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Abstract Background One of the main challenges associated with image-based field phenotyping is the variability of illumination. During a single day’s imaging session, or between different sessions on different days, the sun moves in and out of cloud cover and has varying intensity. How is one to know from consecutive images alone if a plant has become darker over time, or if the weather conditions have simply changed from clear to overcast? This is a significant problem to address as colour is an important phenotypic trait that can be measured automatically from images. Results In this work we use an industry standard colour checker to balance the colour in images within and across every day of a field trial conducted over four months in 2016. By ensuring that the colour checker is present in every image we are afforded a ‘ground truth’ to correct for varying illumination conditions across images. We employ a least squares approach to fit a quadratic model for correcting RGB values of an image in such a way that the observed values of the colour checker tiles align with their true values after the transformation. Conclusions The proposed method is successful in reducing the error between observed and reference colour chart values in all images. Furthermore, the standard deviation of mean canopy colour across multiple days is reduced significantly after colour correction is applied. Finally, we use a number of examples to demonstrate the usefulness of accurate colour measurements in recording phenotypic traits and analysing variation among varieties and treatments.

The emphysema death toll has steadily risen over recent decades, causing the disease to become the third most common cause of death worldwide in 2019. Emphysema is currently incurable and could be due to a genetic condition (Alpha-1 antitrypsin deficiency) or exposure to pollutants/irritants, such as cigarette smoke or poorly ventilated cooking fires. Despite the growing burden of emphysema, the mechanisms behind emphysematous pathogenesis and progression are not fully understood by the scientific literature. A key aspect of emphysematous progression is the destruction of the lung parenchyma extracellular matrix (ECM), causing a drastic shift in the mechanical properties of the lung (known as mechanobiology). The mechanical properties of the lung such as the stiffness of the parenchyma (measured as the elastic modulus) and the stretch forces required for inhalation and exhalation are both reduced in emphysema. Fibroblasts function to maintain the structural and mechanical integrity of the lung parenchyma, yet, in the context of emphysema, these fibroblasts appear incapable of repairing the ECM, allowing emphysema to progress. This relationship between the disturbances in the mechanical cues experienced by an emphysematous lung and fibroblast behaviour is constantly overlooked and consequently understudied, thus warranting further research. Interestingly, the failure of current research models to integrate the altered mechanical environment of an emphysematous lung may be limiting our understanding of emphysematous pathogenesis and progression, potentially disrupting the development of novel treatments. This review will focus on the significance of emphysematous lung mechanobiology to fibroblast activity and current research limitations by examining: (1) the impact of mechanical cues on fibroblast activity and the cell cycle, (2) the potential role of mechanical cues in the diminished activity of emphysematous fibroblasts and, finally, (3) the limitations of current emphysematous lung research models and treatments as a result of the overlooked emphysematous mechanical environment.

Abstract Background Efficacy-safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO), have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in 69 patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated LDLC therapy, we assessed efficacy and safety of ALI and EVO. Methods Post-commercially, we started 29 patients on ALI 75 mg, 18 on ALI 150 mg, and 22 on EVO 140 mg every 2 weeks added to a maximally tolerated LDLC-lowering regimen. Since LDLC lowering did not differ between ALI 150 and EVO 140 mg, ALI 150-EVO 140 data were pooled (ALI-EVO). Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed. Results Of the 69 patients, 25 had HeFH, 25 CVD, and 19 had both. At entry, 23 (33%) took statins and 46 (67%) were statin-intolerant. Mean ± SD and median follow-up were 49 ± 13 and 49 weeks on ALI 75 mg, and 37 ± 12 and 33 weeks on ALI-EVO. In the ALI-EVO group (n = 40), median LDLC fell from 165 mg/dl at entry to 70 mg/dl (median − 59%, p 0.05) between ALI 75 mg and ALI-EVO. Conclusion In patients with HeFH and/or CVD, LDLC decreased from 115 to 68 mg/dl (39%) on ALI 75 mg with mean follow-up of 49 weeks, and from 165 to 70 mg/dl (59%) on ALI-EVO over 37 weeks, p

