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ObjectiveCancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy. Since these same patients often present for palliative aspiration of ascites or pleural effusions, there is a potential opportunity to obtain tumor specimens in the form of multicellular spheroids (MCS) present in malignant effusion fluids. Our objective was to develop a short duration culture of MCS from ovarian cancer malignant effusions in conditions selected to support organoid growth and use them as a platform for empirical drug sensitivity testing.MethodsIn this study, malignant effusion specimens were collected from patients with high-grade serous ovarian carcinoma (HGSOC). MCS were recovered and subjected to culture conditions designed to support organoid growth. In a subset of specimens, RNA-sequencing was performed at two time points during the short-term culture to determine changes in transcriptome in response to culture conditions. Organoid induction was also characterized in these specimens using Ki67 staining and histologic analysis. Drug sensitivity testing was performed on all specimens.ResultsOur model describes organoids formed within days of primary culture, which can recapitulate the histological features of malignant ascites fluid and can be expanded for at least 6 days. RNA-seq analysis of four patient specimens showed that within 6 days of culture, there was significant up-regulation of genes related to cellular proliferation, epithelial-mesenchymal transition, and KRAS signaling pathways. Drug sensitivity testing identified several agents with therapeutic potential.ConclusionsShort duration organoid culture of MCS from HGSOC malignant effusions can be used as a platform for empiric drug sensitivity testing. These ex vivo models may be helpful in screening new or existing therapeutic agents prior to individualized treatment options.

Floating wetland systems potentially can provide a diverse set of ecosystem services that collectively improve urban resilience. Despite the growing studies and use of floating wetlands in temperate and subtropical climates, the design of floating wetlands in tropical climates is still understudied. This paper therefore aims to identify the research gaps in landscape planning and synthesize the design typology that can be applied to tropical urban conditions. The purpose of this research is i) Identify opportunities and challenges in applying floating wetland systems for landscape planning and design, ii) synthesize the design typology that can be applied to urban tropical climate conditions and iii) demonstrate the application of ecological wetland principles for the built environment. This research uses a mixed methods approach by including both a narrative review based on 67 peer-reviewed articles as well as case studies from tropical climates. The review captures the challenges and opportunities of designing ecological floating wetlands in terms of multifunctional usage, site limitation, cost effectiveness, social benefit, and ecological habitat creation. For design typology of floating wetlands in a tropical climate, we discuss design components based on size, floating mat types, structures and materials, planting design, and additional technology. While the first case study showcased a design for an ecological floating wetland, the second case study illustrates how mathematical modeling can guide sizing and performance assessment in planning floating wetland implementation. Ecological floating wetlands can provide a positive impact to the urban environment under tropical conditions, but the main research gaps include an incomplete understanding of contaminant uptake rates associated with different plants, required maintenance of the systems, plant robustness, and community appreciation.

