bluuebunny/crossref_metadata_2025_split huggingface dataset:
Although host-related factors are important for the formation of gut microbiota, environmental factors cannot be ignored
Authors: Jung YeonGyun , Kerfahi Dorsaf , Pham Huy Quang , Son HyunWoo , Ibal Jerald Conrad , Park Min-Kyu , Park Yeong-Jun , Park Chang Eon , Choi Seung-Dae , Jo YoungJae , Kim Min-Chul , Kim Min Ji , Kang Gi Ung , Jo Hyung Woo , Yun Hyunju , Lee Bora , Park Clara Yongjoo , Kim Eun Soo , Kim Sang-Jun , Shin Jae-Ho 
Published: February 2020

ABSTRACTThe gut microbiome is essential to human health. However, little is known about the influence of the environment versus host-related factors (e.g. genetic background, sex, age, and body mass) in the formation of human intestinal microflora. Here, we present evidence in support of the importance of host-related factors in the establishment and maintenance of individual gut assemblages. We collected fecal samples (n = 249) from 44 Korean naval trainees and 39 healthy people living in Korea over eight weeks and sequenced the bacterial 16S rRNA genes. The following hypotheses were tested: 1) microbiome function is linked to its diversity, community structure, and genetic host-related factors, and 2) preexisting host-related factors have a more significant effect on gut microbiome formation and composition than environmental factors. For each individual, the difference between the initial gut microbiota and that after eight weeks was negligible even though the 44 naval trainees lived in the same area and received the same diet, the same amount of exercise, and the same amount of physical stress during the study. This suggests that host-related factors, rather than environmental factors, is a key determinant of individual gut microflora. Moreover, eight weeks of physical training and experiencing the same environmental conditions resulted in an increase in the speciesBifidobacterium,Faecalibacterium, andRoseburiain most trainees, suggesting a healthier intestinal environment.IMPORTANCEIn order to understand the role of human gut microbiome, it is important to know how individual’s gut microbiota are formed. In this study, we tested the host-related factors versus environmental factors to affect gut microbiome and found that the former have a more association. However, we also found that the controlled environment give an effect on the gut microflora as well. This study provides preliminary evidence that differences in the formation and diversity of gut microbiota within a population could be determined by host-related factors rather than environmental factors.
Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer
Authors: Beynon Rhona A , Ingle Suzanne M , Langdon Ryan , May Margaret , Ness Andy , Martin Richard , Suderman Matthew , Ingarfield Kate , Marioni Riccardo , McCartney Daniel , Waterboer Tim , Pawlita Michael , Relton Caroline , Smith George Davey , Richmond Rebecca 
Published: February 2020

AbstractBackgroundEpigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between predicted age from these clocks and chronological age (“epigenetic age acceleration”) has been shown to predict age-related disease and mortality. We aimed to assess the prognostic value of epigenetic age acceleration with all-cause mortality in a prospective clinical cohort of individuals with head and neck cancer: Head and Neck 5000.MethodsWe investigated two markers of intrinsic epigenetic age acceleration (IEAAHorvathandIEAAHannum), one marker of extrinsic epigenetic age acceleration (EEAA), one optimised to predict physiological dysregulation (AgeAccelPheno) and one optimised to predict lifespan (AgeAccelGrim). Cox regression models were first used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations of epigenetic age acceleration with all-cause mortality in people with oropharyngeal cancer (n=408;105 deaths). The added prognostic value of epigenetic measures compared to a clinical model including age, gender, TNM stage and HPV status was then evaluated.ResultsIEAAHannumandAgeAccelGrimwere associated with mortality risk after adjustment for clinical and lifestyle factors [HRs per standard deviation (SD) increase in age acceleration =1.32 (95% CI=1.08, 1.61; p=0.007) and 1.39 (95% CI =1.06, 1.83; p=0.017), respectively]. There was weak evidence that the addition ofAgeAccelGrimto the clinical model improved 3-year mortality prediction (area under the receiver operating characteristic curve: 0.80 vs. 0.77; p-value for difference=0.069).ConclusionOur study demonstrates the potential of epigenetic age acceleration measures to enhance survival prediction in people with oropharyngeal cancer, beyond established prognostic factors.
Machine Learning Can Predict Deaths in Patients with Diverticulitis During their Hospital Stay
Authors: Ahmed Fahad Shabbir , Raza-Ul-Mustafa  , Ali Liaqat , Imad-ud-Deen  , Hameed Tahir , Ikram Asad , Bukhari Syed Ahmad Chan 
Published: February 2020