The objective of this study was to analyze data from the National Football League Player Care Foundation Study of Retired NFL Players to understand potential risks for depressive symptoms in former athletes by investigating the relationship between pain and depressive symptoms in a multivariate context, while simultaneously exploring the potential connection with functional limitations. Descriptive statistics were used to describe the study sample and to conduct bivariate comparisons by race and age cohort. Linear regression models were conducted in the subsample of respondents reporting on depressive symptoms using the PHQ-9. Models examine the relationship of bodily pain, injury as a reason for retirement or not re-signing with a team, length of NFL career, sociodemographic characteristics, chronic conditions, and functional limitations to depression. Interaction terms tested whether race and age moderated the effect of bodily pain and functional limitations on depressive symptoms. Bivariate associations revealed no significant differences between younger and older former players in indicators of pain and only slightly higher functional limitations among younger former players. In the multivariate models, pain was significantly associated with depressive symptoms (β = 0.36; p < .01), net of a range of relevant controls. Adding an index of functional limitations reduced this association by nearly half (β = 0.20; p < .01) and functional limitations was significantly associated with depressive symptoms (β = 0.40; p < .01). No statistically significant interactions were found. Overall, bodily pain was strongly associated with depressive symptoms. After accounting for the effects of functional limitations, this association was notably reduced. These results may be useful in identifying aging-related physical declines in relatively younger adult men who may be at the greatest risk for depression. They highlight how physical functionality and activity may mitigate the risk of depression, even in the presence of significant bodily pain.

Introduction Emergency departments (ED) care for society’s most vulnerable older adults who present with exacerbations of chronic disease at the end of life, yet the clinical paradigm focuses on treatment of acute pathologies. Palliative care interventions in the ED capture high-risk patients at a time of crisis and can dramatically improve patient-centred outcomes. This study aims to implement and evaluate Primary Palliative Care for Emergency Medicine (PRIM-ER) on ED disposition, healthcare utilisation and survival in older adults with serious illness.Methods and analysis This is the protocol for a pragmatic, cluster-randomised stepped wedge trial to test the effectiveness of PRIM-ER in 35 EDs across the USA. The intervention includes four core components: (1) evidence-based, multidisciplinary primary palliative care education; (2) simulation-based workshops; (3) clinical decision support; and (4) audit and feedback. The study is divided into two phases: a pilot phase, to ensure feasibility in two sites, and an implementation and evaluation phase, where we implement the intervention and test the effectiveness in 33 EDs over 2 years. Using Centers for Medicare and Medicaid Services (CMS) data, we will assess the primary outcomes in approximately 300 000 patients: ED disposition to an acute care setting, healthcare utilisation in the 6 months following the ED visit and survival following the index ED visit. Analysis will also determine the site, provider and patient-level characteristics that are associated with variation in impact of PRIM-ER.Ethics and dissemination Institutional Review Board approval was obtained at New York University School of Medicine to evaluate the CMS data. Oversight will also be provided by the National Institutes of Health, an Independent Monitoring Committee and a Clinical Informatics Advisory Board. Trial results will be submitted for publication in a peer-reviewed journal.Trial registration number NCT03424109; Pre-results

In this paper we report on an automated procedure to capture and characterize the detailed structure of a crop canopy by means of stereo imaging. We focus attention specifically on the detailed characteristic of canopy height distribution-canopy shoot area as a function of height-which can provide an elaborate picture of canopy growth and health under a given set of conditions. We apply the method to a wheat field trial involving ten Australian wheat varieties that were subjected to two different fertilizer treatments. A novel camera self-calibration approach is proposed which allows the determination of quantitative plant canopy height data (as well as other valuable phenotypic information) by stereo matching. Utilizing the canopy height distribution to provide a measure of canopy height, the results compare favourably with manual measurements of canopy height (resulting in an R2 value of 0.92), and are indeed shown to be more consistent. By comparing canopy height distributions of different varieties and different treatments, the methodology shows that different varieties subjected to the same treatment, and the same variety subjected to different treatments can respond in much more distinctive and quantifiable ways within their respective canopies than can be captured by a simple trait measure such as overall canopy height.

During the last two decades, Haemophilus influenzae serotype a (Hia) emerged as an important cause of invasive disease in Canadian First Nations and Inuit, and Alaskan Native populations, with the highest rates reported in young children. Immunocompetent adults, in contrast to children, do not typically develop invasive Hia disease. To clarify factors responsible for an increased burden of invasive Hia disease in certain population groups we studied serum bactericidal activity (SBA) against Hia and quantified IgG and IgM specific to Hia capsular polysaccharide in healthy adult members of two First Nations communities: 1) with reported cases of invasive Hia disease (Northern Ontario, NO), and 2) without reported cases (Southern Ontario, SO), in comparison to non-First Nations living in proximity to the NO First Nations community, and non-First Nations elderly non-frail Canadians from across the country (total of 110 First Nations and 76 non-First Nations). To elucidate the specificity of bactericidal antibodies, sera were absorbed with various Hia antigens. Naturally acquired SBA against Hia was detected at higher rates in First Nations (NO, 80%; SO, 96%) than non-First Nations elderly Canadians (64%); the SBA titres in First Nations were higher than in non-First Nations elderly Canadians (P0.05). Among First Nations, SBA was mediated predominantly by IgM, and by both antibodies specific to Hia capsular polysaccharide and lipooligosaccharide. CONCLUSIONS:The SBA against Hia is frequently present in sera of First Nations adults regardless of the burden of Hia disease observed in their community; it may represent part of the natural antibody repertoire, which is potentially formed in this population under the influence of certain epigenetic factors. Although the nature of these antibodies deserves further studies to understand their origin, the data suggest that they may represent important protective mechanism against invasive Hia disease.

