Cross immunity protection and antibody-dependent enhancement in a distributed delay dynamic model

Dengue fever is endemic in tropical and subtropical countries, and certain important features of the spread of dengue fever continue to pose challenges for mathematical modelling. Here we propose a system of integro-differential equations (IDE) to study the disease transmission dynamics that involve multi-serotypes and cross immunity. Our main objective is to incorporate and analyze the effect of a general time delay term describing acquired cross immunity protection and the effect of antibody-dependent enhancement (ADE), both characteristics of Dengue fever. We perform qualitative analysis of the model and obtain results to show the stability of the epidemiologically important steady solutions that are completely determined by the basic reproduction number and the invasion reproduction number. We establish the global dynamics by constructing a suitable Lyapunov functional. We also conduct some numerical experiments to illustrate bifurcation structures, indicating the occurrence of periodic oscillations for a specific range of values of a key parameter representing ADE.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001 LIAM - Laboratory for Industrial and Applied Mathematics, Department of Mathematics and Statistics, York University-CA

Effect of General Cross-Immunity Protection and Antibody- Dependent Enhancement in Dengue Dynamics

A mathematical model to describe the dynamic of a multiserotype infectious disease at the population level is studied. Applied to dengue fever epidemiology, we analyse a mathematical model with time delay to describe the cross-immunity protection period, including a key parameter for the antibody-dependent enhancement (ADE) effect, the well-known features of dengue fever infection. Numerical experiments are performed to show the stability of the coexistence equilibrium, which is completely determined by the basic reproduction number and by the invasion reproduction number, as well as the bifurcation structures for different scenarios of dengue fever transmission in a population. The model shows a rich dynamical behavior, from fixed points and periodic oscillations up to chaotic behaviour with complex attractors.Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, CA

Physiological characterization and transcriptome analysis of Pichia pastoris reveals its response to lignocellulose-derived inhibitors.

The negative efects of lignocellulose-derived inhibitors such as acetic acid and furaldehydes on microbial metabolism constitute a signifcant drawback to the usage of biomass feedstocks for the production of fuels and chemicals. The yeast Pichia pastoris has shown a great biotechnological potential for producing heterologous proteins and renewable chemicals. Despite its relevance, the performance of P. pastoris in presence of lignocellulose-derived inhibitors remains unclear. In this work, our results show for the frst time the dose-dependent response of P. pastoris to acetic acid, furaldehydes (HMF and furfural), and sugarcane biomass hydrolysate, both at physiological and transcriptional levels. The yeast was able to grow in synthetic media with up to 6 g.L-1 acetic acid, 1.75 g.L-1 furaldehydes or hydrolysate diluted to 10% (v/v). However, its metabolism was completely hindered in presence of hydrolysate diluted to 30% (v/v). Additionally, the yeast was capable to co-consume acetic acid and glucose. At the transcriptional level, P. pastoris response to lignocellulose-derived inhibitors relays on the up-regulation of genes related to transmembrane transport, oxidoreductase activities, RNA processing, and the repression of pathways related to biosynthetic processes and central carbon metabolism. These results demonstrate a polygenetic response that involves detoxifcation activi ties, and maintenance of energy and cellular homeostasis. In this context, ALD4, OYE3, QOR2, NTL100, YCT1, and PPR1 were identifed as target genes to improve P. pastoris tolerance. Altogether, this work provides valuable insights into the P. pastoris stress tolerance, which can be useful to expand its use in diferent bioprocesses

Lifetime physical activity and risk of breast cancer in pre-and post-menopausal women