ABSTRACTIntroductionDiverticulitis is the inflammation and/or infection of small pouches known as diverticula that develop along the walls of the intestines. Patients with diverticulitis are at risk of mortality as high as 17% with abscess formation and 45% with secondary perforation, especially patients that get admitted to the inpatient services are at risk of complications including mortality. We developed a deep neural networks (DNN) based machine learning framework that could predict premature death in patients that are admitted with diverticulitis using electronic health records (EHR) to calculate the statistically significant risk factors first and then to apply deep neural network.MethodsOur proposed framework (Deep FLAIM) is a two-phase hybrid works framework. In the first phase, we used National In-patient Sample 2014 dataset to extract patients with diverticulitis patients with and without hemorrhage with the ICD-9 codes 562.11 and 562.13 respectively and analyzed these patients for different risk factors for statistical significance with univariate and multivariate analyses to generate hazard ratios, to rank the diverticulitis associated risk factors. In the second phase, we applied deep neural network model to predict death. Additionally, we have compared the performance of our proposed system by using the popular machine learning models such as DNN and Logistic Regression (LR).ResultsA total of 128,258 patients were used, we tested 64 different variables for using univariate and multivariate (age, gender and ethnicity) cox-regression for significance only 16 factors were statistically significant for both univariate and multivariate analysis. The mortality prediction for our DNN out-performed the conventional machine learning (logistic regression) in terms of AUC (0.977 vs 0.904), training accuracy (0.931 vs 0.900), testing accuracy (0.930 vs 0.910), sensitivity (90% vs 88%) and specificity (95% vs 93%).ConclusionOur Deep FLAIM Framework can predict mortality in patients admitted to the hospital with diverticulitis with high accuracy. The proposed framework can be expanded to predict premature death for other disease.
Cost-effectiveness of real-world administration of chemotherapy and add-on Viscum album L. therapy compared to chemotherapy alone in the treatment of stage IV NSCLC patients
Authors: Thronicke Anja , Reinhold Thomas , von Trott Philipp , Grah Christian , Matthes Burkhard , Matthes Harald , Schad Friedemann 
Published: February 2020

AbstractBackgroundFor stage IV lung cancer patients receiving add-on Viscum album L. treatment an improved overall survival (OS) was observed. Only limited information regarding cost-effectiveness (CE) for comparisons between standard of care and standard of care plus add-on VA in stage IV lung cancer treatment is available. The present study assessed the costs and cost-effectiveness of standard of care plus VA (V) compared to standard of care alone (C) for stage IV non-small cell lung cancer (NSCLC) patients treatment in a hospital in Germany.MethodsAn observational study was conducted using data from the Network Oncology clinical registry. Patients included had stage IV lung cancer at diagnosis and received C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital’s perspective based on routine data from financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis.Results118 patients (C: n=86, V: n=32) were included, mean age 63.8 years, proportion of male patients 55.1%. Adjusted hospital’s total mean costs for patients from the C and V group were €16,289 (over an adjusted mean OS time of 13.4 months) and €17,992 (over an adjusted mean OS time of 19.1 months), respectively. The costs per additional OS year gained (ICER) with the V-treatment compared to C were €3,586.ConclusionBased on our analysis, the assessment of inpatient costs and cost-effectiveness of IO concepts in stage IV lung cancer suggests that the combined use of chemotherapy and VA is clinically effective and was comparably cost-effective to chemotherapy alone in our analysed patient sample. Further randomized and prospective cost-effectiveness studies are mandatory to complement our findings.
A novel mechanism of HIF2-dependent PLK1-mediated metastasis and drug resistance of clear cell Renal Cell Carcinoma
Authors: Dufies Maeva , Verbiest Annelies , Cooley Lindsay S , Ndiaye Papa Diogop , Viotti Julien , He Xingkang , Nottet Nicolas , Souleyreau Wilfried , Hagege Anais , Torrino Stephanie , Parola Julien , Giuliano Sandy , Borchiellini Delphine , Schiappa Renaud , Mograbi Baharia , Zucman-Rossi Jessica , Bensalah Karim , Ravaud Alain , Auberger Patrick , Bikfalvi Andréas , Chamorey Emmanuel , Rioux-Leclercq Nathalie , Mazure Nathalie M. , Beuselinck Benoit , Cao Yihai , Bernhard Jean Christophe , Ambrosetti Damien , Pagès Gilles 
Published: February 2020

