bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Senescence Promotes Skin Carcinogenesis through p38MAPK and p44/42MAPK Signaling
Authors: Alimirah Fatouma , Pulido Tanya , Valdovinos Alexis , Alptekin Sena , Chang Emily , Jones Elijah , Diaz Diego A. , Flores Jose , Velarde Michael C. , Demaria Marco , Davalos Albert R. , Wiley Christopher D. , Limbad Chandani , Desprez Pierre-Yves , Campisi Judith 
Published: July 2020

Abstract

Cellular senescence entails an irreversible growth arrest that evolved in part to prevent cancer. Paradoxically, senescent cells secrete proinflammatory and growth-stimulatory molecules, termed the senescence-associated secretory phenotype (SASP), which is correlated with cancer cell proliferation in culture and xenograft models. However, at what tumor stage and how senescence and the SASP act on endogenous tumor growth in vivo is unknown. To understand the role of senescence in cancer etiology, we subjected p16-3MR transgenic mice, which permit the identification and selective elimination of senescent cells in vivo, to the well-established two-step protocol of squamous cell skin carcinoma, in which tumorigenesis is initiated by a carcinogen 7,12-dimethylbenz[α]anthracene, and then promoted by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We show that TPA promotes skin carcinogenesis by inducing senescence and a SASP. Systemic induction of senescence in nontumor-bearing p16-3MR mice using a chemotherapy followed by the two-step carcinogenesis protocol potentiated the conversion of benign papillomas to carcinomas by elevating p38MAPK and MAPK/ERK signaling. Ablation of senescent cells reduced p38MAPK and MAPK/ERK signaling, thereby preventing the progression of benign papillomas to carcinomas. Thus, we show for the first time that senescent cells are tumor promoters, not tumor initiators, and that they stimulate skin carcinogenesis by elevating p38MAPK and MAPK/ERK signaling. These findings pave the way for developing novel therapeutics against senescence-fueled cancers.

Significance:
These findings identify chemotherapy-induced senescence as a culprit behind tumor promotion, suggesting that elimination of senescent cells after chemotherapy may reduce occurrence of second cancers decades later.
Brain Metastasis Cell Lines Panel: A Public Resource of Organotropic Cell Lines
Authors: Valiente Manuel , Van Swearingen Amanda E.D. , Anders Carey K. , Bairoch Amos , Boire Adrienne , Bos Paula D. , Cittelly Diana M. , Erez Neta , Ferraro Gino B. , Fukumura Dai , Gril Brunilde , Herlyn Meenhard , Holmen Sheri L. , Jain Rakesh K. , Joyce Johanna A. , Lorger Mihaela , Massague Joan , Neman Josh , Sibson Nicola R. , Steeg Patricia S. , Thorsen Frits , Young Leonie S. , Varešlija Damir , Vultur Adina , Weis-Garcia Frances , Winkler Frank 
Published: July 2020

Abstract

Spread of cancer to the brain remains an unmet clinical need in spite of the increasing number of cases among patients with lung, breast cancer, and melanoma most notably. Although research on brain metastasis was considered a minor aspect in the past due to its untreatable nature and invariable lethality, nowadays, limited but encouraging examples have questioned this statement, making it more attractive for basic and clinical researchers. Evidences of its own biological identity (i.e., specific microenvironment) and particular therapeutic requirements (i.e., presence of blood–brain barrier, blood–tumor barrier, molecular differences with the primary tumor) are thought to be critical aspects that must be functionally exploited using preclinical models. We present the coordinated effort of 19 laboratories to compile comprehensive information related to brain metastasis experimental models. Each laboratory has provided details on the cancer cell lines they have generated or characterized as being capable of forming metastatic colonies in the brain, as well as principle methodologies of brain metastasis research. The Brain Metastasis Cell Lines Panel (BrMPanel) represents the first of its class and includes information about the cell line, how tropism to the brain was established, and the behavior of each model in vivo. These and other aspects described are intended to assist investigators in choosing the most suitable cell line for research on brain metastasis. The main goal of this effort is to facilitate research on this unmet clinical need, to improve models through a collaborative environment, and to promote the exchange of information on these valuable resources.
A Complex Systems Model of Breast Cancer Etiology: The Paradigm II Conceptual Model
Authors: Hiatt Robert A. , Engmann Natalie J. , Balke Kaya , Rehkopf David H. 
Published: July 2020

