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Background/Objectives: Endometriosis (END) is a painful gynecological condition. Clinical examination, imaging, and laparoscopy can provide a definitive diagnosis of END. Nonetheless, non-invasive biomarkers could help enhance and streamline the diagnostic process. Micro-RNAs (miRNAs), a family of small non-coding RNAs, could serve as useful non-invasive biomarkers for END. The aim of this study was to perform serum miRNA profiling in a retrospective cohort of women to identify miRNAs that are differentially expressed in END compared to control patients. Methods: RNA was isolated from serum samples of 67 END patients and 60 control women. The expression profile of a 754-miRNA panel was studied with RT-qPCR performed on a QuantStudio 12K Flex with the TaqMan OpenArray miRNA panel. A Censored Regression Model was used for miRNA differential expression analysis. Several gene-enrichment algorithms were employed to identify pathways related to the target genes of differentially expressed miRNAs. Results: One hundred and thirty miRNAs were detected in at least 75% of samples from either the END or the control group. Sixteen miRNAs were significantly modulated between the END and control groups. Enrichment analysis identified targets significantly overrepresented in numerous pathways involved in biological processes related to END, including inflammation, angiogenesis, cellular invasion, cell-cycle/cell proliferation, and estrogen and progesterone hormonal signaling. Conclusions: Our study indicates that differentially expressed miRNAs between END patients and controls can be identified through liquid biopsy. Our findings also suggest a potential role for serum miRNAs in the pathophysiology of END, warranting further investigations for their use as non-invasive biomarkers.

The Association of Peasants of Fondwa (APF), a grassroots organization led by a visionary Haitian Spiritan priest, established the private nonprofit University of Fondwa (UNIF) in Haiti in 2004. The University aims to fill a gap in educational opportunities for rural youth and to develop community leaders able to steward food security, sustainable farm animal husbandry, and small business development. Since the institution’s foundation, University faculty members have explored low-input sustainable agriculture techniques, which were inspired by strategies shared earlier by Cuban agronomists and adapted to the Fondwa region’s mountainous terrain. While the University has faced and continues to confront many challenges related to its sustainability as an institution, this article describes the processes by which its faculty and students have conducted diagnoses of soils and crop choices, the innovations they have developed and introduced to improve harvest productivity in rural Haiti and, especially, the ways and means by which they have sought to share such (re)thinking of traditional practices with local farmers. We argue that the University of Fondwa faculty’s close collaboration with local farmers and the agricultural techniques they have refined thereby have not only improved food security for the families involved but have also contributed to the creation of social capital in the countryside and enabled participating Haitian farmers to imagine a path toward food sovereignty. In addition, by educating farmers and providing them tools to improve their food production, the University has worked to close the deep inequality gap that exists between urban and rural Haiti.

Colorectal cancer represents an important oncological challenge both for its incidence, which makes it an important health problem, and for its biological complexity, which has made clinical results very difficult in terms of outcome for this category of patients. To date these diseases should not be treated as a single entity but it is necessary to distinguish colorectal cancers based on characteristics that nowadays are essential to have greater therapeutic benefits. These include the sideness of the disease, the state of microsatellites, the presence of prognostic and predictive mutations of response to treatments currently available in clinical practice, which are associated with new therapeutic targets. The greatest challenge in the future will be to circumvent the resistance mechanisms that make this disease very difficult to treat with good long-term results by studying effective combination treatments with a good toxicity profile. Once such combinations or targeted treatments are consolidated, it will be desirable to shift the best therapies to the first line treatment to make them immediately accessible to the patient. It will also be essential to refine the selection of patients who can benefit from these treatments.