AbstractPolo-Like Kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a novel hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a new HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response element of the Plk1 promoter. In ccRCC patients, high expression of Plk1 was correlated to poor disease-free survival and overall survival. Loss-of-function of Plk1 in vivo markedly attenuated ccRCC growth and metastasis. High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients.
Can increasing years of schooling reduce type 2 diabetes (T2D)?—Evidence from a Mendelian randomization of T2D and 10 of its risk factors
Authors: Adams Charleen D. , Boutwell Brian B. 
Published: February 2020

AbstractA focus in recent decades has involved examining the potential causal impact of educational attainment (schooling years) on a variety of disease and life-expectancy outcomes. Numerous studies have broadly revealed a link suggesting that as years of formal schooling increase so too does health and wellbeing; however, it is unclear whether the associations are causal. Here we use Mendelian randomization, an instrumental variables technique, to probe whether more years of schooling are causally linked to type 2 diabetes (T2D) and 10 of its risk factors. The results reveal a protective effect of more schooling years against T2D (odds ratio=0.39; 95% confidence interval: 0.26, 0.58; P=3.89 × 10−06), which might be mediated in part by more years of schooling being protective against the following: having a first-degree relative with diabetes, being overweight, and having high blood pressure, higher levels of circulating triglycerides, and lower levels of HDL cholesterol. More schooling years had no effect on risk for gestational diabetes or polycystic ovarian syndrome and was associated with a decreased likelihood of moderate physical activity. These findings imply that strategies to retain adults in higher education may help reduce the risk for a major source of metabolic morbidity and mortality.
Myelin water fraction decrease in mild traumatic brain injury
Authors: Russell-Schulz Bretta , Vavasour Irene , Zhang Jing , MacKay Alex L. , Purcell Victoria , Muller Angela M. , Brucar Leyla , Torres Ivan J. , Panenka William , Virji-Babul Naznin 
Published: February 2020

AbstractThe increased incidence of reported traumatic brain injury (TBI) and its potentially serious long-term consequences have enormous clinical and societal impacts. The diffuse and continually evolving secondary changes after TBI make it challenging to evaluate the changes in brain-behaviour relationships. In this study we used myelin water imaging to evaluate changes in myelin water fraction (MWF) in individuals with chronic brain injury and evaluated their cognitive status using the NIH Toolbox Cognitive Battery. Twenty-two adults with mild or severe brain injury and twelve age, gender and education matched healthy controls took part in this study. We found a significant decrease in global white matter MWF in individuals with mild TBI compared to the healthy controls. Significantly lower MWF was evident in most white matter ROIs examined including the corpus callosum (separated into genu, body and splenium), minor forceps, right anterior thalamic radiation, left inferior longitudinal fasciculus; and right and left superior longitudinal fasciculus and corticospinal tract. No significant correlations were found between MWF in mild TBI and the cognitive measures. These results show for the first time the loss of myelin in chronic mild TBI.
Providing an additional electron sink by the introduction of cyanobacterial flavodiirons enhances the growth ofArabidopsis thalianain varying light
Authors: Tula Suresh , Shahinnia Fahimeh , Melzer Michael , Rutten Twan , Gómez Rodrigo , Lodeyro Anabella F. , Wirén Nicolaus von , Carrillo Néstor , Hajirezaei Mohammad R. 
Published: February 2020

