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Electronic health record (EHR) or medical claims-based algorithms (i.e., operational definitions) can be used to define safety outcomes using real-world data. However, existing tools do not allow researchers and decision-makers to adequately appraise whether a particular algorithm is fit for purpose (FFP) to support regulatory decisions on drug safety surveillance. Our objective was to develop a tool to enable regulatory decision-makers and other stakeholders to appraise whether a given algorithm is FFP for a specific decision context.We drafted a set of 77 generic items informed by regulatory guidance documents, existing instruments, and publications. The outcome of ischemic stroke served as an exemplar to inform the development of draft items. The items were designed to be outcome independent. We conducted a three-round online Delphi panel to develop and refine the tool and achieve consensus on items ( 70% agreement) among panel participants composed of regulators, researchers from pharmaceutical organizations, academic clinicians, methodologists, pharmacoepidemiologists, and cardiologists. We conducted a qualitative analysis of panel responses. Five pairs of reviewers independently evaluated two ischemic stroke algorithm validation studies to test its application. We developed a user guide, with explanation and elaboration for each item, guidance on essential and additional elements for user responses, and an illustrative example of a complete assessment. Furthermore, we conducted a 2-h online stakeholder panel of 16 participants from regulatory agencies, academic institutions, and industry. We solicited input on key factors for an FFP assessment, their general reaction to the Algorithm CErtaInty Tool (ACE-IT), limitations of the tool, and its potential use.The expert panel reviewed and made changes to the initial list of 77 items. The panel achieved consensus on 38 items, and the final version of the ACE-IT includes 34 items after removal of duplicate items. Applying the tool to two ischemic stroke algorithms demonstrated challenges in its application and identified shared concepts addressed by more than one item. The ACE-IT was viewed positively by the majority of stakeholders. They identified that the tool could serve as an educational resource as well as an information-sharing platform. The time required to complete the assessment was identified as an important limitation. We consolidated items with shared concepts and added a preliminary screen section and a summary assessment box based on their input. The final version of the ACE-IT is a 34-item tool for assessing whether algorithm validation studies on safety outcomes are FFP. It comprises the domains of internal validity (24 items), external validity (seven items), and ethical conduct and reporting of the validation study (three items). The internal validity domain includes sections on objectives, data sources, population, outcomes, design and setting, statistical methods, reference standard, accuracy, and strengths and limitations. The external validity domain includes items that assess the generalizability to a proposed target study. The domain on ethics and transparency includes items on ethical conduct and reporting of the validation study.The ACE-IT supports a structured, transparent, and flexible approach for decision-makers to appraise whether electronic health record or medical claims-based algorithms for safety outcomes are FFP for a specific decision context. Reliability and validity testing using a larger sample of participants in other therapeutic areas and further modifications to reduce the time needed to complete the assessment are needed to fully evaluate its utility for regulatory decision-making.

The plant hormones cytokinin (CK) and abscisic acid (ABA) play critical and often opposite roles during plant growth, development, and responses to abiotic and biotic stresses. Rose (Rosa sp.) is an economically important ornamental crop sold as cut flowers. Rose petals are extremely susceptible to gray mold disease caused by the necrotrophic fungal pathogen Botrytis cinerea. The infection of rose petals by B. cinerea leads to tissue collapse and rot, causing severe economic losses. In this study, we showed that CK and ABA play opposite roles in the susceptibility of rose to B. cinerea. Treatment with CK enhanced the disease protection of rose petals to B. cinerea, while ABA promoted disease progression. We further demonstrated that rose flowers activate CK-mediated disease protection via a B. cinerea-induced rose transcriptional repressor, Rosa hybrida (Rh)WRKY13, which is an ortholog of Arabidopsis (Arabidopsis thaliana), AtWRKY40. RhWRKY13 binds to promoter regions of the CK degradation gene CKX3 (RhCKX3) and the ABA-response gene ABA insensitive4 (RhABI4), leading to simultaneous inhibition of their expression in rose petals. The increased CK content and reduced ABA responses result in enhanced protection from B. cinerea. Collectively, these data reveal opposite roles for CK and ABA in the susceptibility of rose petals against B. cinerea infection, which is mediated by B. cinerea-induced RhWRKY13 expression.

New construction has resulted in impervious surfaces increasingly replacing natural landscapes, altering surface radiation, thermal properties, and humidity in urban areas. Based on Landsat-8 data, the temporal and spatial impacts of the construction of Dalian Jinzhouwan Airport and Beijing Daxing Airport on the thermal environment were studied. The local thermal gradient (LTG) of the airport before and after construction is compared. The results showed that after the completion of the airport, the LTG value of Daxing Airport increased by 0.033 and that of Jinzhou Bay Airport increased by 0.009. After the airport operation, LTG values increase again. Daxing Airport added another 0.053, and Jinzhou Bay Airport added another 0.127. Two land classification models (land use type, LUT; local climate zone, LCZ) were used to explore the relationship between land use type and LTG. The results show that the increase of alloy buildings after the completion of the airport has a great influence on the thermal environment of the two study areas. The operation of airports will further enhance this effect. Our study can provide a reference for the influence of large-scale traffic construction on the urban thermal environment.

