Critical Growth Factor Research Articles

Graph-learning-based machine learning improves prediction and cultivation of commercial-grade marine microalgae Porphyridium

A graph learning [Binarized Attributed Network Embedding (BANE)] model enhances the single-target and multi-target prediction performances of random forest and eXtreme Gradient Boosting (XGBoost) by learning complex interrelationships between cultivation parameters of Porphyridium. The BANE-XGBoost has the best prediction performance (train R2 > 0.96 and test R2 > 0.87). Based on Shapley Additive Explanation (SHAP) model, illumination intensity, culture time, and KH2PO4 are the most critical factors for Porphyridium growth. The combined facilitating roles of cultivation parameters are found using the SHAP value-based heat map and group. To reach high biomass and daily production rate concurrently, one-way and two-way partial dependent plots models find the optimal conditions. The top 2 critical parameters (illumination intensity and KH2PO4) were selected to verify using the graphical user interface website based on the optimized model and lab experiments, respectively. This study shows thegraph-learning-based model can improve prediction performance and optimize intricate low-carbon microalgal cultivation.

Growth dynamics of Rathke's Cleft cyst: a risk score system for surgical decision making

ObjectiveRathke's cleft cysts (RCCs) exhibit variable growth patterns, thus posing a challenge in predicting progression. While some RCCs may not cause symptoms, others can insidiously cause pituitary dysfunction, which is often irreversible, even following surgery. Hence, it is crucial to identify asymptomatic RCCs that grow rapidly and pose a higher risk of causing endocrinologic dysfunction. This enables timely surgical intervention to prevent permanent damage. Our study examines the growth rate of RCCs, identifies factors that accelerate growth, and discusses the clinical implications of these findings.MethodsA retrospective analysis of a prospectively maintained electronic database revealed 45 patients aged 18–80 years who underwent endoscopic endonasal surgery (EEA) for RCCs between 2010 and 2022 at our center. Of these, 20 required early operative intervention. The remaining 25 patients were followed closely clinically and radiologically before requiring surgery (initial conservative management group). We conducted an analysis of the factors predicting growth over time in this group. Using a regression model, we constructed a risk score system to predict RCC growth over time.ResultsPatients in the initial conservative group had smaller cysts and were generally older than those in the early surgery group. Patients with preoperative pituitary dysfunction showed a higher median growth of 1.0 mm in the longest diameter compared to those with normal pituitary function, with an increase of 0.5 mm. A sum of annual cyst growth of all (z, y, x) diameters, at a rate of 3 mm or greater, was associated with a clinically significant increase in the risk of pituitary dysfunction, exceeding 50%.The most significant factors predicting rapid growth in RCCs were smoking status, age, and T1-weighted magnetic resonance imaging (MRI) intensity of cysts. Smoking was the most critical risk factor for rapid cyst growth (p = < .001). Our risk score system accurately predicted RCC growth with a 74% accuracy rate, 73% sensitivity, and 75% specificity.ConclusionOur analysis showed a strong link between active smoking and the rapid growth of RCC. This novel finding has significant preventive implications but needs validation by a large population database. Surgical intervention for RCC currently is often reserved for symptomatic cases. However, utilizing our risk-based scoring system to predict rapidly growing cysts may indicate early surgery in minimally symptomatic patients, thereby potentially preserving pituitary function.

Emerging Frontiers in CEA: An IoT-Based System Architecture for Smart, Sustainable, and High-Yielding Controlled Environment Agriculture

Abstract Controlled Environment Agriculture (CEA) cultivates fruits, vegetables, herbs, and other plants in fully or semi-controlled environments. It enables precise manipulation of critical plant growth factors such as temperature, humidity, light intensity, CO2, and nutrients, fostering optimal production. While CEA offers unparalleled yield potential, it has challenges like operational complexities and energy consumption concerns. We propose an IoT (Internet of Things) based system architecture for sensing and controlling CEA systems to address these challenges. The proposed system is designed for a hydroponic-based CEA system. In the system, four IoT devices are used to connect sensors. Each device utilizes various sensors to collect real-time data on key growth factors. IoT devices publish data as Message Queuing Telemetry Transport (MQTT) telemetry messages, accepted by various subscribers for processing and actions. A Microsoft Azure Edge device has been deployed as the data processing and analysis hub. It processes the MQTT messages using software modules packaged as Dockerized containers, extracts relevant information, sends required control signals to actuators and forwards selected results to the Microsoft Azure cloud for further processing and notifications. Four IoT devices are available in the system to control the growth factors at optimal levels. Various actuators are connected to these devices, such as heaters, coolers, humidifiers, dehumidifiers etc.. The dashboard of the system has been built using Node-RED, and it displays the status of the sensors and actuators and can switch between manual mode and AI-controlled auto mode. The system has been tested continuously for twelve hours and the test results indicate that the system can manage and control modern CEA systems.