AbstractThe ability of plants to maintain photosynthesis in a dynamically changing environment is of central importance for their growth. As their photosynthetic machinery typically cannot adapt rapidly to fluctuations in the intensity of radiation, the level of photosynthetic efficiency is not always optimal. Cyanobacteria, algae, non-vascular plants (mosses and liverworts) and gymnosperms all produce flavodiirons (Flvs), a class of proteins not represented in the angiosperms; these proteins act to mitigate the photoinhibition of photosystem I. Here, genes specifying two cyanobacterial Flvs have been expressed in the chloroplasts ofArabidopsis thalianain an attempt to improve the robustness of Photosystem I (PSI). The expression ofFlv1andFlv3together shown to enhance the efficiency of the utilization of light and to boost the plant’s capacity to accumulate biomass. Based on an assessment of the chlorophyll fluorescence in the transgenic plants, the implication was that photosynthetic activity (including electron transport flow and non-photochemical quenching during a dark-to-light transition) was initiated earlier in the transgenic than in wild type plants. The improved photosynthetic performance of the transgenics was accompanied by an increased production of ATP, an acceleration of carbohydrate metabolism and a more pronounced partitioning of sucrose into starch. The indications are that Flvs are able to establish an efficient electron sink downstream of PSI, thereby ensuring that the photosynthetic electron transport chain remains in a more oxidized state. The expression of Flvs in a plant acts to both protect photosynthesis and to control the ATP/NADPH ratio; together, their presence is beneficial for the plant’s growth potential.
Structural adaptation of oxygen tolerance in 4-hydroxybutyrl-CoA dehydratase, a key enzyme of archaeal carbon fixation
Authors: DeMirci Hasan , Tolar Bradley B. , Doukov Tzanko , Petriceks Aldis , Pal Akshaye , Yoshikuni Yasuo , Gomez Aharon , Saez David A. , Vöhringer-Martinez Esteban , Schwander Thomas , Erb Tobias J. , Francis Christopher A. , Wakatsuki Soichi 
Published: February 2020

AbstractAutotrophic microorganisms that convert inorganic carbon into organic matter were key players in the evolution of life on Earth. As the early atmosphere became oxygenated, microorganisms needed to develop mechanisms for oxygen protection, especially those relying on enzymes containing oxygen-sensitive metal clusters (e.g., Fe-S). Here we investigated how 4-hydroxybutyryl-CoA dehydratase (4HBD) - the key enzyme of the 3-hydroxypropionate/4-hydroxybutyrate (HP/HB) cycle for CO2-fixation - adapted as conditions shifted from anoxic to oxic. 4HBD is found in both anaerobic bacteria and aerobic ammonia-oxidizing archaea (AOA). The oxygen-sensitive bacterial 4HBD and oxygen-tolerant archaeal 4HBD share 59 % amino acid identity. To examine the structural basis of oxygen tolerance in archaeal 4HBD, we determined the atomic resolution structure of the enzyme. Two tunnels providing access to the canonical [4Fe-4S] cluster in oxygen-sensitive bacterial 4HBD were closed with four conserved mutations found in all aerobic AOA and other archaea. Further biochemical experiments and molecular dynamics simulations support our findings that restricting access to the active site is the key to oxygen tolerance, explaining how active site evolution drove a major evolutionary transition.Significance statementAutotrophy (primary production) was the first life strategy on Earth. Before photosynthesis (using solar energy to fix carbon dioxide), life relied on chemical reactions for energy. These chemosynthetic reactions are present in all domains of life, including archaea possessing the most energy-efficient carbon fixation pathway - the 3-hydroxypropionate/4-hydroxybutyrate cycle. This efficiency results from enzyme modifications, including enhanced enzyme stability and catalysis of multiple reactions. We reveal the first structure of aerobic 4-hydroxybutyryl-CoA dehydratase (4HBD) from ammonia-oxidizing archaea. These archaea are among the most abundant organisms on the planet, and their 4HBD active site evolved oxygen tolerance to support aerobic metabolism. This modification can provide further insight into enzyme evolution on early earth, as photosynthesis developed and began oxygenating the atmosphere.
How important is CRISPR-Cas for protecting natural populations of bacteria against infections by mobile genetic elements?
Authors: Westra Edze , Levin Bruce 
Published: February 2020

