bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation of blood microbiota in patients with liver cirrhosis
Authors: Kajihara Mikio , Koido Shigeo , Kanai Tomoya , Ito Zensho , Matsumoto Yoshihiro , Takakura Kazuki , Saruta Masayuki , Kato Kumiko , Odamaki Toshitaka , Xiao Jin-zhong , Sato Nobuhiro , Ohkusa Toshifumi 
Published: August 2019

Background and aims
Bacterial infections arising in patients with liver cirrhosis are associated with life-threatening complications such as hepatic encephalopathy and spontaneous bacterial peritonitis in relation to bacterial translocation. To investigate the state of bacterial translocation, we surveyed the peripheral blood microbiota by 16S rRNA gene sequencing and analysed the blood microbial profiles.

Methods
Sixty-six patients with liver cirrhosis were enrolled in this study, whereas 14 healthy individuals were also analysed as controls. Total RNA was purified from the peripheral blood, and an approximately 430 base pair genomic locus which included the V3-V4 region of the 16s rRNA gene was amplified and assessed using bacterial pyrosequencing.

Results
At the genus level, a total of 183 operational taxonomic units were identified in cirrhotic patients, whereas 123 units in controls. Intergroup differences in gut microbiota were analysed by the linear discriminant analysis effect size, which showed that the abundance of Enterobacteriaceae was significantly higher in cirrhotics. On the contrary, the abundance of Akkermansia, Rikenellaceae and Erysipelotrichales were significantly lower in cirrhotics (relative abundance of Akkermansia in cirrhotics and controls: 0% and 0.2%, respectively; Rikenellaceae: 0.1% and 0.92%; Erysipelotrichales: 0.58% and 1.21%).

Conclusion
The present study has demonstrated that various circulating bacteria are present in cirrhotic patients, and the diversity of such bacteria is consistent with the presence of dysbiosis in cirrhotics. Although the clinical significance of the findings remains to be clarified, the findings may potentially facilitate diagnostic and therapeutic attempts to comprehend and furthermore to manipulate bacterial infections in cirrhotic patients.
The correlations between hepatitis B virus infection and hepatocellular carcinoma with portal vein tumor thrombus or extrahepatic metastasis
Authors: Chen Jie , Shi Xianmao , Luo Tao , Zhao Yuan , Ye Jiazhou , Bai Tao , Li Lequn 
Published: August 2019

Background:
Portal vein tumor thrombus (PVTT) and extrahepatic metastasis are associated with the prognosis of hepatocellular carcinoma (HCC). We aimed to investigate the effect of hepatitis B virus (HBV) infection on HCC patients with PVTT or extrahepatic metastasis.

Patients and methods:
The clinical data of 639 patients with HCC from our hospital were retrospectively analyzed to analyze the correlation between HBV and HCC with PVTT or extrahepatic metastasis.

Results:
Univariate analysis revealed that positive hepatitis B virus surface antigen (HBsAg), a detectable serum hepatitis B virus DNA load (>500 IU/ml), cirrhosis and ascites were associated with the presence of PVTT. Positive hepatitis B virus e antigen (HBeAg), cirrhosis and ascites were associated with the presence of extrahepatic metastasis. In a multivariate regression analysis carried out a detectable serum hepatitis B virus DNA load, cirrhosis and ascites were independent risk factors of PVTT. Ascites was an independent risk factor of extrahepatic metastasis. The patients in the PVTT of type III/IV group and the PVTT of type I/II group had a significantly higher rate of positive serum HBsAg, a detectable serum hepatitis B virus DNA load (>500 IU/ml) and HBsAg + HBeAb + HBcAb test positive compared with those in the PVTT-negative group. HBsAg + HBeAb + HBcAb test positive was significantly associated with the presence of extrahepatic metastasis (P=0.028).

Conclusions:
HBV infection and replication status are associated with the formation of PVTT or extrahepatic metastasis in patients with HCC.
The legacy of larval infection on immunological dynamics over metamorphosis
Authors: Critchlow Justin T. , Norris Adriana , Tate Ann T. 
Published: August 2019