AbstractBackground:The etiology of breast cancer is a complex system of interacting factors from multiple domains. New knowledge about breast cancer etiology continues to be produced by the research community, and the communication of this knowledge to other researchers, practitioners, decision makers, and the public is a challenge.Methods:We updated the previously published Paradigm model (PMID: 25017248) to create a framework that describes breast cancer etiology in four overlapping domains of biologic, behavioral, environmental, and social determinants. This new Paradigm II conceptual model was part of a larger modeling effort that included input from multiple experts in fields from genetics to sociology, taking a team and transdisciplinary approach to the common problem of describing breast cancer etiology for the population of California women in 2010. Recent literature was reviewed with an emphasis on systematic reviews when available and larger epidemiologic studies when they were not. Environmental chemicals with strong animal data on etiology were also included.Results:The resulting model illustrates factors with their strength of association and the quality of the available data. The published evidence supporting each relationship is made available herein, and also in an online dynamic model that allows for manipulation of individual factors leading to breast cancer (https://cbcrp.org/causes/).Conclusions:The Paradigm II model illustrates known etiologic factors in breast cancer, as well as gaps in knowledge and areas where better quality data are needed.Impact:The Paradigm II model can be a stimulus for further research and for better understanding of breast cancer etiology.
Multicenter Phase II Study of Cabazitaxel in Advanced Gastroesophageal Cancer: Association of HER2 Expression and M2-Like Tumor-Associated Macrophages with Patient Outcome
Authors: Shah Manish A. , Enzinger Peter , Ko Andrew H. , Ocean Allyson J. , Philip Philip Agop , Thakkar Prashant V. , Cleveland Kyle , Lu Yao , Kortmansky Jeremy , Christos Paul J. , Zhang Chao , Kaur Navjot , Elmonshed Dina , Galletti Giuseppe , Sarkar Sandipto , Bhinder Bhavneet , Pittman Meredith E. , Plotnikova Olga Mikhaylovna , Kotlov Nikita , Frenkel Felix , Bagaev Aleksander , Elemento Olivier , Betel Doron , Giannakakou Paraskevi , Lenz Heinz-Josef 
Published: July 2020

AbstractPurpose:We examined cabazitaxel, a novel next-generation taxoid, in patients with metastatic gastric cancer in a multicenter phase II study.Patients and Methods:Patients who have progressed on one or more prior therapies for locally advanced, unresectable, or metastatic disease were eligible, and prior taxane therapy was allowed. Taxane-naïve and pretreated cohorts were analyzed independently for efficacy. The primary endpoint for both cohorts was progression-free survival (PFS) using RECIST 1.1, using a Simon's two-stage design (10% significance and 80% power) for both cohorts. Comprehensive molecular annotation included whole exome and bulk RNA sequencing.Results:Fifty-three patients enrolled in the taxane-naïve cohort (Arm A) and 23 patients in the prior-taxane cohort (Arm B), from January 8, 2013, to April 8, 2015: median age 61.7 years (range, 35.5–91.8 years), 66% male, 66% Caucasian. The most common adverse events included neutropenia (17% Arm A and 39% Arm B), fatigue/muscle weakness (13%), and hematuria (12%). In Arm A, the 3-month PFS rate was 28% [95% confidence interval (CI), 17%–42%] and did not meet the prespecified efficacy target. The 3-month PFS rate in Arm B was 35% (95% CI, 16%–57%) and surpassed its efficacy target. HER2 amplification or overexpression was associated with improved disease control (P = 0.003), PFS (P = 0.04), and overall survival (P = 0.002). An M2 macrophage signature was also associated with improved survival (P = 0.031).Conclusions:Cabazitaxel has modest activity in advanced gastric cancer, including in patients previously treated with taxanes. Her2 amplification/overexpression and M2 high macrophage signature are potential biomarkers for taxane efficacy that warrant further evaluation.
Nebuliser hygiene in cystic fibrosis: evidence-based recommendations
Authors: Bell Jane , Alexander Lauren , Carson Jane , Crossan Amanda , McCaughan John , Mills Hazel , O'Neill Damian , Moore John E. , Millar B. Cherie 
Published: July 2020