In an essay on architectural representation, Stan Allen (2000) wrote about a paradoxical nature of built forms: “Buildings are presumably more tangible and physically present than drawings, yet it is only in the experience of the building that the most intangible aspects of reality can be made visible.” Documenting a heritage site is difficult since no representational method can make an exact copy without loss. This paper specifically examines panoramic recording media and related technologies as new means to archive and represent architectural heritage. It looks at cost effective and widely available platforms such as 360 video recording, YouTube, and immersive Head Mounted Display (HMD) equipment. Tests with subjects are conducted to probe how the experience of recorded panorama compares to the spatial and temporal experience in the physical space. For instance, the subjects with HMD are tested for the ability of sensing the correct scale and proportion of spatial forms in the playback. Through analysis of the test results, discussions are made as to the roles such systems can play in conveying the spatial environment, especially in representing some of its intangible aspects. The paper shows examples of prototype designs for exhibition that utilize panoramically recorded onsite footage in derivative forms. Recordings of sites such as Palladio’s villas and the Acropolis in Athens are used to demonstrate spatial and temporal editing, interactive panoramic walk-through combined with a map, and creation of a framed-video narrative reduced from panoramic videos. These methods illustrate a range of possibilities that put each dislocated recording back into context while controlling a balance between the viewer’s exploration and the intent of the curation, and shed a light on what is often difficult to achieve by other means of representations.

Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections. Unlike in mouse models, the mechanisms underlying SAg-associated immunosuppression in humans are ill-defined. In this work, we have identified a population of innate-like T cells, called mucosa-associated invariant T (MAIT) cells, as the most powerful source of pro-inflammatory cytokines after exposure to SAgs. We have utilized primary human peripheral blood and hepatic mononuclear cells, mouse MAIT hybridoma lines, HLA-DR4-transgenic mice, MAIThighHLA-DR4+ bone marrow chimeras, and humanized NOD-scid IL-2Rγnull mice to demonstrate for the first time that: i) mouse and human MAIT cells are hyperresponsive to SAgs, typified by staphylococcal enterotoxin B (SEB); ii) the human MAIT cell response to SEB is rapid and far greater in magnitude than that launched by unfractionated conventional T, invariant natural killer T (iNKT) or γδ T cells, and is characterized by production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-2, but not IL-17A; iii) high-affinity MHC class II interaction with SAgs, but not MHC-related protein 1 (MR1) participation, is required for MAIT cell activation; iv) MAIT cell responses to SEB can occur in a T cell receptor (TCR) Vβ-specific manner but are largely contributed by IL-12 and IL-18; v) as MAIT cells are primed by SAgs, they also begin to develop a molecular signature consistent with exhaustion and failure to participate in antimicrobial defense. Accordingly, they upregulate lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin-3 (TIM-3), and/or programmed cell death-1 (PD-1), and acquire an anergic phenotype that interferes with their cognate function against Klebsiella pneumoniae and Escherichia coli; vi) MAIT cell hyperactivation and anergy co-utilize a signaling pathway that is governed by p38 and MEK1/2. Collectively, our findings demonstrate a pathogenic, rather than protective, role for MAIT cells during infection. Furthermore, we propose a novel mechanism of SAg-associated immunosuppression in humans. MAIT cells may therefore provide an attractive therapeutic target for the management of both early and late phases of severe SAg-mediated illnesses.

Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible and biodegradable zinc-tricalcium phosphate (Zn-TCP) as an alternative biomimetic material for bone fracture repair. Zn-TCP samples implanted in a rat tibial defect model for eight weeks were compared with unfilled defect and beta-tricalcium phosphate showing accelerated bone regeneration compared with the control groups, with statistically significant bone mineral density and bone mineral content growth. CT images of the defect showed restoration of cancellous bone in Zn-TCP and only minimal growth in control group. Histological slices reveal bone in-growth within the pores and porous chamber of the material detailing good bone-material integration with the presence of blood vessels. These results exhibit the future potential of biomimetic Zn-TCP as bone grafts for bone fracture repair.