Kate Goldie,1,* Martina Kerscher,2,* Sabrina Guillen Fabi,3 Cyro Hirano,4 Marina Landau,5 Ting Song Lim,6 Heather Woolery-Lloyd,7 Kavita Mariwalla,8 Je-Young Park,9 Yana Yutskovskaya10 1European Medical Aesthetics Ltd, London, UK; 2Division of Cosmetic Science, Department of Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany; 3Department of Dermatology, University of California, San Diego, CA, USA; 4Division of Dermatology General Polyclinic of Rio de Janeiro, Private Practice, CD Clinica Dermatologica, Rio de Janeiro, Brazil; 5Dermatology Unit, Wolfson Medical Center, Holon, Israel; 6Clique Clinic, Kuala Lumpur, Malaysia; 7Department of Ethnic Skin Care, University of Miami Cosmetic Medicine and Research Institute, Miami Beach, FL, USA; 8Mariwalla Dermatology, New York, NY, USA; 9Apkoo-Jung Department, Oracle Dermatology Center, Seoul, Republic of Korea; 10Dermatovenerology and Cosmetology Department, Pacific State Medical University of Health, Moscow, Russia*These authors contributed equally to this workCorrespondence: Martina KerscherDivision of Cosmetic Science, Department of Biochemistry and Molecular Biology, University of Hamburg, Hamburg, GermanyEmail martina.kerscher@uni-hamburg.deIntroduction: Skin quality is an important component of human attractiveness. To date, there are no standardized criteria for good skin quality. To establish a consensus for good skin quality parameters and measurement and treatment options, a virtual skin quality advisory board consisting of a global panel of highly experienced aesthetic dermatologists/aesthetic physicians was convened.Methods: A total of 10 dermatologists/aesthetic physicians served on the advisory board. A modified version of the Delphi method was used to arrive at consensus. Members accessed an online platform to review statements on skin quality criteria from their peers, including treatment and measurement options, and voted to indicate whether they agreed or disagreed. Statements that did not have agreement were modified and the members voted again. Consensus was defined as: strong consensus = greater than 95% agreement; consensus = 75% to 95% agreement; majority consent = 50% to 75% agreement; no consensus = less than 50% agreement.Results: There was strong consensus that good skin quality is defined as healthy, youthful in appearance (appearing younger than a person’s chronological age), undamaged skin and that skin quality can be described across all ethnicities by four emergent perceptual categories (EPCs): skin tone evenness, skin surface evenness, skin firmness, and skin glow. The EPCs can be affected by multiple tissue layers (ie, skin surface quality can stem from and be impacted by deep structures or tissues). This means that topical approaches may not be sufficient. Instead, improving skin quality EPCs can require a multilayer treatment strategy.Conclusion: This global advisory board established strong consensus that skin quality can be described by four EPCs, which can help clinicians determine the appropriate treatment option(s) and the tissue or skin layer(s) to address. Skin quality is important to human health and wellbeing and patients’ perception for the need for aesthetic treatment.Keywords: aesthetic treatment, consensus, emergent perceptual skin quality categories, EPCs, skin quality

ObjectivePatient-derived organoids (PDOs), used in multiple tumor types, have allowed evaluation of tumor characteristics from individual patients. This study aimed to assess the feasibility of applying PDO in vitro culture for endocrine-based and drug sensitivity testing in endometrial cancer.MethodsEndometrial cancer cells were enzymatically dissociated from tumors retrieved from fresh hysterectomy specimens and cultured within basement membrane extract in serum-free medium. An organoid growth assay was developed to assess the inhibitory effects of a variety of drugs including endocrine treatments. Organoid cultures were also prepared for histological and immunohistochemical comparison to the tumors of origin.ResultsFifteen endometrial cancer specimens were successfully cultured as PDOs. Small spherical structures formed within 24 hours, and many continued to grow to larger, denser organoids, providing the basis for an organoid growth assay. The STAT3 transcription factor inhibitor, BBI608 (Napabucasin), strongly inhibited growth in almost all PDO cultures, suggesting that stemness programing is involved in organoid formation and/or growth. Inhibition by different growth factor receptor tyrosine kinase inhibitors was observed in several PDO specimens. Four cultures were inhibited by fulvestrant, implying the importance of estrogen-receptor signaling in some PDO cultures. Organoids closely resembled their tumors of origin in both histomorphology and immunohistochemical expression.ConclusionsThe use of endometrial cancer PDO cultures for development of drug sensitivity testing for individual patient tumors is feasible. The potential value of the PDO model for clinical decision making will require clinical trial evaluation.