Insect metamorphosis promotes the exploration of different ecological niches, as well as exposure to different parasites, across life stages. Adaptation should favour immune responses that are tailored to specific microbial threats, with the potential for metamorphosis to decouple the underlying genetic or physiological basis of immune responses in each stage. However, we do not have a good understanding of how early-life exposure to parasites influences immune responses in subsequent life stages. Is there a developmental legacy of larval infection in holometabolous insect hosts? To address this question, we exposed flour beetle (Tribolium castaneum) larvae to a protozoan parasite that inhabits the midgut of larvae and adults despite clearance during metamorphosis. We quantified the expression of relevant immune genes in the gut and whole body of exposed and unexposed individuals during the larval, pupal and adult stages. Our results suggest that parasite exposure induces the differential expression of several immune genes in the larval stage that persist into subsequent stages. We also demonstrate that immune gene expression covariance is partially decoupled among tissues and life stages. These results suggest that larval infection can leave a lasting imprint on immune phenotypes, with implications for the evolution of metamorphosis and immune systems.This article is part of the theme issue ‘The evolution of complete metamorphosis'.
Antipredator strategies of pupae: how to avoid predation in an immobile life stage?
Authors: Lindstedt Carita , Murphy Liam , Mappes Johanna 
Published: August 2019

Antipredator strategies of the pupal stage in insects have received little attention in comparison to larval or adult stages. This is despite the fact that predation risk can be high during the pupal stage, making it a critical stage for subsequent fitness. The immobile pupae are not, however, defenceless; a wide range of antipredator strategies have evolved against invertebrate and vertebrate predators. The most common strategy seems to be ‘avoiding encounters with predators' by actively hiding in vegetation and soil or via cryptic coloration and masquerade. Pupae have also evolved behavioural and secondary defences such as defensive toxins, physical defences or deimatic movements and sounds. Interestingly, warning coloration used to advertise unprofitability has evolved very rarely, even though the pupal stage often contains defensive toxins in chemically defended species. In some species, pupae gain protection from conspecifics or mimic chemical and auditory signals and thereby manipulate other species to protect them. Our literature survey highlights the importance of studying selection pressures across an individual's life stages to predict how ontogenetic variation in selective environments shapes individual fitness and population dynamics in insects. Finally, we also suggest interesting avenues for future research to pursue.This article is part of the theme issue ‘The evolution of complete metamorphosis’.
Cooking up the perfect insect: Aristotle's transformational idea about the complete metamorphosis of insects
Authors: Reynolds Stuart 
Published: August 2019

Aristotle made important contributions to the study of developmental biology, including the complete metamorphosis of insects. One concept in particular, that of the perfect or complete state, underlies Aristotle's ideas about metamorphosis, the necessity of fertilization for embryonic development, and whether morphogenesis involves an autonomous process of self-assembly. Importantly, the philosopher erroneously views metamorphosis as a necessary developmental response to lack of previous fertilization of the female parent, a view that is intimately connected with his readiness to accept the idea of the spontaneous generation of life. Aristotle's work underpins that of the major seventeenth century students of metamorphosis, Harvey, Redi, Malpighi and Swammerdam, all of whom make frequent reference to Aristotle in their writings. Although both Aristotle and Harvey are often credited with inspiring the later prolonged debate between proponents of epigenesis and preformation, neither actually held firm views on the subject. Aristotle's idea of the perfect stage also underlies his proposal that the eggs of holometabolous insects hatch ‘before their time’, an idea that is the direct precursor of the much later proposals by Lubbock and Berlese that the larval stages of holometabolous insects are due to the ‘premature hatching’ from the egg of an imperfect embryonic stage.This article is part of the theme issue ‘The evolution of complete metamorphosis’.
89Zr-oxine labelling and PET imaging shows lung delivery of a cell/gene cancer therapy
Authors: Patrick P. Stephen , Kolluri Krishna K. , Thin May Z. , Edwards Adam , Sage Elizabeth K. , Sanderson Tom , Weil Benjamin D. , Dickson John C. , Lythgoe Mark F. , Lowdell Mark , Janes Sam M. , Kalber Tammy L. 
Published: August 2019

