bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pattern and distribution of cancers in areas of Iraq exposed to Depleted Uranium
Authors: Aldujaily Esraa , Duabil Ali , Abbas Zwain Kussay M. , Fatlawi Hayder K. , Al-Behadili Ali , saabery Emad Al , Alwaaely Yasseen A. , Joboury Sijal Al , Qassid Omar Layth , Kelabi Liwaa Al 
Published: April 2020

AbstractIntroductionCancer is one of the major causes of death worldwide. Health systems whether in developed or in developing countries like Iraq are burdened with different programs to control cancer. Our study is intended to provide information about cancer in the region of Middle Euphrates Area (MEA) of Iraq, which is one of the major areas in Iraq that exposed to the depleted Uranium (DU) at different time periods. Therefore, we are aiming to explore more information about the behavior of cancers in this region of Iraq (pattern and distribution).Aim: our study aims to describe the landscape of cancer with wide focus on the clinicopathological behavior of different types of cancers in MEA of Iraq to determine whether any differences have cropped up over time in Iraqi patients’ presentations.Patients and methodsThis study is a retrospective descriptive study design. Data were collected from a single tertiary cancer care oncology centre for three consecutive years from 2016 up to 2018. This Database covers nearly the entire Middle Euphrates area of Iraq. All statistical tests performed at a 95% level of significance with a two-sided p-value of 0.05 indicating statistical significance.Results and conclusionAccording to this study, the three most common cancers among the entire population were breast, lung, and brain cancers. Females constituted 57.0% of the entire study. Most cancers including breast cancer presented with aggressive clinicopathological behavior. Middle age groups of both sexes are more at risk of developing different cancers. Such findings are important and pave the way for future scientific cancer control programs in Iraq especially for breast cancer. The cancer appears to be flourishing in Iraq, which could be due to multiple factors. Finding a new strategy to predict the treatment response, recurrence or aggressiveness of cancers in Iraq is crucial.Summary (Strengths and limitations of this study)Whats new in this study is the wide focus of studying the clinicopathological behavior of all cancers in middle Euphrates area of Iraq to establish a solid base for further future studies that aims at developing the health system and cancer control programs in Iraq and middle east. The area of middle and south of Iraq which is named the middle Euphrates area is an area of major interest for researchers and clinicians as the cancer is flourishing in this area. previous studies excuse this increase of cancer incidence to the exposure to cancerous agents like depleted uranium. This fact inspired us to explore more information about the behavior of cancer in Iraq. The limitations of this study are the lack of therapy and survival data that we hope to include them in future studies.
COVID-19 most vulnerable Mexican cities lack the public health infrastructure to face the pandemic: a new temporally-explicit model
Authors: Dáttilo Wesley , e Silva Alcides Castro , Guevara Roger , Fors Ian MacGregor , Ribeiro Sérvio Pontes 
Published: April 2020

AbstractRecently, a wide array of epidemiological models have been developed to guide public health actors in containing the rapid dissemination of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cause of COVID-19. Despite their usefulness, many epidemiological models recently developed to understand the spread of SARS-CoV-2 and infection rates of COVID-19 fall short as they ignore human mobility, limiting our understanding of the spread of the disease, together with the vulnerability of population centers in a broad scale. We developed a new temporally-explicit model and simulated several social distancing scenarios to predict the vulnerability to COVID-19 of 50 Mexican cities that are interconnected by their air transportation network. Additionally, we assessed the sufficiency of the public health infrastructure in the focal cities to face the pandemic over time. Based on our model, we show that the most important cities within the Mexican air transportation network are the most vulnerable to COVID-19, with all assessed public health infrastructure being insufficient to face the modeled scenario for the pandemic after 100 days. Despite these alarming findings, our results show that social distancing could dramatically decrease the total number of infected people (77% drop-off for the 45% distancing scenario when contrasted with no distancing), flattening the growth of infection rate. Thus, we consider that this study provides useful information that may help decision-makers to timely implement health policies to anticipate and lessen the impact of the current pandemic in Mexico.Significance StatementWe used a new temporally-explicit model focused on air transportation networks to predict the vulnerability of 50 focal Mexican cities to COVID-19. We found that most vulnerable cities lack of the required public health infrastructure (i.e., number of inpatient and intensive care unit beds) to face this new pandemic, overloading in all cases after 100 days. However, our results show that a 45% social distancing scenario can reduce the number of infected people by up to 78.7%, flattening the growth rate of people with COVID-19 before infection rates soar exponentially countrywide.
Genetic timestamping of plasma cellsin vivoreveals homeostatic population turnover
Authors: Xu AQ , Barbosa RR , Calado DP 
Published: April 2020