Type-2 Familial Partial Lipodystrophy (FPLD2), a rare lipodystrophy caused by LMNA mutations, is characterized by a loss of subcutaneous fat from the trunk and limbs and excess accumulation of adipose tissue in the neck and face. Several studies have reported that the mineralocorticoid receptor (MR) plays an essential role in adipose tissue differentiation and functionality. We previously showed that brown preadipocytes isolated from a FPLD2 patient’s neck aberrantly differentiate towards the white lineage. As this condition may be related to MR activation, we suspected altered MR dynamics in FPLD2. Despite cytoplasmic MR localization in control brown adipocytes, retention of MR was observed in FPLD2 brown adipocyte nuclei. Moreover, overexpression of wild-type or mutated prelamin A caused GFP-MR recruitment to the nuclear envelope in HEK293 cells, while drug-induced prelamin A co-localized with endogenous MR in human preadipocytes. Based on in silico analysis and in situ protein ligation assays, we could suggest an interaction between prelamin A and MR, which appears to be inhibited by mineralocorticoid receptor antagonism. Importantly, the MR antagonist spironolactone redirected FPLD2 preadipocyte differentiation towards the brown lineage, avoiding the formation of enlarged and dysmorphic lipid droplets. Finally, beneficial effects on brown adipose tissue activity were observed in an FPLD2 patient undergoing spironolactone treatment. These findings identify MR as a new lamin A interactor and a new player in lamin A-linked lipodystrophies.

The interactions between household size, capital, and adaptation to social-ecological change has been widely studied; however, little is known about the differences in everyday adaptation to social-ecological change across household structures. Joint family households are increasing in contexts where the nuclear family had previously been the norm, and remains a prevalent structure throughout the world. Thus, it is important to understand how these structures influence adaptation decision-making processes and outcomes. We draw on a survey of 448 self-identified household heads in three communities in northwestern Pakistan to assess everyday adaptation to social-ecological change. We demonstrate that livelihood and adaptation strategies vary across joint and nuclear family household structures because, in part, of joint family households’ greater access to natural and human capital in comparison to nuclear family households. Finally, household livelihood decision makers often include other family members to expand beyond the often-assumed husband-wife dyad. Our work highlights how everyday adaptations are expressions of existing opportunities in the space in which households are located, access to capital and resources that differ across household structures, and of various dynamics associated with household decision making. This points to the need for a nuanced understanding of how household structure influences everyday adaptation to social-ecological change and thereby shows the ways in which adaptive capacity is embedded within existing social systems and relationships, such as household structures.

Feminist political ecologists have transformed mainstream political ecology since its inception. The foundational and current work of feminist political ecologists indicate that their field is attentive to the epistemological foundations of power, inequities, and inequalities that cut across intersectional identities and hierarchies of difference and at the sites of environmental conflict and governance. Feminist political ecologists have made important theoretical interventions in the interdisciplinary community of political ecologists, but the use of feminist methodologies and 'team-based environmental science' can be expanded. We argue that revisiting feminist methodological commitments is critical for furthering how feminist political ecology examines how, and in what way, power and privilege operate in the contexts where environmental knowledge is produced. We make our argument by drawing upon a multi-year, multi-sited project to describe how collaborative event ethnography (CEE) offers many possibilities to reassess feminist political ecology research designs. We show how the recognition of diverse and plural epistemologies are foundational preconditions to integrating feminist principles in feminist political ecology research. We find that integrating reflexivity, responsibility, and co-production in research designs create opportunities for, and challenges to, carrying out feminist political ecological practice. In so doing, the integration of feminist methodologies are critical to disrupting knowledge hegemonies and providing new modes of practicing feminist political ecologies. Keywords: Collaborative event ethnography, feminist political ecology, feminist methodologies, global environmental governance

BackgroundRadical surgical resection of the primary tumor with mono/bilateral inguinofemoral lymph node dissection is the standard treatment for invasive vulvar squamous cell carcinoma (VSCC) and is frequently related to severe morbidity. Tailoring surgical treatment is of paramount importance, and a comprehensive preoperative evaluation is mandatory. Vascular endothelial growth factor D (VEGF-D) is considered a regulator of lymphangiogenesis involved in tumor spread via lymphatic vessels. The aim of this study was to evaluate the potential of VEGF-D in the prediction of inguinofemoral lymph node metastasis.MethodsWe analyzed the preoperative levels of serum VEGF-D (sVEGF-D) from two independent cohorts of patients with VSCC by enzyme-linked immunosorbent assay and its protein expression on tumor tissue by immunohistochemistry. Logistic regression was performed to identify the independent risk factors for lymph node metastasis, and Cox proportional hazard model was used for survival analysis.ResultsHigh levels of sVEGF-D, but not tissue VEGF-D, significantly correlated with positive groin nodes and a more advanced International Federation of Gynecologists and Obstetricians (FIGO) stage. In multivariable analysis, a high sVEGF-D level was an independent predictor of lymph node metastasis and worse prognosis. A prediction model based on sVEGF-D, tumor grade assessed on biopsy, tumor diameter, and lymph node clinical evaluation was able to predict lymph node metastasis, reaching C-index values of 0.79 and 0.73 in the training and validation cohorts, respectively.ConclusionsThe preoperative sVEGF-D level might be a reliable biomarker for the prediction of lymph node metastasis and prognosis in patients with VSCC, supporting better clinical/surgical decision. Multicenter prospective studies are required to confirm our findings.

