Pathogen genomic epidemiology has the potential to provide a deep understanding of population dynamics, facilitating strategic planning of interventions, monitoring their impact, and enabling timely responses, and thereby supporting control and elimination efforts of parasitic tropical diseases. Plasmodium vivax, responsible for most malaria cases outside Africa, shows high genetic diversity at the population level, driven by factors like sub-patent infections, a hidden reservoir of hypnozoites, and early transmission to mosquitoes. While Latin America has made significant progress in controlling Plasmodium falciparum, it faces challenges with residual P. vivax. To characterize genetic diversity and population structure and dynamics, we have analysed the largest collection of P. vivax genomes to date, including 1474 high-quality genomes from 31 countries across Asia, Africa, Oceania, and America. While P. vivax shows high genetic diversity globally, Latin American isolates form a distinctive population, which is further divided in sub-populations and occasional clonal pockets. Genetic diversity within the continent was associated with the intensity of transmission. Population differentiation exists between Central America and the North Coast of South America, vs. the Amazon Basin, with significant gene flow within the Amazon Basin, but limited connectivity between the Northwest Coast and the Amazon Basin. Shared genomic regions in these parasite populations indicate adaptive evolution, particularly in genes related to DNA replication, RNA processing, invasion, and motility -- crucial for the parasite's survival in diverse environments. Understanding these population-level adaptations is crucial for effective control efforts, offering insights into potential mechanisms behind drug resistance, immune evasion, and transmission dynamics.

Fungal pathogens challenge the integrity of natural environments while threatening global food security and forestry industries. The occurrence of new and emerging plant fungal infections is on the rise, particularly in the context of land use change, but has gone largely unnoticed because of inadequate detection methods. To effectively address existing knowledge gaps relating to the emergence of fungal pathogens associated with land use change, an interdisciplinary approach to research is required. Such research should bridge gaps between the fundamental studies of taxonomy, ecology and distribution modelling, as well as the applied sciences related to land use management, agricultural production and plantation forests. Without a cohesive plan linking these disciplines and sectors, it would be impossible to fully understand how fungal pathogens enter an ecosystem and how to mitigate the resultant damage in the future. There is a need to develop sustainable plant protection strategies, requiring fresh insight into the biology and evolution of the corresponding pathogens. Currently, there are very few early warning systems or mechanisms for predicting a fungal pathogen outbreak in agricultural or tree-based systems; it is thus imperative that, as a first step, we generate a fundamental understanding of how these outbreaks occur. In the following chapter, we aim to discuss these issues and make suggestions on how to better research and manage land use change and the related fungal pathogens. We suggest that in order to better predict how or when an outbreak might occur, scientists should begin by studying the natural reservoirs of fungal pathogens before determining stable states in fungal communities and associated communities of fungal pathogens. Next, it is important to determine how these communities change as they are exposed to external pressures, such as land use conversion. Finally, it is crucial to better understand what environmental triggers lead to increased pathogenicity in fungal pathogens and related shifts in life mode strategies, causing beneficial fungi to shift into a pathogenic mode.

In recent years, how to inhibit the proliferation of tumor cells and the expression of stem genes has become one of the focuses of scientists in treating cancer. Cancer stem cell (CSC) is a kind of cell group with self-renewal ability in tumors, and is considered as one of the driving factors in the process of tumorigenesis. The Hippo signaling pathway is a highly conserved signaling pathway in biological evolution that plays an important role in cell proliferation, tissue development, and organ size. In this article, Hippo signaling pathway and its mechanism in Cancer stem cell were briefly reviewed, and the prospect of tumor treatment was proposed.

