Comprehensive intellectual property ability and firm productivity: A quasi-natural experiment based on national intellectual property demonstration advantage firm policy in China.

Intellectual property is crucial for the development of firms. At the micro level, firm comprehensive intellectual property ability involves abilities about intellectual property creation, utilization, protection, and management. In order to develop the comprehensive intellectual property ability of firms, the China National Intellectual Property Administration began to implement the national intellectual property demonstration advantage firm (NIPDAF) policy in 2013. Based on this exogenous policy shock, using data from listed companies from 2011 to 2020 as the research sample, the time-varying DID method is used to test the impact of the NIPDAF policy intended to cultivate comprehensive intellectual property ability on firm productivity. The results show that after policy implementation, the total factor productivity of NIPDAFs increased by about 3.3% compared to the control group. This finding is robust after a series of tests. Furthermore, the NIPDAF policy promotes firm productivity through stimulating technology innovation, improving investment efficiency, and enhancing competitive advantage. In addition, the NIPDAF policy has a more significant incentive effect on the total factor productivity of non-state-owned enterprises, firms in the eastern region, and firms in patent intensive industries.

Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Establishment of a modified QuEChERS extraction and liquid chromatography-tandem mass spectrometry method for multiple pesticide residues followed by determination of the residue levels and exposure assessment in livestock urine.

The establishment of an analytical method for pesticide residues in livestock urine can realize the real-time monitoring of pesticide pollution in livestock breeding. In this study, a novel method was developed for the determination of 106 pesticide residues in livestock urine based on a modified QuEChERS extraction and liquid chromatography-tandem mass spectrometry. Acetonitrile was used to extract target analytes through acidic and alkaline switching of the sample environment. The purification effect of captiva EMR-Lipid on samples was investigated. Three kinds of materials, C18, polar enhanced polymer (PEP), N-propylethylenediamine (PSA), were selected from 20 kinds of materials as adsorbents for QuEChERS. A mass analysis was carried out using simultaneous scanning in both positive and negative ion mode and multiple reaction monitoring mode. All analytes showed good linearity, with correlation coefficients (R2) greater than 0.9923; their limits of quantification were 0.02-1.95 ng/mL. The average recoveries at low, medium, and high spiked levels were in the range of 70.1 %-117.3 %, with intra-day precision ranging from 3.4 % to 16.9 % and inter-day precision ranging from 4.0 % to 19.3 %. The established analytical method was used to analyze the pesticide residue in swine urine and bovine urine collected from farms in Yining, Xinjiang, China. A total of 8 pesticides were detected, and the residue ranged from less than the limit of quantitation to 22.4 ng/mL. The top three pesticides with the highest detection frequency were clothianidin, thiamethoxam, and dinotefuran. The exposure assessment based on the monitored pesticide residue concentration levels showed that the detected pesticides could pose little risk to cattle and pigs.

A review of toxicity assessment procedures of solar photovoltaic modules.

Environmental management of solar photovoltaic (PV) modules is attracting attention as a growing number of field-operated PV modules approach end of life (EoL). PV modules may contain small amounts of toxic metals, and the procedures for assessing and regulating the toxic metal content and release of such materials at EoL differ widely across nations. This paper provides an overview of the metal composition of PV modules and common procedures for toxicity assessment through extensive research and review of technical literature and legislative documents. This review focuses on three primary aspects: first, it explores the distribution of toxic elements within current and emerging PV module designs, with a specific focus on obtaining representative samples for proportional toxicity testing within different module laminate areas. Second, it examines a sampling standard and the diverse toxicity testing methods and regulations employed in various regions, encompassing standards like the Environmental Protection Agency (EPA) Test Method 1311 (Toxicity Characteristic Leaching Procedure, TCLP) in the U.S., Restriction of Hazardous Substances (RoHS) in Europe, and the Waste Extraction Test (WET) in California. Third, the review examines the sources of variability in toxicity testing outcomes, including techniques for securing homogeneous samples from non-uniform PV modules, selecting particle sizes representative of landfill conditions in extracted samples, determining appropriate leachate characteristics such as leaching agents and pH levels, and considering factors like test duration and temperatures. In summary, this review summarizes relevant regulations and offers a comprehensive overview of the strengths and limitations associated with several toxicity assessment procedures currently in practice.