The impact of administrative efficiency on SME Growth and Sustainability

enterprises (SMEs). This review examines the relationship between efficient administrative processes and the long-term success of SMEs, emphasizing how streamlined operations, resource management, and decision-making can enhance business performance. SMEs often struggle with limited resources, resulting in operational bottlenecks and inefficiencies that hinder their capacity to scale and sustain growth. By improving administrative efficiency through the adoption of technology, organizational restructuring, and optimized processes, SMEs can achieve greater productivity, reduce costs, and make informed decisions that promote sustainability. The review employs a case study approach, analyzing SMEs across different sectors—manufacturing, retail, and services to demonstrate the tangible benefits of administrative efficiency. The research includes qualitative interviews, operational data analysis, and performance evaluations before and after implementing efficiency-enhancing measures. Key findings highlight improvements in areas such as time management, cost reduction, and customer satisfaction, all contributing to accelerated growth and competitive advantage. Additionally, the study explores how administrative efficiency supports sustainable practices, such as resource optimization and risk management, leading to long-term business viability. Despite these advantages, challenges such as resistance to change, lack of skilled personnel, and financial constraints pose barriers to achieving administrative efficiency in SMEs. The review concludes by offering practical recommendations for overcoming these challenges, including investing in digital tools, employee training, and organizational restructuring. Ultimately, the research underscores the importance of administrative efficiency as a critical factor for SME growth and sustainability, providing insights for policymakers, business owners, and managers aiming to enhance the operational performance of small businesses in a competitive market.

Discrete Choice Model Applications for Air Passenger Airport Choices: A Literature Review

Airport development is a critical factor for regional growth, improving connectivity, and stimulating economic growth. Considering the complexity of planning and policy making in this area, multiple models and frameworks have been introduced to support decision-making processes. Among these, Discrete Choice Models (DCM) stand out for their capacity to project market flows, assess the validity and benefits of implementing airport modifications, tailor policies, improve the operations’ service level, and boost revenues. Given their extensive use and importance, a thorough review of DCM applications within the context of air transportation is both timely and necessary. This review organizes and evaluates the use of DCMs in air transport research. Both descriptive and predictive applications of DCMs are analyzed, focusing on choices related to airports and related levels, such as access mode and airline decisions. Each reviewed study is classified based on the type of model used, application context, data characteristics, employed variables, and methodological contributions. Through this analysis, six prevailing gaps are identified in the current state of DCM application in air transportation: improve data quality, enhance models with detailed trip and passenger information, explore advanced modeling techniques, incorporate general correlation and substitution structures, consider non-compensatory decision-making processes, and extend applications to new geographic and temporal contexts.

The establishment of kidney cancer organoid line in drug testing.

Kidney cancer is a common urological malignancy worldwide with an increasing incidence in recent years. Among all subtypes, renal cell carcinoma (RCC) represents the most predominant malignancy in kidney. Clinicians faced a major challenge to select the most effective and suitable treatment regime for patients from a wide range of modalities, despite improved understanding and diagnosis of RCC. Recently, organoid culture gained more interest as the 3D model is shown to be highly patient specific which is hypothetically beneficial to the investigation of precision medicine. Nonetheless, the development and application of organotypic culture in RCC is still immature, therefore, the primary objective of this study was to establish an organoid model for RCC. Patients diagnosed with renal tumor and underwent surgical intervention were recruited. RCC specimen was collected and derived into organoids. Derived organoids were validated by histological examminations, sequencing and xenograft. Drug response of organoids were compared with resistance cell line and patients' clinical outcomes. Our results demonstrated that organoids could be successfully derived from renal tumor and they exhibited high concordance in terms of immunoexpressional patterns. Sequencing results also depicted concordant mutations of driver genes in both organoids and parental tumor tissues. Critical and novel growth factors were discovered during the establishment of organoid model. Besides, organoids derived from renal tumor exhibited tumorigenic properties in vivo. In addition, organoids recapitulated patient's in vivo drug resistance and served as a platform to predict responsiveness of other therapeutic agents. Our RCC organoid model recaptiluated histological and genetic features observed in primary tumors. It also served as a potential platform in drug screening for RCC patients, though future studies are necessary before translating the outcomes into clinical practices.