Aim The Arctic ecosystems are exposed to amplified climate warming and, in some regions, to rapidly developing economic activities. This study assesses, models and maps the geographic patterns of community-level plant species richness in the Western Siberian Arctic and estimates the relative impact of environmental and anthropogenic factors driving these patterns. With our study, we aim at contributing towards conservation efforts for Arctic plant diversity. Location Western Siberian Arctic, Russia. Methods We investigated the relative importance of environmental and anthropogenic predictors of community-level plant species richness in the Western Siberian Arctic using macroecological models trained with an extensive geobotanical dataset. We included vascular plants, mosses and lichens in our analysis, as non-vascular plants substantially contribute to species richness in the Arctic. Results We found that the mean community-level plant species richness in this vast Arctic region does not decrease with increasing latitude. Instead, we identified an increase in species richness from South-West to North-East, which can be explained by environmental factors. We found that paleoclimatic factors exhibit higher explained deviance compared to contemporary climate, potentially indicating a lasting impact of ancient climate on tundra species richness. We also show that the existing protected areas cover only a small fraction of the regions with highest species richness. Conclusions Our results reveal complex spatial patterns of community-level species richness in the Western Siberian Arctic. We show that climatic factors such as temperature (including paleotemperature) and precipitation are the main drivers of plant species richness in this area, and the role of relief is secondary. We suggest that while plant species richness is mostly driven by environmental factors, an improved spatial sampling is needed to robustly assess anthropogenic impact on species richness. Our approach can be used to design conservation strategies and to investigate drivers of plant species richness in other arctic regions.

Accurate short-term forecasting of carryover storage is crucial for effective reservoir management and water resource decision-making. Real-time information plays a vital role in reservoir operation decisions, highlighting the need to incorporate such information in carryover storage forecasting. In this study, we propose a dynamic prediction model (DPM) that integrates static and dynamic factors, including runoff forecasting, real-time water level, and remaining time from carryover level, to improve short-term reservoir operation. The model is applied to three reservoirs in China, and its performance is evaluated using statistical measures. The results demonstrate that the DPM surpasses the traditional static prediction model, yielding enhanced accuracy in reservoir carryover storage prediction. The inclusion of weakly correlated real-time information contributes to the improvement of forecasting accuracy. Moreover, we observe variations in the importance of dynamic factor combinations across different seasons. Notably, in the wet season, the combination of runoff forecasting and real-time water level factors significantly enhances forecast accuracy. This study highlights the potential of employing DPMs that incorporate real-time information for short-term reservoir operation, leading to improved reservoir management and decision-making. The findings emphasize the importance of considering real-time information and seasonality in carryover storage forecasting, thereby facilitating more effective water resource utilization and reducing the risks associated with floods and droughts.

Semantic communication has attracted significant attention as a key technology for emerging 6G communications. Though it has lots of potentials specially for high volume media communications, still there is no proper quality metric for modelling the semantic noise in semantic communications. This paper proposes an autoencoder based image quality metric to quantify the semantic noise. An autoencoder is initially trained with the reference image to generate the encoder decoder model and calculate its latent vector space. Once it is trained, a semantically generated/received image is inserted to the same autoencoder to create the corresponding latent vector space. Finally, both vector spaces are used to define the Euclidean space between two spaces to calculate the Mean Square Error between two vector spaces, which is used to measure the effectiveness of the semantically generated image. Results indicate that the proposed model has a correlation coefficient of 88% with the subjective quality assessment. Furthermore, the proposed model is tested as a metric to evaluate the image quality in conventional image coding. Results indicate that the proposed model can also be used to replace conventional image quality metrics such as PSNR,SSIM,MSSIM,UQI, VIFP, and SSC whereas these conventional metrics completely failed in semantic noise modelling.