AbstractPlasma cells (PC)s are essential for protection from infection, and at the origin of incurable cancers. Current studies do not circumvent limitations of removing PCs from their microenvironment and confound formation and maintenance. This is in part due to the lack of tools to perform specific genetic manipulationin vivo. Also, studies of PC population dynamics have mostly relied on the use of nucleotide analog incorporation that does not label quiescent cells, a property of most PCs. Here we characterize in detail a genetic tool (JchaincreERT2) that permits first-ever specific genetic manipulation in PCin vivo, across immunoglobulin isotypes. Using this tool we found that PC numbers remained constant over-time and that PC decay was compensated by the emergence of new cells, supporting an homeostatic turnover of the population. TheJchaincreERT2genetic tool paves the way for in-depth mechanistic understanding of PC biology and pathologyin vivo, in their microenvironment.HighlightsJchainexpression occurs in most plasma cells across immunoglobulin isotypesJchaincreERT2mediated genetic manipulation is effective only in plasma cellsGenetic timestamping of plasma cells reveals homeostatic regulation
Ahr-bacterial diet interaction modulates aging and associated pathologies inC. elegans
Authors: Brinkmann Vanessa , Schiavi Alfonso , Shaik Anjumara , Puchta Daniel R. , Ventura Natascia 
Published: April 2020

AbstractGenetic and environmental factors concurrently shape the aging process. The nematodeCaenorhabditis eleganshas been instrumental in the past 30 years to identify most genes and interventions nowadays known to modulate aging (Lopez-Otin et al. 2013, Tigges et al. 2014, Dato et al. 2017). The aryl-hydrocarbon-receptor (AhR) was discovered as a dioxin-binding transcription factor involved in the metabolism of different environmental toxicants and xenobiotics (Poland et al. 1976). Since then, the variety of pathophysiological processes regulated by the AhR has rapidly grown, ranging from the immune response to cell death and metabolic pathways, and we disclosed it promotes aging phenotypes across species (Eckers et al. 2016, Esser et al. 2018). Interestingly, many AhR modulators may impact on aging and age-associated pathologies, but, whether their effects are actually AhR-dependent has never been explored. Here, we show for the first time that lack ofC. elegansAHR-1 affects health and lifespan in a context-dependent manner. Using known mammalian AhR modulators we found that, similar to mammals,ahr-1has protective effects against environmental insults and identified a new role for AhR-bacterial diet interaction in animal lifespan, stress resistance, and age-associated pathologies. We narrowed down the dietary factor involved in the observed AhR-dependent features to a bacterially-extruded metabolite likely involved in tryptophan metabolism. This is the first study clearly establishingC. elegansas a good model organism to investigate evolutionarily conserved functions of AhR-modulators and -regulated processes, indicating it can be exploited to contribute to the discovery of novel information about AhR in mammals.Significance StatementThe roundwormC. eleganshas been instrumental for the identification of many of the genetic and environmental factors known to concurrently shape the aging process. The aryl-hydrocarbon-receptor (AhR) was originally discovered as a dioxin-binding transcription factor involved in the metabolism of environmental toxicants and, in the past, we found it promotes aging phenotypes across species. Many AhR modulators may impact on aging and age-associated pathologies, but, whether their effects are actually AhR-dependent has never been explored. We show here for the first time thatC. elegansAhR has protective effects against environmental insults such as UVB radiations and the xenobiotic BaP and identified a new critical role for AhR-bacterial diet interaction in animal lifespan, stress resistance, and age-associated pathologies.
SETD2 is an actin lysine methyltransferase
Authors: Seervai Riyad N.H. , Jangid Rahul K. , Karki Menuka , Tripathi Durga Nand , Jung Sung Yun , Kearns Sarah E. , Verhey Kristen J. , Cianfrocco Michael A. , Millis Bryan A. , Tyska Matthew J. , Mason Frank M. , Rathmell W. Kimryn , Park In Young , Dere Ruhee , Walker Cheryl L. 
Published: April 2020

