Designing a Consumer-centric Care Management Program by Prioritizing Interventions Using Deep Learning Causal Inference.

Care management is a team-based and patient-centered approach to reduce health risks and improve outcomes for managed populations. Post Discharge Management (PDM) is an important care management program at Elevance Health, which is aimed at reducing 30-day readmission risk for recently discharged patients. The current PDM program suffers from low engagement. When assigning interventions to patients, case managers choose the interventions to be conducted in each call only based on their limited personal experiences. In this work, we use deep learning causal inference to analyze the impact of interventions conducted on the first call on consumer engagement in the PDM program, which provides a reliable reference for case managers to select interventions to promote consumer engagement. With three experiments cross-validating the results, our results show that consumers will engage more in the program if the case manager conducts interventions that require more nurse-patient interactions on the first call. On the other hand, conducting less interactive and more technical interventions on the first call leads to relatively poor consumer engagement. These findings correspond to the clinical sense of experienced nurses and are consistent with previous findings in patient engagement in hospital settings.

Gender- and Age-Related Characterization of Lower Eyelid Morphology: Three-Dimensional Analysis in a Chinese Population.

BACKGROUND: The lower eyelid region is a critical component of the face. It is essential to establish anthropometric reference values for the evaluation of aging, surgical planning and assessment of outcomes in periocular esthetic and rejuvenation procedures. This study aims to provide comprehensive anthropometric data on the Chinese lower eyelid region, into account factors such as sex and age, through three-dimensional imaging analysis. METHOD: Three-dimensional facial images were obtained from 84 healthy Chinese individuals aged between 20-35 and 50-65 years, as well as eight patients aged between 20 and 35 who presented with eyelid bags. A total of 27 landmarks were identified, leading to the generation of corresponding 21 lines, 5 curves, 4 angles, 2 areas and 5 ratios. The measurements were compared among different age groups, genders and young patients with or without eyelid bags. RESULTS: Compared to females, males exhibited a more elongated palpebral fissure, lower tear trough and lid-cheek junction, smaller inner and outer canthus angles, as well as a larger area and proportion of the lower palpebral region. As age progressed, the height and width of the palpebral fissure and inner canthus angle decreased gradually, which was accompanied by sagging of the tear trough and lid-cheek junction, an increase in lower eyelid area and swelling of the lower eyelid. Young patients undergoing eyelid bags demonstrated larger and more swelling lower eyelid which held clinical significance for rejuvenation surgery. CONCLUSION: Males exhibited a higher proportion of the brow-eye unit occupied by the lower eyelid region compared to females. Elderly individuals displayed noticeable drooping of the tear trough and lid-cheek junction, accompanied by swelling in the lower palpebral region. These findings can serve as standard references for esthetic procedures and reconstructive periocular operations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Competition between Self-Assembly and Phase Separation Governs High-Temperature Condensation of a DNA Liquid.

In many biopolymer solutions, attractive interactions that stabilize finite-sized clusters at low concentrations also promote phase separation at high concentrations. Here we study a model biopolymer system that exhibits the opposite behavior, whereby self-assembly of DNA oligonucleotides into finite-sized, stoichiometric clusters tends to inhibit phase separation. We first use microfluidics-based experiments to map a novel phase transition in which the oligonucleotides condense as the temperature increases at high concentrations of divalent cations. We then show that a theoretical model of competition between self-assembly and phase separation quantitatively predicts changes in experimental phase diagrams arising from DNA sequence perturbations. Our results point to a general mechanism by which self-assembly shapes phase boundaries in complex biopolymer solutions.

Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing.

Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

Structures of the mumps virus polymerase complex via cryo-electron microscopy.

The viral polymerase complex, comprising the large protein (L) and phosphoprotein (P), is crucial for both genome replication and transcription in non-segmented negative-strand RNA viruses (nsNSVs), while structures corresponding to these activities remain obscure. Here, we resolved two L-P complex conformations from the mumps virus (MuV), a typical member of nsNSVs, via cryogenic-electron microscopy. One conformation presents all five domains of L forming a continuous RNA tunnel to the methyltransferase domain (MTase), preferably as a transcription state. The other conformation has the appendage averaged out, which is inaccessible to MTase. In both conformations, parallel P tetramers are revealed around MuV L, which, together with structures of other nsNSVs, demonstrates the diverse origins of the L-binding X domain of P. Our study links varying structures of nsNSV polymerase complexes with genome replication and transcription and points to a sliding model for polymerase complexes to advance along the RNA templates.