© 2015 Springer Science+Business Media New York To investigate the association between different types of physical activity (PA) and breast cancer. A case–control study of breast cancer was conducted in Western Australia from 2009 to 2011, in which 1205 women with breast cancer and 1789 frequency age-matched breast cancer-free control women were recruited. A self-administered questionnaire was used to collect information about lifetime and age-period recreational, household, occupational and transport physical activities. Detailed questions about demographic characteristics, and relevant reproductive, medical and lifestyle factors were also included. Logistic regression and restrictive cubic spline analyses were applied to investigate the association and dose–response relationship between PA and breast cancer risk. Subgroup analysis was performed regarding menopausal status. We found non-linear dose–response associations between PA and risk of breast cancer. Overall, 95–130 MET-hours/week of total lifetime PA was associated with the lowest breast cancer risk. The effects were stronger among post-menopausal women. We also found that the medium amounts of recreational PA (up to 21 MET-hours/week) were associated with lower breast cancer risk among post-menopausal women. Further analysis on the intensity of recreational PA demonstrated different dose–response associations between moderate- and vigorous-intensity recreational PA and breast cancer risk. We found that PA was associated with a reduced risk of breast cancer among post-menopausal women, but not in a linear fashion. Recreational PA of different intensities may have different dose–response associations with risk of breast cancer

Post-diagnosis physical activity and sedentary behaviour and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis

\ua9 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. Low physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post-diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post-diagnosis physical activity, and/or sedentary behaviour in relation to all-cause and cause-specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non-linear dose–response random-effects meta-analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non-overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%–60% estimated reductions in risk. Sedentary behaviour was positively associated with all-cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited-suggestive evidence for recreational physical activity with all-cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited-no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders

Post-diagnosis adiposity and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis

\ua9 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. The adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta-analysis on post-diagnosis adiposity measures (body mass index [BMI], waist circumference, waist-to-hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random-effects meta-analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta-analyses were possible for BMI and all-cause mortality, colorectal cancer-specific mortality, and cancer recurrence/disease-free survival. Non-linear meta-analysis indicated a reverse J-shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m2). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m2), namely 60% and 23% higher risk for all-cause mortality; 95% and 26% for colorectal cancer-specific mortality; and 37% and 24% for cancer recurrence/disease-free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow-up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity-outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well-designed observational studies and interventional trials are needed to provide further clarification

Body fatness and physical activity at young ages and the risk of breast cancer in premenopausal women

We examined the relationship between body fatness, sports participation and breast cancer risk in 1560 premenopausal cases and 1548 controls, from three related population-based case–control studies in the UK. Half of the women with breast cancer were aged less than 36 years at diagnosis. Women who perceived themselves as plump at age 10 years had a relative risk of 0.83 (95% confidence interval 0.69–0.99, P=0.03) as compared with those who perceived themselves as thin. Self-reported obesity compared with leanness at diagnosis was associated with a relative risk of 0.78 (95% confidence interval 0.56–1.06, P=0.11). Women who reported having been plump at age 10 years and overweight or obese at diagnosis had a relative risk of 0.75 (95% confidence interval 0.56–1.01, P=0.06) as compared with those who reported being thin at age 10 years and at diagnosis. Findings for three related measures of body fatness suggested that obesity is associated with a reduced risk of premenopausal breast cancer. There was no association between sports participation and breast cancer risk in these premenopausal women. The relative risk for spending an average of more than 1 h per week in sports compared with less from ages 12 to 30 years was 1.00 (95% CI 0.86–1.16, P=0.98)