Nebulised therapies are extensively used in the daily therapeutic management of cystic fibrosis both for mucociliary clearance and for the management of chronic infections. Extensive developments have been made in relation to nebulised drug delivery mechanisms and drug formulations, and guidelines have been prepared that have addressed the appropriate use of such therapies. However, due to these developments, a plethora of nebuliser devices and drug chambers exist, and frequently, the limited guidance provided in relation to nebuliser hygiene is to follow manufacturers' instructions. Such instructions are inconsistent and at times confusing, translating to an increase in the burden associated with nebuliser maintenance. An evidence-based universal guideline relating to nebuliser care and hygiene is urgently required that is applicable to both at-home use and inpatient use. This article reviews the scientific literature in order to propose an evidence-based approach to nebuliser hygiene to ensure optimum drug delivery, and infection prevention and control.Educational aimsTo understand the reasons why nebuliser hygiene is important.To give an overview of the current nebuliser care instructions that have been described by manufacturers, societies and the scientific literature.To outline the current nebuliser hygiene practices used by persons with cystic fibrosis in the home and hospital settings.To highlight areas that need further evaluation to promote optimum nebuliser care.To establish an evidence-based guideline for nebuliser hygiene in relation to cystic fibrosis.
The Establishment and Application Studies on Precise Lysosome pH Indicator Based on Self-Decomposable Nanoparticles
Authors: Pang Cui , Song Chaojun , Li Yize , Wang Qiaofeng , Zhu Xiaosheng , Wu Jianwei , Tian Yi , Fan Hao , Hu Jinwei , Li Chen , Wang Baolong , Li Xiaoye , Liu Wenchao , Fan Li 
Published: July 2020

AbstractAcidic pH of lysosomes is closely related to autophagy; thus, well known of the precise lysosomes, pH changes will give more information on the autophagy process and status. So far, however, only pH changes in a relatively broad range could be indicated, the exact lysosomes pH detection has never arrived. In our study, we established an endo/lysosome pH indicator based on the self-decomposable SiO2 nanoparticle system with specific synthesis parameters. The central concentrated methylene blue (MB) in the central-hollow structural nanoparticles presented sensitive release as a function of pH values from pH 4.0–4.8, which is exactly the pH range of lysosomes. The linear correlation of the optical density (OD) values and the pH values has been built up, which has been used for the detection of lysosomes pH in 6 different cell lines. Moreover, by this system, we succeeded in precisely detecting the pH average changes of lysosomes before and after black mesoporous silicon (BPSi) NP endocytosis, clarifying the mechanism of the autophagy termination after BPSi endocytosis. So, the self-decomposable nanoparticle-based luminal pH indicator may provide a new methodology and strategy to know better of the lysosome pH, then indicate more details on the autophagy process or other important signaling about metabolisms.
HEnRY: a DZIF LIMS tool for the collection and documentation of biomaterials in multicentre studies
Authors: Heinen Stephanie , Schulze Nick , Franke Bernd , Klein Florian , Lehmann Clara , Vehreschild Maria J. G. T. , Gloistein Claas , Stecher Melanie , Vehreschild Jörg Janne 
Published: July 2020

