bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Quality Genome Sequence of Xanthomonas axonopodis pv. glycines Strain 12609 Isolated in Taiwan
Authors: Weng Shu-Fen , Luo An-Chi , Lin Che-Jui , Tseng Tsai-Tien 
Published: February 2017

ABSTRACT

The genomic sequence was determined for
Xanthomonas axonopodis
pv. glycines strain 12609, isolated in Taiwan. Based on the genome sequence, we predicted the encoded genes, rRNA, tRNA, a plasmid sequence, secretion systems, cyclic GMP- and cyclic di-GMP-mediated pathways, and the gene cluster
rpfABCHGDE
(regulation of pathogenicity factor).
Targeting Phenotypically TolerantMycobacterium tuberculosis
Authors: Gold Ben , Nathan Carl 
Published: February 2017

ABSTRACTWhile the immune system is credited with averting tuberculosis in billions of individuals exposed toMycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, ofM. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, renderM. tuberculosisprofoundly tolerant to many of the antibiotics that are given to tuberculosis patients in clinical settings. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of posttreatment relapse. Some promising drugs to treat tuberculosis, such as rifampin and bedaquiline, only kill nonreplicatingM. tuberculosisin vitroat concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicatingM. tuberculosis. With this goal, we review methods of high-throughput screening to target nonreplicatingM. tuberculosisand methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicatingM. tuberculosisrevealed a rich diversity in pharmacophores.
Cutaneous Tuberculosis
Authors: Hill Michael K. , Sanders Charles V. 
Published: February 2017

ABSTRACT

Cutaneous tuberculosis (TB) may present in various clinical manifestations. Skin involvement may occur as a result of exogenous inoculation, contiguous spread from a nearby focus of infection, or by hematogenous spread from a distant focus. Because the clinical presentation of cutaneous TB can vary widely, it is important to have a high index of suspicion in appropriate clinical settings. In this chapter, the various clinical manifestations of clinical TB are classified by source of infection (exogenous, endogenous, and hematogenous spread). These are linked to the clinical appearance and histology of the skin lesions. Hopefully, this will resolve the confusion created by the myriad of terms previously used in the medical literature. Once a diagnosis of cutaneous TB is entertained, a biopsy for both culture and histopathology should be submitted. In some cases histopathology may show nonspecific inflammation without classic granuloma formation. In these cases, monoclonal antibodies and polymerase chain reaction (PCR) testing may be useful. In fact, in recent years, PCR amplification has proven to be invaluable in assisting identification of
M. tuberculosis
from skin biopsies in patients with negative TB cultures. In most instances, treatment of cutaneous TB requires combination chemotherapy. This is especially important in patients with extra cutaneous disease, multiple skin lesions, and those with profound immunosuppression. Surgery also may play both a diagnostic and therapeutic role.
Tuberculosis of the Liver, Biliary Tract, and Pancreas
Authors: McMullan G. Shelton , Lewis James H. 
Published: February 2017

ABSTRACTTuberculosis of the liver, biliary tract, and pancreas is discussed. In addition, tuberculosis in the setting of HIV-AIDS and liver transplantation is explored. Drug-induced liver injury secondary to antituberculosis medication and monitoring and prophylactic treatment for such injury is also considered.
Characteristics and prognoses of patients treated by an anaesthesiologist-manned prehospital emergency care unit. A retrospective cohort study
Authors: Mikkelsen Søren , Lossius Hans Morten , Toft Palle , Lassen Annmarie Touborg 
Published: February 2017

