficiency solar cells are difficult to satisfy simultaneously in a single material. In this work, several van der Waals ZnIn2X4 (X = S, Se, and Te) heterostructures were designed based on density functional theory. Our results suggest that both ZnIn2S4/ZnIn2Se4 and ZnIn2Se4/ZnIn2Te4 heterostructures are direct bandgap semiconductors at the Γ point. Besides, obvious carrier spatial separations were observed in the ZnIn2S4/ZnIn2Se4 and ZnIn2Se4/ZnIn2Te4 heterostructures. Interestingly, the ZnIn2S4/ZnIn2Se4 heterostructure has a suitable bandgap of 1.43 eV with good optical absorption in the visible light range. The calculated maximum theoretical photoelectric conversion efficiency of ZnIn2S4/ZnIn2Se4 heterostructure was 32.1%, and it can be further enhanced to 32.9% under 2% tensile strain. Compared to single-layer ZnIn2X4 materials, the electron effective mass of the ZnIn2S4/ZnIn2Se4 heterostructure is relatively low, which results in high electron mobility in the heterostructure. The suitable bandgap, obvious carrier separation, high electron mobility, and excellent theoretical photoelectric conversion efficiency of the ZnIn2S4/ZnIn2Se4 heterostructure make it a promising candidate for novel 2D-based photoelectronic devices and solar cells.

Pose-Aware 3D Talking Face Synthesis using Geometry-guided Audio-Vertices Attention.

Most of the existing 3D talking face synthesis methods suffer from the lack of detailed facial expressions and realistic head poses, resulting in unsatisfactory experiences for users. In this paper, we propose a novel pose-aware 3D talking face synthesis method with a novel geometry-guided audio-vertices attention. To capture more detailed expression, such as the subtle nuances of mouth shape and eye movement, we propose to build hierarchical audio features including a global attribute feature and a series of vertex-wise local latent movement features. Then, in order to fully exploit the topology of facial models, we further propose a novel geometry-guided audio-vertices attention module to predict the displacement of each vertex by using vertex connectivity relations to take full advantage of the corresponding hierarchical audio features. Finally, to accomplish pose-aware animation, we expand the existing database with an additional pose attribute, and a novel pose estimation module is proposed by paying attention to the whole head model. Numerical experiments demonstrate the effectiveness of the proposed method on realistic expression and head movements against state-of-the-art methods.

Enhanced OER catalytic activity of single metal atoms supported by the pentagonal NiN2 monolayer: insight from density functional theory calculations.

Two-dimensional material-supported single metal atom catalysts have been extensively studied and proved effective in electrocatalytic reactions in recent years. In this work, we systematically investigate the OER catalytic properties of single metal atoms supported by the NiN2 monolayer. Several typical transition metals with high single atom catalytic activity, such as Fe, Co, Ru, Rh, Pd, Ir, and Pt, were selected as catalytic active sites. The energy calculations show that transition metal atoms (Fe, Co, Ru, Rh, Pd, Ir, and Pt) are easily embedded in the NiN2 monolayer with Ni vacancies due to the negative binding energy. The calculated OER overpotentials of Fe, Co, Ru, Rh, Pd, Ir and Pt embedded NiN2 monolayers are 0.92 V, 0.47 V, 1.13 V, 0.66 V, 1.25 V, 0.28 V, and 0.94 V, respectively. Compared to the 0.57 V OER overpotential of typical OER noble metal catalysts IrO2, Co@NiN2 and Ir@NiN2 exhibit high OER catalytic activity due to lower overpotential, especially for Ir@NiN2. The high catalytic activity of the Ir embedded NiN2 monolayer can be explained well by the d-band center model. It is found that the adsorption strength of the embedded TM atoms with intermediates follows a linear relationship with their d-band centers. Besides, the overpotential of the Ir embedded NiN2 monolayer can be further reduced to 0.24 V under -2% biaxial strain. Such findings are expected to be employed in more two-dimensional material-supported single metal atom catalyzed reactions.

Low-Dose CT Image Super-resolution Network with Noise Inhibition Based on Feedback Feature Distillation Mechanism.