Introduction: While several studies have examined the role of T cells and related cytokines in the development of chronic spontaneous urticaria (CSU), there is a limited amount of research focusing on the changes in cytokine levels during omalizumab treatment. The primary objective of this study was to investigate the inflammatory cytokine profile (including IL-4, IL-5, IL-10, IL-13, IL-17, IL-31, IL-33, and TNFα) among CSU patients undergoing to omalizumab treatment. Materials and Methods: Plasma levels of cytokines were measured using ELISA. Measurements were taken before CSU treatment, at the 3rd and 6th months of omalizumab treatment, and once in the control group. The severity of the patients’ disease was assessed using the weekly Urticaria Activity Score(UAS7), and disease control was evaluated using the Urticaria Control Test(UCT). Results: Thirty-one CSU patients and 56 age- and gender-matched healthy controls were included. Plasma levels of IL-4 and IL-33 were significantly lower in patients with CSU compared to healthy controls (p=0.001; p=0.038, respectively). During omalizumab treatment, IL-4 levels showed a significant increase in the 3rd month compared to baseline (p=0.01), and IL-5 levels significantly decreased in the 6th month compared to both the 3rd month and baseline (6th month vs baseline; p=0.006, 6th month vs 3rd month; p=0.001). Discussion: One potential mechanism of action for omalizumab may involve its regulatory effects on type 2 inflammatory cytokines in CSU patients. This finding partially explains the efficacy of anti-IL-4/13 treatments in chronic spontaneous urticaria. Further investigations on drugs targeting type 2 inflammatory cytokines in CSU are warranted.

The coupling between subducted slabs and trailing plates is often conceptualised in terms of a net in-plane force. If a significant fraction of upper-mantle slab buoyancy (e.g. ~ 25%) were transferred in this manner, a net in-plane force on the order of 5-10 TN/m would be typical of the trailing plates. Results from a numerical subduction model are presented here which question both the magnitude and-perhaps more profoundly-the mode of force transmission. In this model the subducting plate (SP) driving force is predominantly supplied by differences in gravitational potential energy (GPE). The GPE associated with plate downbending (flexural topography) provides about half the total driving force. The magnitude of the trench GPE is related to the amplitude of topography, but is mediated by the internal stress distributions associated with bending. Above the elastic core, the stress is Andersonian and vertical normal stresses are lithostatic. This implies horizontal gradients in the vertical normal stress, across columns of different elevation in the outer slope. The bulk of the trench GPE arises from this upper, extensional section the lithosphere. Vertical shear stress (and horizontal gradients thereof) are concentrated in the elastic core of the slab, where principal stresses rotate through 90 degrees. In this region, horizontal gradients in vertical normal stress rapidly diminish; they fully equilibrate at about twice the neutral plane depth. For the deepest trenches on Earth, these relationships imply trench GPE of up to about 5 TN/m. The model demonstrates that mantle slabs can drive plate tectonics simply through downbending, where the predominant mode of slab-plate coupling is via the vertical shear force and bending moment. 

Many animals have colorations that resemble eyes, but the functions of such eyespots are debated. Caligo martia (Godart, 1824) butterflies have large ventral hind wing eyespots, and we aimed to test whether these eyespots act to deflect or to thwart bird attacks through intimidation in a natural community in a Restinga Forest in austral South America. We used four types of paper facsimiles: unmanipulated C. martia (with eyespots, WE), facsimiles with UV enhanced eyespots (UV), camouflaged facsimiles lacking eyespots (CM), and light-coloured facsimiles that were not camouflaged and lacked eyespots (NC). Two experiments were performed: Experiment 1 used facsimiles in a natural resting position, and in Experiment 2 facsimiles were positioned with the wings open, with ventral wing surfaces and body exposed to viewers. In both experiments facsimiles were placed in two forest sites, organized in 50 blocks with four facsimiles each, and checked for predator attacks every 24 h for five consecutive days. While WE and UV facsimiles were mostly attacked in non-vital areas (wings), most bird attacks on CM were directed at vital body areas. Notably, CM facsimiles had lower attack probability than WE, UV and NC. Our results indicate that C. martia eyespots appear to have a deflection function. Eyespots did not appear to reduce attack rates, suggesting that local bird species were not intimidated. Both eyespots and camouflage can be considered efficient functional traits in defence against predation in forest environments, and experiments focusing on local predators and prey are key to our understanding of wing pattern evolution in Lepidoptera.