ObjectiveWhen planning and dimensioning an emergency medical system, knowledge of the population serviced is vital. The amount of literature concerning the prehospital population is sparse. In order to add to the current body of literature regarding prehospital treatment, thus aiding future public health planning, we describe the workload of a prehospital anaesthesiologist-manned mobile emergency care unit (MECU) and the total population it services in terms of factors associated with mortality.ParticipantsThe study is a register-based study investigating all missions carried out by a MECU operating in a mixed urban/rural area in Denmark from 1 May 2006 to 31 December 2014. Information on missions was extracted from the local MECU registry and linked at the individual level to the Danish population-based databases, the National Patient Registry and the Civil Registration System.Primary and secondary outcome measuresPrimary outcome measures were number of missions and number of patient contacts. Secondary patient variables were mortality and association between mortality and age, sex, comorbidity, prior admission to hospital and response time.ResultsThe MECU completed 41 513 missions (mean 13.1 missions/day) having 32 873 patient contacts, corresponding to 19.2 missions and 15.2 patient encounters per 1000 patient years. Patient variables: the median age was 57 years (range 0–108 years), 42.8% (42.3% to 43.4%) were women. For patients admitted to hospital alive, 30-day mortality was 5.7% (5.4% to 6.0%); 90-day mortality was 8.1% (7.8% to 8.5%) while 2-year mortality was 16.4% (16.0% to 16.8%). Increasing age, male sex, comorbidity and prior admission to hospital but not response time were associated with mortality.ConclusionsMortality following an incident requiring the assistance of a MECU was high in the first 2 years following the incident. MECU response time assessed as a continuous parameter was not associated with patient outcome.
Statistical process control charts for monitoring military injuries
Authors: Schuh Anna , Canham-Chervak Michelle , Jones Bruce H 
Published: February 2017

BackgroundAn essential aspect of an injury prevention process is surveillance, which quantifies and documents injury rates in populations of interest and enables monitoring of injury frequencies, rates and trends. To drive progress towards injury reduction goals, additional tools are needed. Statistical process control charts, a methodology that has not been previously applied to Army injury monitoring, capitalise on existing medical surveillance data to provide information to leadership about injury trends necessary for prevention planning and evaluation.MethodsStatistical process control Shewhart u-charts were created for 49 US Army installations using quarterly injury medical encounter rates, 2007–2015, for active duty soldiers obtained from the Defense Medical Surveillance System. Injuries were defined according to established military injury surveillance recommendations. Charts display control limits three standard deviations (SDs) above and below an installation-specific historical average rate determined using 28 data points, 2007–2013. Charts are available in Army strategic management dashboards.ResultsFrom 2007 to 2015, Army injury rates ranged from 1254 to 1494 unique injuries per 1000 person-years. Installation injury rates ranged from 610 to 2312 injuries per 1000 person-years. Control charts identified four installations with injury rates exceeding the upper control limits at least once during 2014–2015, rates at three installations exceeded the lower control limit at least once and 42 installations had rates that fluctuated around the historical mean.ConclusionsControl charts can be used to drive progress towards injury reduction goals by indicating statistically significant increases and decreases in injury rates. Future applications to military subpopulations, other health outcome metrics and chart enhancements are suggested.
No impact of concomitant methotrexate use on serious adverse event and serious infection risk in patients with rheumatoid arthritis treated with bDMARDs: a systematic literature review and meta-analysis
Authors: Baradat Claire , Degboé Yannick , Constantin Arnaud , Cantagrel Alain , Ruyssen-Witrand Adeline 
Published: February 2017

ObjectivesTo compare the risk of serious adverse events, serious infections and death caused by methotrexate and biological disease-modifying antirheumatic drug (bDMARD) combination therapy versus a bDMARD prescribed as monotherapy in rheumatoid arthritis (RA).MethodsA systematic literature review was conducted until February 2016 in PubMed, Embase and Cochrane Library databases by selecting randomised controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy in RA. The meta-analysis compared the occurrence of (1) serious adverse events, (2) serious infections and (3) death among these groups by the Mantel-Haenszel method.ResultsThe literature review selected 16 controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy. After meta-analysis comparing patients under monotherapy to those under combination therapy: (1) the risk of occurrence of serious adverse events was comparable in 12 trials: RR (95% CI) 0.92 (0.78 to 1.08). (2) No significant difference was observed in the risk of occurrence of serious infections in 13 trials: RR (95% CI) 1.15 (0.84 to 1.58). We noted a trend, although insignificant, towards a high risk of the occurrence of tuberculosis in 10 studies: RR (95% CI) 1.78 (0.63 to 4.99). (3) The risk of death was comparable in 12 trials: RR (95% CI) 0.73 (0.40 to 1.35).ConclusionsThe results showed no significant difference between the two groups, confirming that the use of methotrexate and bDMARD combination therapy in RA does not cause an increased risk of serious adverse events or serious infections or death compared with bDMARD monotherapy.
Tsunami hazard in Central America: history and future
Authors: Lindholm Conrad , Strauch Wilfried , Fernández Mario 
Published: February 2017