Low-dose computed tomography (LDCT) has been widely used in medical diagnosis. In practice, doctors often zoom in on LDCT slices for clearer lesions and issues, while, a simple zooming operation fails to suppress low-dose artifacts, leading to distorted details. Therefore, numerous LDCT super-resolution (SR) methods have been proposed to promote the quality of zooming without the increase of the dose in CT scanning. However, there are still some drawbacks that need to be addressed in existing methods. First, the region of interest (ROI) is not emphasized due to the lack of guidance in the reconstruction process. Second, the convolutional blocks extracting fix-resolution features fail to concentrate on the essential multi-scale features. Third, a single SR head cannot suppress the residual artifacts. To address these issues, we propose an LDCT CT joint SR and denoising reconstruction network. Our proposed network consists of global dual-guidance attention fusion modules (GDAFMs) and multi-scale anastomosis blocks (MABs). The GDAFM directs the network to focus on ROI by fusing the extra mask guidance and average CT image guidance, while the MAB introduces hierarchical features through anastomosis connections to leverage multi-scale features and promote the feature representation ability. To suppress radial residual artifacts, we optimize our network using the feedback feature distillation mechanism (FFDM) which shares the backbone to learn features corresponding to the denoising task. We apply the proposed method to the 3D-IRCADB and PANCREAS datasets to evaluate its ability on LDCT image SR reconstruction. The experimental results compared with state-of-the-art methods illustrate the superiority of our approach with respect to peak signal-to-noise (PSNR), structural similarity (SSIM), and qualitative observations. Our proposed LDCT joint SR and denoising reconstruction network has been extensively evaluated through ablation, quantitative, and qualitative experiments. The results demonstrate that our method can recover noise-free and detail-sharp images, resulting in better reconstruction results. Code is available at https://github.com/neu-szy/ldct_sr_dn_w_ffdm .

A screen for regeneration-associated silencer regulatory elements in zebrafish.

Regeneration involves gene expression changes explained in part by context-dependent recruitment of transcriptional activators to distal enhancers. Silencers that engage repressive transcriptional complexes are less studied than enhancers and more technically challenging to validate, but they potentially have profound biological importance for regeneration. Here, we identified candidate silencers through a screening process that examined the ability of DNA sequences to limit injury-induced gene expression in larval zebrafish after fin amputation. A short sequence (s1) on chromosome 5 near several genes that reduce expression during adult fin regeneration could suppress promoter activity in stable transgenic lines and diminish nearby gene expression in knockin lines. High-resolution analysis of chromatin organization identified physical associations of s1 with gene promoters occurring preferentially during fin regeneration, and genomic deletion of s1 elevated the expression of these genes after fin amputation. Our study provides methods to identify "tissue regeneration silencer elements" (TRSEs) with the potential to reduce unnecessary or deleterious gene expression during regeneration.

The Role of Water Molecules on Polaron Behavior at Rutile (110) Surface: A Constrained Density Functional Theory Study.

Understanding the behavior of a polaron in contact with water is of significant importance for many photocatalytic applications. We investigated the influence of water on the localization and transport properties of polarons at the rutile (110) surface by constrained density functional theory. An excess electron at a dry surface favors the formation of a small polaron at the subsurface Ti site, with a preferred transport direction along the [001] axis. As the surface is covered by water, the preferred spatial localization of the polarons is moved from the subsurface to the surface. When the water coverage exceeds half a monolayer, the preferred direction of polaron hopping is changed to the [110] direction toward the surface. This characteristic behavior is related to the Ti3d-orbital occupations and crystal field splitting induced by different distorted structures under water coverage. Our work describes the reduced sites that might eventually play a role in photocatalysis for rutile (110) surfaces in a water environment.

Electronic health record and primary care physician self-reported quality of care: a multilevel study in China.

