Complex adaptive systems-based framework for modeling the health impacts of climate change.

Introduction: Climate change is a global phenomenon with far-reaching consequences, and its impact on human health is a growing concern. The intricate interplay of various factors makes it challenging to accurately predict and understand the implications of climate change on human well-being. Conventional methodologies have limitations in comprehensively addressing the complexity and nonlinearity inherent in the relationships between climate change and health outcomes. Objectives: The primary objective of this paper is to develop a robust theoretical framework that can effectively analyze and interpret the intricate web of variables influencing the human health impacts of climate change. By doing so, we aim to overcome the limitations of conventional approaches and provide a more nuanced understanding of the complex relationships involved. Furthermore, we seek to explore practical applications of this theoretical framework to enhance our ability to predict, mitigate, and adapt to the diverse health challenges posed by a changing climate. Methods: Addressing the challenges outlined in the objectives, this study introduces the Complex Adaptive Systems (CAS) framework, acknowledging its significance in capturing the nuanced dynamics of health effects linked to climate change. The research utilizes a blend of field observations, expert interviews, key informant interviews, and an extensive literature review to shape the development of the CAS framework. Results and discussion: The proposed CAS framework categorizes findings into six key sub-systems: ecological services, extreme weather, infectious diseases, food security, disaster risk management, and clinical public health. The study employs agent-based modeling, using causal loop diagrams (CLDs) tailored for each CAS sub-system. A set of identified variables is incorporated into predictive modeling to enhance the understanding of health outcomes within the CAS framework. Through a combination of theoretical development and practical application, this paper aspires to contribute valuable insights to the interdisciplinary field of climate change and health. Integrating agent-based modeling and CLDs enhances the predictive capabilities required for effective health outcome analysis in the context of climate change. Conclusion: This paper serves as a valuable resource for policymakers, researchers, and public health professionals by employing a CAS framework to understand and assess the complex network of health impacts associated with climate change. It offers insights into effective strategies for safeguarding human health amidst current and future climate challenges.

Feasibility of three-dimensional artificial intelligence algorithm integration with intracardiac echocardiography for left atrial imaging during atrial fibrillation catheter ablation.

AIMS: Intracardiac echocardiography (ICE) is a useful but operator-dependent tool for left atrial (LA) anatomical rendering during atrial fibrillation (AF) ablation. The CARTOSOUND FAM Module, a new deep learning (DL) imaging algorithm, has the potential to overcome this limitation. This study aims to evaluate feasibility of the algorithm compared to cardiac computed tomography (CT) in patients undergoing AF ablation. METHODS AND RESULTS: In 28 patients undergoing AF ablation, baseline patient information was recorded, and three-dimensional (3D) shells of LA body and anatomical structures [LA appendage/left superior pulmonary vein/left inferior pulmonary vein/right superior pulmonary vein/right inferior pulmonary vein (RIPV)] were reconstructed using the DL algorithm. The selected ultrasound frames were gated to end-expiration and max LA volume. Ostial diameters of these structures and carina-to-carina distance between left and right pulmonary veins were measured and compared with CT measurements. Anatomical accuracy of the DL algorithm was evaluated by three independent electrophysiologists using a three-anchor scale for LA anatomical structures and a five-anchor scale for LA body. Ablation-related characteristics were summarized. The algorithm generated 3D reconstruction of LA anatomies, and two-dimensional contours overlaid on ultrasound input frames. Average calculation time for LA reconstruction was 65 s. Mean ostial diameters and carina-to-carina distance were all comparable to CT without statistical significance. Ostial diameters and carina-to-carina distance also showed moderate to high correlation (r = 0.52-0.75) except for RIPV (r = 0.20). Qualitative ratings showed good agreement without between-rater differences. Average procedure time was 143.7 ± 43.7 min, with average radiofrequency time 31.6 ± 10.2 min. All patients achieved ablation success, and no immediate complications were observed. CONCLUSION: DL algorithm integration with ICE demonstrated considerable accuracy compared to CT and qualitative physician assessment. The feasibility of ICE with this algorithm can potentially further streamline AF ablation workflow.

Fully 3D Printed Tin Selenide (SnSe) Thermoelectric Generators with Alternating n-Type and p-Type Legs.