ABSTRACTSET-domain-containing-2 (SETD2) was identified as the methyltransferase responsible for the histone 3 lysine 36 trimethyl (H3K36me3) mark of the histone code. Most recently, SETD2 has been shown to be a dual-function remodeler that regulates genome stability via methylation of dynamic microtubules during mitosis and cytokinesis. Here we show that actin is abona fidetarget for methylation by SETD2in vitroand in cells. Antibodies against the SETD2 trimethyl lysine epitope recognize methylated actin, with this methyl mark localizing to areas of active actin cytoskeleton reorganization in migrating cells. Disruption of this methylation activity causes defects in actin polymerization and impairs collective cell migration. Together, these data identify SETD2 as a multifunctional cytoskeletal remodeler regulating methylation and polymerization of actin filaments, and provide new avenues for understanding how defects in SETD2 drive disease via aberrant cytoskeletal methylation.
Enhancement of trans-cleavage activity of Cas12a with engineered crRNA enables amplified nucleic acid detection
Authors: Nguyen Long T. , Smith Brianna M. , Jain Piyush K. 
Published: April 2020

AbstractThe CRISPR/Cas12a RNA-guided complexes have a tremendous potential for nucleic acid detection due to its ability to indiscriminately cleave ssDNA once bound to a target DNA. However, the current CRISPR/Cas12a systems are limited to detecting DNA in a picomolar detection limit without an amplification step. Here, we developed a platform with engineered crRNAs and optimized conditions that enabled us to detect DNA, DNA/RNA heteroduplex and methylated DNA with higher sensitivity, achieving a limit of detection of in femtomolar range without any target pre-amplification step. By extending the 3’- or 5’-ends of the crRNA with different lengths of ssDNA, ssRNA, and phosphorothioate ssDNA, we discovered a new self-catalytic behavior and an augmented rate of LbCas12a-mediated collateral cleavage activity as high as 3.5-fold compared to the wild-type crRNA. We applied this sensitive system to detect as low as 25 fM dsDNA from the PCA3 gene, an overexpressed biomarker in prostate cancer patients, in simulated urine over 6 hours. The same platform was used to detect as low as ~700 fM cDNA from HIV, 290 fM RNA from HCV, and 370 fM cDNA from SARS-CoV-2, all within 30 minutes without a need for target amplification. With isothermal amplification of SARS-CoV-2 RNA using RT-LAMP, the modified crRNAs were incorporated in a paper-based lateral flow assay that could detect the target with up to 23-fold higher sensitivity within 40-60 minutes.
Genetic determinants ofEGFR-Driven Lung Cancer Growth and Therapeutic ResponseIn Vivo
Authors: Foggetti Giorgia , Li Chuan , Cai Hongchen , Hellyer Jessica A. , Lin Wen-Yang , Ayeni Deborah , Hastings Katherine , Choi Jungmin , Wurtz Anna , Andrejka Laura , Maghini Dylan , Rashleigh Nicholas , Levy Stellar , Homer Robert , Gettinger Scott , Diehn Maximilian , Wakelee Heather A. , Petrov Dmitri A. , Winslow Monte M. , Politi Katerina 
Published: April 2020

AbstractCancer genome sequencing has uncovered substantial complexity in the mutational landscape of tumors. Given this complexity, experimental approaches are necessary to establish the impact of combinations of genetic alterations on tumor biology and to uncover genotype-dependent effects on drug sensitivity. In lung adenocarcinoma,EGFRmutations co-occur with many putative tumor suppressor gene alterations, however the extent to which these alterations contribute to tumor growth and their response to therapyin vivohas not been explored experimentally. By integrating a novel mouse model of oncogenicEGFR-drivenTrp53-deficient lung adenocarcinoma with multiplexed CRISPR–Cas9-mediated genome editing and tumor barcode sequencing, we quantified the effects of inactivation of ten putative tumor suppressor genes. Inactivation ofApc,Rb1, orRbm10most strongly promoted tumor growth. Unexpectedly, inactivation ofLkb1orSetd2 –which are the strongest drivers of tumor growth in an oncogenicKras-driven model – reducedEGFR-driven tumor growth. These results are consistent with the relative frequency of these tumor suppressor gene alterations in humanEGFR-andKRAS-driven lung adenocarcinomas. Furthermore,Keap1inactivation reduces the sensitivity ofEGFR-drivenTrp53-deficient tumors to the EGFR inhibitor osimertinib. Importantly, in humanEGFR/TP53mutant lung adenocarcinomas, mutations in the KEAP1 pathway correlated with decreased time on tyrosine kinase inhibitor treatment. Our study highlights how genetic alterations can have dramatically different biological consequences depending on the oncogenic context and that the fitness landscape can shift upon drug treatment.
Cabozantinib unlocks efficientin vivotargeted delivery of neutrophil-loaded nanoparticles into murine prostate tumors
Authors: Chaudagar Kiranj , Landon-Brace Natalie , Solanki Aniruddh , Hieromnimon Hanna M. , Hegermiller Emma , Li Wen , Shao Yue , Wilkins Devan , Bynoe Kaela , Li Xiang-Ling , Clohessy John , Ullas Soumya , Karp Jeffrey M , Patnaik Akash 
Published: April 2020