Assessing parameter efficient methods for pre-trained language model in annotating scRNA-seq data.

Annotating cell types of single-cell RNA sequencing (scRNA-seq) data is crucial for studying cellular heterogeneity in the tumor microenvironment. Recently, large-scale pre-trained language models (PLMs) have achieved significant progress in cell-type annotation of scRNA-seq data. This approach effectively addresses previous methods' shortcomings in performance and generalization. However, fine-tuning PLMs for different downstream tasks demands considerable computational resources, rendering it impractical. Hence, a new research branch introduces parameter-efficient fine-tuning (PEFT). This involves optimizing a few parameters while leaving the majority unchanged, leading to substantial reductions in computational expenses. Here, we utilize scBERT, a large-scale pre-trained model, to explore the capabilities of three PEFT methods in scRNA-seq cell type annotation. Extensive benchmark studies across several datasets demonstrate the superior applicability of PEFT methods. Furthermore, downstream analysis using models obtained through PEFT showcases their utility in novel cell type discovery and model interpretability for potential marker genes. Our findings underscore the considerable potential of PEFT in PLM-based cell type annotation, presenting novel perspectives for the analysis of scRNA-seq data.

Tracking Fat Grafts by Magnetic Resonance Imaging: A Comparative Study of Adolescent and Adult Patients with Stable Localized Scleroderma.

BACKGROUND: The optimal timing of reconstruction for patients with facial localized scleroderma is uncertain. The purpose of this study was to compare the outcomes of autologous fat transplantation in adolescent and adult patients with stable localized scleroderma. METHODS: Adolescent (age 10-19 years) and adult (age >19 years) patients with no previous surgery were enrolled (n = 10, each group). Preoperative magnetic resonance imaging (MRI), blood tests and dermatological assessments were used for disease activity assessment. All patients underwent autologous fat transplantation for anatomic facial fat restoration with preoperative MRI planning. Preoperative, immediate and one-year postoperative 3D Dixon MRI scans with image registration and fusion techniques were used for fat graft tracking. Patient satisfaction was assessed with a 5-point Likert scale. RESULTS: There was no significant difference in sex, body mass index, disease severity, or volume of injected fat between the two groups (p > 0.05), except for age (p < 0.05). The one-year postoperative fat graft retention rate was not significantly different, with 36.6 ± 2.4% (ranging from 25.3 to 49.3%) in the adolescent group and 32.9 ± 1.7% (ranging from 27.3 to 40.1%) in the adult group (p > 0.05). Surgical outcomes were favorable in all patients, with satisfaction scores of 3.8 ± 0.2 points in the adolescent group and 3.6 ± 0.2 points in the adult group (p > 0.05). CONCLUSION: In stable localized scleroderma, the initial autologous fat transplantation was equally effective for facial contour deformity improvement, with no significant difference in fat graft retention or satisfaction.

Facial adult female acne in China: An analysis based on artificial intelligence over one million.

BACKGROUND: To further clarify the acne profile of Chinese adult women, we included 1,156,703 adult women. An artificial intelligence algorithm was used to analyze images taken by high-resolution mobile phones to further explore acne levels in Chinese adult women. METHOD: In this study, we assessed the severity of acne by evaluating patients' selfies through a smartphone application. Furthermore, we gathered basic user information through a questionnaire, including details such as age, gender, skin sensitivity, and dietary habits. RESULTS: This study showed a gradual decrease in acne severity from the age of 25 years. A trough was reached between the ages of 40 and 44, followed by a gradual increase in acne severity. In terms of skin problems and acne severity, we have found that oily skin, hypersensitive skin, frequent makeup application and unhealthy dietary habits can affect the severity of acne. For environment and acne severity, we observed that developed city levels, cold seasons and high altitude and strong radiation affect acne severity in adult women. For the results of the AI analyses, the severity of blackheads, pores, dark circles and skin roughness were positively associated with acne severity in adult women. CONCLUSIONS: AI analysis of high-res phone images in Chinese adult women reveals acne severity trends. Severity decreases after 25, hits a low at 40-44, then gradually rises. Skin type, sensitivity, makeup, diet, urbanization, seasons, altitude, and radiation impact acne. Blackheads, pores, dark circles, and skin roughness are linked to acne severity. These findings inform personalized skincare and public health strategies for adult women.

Mobile phone-assisted imprinted nanozyme for bicolor colorimetric visual detection of erythromycin in river water and milk samples.