AbstractPurposeMSCTRAIL is a new stem cell-based therapy for lung cancer, currently in phase I evaluation (ClinicalTrials.gov ref: NCT03298763). Biodistribution of cell therapies is rarely assessed in clinical trials, despite cell delivery to the target site often being critical to presumed mechanism of action. This preclinical study demonstrates that MSCTRAIL biodistribution dynamics can be detected non-invasively using 89Zr-oxine labelling and PET imaging, thus supporting use of this cell tracking technology in phase II evaluation.MethodsMSCTRAIL were radiolabelled with a range of 89Zr-oxine doses, and assayed for cell viability, phenotype and therapeutic efficacy post-labelling. Cell biodistribution was imaged in a mouse model of lung cancer using PET imaging and bioluminescence imaging (BLI) to confirm cell viability and location in vivo up to 1 week post-injection.ResultsMSCTRAIL retained therapeutic efficacy and MSC phenotype at doses up to and above those required for clinical imaging. The effect of 89Zr-oxine labelling on cell proliferation rate was dose and time-dependent. PET imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer, with PET signal correlating with the presence of viable cells as assessed by bioluminescence imaging, ex vivo autoradiography and matched fluorescence imaging on lung tissue sections. Human dosimetry estimates were produced using simulations and preclinical biodistribution data.Conclusion89Zr-oxine labelling and PET imaging present an attractive method of evaluating the biodistribution of new cell-therapies, such as MSCTRAIL. This offers to improve understanding of mechanism of action, migration dynamics and interpatient variability of MSCTRAIL and other cell-based therapies.
HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction
Authors: Schrenk-Siemens Katrin , Pohle Jörg , Rostock Charlotte , El Hay Muad Abd , Lam Ruby M. , Szczot Marcin , Lu Shiying , Chesler Alexander T. , Siemens Jan 
Published: August 2019

AbstractSomatosensation, the detection and transduction of external and internal stimuli, has fascinated scientists for centuries. But still, some of the mechanisms how distinct stimuli are detected and transduced are not entirely understood. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification. Additionally, the accessibility to human pluripotent stem cells and the possibility to generate and study human sensory neurons has enriched the somatosensory research field.Based on our previous work, the generation of functional human mechanoreceptors, we describe here the generation of hESC-derived nociceptor-like cells. We show that by varying the differentiation strategy, we can produce different nociceptive subpopulations. One protocol in particular allowed the generation of a sensory neuron population, homogeneously expressing TRPV1, a prototypical marker for nociceptors. Accordingly, we find the cells to homogenously respond to capsaicin, to become sensitized upon inflammatory stimuli, and to respond to temperature stimulation.Surprisingly, all of the generated subtypes show mechano-nociceptive characteristics and, quite unexpectedly, loss of mechanotransduction in the absence of PIEZO2.
Population genetics of Bull Trout (Salvelinus confluentus) in the Upper Athabasca river basin
Authors: Carroll Emma K. T. , Vamosi Steven M. 
Published: August 2019

AbstractAcross its native range, Bull Trout (Salvelinus confluentus) extent and abundance are in decline due to historic overharvest and habitat degradation. Because Bull Trout are dependent on extensively connected, cold, clean headwater habitats, fragmentation from land use changes causes difficulty when determining the true extent and health of their populations, with Bull Trout of Alberta’s Eastern Slope region being no exception. Across this region, 431 Bull Trout from 20 sites were sampled from the Athabasca and Saskatchewan River basins and compared using 10 microsatellite loci to characterize within- and among-population genetic variation. The Saskatchewan and Athabasca River basins contained similar levels of heterozygosity but were differentiated from one another. Within the Athabasca River basin, five genetically differentiated clusters were found. Additionally, no isolation-by-distance pattern was observed between these sites. These results suggest these populations have ample genetic diversity, but genetic differentiation should be considered when deciding whether and how to alter connectivity between populations.
Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer
Authors: Agbo Kimberley C. , Huang Jessie Z. , Ghaleb Amr M. , Williams Jennie L. , Shroyer Kenneth R. , Bialkowska Agnieszka B. , Yang Vincent W. 
Published: August 2019

AbstractColorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examines the relationship between KLF4 and markers of EMT in CRC.MethodsImmunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer.ResultsWe found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin.ConclusionThese findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.
Impact of crowding on the diversity of expanding populations
Authors: Schreck Carl F. , Fusco Diana , Karita Yuya , Martis Stephen , Kayser Jona , Duvernoy Marie-Cécilia , Hallatschek Oskar 
Published: August 2019