Computation of the critical point of complex fluid mixtures is an important part of thermodynamic phase behaviour computations. While algorithms for these calculations are well established, they are often slow when the number of constituting components is large. In this work, we propose a new procedure to significantly accelerate critical point calculations by leveraging deep neural network (DNN) models. A DNN model for critical point predictions of a given mixture is first trained based on the critical points of such a mixture with various compositions. Such a DNN model is then used to initialize both of the commonly used algorithms for mixture critical point calculations: root finding and global minimization. We demonstrate that when using the DNN-based predictions to initialize the root-finding-based and optimization-based algorithms, we can achieve 50-90% and 80-90% reductions in the number of required iterations, respectively.

With the rapid development of modern industry, it is necessary to effectively recycle precious metals such as gold and palladium from e-waste. IL (ionic liquid) is an efficient extractant with high boiling points, non-flammability, and high thermal stability. The properties of IL can be improved by modifying the n-substituted groups of their cations, enhancing the separation efficiency of noble metals. Thus, two guanidinium ILs, with the substituents of -R and -OR, were synthesized to extract Au(III) from a hydrochloric acid medium. These ILs exhibited excellent extraction properties, including high selectivities, rapid kinetics, and significant extraction capacities. The maximum extraction capacities of Au(Ⅲ) by [diMTMG][Tf2N] and [diPTMG][Tf2N] were 519.4mg/g and 427.9mg/g, respectively, achieving rapid extraction equilibrium within 30s. The introduction of o-containing functional atoms enhanced extraction capacity and selectivity. The extraction mechanism involving anion exchange was confirmed by slope method, jobs method, as well as ultraviolet and nuclear magnetic resonance analysis.

MicroRNAs (miRNAs) are a kind of tiny RNA that regulates gene expression by snatching up mRNA. MicroRNAs (miRNAs) may have a role in either promoting or inhibiting tumor growth depending on the activity of the genes they target. Even though DCIS is often misdiagnosed as breast cancer, it may be a precursor to invasive ductal carcinoma. The preinvasive stage of DCIS is characterized by alterations in the expression of miRNAs and other genetic processes necessary for the invasive development of DCIS. MicroRNAs have been shown to have a role in breast cancer development by regulating oncogenic and tumor-suppressive pathways. Hormone signaling, cell-cell adhesion, epithelial-to-mesenchymal transition, transforming growth factor signaling, maintenance of cancer stem cells, and manipulation of the extracellular matrix are all processes that have been demonstrated to be influenced by miRNAs in DCIS. Furthermore, exosomal DCIS miRNAs may enhance invasive growth by altering the tumor microenvironment. In this article, we take a look back at the miRNAs that have been linked to DCIS and how they may play a role in the development of invasive disease. We also briefly review the present status of miRNA treatment development and the problems that have been encountered so far, as well as the important future prospects for research into miRNA function with the goal of miRNA therapy development for DCIS.

Evaluating the relative impacts of land use and climate change on community change is challenging – and their impact may be contextdependent. Here, we use long-term nocturnal macro-moth community data to evaluate the relative impacts of changing habitats vs. changing climates on community composition and diversity of moths in different landscape settings and for moth species associated with different traits. We used Hierarchical Modelling of Species Communities to pinpoint moth species’ responses to climate and habitat composition in 109 sites across Finland. To characterise context-dependence, we extended this framework with conditional variance partitioning analysis. We used the model predictions to evaluate the relative effect of drivers on community diversity across Finland. The landscape context (i.e. the habitat composition around the site and its changes) emerged as the dominant driver of macro-moth communities. At the site level, where forests or shrub-like vegetation dominates, variation in species occurrence was mostly explained by local habitat conditions. In heterogeneous and water-dominated habitats, both habitat and climate variability contributed equally to patterns in species occurrence. At the species level, macro-moth responses to drivers of change varied according to their host plant affinity but independently of their wingspan. Climate and habitat changes can thus contribute congruently or unequally to community change, depending on the habitat. At the community level, traits also give insights into trends in and temporal variability of biogeographic patterns. Our results underpin the importance of land-use change as a key driver of community change – even among heatsensitive ectotherms. We also demonstrate that the sensitivity of local communities to climate and land use change varies among habitat profiles. Overall, our results highlight the importance of accounting for local conditions to understand and predict community patterns under global change.