Solar collectors are more efficient and commercial devices for collecting solar energy, compared to other solar energy utilizations. To improve the efficiency of solar collectors, it is important to prepare a liquid heat-collecting medium, which is stable and has high photothermal properties. Therefore, in this work, we develop a droplet–droplet mixing technique to prepare Fe3O4-H2O magnetic nanofluid. The results show that magnetic nanofluids prepared using the droplet–droplet mixing technique have more stable performance and a better encapsulation of dispersants than those prepared via traditional liquid–liquid mixing. Then, the thermal conductivity and photothermal properties of Fe3O4-H2O magnetic nanofluids are investigated experimentally and theoretically. The thermal conductivity and temperature of the magnetic nanofluid with Fe3O4 nanoparticles of a 1.0% volume fraction can reach the maximum value of 0.95 W/m∙K and 73.9 °C when the magnetic field strength is equal to the saturation magnetic field of 800 Gs. These findings provide insights into the potential applications of Fe3O4-H2O magnetic nanofluids in direct absorption solar collectors, heat exchangers, automobile radiators, etc.

With the booming development of Internet information technology, e-commerce platforms in the era of network economy have undergone great changes, triggering a new marketing model change. Innovative research on marketing models can help the transformation and development of small and medium-sized e-commerce companies, which has important practical significance and theoretical value. The prediction of e-commerce sales is one of the key aspects of the evaluation of innovative marketing models, and only an accurate prediction of future sales can lead to a reasonable marketing plan. Therefore, a big data-driven e-commerce sales forecasting method is proposed. First of all, for 1703 real e-commerce companies, a large number of relevant data that affect sales are selected, including sales records, product information, product evaluation, and other information. A knowledge graph was then used to preprocess the data samples to produce a sample set containing concepts, entities, and relationships. Next, the knowledge graph K-modes clustering model is established. By fixing the affiliation matrix and the clustering cluster matrix in turn, the minimum of the objective function is continuously solved to obtain the cluster centres. Finally, sales prediction is achieved based on the clustering results. The experimental results show that the proposed clustering model is able to obtain better performance in terms of cluster purity, NMI, and F-value. The proposed clustering model has high sales prediction accuracy and has certain reference value for e-commerce enterprises of different scales to formulate innovative marketing models.

BACKGROUND: Gynecological diseases threaten women’s health, and vaginal microecological testing is a common method for detecting gynecological diseases. Efficient and accurate microecological testing methods have always been the goal pursued by gynecologists. OBJECTIVE: In order to automatically identify different types of microbial images in vaginal micromorphology detection, this paper proposes a vaginal microecological image recognition method based on Gabor texture analysis combined with long and short-term memory network (LSTM) model. METHOD: Firstly, we denoise the microecological morphological im-ages, which selects the area of interest and sets the label of the microorganism according to the doctors label. Secondly, texture analysis is carried out for the region of interest, which uses Gabor filters with 8 directions and 5 scales to filter the region of interest to extract the texture features on the image. Comparing the differences between different microbial image features, and screening suitable features to reduce the number of features. Then, we design an LSTM model to analyze the relationship of image features in different categories of microorganisms. Finally, we use the full connection layer and Softmax function to realize the automatic recognition of different microbial images. RESULTS: The experimental results show that the image classification accuracy of 8 common microorganisms is 81.26%. CONCLUSION: Texture analysis combined with LSTM network strategy can identify different kinds of vaginal micro ecological images. Gabor-LSTM model has better classification effect on imbalanced data sets.

Neural precursor cell (NPC) dysfunction has been consistently implicated in autism. Induced pluripotent stem cell (iPSC)-derived NPCs from two autism groups (three idiopathic [I-ASD] and two 16p11.2 deletion [16pDel]) were used to investigate if proliferation is commonly disrupted. All five individuals display defects, with all three macrocephalic individuals (two 16pDel, one I-ASD) exhibiting hyperproliferation and the other two I-ASD subjects displaying hypoproliferation. NPCs were challenged with bFGF, and all hyperproliferative NPCs displayed blunted responses, while responses were increased in hypoproliferative cells. mRNA expression studies suggest that different pathways can result in similar proliferation phenotypes. Since 16pDel deletes MAPK3, P-ERK was measured. P-ERK is decreased in hyperproliferative but increased in hypoproliferative NPCs. While these P-ERK changes are not responsible for the phenotypes, P-ERK and bFGF response are inversely correlated with the defects. Finally, we analyzed iPSCs and discovered that 16pDel displays hyperproliferation, while idiopathic iPSCs were normal. These data suggest that NPC proliferation defects are common in ASD.