Nanobioactive blood-derived shear-thinning biomaterial for tissue engineering applications

The conventional technique for successful bone grafts, involving the use of a patient's own tissue (autografts), is challenged by limited availability and donor site morbidity. While allografts and xenografts offer alternatives, they come with the risk of rejection. This underscores the pressing need for tailor-made artificial bone graft materials. In this context, injectable hydrogels are emerging as a promising solution for bone regeneration, especially in complex maxillofacial reconstruction cases. These hydrogels can seamlessly adapt to irregular shapes and conservatively fill defects. Our study introduces a shear-thinning biomaterial by blending silicate nanoplatelets (SNs) enriched with human blood-derived plasma rich in growth factors (PRGF) for personalized applications. Notably, our investigations unveil that injectable hydrogel formulations comprising 7.5 % PRGF yield sustained protein and growth factor release, affording precise control over critical growth factors essential for tissue regeneration. Moreover, our hydrogel exhibits exceptional biocompatibility in vitro and in vivo and demonstrates hemostatic properties. The hydrogel also presents a robust angiogenic potential and an inherent capacity to promote bone differentiation, proven through Alizarin Red staining, gene expression, and immunostaining assessments of bone-related biomarkers. Given these impressive attributes, our hydrogel stands out as a leading candidate for maxillofacial bone regeneration application. Beyond this, our findings hold immense potential in revolutionizing the field of regenerative medicine, offering an influential platform for crafting precise and effective therapeutic strategies.

Deciphering Microbial Adaptation in the Rhizosphere: Insights into Niche Preference, Functional Profiles, and Cross-Kingdom Co-occurrences

Rhizosphere microbial communities are to be as critical factors for plant growth and vitality, and their adaptive differentiation strategies have received increasing amounts of attention but are poorly understood. In this study, we obtained bacterial and fungal amplicon sequences from the rhizosphere and bulk soils of various ecosystems to investigate the potential mechanisms of microbial adaptation to the rhizosphere environment. Our focus encompasses three aspects: niche preference, functional profiles, and cross-kingdom co-occurrence patterns. Our findings revealed a correlation between niche similarity and nucleotide distance, suggesting that niche adaptation explains nucleotide variation among some closely related amplicon sequence variants (ASVs). Furthermore, biological macromolecule metabolism and communication among abundant bacteria increase in the rhizosphere conditions, suggesting that bacterial function is trait-mediated in terms of fitness in new habitats. Additionally, our analysis of cross-kingdom networks revealed that fungi act as intermediaries that facilitate connections between bacteria, indicating that microbes can modify their cooperative relationships to adapt. Overall, the evidence for rhizosphere microbial community adaptation, via differences in gene and functional and co-occurrence patterns, elucidates the adaptive benefits of genetic and functional flexibility of the rhizosphere microbiota through niche shifts.

Hybrid Bioactive Hydrogel Promotes Liver Regeneration through the Activation of Kupffer Cells and ECM Remodeling After Partial Hepatectomy.