BACKGROUND: Health information technology is one of the building blocks of a high-performing health system. However, the evidence regarding the influence of an electronic health record (EHR) on the quality of care remains mixed, especially in low- and middle-income countries. OBJECTIVE: This study examines the association between greater EHR functionality and primary care physician self-reported quality of care. METHODS: A total of 224 primary care physicians from 38 community health centres (CHCs) in four large Chinese cities participated in a cross-sectional survey to assess CHC care quality. Each CHC director scored their CHC's EHR functionality on the availability of ten typical features covering health information, data, results management, patient access, and clinical decision support. Data analysis utilised hierarchical linear modelling. RESULTS: The availability of five EHR features was positively associated with physician self-reported clinical quality: share records online with providers outside the practice (ß = 0.276, p = 0.04), access records online by the patient (ß = 0.325, p = 0.04), alert provider of potential prescription problems (ß = 0.353, p = 0.04), send the patient reminders for care (ß = 0.419, p = 0.003), and list patients by diagnosis or health risk (ß = 0.282, p = 0.04). However, no association was found between specific features availability or total features score and physician self-reported preventive quality. CONCLUSIONS: This study provides evidence that the availability of EHR systems, and specific features of these systems, was positively associated with physician self-reported quality of care in these 38 CHCs. Future longitudinal studies focused on standardised quality metrics, and designed to control known confounding variables, will further inform quality improvement efforts in primary care.

Nuclear isoform of RAPH1 interacts with FOXQ1 to promote aggressiveness and radioresistance in breast cancer.

Radioresistance limits the efficacy of radiotherapy against breast cancer, especially the most lethal subtype of breast cancer, triple-negative breast cancer (TNBC). Epithelial-to-mesenchymal transition (EMT) is closely related to tumor radioresistance. In this work, we attempted to identify the key EMT-related transcription factor(s) that can induce radioresistance in breast cancer cells. A set of 44 EMT transcription factors were analyzed in parental and radioresistant TNBC cell lines. The function of FOXQ1, a differentially expressed transcription factor, was determined in TNBC radioresistance. FOXQ1-interacting proteins were identified by co-immunoprecipitation and mass spectrometry. Compared with parental cells, FOXQ1 was significantly upregulated in radioresistant TNBC cells. Silencing of FOXQ1 increased the radiosensitiviy of radioresistant TNBC cells both in vitro and in vivo. FOXQ1 associated with a nuclear isoform of RAPH1 (named RAPH1-i3) in radioresistant TNBC cells. Overexpression of RAPH1-i3 enhanced TNBC cell proliferation and migration, and most interestingly, induced radioresistance in parental TNBC cells when co-expressed with FOXQ1. Similar findings were observed in estrogen receptor-positive breast cancer cell lines that had co-expression of RAPH1-i3 and FOXQ1. Mechanistically, co-expression of RAPH1-i3 and FOXQ1 activated STAT3 signaling and increased the expression of CCND1, MCL1, Bcl-XL, and MMP2. Depletion of RAPH1-i3 impaired the radioresistance of radioresistant TNBC cells. Additionally, RAPH1-i3 upregulation was associated with advanced tumor stage and reduced disease-free survival in TNBC patients. These results collectively show that RAPH1-i3 interacts with FOXQ1 to promote breast cancer progression and radioresistance. RAPH1-i3 and FOXQ1 represent therapeutic targets for the treatment of breast cancer including TNBC.

Barriers to and Facilitators of the Implementation of a Micronutrient Powder Program for Children: A Systematic Review Based on the Consolidated Framework for Implementation Research.

BACKGROUND: As one of the most cost-effective investments for improving child nutrition, micronutrient powder (MNP) has been widely used in many countries to underpin the Sustainable Development Goals, yet challenges remain regarding its implementation on a large scale. However, few studies have explored the factors that facilitate or impede the implementation process using implementation science theories and frameworks. To address this gap, we adopted the Consolidated Framework of Implementation Research (CFIR) and conducted a systematic review of studies on the implementation barriers to and facilitators of MNP interventions. METHOD: Five publication databases, including EMBASE, Medline, PubMed, Web of Science, and Scopus, were searched for studies on the influencing factors of MNP interventions. Based on the CFIR framework, the facilitators and barriers for the MNP program implementation reported in the included studies were extracted and synthesized by five domains: intervention characteristics, outer setting, inner setting, individual characteristics, and process. RESULTS: A total of 50 articles were eligible for synthesis. The majority of the studies were conducted in lower-middle-income countries (52%) through the free delivery model (78%). The inner setting construct was the most prominently reported factor influencing implementation, specifically including available resources (e.g., irregular or insufficient MNP supply), structural characteristics (e.g., public-driven community-based approach), and access to information and knowledge (e.g., lack of training for primary-level workers). The facilitators of the engagement of private sectors, external guidelines, and regular program monitoring were also highlighted. On the contrary, monotonous tastes and occasional side effects impede intervention implementation. Additionally, we found that the inner setting had an interrelation with other contributing factors in the MNP program implementation. CONCLUSION: Our results suggest that MNP program implementation was prominently influenced by the available resources, organizational structure, and knowledge of both providers and users. Mobilizing local MNP suppliers, engaging public-driven free models in conjunction with market-based channels, and strengthening the training for primary-level health workers could facilitate MNP interventions.

Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells.

BACKGROUND: Chronic limb-threatening ischemia (CLTI), a severe manifestation of peripheral arterial disease (PAD), is associated with a 1-year limb amputation rate of approximately 15-20% and substantial mortality. A key feature of CLTI is the compromised regenerative ability of skeletal muscle; however, the mechanisms responsible for this impairment are not yet fully understood. In this study, we aim to delineate pathological changes at both the cellular and transcriptomic levels, as well as in cell-cell signaling pathways, associated with compromised muscle regeneration in limb ischemia in both human tissue samples and murine models of CLTI. METHODS: We performed single-cell transcriptome analysis of ischemic and non-ischemic muscle from the same CLTI patients and from a murine model of CLTI. In both datasets, we analyzed gene expression changes in macrophage and muscle satellite cell (MuSC) populations as well as differential cell-cell signaling interactions and differentiation trajectories. RESULTS: Single-cell transcriptomic profiling and immunofluorescence analysis of CLTI patient skeletal muscle demonstrated that ischemic-damaged tissue displays a pro-inflammatory macrophage signature. Comparable results were observed in a murine CLTI model. Moreover, integrated analyses of both human and murine datasets revealed premature differentiation of MuSCs to be a key feature of failed muscle regeneration in the ischemic limb. Furthermore, in silico inferences of intercellular communication and in vitro assays highlight the importance of macrophage-MuSC signaling in ischemia induced muscle injuries. CONCLUSIONS: Collectively, our research provides the first single-cell transcriptome atlases of skeletal muscle from CLTI patients and a murine CLTI model, emphasizing the crucial role of macrophages and inflammation in regulating muscle regeneration in CLTI through interactions with MuSCs.

The pan-Canadian Tiered Pricing Framework and Chinese National Volume-Based Procurement: A comparative study using Donabedian's structure-process-outcome framework.

Background: Generic drugs have been seen as a potentially powerful way to alleviate the financial burden on patients and health care systems. Two strategies for achieving rational prices of generic drugs are tiered pricing framework and pooled purchasing power. We compare the pan-Canadian Tiered Pricing Framework (TPF) and the Chinese National Volume-Based Procurement (NVBP) as comparators to explore the similarities and differences between the two mechanisms and summarise lessons for other jurisdictions. Methods: This comparative study applies Donabedian's structure-process-outcome framework to systematically analyse the macro contexts, procedures, and long- and short-term results of each pricing mechanism, and the interactions between them. Results: Structure: TPF is an upstream initiative aimed at lowering the prices of generic drugs and increasing coverage and price consistency. NVBP is a downstream national initiative prioritised for reducing drug prices to achieve value-based purchasing. Process: By associating the number of manufacturers with price cuts, TPF leaves the choice to manufacturers to decide if they want to enter a specific market. In contrast, the Chinese government determines NVBP list and has the authority to choose manufacturer(s) with the lowest price(s). TPF provides clear price information to potential suppliers with unclear order quantity. The NVBP drug price is determined by tendering, while procurement volume is clear and massive. Outcome: The effectiveness of TPF and NVBP is similar, with both achieving a 53% price cut. Both TPF and NVBP experienced efficiency improvement since their establishment, with 98 and 86 drugs priced per year. By comparing 60 drugs covered by both programmes, the NVBP price is 57% of that of the TPF counterpart on average (1.1 to 301.6%), by purchase power parity. Conclusions: The tiered pricing scheme is feasible in regions with a stable and mature pharmaceutical market, typically seen in high-income countries, while tendering is more workable in low- and middle-income countries where the pharmaceutical market is weak and unstable. Experience in the two countries shows that a coordinated pricing mechanism involves many piecemeal interactive problems, which a sophisticated system with a robust long-range plan may address better.