Intact Forest Landscapes (IFLs) are global conservation units that aim to combat fragmentation, alteration, degradation, and loss of global forests. ILFs are typically recognized for their biodiversity, carbon storage, protection of hydroecological systems and other ecosystem services. However, IFLs are distinctive among other conservation efforts because they do not immediately prioritize conservation approaches that have goals of alleviating human poverty or improving well-being. The prevailing view is that IFL conservation should engage with ecocentric models of conservation. In this article, we leverage political ecology's analytical attention to power, institutions, identities, and scales to make suggestions on ways in which to integrate biocentric conservation considerations into IFL practices. From a scoping literature review, we found the following areas are especially critical for the future of IFL conservation: (1) prioritizing Indigenous Peoples and Local Communities (IPLC) as actors and beneficiaries of conservation; (2) identifying the value of knowledge integration and co-production for conservation; (3) addressing heterogenous communities and equity impacts, and (4) the need for procedural mechanisms in conservation initiatives that support nesting Indigenous Peoples and Local Communities management and governance in polycentric systems. Furthermore, the development of diagnostic questions of scaling community-based conservation and adaptive strategies beyond their original scope in terms of community definitions, landscape and political context may be beneficial for addressing multi-stakeholder needs, identifying more equitable approaches, sharing strategies and obtaining successful outcomes in IFL conservation. Keywords: Indigenous peoples and local communities, large intact landscapes, forests, conservation

Environmental social science research designs have shifted over the past several decades to include an increased commitment to multi-, inter-, and transdisciplinary team-based work that have had dual but complementary foci. These address power and equity in the substantive aspects of research, and also to adopt more engaged forms of practice, including decolonial approaches. The fields of political ecology, human geography, and environmental anthropology have been especially open to converge with indigenous scholarship, particularly decolonial and settler colonial theories and research designs, within dominant human-environmental social science paradigms. Scholars at the forefront of this dialogue highlight the ontological (ways of knowing), epistemological (how we know), and institutional (institutions of higher education) transformations that need to occur in order for this to take place. In this article we contribute to this literature in two ways. First, we highlight the synergies between political ecology and decolonial scholarship, particularly focusing on the power dynamics in research programs and historical legacies of human-environmental relationships, including those of researchers. Second, we explore how decolonial research pushes political ecologists and other environmental social scientists to not only consider adopting international and local standards of working with, by and for Indigenous Peoples within research programs but how this work ultimately extends to research and education within their home institutions and organizations. Through integrating decolonized research practices in the environmental social sciences, we argue that synthesizing multiple knowledge practices and transforming institutional structures will enhance team-based environmental social science work to improve collaboration with Indigenous scientists, subsistence practitioners, agency representatives, and sovereign members of Indigenous communities. Keywords: Alaska; collaboration; co-production; decolonial; Indigenous Knowledges; Iñupiaq Peoples

Background: No data are available regarding long-term survival of out-of-hospital cardiac arrest (OHCA) patients based on different Utstein subgroups, which are expected to significantly differ in terms of survival. We aimed to provide the first long-term survival analysis of OHCA patients divided according to Utstein categories.Methods: We analyzed all the 4,924 OHCA cases prospectively enrolled in the Lombardia Cardiac Arrest Registry (Lombardia CARe) from 2015 to 2019. Pre-hospital data, survival, and cerebral performance category score (CPC) at 1, 6, and 12 months and then every year up to 5 years after the event were analyzed for each patient.Results: A decrease in survival was observed during the follow-up in all the Utstein categories. The risk of death of the “all-EMS treated” group exceeded the general population for all the years of follow-up with standardized mortality ratios (SMRs) of 23 (95%CI, 16.8–30.2), 6.8 (95%CI, 3.8–10.7), 3.8 (95%CI, 1.7–6.7), 4.05 (95%CI, 1.9–6.9), and 2.6 (95%CI, 1.03–4.8) from the first to the fifth year of follow-up. The risk of death was higher also for the Utstein categories “shockable bystander witnessed” and “shockable bystander CPR”: SMRs of 19.4 (95%CI, 11.3–29.8) and 19.4 (95%CI, 10.8–30.6) for the first year and of 6.8 (95%CI, 6.6–13) and 8.1 (95%CI, 3.1–15.3) for the second one, respectively. Similar results were observed considering the patients discharged with a CPC of 1–2.Conclusions: The mortality of OHCA patients discharged alive from the hospital is higher than the Italian standard population, also considering those with the most favorable OHCA characteristics and those discharged with good neurological outcome. Long-term follow-up should be included in the next Utstein-style revision.

Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3+ T-cells and CD163+ tumor-associated macrophages (TAMs) densities identify a subgroup of immune infiltrated high-grade serous carcinomas (HGSCs) with better outcomes and superior response to platinum-based therapies. On the contrary, in most clear cell carcinomas (CCCs) showing poor prognosis and refractory to platinum, a high TAM density is associated with low T cell frequency. Immune infiltrated HGSC are characterized by the 30-genes signature (OC-IS30) covering immune activation and IFNγ polarization and predicting good prognosis (n = 312, TCGA). Immune infiltrated HGSC contain CXCL10 producing M1-type TAM (IRF1+pSTAT1Y701+) in close proximity to T-cells. A fraction of these M1-type TAM also co-expresses TREM2. M1-polarized TAM were barely detectable in T-cell poor CCC, but identifiable across various immunogenic human cancers. Single cell RNA sequencing data confirm the existence of a tumor-infiltrating CXCL10+IRF1+STAT1+ M1-type TAM overexpressing antigen processing and presentation gene programs. Overall, this study highlights the clinical relevance of the CXCL10+IRF1+STAT1+ macrophage subset as biomarker for intratumoral T-cell activation and therefore offers a new tool to select patients more likely to respond to T-cell or macrophage-targeted immunotherapies.

Fat tissue disorders: Dysfunctional fat cell differentiation An abnormal distribution of fatty tissues associated with certain tissue disorders is driven by disrupted fat cell differentiation. Type 2 familial partial lipodystrophy (FPLD2) is a genetic condition that results in fat being lost from the limbs and accumulating in the face and neck. Giovanna Lattanzi at the National Research Council of Italy in Bologna and co-workers found that fat cell (adipocyte) precursors did not clearly differentiate into either of the two main fatty tissue types, brown or white, in FPLD2 patients. White adipocyte precursors exhibited impaired lipid formation and abnormal levels of brown tissue markers. Conversely, brown adipocyte precursors showed high lipid levels and increased autophagy, a natural process involving degradation and recycling of cellular components. The neck is normally where brown fat accumulates, but FPLD2 patients had adipocytes there displaying white fat characteristics.

In spite of the effective implementation of screening programs, uterine cervical carcinoma (UCC) remains one of the major causes of cancer death among women around the world. The aim of this study was to investigate the prognostic value of serum human epididymis protein 4 (HE4) in UCC. Pre-treatment serum samples from 109 UCC patients and 99 healthy women were analyzed for HE4 levels by a quantitative chemiluminescent microparticle immunoassay on the automated ARCHITECT instrument. HE4 serum (sHE4) levels were significantly higher in UCC patients, regardless of tumor stage, compared with healthy controls. Elevated sHE4 levels were significantly associated with advanced FIGO stage and absence of disease-free interval after treatment. In univariable analysis, higher sHE4 levels were significantly correlated with shorter overall survival and progression-free survival. In multivariable analysis, sHE4 retained its significance as independent adverse prognostic factor for both survival endpoints. This study indicates that sHE4 is associated with a more aggressive tumor phenotype and a worse patient's prognosis. These results suggest the potential role of sHE4 as a novel prognostic marker and as an indicator of high-risk UCC patients for a tailored surgical and adjuvant therapy.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of taxanes, with no effective prevention or treatment available and a highly negative impact on patient quality of life. The aim of this study is to asses that the constant application of cooled cuffs on the hands and feet prevent and mitigate CIPN. Methods: Patients with breast, gynecologic, and pancreatic cancer who received weekly paclitaxel (PTX), PTX/carboplatin, and nab-paclitaxel (nab-PTX)/gemcitabine for any indication at the therapeutic scheduled dosage were included in this prospective study. Hilotherm Chemo care device forms a closed-loop system with cuffs and tubes through which a coolant flows at a temperature of 10 °C. CIPN was monitored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (edition 3.0), and the tolerability and side effects were scored by using the Common Terminology Criteria for Adverse Events (T4.03 2017). Results: To date, we have enrolled 64 patients. Of these, 54 (84%) completed all cooling cycles. Continuous cooling was well tolerated by all patients. No patients had grade >2 CIPN or had serious or lasting adverse events as a result of Hilotherapy. The median time to CIPN onset was 77 days for the entire population. Conclusion: Hilotherapy has good effectiveness and tolerability and seems to be able to prevent or reduce the symptoms of CIPN. We are still recruiting patients to obtain more data and to collect data at 3 months after the end of chemotherapy. Prospective studies seem to be warranted.