Partial hepatectomy is an essential surgical technique used to treat advanced liver diseases such as liver tumors, as well as for performing liver transplants from living donors. However, postoperative complications such as bleeding, abdominal adhesions, wound infections, and inadequate liver regeneration pose significant challenges and increase morbidity and mortality rates. A self-repairing mixed hydrogel (O5H2/Cu2+/SCCK), containing stem cell derived cytokine (SCCK) derived from human umbilical cord mesenchymal stem cells (HUMSCs) treated with the traditional Chinese remedy Tanshinone IIA (TSA), is developed. This SCCK, in conjunction with O5H2, demonstrates remarkable effects on Kupffer cell activation and extracellular matrix (ECM) remodeling. This leads to the secretion of critical growth factors promoting enhanced proliferation of hepatocytes and endothelial cells, thereby facilitating liver regeneration and repair after partial hepatectomy. Furthermore, the hydrogel, featuring macrophage-regulating properties, effectively mitigates inflammation and oxidative stress damage in the incision area, creating an optimal environment for postoperative liver regeneration. The injectability and strong adhesion of the hydrogel enables rapid hemostasis at the incision site, while its physical barrier function prevents postoperative abdominal adhesions. Furthermore, the hydrogel's incorporation of Cu2+ provides comprehensive antibacterial effects, protecting against a wide range of bacteria types and reducing the chances of infections after surgery.

Customer Churn Prediction

In today’s highly competitive business landscape, customer retention revenue preservation, customer experience improvement, and marketing optimisation are critical factors for sustained growth and profitability. Customer churn predictionis discontinuing their services or purchases, which presents asignificant challenge for businesses across various industries. This project focuses on developing a predictive model to expect customer churn in the banking sector using machine learning techniques. The project involves the collection and analysis of historical customer data, confined account activity, transaction history, demographic information, and customer service interactions. By extracting the right features from this data, a machine learning model is trained to forecast which bank customers are at the highest risk of churning. A critical step in this study was the selection of relevant features that influence customerchurn. Feature selection was guided by domain knowledge and feature importance analysis. The different classifiers were used and then trained on the training dataset further ensuringthe model’s optimal performance. The model’s performance is assessed through various evaluation metrics, including accuracy, precision, and recall. Additionally, the project explores a model illustration to uncover the influential factors contributing to customer churn within the banking context. This project’s outcomes can empower banks to take proactive measures in retaining customers, enhancing their overall experience, and thereby preserving revenue streams. By addressing customer churn, banks can foster long-term relationships, reduce customer acquisition costs, and boost their competitiveness in the financial industry. The results of this project are expected to assist businesses in proactively retaining customers by targeting those at the highest risk of churning. Ultimately, reducing customer churn can lead to increased customer satisfaction, revenue, and long-term business sustainability.

Abstract 7458: Inhibition of brain cancer progression via resolution of inflammation

Abstract While inflammation is a hallmark of cancer, the mechanisms that disrupt its resolution in cancer are not well understood. A paradigm shift is emerging in our understanding that the resolution of inflammation is an active process controlled by specialized pro-resolving mediators (SPMs), including protectins and resolvins, which are endogenous lipid autacoids present in multiple tissues including the brain and cerebrospinal fluid. SPMs counter-regulate pro-inflammatory cytokine production and stimulate phagocytosis of cellular debris (“pro-resolution”) without being immunosuppressive. We hypothesized treatment with pro-resolving agonists such as SPMs presents a novel debris-clearing and resolution-enhancing therapeutic approach to complement cytotoxic brain cancer therapies. Here, we demonstrate the failure of resolution of inflammation via dysregulated SPMs may be a critical risk factor for aggressive brain cancer growth. Moreover, chemotherapy and targeted therapy further disrupt inflammation resolution via a tumor cell death (“debris”)-induced cytokine storm by macrophages. The SPM receptors GPR37 (protectin D1), GPR18/DRV2 (resolvin (Rv) D2), GPR32 (RvD1), and ChemR23/ERV (RvE1) are expressed in tumor-infiltrating macrophages and endothelial cells in the brain tumor microenvironment. Plasma levels of SPMs were significantly reduced in the medulloblastoma-bearing mice, suggesting that brain cancer progression is associated with a failure of endogenous resolution of inflammation. To determine whether failed resolution in brain cancer can be rescued by lipid mediator agonists, we systemically administered SPMs to subcutaneous and orthotopic glioblastoma and medulloblastoma murine brain tumor models. Significantly, RvD1 and RvD2 each inhibited the growth of human glioblastoma tumors by 15-fold at nanogram concentrations without toxicity. Likewise, RvD2 inhibited the growth of human medulloblastoma tumors by 3-fold. Protectins, PDX and PD1n-3, each inhibited growth of human medulloblastoma in mice by approximately 5-fold. Systemic administration of PDX or RvD2 prolonged survival of mice injected with orthotopic human D556 medulloblastoma and also glioblastoma models. Flow cytometry analysis of orthotopic glioblastoma tumors revealed increased immune infiltration into the brain tumor microenvironment in the PCTR1-treatment group when compared to the tumor-bearing non-treated group. At nanogram per day doses, protectins and resolvins suppressed orthotopic debris-stimulated brain tumor growth by activating macrophage and microglial phagocytosis of tumor cell debris and counter-regulating pro-inflammatory cytokines, including TNF-α, CCL2, CXCL1, and CCL4. Thus, stimulating the resolution of inflammation via the clearance of cellular debris with pro-resolving agonists represents a novel therapeutic approach to brain cancer, including glioblastoma and medulloblastoma. Citation Format: Jacqueline Capuano, Kimberly Vasquez, Katherine Quinlivan, Rachel Bayer, Sarina Virani, Michael Gillespie, Mark Kieran, Charles Serhan, Diane Bielenberg, Dipak Panigrahy. Inhibition of brain cancer progression via resolution of inflammation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7458.