The most prevalent form of cancer in women, breast cancer displays molecular heterogeneity. Recent years have seen a shift toward more physiologically based medicines in an effort to lessen the potentially devastating side effects of treating molecular variety. The Hippo signaling pathway has been linked to the alpha subtype of estrogen receptors in their ability to influence cell destiny in human breast cells. This route controls cell differentiation, which in turn controls organ growth, regeneration, and healing. It also controls the survival of tissue-specific stem cells, cell proliferation, and cell death. Hippo signaling is mediated by the kinases MST1, MST2, LATS1, and LATS2, as well as the adaptor proteins SAV1 and MOB. By phosphorylating yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), two effectors of the Hippo pathway, these kinases inhibit the expression of their downstream target genes. The kinase cascade of the Hippo signaling pathway is critically involved in every kind of cancer. Preventing breast cancer requires an understanding of the concepts behind this kinase cascade. The development of numerous cancers, including breast cancer, has been linked to microRNAs in recent years. In contrast, our understanding of the relationships between miRNAs and the key proteins of the Hippo signaling pathway in the breast is still in its infancy. In this overview, we have centered our attention on the Hippo signaling system, its components, its role in breast cancer, and the miRNAs and associated pathways that regulate it.

Breast cancer therapy may fail due to the disease's limiting pathogenesis processes, including as epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), and drug resistance. Functionally significant mediators in these pathogenic processes include lncRNAs and miRNAs, which are master regulators of gene expression. Complex regulatory networks of post-transcriptional gene control are formed by the intricate crosstalks between these non-coding RNAs. The lncRNA-miRNA axis may have tumor suppressor or oncogenic effects depending on the individual lncRNA/miRNA interaction, making its definition crucial for establishing targetability. We provide a comprehensive review of the literature on lncRNA-miRNA interactions in breast cancer, highlighting their role in the molecular pathways that control EMT, CSCs, and treatment resistance. We also discuss the possible new mechanisms of lncRNA-miRNA interactions in breast cancer and examine the well-studied mechanisms already known to exist.

The purpose of this article is to provide light on the function of microRNAs in triple-negative breast cancer (TNBC). We used search engines like PubMed, ScienceDirect, and Springer to get the information we needed. Only 197 of the articles were given a thorough evaluation. We chose papers that not only discussed TNBC but also various forms of breast cancer using miRNA profiling and/or analysis. Our in-depth analysis led to the classification of miRNAs into groups in which individual member's miRNAs have important roles in TNBC via many mechanisms including tumorigenesis, invasion, and metastasis. Diagnostics, prognosis, therapy, and apoptosis. TNBC is a particularly deadly kind of breast cancer. Thus, new methods are required for correct diagnosis, prognosis, and therapy. In this study, we compile the most recent data on miRNA profiling to help with diagnosis, therapy, and prognosis. bolster the strategy for managing TNBC.

In 2018, there were an estimated 8.6 million new cases of cancer in women and 4.2 million deaths from cancer worldwide. In addition, 20% of women who are diagnosed with breast cancer will go on to develop metastases. Therefore, there is an urgent need to discover new molecular markers for the diagnosis and prognostic prediction of metastatic illness and to create novel treatment agents. MicroRNAs (miRNAs) have been studied extensively in breast cancer and have been shown to induce numerous alterations in the expression of genes involved in carcinogenesis. In this review, we compile recent information on breast cancer-specific miRNA expression profiles and their role in regulating invasive processes, in conjunction with alterations in cytoskeletal structure, cell-cell adhesion junctions, cancer cell-extracellular matrix interactions, tumor microenvironments, epithelial-to-mesenchymal transitions, and cancer cell stem abilities. Finally, we discussed the role of miRNA isoforms and exosome-mediated miRNA transfer in cancer invasiveness, and we focused on how epigenetic regulation affects individual miRNAs and how those miRNAs interact with other regulatory genes. While more work is needed to fully understand the role of miRNAs in cancer, the findings presented here help advance the treatment of metastatic disease.