High-grade serous ovarian carcinoma (HGSOC) usually spreads directly into the peritoneal cavity following a transcoelomic dissemination route, although distant hematogenous metastasis exist and have been reported. However, no tumor markers can currently predict the risk of distant metastases in HGSOC. Claudins, belonging to tight-junction proteins, are dysregulated in HGSOC and functionally related to cancer progression. Here we analyzed claudin-3, -4, and -7 expression as potential markers of distant metastases. Using quantitative RT-PCR and immunohistochemistry we assessed the expression of claudins in primary HGSOC tissues, normal ovarian, and normal fallopian tube epithelia and correlated it with clinicopathological features, including the site of metastasis and the route of dissemination. Gene set enrichment analysis was performed on microarray-generated gene expression data to investigate key pathways in patients with distant metastases. We found the overall expression level of claudin-3, -4, and -7 mRNA decreased in HGSOC compared to normal tubal epithelium, currently considered the potential site of origin of many HGSOC. The reduced expression of claudin-7 is significantly associated with the development of distant metastases (p = 0.016), mainly by hematogenous route (p = 0.025). In patients with diminished expression of claudin-7, immunohistochemical staining revealed a heterogeneous pattern of membranous staining with discontinuous expression of claudin-7 along the cell border, indicative of a dischoesive architecture. The estimated reduction in the probability of distant disease is of 39% per unit increase in the level of claudin-7 (p = 0.03). Genes involved in epithelial to mesenchymal transition, hypoxia, and angiogenesis processes resulted strongly associated to hematogenous recurrence. Our data suggest a potential role of claudin-7 in discriminating distant metastatic events in HGSOC patients. The quantification of its expression levels could be a useful tool to identify patient deserving a personalized follow-up in terms of clinical and radiological assessment.

Indigenous and local knowledge (ILK) systems are critical for achieving biodiversity conservation, climate change adaptation, and other environmental goals. However, ILK systems around the world are increasingly threatened by multiple stressors. Our study assesses the effect of climate change on ILK held by crop farmers in Peru's Colca Valley. We collected qualitative data on farmers' ILK through semi-structured interviews, which we supplemented with climatological trend analysis in four Colca Valley districts. We found that shifts in the rainy season together with warmer weather affected farmers' ILK, which was less effective for informing crop planting and irrigation practices in the context of climate uncertainty and unpredictability. Changing and uncertain ILK poses obstacles to adaptation strategies that require long-term institution building from local resource users, who may prioritize short-term solutions addressing urgent needs.

Abstract Some aspects of endometrial cancer (EC) preoperative work-up are still controversial, and debatable are the roles played by lymphadenectomy and radical surgery. Proper preoperative EC staging can help design a tailored surgical treatment, and this study aims to propose a new algorithm able to predict extrauterine disease diffusion. 293 EC patients were consecutively enrolled, and age, BMI, children’s number, menopausal status, contraception, hormone replacement therapy, hypertension, histological grading, clinical stage, and serum HE4 and CA125 values were preoperatively evaluated. In order to identify before surgery the most important variables able to classify EC patients based on FIGO stage, we adopted a new statistical approach consisting of two-steps: 1) Random Forest with its relative variable importance; 2) a novel algorithm able to select the most representative Regression Tree (RERT) from an ensemble method. RERT, built on the above mentioned variables, provided a sensitivity, specificity, NPV and PPV of 90%, 76%, 94% and 65% respectively, in predicting FIGO stage > I. Notably, RERT outperformed the prediction ability of HE4, CA125, Logistic Regression and single cross-validated Regression Tree. Such algorithm has great potential, since it better identifies the true early-stage patients, thus providing concrete support in the decisional process about therapeutic options to be performed.