Abstract
Central America is a small and culturally homogeneous region that, since the 1990s, has experienced economic and political integration of its six countries, which share the same threats of volcanic eruptions, disastrous earthquakes and tsunamis. The Pacific coastline of 1700 km is common for Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica and Panama, and the Pacific subduction zone has the potential for creating huge tsunamis that threaten this coast. In addition to the natural hazard, the growing tourist industry is expanding its infrastructure along the Pacific beaches, which again enhances the exposure and tsunami risk. Even though the 1992 tsunami disaster in Nicaragua did not severely hit the tourist beaches, it raised the risk awareness, and special attention is now given to ‘slow’ earthquakes that may be modest in shaking while still having a large tsunami potential. The tsunami hazard mapping is well advanced in Nicaragua, Costa Rica and El Salvador, and initiatives are ongoing to improve the mapping in all countries. National systems for early warning were established in Nicaragua and El Salvador, while the other four countries rely on rapid information from the Pacific Tsunami Warning Center. Mitigation measures and information campaigns are presently conducted on a national basis in all countries, but a regional centre for early tsunami warning and coordinated information campaigns (CATAC) is expected to become operational in the near future.
A global probabilistic tsunami hazard assessment from earthquake sources
Authors: Davies Gareth , Griffin Jonathan , Løvholt Finn , Glimsdal Sylfest , Harbitz Carl , Thio Hong Kie , Lorito Stefano , Basili Roberto , Selva Jacopo , Geist Eric , Baptista Maria Ana 
Published: February 2017

Abstract
Large tsunamis occur infrequently but have the capacity to cause enormous numbers of casualties, damage to the built environment and critical infrastructure, and economic losses. A sound understanding of tsunami hazard is required to underpin management of these risks, and while tsunami hazard assessments are typically conducted at regional or local scales, globally consistent assessments are required to support international disaster risk reduction efforts, and can serve as a reference for local and regional studies. This study presents a global-scale probabilistic tsunami hazard assessment (PTHA), extending previous global-scale assessments based largely on scenario analysis. Only earthquake sources are considered, as they represent about 80% of the recorded damaging tsunami events. Globally extensive estimates of tsunami run-up height are derived at various exceedance rates, and the associated uncertainties are quantified. Epistemic uncertainties in the exceedance rates of large earthquakes often lead to large uncertainties in tsunami run-up. Deviations between modelled tsunami run-up and event observations are quantified, and found to be larger than suggested in previous studies. Accounting for these deviations in PTHA is important, as it leads to a pronounced increase in predicted tsunami run-up for a given exceedance rate.
An international collaboration studying the physiological and anatomical cerebral effects of carbon dioxide during head-down tilt bed rest: the SPACECOT study
Authors: Marshall-Goebel Karina , Mulder Edwin , Donoviel Dorit , Strangman Gary , Suarez Jose I. , Venkatasubba Rao Chethan , Frings-Meuthen Petra , Limper Ulrich , Rittweger Jörn , Bershad Eric M. 
Published: February 2017