Tin selenide (SnSe) has attracted much attention in the field of thermoelectrics since the discovery of the record figure of merit (zT) of 2.6 ± 0.3. While there have been many publications on p-type SnSe, to manufacture efficient SnSe thermoelectric generators, ann-type is also required. Publications on n-type SnSe, however, are limited. This paper reports a pseudo-3D-printing technique to fabricate bulk n-type SnSe elements, by utilizing Bi as a dopant. Various Bi doping levels are investigated and characterized over a wide range of temperatures and through multiple thermal cycles. Stable n-type SnSe elements are then combined with printed p-type SnSe elements to fabricate a fully printed alternating n- and p-type thermoelectric generator, which is shown to produce 145 µW at 774 K.

Toward improved sediment management and coastal resilience through efficient permitting in California.

The value of sediment for helping coastal habitats and infrastructure respond to sea level rise is widely recognized. Across the country, coastal managers are seeking ways to beneficially use sediment sourced from dredging and other projects to counter coastal erosion and protect coastal resources. However, these projects are difficult to permit and have been slow to actualize. This paper draws on interviews with sediment managers and regulators in California to explore the challenges and opportunities for habitat restoration and beach nourishment within the current permitting regime. We find that permits are costly, difficult to obtain, and sometimes stand as a barrier to more sustainable and adaptive sediment management. We next characterize streamlining approaches and describe entities and ongoing efforts within California that apply them. Finally, we conclude that to keep pace with coastal losses due to climate change impacts, efforts toward efficient permitting must be accelerated and approaches diversified to support coastal resilience practices state-wide, in a timeframe that will allow coastal managers to innovate and adapt.

Immersive virtual reality simulated learning environment versus role-play for empathic clinical communication training.

INTRODUCTION: The use of immersive virtual reality simulated learning environments (VR SLEs) for improving clinical communication can offer desirable qualities including repetition and determinism in a safe environment. The aim of this study was to establish whether the mode of delivery, VR SLE versus clinical role-play, could have a measurable effect on clinical empathic communication skills for MRI scenarios. METHODS: A split-cohort study was performed with trainee practitioners (n = 70) and qualified practitioners (n = 9). Participants were randomly assigned to four groups: clinician VR (CVR), clinician role-play (CRP), trainee VR (TVR), and trainee RP (TRP). Clinical communication skills were assessed using two methods: firstly, a self-reported measure - the SE-12 communication questionnaire and, secondly, a training and assessment tool developed by a panel of experts. RESULTS: Participants in the VR trainee (TVR) and clinician (CVR) groups reported 11% (P < 0.05) and 7.2% (P < 0.05) improvements in communication confidence post training, whereas trainees assigned to the role-play (TRP) intervention reported a 4.3% (P < 0.05) improvement. Empirical assessment of communication training scores assessing a participant's ability to select empathic statements showed the TVR group performed 5% better on average than their role-play counterparts (P < 0.05). CONCLUSION: The accuracy of participant's selection of appropriate empathic responses was shown to differ significantly following the training intervention designed to improve interactions with patients that present for an MRI scan. The results may demonstrate the capacity for immersion into an emotional narrative in a VR environment to increase the user's susceptibility for recalling and selecting empathic terminology.

"Innocent as a LAMS": Does Spontaneous Fistula Closure (Secondary Intention), After EUS-Directed Transgastric ERCP (EDGE) via 20-mm Lumen-Apposing Metal Stent, Confer an Increased Risk of Persistent Fistula and Unintentional Weight Gain?