Abstract 6817: Control of breast cancer via pro-resolving mediators

Abstract Tumor recurrence is the principal cause of mortality in breast cancer, yet the underlying mechanisms are not well understood. Anti-estrogen therapy, including tamoxifen, reduces tumor burden by inducing apoptosis and necrosis of cancerous tissue. The resulting cellular debris may stimulate tumor growth by disrupting inflammation resolution and creating pro-inflammatory and pro-tumorigenic microenvironments. Compared to estrogen receptor (ER)-positive breast cancer, ER-negative behaves aggressively, and patients have a poor prognosis due to the lack of treatment options. Here, we demonstrate that breast tumor cells killed by cytotoxic anti-estrogen therapy or chemotherapy (“tumor cell debris”) stimulate primary tumor growth when co-injected with a subthreshold (nontumorigenic) inoculum of tumor cells by triggering a macrophage-derived pro-inflammatory and pro-angiogenic “cytokine storm.” Thus, tumor cell debris is a critical risk factor for aggressive breast cancer growth. To assess whether stimulating the clearance of debris would impact breast cancer progression in vivo, we utilized maresin 1 (MaR1), maresin conjugates in tissue regeneration (MCTR1, MCTR2) and protectin conjugates in tissue regeneration (PCTRs), which are specialized pro-resolving lipid autacoid mediators (SPMs). We treated established models of ER-positive (EO771) and negative (4T1) breast cancer. Each maresin sharply reduced tumor growth in debris-stimulated and spontaneous (e.g. MMTV-PyMT) breast cancer models at nanogram concentrations without toxicity. Notably, PCTR1 inhibited orthotopic triple-negative (4T1) growth and proliferation compared to chemotherapy (paclitaxel) or immunotherapy (anti-cytotoxic T-lymphocyte-associated protein 4, CTLA4). Similarly, PCTR1 alone or in combination with chemotherapy (paclitaxel) reduced gene expression and protein levels of pro-angiogenic factor CXCL12/SDF1 in the ER-negative (4T1) tumor microenvironment. In ER-positive (EO771), a triple combination of PCTR1, chemotherapy (paclitaxel), and immunotherapy (anti-CTLA4) treatment potentiated the immune checkpoint blockade. Maresins also stimulated macrophage phagocytosis of therapy-generated breast tumor cell debris, inhibited tumor angiogenesis, and dampened a therapy-induced cytokine storm, including TNF-α, MIP-2/CXCL2, CCL2/MCP-1, IL- 1ra/IL-1F3, and G-CSF. Expression of SPM receptors (e.g. resolvin D1 (RvD1) receptor ALX/FPR2, resolvin D2 (RvD2) receptor GPR18, maresin 1 (MaR1) receptor LGR6, and resolvin E1 (RvE1) receptor ChemR23) were specifically identified in breast cancer tissue. Taken together, the maresin and protectin pathway mediators may represent a new therapeutic approach to stimulate the resolution of inflammation in breast cancer. Citation Format: Sarina A. Virani, Michael Gillespie, Haixia Yang, Diane R. Bielenberg, Mark W. Kieran, Sui Huang, Charles N. Serhan, Dipak Panigrahy. Control of breast cancer via pro-resolving mediators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6817.