Exposure to the microgravity environment results in various adaptive and maladaptive physiological changes in the human body, with notable ophthalmic abnormalities developing during 6-mo missions on the International Space Station (ISS). These findings have led to the hypothesis that the loss of gravity induces a cephalad fluid shift, decreased cerebral venous outflow, and increased intracranial pressure, which may be further exacerbated by increased ambient carbon dioxide (CO2) levels on the ISS. Here we describe the SPACECOT study (studying the physiological and anatomical cerebral effects of CO2 during head-down tilt), a randomized, double-blind crossover design study with two conditions: 29 h of 12° head-down tilt (HDT) with ambient air and 29 h of 12° HDT with 0.5% CO2. The internationally collaborative SPACECOT study utilized an innovative approach to study the effects of headward fluid shifting induced by 12° HDT and increased ambient CO2 as well as their interaction with a focus on cerebral and ocular anatomy and physiology. Here we provide an in-depth overview of this new approach including the subjects, study design, and implementation, as well as the standardization plan for nutritional intake, environmental parameters, and bed rest procedures. NEW & NOTEWORTHY A new approach for investigating the combined effects of cephalad fluid shifting and increased ambient carbon dioxide (CO2) is presented. This may be useful for studying the neuroophthalmic and cerebral effects of spaceflight where cephalad fluid shifts occur in an elevated CO2 environment.
Inhibition of Age-Related Therapy Resistance in Melanoma by Rosiglitazone-Mediated Induction of Klotho
Authors: Behera Reeti , Kaur Amanpreet , Webster Marie R. , Kim Suyeon , Ndoye Abibatou , Kugel Curtis H. , Alicea Gretchen M. , Wang Joshua , Ghosh Kanad , Cheng Phil , Lisanti Sofia , Marchbank Katie , Dang Vanessa , Levesque Mitchell , Dummer Reinhard , Xu Xiaowei , Herlyn Meenhard , Aplin Andrew E. , Roesch Alexander , Caino Cecilia , Altieri Dario C. , Weeraratna Ashani T. 
Published: February 2017

Abstract
Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical cells in a young microenvironment. This is dependent on age-related secreted factors. Klotho is an age-related protein whose serum levels decrease dramatically by age 40. Most studies on klotho in cancer have focused on the expression of klotho in the tumor cell. We have shown that exogenous klotho inhibits internalization and signaling of Wnt5A, which drives melanoma metastasis and resistance to targeted therapy. We investigate here whether increasing klotho in the aged microenvironment could be an effective strategy for the treatment of melanoma.
Experimental Design: PPARγ increases klotho levels and is increased by glitazones. Using rosiglitazone, we queried the effects of rosiglitazone on Klotho/Wnt5A cross-talk, in vitro and in vivo, and the implications of that for targeted therapy in young versus aged animals.
Results: We show that rosiglitazone increases klotho and decreases Wnt5A in tumor cells, reducing the burden of both BRAF inhibitor–sensitive and BRAF inhibitor–resistant tumors in aged, but not young mice. However, when used in combination with PLX4720, tumor burden was reduced in both young and aged mice, even in resistant tumors.
Conclusions: Using glitazones as adjuvant therapy for melanoma may provide a new treatment strategy for older melanoma patients who have developed resistance to vemurafenib. As klotho has been shown to play a role in other cancers too, our results may have wide relevance for multiple tumor types. Clin Cancer Res; 23(12); 3181–90. ©2017 AACR.
The E3 Ligase CHIP Mediates p21 Degradation to Maintain Radioresistance
Authors: Biswas Kuntal , Sarkar Sukumar , Du Kangping , Brautigan David L. , Abbas Tarek , Larner James M. 
Published: February 2017

Abstract
Lung cancer resists radiotherapy, making it one of the deadliest forms of cancer. Here, we show that human lung cancer cell lines can be rendered sensitive to ionizing radiation (IR) by RNAi knockdown of C-terminus of Hsc70-interacting protein (CHIP/STUB1), a U-box-type E3 ubiquitin ligase that targets a number of stress-induced proteins. Mechanistically, ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor, p21 protein, is reduced by CHIP knockdown, leading to enhanced senescence of cells in response to exposure to IR. Cellular senescence and sensitivity to IR is prevented by CRISPR/Cas9-mediated deletion of the p21 gene (CDKN1A) in CHIP knockdown cells. Conversely, overexpression of CHIP potentiates p21 degradation and promotes greater radioresistance of lung cancer cells. In vitro and cell-based assays demonstrate that p21 is a novel and direct ubiquitylation substrate of CHIP that also requires the CHIP-associated chaperone HSP70. These data reveal that the inhibition of the E3 ubiquitin ligase CHIP promotes radiosensitivity, thus suggesting a novel strategy for the treatment of lung cancer.
Implications: The CHIP-HSP70-p21 ubiquitylation/degradation axis identified here could be exploited to enhance the efficacy of radiotherapy in patients with non–small cell lung cancer. Mol Cancer Res; 15(6); 651–9. ©2017 AACR.
Simultaneous Multiple Intracerebral Hemorrhages (SMICH)
Authors: Wu Teddy Y. , Yassi Nawaf , Shah Darshan G. , Ma Minmin , Sharma Gagan , Putaala Jukka , Strbian Daniel , Campbell Bruce C.V. , Yan Bernard , Tatlisumak Turgut , Desmond Patricia M. , Davis Stephen M. , Meretoja Atte 
Published: February 2017