Comparative analysis of algorithm-guided treatment and predefined duration treatment programmes for depression: exploring cost-effectiveness using routine care data.

BACKGROUND: More knowledge on the cost-effectiveness of various depression treatment programmes can promote efficient treatment allocation and improve the quality of depression care. OBJECTIVE: This study aims to compare the real-world cost-effectiveness of an algorithm-guided programme focused on remission to a predefined duration, patient preference-centred treatment programme focused on response using routine care data. METHODS: A naturalistic study (n=6295 in the raw dataset) was used to compare the costs and outcomes of two programmes in terms of quality-adjusted life years (QALY) and depression-free days (DFD). Analyses were performed from a healthcare system perspective over a 2-year time horizon. Incremental cost-effectiveness ratios were calculated, and the uncertainty of results was assessed using bootstrapping and sensitivity analysis. FINDINGS: The algorithm-guided treatment programme per client yielded more DFDs (12) and more QALYs (0.013) at a higher cost (€3070) than the predefined duration treatment programme. The incremental cost-effectiveness ratios (ICERs) were around €256/DFD and €236 154/QALY for the algorithm guided compared with the predefined duration treatment programme. At a threshold value of €50 000/QALY gained, the programme had a probability of <10% of being considered cost-effective. Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: The algorithm-guided programme led to larger health gains than the predefined duration treatment programme, but it was considerably more expensive, and hence not cost-effective at current Dutch thresholds. Depending on the preferences and budgets available, each programme has its own benefits. CLINICAL IMPLICATION: This study provides valuable information to decision-makers for optimising treatment allocation and enhancing quality of care cost-effectively.

Projections of mortality risk attributable to short-term exposure to landscape fire smoke in China, 2021-2100: a health impact assessment study.

BACKGROUND: Landscape fire smoke, including smoke from all vegetation burning in natural and cultural landscapes, remains a threat to the health of the population. However, the future health impacts of landscape fire smoke in China have not been sufficiently investigated. We aimed to estimate the mortality risk attributable to landscape fire-related PM2·5 under different scenarios. METHODS: In this health impact assessment study, we used the projected population and landscape fire-related PM2·5 concentration to calculate deaths attributable to short-term exposure to landscape fire smoke PM2·5 during 2021-2100. We did the analysis in three defined future periods: 2021-40 (near term), 2051-70 (medium term), and 2081-2100 (long term), with 1986-2005 as the historical period. We used fire-specific short-term epidemiological functions with the regional parameters specific to China. We assessed the mortality risks of landscape fire-related smoke and further identified their spatiotemporal distribution under two shared socioeconomic pathway (SSP) scenarios: SSP1-2·6, an optimistic scenario with strict control of carbon emissions, and SSP2-4·5, an intermediate scenario with weaker control of carbon emissions. FINDINGS: The national mortality rate attributable to short-term exposure (ie, a few days) to landscape fire-related PM2·5 is projected to increase compared with historical values. The national deaths attributable to landscape fire smoke PM2·5 could peak in 2021-40, with increases of 28·10% (95% CI 14·08-53·11) under the SSP1-2·6 scenario and 37·38% (14·08-53·11) under the SSP2-4·5 scenario. Deaths would then decrease slightly during 2051-70 and 2081-2100. The provinces with the highest projected number of deaths attributable to landscape fire-related PM2·5 are located in east and south-central China, and those with the largest percentage increase in projected deaths are located in northwest and southwest China. INTERPRETATION: Our results suggest that global warming could increase the contribution of landscape fire smoke to the total PM2·5 concentration, leading to an increase in the mortality rate in China. Our findings could help policy makers implement effective interventions in hotspot areas during different periods to reduce the impact of landscape fire smoke on human health. FUNDING: The National Natural Science Foundation of China, National Key Research and Development Program of China, and the Wellcome Trust.

Pain Prevalence and Management in a General Hospital Through Repeated Cross-Sectional Surveys in 2011 and 2021.