A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP) and transforming growth factor beta (TGF-β) exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use.

In this article we propose a novel tool that takes an initial segmented image and returns a more accurate segmentation that accurately captures sharp features such as leaf tips, twists and axils. Our algorithm utilizes basic a-priori information about the shape of plant leaves and local image orientations to fit active contour models to important plant features that have been missed during the initial segmentation. We compare the performance of our approach with three state-of-the-art segmentation techniques, using three error metrics. The results show that leaf tips are detected with roughly one half of the original error, segmentation accuracy is almost always improved and more than half of the leaf breakages are corrected.

This study evaluates an aerial and ground imaging platform for assessment of canopy development in a wheat field. The dependence of two canopy traits, height and vigour, on fertilizer treatment was observed in a field trial comprised of ten varieties of spring wheat. A custom-built mobile ground platform (MGP) and an unmanned aerial vehicle (UAV) were deployed at the experimental site for standard red, green and blue (RGB) image collection on five occasions. Meanwhile, reference field measurements of canopy height and vigour were manually recorded during the growing season. Canopy level estimates of height and vigour for each variety and treatment were computed by image analysis. The agreement between estimates from each platform and reference measurements was statistically analysed. Estimates of canopy height derived from MGP imagery were more accurate (RMSE = 3.95 cm, R2 = 0.94) than estimates derived from UAV imagery (RMSE = 6.64 cm, R2 = 0.85). In contrast, vigour was better estimated using the UAV imagery (RMSE = 0.057, R2 = 0.57), compared to MGP imagery (RMSE = 0.063, R2 = 0.42), albeit with a significant fixed and proportional bias. The ability of the platforms to capture differential development of traits as a function of fertilizer treatment was also investigated. Both imaging methodologies observed a higher median canopy height of treated plots compared with untreated plots throughout the season, and a greater median vigour of treated plots compared with untreated plots exhibited in the early growth stages. While the UAV imaging provides a high-throughput method for canopy-level trait determination, the MGP imaging captures subtle canopy structures, potentially useful for fine-grained analyses of plants.

The morphology of plant root anatomical features is a key factor in effective water and nutrient uptake. Existing techniques for phenotyping root anatomical traits are often based on manual or semi-automatic segmentation and annotation of microscopic images of root cross sections. In this article, we propose a fully automated tool, hereinafter referred to as RootAnalyzer, for efficiently extracting and analyzing anatomical traits from root-cross section images. Using a range of image processing techniques such as local thresholding and nearest neighbor identification, RootAnalyzer segments the plant root from the image's background, classifies and characterizes the cortex, stele, endodermis and epidermis, and subsequently produces statistics about the morphological properties of the root cells and tissues. We use RootAnalyzer to analyze 15 images of wheat plants and one maize plant image and evaluate its performance against manually-obtained ground truth data. The comparison shows that RootAnalyzer can fully characterize most root tissue regions with over 90% accuracy.

The aim of this study was to examine the bone regeneration properties of beta-tricalcium phosphate hydrothermally converted from foraminifera carbonate exoskeleton in the repair of rat calvarial defect. These natural materials possess unique interconnected porous network with uniform pore size distribution, which can be potentially advantageous. In total, 20 adult male Wistar rats received full-thickness calvarial defect with a diameter of 5 mm. The rate of newly formed bone was measured radiologically by X-ray and micro-computed tomography and by histologic examination. After 2 weeks, the beta-tricalcium phosphate group exhibited full closure of the defect site, while control group remained unrestored at the end of the 6-week experimentation. It was observed that the newly regenerated bone thickened over the course of the experiment in the beta-tricalcium phosphate group. No soft tissue reaction was observed around the beta-tricalcium phosphate implant and the rats remained healthy. These results showed that repair of the calvarial defect can be achieved by biomimetic beta-tricalcium phosphate macrospheres, which hold potential for application as bone grafts for bone augmentation surgeries.

