bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging Existing 16S rRNA Gene Surveys To Identify Reproducible Biomarkers in Individuals with Colorectal Tumors
Authors: Sze Marc A. , Schloss Patrick D. 
Published: June 2018

ABSTRACTAn increasing body of literature suggests that both individual and collections of bacteria are associated with the progression of colorectal cancer. As the number of studies investigating these associations increases and the number of subjects in each study increases, a meta-analysis to identify the associations that are the most predictive of disease progression is warranted. We analyzed previously published 16S rRNA gene sequencing data collected from feces and colon tissue. We quantified the odds ratios (ORs) for individual bacterial taxa that were associated with an individual having tumors relative to a normal colon. Among the fecal samples, there were no taxa that had significant ORs associated with adenoma and there were 8 taxa with significant ORs associated with carcinoma. Similarly, among the tissue samples, there were no taxa that had a significant OR associated with adenoma and there were 3 taxa with significant ORs associated with carcinoma. Among the significant ORs, the association between individual taxa and tumor diagnosis was equal to or below 7.11. Because individual taxa had limited association with tumor diagnosis, we trained Random Forest classification models using only the taxa that had significant ORs, using the entire collection of taxa found in each study, and using operational taxonomic units defined based on a 97% similarity threshold. All training approaches yielded similar classification success as measured using the area under the curve. The ability to correctly classify individuals with adenomas was poor, and the ability to classify individuals with carcinomas was considerably better using sequences from feces or tissue.IMPORTANCEColorectal cancer is a significant and growing health problem in which animal models and epidemiological data suggest that the colonic microbiota have a role in tumorigenesis. These observations indicate that the colonic microbiota is a reservoir of biomarkers that may improve our ability to detect colonic tumors using noninvasive approaches. This meta-analysis identifies and validates a set of 8 bacterial taxa that can be used within a Random Forest modeling framework to differentiate individuals as having normal colons or carcinomas. When models trained using one data set were tested on other data sets, the models performed well. These results lend support to the use of fecal biomarkers for the detection of tumors. Furthermore, these biomarkers are plausible candidates for further mechanistic studies into the role of the gut microbiota in tumorigenesis.
Candida albicans-Induced Epithelial Damage Mediates Translocation through Intestinal Barriers
Authors: Allert Stefanie , Förster Toni M. , Svensson Carl-Magnus , Richardson Jonathan P. , Pawlik Tony , Hebecker Betty , Rudolphi Sven , Juraschitz Marc , Schaller Martin , Blagojevic Mariana , Morschhäuser Joachim , Figge Marc Thilo , Jacobsen Ilse D. , Naglik Julian R. , Kasper Lydia , Mogavero Selene , Hube Bernhard 
Published: June 2018

ABSTRACT

Life-threatening systemic infections often occur due to the translocation of pathogens across the gut barrier and into the bloodstream. While the microbial and host mechanisms permitting bacterial gut translocation are well characterized, these mechanisms are still unclear for fungal pathogens such as
Candida albicans
, a leading cause of nosocomial fungal bloodstream infections. In this study, we dissected the cellular mechanisms of translocation of
C. albicans
across intestinal epithelia
in vitro
and identified fungal genes associated with this process. We show that fungal translocation is a dynamic process initiated by invasion and followed by cellular damage and loss of epithelial integrity. A screen of >2,000
C. albicans
deletion mutants identified genes required for cellular damage of and translocation across enterocytes. Correlation analysis suggests that hypha formation, barrier damage above a minimum threshold level, and a decreased epithelial integrity are required for efficient fungal translocation. Translocation occurs predominantly via a transcellular route, which is associated with fungus-induced necrotic epithelial damage, but not apoptotic cell death. The cytolytic peptide toxin of
C. albicans
, candidalysin, was found to be essential for damage of enterocytes and was a key factor in subsequent fungal translocation, suggesting that transcellular translocation of
C. albicans
through intestinal layers is mediated by candidalysin. However, fungal invasion and low-level translocation can also occur via non-transcellular routes in a candidalysin-independent manner. This is the first study showing translocation of a human-pathogenic fungus across the intestinal barrier being mediated by a peptide toxin.