Background: There is great scope for improving the quality of pain management. Although pain prevalence has been investigated in several countries, few studies have comparatively assessed changes in pain prevalence and management over a span of multiple years. Aim: This work was aimed at determining the pain prevalence and evaluating the condition of pain management in a Chinese general hospital in 2021 and comparing them with corresponding data from 10 years ago. Methods: Repeated single-center cross-sectional studies were initiated on June 14th, 2011, and September 2nd, 2021, in the same tertiary grade A Chinese general hospital. The same structured questionnaire was used to collect inpatient data on pain intensity and classification and pain management outcomes. We performed statistical analyses to compare categorical variables to assess changes over time. Results: The sample sizes for the investigations in 2011 and 2021 were 2323 and 4454, respectively. In 2021, 24.34% of patients experienced pain; this percentage was significantly lower than that in 2011. Meanwhile, the prevalence of moderate and severe pain decreased from 14.73% in 2011 to 4.98% in 2021. The other six indicators of pain management outcomes also improved significantly. The percentages of patients using painkillers, opioid analgesics, and multiple analgesics increased from 44.61 to 51.38%, 24.01% to 44.61%, and 6.82% to 14.11%, respectively. Furthermore, the percentages of patients who received pain information and who actively reported pain increased from 27.56% to 96.5% and from 85.54% to 98.71%, respectively. The percentage of patients qualified to accurately use the Numerical Rating Scale increased from 10.5% to 79.98%. Conclusion: The quality and outcomes of pain management improved greatly after the establishment and implementation of the pain management system. Nonetheless, pain of different intensities is common after major surgeries, and it is recommended that hospitals popularize and implement perioperative multimodal analgesia strategies to reduce the incidence of postoperative pain.

A scoring diagnostic system based on biparametric ultrasound features for prostate cancer risk assessment.

Background: Ultrasound has advantages in prostate cancer (PCa) detection and biopsy guidance but lacks a comprehensive quantitative evaluation model with multiparametric features. We aimed to construct a biparametric ultrasound (BU) scoring system for PCa risk assessment and to provide an option for clinically significant prostate cancer (csPCa) detection. Methods: From January 2015 to December 2020, 392 consecutive patients at Chongqing University Cancer Hospital who underwent BU (grayscale, Doppler flow imaging, and contrast-enhanced ultrasound) and multiparametric magnetic resonance imaging (mpMRI) before biopsy were retrospectively enrolled in the training set to construct the scoring system. From January 2021 to May 2022, 166 consecutive patients at Chongqing University Cancer Hospital were retrospectively enrolled in the validation set. The ultrasound system was compared with mpMRI, and the gold standard was a biopsy. The primary outcome was the detection of csPCa in any area with a Gleason score (GS) ≥3+4, and the secondary outcome was defined as a GS ≥4+3 and/or maximum cancer core length (MCCL) ≥6 mm. Results: Malignant association features in the nonenhanced biparametric ultrasound (NEBU) scoring system included echogenicity, capsule, and gland asymmetrical vascularity. In the biparametric ultrasound scoring system (BUS), the feature of contrast agent arrival time was added. In the training set, the area under the curves (AUCs) of the NEBU scoring system, BUS, and mpMRI were 0.86 [95% confidence interval (CI): 0.82-0.90], 0.86 (95% CI: 0.82-0.90), and 0.86 (95% CI: 0.83-0.90), respectively (P>0.05). Similar results were also observed in the validation set, in which the areas under the curves were 0.89 (95% CI: 0.84-0.94), 0.90 (95% CI: 0.85-0.95), and 0.88 (95% CI: 0.82-0.94), respectively (P>0.05). Conclusions: We constructed a BUS that showed efficacy and value for csPCa diagnosis as compared with mpMRI. However, in limited circumstances, the NEBU scoring system may also be an option.

Systematic design and data-driven evaluation of social determinants of health ontology (SDoHO).

OBJECTIVE: Social determinants of health (SDoH) play critical roles in health outcomes and well-being. Understanding the interplay of SDoH and health outcomes is critical to reducing healthcare inequalities and transforming a "sick care" system into a "health-promoting" system. To address the SDOH terminology gap and better embed relevant elements in advanced biomedical informatics, we propose an SDoH ontology (SDoHO), which represents fundamental SDoH factors and their relationships in a standardized and measurable way. MATERIAL AND METHODS: Drawing on the content of existing ontologies relevant to certain aspects of SDoH, we used a top-down approach to formally model classes, relationships, and constraints based on multiple SDoH-related resources. Expert review and coverage evaluation, using a bottom-up approach employing clinical notes data and a national survey, were performed. RESULTS: We constructed the SDoHO with 708 classes, 106 object properties, and 20 data properties, with 1,561 logical axioms and 976 declaration axioms in the current version. Three experts achieved 0.967 agreement in the semantic evaluation of the ontology. A comparison between the coverage of the ontology and SDOH concepts in 2 sets of clinical notes and a national survey instrument also showed satisfactory results. DISCUSSION: SDoHO could potentially play an essential role in providing a foundation for a comprehensive understanding of the associations between SDoH and health outcomes and paving the way for health equity across populations. CONCLUSION: SDoHO has well-designed hierarchies, practical objective properties, and versatile functionalities, and the comprehensive semantic and coverage evaluation achieved promising performance compared to the existing ontologies relevant to SDoH.