Abstract Background The existence of cancer stem cells (CSCs) within a tumor bulk has been demonstrated for many solid tumors including epithelial ovarian carcinoma (EOC). CSCs have been associated to tumor invasion, metastasis and development of chemoresistant recurrences. In this context, we aim to characterize EOC CSCs from the molecular point of view in order to identify potential biomarkers associated with chemoresistance. Methods We isolated a population of cells with stem-like characteristics (OVA-BS4 spheroids) from a primary human EOC cell line under selective conditions. OVA-BS4 spheroids were characterized for drug response by cytotoxicity assays and their molecular profile was investigated by microarray and RT-qPCR. Finally, we performed a gene expression study in a cohort of 74 high-grade serous EOC (HGSOC) patients by RT-qPCR. Results Spheroids exhibited properties of self-renewal and a pronounced expression of well-known stem cell genes. Moreover, they demonstrated greater resistance towards several anticancer drugs compared to parent cell line, consistent with their higher ABCG2 gene expression. From microarray studies MAL (T-cell differentiation protein) emerged as the most up-regulated gene in spheroids, compared to parent cell line. In HGSOC patients, MAL was significantly overexpressed in platinum-resistant compared to platinum-sensitive patients and resulted as an independent prognostic marker of survival. Conclusions This investigation provides an important contribution to the identification of molecular markers of ovarian CSCs and chemoresistance. Successful translation of molecular findings would lead to a better comprehension of the mechanisms triggering chemoresistant recurrences, to the individuation of novel therapeutic targets and to the personalization of treatment regimens.

Abstract Background Epithelial ovarian cancer (EOC) is a spectrum of different diseases, which makes their treatment a challenge. Forkhead box M1 (FOXM1) is an oncogene aberrantly expressed in many solid cancers including serous EOC, but its role in non-serous EOCs remains undefined. We examined FOXM1 expression and its correlation to prognosis across the three major EOC subtypes, and its role in tumorigenesis and chemo-resistance in vitro. Methods Gene signatures were generated by microarray for 14 clear-cell and 26 endometrioid EOCs, and 15 normal endometrium snap-frozen biopsies. Validation of FOXM1 expression was performed by RT–qPCR and immunohistochemistry in the same samples and additionally in 50 high-grade serous EOCs and in their most adequate normal controls (10 luminal fallopian tube and 20 ovarian surface epithelial brushings). Correlations of FOXM1 expression to clinic-pathological parameters and patients’ prognosis were evaluated by Kaplan-Meier and Cox proportional-hazards analyses. OVCAR-3 and two novel deeply characterized EOC cell lines (EOC-CC1 and OSPC2, with clear-cell and serous subtype, respectively) were employed for in vitro studies. Effects of FOXM1 inhibition by transient siRNA transfection were evaluated on cell-proliferation, cell-cycle, colony formation, invasion, and response to conventional first- and second-line anticancer agents, and to the PARP-inhibitor olaparib. Gene signatures of FOXM1-silenced cell lines were generated by microarray and confirmed by RT-qPCR. Results A significant FOXM1 mRNA up-regulation was found in EOCs compared to normal controls. FOXM1 protein overexpression significantly correlated to serous histology (p = 0.001) and advanced FIGO stage (p = 0.004). Multivariate analyses confirmed FOXM1 protein overexpression as an independent indicator of worse disease specific survival in non-serous EOCs, and of shorter time to progression in platinum-resistant cases. FOXM1 downregulation in EOC cell lines inhibited cell growth and clonogenicity, and promoted the cytotoxic effects of platinum compounds, doxorubicin hydrochloride and olaparib. Upon FOXM1 knock-down in EOC-CC1 and OSPC2 cells, microarray and RT-qPCR analyses revealed the deregulation of several common and other unique subtype-specific FOXM1 putative targets involved in cell cycle, metastasis, DNA repair and drug response. Conclusions FOXM1 is up-regulated in all three major EOCs subtypes, and is a prognostic biomarker and a potential combinatorial therapeutic target in platinum resistant disease, irrespective of tumor histology.