Adipose tissue-derived stromal cells, termed ASCs, play an important role in regenerative applications. They resemble mesenchymal stem cells owing to their inexhaustibility, general differentiation potential, and plasticity and display a series of cell-specific and cluster-of-differentiation (CD) marker profiles similar to those of other somatic stem cells. Variations in phenotypes or differentiation are intimately associated with CD markers. The purpose of our study was to exhibit distinct populations of ASCs with differing characteristics for osteogenic differentiation. The primary cell batch of murine-derived ASCs was extracted from subcutaneous adipose tissue and the cells were sorted for the expression of the surface protein molecules CD90 and CD105 using flow cytometry. Each cell population sorted for CD90 and CD105 was analyzed for osteogenic potency after cell culture. The results suggested that ASCs exhibit distinct populations with differing characteristics for osteogenic differentiation: unsorted ASCs stimulated comparable mineralized nodule formation as bone marrow stromal cells (BMSCs) in osteogenic medium and viral transfection for BMP2 accelerated the formation of mineralized nodules in CD90 and/or CD105 positive ASCs with observation of decrease in CD105 expression after 14 days. Future studies assessing different immunophenotypes of ASCs should be undertaken to develop cell-based tissue engineering.

Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin.

The aim of this study was to evaluate the therapeutic efficacy of biomimetic zinc-containing tricalcium phosphate (ZnTCP) produced by hydrothermally converting calcium carbonate exoskeletons from foraminifera, in the treatment of osteoporotic mice. X-Ray powder diffraction showed crystallographic structures matching JCPDS profile for tricalcium phosphate. Mass spectroscopy used to calculate total composition amount showed similar amount of calcium (5×10(4) µg/g) and phosphate (4×10(4) ppm) after conversion and the presence of zinc (5.18×10(3) µg/g). In vitro zinc release showed no release in PBS buffer and

Accumulation of 7-Ketocholesterol (7KCh) in lipid deposits has been implicated in a variety of chronic diseases including atherosclerosis, Alzheimer's disease and age-related macular degeneration. 7KCh is known to be pro-inflammatory and cytotoxic to various types of cultured cells but little is known about its effects in vivo. In this study we have investigated the effects of 7KCh in vivo by implanting biodegradable wafers into the anterior chamber of the rat eye. The wafers were prepared using a mixture of two biodegradable polymers with different amounts of 7KCh. The 7KCh-containing implants induced massive angiogenesis and inflammation. By contrast, no angiogenesis and very little inflammation were observed with cholesterol-containing implants. The neovessel growth was monitored by fluorescein angiography. Neovessels were observed 4 days post implantation and peaked between 7 to 10 days. The angiography and isolectin IB(4) labeling demonstrated that the neovessels originated from the limbus and grew through the cornea. Immunolabeling with anti-CD68 suggested that the 7KCh-containing implants had extensive macrophage infiltration as well as other cell types. A significant increase in VEGF was also observed in 7KCh-containing implants by fluorescent immunolabeling and by immunoblot of the aqueous humor (AH). Direct measurement of VEGF, IL-1β and GRO/KC demonstrated a marked elevation of these factors in the AH of the 7KCh-implants. In summary this study demonstrates two important things: 1) 7KCh is pro-angiogenic and pro-inflammatory in vivo and 2) implants containing 7KCh may be used to create a novel angiogenesis model in rats.

We report a 15-year-old girl who underwent a mid-carpal fusion for undiagnosed impaction-fractures of the capitate, lunate, and triquetrum after a fall on her outstretched left hand in a dorsiflexed and radially deviated position. The joint was dis-impacted, and the height of the lunate was restored using a cortical bone graft. The damaged proximal capitate articular surface was decorticated to facilitate fusion, as was the lunotriquetral articulation. Kirschner wires were inserted along the coronal plane. At the one-year follow-up, the patient had achieved a satisfactory range of motion and fusion of the capitate-lunate-triquetral articulations.

In RNA-seq data analysis, condensing the gene count matrix size is pivotal for downstream investigations, particularly pathway analysis. For this purpose, harnessing machine learning attracts increasing interest, while conventional methodologies depend on p-value comparisons. In this study, 20 tissue samples from real-world cervical cancers were subjected to sequencing, followed by the application of the Mclust algorithm to delineate an optimal cluster. By stratifying tumor budding into high and low groups and quantifying the epithelial-to-mesenchymal transition (EMT) score to scrutinize tumor budding, we discerned 24 EMT-related genes, with 5 showing strong associations with cervical cancer prognosis. Our observations elucidate a biological flow wherein EMT, Matrix Metallopep-tidase 2 (MMP2), and extracellular matrix (ECM) degradation are interconnected, ultimately leading to collagen type VI and exacerbating the prognosis of cervical cancer. The present study underscores an alternative method for selecting useful EMT-related genes by employing an appropriate clustering algorithm, thereby avoiding classical methods while unveiling novel insights into cervical cancer etiology and prognosis. Moreover, when comparing high and low tumor budding, collagen type VI emerges as a potential gene marker for the prognosis of cervical cancer.