Short- and medium-chain chlorinated paraffins in agricultural and industrial soils from Shanghai, China: surface and vertical distribution, penetration behavior, and health risk assessment.

The widespread contamination of chlorinated paraffins (CPs) of the soil environment has raised global concern due to their highly persistent and toxic properties. However, little information is available regarding these industrial toxicants' spatial-vertical distribution and penetration potentials. In this study, short- and medium-chain chlorinated paraffins (SCCPs and MCCPs, respectively) were analyzed in pooled surface and core soils (0-45 cm) samples collected from agricultural and industrial areas in Shanghai. ∑SCCP concentrations in agricultural and industrial surface soils ranged from 52.6 to 237.6 and 98.3 to 977.1 ng/g dry weight (dw), respectively. ∑MCCP levels were comparatively higher and ranged from 417.2 to 1690.8 and 370.9 to 10,712.7 ng/g dw in agricultural and industrial soils, respectively. C10Cl5-10 SCCPs and C14-15Cl5-7 MCCPs were the predominant homologues in all samples. Analysis of the soil vertical profiles revealed that MCCP concentrations decreased significantly with depth (P < 0.01). SCCPs more efficiently penetrated into the soils than MCCPs because of their higher water solubility and less octanol-water partition coefficient (Kow) values. A preliminary risk assessment suggested no potential health risks caused by non-dietary exposure. The daily exposure doses of CPs via ingestion were significantly (P < 0.01) higher for children (5.41 ± 2.11 × 10-3 and 1.68 ± 1.03 × 10-2 µg kg-1 day-1) and adults (2.56 ± 0.99 × 10-4 and 7.94 ± 4.87 × 10-4 µg kg-1 day-1) than dermal permeation exposure. Furthermore, CPs at current levels posed low ecological risks (0.1 ≤ RQ < 1) according to the risk quotient model. This study enhanced our understanding of the fates and behaviors of CPs in the terrestrial environment.

Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.

Prediction of complications in health economic models of type 2 diabetes: a review of methods used.

AIM: Diabetes health economic (HE) models play important roles in decision making. For most HE models of diabetes 2 diabetes (T2D), the core model concerns the prediction of complications. However, reviews of HE models pay little attention to the incorporation of prediction models. The objective of the current review is to investigate how prediction models have been incorporated into HE models of T2D and to identify challenges and possible solutions. METHODS: PubMed, Web of Science, Embase, and Cochrane were searched from January 1, 1997, to November 15, 2022, to identify published HE models for T2D. All models that participated in The Mount Hood Diabetes Simulation Modeling Database or previous challenges were manually searched. Data extraction was performed by two independent authors. Characteristics of HE models, their underlying prediction models, and methods of incorporating prediction models were investigated. RESULTS: The scoping review identified 34 HE models, including a continuous-time object-oriented model (n = 1), discrete-time state transition models (n = 18), and discrete-time discrete event simulation models (n = 15). Published prediction models were often applied to simulate complication risks, such as the UKPDS (n = 20), Framingham (n = 7), BRAVO (n = 2), NDR (n = 2), and RECODe (n = 2). Four methods were identified to combine interdependent prediction models for different complications, including random order evaluation (n = 12), simultaneous evaluation (n = 4), the 'sunflower method' (n = 3), and pre-defined order (n = 1). The remaining studies did not consider interdependency or reported unclearly. CONCLUSIONS: The methodology of integrating prediction models in HE models requires further attention, especially regarding how prediction models are selected, adjusted, and ordered.

The impact of pharmacist practice of medication therapy management in ambulatory care: an experience from a comprehensive Chinese hospital.