ZmARF1 positively regulates low phosphorus stress tolerance via modulating lateral root development in maize.

Phosphorus (P) deficiency is one of the most critical factors for plant growth and productivity, including its inhibition of lateral root initiation. Auxin response factors (ARFs) play crucial roles in root development via auxin signaling mediated by genetic pathways. In this study, we found that the transcription factor ZmARF1 was associated with low inorganic phosphate (Pi) stress-related traits in maize. This superior root morphology and greater phosphate stress tolerance could be ascribed to the overexpression of ZmARF1. The knock out mutant zmarf1 had shorter primary roots, fewer root tip number, and lower root volume and surface area. Transcriptomic data indicate that ZmLBD1, a direct downstream target gene, is involved in lateral root development, which enhances phosphate starvation tolerance. A transcriptional activation assay revealed that ZmARF1 specifically binds to the GC-box motif in the promoter of ZmLBD1 and activates its expression. Moreover, ZmARF1 positively regulates the expression of ZmPHR1, ZmPHT1;2, and ZmPHO2, which are key transporters of Pi in maize. We propose that ZmARF1 promotes the transcription of ZmLBD1 to modulate lateral root development and Pi-starvation induced (PSI) genes to regulate phosphate mobilization and homeostasis under phosphorus starvation. In addition, ZmERF2 specifically binds to the ABRE motif of the promoter of ZmARF1 and represses its expression. Collectively, the findings of this study revealed that ZmARF1 is a pivotal factor that modulates root development and confers low-Pi stress tolerance through the transcriptional regulation of the biological function of ZmLBD1 and the expression of key Pi transport proteins.

The plant growth promoting rhizobacterium Achromobacter sp. 5B1, rescues Arabidopsis seedlings from alkaline stress by enhancing root organogenesis and hormonal responses

Soil alkalinity is a critical environmental factor for plant growth and distribution in ecosystems. An alkaline condition (pH > 7) is imposed by the rising concentration of hydroxides and cations, and prevails in semiarid and arid environments, which represent more than 25% of the total arable land of the world. Despite the great pressure exerted by alkalinity for root viability and plant survival, scarce information is available to understand how root microbes contribute to alkaline pH adaptation. Here, we assessed the effects of alkalinity on shoot and root biomass production, chlorophyll content, root growth and branching, lateral root primordia formation, and the expression of CYCB1, TOR kinase, and auxin and cytokinin-inducible trangenes in shoots and roots of Arabidopsis seedlings grown in Petri plates with agar-nutrient medium at pH values of 7.0, 7.5, 8.0, 8.5, and 9.0. The results showed an inverse correlation between the rise of pH and most growth, hormonal and genetic traits analyzed. Noteworthy, root inoculation with Achromobacter sp. 5B1, a beneficial rhizospheric bacterium, with plant growth promoting and salt tolerance features, increased biomass production, restored root growth and branching and enhanced auxin responses in WT seedlings and auxin-related mutants aux1–7 and eir1, indicating that stress adaptation operates independently of canonical auxin transporter proteins. Sequencing of the Achromobacter sp. 5B1 genome unveiled 5244 protein-coding genes, including genes possibly involved in auxin biosynthesis, quorum-sensing regulation and stress adaptation, which may account for its plant growth promotion attributes. These data highlight the critical role of rhizobacteria to increase plant resilience under high soil pH conditions potentially through genes for adaptation to an extreme environment and bacteria-plant communication.

Expounding the Environment of Small and Medium Enterprises (SMEs): A Qualitative Study Conducted in Pakistan