IMPORTANCE
Candida albicans
, usually a harmless fungus colonizing human mucosae, can cause lethal bloodstream infections when it manages to translocate across the intestinal epithelium. This can result from antibiotic treatment, immune dysfunction, or intestinal damage (e.g., during surgery). However, fungal processes may also contribute. In this study, we investigated the translocation process of
C. albicans
using
in vitro
cell culture models. Translocation occurs as a stepwise process starting with invasion, followed by epithelial damage and loss of epithelial integrity. The ability to secrete candidalysin, a peptide toxin deriving from the hyphal protein Ece1, is key:
C. albicans
hyphae, secreting candidalysin, take advantage of a necrotic weakened epithelium to translocate through the intestinal layer.
DDX41 Recognizes RNA/DNA Retroviral Reverse Transcripts and Is Critical for
In Vivo
Control of Murine Leukemia Virus Infection
Authors: Stavrou Spyridon , Aguilera Alexya N. , Blouch Kristin , Ross Susan R. 
Published: June 2018

ABSTRACT

Host recognition of viral nucleic acids generated during infection leads to the activation of innate immune responses essential for early control of virus. Retrovirus reverse transcription creates numerous potential ligands for cytosolic host sensors that recognize foreign nucleic acids, including single-stranded RNA (ssRNA), RNA/DNA hybrids, and double-stranded DNA (dsDNA). We and others recently showed that the sensors cyclic GMP-AMP synthase (cGAS), DEAD-box helicase 41 (DDX41), and members of the Aim2-like receptor (ALR) family participate in the recognition of retroviral reverse transcripts. However, why multiple sensors might be required and their relative importance in
in vivo
control of retroviral infection are not known. Here, we show that DDX41 primarily senses the DNA/RNA hybrid generated at the first step of reverse transcription, while cGAS recognizes dsDNA generated at the next step. We also show that both DDX41 and cGAS are needed for the antiretroviral innate immune response to murine leukemia virus (MLV) and HIV in primary mouse macrophages and dendritic cells (DCs). Using mice with cell type-specific knockout of the
Ddx41
gene, we show that DDX41 sensing in DCs but not macrophages was critical for controlling
in vivo
MLV infection. This suggests that DCs are essential
in vivo
targets for infection, as well as for initiating the antiviral response. Our work demonstrates that the innate immune response to retrovirus infection depends on multiple host nucleic acid sensors that recognize different reverse transcription intermediates.

IMPORTANCE
Viruses are detected by many different host sensors of nucleic acid, which in turn trigger innate immune responses, such as type I interferon (IFN) production, required to control infection. We show here that at least two sensors are needed to initiate a highly effective innate immune response to retroviruses—DDX41, which preferentially senses the RNA/DNA hybrid generated at the first step of retrovirus replication, and cGAS, which recognizes double-stranded DNA generated at the second step. Importantly, we demonstrate using mice lacking DDX41 or cGAS that both sensors are needed for the full antiviral response needed to control
in vivo
MLV infection. These findings underscore the need for multiple host factors to counteract retroviral infection.
Diabetes, driving and fasting during Ramadan: the interplay between secular and religious law
Authors: Ghouri Nazim , Hussain Sufyan , Mohammed Ruzwan , Beshyah Salem Arifi , Chowdhury Tahseen A , Sattar Naveed , Sheikh Aziz 
Published: June 2018