BackgroundRelapses of multiple sclerosis decrease during pregnancy, when the hormone estriol is increased. Estriol treatment is anti-inflammatory and neuroprotective in preclinical studies. In a small single-arm study of people with multiple sclerosis estriol reduced gadolinium-enhancing lesions and was favourably immunomodulatory. We assessed whether estriol treatment reduces multiple sclerosis relapses in women.MethodsWe did a randomised, double-blind, placebo-controlled phase 2 trial at 16 academic neurology centres in the USA, between June 28, 2007, and Jan 9, 2014. Women aged 18-50 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1) with a random permuted block design to either daily oral estriol (8 mg) or placebo, each in combination with injectable glatiramer acetate 20 mg daily. Patients and all study personnel, except for pharmacists and statisticians, were masked to treatment assignment. The primary endpoint was annualised relapse rate after 24 months, with a significance level of p=0.10. Relapses were confirmed by an increase in Expanded Disability Status Scale score assessed by an independent physician. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00451204.FindingsWe enrolled 164 patients: 83 were allocated to the estriol group and 81 were allocated to the placebo group. The annualised confirmed relapse rate was 0.25 relapses per year (95% CI 0.17-0.37) in the estriol group versus 0.37 relapses per year (0.25-0.53) in the placebo group (adjusted rate ratio 0.63, 95% CI 0.37-1.05; p=0.077). The proportion of patients with serious adverse events did not differ substantially between the estriol group and the placebo group (eight [10%] of 82 patients vs ten [13%] of 76 patients). Irregular menses were more common in the estriol group than in the placebo group (19 [23%] vs three [4%], p=0.0005), but vaginal infections were less common (one [1%] vs eight [11%], p=0.0117). There were no differences in breast fibrocystic disease, uterine fibroids, or endometrial lining thickness as assessed by clinical examination, mammogram, uterine ultrasound, or endometrial lining biopsy.InterpretationEstriol plus glatiramer acetate met our criteria for reducing relapse rates, and treatment was well tolerated over 24 months. These results warrant further investigation in a phase 3 trial.FundingNational Institutes of Health, National Multiple Sclerosis Society, Conrad N Hilton Foundation, Jack H Skirball Foundation, Sherak Family Foundation, and the California Community Foundation.

VonAalst (2010) used Google Scholar to identify the top four science education research journals: "Journal of Research in Science Teaching," "Science Education," "International Journal of Science Education," and "Journal of Science Teacher Education." U.S. institutional productivity for 2000-2009 for the above journals was the data for the study. The major domestic science education programs were identified for raw and weighted counts. For the top 10, there was a 100% agreement with different ranks while there was only a 60% agreement among the bottom 10. These results demonstrated that dominant science education faculty published their research in multiple empirical journals.

Microbial communities play a vital role in nitrogen (N) removal in constructed wetlands (CWs). However, the lack of studies on microbial characteristics of wetland systems designed to treat stormwater demonstrates the importance of comprehensive investigation on microbial response to wetland fluctuations. Moreover, the observed inconsistency in N removal, and detected links between microbial shifts and wetland water level fluctuations is an area of research interest perculiar to stormwater applications. This study surveyed nearly 150 publications to provide a summary and evaluation of N removal efficiency in different types of CWs where microbial communities and their behavior have been correlated to regulating factors. Factors such as flow regime, plants, and physico-chemical properties (e.g., temperature, dissolved oxygen, pH, and nitrogen concentration) were found to significantly influence microbial diversity and composition. Although many studies have analyzed microbial N removal, a majority conducted their studies in bioretention systems. Accordingly, some of the microbial pathways in CWs designed for stormwater treatment have not been investigated. As such, it is suggested that pathways, such as dissimilatory nitrate reduction to ammonium (DNRA) and comammox activity and their changes over dry-wet cycles in stormwater constructed wetlands be investigated. This information could assist engineers to take advantage of the presence of other N transforming communities which could improve microbial diversity within wetland systems. Moreover, it is recommended to track microbial functional genes and their changes over wetland water fluctuation to develop an ecosystem with conditions favorable for microbial pathways with higher N removal potential. In conclusion, the findings of the current literature review reinforce the importance of stormwater runoff treatment and the implementation of new design strategies that are able to enhance microbial activity and diversity leading to a better treatment outcome.