The aim of this study is to expound the environment of SMEs by way of identifying, ranking and classifying factors that affect growth of SMEs. The overall design of the study comprises of review of literature, data collection from primary sources and application of modeling techniques. This is a qualitative study that comprises of literature review along with experts’ opinion for exploring environmental factors affecting growth of SMEs. The experts are selected on the basis of non-probability based purposive sampling and data is collected by face to face interview through a questionnaire. The factors are ranked in different levels of importance using Interpretive Structural Model (ISM) which later on are classified in independent, dependent, autonomous and linkage using MICMAC. The results of literature review and experts’ opinion show that there are fifteen important factors that are critical. The results of ISM show that the least critical factors occupying Level I includes ‘age of enterprise’, ‘experience of owner’ and ‘education of owner’, whereas, ‘trade internationalization’ is the most critical factor occupying Level IX. Remaining eleven factors are with effects that range on the continuum of moderate to severe moderate occupying middle position of the model. The results of MICMAC reveal that trade internationalization is categorized as the important independent factor along with seven other factors. Six factors are categorized as dependent factors. Only one factor is classified as autonomous, and as such no factor is categorized in linkage. This is a seminal research study that contributes to the literature by providing new firsthand information on the phenomenon under study by using novel mathematical modeling techniques. This study is helpful to all stakeholders including Government, industry, researchers and academicians in prioritizing the critical factors for revolutionary growth of SME sector.

CREATIVE INDUSTRY OF CITIES AND REGIONS: MAIN FEATURES

The article focuses on the importance of the developing creative industries in cities and regions as impulses for increasing the economic potential of territories and expanding the range of goods and services produced within territories. They could also be of tremendous importance working as translators of the territory’s local identity to the global world. Analysis of recent research and publications underscores the creative sector's importance as a critical growth factor and a magnet for intellectual, creative personnel in the global arena. Theoretical and methodological foundations of the creative economy, popularized in recent decades, continue to be promising scientific developments in the search for progressive drivers of economic growth. Unresolved components within the creative industry demand meticulous examination, outlining primary challenges that persist and merit further exploration. The objectives of the article are to illuminate the pivotal role of creative industries in urban and regional development, emphasizing their contribution to economic, social, and cultural dynamics. The study explores stimulating conditions and production factors propelling the development of creative spheres, contributing to the ongoing discourse on progressive drivers of economic development in the contemporary world. Beyond economic parameters, the paper elucidates the profound intellectual and cultural implications of the creative industry. It serves as a reservoir for generating new knowledge, ideas, and technologies, preserving cultural heritage, promoting intercultural interaction, and transferring knowledge to subsequent generations. The main material of the research emphasizes the role of creative spheres as a special human activity meeting modern requirements for progressive development. The creative industry, as a branch of the economy, is based on the development of ideas, human intellectual activity, and technologies. It is concluded that the main feature of creative industries is the presence of a source of individual creativity, skills and talent with the potential to create jobs and well–being through the production and exploitation of intellectual property. A number of positive effects of developing creative industries (economic, social, cultural, innovative) are highlighted, allowing flexible integration into the new economic reality and contributing to the implementation of mechanisms for generating the creative potential of cities and regions. The development of creative industries ensures the disclosure of creative, intellectual, and innovative potential, adapting to deep and dynamic changes.

Microfluidic-based spatiotemporal control of oxygen concentration in bacteria suspension culture from bulk to the single cells

Oxygen plays a crucial role in microbial growth and metabolism. However, the detailed bacterial responses and regulatory mechanisms toward the change of oxygen are still not completely understood partly due to the lack of real-time measurement and control of dissolved oxygen (DO). Here, we present a novel platform for spatiotemporal and real-time controls of oxygen concentrations by a simple microfluidic design in bacteria suspension culture on chip. The DO concentrations are precisely controlled or flexibly tuned in bioreactor arrays in nanoliter scale. Multiple bioreactor groups with diverse DO control strategies are integrated on a single chip. With our platform, adequate oxygen existed in the microfluidic culture channels and may be the critical factor for the fast growth during bacteria suspension culture. Notably, we extend our platform to mimic the DO oscillation environment and monitor the growth of bulk and single bacterium for many generations. This microfluidic platform exhibits the unique capability of spatiotemporal gas control and detection for microbial suspension culture in nanoliter scale, which can be applied for screening, studying, and culturing the industrial or niche-specific environmental microbiome, at bulk, single cell, or consortia level, responding to oxygen or other gas environment, such as carbon dioxide, ammonia, etc.

Microenvironment-dependent growth of Sezary cells in humanized IL-15 mice.

Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small-animal models. Here, we demonstrate that IL-15 is a critical CTCL growth factor. Importantly, an immunodeficient knock-in mouse model genetically engineered to express human IL-15 uniquely supported the growth of SS patient samples relative to conventional immunodeficient mouse strains. SS patient-derived xenograft (PDX) models recapacitated key pathological features of the human disease, including skin infiltration and spread of leukemic cells to the periphery, and maintained the dependence on human IL-15 upon serial in vivo passaging. Detailed molecular characterization of the engrafted cells by single-cell transcriptomic analysis revealed congruent neoplastic gene expression signatures but distinct clonal engraftment patterns. Overall, we document an important dependence of Sezary cell survival and proliferation on IL-15 signaling and the utility of immunodeficient humanized IL-15 mice as hosts for SS - and potentially other T and NK cell-derived hematologic malignancies - PDX model generation. Furthermore, these studies advocate the thorough molecular understanding of the resultant PDX models to maximize their translational impact.

Simulating the effects of vegetation restoration and climate change on the long-term soil water balance on the Loess Plateau, 2021–2050

In water-limited areas, soil water content (SWC) is a critical factor for plant growth and ecosystem stability. To understand the long-term effects of three different land uses (Vigna radiata: VR, Stipa bungeana: SB, and Medicago sativa: MS) and two climate scenarios (representative concentration pathway 4.5 (RCP45) and nonclimate change (Non_CC)) on water budgets and the mechanisms of dried soil layer (DSL) formation, a new complete multilayered model, OpenKarHydro, was developed. The results showed that the model adequately captured the water budget for different land uses, with root mean square errors (RMSEs) of 0.058, 0.046, and 0.046 and coefficients of determination (R2) of 0.615, 0.605, and 0.582, respectively, for SWC dynamics. This model performance was also demonstrated by the verification of runoff. Sensitivity analysis indicated that the soil porosity (n) was the most sensitive parameter in all land uses. The DSL was primarily caused by higher evapotranspiration (VR: 83.16% vs. 82.48%, SB: 80.62% vs. 77.69%, and MS: 79.93% vs. 76.26%) and canopy interception (VR: 11.92% vs. 11.99%, SB: 17.56% vs. 23.15% and MS: 22.60% vs. 26.19%) in the Non_CC climate pattern than in the RCP45 climate pattern. Climate change has caused an increase in evapotranspiration and interception for all land uses, reducing bottom leakage. Rainfall is sufficient to meet the water demand in the VR plot regardless of climate change; however, the additional water consumption caused by climate warming cannot be offset by the increased rainfall for the SB and MS plots. Compared to Non_CC, RCP45 resulted in increases of 0%, 54.19%, and 57.62% in proportion with extreme drought and decreases of 4.70%, 38.74%, and 5.24% in proportion with no drought for the soil profiles of VR, SB, and MS, respectively. For MS, RCP45 (2026) caused the DSL to penetrate the soil profile (>400 cm) 4 years earlier than in the Non_CC (2030), which should take no more than 5 and 9 years, respectively. OpenKarHydro is a useful tool for optimal water resource management and ecological restoration in water-limited areas.

Epidemiology of Maternal Nutritional Status and Risk of Adverse Birth Outcomes in Undernourished Mothers with Sickle Cell Disease: A Systematic Review and Meta-Analysis Protocol.

In pregnancies complicated by sickle cell disease (SCD), the maternal-fetal dyad is at high risk for mortality and morbidity. In healthy pregnancies, maternal nutritional status is a critical factor for the healthy growth and development of the fetus. However, there are no reviews of the current research on the nutritional status of pregnant women with SCD and pregnancy outcomes. First, we aim to assess the burden of malnutrition in pregnant women with SCD. Next, we aim to systematically evaluate if pregnant women with SCD who have poor nutritional status are at increased risk for adverse birth outcomes compared to pregnant women with sickle cell disease and normal nutritional status. We will systematically search multiple electronic databases. Our exposure is pregnant women with SCD and poor nutritional status. The primary outcomes of interest include low birth weight (categorical) and birth weight z-scores (continuous). We will also evaluate maternal and perinatal outcomes as secondary outcomes. We will evaluate the risk of bias and overall certainty of evidence with Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I), and the overall evidence will be assessed using Grading of Recommendation Assessment, Development, and Evaluation (GRADE) criteria. We will pool findings with a meta-analysis if sufficient homogeneity exists among studies. Findings will be published in a peer-reviewed journal and disseminated to SCD advocacy groups. PROSPERO registration number: 429412.