AbstractA major barrier to the successful application of nanotechnology for cancer treatment is the efficient delivery of therapeutic payloads to metastatic tumor deposits. We have previously discovered that cabozantinib, a tyrosine kinase inhibitor, triggers neutrophil-mediated anti-cancer innate immunity, resulting in tumor regression in an aggressive PTEN/p53-deficient genetically engineered murine model of advanced prostate cancer. Here, we specifically investigated the potential of cabozantinib-induced neutrophil activation and recruitment to enhance delivery of bovine serum albumin (BSA)-coated polymeric nanoparticles (NPs) into murine PTEN/p53-deficient prostate tumors. Based on the observation that BSA-coating of NPs enhanced association and internalization by activated neutrophilsin vitro, relative to uncoated NPs, we systemically injected BSA-coated, dye-loaded NPs into prostate-specific PTEN/p53-deficient mice that were pre-treated with cabozantinib. Flow cytometric analysis revealed a 4-fold increase of neutrophil-associated NPs within the tumor microenvironment (TME) of mice pre-treated with cabozantinib relative to untreated controls. At steady-state, following 3 days of cabozantinib/NP administration, 1% of systemically injected dye-loaded NPs selectively accumulated within the TME of mice that were pre-treated with cabozantinib, compared to 0.11% uptake for mice that did not receive cabozantinib pre-treatment. Strikingly, neutrophil depletion with Ly6G antibody abolished NP accumulation in tumors to baseline levels, demonstrating targeted neutrophil-mediated NP delivery to the prostate TME. In summary, we have discovered a novel nano-immunotherapeutic strategy for enhanced intratumoral delivery of injected NPs, which results in significantly higher NP accumulation than reported strategies in the nanotechnology literature to-date.
IRIS: an accurate and efficient barcode calling tool forin situsequencing
Authors: Zhou Yang , Yu Hao , Li Qiye , Ke Rongqin , Zhang Guojie 
Published: April 2020

AbstractSummaryThe emergingin situRNA sequencing technologies which can capture and amplify RNA within the original tissues provides efficient solution for producing spatial expression map from dozens to thousands of genes. Most ofin situRNA-seq strategies developed recently infer the expression patterns based on the fluorescence signals from the images taken during sequencing. However, an automate and convenient tool for decoding signals from image information is still absent. Here we present an easy-to-use software named IRIS to efficiently decode image signals fromin situsequencing into nucleotide sequences. This software can record the quality score and the spatial information of the sequencing signals. We also develop an interactive R shiny app named DAIBC for data visualization. IRIS is designed in modules so that it could be easily extended and compatible to new technologies.Availability and implementationIRIS and DAIBC are freely available under BSD 3-Clause License at:https://github.com/th00516/ISS_pyIRIS.Contactguojie.zhang@bio.ku.dk
Neurophysiological signatures in the retrieval of individual autobiographical memories of real-life episodic events
Authors: Nicolás Berta , Wu Xiongbo , Dimiccolli Mariella , Sierpowska Joanna , Saiz-Masvidal Cristina , Soriano-Mas Carles , Radeva Petia , Fuentemilla Lluís 
Published: April 2020