AbstractBackgroundWell-characterized biomaterials of high quality have great potential for acceleration and quality improvement in translational biomedical research. To improve accessibility of local sample collections, efforts have been made to create central biomaterial banks and catalogues. Available technical solutions for creating professional local sample catalogues and connecting them to central systems are cost intensive and/or technically complex to implement. Therefore, the Translational Thematic Unit HIV of the German Center for Infection Research (DZIF) developed a Laboratory Information and Management System (LIMS) called HIV Engaged Research Technology (HEnRY) for implementation into the Translational Platform HIV (TP-HIV) at the DZIF and other research networks.ResultsHEnRY is developed at the University Hospital of Cologne. It is an advanced LIMS to manage processing and storage of samples and aliquots of different sample types. Features include:monitoring of stored samples and associated informationdata selection via query tools or Structured Query Language (SQL)preparation of summary documents, including scannable search listscentralized management of the practical laboratory part of multicentre studies (e.g. import of drawing schemes and sample processing steps),preparation of aliquot shipments, including associated documents to be added to shipmentsunique and secure identification of aliquots through use of customizable Quick Response (QR) code labels directly from HEnRYsupport of aliquot data transmission to central registries.In summary, HEnRY offers all features necessary for a LIMS software. In addition, the structure of HEnRY provides sufficient flexibility to allow the implementation in other research areas.ConclusionHEnRY is a free biobanking tool published under the MIT license. While it was developed to support HIV research in Germany, the feature set and language options, allow much broader applications and make this a powerful free research tool.
Critique of the pairwise method for estimating qPCR amplification efficiency: beware of correlated data!
Authors: Tellinghuisen Joel 
Published: July 2020

Abstract
Background
A recently proposed method for estimating qPCR amplification efficiency E analyzes fluorescence intensity ratios from pairs of points deemed to lie in the exponential growth region on the amplification curves for all reactions in a dilution series. This method suffers from a serious problem: The resulting ratios are highly correlated, as they involve multiple use of the raw data, for example, yielding ~ 250 E estimates from ~ 25 intensity readings. The resulting statistics for such estimates are falsely optimistic in their assessment of the estimation precision.

Results
Monte Carlo simulations confirm that the correlated pairs method yields precision estimates that are better than actual by a factor of two or more. This result is further supported by estimating E by both pairwise and Cq calibration methods for the 16 replicate datasets from the critiqued work, and then comparing the ensemble statistics for these methods.

Conclusion
Contrary to assertions in the proposing work, the pairwise method does not yield E estimates a factor of 2 more precise than estimates from Cq calibration fitting (the standard curve method). On the other hand, the statistically correct direct fit of the data to the model behind the pairwise method can yield E estimates of comparable precision. Ways in which the approach might be improved are discussed briefly.
Molecular docking and machine learning analysis of Abemaciclib in colon cancer
Authors: Liñares-Blanco Jose , Munteanu Cristian R. , Pazos Alejandro , Fernandez-Lozano Carlos 
Published: July 2020

AbstractBackgroundThe main challenge in cancer research is the identification of different omic variables that present a prognostic value and personalised diagnosis for each tumour. The fact that the diagnosis is personalised opens the doors to the design and discovery of new specific treatments for each patient. In this context, this work offers new ways to reuse existing databases and work to create added value in research. Three published signatures with significante prognostic value in Colon Adenocarcinoma (COAD) were indentified. These signatures were combined in a new meta-signature and validated with main Machine Learning (ML) and conventional statistical techniques. In addition, a drug repurposing experiment was carried out through Molecular Docking (MD) methodology in order to identify new potential treatments in COAD.ResultsThe prognostic potential of the signature was validated by means of ML algorithms and differential gene expression analysis. The results obtained supported the possibility that this meta-signature could harbor genes of interest for the prognosis and treatment of COAD. We studied drug repurposing following a molecular docking (MD) analysis, where the different protein data bank (PDB) structures of the genes of the meta-signature (in total 155) were confronted with 81 anti-cancer drugs approved by the FDA. We observed four interactions of interest: GLTP - Nilotinib, PTPRN - Venetoclax, VEGFA - Venetoclax and FABP6 - Abemaciclib. The FABP6 gene and its role within different metabolic pathways were studied in tumour and normal tissue and we observed the capability of the FABP6 gene to be a therapeutic target. Our in silico results showed a significant specificity of the union of the protein products of the FABP6 gene as well as the known action of Abemaciclib as an inhibitor of the CDK4/6 protein and therefore, of the cell cycle.ConclusionsThe results of our ML and differential expression experiments have first shown the FABP6 gene as a possible new cancer biomarker due to its specificity in colonic tumour tissue and no expression in healthy adjacent tissue. Next, the MD analysis showed that the drug Abemaciclib characteristic affinity for the different protein structures of the FABP6 gene. Therefore, in silico experiments have shown a new opportunity that should be validated experimentally, thus helping to reduce the cost and speed of drug screening. For these reasons, we propose the validation of the drug Abemaciclib for the treatment of colon cancer.
Unveiling the genetic basis of Sclerotinia head rot resistance in sunflower
Authors: Filippi C. V. , Zubrzycki J. E. , Di Rienzo J. A. , Quiroz F. J. , Puebla A. F. , Alvarez D. , Maringolo C. A. , Escande A. R. , Hopp H. E. , Heinz R. A. , Paniego N. B. , Lia V. V. 
Published: July 2020