The study of shadows is a common elementary science topic that facilitates students' development of understanding about light and associated waves. All elementary students have observed numerous shadows, but need assistance in developing understanding. Previous research studies about shadows were utilized in organizing aspects associated with shadows. This review paper encourages teachers to utilize three principles of learning: students' prior knowledge about shadows, factual and conceptual knowledge related to shadows, and metacognition requiring students to think about their personal understanding about shadows; thereby, promoting students' science literacy.

A series of magnet trade books were analyzed against a validated list of magnet concepts (Barrow, 1990a) and their Flesch (1974) Readability was determined. These trade books were used to supplement a second grade unit on magnetism locally constructed from AIM's "Mostly Magnets" (1991). All trade books accurately described how like and unlike poles behave and operation of a compass. Considerable variation in readability was noted. Suggestions are provided on appropriate use of trade books of varying concepts and readability. (Contains 4 tables.)

The purpose of this study was to analyze science education searches and hiring practices for faculty positions listed in The Chronicle of Higher Education for an academic year. Chairs of searches completed a survey about successful and unsuccessful searches. Over 70% of searches were successful in hiring new science education faculty with 33% being veteran science education faculty.

The symbiotic relationship between animals and their resident microorganisms has profound effects on host immunity. The human microbiota comprises bacteria that reside in the gastrointestinal tract and are involved in a range of inflammatory and autoimmune diseases. The gut microbiota’s immunomodulatory effects extend to extraintestinal tissues, including the central nervous system (CNS). Specific symbiotic antigens responsible for inducing immunoregulation have been isolated from different bacterial species. Polysaccharide A (PSA) of Bacteroides fragilis is an archetypical molecule for host-microbiota interactions. Studies have shown that PSA has beneficial effects in experimental disease models, including experimental autoimmune encephalomyelitis (EAE), the most widely used animal model for multiple sclerosis (MS). Furthermore, in vitro stimulation with PSA promotes an immunomodulatory phenotype in human T cells isolated from healthy and MS donors. In this review, we discuss the current understanding of the interactions between gut microbiota and the host in the context of CNS inflammatory demyelination, the immunomodulatory roles of gut symbionts. More specifically, we also discuss the immunomodulatory effects of B. fragilis PSA in the gut-brain axis and its therapeutic potential in MS. Elucidation of the molecular mechanisms responsible for the microbiota’s impact on host physiology offers tremendous promise for discovering new therapies.

Aquaculture continues to significantly expand its production, making it the fastest-growing food production sector globally. However, the sustainability of the sector is at stake due to the predicted effects of climate change that are not only a future but also a present reality. In this paper, we review the potential effects of climate change on aquaculture production and its implications on the sector's sustainability. Various elements of a changing climate, such as rising temperatures, sea-level rise, diseases and harmful algal blooms, changes in rainfall patterns, the uncertainty of external inputs supplies, changes in sea surface salinity, and severe climatic events have been discussed. Furthermore, several adaptation options have been presented as well as some gaps in existing knowledge that require further investigations. Overall, climate change effects and implications on aquaculture production sustainability are expected to be both negative and positive although, the negative effects outweigh the positive ones. Adapting to the predicted changes in the short-term while taking mitigation measures in the long-term could be the only way toward sustaining the sector's production. However, successful adaptation will depend on the adaptive capacity of the producers in different regions of the world.

The intestinal microbiota constitutes a complex ecosystem in constant reciprocal interactions with the immune, neuroendocrine, and neural systems of the host. Recent molecular technological advances allow for the exploration of this living organ and better facilitates our understanding of the biological importance of intestinal microbes in health and disease. Clinical and experimental studies demonstrate that intestinal microbes may be intimately involved in the progression of diseases of the central nervous system (CNS), including those of affective and psychiatric nature. Gut microbes regulate neuroinflammatory processes, play a role in balancing the concentrations of neurotransmitters and could provide beneficial effects against neurodegeneration. In this review, we explore some of these reciprocal interactions between gut microbes and the CNS during experimental disease and suggest that therapeutic approaches impacting the gut-brain axis may represent the next avenue for the treatment of psychiatric disorders.