ABSTRACTCrowding effects are key to the self-organization of densely packed cellular assemblies, such as biofilms, solid tumors, and developing tissues. When cells grow and divide they push each other apart, remodeling the structure and extent of the population’s range. It has recently been shown that crowding has a strong impact on the strength of natural selection. However, the impact of crowding on neutral processes remains unclear, which controls the fate of new variants as long as they are rare. Here, we quantify the genetic diversity of expanding microbial colonies and uncover signatures of crowding in the site frequency spectrum. By combining Luria-Delbrück fluctuation tests, lineage tracing in a novel microfluidic incubator, cell-based simulations, and theoretical modeling, we find that the majority of mutations arise behind the expanding frontier, giving rise to clones that are mechanically “pushed out” of the growing region by the proliferating cells in front. These excluded-volume interactions result in a clone size distribution that solely depends on where the mutation first arose relative to the front and is characterized by a simple power-law for low-frequency clones. Our model predicts that the distribution only depends on a single parameter, the characteristic growth layer thickness, and hence allows estimation of the mutation rate in a variety of crowded cellular populations. Combined with previous studies on high-frequency mutations, our finding provides a unified picture of the genetic diversity in expanding populations over the whole frequency range and suggests a practical method to assess growth dynamics by sequencing populations across spatial scales.Significance StatementGrowing cell populations become densely packed as cells proliferate and fill space. Crowding prevents spatial mixing of individuals, significantly altering the evolutionary outcome from established results for well-mixed populations. Despite the fundamental differences between spatial and well-mixed populations, little is known about the impact of crowding on genetic diversity. Looking at microbial colonies growing on plates, we show that the allele frequency spectrum is characterized by a simple power law for low frequencies. Using cell-based simulations and microfluidic experiments, we identify the origin of this distribution in the volume-exclusion interactions within the crowded cellular environment, enabling us to extend this findings to a broad range of densely packed populations. This study highlights the importance of cellular crowding for the emergence of rare genetic variants.
An Active Inference Approach to Dissecting Reasons for Non-Adherence to Antidepressants
Authors: Smith Ryan , Khalsa Sahib , Paulus Martin 
Published: August 2019

AbstractBackgroundAntidepressant medication adherence is among the most important problems in health care worldwide. Interventions designed to increase adherence have largely failed, pointing towards a critical need to better understand the underlying decision-making processes that contribute to adherence. A computational decision-making model that integrates empirical data with a fundamental action selection principle could be pragmatically useful in 1) making individual level predictions about adherence, and 2) providing an explanatory framework that improves our understanding of non-adherence.MethodsHere we formulate a partially observable Markov decision process model based on the active inference framework that can simulate several processes that plausibly influence adherence decisions.ResultsUsing model simulations of the day-to-day decisions to take a prescribed selective serotonin reuptake inhibitor (SSRI), we show that several distinct parameters in the model can influence adherence decisions in predictable ways. These parameters include differences in policy depth (i.e., how far into the future one considers when deciding), decision uncertainty, beliefs about the predictability (stochasticity) of symptoms, beliefs about the magnitude and time course of symptom reductions and side effects, and the strength of medication-taking habits that one has acquired.ConclusionsClarifying these influential factors will be an important first step toward empirically determining which are contributing to non-adherence to antidepressants in individual patients. The model can also be seamlessly extended to simulate adherence to other medications (by incorporating the known symptom reduction and side effect trajectories of those medications), with the potential promise of identifying which medications may be best suited for different patients.
DNA Replication Stress Generates Distinctive Landscapes of DNA Copy Number Alterations and Chromosome Scale Losses
Authors: Mazzagatti Alice , Shaikh Nadeem , Bakker Bjorn , Spierings Diana Carolina Johanna , Wardenaar René , Maniati Eleni , Wang Jun , Boemo Michael A. , Foijer Floris , McClelland Sarah Elizabeth 
Published: August 2019

AbstractBackgroundWe previously showed that a major driver of cancer chromosomal instability (CIN) is replication stress, the slowing or stalling of DNA replication. However, the precise drivers of replication stress in cancer and the mechanisms by which these cause CIN and influence tumour evolution remain unclear. Common fragile sites are well-known genomic locations of breakage after aphidicolin-induced replication stress, but their precise causes of fragility are debated, and additional genomic consequences of replication stress are not fully explored.ResultsUsing single cell sequencing we detected DNA copy number alterations (CNAs) caused by one cell cycle under replication stress in diploid non-transformed cells. Aphidicolin-induced replication stress caused multiple types of CNAs associated with different genomic regions and features. Coupling cell type-specific analysis of CNAs to gene expression and single cell replication timing analyses allowed us to pinpoint the causative large genes of the most recurrent chromosome-scale CNAs. In RPE1 cells these were largely confined to three sites on chromosomes 1, 2 and 7 and generated acentric lagging chromatin and micronuclei containing these chromosomes. Different replicative stresses generated distinct profiles of CNAs providing the potential to interpret specific replication stress mechanisms from cancer cells.ConclusionsChromosomal instability driven by replication stress occurs via focal CNAs and chromosome arm-scale changes, with the latter confined to a very small subset of chromosome regions, potentially heavily skewing cancer genome evolution trajectories. Single cell CNA analysis thus reveals new insights into the impact of replication stress on the genome and provides a platform to further dissect molecular mechanisms involved in the replication stress response and to gain insights into how replication stress fuels chromosomal instability in cancer.