The residues of erythromycin (ERY) may have negative impacts on the ecological environment, health, and food safety. How to detect ERY effectively and visually is a challenging issue. Herein, we synthesized a molecularly imprinted polymer based nanozymes for selective detection of erythromycin (ERY-MIPNs) at neutral pH, and developed a mobile phone-assisted bicolor colorimetric detection system. This system produced a wide range of color changes from blue to pinkish purple as the ERY concentration increased, making it easy to capture the visualization result. Also, the system showed good sensitivity to ERY ranging from 15 to 135 µM, with a detection limit of 1.78 µM. In addition, the system worked well in the detection of ERY in river water and milk, with the recoveries of 95.57% âˆ¼ 103.20%. These data suggests that this strategy is of considerable potential for practical applications and it provides a new idea for visual detection with portable measurement.

Bacillus sp. alone or combined with salicylic acid inhibited Trichoderma spp. infection on harvested white Hypsizygus marmoreus.

Introduction: White Hypsizygus marmoreus is a popular edible mushroom. It is rich in nutrition and flavor but vulnerable to fungal disease, resulting in nutrient loss and aging. Methods: In this study, the pathogenic fungus Trichoderma spp. BBP-6 and its antagonist Bacillus sp. 1-23 were isolated and identified. The negative effects caused by this pathogen were judged by detecting a series of changes in the infected white H. marmoreus. The effects of Bacillus sp. 1-23 on Trichoderma spp. BBP-6 and the infected white H. marmoreus were detected. The effect of Bacillus sp. 1-23 treatment combined with salicylic acid (SA) was also considered. Results: The results showed that Trichoderma spp. BBP-6 could affect the activities of antioxidant enzymes PAL, POD, CAT, SOD, GR, PPO, and APX to interfere with the stability of the white H. marmoreus antioxidant enzyme system and cause the mushroom severe browning and nutrition loss, as well as general quality deterioration. Bacillus sp. 1-23 could produce chitinase and chitosanase enzymes to inhibit Trichoderma spp. BBP-6 directly. SA reinforced this inhibitory. Bacillus sp. 1-23 alone or combined with SA could help white H. marmoreus from the Trichoderma spp. BBP-6 infection to effectively maintain nutrients, restore and stabilize the antioxidant system, and reduce the production of malondialdehyde, superoxide anion and hydrogen peroxide. Discussion: Thus, such treatments could be considered potential methods to alleviate damage from disease and extend the shelf life of white H. marmoreus.

Fe3O4/biochar modified with molecularly imprinted polymer as efficient persulfate activator for salicylic acid removal from wastewater: Performance and specific recognition mechanism.

In this study, a novel Fe3O4-based biochar coupled surface-imprinted polymer was constructed via simple hydrothermal route for salicylic acid recognition and degradation in advanced oxidation processes. The material exhibited excellent adsorption capability, up to 118.23 mg g-1, and efficient degradation performance, 87.44% removal rate within 240 min, based on integrating the advantages of both huge specific surface area as well as abundant functional groups from biochars and specific recognition sites from imprinted cavities. Moreover, high selectivity coefficient (11.67) showed stable recognition in single and binary systems. SO4•- and •OH were confirmed as reactive oxygen species in catalytic reaction according to quenching experiments and EPR analysis. The degradation mechanism and pathway were unraveled by DFT calculations and LC-MS. Furthermore, the results of toxicity evaluation, stability and reusability demonstrated application potential in the field of water environment restoration. This study confirmed that molecular imprinting provided a promising solution to targeted removal of emerging environmental pollutants by degrading after the enrichment of pollutants to the composites surface.

Application of Chlorophyll Fluorescence Analysis Technique in Studying the Response of Lettuce (Lactuca sativa L.) to Cadmium Stress.

To reveal the impact of cadmium stress on the physiological mechanism of lettuce, simultaneous determination and correlation analyses of chlorophyll content and photosynthetic function were conducted using lettuce seedlings as the research subject. The changes in relative chlorophyll content, rapid chlorophyll fluorescence induction kinetics curve, and related chlorophyll fluorescence parameters of lettuce seedling leaves under cadmium stress were detected and analyzed. Furthermore, a model for estimating relative chlorophyll content was established. The results showed that cadmium stress at 1 mg/kg and 5 mg/kg had a promoting effect on the relative chlorophyll content, while cadmium stress at 10 mg/kg and 20 mg/kg had an inhibitory effect on the relative chlorophyll content. Moreover, with the extension of time, the inhibitory effect became more pronounced. Cadmium stress affects both the donor and acceptor sides of photosystem II in lettuce seedling leaves, damaging the electron transfer chain and reducing energy transfer in the photosynthetic system. It also inhibits water photolysis and decreases electron transfer efficiency, leading to a decline in photosynthesis. However, lettuce seedling leaves can mitigate photosystem II damage caused by cadmium stress through increased thermal dissipation. The model established based on the energy captured by a reaction center for electron transfer can effectively estimate the relative chlorophyll content of leaves. This study demonstrates that chlorophyll fluorescence techniques have great potential in elucidating the physiological mechanism of cadmium stress in lettuce, as well as in achieving synchronized determination and correlation analyses of chlorophyll content and photosynthetic function.

IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/ß-catenin signaling.

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

Promoting Catalytic Performance Involving Hydrogen Spillover by Ion Exchange of Pt@A Catalysts to Regulate Reactant Adsorption.

Zeolite-encapsulated metal nanoparticle systems have exhibited interesting catalytic performances via the hydrogen spillover process, yet how to further utilize the function of zeolite supports to promote catalytic properties in such a process is still challenging and has rarely been investigated. Herein, to address this issue, the strategy to strengthen the adsorption energy of reactant onto the zeolite surface via a simple ion exchange method has been implemented. Ion-exchanged linde type A (LTA) zeolite-encapsulated platinum nanoclusters (Pt@NaA, Pt@HA, Pt@KA, and Pt@CaA) were prepared to study the influence of ion exchange on the catalytic performance in the model reaction of hydrogenation of acetophenone to 1-phenylethanol. The reaction results showed that the Pt@CaA catalyst exhibited the best catalytic activity in the series of encapsulated catalysts, and the selectivity of 1-phenylethanol approached 100%. As revealed by density functional theory (DFT) calculations and acetophenone temperature-programmed desorption (acetophenone-TPD) experiments, in comparison with introduced cations of Na+, H+, and K+, ion-exchanged Ca2+ on the zeolite maximumly enhanced the adsorption of carbonyl groups in acetophenone, playing a critical role in achieving the highest activity and excellent catalytic selectivity among the Pt@A catalysts.

Long non-coding RNA CCAT1 acts as an oncogene to promote radiation resistance in lung adenocarcinoma: an epigenomics-based investigation.

Long non-coding RNAs (lncRNAs) appear to be the crucial modulators in various processes and critically influence the oncogenesis. As one of the LncRNAs, LncRNA CCAT1 has been reported to be closely associated with the progression multiple cancers, but its role in modulating the radioresistance of lung adenocarcinoma (LUAD) remains unclear. In our present study, we screened the potential radioresistance related LncRNAs in LUAD based on the data from The Cancer Genome Atlas (TCGA) database. Data suggested that CCAT1 was abundantly expressed in LUAD and CCAT1 was significantly associated with poor prognosis and radioresistance. Moreover, our in vitro experiments showed that radiation treatment could trigger elevated expression of CCAT1 in the human LUAD cell lines. Further loss/gain-of-function investigations indicated that CCAT1 knockdown significantly inhibited cell proliferation, migration and promoted cell apoptosis in NCI-H1299 cells under irradiation, whereas CCAT1 overexpression in A549 cells yield the opposite effects. In summary, we identified the promoting role of CCAT1 in radioresistance of LUAD, which may provide a theoretical basis for radiotherapy sensitization of LUAD.

Microplastic pollution interaction with disinfectant resistance genes: research progress, environmental impacts, and potential threats.

The consumption of disposable plastic products and disinfectants has surged during the global COVID-19 pandemic, as they play a vital role in effectively preventing and controlling the spread of the virus. However, microplastic pollution and the excessive or improper use of disinfectants contribute to the increased environmental tolerance of microorganisms. Microplastics play a crucial role as vectors for microorganisms and plankton, facilitating energy transfer and horizontal gene exchange. The increase in the use of disinfectants has become a driving force for the growth of disinfectant resistant bacteria (DRB). A large number of microorganisms can have intense gene exchange, such as plasmid loss and capture, phage transduction, and cell fusion. The reproduction and diffusion rate of DRB in the environment is significantly higher than that of ordinary microorganisms, which will greatly increase the environmental tolerance of DRB. Unfortunately, there is still a huge knowledge gap in the interaction between microplastics and disinfectant resistance genes (DRGs). Accordingly, it is critical to comprehensively summarize the formation and transmission routes of DRGs on microplastics to address the problem. This paper systematically analyzed the process and mechanisms of DRGs formed by microbes. The interaction between microplastics and DRGs and the contribution of microplastic on the diffusion and spread of DRGs were expounded. The potential threats to the ecological environment and human health were also discussed. Additionally, some challenges and future priorities were also proposed with a view to providing useful basis for further research.