BACKGROUND AND AIMS: Persistent gastrogastric or jejunogastric fistula is theoretically a concerning sequela of EUS-directed transgastric ERCP/EUS (EDGE), as it may functionally reverse the malabsorptive mechanism of Roux-en-Y gastric bypass (RYGB). Prior EDGE studies, using predominantly 15-mm (diameter) lumen-apposing metal stents (LAMS) and fistula closure by primary intent, collectively report 9% persistent fistula rate, without a clear weight gain association. Our study determines the incidence of persistent fistula, and its association with unintentional weight gain, among recipients of EDGE via 20-mm LAMS followed by spontaneous fistula closure (secondary intent). METHODS: We conducted a dual-center prospective cohort study of 22 RYGB patients who underwent EDGE using 20-mm between 3/2018 and 10/2019. After LAMS extraction, all GGFs/JGFs were allowed to heal spontaneously. Objective testing for persistent fistula and total body weight (TBW) occurred a minimum of 8 weeks after LAMS extraction. RESULTS: Persistent fistula was identified in 9 patients (41%). Longer LAMS dwell time (median 77-days) was observed in the persistent fistula group, compared to those with durable spontaneous fistula closure (median 35-days) (p = 0.03). Weight gain of ≥ 5% TBW occurred in 56% (n = 5) of patients with persistent fistula, compared to 15% (n = 2) of patients with spontaneous fistula closure (p = 0.128). Four patients with symptomatic persistent fistulas underwent attempted endoscopic fistula closure a median 7.5 months after LAMS extraction. Durable fistula closure occurred in the single patient who received argon plasma coagulation plus endoscopic suturing, whereas fistula dehiscence occurred in 3/3 (100%) patients with endoscopic suturing monotherapy. CONCLUSIONS: Larger LAMS diameter (20-mm), longer LAMS dwell time, and spontaneous fistula closure may be technical factors that increase the likelihood of post-EDGE persistent fistula. Post-EDGE persistent fistula has not been shown by ours or other studies to be significantly associated with unintentional weight gain; however, this may be due to small sample size. We question the utility of routine fistula closure by primary intent and suggest a personalized approach to post-EDGE fistula management.

Quantification of Student Radiographic Patient Positioning Using an Immersive Virtual Reality Simulation.

INTRODUCTION: Immersive virtual reality (VR) simulation environments facilitate novel ways for users to visualize anatomy and quantify performance relative to expert users. The ability of software to provide positional feedback before a practitioner progresses with subsequent stages of examinations has broad implications for primary and allied healthcare professionals, particularly with respect to health and safety (eg, exposing to x-rays). The effect of training student-radiographers (radiology technicians), with a VR simulation environment was quantitatively assessed. METHODS: Year 1 radiography students (N = 76) were randomly split into 2 cohorts, each of which were trained at performing the same tasks relating to optimal hand positioning for projection x-ray imaging; group 1 was trained using the CETSOL VR Clinic software, whereas group 2 was trained using conventional simulated role-play in a real clinical environment. All participants completed an examination 3 weeks after training. The examination required both posterior-anterior and oblique hand x-ray positioning tasks to be performed on a real patient model. The analysis of images from the examination enabled quantification of the students' performance. The results were contextualized through a comparison with 4 expert radiographers. RESULTS: Students in group 1 performed on average 36% (P < 0.001) better in relation to digit separation, 11% (P ≤ 0.001) better in terms of palm flatness and 23% (P < 0.05) better in terms of central ray positioning onto the third metacarpal. CONCLUSION: A significant difference in patient positioning was evident between the groups; the VR clinic cohort demonstrated improved patient positioning outcomes. The observed improvement is attributed to the inherent task deconstruction and variety of visualization mechanisms available in immersive VR environments.

Light-Induced Reversible DNA Ligation of Gold Nanoparticle Superlattices.

DNA-mediated self-assembly of nanoparticles has been of great interest because it enables access to nanoparticle superstructures that cannot be synthesized otherwise. However, the programmability of higher order nanoparticle structures can be easily lost under DNA denaturing conditions. Here, we demonstrate that light can be employed as an external stimulus to master the stability of nanoparticle superlattices (SLs) via the promotion of a reversible photoligation of DNA in SLs. The oligonucleotides attached to the nanoparticles are encoded to ligate using 365 nm light, effectively locking the SLs and rendering them stable under DNA denaturing conditions. The reversible process of unlocking these structures is possible by irradiation with light at 315 nm, recovering the structures to their natural state. Our work inspires an alternative research direction toward postassembly manipulation of nanoparticle superstructures using external stimuli as a tool to enrich the library of additional material forms and their application in different media and environments.

Importance of publishing research varies by doctors' career stage, specialty and location of work.

