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[...]the discovery of numerous druggable oncogenic drivers has broadened treatment options; molecularly directed targeted agents and immunotherapy have transformed systemic therapy options. 1–4 Therapeutic advances in minimally invasive surgery and highly precise radiation techniques have substantially improved outcomes of local therapy. 1 We have increasing evidence that low-dose CT scanning in high-risk smokers saves lives. 11 Improvements in diagnostics, including nuclear medicine, molecular diagnostics, and minimally invasive staging, have resulted in more accurate diagnosis and staging, enabling personalised therapy. 1 The International Association for the Study of Lung Cancer (IASLC)– Lancet Commission on Lung Cancer represents a bold departure from accepting the status quo, and will propose actionable solutions for global lung cancer control. [...]the growing incidence of non-smoking lung cancer calls for concerted action from climate change experts, city planners, and other stakeholders to address clean energy transition, air pollution, and occupational health reforms. 8,9 Expanding molecular diagnostics access would not only require cost reductions but also capacity building both in laboratory infrastructure and human resources, and further downstream, affordable medicines. CSP reports institutional research funding from Cancer Research UK, DBT-Wellcome India Alliance, and the Gates Foundation; is an advisory board member of the Association of American Cancer Institutes, the Princess Margaret Cancer Centre (PMCC), Toronto, the PMCC Global Oncology Program, and Koita Centre for Digital Health; is a member of the Board of Directors of the Union for International Cancer Control; is the Director of Tata Memorial Hospital and Convener of the National Cancer Grid, India; and is a member of the American Society of Clinical Oncology's International Affairs Committee, IASLC's Global Policy & Partnerships Committee, and the European Society for Medical Oncology's Faculty Group (gastrointestinal, non-colorectal).

Surface Ig (sIg) of follicular lymphoma (FL) is vital for tumor cell survival. We found previously that the Ig in FL is unusual, because the variable region genes carry sequence motifs for N-glycan addition. These are introduced by somatic mutation and are tumor specific. Unexpectedly, added glycans terminate at high mannose, suggesting a potentially important interaction of FL cells with mannose-binding lectins of the innate immune system. We have now identified mannosylated IgM at the surface of primary lymphoma cells. Recombinant lectin domains of the mannose receptor (MR) or DC-SIGN bind mannosylated Igs in vitro and bind to FL cells, signaling sIgM-associated increases in intracellular Ca²⁺. Lectins also bind to normal B cells but fail to signal. In contrast, anti-Ig signaled similarly in both FL and normal B cells. Mannosylation patterns were mimicked by FL Ig-derived single-chain Fvs (scFv), providing probes for potential receptors. Mannosylated scFv bound specifically to the lectin domains of the MR and DC-SIGN and blocked signaling. Mannosylated scFv also bound to DC-SIGN on the surface of dendritic cells. This unique lymphoma-specific interaction of sIg with lectins of innate immunity reveals a potential route for microenvironmental support of tumor cells, mediated via the key B-cell receptor.

Using a unique sterile design intended to eliminate outside seed contamination of horse feces, we investigated whether weed seeds germinate after digestion by horses. Feces were collected from selected National Parks and other locations in central and northern California. All potted fecal samples were irrigated and grown in an enclosed sterile nursery environment. Thirty-two plant species emerged from these fecal samples, 24 of which were not native to California. None of these were identified on the California Department of Agriculture's Noxious Weed List, which is used as a basis to certify equine feed as weed free. However, seven of the non-native species are identified as moderately invasive on the California Invasive Plant Council's (Cal-IPC) list. These species are: Hirschfeldia incana, Hordeum marinum, Lolium multiflorum, Mentha pulegium, Rumex acetosella, Trifolium hirtum, and Vulpia myuros. In addition, the following four non-native plants are listed at the limited invasiveness level on the Cal-IPC list: Hypochaeris glabra, Lythrum hyssopifolium, Medicago polymorpha, and Poa pratensis. Because we did not survey invasive plant cover in locations from which we sampled, we cannot guarantee that species identified in our samples would have also germinated in the field. Our results add to a growing body of literature documenting germination of seeds after passing through the digestive system of horses and suggest that conscientious horse owners should select feed sources that are free of weeds. We also find that the current list of noxious weeds used to certify weed-free feed for equines should be comprehensive.