A large proportion of the Muslim population fasts during Ramadan. The risk of hypoglycemia is increased with fasting during Ramadan in people with diabetes who are on insulin and insulin secretagogues. Therefore, the combination of fasting with diabetes and driving presents a challenging situation, with legal implications for such individuals and their healthcare professionals. This novel, narrative, non-systematic review discusses the importance of addressing hypoglycemia in fasting with reference to secular legal guidance on driving with diabetes. We discuss religious aspects relating to fasting and driving in Islam. While there is no clear guidance or legal position on diabetes and driving for individuals who are fasting, Islamic law provides a logical framework to address this. Healthcare professionals need to raise and facilitate discussions on this often-overlooked topic with people with diabetes who are planning on fasting to minimize the potential for public harm. For some individuals fasting perhaps should be avoided when driving and that this religiously compatible position would best be adopted when one is dependent on driving for livelihood. Ultimately further research on glycemic control and management when fasting and driving, as well as a formal legal guidance on this topic, is required to safeguard healthcare professionals and the public from the potential dangers of driving with diabetes and fasting.
Prevalence of a definitive airway in patients with severe traumatic brain injury received at four urban public university hospitals in India: a cohort study
Authors: Khajanchi Monty Uttam , Kumar Vineet , Wärnberg Gerdin Ludvig , Soni Kapil Dev , Saha Makhan Lal , Roy Nobhojit , Gerdin Wärnberg Martin 
Published: June 2018

AimTo estimate the proportion of patients arriving with a Glasgow Coma Scale (GCS) less than 9 who had a definitive airway placed prior to arrival.MethodsWe conducted a retrospective analysis of the data from a multicentre, prospective observational research project entitled Towards Improved Trauma Care Outcomes in India. Adults aged ≥18 years with an isolated traumatic brain injury (TBI) who were transferred from another hospital to the emergency department of the participating hospital with a GCS less than 9 were included. Our outcome was a definitive airway, defined as either intubation or surgical airway, placed prior to arrival at a participating centre.ResultsThe total number of patients eligible for this study was 1499. The median age was 40 years and 84% were male. Road traffic injuries and falls comprised 88% of the causes of isolated TBI. The number of patients with GCS<9 who had a definitive airway placed before reaching the participating centres was 229. Thus, the proportion was 0.15 (95% CI 0.13 to 0.17). The proportions of patients with a definitive airway who arrived after 24 hours (19%) were approximately double the proportion of patients who arrived within 6 hours (10%) after injury to the definitive care centre.ConclusionThe rates of definitive airway placement are poor in adults with an isolated TBI who have been transferred from another health facility to tertiary care centres in India.
Trends in hip fracture in patients with rheumatoid arthritis: results from the Spanish National Inpatient Registry over a 17-year period (1999–2015). TREND-AR study
Authors: Mazzucchelli Ramón , Pérez Fernandez Elia , Crespí-Villarías Natalia , Quirós-Donate Javier , García Vadillo Alberto , Espinosa María , Peña Marina , Macía-Villa Cristina , Morell-Hita Jose Luis , Martinez-Prada Cristina , Villaverde Virginia , Morado Quiroga Inmaculada , Guzón-Illescas Olalla , Barbadillo Carmen , Fernández Prada Manuel , Godoy Hilda , Herranz Varela Angela , Galindo Izquierdo María , Rodriguez Caravaca Gil 
Published: June 2018

PurposeTo analyse trends in hip fracture (HF) rates in patients with rheumatoid arthritis (RA) over an extended time period (17 years).MethodsThis observational retrospective survey was performed by reviewing data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. All hospitalisations of patients with RA and HF that were reported from 1999 to 2015 were analysed. Codes were selected using the Ninth International Classification of Diseases, Clinical Modification: ICD-9-CM: RA 714.0 to 714.9 and HF 820.0 to 820.3. The crude and age-adjusted incidence rate of HF was calculated by age and sex strata over the last 17 years. General lineal models were used to analyse trends.ResultsBetween 1999 and 2015, 6656 HFs occurred in patients with RA of all ages (84.25% women, mean age 77.5 and 15.75% men, mean age 76.37). The age-adjusted osteoporotic HF rate was 221.85/100 000 RA persons/ year (women 227.97; men 179.06). The HF incidence rate increased yearly by 3.1% (95% CI 2.1 to 4.0) during the 1999–2015 period (p<0.001) and was more pronounced in men (3.5% (95% CI 2.1 to 4.9)) than in women (3.1% (95% CI 2.3 to 4.1)). The female to male ratio decreased from 1.54 in 1999 to 1.14 in 2015. The average length of hospital stays (ALHS) decreased (p<0.001) from 16.76 days (SD 15.3) in 1999 to 10.78 days (SD 7.72) in 2015. Age at the time of hospitalisation increased (p<0.001) from 75.3 years (SD 9.33) in 1999 to 79.92 years (SD 9.47) in 2015. There was a total of 326 (4.9%) deaths during admission, 247 (4.4%) in women and 79 (7.5%) in men (p<0.001).ConclusionIn Spain, despite the advances that have taken place in controlling disease activity and in treating osteoporosis, the incidence rate of HF increased in both male and female patients with RA.
The XPO1 Inhibitor Selinexor Inhibits Translation and Enhances the Radiosensitivity of Glioblastoma Cells Grown In Vitro and In Vivo
Authors: Wahba Amy , Rath Barbara H. , O'Neill John W. , Camphausen Kevin , Tofilon Philip J. 
Published: June 2018