Background: The combination of pelvic fractures with lower urinary tract injuries (LUTIs) is a severe traumatic injury. This study was performed to determine the relationship between LUTIs and pelvic fracture types. Methods: Patients who sustained pelvic fractures combined with LUTIs between 1 January 2018 and 1 January 2022 in our institution were retrospectively analyzed. The patients’ demographics, mechanism of injury, presence of open pelvic fractures, types of pelvic fractures, patterns of LUTIs, and early complications were analyzed. The association between pelvic fracture types and the identified LUTIs was statistically analyzed. Results: This study involved 54 patients diagnosed with pelvic fractures combined with LUTIs. The overall incidence of pelvic fractures combined with LUTIs was 7.7% (n = 54/698). All patients had unstable pelvic fractures. The male:female ratio was approximately 2.4:1.0. The incidence of LUTIs was higher in men than women with pelvic fractures (9.1% vs. 4.4%). Bladder injuries occurred at roughly equal rates in men and women (4.5% vs. 4.4%, p = 0.966), but urethral injuries were more frequent in men (6.1% vs. 0.5%, p = 0.001). The most common pelvic injury pattern was a type C fracture according to the Tile classification and a vertical-shear-type fracture according to the Young–Burgess classification. The Young–Burgess fracture classification was related to the severity of bladder injury in men (p = 0.037). There was no significant difference in bladder injury according to the two classifications among women (p = 0.524 vs. p = 1.000) or among the entire cohort (p = 0.454 vs. p = 0.342). Conclusions: Men and women are equally likely to sustain a bladder injury, but a urethral injury with pelvic fracture is more frequent in men. LUTIs tend to be accompanied by unstable pelvic fractures. It is imperative to be vigilant for potential bladder injury when men sustain vertical-shear-type pelvic fractures.

Precise regulation of DNA damage response is crucial for cellular survival after DNA damage, and its abrogation often results in genomic instability in cancer. Phosphorylated histone H2AX (γH2AX) forms nuclear foci at sites of DNA damage and facilitates DNA damage response and repair. MicroRNAs (miRNA) are short, nonprotein-encoding RNA molecules, which posttranscriptionally regulate gene expression by repressing translation of and/or degrading mRNA. How miRNAs modulate DNA damage response is largely unknown. In this study, we developed a cell-based screening assay using ionizing radiation (IR)-induced γH2AX foci formation in a human osteosarcoma cell line, U2OS, as the readout. By screening a library of human miRNA mimics, we identified several miRNAs that inhibited γH2AX foci formation. Among them, miR-138 directly targeted the histone H2AX 3′-untranslated region, reduced histone H2AX expression, and induced chromosomal instability after DNA damage. Overexpression of miR-138 inhibited homologous recombination and enhanced cellular sensitivity to multiple DNA-damaging agents (cisplatin, camptothecin, and IR). Reintroduction of histone H2AX in miR-138 overexpressing cells attenuated miR-138–mediated sensitization to cisplatin and camptothecin. Our study suggests that miR-138 is an important regulator of genomic stability and a potential therapeutic agent to improve the efficacy of radiotherapy and chemotherapy with DNA-damaging agents. Mol Cancer Res; 9(8); 1100–11. ©2011 AACR.

E-cadherin is an important tumor suppressor gene whose expression is lost when cells acquire a metastatic phenotype. We analyzed the role of E-cadherin missplicing as a mechanism of its downregulation by analyzing a misspliced E-cadherin transcript that lacks exon 11 of this gene. This results in a frameshift and a premature termination codon that targets this transcript for degradation. Tumor tissues, including breast (20%, n = 9), prostate (30%, n = 9) and head and neck (75%, n = 8) cancer, express the exon 11-skipped transcripts (vs. nonmalignant controls) and its levels inversely correlate with E-cadherin expression. This is a novel mechanism of E-cadherin downregulation by missplicing in tumor cells, which is observed in highly prevalent human tumors. In the head and neck cancer model, nontumorigenic keratinocytes express exon 11–skipped splice product two- to sixfold lower than the head and neck tumor cell lines. Mechanistic studies reveal that SFRS2 (SC35), a splicing factor, as one of the regulators that increases missplicing and downregulates E-cadherin expression. Furthermore, this splicing factor was found to be overexpressed in 5 of 7 head and neck cell lines and primary head and neck tumors. Also, methylation of E-cadherin gene acts as a regulator of this aberrant splicing process. In 2 head and neck cell lines, wild-type transcript expression increased 16- to 25-folds, whereas the percentage of exon 11-skipped transcripts in both the cell lines decreased five- to 30-folds when cells were treated with a hypomethylating agent, azacytidine. Our findings reveal that promoter methylation and an upregulated splicing factor (SFRS2) are involved in the E-cadherin missplicing in tumors. Mol Cancer Ther; 10(9); 1751–9. ©2011 AACR.

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XLS file - 13K, List of 100 top most downregulated genes in the array. Average of 5 cell H&N cell lines compared to Tert Kert cells

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