Recombinant antibody fusion constructs with heterologous functional domains are a promising approach to new therapeutic targeting strategies. However, expression of such constructs is mostly limited to cost and labor-intensive mammalian expression systems. Here we report on the employment of Pichia pastoris for the expression of heterologous antibody fusion constructs with green fluorescent protein, A33scFv::GFP, or with cytosine deaminase, A33scFv::CDy, their production in a biofermenter and a modified purification strategy. Combined, these approaches improved production yields by about thirty times over established standard protocols, with extracellular secretion of the fusion construct reaching 12.0 mg/l. Bifunctional activity of the fusion proteins was demonstrated by flow cytometry and an in-vitro cytotoxicity assay. With equal amounts of purified protein, the modified purification method lead to higher functional results. Our results demonstrate the suitability of methylotrophic Pichia expression systems and laboratory-scale bioreactors for the production of high quantities of bifunctionally active heterologous single-chain fusion proteins.

Purpose – The purpose of this study was to establish an objective mathematical decision-making procedure to help universities prioritize credits, while using the Sustainability Tracking, Assessment and Rating System (STARS) framework developed by the Association for Advancement of Sustainability in Higher Education (AASHE), when pursuing their sustainability goals in the short-, medium- and long-term. The authors used the assessment data from Dominican University of California (DUofC), as our case study. Design/methodology/approach – Two criteria, the number of possible points available and overall priority, were developed to classify credits in the STARS version 1.2 framework into six groups from lowest to highest level of difficulty. Two mathematical credit-selecting models based on how many points were available per credit, partial or full amount, were also established to produce short-, medium- and long-term plans. Findings – Our results show that DUofC can reach the Silver level in three years by working on 25 credits; Gold level in nine years by focusing its efforts in 28 additional credits; and Platinum level in 15 years by improving another 10 credits. Originality/value – The procedure developed in this study can be applied to other universities and other versions of the STARS framework.

The trophic behaviour, stomach contents, and morphology of the feeding appendages, with emphasis on setae, of a species of Laomediidae, Axianassa australis (Crustacea: Decapoda: Thalassinidea), were investigated. This species is a deposit feeder. The 32 described setal types were clustered in four main categories: plumed, serrate, plumodenticulate and simple. By examining the setae and spatial position of the segments of the appendages, it is possible to infer that the main function of the 1st and 2nd pereiopods, the 3rd pair of maxillipeds, as well as the dactylus, propodus, carpus and merus of the 2nd maxilliped, is to brush particles. The ischium, basis and coxa of the 2nd maxilliped appear to be specialized for particle retention. For the remaining mouthparts, brushing is generally the main function of the basal endites, while the coxal endites retain particles. Patterns of morphological adaptations to feeding habits are proposed for the Thalassinidea based on a review of the literature. Setal diversity, ratio of plumodenticulate to serrate setal types and mandible morphology are linked to ecological adaptations to trophic modes. Conversely, the presence and degree of development of the crista dentata appear to be related to phylogenetic heritage rather than to feeding mechanisms. Stomach contents are also indicative of trophic modes used by the species; while the predominance of small particles can indicate either filter or deposit feeding, stomach contents with high quantities of large particles suggest deposit feeding as the exclusive trophic mechanism.

The cell-surface marker, gpA33, a new member of the immunoglobulin superfamily, is expressed by gastrointestinal cells and by 95% of colon cancers. It has become a promising target of immunologic therapy strategies, but its biologic function and potential role in tumorigenesis are unknown. In this study, we have investigated the expression of gpA33 on the mRNA and cell-surface protein levels by quantitative reverse transcriptase polymerase chain reaction and flow cytometry, respectively, in response to cell density in the culture and to cell-cycle arrest in the G1, S, or G2/M phases. As internalization of the surface protein had previously been reported, we also investigated the binding and intracellular migration of an anti-gpA33 fluobody with green fluorescent protein (A33scFv::GFP) by laser confocal microscopy. Contrary to intuition, we found that gpA33 surface expression and mRNA levels do only partly correlate under the conditions tested. Dependent on cell density in culture, gpA33 surface expression peaked at the point of confluence. Dependent on cell-cycle phase, it peaked in the G2/M phase but was lowest in the S phase, whereas mRNA levels were highest in S, but almost absent in G1. Laser confocal microscopy clearly demonstrated the intracellular uptake of A33scFv::GFP and showed the migration of microvesicles over time. These findings are, in part, concordant with the putative role of gpA33 as an adhesion molecule. However, intracellular traffic and recycling to the cell surface appear to play a major role in its function and to have an influence on its surface density superseding translational regulation.