Abstract
Analysis of the radiation-induced translatome of glioblastoma stem-like cells (GSC) identified an interacting network in which XPO1 serves as a major hub protein. To determine whether this nuclear export protein provides a target for radiosensitization, we defined the effects of clinically relevant XPO1 inhibitor selinexor on the radiosensitivity of glioblastoma cells. As determined by clonogenic survival analysis, selinexor enhanced the radiosensitivity of GSCs but not normal fibroblast cell lines. On the basis of γH2AX foci and neutral comet analyses, selinexor inhibited the repair of radiation-induced DNA double-strand breaks in GSCs, suggesting that the selinexor-induced radiosensitization is mediated by an inhibition of DNA repair. Consistent with a role for XPO1 in the nuclear to cytoplasm export of rRNA, selinexor reduced 5S and 18S rRNA nuclear export in GSCs, which was accompanied by a decrease in gene translation efficiency, as determined from polysome profiles, as well as in protein synthesis. In contrast, rRNA nuclear export and protein synthesis were not reduced in normal cells treated with selinexor. Orthotopic xenografts initiated from a GSC line were then used to define the in vivo response to selinexor and radiation. Treatment of mice bearing orthotopic xenografts with selinexor decreased tumor translational efficiency as determined from polysome profiles. Although selinexor treatment alone had no effect on the survival of mice with brain tumors, it significantly enhanced the radiation-induced prolongation of survival. These results indicate that selinexor enhances the radiosensitivity of glioblastoma cells and suggest that this effect involves the global inhibition of gene translation. Mol Cancer Ther; 17(8); 1717–26. ©2018 AACR.
Thymidine Kinase 1 Loss Confers Trifluridine Resistance without Affecting 5-Fluorouracil Metabolism and Cytotoxicity
Authors: Edahiro Keitaro , Iimori Makoto , Kobunai Takashi , Morikawa-Ichinose Tomomi , Miura Daisuke , Kataoka Yuki , Niimi Shinichiro , Wakasa Takeshi , Saeki Hiroshi , Oki Eiji , Kitao Hiroyuki , Maehara Yoshihiko 
Published: June 2018

Abstract
Acquired resistance to therapeutic drugs is a serious problem for patients with cancer receiving systemic treatment. Experimentally, drug resistance is established in cell lines in vitro by repeated, continuous exposure to escalating concentrations of the drug; however, the precise mechanism underlying the acquired resistance is not always known. Here, it is demonstrated that the human colorectal cancer cell line DLD1 with acquired resistance to trifluridine (FTD), a key component of the novel, orally administered nucleoside analogue-type chemotherapeutic drug trifluridine/tipiracil, lacks functional thymidine kinase 1 (TK1) expression because of one nonsense mutation in the coding exon. Targeted disruption of the TK1 gene also conferred severe FTD resistance, indicating that the loss of TK1 protein expression is the primary cause of FTD resistance. Both FTD-resistant DLD1 cells and DLD1-TK1−/− cells exhibited similar 5-fluorouracil (5-FU) sensitivity to that of the parental DLD1 line. The quantity of cellular pyrimidine nucleotides in these cells and the kinetics of thymidylate synthase ternary complex formation in 5-FU–treated cells is similar to DLD1 cells, indicating that 5-FU metabolism and cytotoxicity were unaffected. The current data provide molecular-based evidence that acquired resistance to FTD does not confer 5-FU resistance, implying that 5-FU–based chemotherapy would be effective even in tumors that become refractory to FTD during trifluridine/tipiracil treatment. Mol Cancer Res; 16(10); 1483–90. ©2018 AACR.
Pope Francis and Catholic Social Teaching on Ecology
Authors: Guitián Gregorio 
Published: June 2018