AbstractAutobiographical memory (AM) refers to recollected events that belong to an individual’s past. In a classical episodic retrieval experiment in a laboratory, the events to be remembered are words or pictures that have hardly any personal relevance. While such stimuli provide necessary experimental and controlled conditions helping to advance in the understanding of memory, they do not capture the whole complexity of real-world stimuli. Recently, the incorporation of wearable cameras has allowed us to study the cognitive and neural bases of AM retrieval without active participant involvement, and they have been demonstrated to elicit a strong sense of first-person episodic recollection enhancing ecological validity. Here, we provide a new approach to understanding the retrieval of personal events, implementing a convolution network-based algorithm for the selection of the stimuli while monitoring participants’ memory retrieval with scalp EEG recordings over three periods of time after encoding (1 week, 2 weeks, and 6 to 12 months). We also examined an individual with a condition termed Aphantasia that provided more insights into the sensitivity of our protocol in the investigation of individual AM using real-life sequences.
Mindfulness Improves Brain Computer Interface Performance by Increasing Control over Neural Activity in the Alpha Band
Authors: Stieger James R. , Engel Stephen , Jiang Haiteng , Cline Christopher C. , Kreitzer Mary Jo , He Bin 
Published: April 2020

AbstractBrain-computer interfaces (BCIs) are promising tools for assisting patients with paralysis, but suffer from long training times and variable user proficiency. Mind-body awareness training (MBAT) can improve BCI learning, but how it does so remains unknown. Here we show that MBAT allows participants to learn to volitionally increase alpha band neural activity during BCI tasks that incorporate intentional rest. We trained individuals in mindfulness-based stress reduction (MBSR; a standardized MBAT intervention) and compared performance and brain activity before and after training between randomly assigned trained and untrained control groups. The MBAT group showed reliably faster learning of BCI than the control group throughout training. Alpha-band activity in EEG signals, recorded in the volitional resting state during task performance, showed a parallel increase over sessions, and predicted final BCI performance. The level of alpha-band activity during the intentional resting state correlated reliably with individuals’ mindfulness practice as well as performance on a sustained attention task. Collectively, these results show that MBAT modifies a specific neural signal used by BCI. MBAT, by increasing patients’ control over their brain activity during rest, may increase the effectiveness of BCI in the large population who could benefit from alternatives to direct motor control.
Tissue and regional expression patterns of dicistronic tRNA-mRNA transcripts in grapevine (Vitis vinifera) and their evolutionary co-appearance with vasculature in land plants
Authors: Fabres Pastor Jullian , Anand Lakshay , Sai Na , Pederson Stephen , Zheng Fei , Stewart Alexander A. , Clements Benjamin , Lampugnani Edwin R , Breen James , Gilliham Matthew , Tricker Penny , López Carlos M. Rodríguez , David Rakesh 
Published: April 2020

AbstractTransfer RNAs (tRNA) are crucial adaptor molecules between messenger RNA (mRNA) and amino acids. Recent evidence in plants suggests that dicistronic tRNA-like structures also act as mobile signals for mRNA transcripts to move between distant tissues. Co-transcription is not a common feature in the plant nuclear genome and, in the few cases where polycistronic transcripts have been found, they include non-coding RNA species such as small nucleolar RNAs and microRNAs. It is not known, however, the extent to which dicistronic transcripts of tRNA and mRNAs are expressed in field-grown plants, or the factors contributing to their expression. We analysed tRNA-mRNA dicistronic transcripts in the major horticultural crop grapevine (Vitis vinifera) using a novel pipeline developed to identify dicistronic transcripts from high-throughput RNA sequencing data. We identified dicistronic tRNA-mRNA in leaf and berry samples from 22 commercial vineyards. Of the 124 tRNA genes that were expressed in both tissues, 18 tRNA were expressed forming part of 19 dicistronic tRNA-mRNAs. The presence and abundance of dicistronic molecules was tissue and geographic sub-region specific. In leaves, the expression patterns of dicistronic tRNA-mRNAs significantly correlated with tRNA expression, suggesting that their transcriptional regulation might be linked. We also found evidence of syntenic genomic arrangements of tRNAs and protein coding genes between grapevine andArabidopsis thaliana, and widespread prevalence of dicistronic tRNA-mRNA transcripts among vascular land plants but no evidence of these transcripts in nonvascular lineages. This suggests that the appearance of plant vasculature and tRNA-mRNA occurred concurrently during the evolution of land plants.