PURPOSE: To investigate whether publishing research is an important aspect of medical careers, and how it varies by specialty and rural or metropolitan location. METHODS: Annual national panel survey (postal or online) of Australian doctors between 2008 and 2016, with aggregated participants including 11 263 junior doctors not enrolled in a specialty ('pre-registrars'), 9745 junior doctors enrolled as specialist trainees, non-general practitioner (GP) ('registrars') and 35 983 qualified as specialist consultants, non-GP ('consultants'). Main outcome was in agreement that 'research publications are important to progress my training' (junior doctors) or 'research publications are important to my career' (consultants). RESULTS: Overall, the highest proportion agreeing were registrars (65%) and pre-registrars (60%), compared with consultants (36%). After accounting for key covariates, rural location was significantly associated with lower importance of publishing research for pre-registrars (OR 0.69, 95% CI 0.61 to 0.78) and consultants (OR 0.69, 95% CI 0.63 to 0.76), but not for registrars. Compared with anaesthetics, research importance was significantly higher for pre-registrars pursuing surgery (OR 4.46, 95% CI 3.57 to 5.57) and obstetrics/gynaecology careers, for registrars enrolled in surgery (OR 2.97, 95% CI 2.34 to 3.75) and internal medicine training, and consultants of internal medicine (OR 1.84, 95% CI 1.63 to 2.08), pathology, radiology and paediatrics. CONCLUSIONS: This study provides new quantitative evidence showing that the importance of publishing research is related to medical career stages, and is most important to junior doctors seeking and undertaking different specialty training options. Embedding research requirements more evenly into specialty college selection criteria may stimulate uptake of research. Expansion of rural training pathways should consider capacity building to support increased access to research opportunities in these locations.

Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos.

Regulating nuclear histone balance is essential for survival, yet in early Drosophila melanogaster embryos many regulatory strategies employed in somatic cells are unavailable. Previous work had suggested that lipid droplets (LDs) buffer nuclear accumulation of the histone variant H2Av. Here, we elucidate the buffering mechanism and demonstrate that it is developmentally controlled. Using live imaging, we find that H2Av continuously exchanges between LDs. Our data suggest that the major driving force for H2Av accumulation in nuclei is H2Av abundance in the cytoplasm and that LD binding slows nuclear import kinetically, by limiting this cytoplasmic pool. Nuclear H2Av accumulation is indeed inversely regulated by overall buffering capacity. Histone exchange between LDs abruptly ceases during the midblastula transition, presumably to allow canonical regulatory mechanisms to take over. These findings provide a mechanistic basis for the emerging role of LDs as regulators of protein homeostasis and demonstrate that LDs can control developmental progression.

The Diagnosis of Pleural Tumors Other Than Mesothelioma.

CONTEXT: - Pleural pathology has been dominated by discussions relating to the diagnosis, prognosis, etiology, and management of malignant mesothelioma. However, there exists a diverse group of other neoplasms that involve the pleura; the most common by far is metastatic carcinoma, usually of pulmonary origin. Other metastatic tumors of varied histogenesis do occur but are less common. Primary pleural neoplasms other than diffuse malignant mesothelioma are either uncommon or rare and have received less attention. OBJECTIVE: - To provide a review of those diverse tumors that can involve the pleura other than mesothelioma in order to facilitate their accurate diagnosis. DATA SOURCES: - Review of relevant literature published via PubMed and other search engines. CONCLUSIONS: - A wide variety of tumors can involve the pleura. In most cases, the approach of considering the morphologic features with appropriate immunohistochemistry, in the correct clinical context, allows for a confident diagnosis. For a number of those soft tissue tumors that are well recognized in the pleura, such as solitary fibrous tumor, desmoid-type fibromatosis, synovial sarcoma, and epithelioid hemangioendothelioma, novel markers now exist based on an understanding of the individual tumors' molecular characteristics. Primary pleural lymphomas are rare with poor prognosis. They represent localized specific diffuse large B-cell lymphomas, with either post-germinal center B-cell or plasma cell lineage, arising in the context of either immunodeficiency or immune sequestration and with viral infection.

Compounding effects of sea level rise and fluvial flooding.

Sea level rise (SLR), a well-documented and urgent aspect of anthropogenic global warming, threatens population and assets located in low-lying coastal regions all around the world. Common flood hazard assessment practices typically account for one driver at a time (e.g., either fluvial flooding only or ocean flooding only), whereas coastal cities vulnerable to SLR are at risk for flooding from multiple drivers (e.g., extreme coastal high tide, storm surge, and river flow). Here, we propose a bivariate flood hazard assessment approach that accounts for compound flooding from river flow and coastal water level, and we show that a univariate approach may not appropriately characterize the flood hazard if there are compounding effects. Using copulas and bivariate dependence analysis, we also quantify the increases in failure probabilities for 2030 and 2050 caused by SLR under representative concentration pathways 4.5 and 8.5. Additionally, the increase in failure probability is shown to be strongly affected by compounding effects. The proposed failure probability method offers an innovative tool for assessing compounding flood hazards in a warming climate.