BACKGROUD: With the reform of medical system in China, Beijing municipal hospitals explored a new pharmaceutical care model and set up medication therapy management services (MTMs) in ambulatory care since 2019. We were one of the first hospitals to set up this service in China. At the present, there were relatively few reports about the effect of MTMs in China. In this study, we summarized the implementation of MTMs in our hospital, explore the feasibility of pharmacist-led MTMs in ambulatory care and the impact of MTMs on patients' medical costs. METHODS: A retrospective study was conducted in a university-affiliated, tertiary comprehensive hospital in Beijing, China. The patients who received at least one MTMs and with complete medical records and pharmaceutical documents from May 2019 to February 2020 were included. Pharmacists provided pharmaceutical care for patients according to the MTMs standards issued by the American Pharmacists Association, identified the numbers and classification of the patients' perceived medication-related demands, identified medication-related problems (MRPs), and developed the medication-related action plans (MAPs). All MRPs found by pharmacists, pharmaceutical interventions, and resolving recommendations were documented, and calculate the cost of treatment drugs that patients can reduce. RESULTS: A total of 112 patients received MTMs in ambulatory care, among them 81 cases with the completed record were included in this study. 67.9% of patients had five or more diseases, 83% of them co-took over 5 drugs. While performing MTMs, 128 patients' perceived medication-related demands were recorded in all, monitoring and judgment of adverse drug reaction (ADR) (17.19%) was the most common demand. 181 MRPs were found, with an average of 2.55 MPRs per patient. Nonadherence (38%), excessive drug treatment (20%), and adverse drug events (17.12%) were the top three MRPs. Pharmaceutical care (29.77%), adjustment of drug treatment plan (29.10%) and referral to the clinical department (23.41%) were the top three MAPs. Whereby the MTMs provided by pharmacists, the cost-saving of each patient was about $ 43.2 monthly. CONCLUSION: By participating in the MTMs of outpatients, the pharmacists could identify more MRPs and develop personalized MAPs timely for patients, thereby promoting rational drug use and reducing medical expenses.

Environmental assessment of fabric wet processing from gate-to-gate perspective: Comparative study of weaving and materials.

Textile industry has yet to be developed beyond low efficiency, high resources consumption, and toxic emissions, with wet processing process a dominant contributor to resources consumption and pollution emissions. Recognition of the environmental impact of the representative wet processing is essential to achieve eco-friendly development of textile industry. Using Life Cycle Assessment (LCA), this study addressed the environmental impacts of wet processing of woven/knitted cotton and polyester fabrics from 4 textile enterprises in China by deploying gate to gate system boundary. One ton of grey cloth was chosen as the functional unit. Eighteen midpoint impact categories and three endpoint impact categories were assessed via ReCiPe 2016 v1.1 (H) method. The results indicated "dyeing unit" as the dominant unit for all the impact categories at the midpoint, which was mainly derived from electricity consumed by cotton wet processing and detergents used in polyester wet processing. Among 4 different fabric wet processing, woven polyester wet processing exhibited the highest impact, while the least impact was assigned to knitted cotton. In the midpoint categories of water use, dyeing unit was also the major contributor in wet processing of knitted cotton (41.20 m3) and knitted polyester (44.70 m3). Pretreatment accounted for an overwhelming percentage of water use in woven cotton (48.00 %) and woven polyester (56.00 %). Woven polyester wet processing was also the most energy-intensive and resource-consuming industry among all scenarios, with a 3.37-fold higher fossil resource scarcity per ton of fabric compared with woven cotton. The results recommend measures for cleaner production in the wet processing.

Comparison of area measurement methods in the routine assessment of diabetic foot ulcers-A consistency analysis method.

BACKGROUND: Ulcer area is a critical parameter in diabetic foot ulcer assessment but existing methods have deficiencies for routine measurement. AIM: We hypothesized that the Image J-based Computer Analysis method has a high level of agreement with the commonly used Maximum Length and Width and the Transparent Dressing-based Square Grid methods and aimed to test the consistency and verify the feasibility of the Image J-based Computer Analysis method in the routine assessment of ulcers. METHODS: Outpatient attendees with diabetic foot ulcers at the Department of Endocrinology of Sun Yat-sen Memorial Hospital were enrolled between October 2020 and October 2021. The three methods sequentially assessed the area of 65 included ulcers. Results were analysed using one-way analysis of variance and Bland-Altman plots to perform consistency analysis. RESULTS: The mean ± standard deviation ulcer area measured using the three methods were 14.79 ± 5.39, 14.35 ± 5.26, and 14.30 ± 5.26 cm2 , respectively. The measurement differences among the three groups or between any two were not statistically significant. Bland-Altman plots showed good consistency between the Image J-based Computer Analysis and the other two methods. CONCLUSION: The Image J-based Computer Analysis method can be interchanged with the other methods to assess ulcer areas. It is freely accessible, accurate and home-operable, thus worth consideration by nurses for routine ulcer area assessment.