Background and Purpose—
Simultaneous multiple intracerebral hemorrhages (SMICHs) are uncommon. Few single-center studies have analyzed characteristics and outcome of SMICH. We analyzed clinical characteristics and outcome of SMICH patients from 2 comprehensive stroke centers.

Methods—
Baseline imaging from consecutive intracerebral hemorrhage (ICH) patients (n=1552) from Helsinki ICH study and Royal Melbourne Hospital ICH study was screened for SMICH. ICH pathogenesis was classified according to the structural lesion, medication, amyloid angiopathy, systemic/other disease, hypertension, undetermined classification system (SMASH-U). ICH caused by trauma, tumor, and aneurysmal rupture was excluded. Baseline clinical and radiological characteristics and 90-day mortality were compared between SMICH and single ICH patients. Association of SMICH with 90-day mortality was assessed in multivariable logistic regression models adjusted for predictors of ICH outcome.

Results—

Of 1452 patients, 85 (5.9%) were classified as SMICH. SMICH were more often female (58% versus 42%;
P
=0.004), had lower baseline Glasgow Coma Scale (12 versus 14;
P
=0.008), and more frequent lobar location (59% versus 34%;
P
<0.001) compared with single ICH. The SMASH-U pathogenesis of SMICH patients was less often hypertensive (20% versus 37%;
P
=0.001), more often systemic coagulopathy (12% versus 3%;
P
<0.001), and trended toward more cerebral amyloid angiopathy (32% versus 23%;
P
=0.071). SMICH was not associated with 90-day mortality on univariate (37% versus 35%;
P
=0.610), multivariable (odds ratio, 0.783; 95% confidence interval, 0.401–1.529;
P
=0.473), or propensity score–matched analyses (odds ratio, 0.760; 95% confidence interval, 0.352–1.638;
P
=0.484).

Conclusions—
SMICH occurs in ≈1 in 20 ICH, more commonly with lobar located hematomas and systemic coagulopathy with less hypertensive angiopathy. The associated mortality is similar to single ICH. Given varied etiologies, SMICH management should target the underlying pathology.
A Stochastic Perturbed Parameterization Tendency Scheme for Diffusion (SPPTD) and Its Application to an Idealized Supercell Simulation
Authors: Qiao Xiaoshi , Wang Shizhang , Min Jinzhong 
Published: February 2017

Abstract
Diffusion plays an important role in supercell simulations. A stochastically perturbed parameterization tendency scheme for diffusion (SPPTD) is developed to incorporate diffusive uncertainties in ensemble forecasts. This scheme follows the same procedure as the previously published stochastically perturbed parameterization tendencies (SPPT) scheme but uses a recursive filter to generate smooth perturbations. It also employs horizontal and vertical localization to retain the impact of perturbation in areas with strong shear. Three additional restrictions are added for the sake of integration stability; these restrictions determine the area and amplitude of the perturbation and the situation to suspend SPPTD.
The performance of this scheme is examined by using an idealized supercell storm. The model errors are simulated using different resolutions in the truth run (1 km) and ensemble forecasts (2 km). The results indicate that the ensemble forecasts using SPPTD encompass the intensity and displacement of maximum updraft helicity in the truth run. This scheme yields better results than can be obtained using initial perturbations or larger computational mixing coefficients.
The sensitivity of SPPTD to each of its parameters is also examined. The results indicate that the optimal horizontal and temporal scales for SPPTD are 40 km and 30 min, respectively. Moderately adjusting the spatiotemporal scale by 10 km or 10 min does not significantly change the SPPTD performance. In this case study, an ensemble size of 20 is sufficient. Perturbing the diffusion terms of all variables using the same approach does not provide additional benefits other than that of selected variables and thus requires further study.