The interdisciplinary Electronic Life Histories Project integrates behavioral archaeology, engineering, anthropology, art, material culture, and science and technology studies to employ a life history model, community-based research and creative engagement to address the making of electronic waste. Focused in the Greater Lafayette area of Indiana, which is home to a major university, this project examines the entanglements among people, electronics and waste-making. Specifically, this paper focuses on a significant interstitial stage between reuse and discard. We consider the stories and meanings affixed to electronic objects once they have entered people’s homes, and the complex lives they have before they are discarded, reused, or repurposed. We find ‘closet fill’ or junk drawers of electronic devices, bits, bytes and peripherals are often unintentional collections that are situationally valued through a constellation of factors that include emotional attachments, technological obsolescence, imagined use-value, as well as discrepancies between perceived value and market value. While the problem of closet fill has been discussed by scholars, how electronics enter this interstitial stage, why they remain and what motivates movement out of this part of the life history of objects have not been closely examined. We suggest a life history approach can make these interstitial phases visible in a way that illuminates the key factors in keeping electronics versus discarding. As opposed to descriptions of waste as disorderly, abject, or disgusting, our work shows that objects at the interstices of wasting practices embody, represent, and express many meanings to participants socially, spatially, and structurally.

Salchichón Primavera, un colectivo de curiosos, historiadores, guionistas, espigadores, con la intención, intuición, obstinación de indagar sobre los diferentes márgenes de la sociedad, sobre los cuerpos vulnerados, golpeados constantemente por el desamor. Armamos, hicimos, investigamos, filmamos, construimos, pensamos, nos volvimos locas, nos abrazamos y resucitamos en el latir de “La Condesa”. Laura Dominique Pillieri, conocida como La Condesa, nuestra aliada. Iba ser una compañera en esta búsqueda de reconstrucción de su propia historia de vida – estuvo presa 19 años, quedó en “libertad” en septiembre del 2015, al mes murió de un ataque al corazón en su casa de barrio San Martin – fue nuestra protagonista en este viaje. Es.

This article focuses on the debates among resilience, sustainability, adaptation, and transformation concepts. The conceptualization and application of sustainability and resilience thinking in the human-environmental interactions, social-ecological systems, and global environmental change literature remain dominant, which provide a common interdisciplinary and policy language where research in socio-environmental systems can converge. Yet, the lack of clarity and multiplicity among and between these concepts and paradigms allows them to continue to be widely adopted in different sectors of society. Drawing on five case studies from different geographical locations, these diverse applications of resilience, sustainability, adaptation, and transformation are explored from disciplinary and interdisciplinary perspectives. The diversity in the operationalization and use of the concepts and paradigms can result in applications that undermine goals of sustainability or resilience when a particular resource is prioritized over others or is applied in a way that results in inequitable outcomes. Findings from the cases reinforce the importance of being explicit about the spatial, temporal, and institutional boundaries drawn because proposed solutions will vary in their effectiveness if attention to scale, stressors, worldviews, and actors are not addressed holistically. We suggest the ongoing adoption of sustainability, resilience, adaptation, and transformation requires clear and explicit definitions, that draw from decolonized methodologies, goals, in-depth analysis of potential unintended consequences, and situated understanding of how these concepts and the associated paradigms are embedded in particular contexts.

One key strand of political ecology inquiry draws attention to different scalar aspects of territorial control and environmental governance, especially as they relate to inequity, power, and marginality in the rural South. Simultaneously, in the past several decades scholars have argued for a more meaningful engagement with space and place, as global forces of capitalism and geographies of difference make and unmake places in surprising and often violent ways. In this article, I interweave political ecology and anthropology of space and place approaches to territorial practices in the Brazilian Amazon to demonstrate how multiscalar politics of territorial retention and use are layered alongside local, spatial practices. In the Brazilian Amazon, indigenous rights are closely linked to the territorial demarcation and protection of federally defined Indigenous Lands. To that end, a general pattern has been observed across Amazonia that colonization and state-making agendas regarding territorial control have coincided to an increased sedentism of indigenous peoples. This narrative elides the present and ongoing importance local ideas about territories and place have for indigenous communities. Ethnographic data from research with the Kayapó, an indigenous group in Brazil, is presented to draw attention to the complexities of the local responses to the past several decades of change that have resulted in a federally defined territorial homeland and shifting spatial practices within those lands. The Kayapó response is a particularly well-suited case study for this type of analysis, as the tribe is known ethnographically for their fissioning and trekking patterns. I show that movement, mobility, and travel still figure into everyday practices in meaningful ways. While far from homogenous, movement through the landscape is part of responding to current demands to their ways of life. I also argue that travel also affirms the Kayapó notions of knowing (kukradjà), beauty (mê), and strength (tycht). Keywords: political ecology, Amazonia, travel, territoriality, space and place