Abstract
In his visit to the United States, Pope Francis stressed the Christian message on ecology, which includes a calling to an “ecological conversion”. However, a recent paper on the influence of Christian religiosity on managerial decisions concerning the environment argues that Christian faith discourages managers’ environmental-friendly decisions. Francis message on ecology is part of the Catholic Social Teaching (CST), which contains valuable contributions, but it is still to be known. We present a synthetic view of CST on ecology and its implications for businesses, shareholders and consumers, which can also interest non-Christians concerned with the natural environment. Ultimately, we want to explain why Christians involved in economic activity should be concerned with the natural environment. We offer a moral qualification of acts regarding the natural environment, and conclude with some observations for Christian churches and business schools.
A 22-Year Climatology of Cool Season Hourly Precipitation Thresholds Conducive to Shallow Landslides in California
Authors: Oakley N. S. , Lancaster J. T. , Hatchett B. J. , Stock J. , Ralph F. M. , Roj S. , Lukashov S. 
Published: June 2018

Abstract
California’s winter storms produce intense rainfall capable of triggering shallow landslides, threatening lives and infrastructure. This study explores where hourly rainfall in the state meets or exceeds published values thought to trigger landslides after crossing a seasonal antecedent precipitation threshold. We answer the following questions: 1) Where in California are overthreshold events most common? 2) How are events distributed within the cool season (October–May) and interannually? 3) Are these events related to atmospheric rivers? To do this, we compile and quality control hourly precipitation data over a 22-yr period for 147 Remote Automated Weather Stations (RAWS). Stations in the Transverse and Coast Ranges and portions of the northwestern Sierra Nevada have the greatest number of rainfall events exceeding thresholds. Atmospheric rivers coincide with 60%–90% of these events. Overthreshold events tend to occur in the climatological wettest month of the year, and they commonly occur multiple times within a storm. These statewide maps depict where to expect intense rainfalls that have historically triggered shallow landslides. They predict that some areas of California are less susceptible to storm-driven landslides solely because high-intensity rainfall is unlikely.
A case of rectus sheath haematoma related to severe coughing in a patient with acute exacerbation of chronic obstructive pulmonary disease
Authors: Wong Ching Hin Kevin , Tsang Ho Kai Patrick , Wong Oi Fung , Ma Hing Man , Lit Chau Hung Albert 
Published: June 2018

Introduction: Rectus sheath haematoma is a rare condition which is often misdiagnosed. Apart from abdominal trauma and anticoagulation, severe coughing is an uncommon precipitating cause of this rare condition. Case presentation: An elderly gentleman with history of ischaemic heart disease on aspirin developed rectus sheath haematoma due to severe coughing during an episode of acute exacerbation of chronic obstructive pulmonary disease. He developed severe abdominal pain and was noted to have epigastric bruising extending to bilateral loins. Ultrasound abdomen and computed tomography of the abdomen with contrast revealed haematoma over bilateral upper rectus abdominis muscles, which subsided with conservative management. Discussion and conclusion: Rectus sheath haematoma can be related to severe coughing. In patients, especially those with predisposing factors, presenting with abdominal pain and palpable painful abdominal mass, clinicians should raise the suspicion of this uncommon cause so that timely and appropriate management can be provided.