Single-minded homolog 2 as a potential prognostic signature and assessment of its correlation with immune cell infiltration in pancreatic cancer.

Single-minded homolog 2 (SIM2) has been identified as a potential contributor to the development of solid tumors. Despite this, there is a lack of comprehensive research regarding its biological role and underlying mechanism within pancreatic cancer (PC), as well as its prognostic impact. This study systematically evaluated the expression level and clinical significance of SIM2 in patients with PC using various databases, including The Cancer Genome Atlas, KM Plotter, and gene expression profiling interactive analysis. To investigate the relationship between SIM2 expression and immune cell infiltration, we conducted ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) analyses. Single-minded homolog 2 was up-regulated in patients with PC. Pancreatic cancer patients with higher SIM2 expression had poorer overall survival rates. Gene set enrichment analysis results suggested that SIM2 may have a significant impact on the progression of PC and the regulation of immune responses. According to the ssGSEA algorithm, SIM2 has a negative correlation with the levels of infiltrating TFH, mast cells, and pDC. Our study demonstrated that SIM2 serves as a biomarker, and is associated with both prognosis and immune infiltration in PC. This provides a solid foundation for future investigations into the precise role of SIM2 in the carcinogenesis and progression of PC.

Ultra-Widefield Swept-Source Optical Coherence Tomography Angiography in the Assessment of Choroidal Changes in Young Adults With Myopia.

Purpose: To evaluate choroidal changes in young adults with myopia using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Methods: This study enrolled 105 eyes of 105 participants who underwent SS-OCTA imaging (24 mm × 20 mm) centered on the fovea. Eyes were categorized as low myopia, moderate myopia, or high myopia. Choroidal thickness, choroidal capillary plexus (CCP) vessel density, and choroidal Sattler's and Haller's layer (CSHL) vessel density were analyzed in nine grids using built-in angiography analysis software. Results: A significant decrease in choroidal thickness was found in most grids (P < 0.01) in high myopia. The CSHL vessel density also showed a significant decrease in most grids (P < 0.05) in high myopia. Choroidal thickness was negatively correlated with axial length in most grids (P < 0.05). Choroidal thinning was most evident in the macular grid (ß = -22.55, P < 0.001). CSHL vessel density was negatively correlated with axial length in most grids (P < 0.05). Conclusions: Choroidal changes could be quantified using ultra-widefield SS-OCTA. Choroidal thinning with increasing axial length indicated regional differences in eyes with myopia, which were most evident in the macular area. Decreased CSHL vessel density with increasing axial length also indicated regional differences in eyes with myopia. Translational Relevance: This study explored choroidal changes with a wider field of view than has been currently available.

Comprehensive Assessment of Subtyping Methods for Improved Surveillance of Foodborne Salmonella.