The importance of the immune system as a potent anti-tumor defense has been consolidated in recent times, and novel immune-related therapies are today demonstrating a strong clinical benefit in the setting of several solid neoplasms. Tumor-infiltrating lymphocytes reflect the attempt of the host to eradicate malignancies, and during the last decades, they have been shown to possess an interesting prognostic utility for breast cancer, especially in case of HER2 positive and triple-negative molecular subtypes. In parallel, the clinical evaluation of tumor-infiltrating lymphocytes has been shown to effectively predict treatment outcomes in both neoadjuvant and adjuvant settings. Currently, tumor-infiltrating lymphocytes are promising further predictive utility in view of novel immune-related therapeutic strategies which are coming into the clinical setting launching a solid rationale for the future next-generation treatment options. In this scenario, tumor-infiltrating lymphocytes might represent an important resource for the selection of the most appropriate therapeutic strategy, as well as further evaluations of the molecular mechanisms underlying tumor-infiltrating lymphocytes and the immunoediting process would eventually provide new insights to augment therapeutic success. Considering these perspectives, we review the potential utility of tumor-infiltrating lymphocytes in the definition of breast cancer prognosis and in the prediction of treatment outcomes, along with the new promising molecular-based therapeutic discoveries.

Despite widespread recognition of the importance of community-conservation partnerships, problems continue to emerge. In this paper we examine one such interaction to propose that outside organisations have wrongly associated the delimitations of the habitational space with the extent of community allegiances and moral economies. Such oversights can lead to project withdrawal, as they did in one case of an ecotourism proposal among the indigenous Kayapσ of the southeastern Amazon. The case study points to the challenges in the processes of partnering with local villages where histories of fissioning and factioning contain within them their own processual relations and moral obligations. These models, by which people group themselves into communities of loyalty, affectivity, and belonging, may be elusive to outsiders and account for many challenges in local-international collaborations. Western planners are often unprepared for the long reach of relationships relevant to project planning and benefit sharing. We suggest that in order to move forward with effective multi-participant community-based projects, project planners should take into account supra-spatial, and dynamic, moral economies.

Accurate normalization is a primary component of a reliable gene expression analysis based on qRT-PCR technique. While the use of one or more reference genes as internal controls is commonly accepted as the most appropriate normalization strategy, many qPCR-based published studies still contain data poorly normalized and reference genes arbitrarily chosen irrespective of the particular tissue and the specific experimental design. To date, no validated reference genes have been identified for endometrial cancer tissues. In this study, 10 normalization genes (GAPDH, B2M, ACTB, POLR2A, UBC, PPIA, HPRT1, GUSB, TBP, H3F3A) belonging to different functional and abundance classes in various tissues and used in different studies, were analyzed to determine their applicability. In total, 100 endometrioid endometrial cancer samples, which were carefully balanced according to their tumor grade, and 29 normal endometrial tissues were examined using SYBR Green Real-Time RT-PCR. The expression stability of candidate reference genes was determined and compared by means of geNorm and NormFinder softwares. Both algorithms were in agreement in identifying GAPDH, H3F3A, PPIA, and HPRT1 as the most stably expressed genes, only differing in their ranking order. Analysis performed on the expression levels of all candidate genes confirm HPRT1 and PPIA as the most stably expressed in the study groups regardless of sample type, to be used alone or better in combination. As the stable expression of HPRT1 and PPIA between normal and tumor endometrial samples fulfill the basic requirement of a reference gene to be used for normalization purposes, HPRT1 expression showed significant differences between samples from low-grade and high-grade tumors. In conclusion, our results recommend the use of PPIA as a single reference gene to be considered for improved reliability of normalization in gene expression studies involving endometrial tumor samples at different tumor degrees.