The burrow morphology, burrowing behavior and feeding mechanisms of the thalassinidean shrimp Upogebia omissa were studied. Twenty burrow casts were made in situ with epoxy resin, and an overall 'Y' shape was most frequently observed. Several burrows consisted of a single, oblique tunnel; burrow diameter was positively correlated with burrow length, maximum depth and distance between openings. Additionally, burrow length was positively associated with maximum depth, indicating that as burrow length increased burrow depth increased; i.e. burrows spread vertically rather than horizontally. Total sediment displacement by the burrows accounted for 2.6% of sediment to a depth of 30 cm. The sediment-water interface increased by 290% in areas containing burrows compared to areas without burrows. Solitary adults were trapped in 15 casts. Three casts were interconnected, but each burrow contained only 1 shrimp. Regression analysis revealed shrimp length to be positively correlated with burrow diameter and area. In aquaria, U. omissa displayed a dual feeding behavior: the shrimp filtered suspended particles, and also fed directly on the sediment. Filter-feeding occurred mainly within U-shaped tunnels, while deposit-feeding was observed in association with the oblique tunnels of the burrow. Although filter-feeding has been considered as the main trophic mode in upogebiids, we present evidence that U. omissa may have a more pronounced deposit-feeding behavior than described for other species of this group. Based on our findings, we suggest that current models on the functional morphology of burrows in relation to feeding should be used cautiously in inferring the trophic behavior of these shrimp.

Introdução: A estabilidade pode ser alterada devido a um atraso no início da ativação em eletromiografia e/ou na sequência da ativação muscular e/ou na intensidade da ativação, predispondo o indivíduo a distúrbios de controlo motor, incluindo dor lombopélvica (DLP). A eletromiografia de superfície (EMGs) é uma forma de avaliar estes parâmetros. Objetivo: Verificar diferenças do início da ativação na eletromiografia (EMG) e sequência da ativação muscular do transverso abdominal/oblíquo interno (TrA/OI), reto abdominal (RA) e oblíquo externo (OE), usando a EMGs, durante rápidos movimentos de flexão, abdução e extensão do braço, em indivíduos com e sem dor lombopélvica. Métodos: Estudo transversal cuja amostra foi constituída por um grupo de 56 indivíduos que nunca sentiram dor lombopélvica (grupo de Não Dor Lombopélvica – GNDLP) e por outro grupo de 59 indivíduos que tiveram pelo menos um episódio de dor lombopélvica (GDLP), nos últimos 6 meses. Através da EMGs foi captado o sinal eletromiográfico dos músculos deltoide (fibras anteriores, médias e posteriores), TrA/OI, OE e RA. Analisou-se o início da ativação e respetiva sequência de ativação. Os dados estatísticos foram processados no programa SPSS, versão 20.0 para MAC OS, com um nível de significância de 0.05. Resultados: Foram encontradas diferenças significativas entre os dois grupos no início da ativação na EMG do TrA/OI (t=-15.842; p<0.001), OE (t=-3.080; p=0.008) e RA (t=-3.646; p=0.001) durante a rápida flexão do braço; TrA/OI (t=-12.073; p<0.001), OE (t=-3.238; p=0.005) durante a rápida abdução do braço; TrA/OI (t= 29.757; p<0.001), OE (t=-12.308; p<0.001) e RA (t=-4.180; p<0.001) durante a rápida extensão do braço. Em ambos os grupos, houve diferenças significativas na análise entre todos os pares de músculos (p<0.001). Conclusão: Observou-se que o GDLP mostrou um atraso significativo no início da ativação EMG do TRA/OI, OE e RA, durante todos os movimentos, e houve uma sequência na ativação muscular consistente entre os dois grupos, exceto no movimento de extensão do braço. Também se verificou, no GDLP, um padrão de ativação muscular similar entre os músculos superficiais/globais e profundos/locais da região lombopélvica em todas as direções de movimento realizadas.

Este trabalho tem como objetivo abordar e compreender melhor a cultura cigana no geral, de modo a perceber em que medida as transformações culturais ocorridas na sociedade portuguesa têm afetado a comunidade cigana em relação à comunidade alcobacense.Será estudada mais em pormenor a comunidade cigana de Alcobaça e a sua integração na comunidade alcobacense.O facto de residirem num bairro que foi construído apenas para a comunidade cigana, também será abordado, de modo a tentar perceber-se até que ponto foi benéfico ou prejudicou a etnia a nível da integração e inclusão na comunidade maioritária.Pretende-se com este estudo perceber se o processo de aculturação existente até agora, terá influência nas famílias de etnia cigana para a inclusão destes na comunidade dominante e dar a conhecer um pouco do que se “esconde” nesta etnia, ainda tão isolada na cidade de Alcobaça, de modo a desconstruir a cultura cigana perante os alcobacenses para que o preconceito por eles sentido se vá dissipando.Deste modo a investigação irá incidir no Bairro Social da Bela Vista em Alcobaça e numa pequena amostra da comunidade em geral, irei utilizar como metodologia os inquéritos por questionário e entrevista.