High-resolution and efficient typing for the bacterial pathogen is essential for tracking the sources, detecting or diagnosing variants, and conducting a risk assessment. However, a systematic in-field investigation of Salmonella along the food chain has not been documented. This study assessed 12 typing methods, such as antimicrobial-resistance (AMR) gene profile typing, Core Genome Multilocus Sequence Typing (cgMLST), and CRISPR multi-virulence locus sequence typing (CRISPR-MVLST), to evaluate their effectiveness for use in routine monitoring of foodborne Salmonella transmission along the poultry production chain. During 2015-16, a total of 1,064 samples were collected from poultry production chain, starting from breeding farms and slaughterhouses to the markets of Zhejiang province in China. A total of 61 consecutive unique Salmonella isolates recovered from these samples were selected for genome sequencing and further comparative typing analysis. Traditional typing methods, including serotyping, AMR phenotype-based typing, as well as modern genotyping approaches, were evaluated and compared by their discrimination index (DI). The results showed that the serotyping method identified nine serovars. The gold standard cgMLST method indicated only 18 different types (DI = 0.8541), while the CRISPR-MVLST method detected 30 types (DI = 0.9628), with a higher DI than all examined medium-resolution WGS-based genotyping methods. We demonstrate that the CRISPR-MVLST might be used as a tool with high discriminatory power, comparable ease of use, ability of tracking the source of Salmonella strains along the food chain and indication of genetic features especially virulence genes. The available methods with different purposes and laboratory expertise were also illustrated to assist in rational implementation. IMPORTANCE In public health field, high-resolution and efficient typing of the bacterial pathogen is essential, considering source-tracking and risk assessment are fundamental issues. Currently, there are no recommendations for applying molecular characterization methods for Salmonella along the food chain, and a systematic in-field investigation comparing subtyping methods in the context of routine surveillance was partially addressed. Using 1,064 samples along a poultry production chain with a considerable level of Salmonella contamination, we collected representative isolates for genome sequencing and comparative analysis by using 12 typing techniques, particularly with whole-genome sequence (WGS) based methods and a recently invented CRISPR multi-virulence locus sequence typing (CRISPR-MVLST) method. CRISPR-MVLST is identified as a tool with higher discriminatory power compared with medium-resolution WGS-based typing methods, comparable ease of use and proven ability of tracking Salmonella isolates. Besides, we also offer recommendations for rational choice of subtyping methods to assist in better implementation schemes.

Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine.

In influenza vaccine development, Madin-Darby canine kidney (MDCK) cells provide multiple advantages, including large-scale production and egg independence. Several cell-based influenza vaccines have been approved worldwide. We cultured H5N1 virus in a serum-free MDCK cell suspension. The harvested virus was manufactured into vaccines after inactivation and purification. The vaccine effectiveness was assessed in the Wuhan Institute of Biological Products BSL2 facility. The pre- and postvaccination mouse serum titers were determined using the microneutralization and hemagglutination inhibition tests. The immunological responses induced by vaccine were investigated using immunological cell classification, cytokine expression quantification, and immunoglobulin G (IgG) subtype classification. The protective effect of the vaccine in mice was evaluated using challenge test. Antibodies against H5N1 in rats lasted up to 8 months after the first dose. Compared with those of the placebo group, the serum titer of vaccinated mice increased significantly, Th1 and Th2 cells were activated, and CD8+ T cells were activated in two dose groups. Furthermore, the challenge test showed that vaccination reduced the clinical symptoms and virus titer in the lungs of mice after challenge, indicating a superior immunological response. Notably, early after vaccination, considerably increased interferon-inducible protein-10 (IP-10) levels were found, indicating improved vaccine-induced innate immunity. However, IP-10 is an adverse event marker, which is a cause for concern. Overall, in the case of an outbreak, the whole-virion H5N1 vaccine should provide protection.

A Promising Approach to Optimizing Sequential Treatment Decisions for Depression: Markov Decision Process.

The most appropriate next step in depression treatment after the initial treatment fails is unclear. This study explores the suitability of the Markov decision process for optimizing sequential treatment decisions for depression. We conducted a formal comparison of a Markov decision process approach and mainstream state-transition models as used in health economic decision analysis to clarify differences in the model structure. We performed two reviews: the first to identify existing applications of the Markov decision process in the field of healthcare and the second to identify existing health economic models for depression. We then illustrated the application of a Markov decision process by reformulating an existing health economic model. This provided input for discussing the suitability of a Markov decision process for solving sequential treatment decisions in depression. The Markov decision process and state-transition models differed in terms of flexibility in modeling actions and rewards. In all, 23 applications of a Markov decision process within the context of somatic disease were included, 16 of which concerned sequential treatment decisions. Most existing health economic models relating to depression have a state-transition structure. The example application replicated the health economic model and enabled additional capacity to make dynamic comparisons of more interventions over time than was possible with traditional state-transition models. Markov decision processes have been successfully applied to address sequential treatment-decision problems, although the results have been published mostly in economics journals that are not related to healthcare. One advantage of a Markov decision process compared with state-transition models is that it allows extended action space: the possibility of making dynamic comparisons of different treatments over time. Within the context of depression, although existing state-transition models are too basic to evaluate sequential treatment decisions, the assumptions of a Markov decision process could be satisfied. The Markov decision process could therefore serve as a powerful model for optimizing sequential treatment in depression. This would require a sufficiently elaborate state-transition model at the cohort or patient level.