Grade Level: [Suitable grade level, e.g., 6-8]Duration: 50 minutes

In 2018, there were significant cancer statistics indicating 8.6 million cases of female cancers and a global count of 4.2 million cancer-related deaths. Among these, breast cancer emerged as the most common malignancy in females, with approximately twenty percent of cases progressing to metastasis. Unfortunately, metastatic breast cancer poses a formidable challenge for successful treatment, necessitating the urgent identification of new molecular markers for diagnosis and prognostic prediction, as well as the development of innovative therapeutic approaches. One area of focus in breast cancer research involves differentially expressed microRNAs (miRNAs) and their role in modifying the expression of genes associated with tumor growth. These miRNAs have been extensively studied in the context of breast cancer. In this overview, we summarize recent data regarding the specific miRNA expression profiles observed in breast cancer and their involvement in regulating various invasive processes. These processes encompass changes in cytoskeletal structure, cell-cell adhesion junctions, interactions between cancer cells and the extracellular matrix, tumor microenvironments, epithelial-to-mesenchymal transitions, and the acquisition of cancer stem cell-like properties. Additionally, we explore the epigenetic regulation of individual miRNAs and their interactions with other regulatory genes. Furthermore, we examine the function of miRNA isoforms and the transfer of miRNAs through exosomes, elucidating their contribution to cancer invasiveness. While ongoing research continues to unravel the full extent of miRNA functioning in cancer, the outcomes presented here contribute to the advancement of metastatic cancer management and offer insights into potential therapeutic strategies.

The objective of this study was to explore the dynamics of efficiency and productivity of Greek public hospitals during the crisis, as well as to review the effect of implemented policies on hospital efficiency before and the implementation of the claw-back for hospital pharmaceutical expenditure. We implemented Data Envelopment Analysis and decomposed the Malmquist productivity index (MPI) to investigate the fluctuations of the Greek public hospital productivity frontier and therefore their technical efficiency between 2009 and 2019. The MPI components allowed us to capture the frontier shift, as well as pure efficiency changes and scale efficiency changes. Through the period 2009-2019 hospital inputs were reduced drastically. Doctors were reduced by 54% while beds were reduced by 15%. Hospital expenditure was decreasing between 2009 and 2015 but increased by 23% since due to fixed hospital budgets and the “claw-back”. Moreover, output seems to have increased. Patient discharges increased by 14% while diagnostic procedures were reduced by 10% between 2009 and 2016 but have been continuously rising since. Nonetheless, under variable returns to scale (VRS) average hospital efficiency was stable (~75%) for most of the period under study while declining since 2016. Policymakers in Greece have always chosen to implement cost- or input-oriented policies, instead of opting to improve outputs and quality of services. Our analysis indicated that fixed-budget-oriented reforms have impacted hospital efficiency negatively by creating a counterincentive to adopting best practices and improving hospital efficiency. Highlights Technical Efficiency under CRS was stable in Greece (0.70) over the period 2012-2016, and declined to 0.51 in 2019. Hospital Fixed Budget reforms had a negative impact on hospital efficiency. During the economic crisis 2009-2019 hospital inputs were reduced drastically Memorandum Policies introduced by Troika focused exclusively in reducing cost and not improving efficiency.

To detect hydrogen in materials at the atomic scale, atom probe tomography is now regularly used. In order to avoid cumbersome cryo-preparation to suppress diffusion, often hydrogen is charged only into the finished specimen. Here, the use of hydrogen gas over electrochemical hydrogen has the advantage that the specimen is not contaminated with an electrolyte. So far, this ‘charging’ has been done in large, expensive systems. Here, we introduce small devices that enable the exposure of atom probe specimens to hydrogen and potentially other gases, using only very small gas volumes. This enables the operation in regular laboratory environments without additional safety measures. These devices can be used to expose the specimen to hydrogen up to 10 bar / 90 °C. Higher temperatures may be attained with small changes. Validation of the success of charging with these setups is demonstrated through experiments employing deuterium charging of palladium atom probe tips.