Adversity, emotion recognition, and empathic concern in high-risk youth.

Little is known about how emotion recognition and empathy jointly operate in youth growing up in contexts defined by persistent adversity. We investigated whether adversity exposure in two groups of youth was associated with reduced empathy and whether deficits in emotion recognition mediated this association. Foster, rural poor, and comparison youth from Swaziland, Africa identified emotional expressions and rated their empathic concern for characters depicted in images showing positive, ambiguous, and negative scenes. Rural and foster youth perceived greater anger and happiness in the main characters in ambiguous and negative images than did comparison youth. Rural children also perceived less sadness. Youth's perceptions of sadness in the negative and ambiguous expressions mediated the relation between adversity and empathic concern, but only for the rural youth, who perceived less sadness, which then predicted less empathy. Findings provide new insight into processes that underlie empathic tendencies in adversity-exposed youth and highlight potential directions for interventions to increase empathy.

Impaired burrowing is the most prominent behavioral deficit of aging htau mice.

htau mice are deficient of murine tau but express all six human tau isoforms, leading to gradual tau misprocessing and aggregation in brain areas relevant to Alzheimer's disease. While histopathological changes in htau mice have been researched in the past, we focused here on functional consequences of human tau accumulation. htau mice and their background controls - murine tau knock-out (mtau(-/-)) and C57Bl/6J mice - underwent a comprehensive trial battery to investigate species-specific behavior, locomotor activity, emotional responses, exploratory traits, spatial and recognition memory as well as acquisition, retention and extinction of contextual fear at two, four, six, nine and twelve months of age. In htau mice, tau pathology was already present at two months of age, whereas deficits in food burrowing and spatial working memory were first noted at four months of age. At later stages the presence of human tau on a mtau(-/-) background appeared to guard cognitive performance; as mtau(-/-) but not htau mice differed from C57Bl/6J mice in the food burrowing, spontaneous alternation and object discrimination tasks. Aging mtau(-/-) mice also exhibited increased body mass and locomotor activity. These data highlight that reduced food-burrowing performance was the most robust aspect of the htau phenotype with aging. htau and mtau(-/-) deficits in food burrowing pointed at the necessity of intact tau systems for daily life activities. While some htau and mtau(-/-) deficits overlap, age differences between the two genotypes may reflect distinct functional effects and compared to C57Bl/6J mice, the htau phenotype appeared stronger than the mtau(-/-) phenotype at young ages but milder with aging.

Enchondroma Protuberans of the Ulna in a Pediatric Patient: A Case Report.

CASE: We report the case of a 3-year-old boy who presented with a distal ulnar fracture through a mixed sclerotic and lytic expansile lesion. The underlying lesion, an enchondroma protuberans, can mimic either benign or malignant bone tumors. It was successfully treated with casting and intralesional treatment. CONCLUSION: Enchondroma protuberans is a rare entity that mimics enchondroma, osteochondroma, periosteal chondroma, or chondrosarcoma. Diagnosis is typically made through both radiographic and histologic means. In this case, the pathologic fracture was successfully treated with casting followed by intralesional curettage and bone-grafting. There was no evidence of recurrence at 18 months.

Spatial access disparities to primary health care in rural and remote Australia.

Poor spatial access to health care remains a key issue for rural populations worldwide. Whilst geographic information systems (GIS) have enabled the development of more sophisticated access measures, they are yet to be adopted into health policy and workforce planning. This paper provides and tests a new national-level approach to measuring primary health care (PHC) access for rural Australia, suitable for use in macro-level health policy. The new index was constructed using a modified two-step floating catchment area method framework and the smallest available geographic unit. Primary health care spatial access was operationalised using three broad components: availability of PHC (general practitioner) services; proximity of populations to PHC services; and PHC needs of the population. Data used in its measurement were specifically chosen for accuracy, reliability and ongoing availability for small areas. The resultant index reveals spatial disparities of access to PHC across rural Australia. While generally more remote areas experienced poorer access than more populated rural areas, there were numerous exceptions to this generalisation, with some rural areas close to metropolitan areas having very poor access and some increasingly remote areas having relatively good access. This new index provides a geographically-sensitive measure of access, which is readily updateable and enables a fine granulation of access disparities. Such an index can underpin national rural health programmes and policies designed to improve rural workforce recruitment and retention, and, importantly, health service planning and resource allocation decisions designed to improve equity of PHC access.