Abstract
Background
Sclerotinia sclerotiorum is a necrotrophic fungus that causes Sclerotinia head rot (SHR) in sunflower, with epidemics leading to severe yield losses. In this work, we present an association mapping (AM) approach to investigate the genetic basis of natural resistance to SHR in cultivated sunflower, the fourth most widely grown oilseed crop in the world.

Results
Our association mapping population (AMP), which comprises 135 inbred breeding lines (ILs), was genotyped using 27 candidate genes, a panel of 9 Simple Sequence Repeat (SSR) markers previously associated with SHR resistance via bi-parental mapping, and a set of 384 SNPs located in genes with molecular functions related to stress responses. Moreover, given the complexity of the trait, we evaluated four disease descriptors (i.e, disease incidence, disease severity, area under the disease progress curve for disease incidence, and incubation period). As a result, this work constitutes the most exhaustive AM study of disease resistance in sunflower performed to date.
Mixed linear models accounting for population structure and kinship relatedness were used for the statistical analysis of phenotype-genotype associations, allowing the identification of 13 markers associated with disease reduction. The number of favourable alleles was negatively correlated to disease incidence, disease severity and area under the disease progress curve for disease incidence, whereas it was positevily correlated to the incubation period.

Conclusions
Four of the markers identified here as associated with SHR resistance (HA1848, HaCOI_1, G33 and G34) validate previous research, while other four novel markers (SNP117, SNP136, SNP44, SNP128) were consistently associated with SHR resistance, emerging as promising candidates for marker-assisted breeding. From the germplasm point of view, the five ILs carrying the largest combination of resistance alleles provide a valuable resource for sunflower breeding programs worldwide.
Social and behavioural risk factors in the prevention and management of cardiovascular disease in Kerala, India: a catchment area population survey
Authors: Madavanakadu Devassy Saju , Webber Martin , Scaria Lorane , Amuthavalli Thiyagarajan Jotheeswaran , Fendt-Newlin Meredith , Joubert Jacques , Benny Anuja Maria , Nannatt Anjana , Joubert Lynette 
Published: July 2020

AbstractBackgroundCardiovascular disease (CVD) is the leading cause of mortality in India. Social and behavioural factors are strongly interrelated in the prevention and control of CVD. The ability to make lifestyle changes to control hypertension and diabetes (major risk factors for CVD) is determined by factors such as education, gender, caste, poverty, and urbanicity. This study aimed to improve our understanding of the inter-relationship of social and behavioural factors in the management of elevated serum glucose and high blood pressure and co-morbid mental health conditions.MethodsA population-based catchment area cross sectional survey was conducted in Kerala, India. Data were collected from residents aged over 30 years (n = 997) using standardized tools and clinical measures. We performed latent class analysis incrementally to extract homogeneous latent classes of individuals based on their responses to social and behavioural risk factors in the survey. Using structural equation models, we assessed the mediating effect of depression and anxiety, and social or behavioural risk factors, on management of high blood pressure and raised serum glucose levels.ResultsThe prevalence of high blood pressure and blood glucose in the sample was 33 and 26% respectively. Latent class analysis found three clusters of risk factors. One had a predominance of behavioural characteristics, another of social risk factors and the third was a low risk group. Age, female sex, and marital status had an effect on high blood pressure and high glucose, though were mediated by mental health, social and behavioural risk factors.ConclusionsInterventions to improve the management of risk factors for CVD need to address social risk factors and be sensitive to the needs of population sub-groups that may require additional support to access health services. An integration of social and health services may be required to achieve this.