Paired single-B-cell transcriptomics and receptor sequencing reveal activation states and clonal signatures that characterize B cells in acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is associated with a dismal prognosis. Immune checkpoint blockade (ICB) to induce antitumor activity in AML patients has yielded mixed results. Despite the pivotal role of B cells in antitumor immunity, a comprehensive assessment of B lymphocytes within AML's immunological microenvironment along with their interaction with ICB remains rather constrained. METHODS: We performed an extensive analysis that involved paired single-cell RNA and B-cell receptor (BCR) sequencing on 52 bone marrow aspirate samples. These samples included 6 from healthy bone marrow donors (normal), 24 from newly diagnosed AML patients (NewlyDx), and 22 from 8 relapsed or refractory AML patients (RelRef), who underwent assessment both before and after azacitidine/nivolumab treatment. RESULTS: We delineated nine distinct subtypes of B cell lineage in the bone marrow. AML patients exhibited reduced nascent B cell subgroups but increased differentiated B cells compared with healthy controls. The limited diversity of BCR profiles and extensive somatic hypermutation indicated antigen-driven affinity maturation within the tumor microenvironment of RelRef patients. We established a strong connection between the activation or stress status of naïve and memory B cells, as indicated by AP-1 activity, and their differentiation state. Remarkably, atypical memory B cells functioned as specialized antigen-presenting cells closely interacting with AML malignant cells, correlating with AML stemness and worse clinical outcomes. In the AML microenvironment, plasma cells demonstrated advanced differentiation and heightened activity. Notably, the clinical response to ICB was associated with B cell clonal expansion and plasma cell function. CONCLUSIONS: Our findings establish a comprehensive framework for profiling the phenotypic diversity of the B cell lineage in AML patients, while also assessing the implications of immunotherapy. This will serve as a valuable guide for future inquiries into AML treatment strategies.

CancerGPT for few shot drug pair synergy prediction using large pretrained language models.

Large language models (LLMs) have been shown to have significant potential in few-shot learning across various fields, even with minimal training data. However, their ability to generalize to unseen tasks in more complex fields, such as biology and medicine has yet to be fully evaluated. LLMs can offer a promising alternative approach for biological inference, particularly in cases where structured data and sample size are limited, by extracting prior knowledge from text corpora. Here we report our proposed few-shot learning approach, which uses LLMs to predict the synergy of drug pairs in rare tissues that lack structured data and features. Our experiments, which involved seven rare tissues from different cancer types, demonstrate that the LLM-based prediction model achieves significant accuracy with very few or zero samples. Our proposed model, the CancerGPT (with ~ 124M parameters), is comparable to the larger fine-tuned GPT-3 model (with ~ 175B parameters). Our research contributes to tackling drug pair synergy prediction in rare tissues with limited data, and also advancing the use of LLMs for biological and medical inference tasks.

Global research status of localised scleroderma reported over the period 1993-2022: A 30-year bibliometric analysis.

Localised scleroderma predominantly affects the skin with an unknown aetiology. Despite its clinical importance, no comprehensive bibliometric analysis has been conducted to assess the existing research landscape and future prospects for localised scleroderma. The articles related to localised scleroderma were retrieved from the WoSCC database and analysed by VOSviewer 1.6.10.0 (Leiden University, Netherlands), CiteSpace 6.1.R1 (Dreiser University, USA), and HistCite 2.1 (New York, United States). 2049 research papers pertaining to localised scleroderma spanning the years from 1993 to 2022 were extracted from the WoSCC database. The United States exhibited the highest productivity with 644 papers, accounting for 31.43% of the total output, followed by Germany with 206 papers (10.05%) and Italy with 200 papers (9.76%). Regarding academic institutions and journals, the University of Texas System and Dermatology published the most significant number of papers, and Professor Ihn, H emerged as the most prolific contributor among scholars. The top 10 cited references primarily concentrated on the diagnosis and treatment of localised scleroderma. "Phototherapy" and "methotrexate (MTX)" surfaced as the most recent and noteworthy keywords, representing the research hotspots in the domain of localised scleroderma. This bibliometric analysis furnishes valuable insights into the contemporary research landscape of localised scleroderma.