In the human pathogen Staphylococcus aureus, branched-chain fatty acids (BCFAs) are the most abundant fatty acids in membrane phospholipids, and strains deficient for their synthesis experience BCFAs auxotrophy in laboratory culture and attenuated virulence during infection. Thus, membrane integrity is essential for S. aureus pathogenesis. Furthermore, the membrane of S. aureus is among the main targets for antibiotic therapy. Therefore, determining the mechanisms involved in BCFAs synthesis is critical to manage S. aureus infections. Here, we report that overexpression of the bona fide acyl-CoA synthetase gene mbcS (formerly SAUSA300_2542) restores BCFAs synthesis in strains lacking the canonical biosynthetic pathway catalyzed by the branched-chain a-keto acid dehydrogenase (BKDH) complex. We demonstrate that the acyl-CoA synthetase activity of MbcS activates branched-chain carboxylic acids, and is required by S. aureus to utilize the isoleucine derivative 2-methylbutyraldehyde to restore BCFAs synthesis in S. aureus. Based on the ability of some staphylococci to convert branched-chain aldehydes into their respective branched-chain carboxylic acids and our findings demonstrating that branched-chain aldehydes are in fact BCFAs precursors, we propose that MbcS promotes the scavenging of exogenous branched-chain carboxylic acids (BCCAs) and mediates branched-chain fatty acids synthesis via a de novo alternative pathway.

The effect of pruning severity on tree growth was analyzed by change point detection using segmented regression. The present study applied this analysis to a well-known published data set including diameter growth response, tree age, pruning severity and pretreatment crown size. First, multiple regression analysis was performed to assess the effect of tree age, pruning severity and pretreatment crown size on diameter growth response. Next. segmented regression analysis was performed to assess the effect of pruning severity on diameter growth response. The results of the multiple regression showed that diameter growth response was significantly influenced by pruning severity and pretreatment crown size. The results of the segmented regression showed that in the whole data set, an abrupt change toward a decrease in diameter growth response was detected at 25% of the live crown removed. However, in the group of fully crowned and open-grown, diameter growth response continuously decreased with increasing pruning severity with no significant abrupt change, whereas in the group of 70-90% live crown, diameter growth response did not significantly decrease up to the break point (53% crown removed) and then abruptly decreased. This may be the first study to show the numerical evaluation of the effect of pruning severity on tree growth by change point analysis.

Background: Gastric cancer(GC) is a common and poor prognosis malignant solid tumour, the application of immunotherapy has improved the prognosis of patients greatly, but the precise immunotherapy strategy is still the difficult problem of immunotherapy. Mendel randomization is a way to demonstrate exposure and outcomes at a causal level. Mendel randomization trial is therefore an excellent way of looking at the causal link between immune cells and the risk of GC, with the aim of providing new insights into immunotherapy regimens for GC patients. Method: Genetic instrumental variables(IVs) for GC were obtained from a genome wide association study (GWAS). Inverse-variance weighted (IVW) method was used as the primary analysis. Simple-median method, weighted-median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used as the further analysis. Uni-cox and lasso were used to select genes related to GC and survival model was constructed. Through many data of GC patients, we further explored the relationship between risk models and prognosis of GC patients, association between tumour mutation load(TMB) and microsatellite instability state(MSI). Result: We obtained 731 immune cells from previous studies. From these cells, we screened six immune cells closely associated with GC. Based on the SNPs of 6 immune cells, we obtained 77 genes. After Cox and lasso analysis, we obtained 5 immune cell related genes. The 5-gene risk model can divide patients into two GC groups with different prognosis. High risk GC patients had higher suppressive immune cell infiltration, lower TMB, lower tumour cell stemness, and higher TIDE scores. Conclusion: This study based on a variety of data from MR analysis demonstrated the association between immune cells and GC risk at the causal level. 6 immune cell-related genes are associated with TMB, MSI and immunotherapy sensitivity in GC patients.