The Porto European Cancer Research Summit 2021

Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high-quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures – namely translational research, clinical/prevention trials and outcomes research – were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next-generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health-related quality-of-life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU-wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost.Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. JT reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, DaiichiSankyo, F. Hoffmann‐La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc. And also educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER). JT also declares institutional financial interest in form of financial support for clinical trials or contracted research for Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann‐La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen‐Cilag SA, MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc, Spanish Association Against Cancer Scientific Foundation and Cancer Research UK. MB has received funding for his research projects and for educational grants to the University of Dresden by Bayer AG (2016‐2018), Merck KGaA (2014‐open) and Medipan GmbH (2014‐2018). He is on the supervisory board of HI‐STEM GmbH (Heidelberg) for the German Cancer Research Center (DKFZ, Heidelberg) and also member of the supervisory body of the Charité University Hospital, Berlin. As former chair of OncoRay (Dresden) and present CEO and Scientific Chair of the German Cancer Research Center (DKFZ, Heidelberg), he has been or is responsible for collaborations with a multitude of companies and institutions, worldwide. In this capacity, he has discussed potential projects and signed contracts for research funding and/or collaborations with industry and academia for his institute(s) and staff, including but not limited to pharmaceutical companies such as Bayer, Boehringer Ingelheim, Bosch, Roche and other companies such as Siemens, IBA, Varian, Elekta, Bruker, etc. In this role, he was/is also responsible for the commercial technology transfer activities of his institute(s), including the creation of start‐ups and licensing. This includes the DKFZ‐PSMA617 related patent portfolio [WO2015055318 (A1), ANTIGEN (PSMA)] and similar IP portfolios. MB confirms that, to the best of his knowledge, none of the above funding sources were involved in the preparation of this paper. BB has received research funding from 4D Pharma, Abbvie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi‐Sankyo, Eli Lilly, GSK, Inivata, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche‐Genentech, Sanofi, Takeda, Tolero Pharmaceuticals. FC declares consultancy role for: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi‐Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Medscape, Merck‐Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre‐Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva. SF is a consulting or advisory board member at Bayer, Illumina, Roche; has received honoraria from Amgen, Eli Lilly, PharmaMar, Roche; has received research funding from AstraZeneca, Pfizer, PharmaMar, Roche; has received sponsorship of travel or accommodation expenses by Amgen, Eli Lilly, Illumina, PharmaMar, Roche. SG owns AstraZeneca stock and is a full‐time employee of AstraZeneca. PN has had an advisory role at Bayer, MSD Oncology, has received honoraria from Bayer, Novartis and MSD Oncology, and has had travel expenses paid by Novartis. JO has been an advisory board member at Roche, Novartis, Bayer, Merck, Eisai, Astrazeneca, Pierre Fabre Medicament and Bristol‐Myers Squibb. He has also received research funding by IPO Porto, Astrazeneca, Fundação para a Ciencia e a Tecnologia (FCT) and Liga Portuguesa Contra o Cancro (LPCC). AR is an employee of European Federation of Pharmaceutical Industries and Associations, Brussels, MSD International Business GmbH, Kriens, Switzerland[CvG1], and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA, who may own stock and/or hold stock options in the Company.RS serves as principal investigator of the ASCO TAPUR study. ASCO receives research grants from the following companies in support of the study: Astra‐Zeneca, Bayer, Boehringer‐Ingelheim, Bristol Myers Squibb, Genentech, Lilly, Merck, Pfizer, Seattle Genetics. Dr. Schilsky serves as a member of the managing board of Clariifi and as a consultant to Bryologyx, Cellworks Group, EQRx, and Scandion Oncology. The Netherlands Cancer Institute receives research support via EV from Roche, Astrazeneca, Eisai, Novartis, GSK, Clovis, BMS, MSD, Pfizer, Amgen, Bayer, Lilly, Janssen and Seagen. LZ is founder of everImmune, member of the board of directors of Transgene, member of the scientific advisory board of Transgene, EpiVax, Lytix Biopharma. LZ has also had research contracts with: Merus, Roche, Tusk, Kaleido, GSK, BMS, Incyte, Pileje, Innovate Pharma, and Transgene and has received honoraria by Transgene. All other authors have no conflicts of interest to declare. Regarding the design of innovative and adaptive clinical trials, two examples were illustrated: the first European multimodular, two‐part academic CCE‐endorsed Basket of Baskets (BoB) study, and the recently launched CCE Building Data Rich Clinical Trials (DART) Consortium, which is supported by EU’s Horizon 2020 research and innovation programme (Box 13 ). We are grateful for the support by Carolina Espina, International Agency for Research on Cancer; Christina von Gertten, European Academy of Cancer Sciences; Ana Augusta Silva, Portuguese Oncology Institute of Porto; and Teresa Tavares, Ministry of Science, Technology and Higher Education, Portugal for their excellent cooperation. Carmen Jeronimo, Portuguese Oncology Institute of Porto, collaborated in the presentation of Porto Comprehensive Cancer Center by Raquel Seruca