AbstractArticles on CRISPR commonly open with some variant of the phrase ‘these short-palindromic repeats and their associated endonucleases (Cas) are an adaptive immune system that exists to protect bacteria and archaea from viruses and infections with other mobile genetic elements’. There is an abundance of genomic data consistent with the hypothesis that CRISPR plays this role in natural populations of bacteria and archaea, and experimental demonstrations with a few species of bacteria and their phage and plasmids show that CRISPR-Cas systems can play this rolein vitro. Not at all clear are the ubiquity, magnitude and nature of the contribution of CRISPR-Cas systems to the ecology and evolution of natural populations of microbes, and the strength of selection mediated by different types of phage and plasmids to the evolution and maintenance of CRISPR-Cas systems. In this perspective, with the aid of heuristic mathematical-computer simulation models, we explore thea prioriconditions under which exposure to lytic and temperate phage and conjugative plasmids will select for and maintain CRISPR-Cas systems in populations of bacteria and archaea. We review the existing literature addressing these ecological and evolutionary questions and highlight the experimental and other evidence needed to fully understand the conditions responsible for the evolution and maintenance of CRISPR-Cas systems and the contribution of these systems to the ecology and evolution of bacteria, archaea and the mobile genetic elements that infect them.SignificanceThere is no question about the importance and utility of CRISPR-Cas for editing and modifying genomes. On the other hand, the mechanisms responsible for the evolution and maintenance of these systems and the magnitude of their importance to the ecology and evolution of bacteria, archaea and their infectious DNAs, are not at all clear. With the aid of heuristic mathematical – computer simulation models and reviews of the existing literature, we raise questions that have to be answered to elucidate the contribution of selection – mediated by phage and plasmids – to the evolution and maintenance of this adaptive immune system and its consequences for the ecology and evolution of prokaryotes and their viruses and plasmids.
High-speed, long-term, 4Din vivolifetime imaging in intact and injured zebrafish and mouse brains by instant FLIM
Authors: Zhang Yide , Guldner Ian H. , Nichols Evan L. , Benirschke David , Smith Cody J. , Zhang Siyuan , Howard Scott S. 
Published: February 2020

AbstractTraditional fluorescence microscopy is blind to molecular microenvironment information that is present in fluorescence lifetime, which can be measured by fluorescence lifetime imaging microscopy (FLIM). However, existing FLIM techniques are typically slow to acquire and process lifetime images, difficult to implement, and expensive. Here, we present instant FLIM, an analog signal processing method that allows real-time streaming of fluorescence intensity, lifetime, and phasor imaging data through simultaneous image acquisition and instantaneous data processing. Instant FLIM can be easily implemented by upgrading an existing two-photon microscope using cost-effective components and our open-source software. We further improve the functionality, penetration depth, and resolution of instant FLIM using phasor segmentation, adaptive optics, and super-resolution techniques. We demonstrate through-skull intravital 3D FLIM of mouse brains to depths of 300 μm and present the firstin vivo4D FLIM of microglial dynamics in intact and injured zebrafish and mouse brains up to 12 hours.