Accessing doctors at times of need-measuring the distance tolerance of rural residents for health-related travel.

BACKGROUND: Poor access to doctors at times of need remains a significant impediment to achieving good health for many rural residents. The two-step floating catchment area (2SFCA) method has emerged as a key tool for measuring healthcare access in rural areas. However, the choice of catchment size, a key component of the 2SFCA method, is problematic because little is known about the distance tolerance of rural residents for health-related travel. Our study sought new evidence to test the hypothesis that residents of sparsely settled rural areas are prepared to travel further than residents of closely settled rural areas when accessing primary health care at times of need. METHODS: A questionnaire survey of residents in five small rural communities of Victoria and New South Wales in Australia was used. The two outcome measures were current travel time to visit their usual doctor and maximum time prepared to travel to visit a doctor, both for non-emergency care. Kaplan-Meier charts were used to compare the association between increased distance and decreased travel propensity for closely-settled and sparsely-settled areas, and ordinal multivariate regression models tested significance after controlling for health-related travel moderating factors and town clustering. RESULTS: A total of 1079 questionnaires were completed with 363 from residents in closely-settled locations and 716 from residents in sparsely-settled areas. Residents of sparsely-settled communities travel, on average, 10 min further than residents of closely-settled communities (26.3 vs 16.9 min, p < 0.001), though this difference was not significant after controlling for town clustering. Differences were more apparent in terms of maximum time prepared to travel (54.1 vs 31.9 min, p < 0.001). Differences of maximum time remained significant after controlling for demographic and other constraints to access, such as transport availability or difficulties getting doctor appointments, as well as after controlling for town clustering and current travel times. CONCLUSIONS: Improved geographical access remains a key issue underpinning health policies designed to improve the provision of rural primary health care services. This study provides empirical evidence that travel behaviour should not be implicitly assumed constant amongst rural populations when modelling access through methods like the 2SFCA.

High EMT Signature Score of Invasive Non-Small Cell Lung Cancer (NSCLC) Cells Correlates with NFκB Driven Colony-Stimulating Factor 2 (CSF2/GM-CSF) Secretion by Neighboring Stromal Fibroblasts.

We established co-cultures of invasive or non-invasive NSCLC cell lines and various types of fibroblasts (FBs) to more precisely characterize the molecular mechanism of tumor-stroma crosstalk in lung cancer. The HGF-MET-ERK1/2-CREB-axis was shown to contribute to the onset of the invasive phenotype of Calu-1 with HGF being secreted by FBs. Differential expression analysis of the respective mono- and co-cultures revealed an upregulation of NFκB-related genes exclusively in co-cultures with Calu-1. Cytokine Array- and ELISA-based characterization of the "cytokine fingerprints" identified CSF2 (GM-CSF), CXCL1, CXCL6, VEGF, IL6, RANTES and IL8 as being specifically upregulated in various co-cultures. Whilst CXCL6 exhibited a strictly FB-type-specific induction profile regardless of the invasiveness of the tumor cell line, CSF2 was only induced in co-cultures of invasive cell lines regardless of the partnered FB type. These cultures revealed a clear link between the induction of CSF2 and the EMT signature of the cancer cell line. The canonical NFκB signaling in FBs, but not in tumor cells, was shown to be responsible for the induced and constitutive CSF2 expression. In addition to CSF2, cytokine IL6, IL8 and IL1B, and chemokine CXCL1 and CXCL6 transcripts were also shown to be increased in co-cultured FBs. In contrast, their induction was not strictly dependent on the invasiveness of the co-cultured tumor cell. In a multi-reporter assay, additional signaling pathways (AP-1, HIF1-α, KLF4, SP-1 and ELK-1) were found to be induced in FBs co-cultured with Calu-1. Most importantly, no difference was observed in the level of inducibility of these six signaling pathways with regard to the type of FBs used. Finally, upon tumor fibroblast interaction the massive induction of chemokines such as CXCL1 and CXCL6 in FBs might be responsible for increased recruitment of a monocytic cell line (THP-1) in a transwell assay.