bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of carbapenem‐resistant Klebsiella pneumoniae (CR‐KP) infections in kidney transplantation
Authors: Varotti Giovanni , Dodi Ferdinando , Terulla Alessia , Santori Gregorio , Mariottini Gabriele , Bertocchi Massimo , Marchese Anna , Fontana Iris 
Published: August 2017

AbstractBackgroundCarbapenem‐resistant Klebsiella pneumoniae (CR‐KP) infections in solid organ transplant patients are progressively increasing and are associated with worse outcomes, although potential risk factors and therapeutic strategies are still not well defined.MethodsWe conducted a retrospective matched‐pair analysis in which we compared 26 recipients CR‐KP‐positive after kidney transplantation (KT) with 52 CR‐KP‐negative patients transplanted in the same period, during a CR‐KP outbreak that occurred in our hospital. Twenty‐one patients (80%) received a combined antibiotic treatment. At the end of the follow‐up, of the 26 CR‐KP infected patients, 11 (42.3%) experienced at least one episode of re‐infection, 9 (34.6%) remained colonized, and 6 (23.0%) had a symptomatic infection. Two of the 11 patients with re‐infection died, while 9 were colonized at the end of the study.ResultsA significantly better patient (P = .043) and graft (P < .001) survival was observed in CR‐KP‐negative patients. Univariate analysis identified the following variables as potential risk factors associated with CR‐KP infection after KT: lower body mass index (P = .020); higher creatinine levels at post‐transplant days 7 (P = .009), 15 (P = .026), and 30 (P = .019); longer hospital stay (P = .007); longer cold ischemia time (P = .004); delayed graft function (P = .020); and higher Clavien‐Dindo score (P = .006).ConclusionThe study confirmed that a CR‐KP positivity may affect the outcome of a kidney transplant population. In severe CR‐KP infections with sepsis, a combined antibiotic treatment seems to be advisable.
Safe and effective administration of BCG for bladder carcinoma in situ after umbilical cord blood stem cell transplantation
Authors: Magaribuchi Toshihiro , Akamatsu Shusuke , Kobayashi Takashi , Kawabata Hiroshi , Yamasaki Toshinari , Inoue Takahiro , Ogawa Osamu 
Published: August 2017

AbstractAlthough intravesical Bacillus Calmette‐Guérin (BCG) instillation is the standard treatment for carcinoma in situ of the bladder, it is generally contraindicated in immunocompromised patients. Here we report the first case, to our knowledge, of BCG treatment for a bladder cancer patient who had received umbilical cord blood stem cell transplantation (UCBSCT). BCG can be given safely and effectively in select cases where reconstitution of the immune system has been achieved at least 2 years after UCBSCT.
Evaluation of the use of shock index in identifying acute blood loss in healthy blood donor dogs
Authors: McGowan Erin E. , Marryott Kimberly , Drobatz Kenneth J. , Reineke Erica L. 
Published: August 2017

AbstractObjectiveTo determine if shock index (SI) would increase following blood donation and if it would be a more sensitive assessment of acute blood loss as compared with heart rate (HR), blood pressure, and plasma lactate.DesignProspective study.SettingUniversity teaching hospital.AnimalsTwenty client‐owned clinically normal dogs.InterventionsPeripheral venous blood measurements and blood donation.Measurements and Main ResultsData were collected at 3 time points: prior to donation (Tpre), immediately after donation (T0), and 10 minutes following completion of donation (T10). HR and systolic blood pressure (SBP) were recorded and used to calculate SI at time pointsTpre,T0, andT10. Packed cell volume (PCV), total plasma protein (TPP), and plasma lactate were evaluated from a peripheral venous blood sample atTpreandT10.The mean SI was significantly increased at both time points following blood donation as compared to baseline (SIpre= 0.88 ± 0.19 vs SI0= 1.17 ± 0.21 vs SI10= 1.12 ± 0.25 (P= 0.0002 and 0.0003, respectively). Following blood donation, the mean SBP was significantly lower (SBPpre= 149 ± 24 mm Hg, SBP0= 118 ± 20 mm Hg;P= 0.0001, SBP10= 133 ± 21 mm Hg;P= 0.011). The mean HR was not significantly different atT0but was significantly increased atT10(HRpre= 128 ± 21/min, HR0= 136 ± 25/min,P= 0.193; HR10= 146 ± 29/min,P= 0.003). There was no significant difference in mean PCV (PCVpre= 50 ± 4%, PCV10= 48 ± 4%,P= 0.08). The mean TPP and plasma lactate were significantly different following donation but still within the reference interval (TPPpre= 6.8 ± 0.4 g/dL, TPP10= 6.4 ± 0.4 g/dL,P= 0.0014; Lacpre= 1.7 ± 0.7mmol/L, Lac10= 1.9 ± 0.8 mmol/L,P= 0.04). A receiver operating characteristic (ROC) analysis comparing area under the curve (AUC) for SI, HR, and SBP atT0andT10compared toTprefound that SI (AUC atT0: 0.858, CI: 0.730, 0.984 AUC atT10: 0.769 CI: 0.617, 0.921) was a better indicator of blood loss than SBP at bothT0(AUC 0.165, CI: 0.0384, 0.292,P < 0.0001) andT10(AUC 0.288, CI: 0.124, 0.451,P < 0.001) and better than HR atT0(AUC 0.574, CI: 0.392, 0.756,P < 0.001). An SI cut‐off of 1.064 was 80% specific and 85% sensitive atT0for detecting blood loss.ConclusionsAn SI > 1.0 is a sensitive and specific tool for detecting acute small volume blood loss in healthy dogs.
Interventions to Reduce Perceived Stress Among Graduate Students: A Systematic Review With Implications for Evidence‐Based Practice
Authors: Stillwell Susan B. , Vermeesch Amber L. , Scott Jane G. 
Published: August 2017

ABSTRACTBackgroundStress is a part of daily life for graduate students, including graduate nursing students. Contemporary graduate nursing students are facing unprecedented challenges to meet rigorous academic standards as they prepare for their advanced professional role to meet the demands of the nation's complex and ever‐changing healthcare system. Empowering graduate nursing students to ease their perceived stress and minimize undesirable health effects may benefit their capacity to adapt and successfully manage perceived stress in their future healthcare role.AimsTo conduct a systematic review to evaluate the existing evidence with the aim of identifying evidence‐based self‐care interventions for coping with perceived stress.MethodsWe conducted a systematic review, searching CINAHL Plus with Full Text, PsycINFO, and MEDLINE. Inclusion criteria included self‐care, graduate students, perceived stress as measured by Perceived Stress Scale, quantitative analysis, conducted within the United States, English language, and peer reviewed. Two authors completed an asynchronous review of the articles, and one expert evidence‐based practice mentor and one wellness expert conducted rigorous appraisal of the eight identified studies. Evidence was evaluated and synthesized, and recommendations for practice were determined.ResultsEight studies meeting the criteria for this systematic review were critically appraised. The interventions varied from a stress management course to mind‐body‐stress‐reduction (MBSR) techniques, such as yoga, breath work, meditation, and mindfulness. All studies measured the outcome of stress with the Perceived Stress Scale. Each study demonstrated a reduction in perceived stress postintervention.Linking Evidence to ActionMost effective self‐care MBSR interventions include (a) a didactic component, (b) a guided MBSR practice session, and (c) homework. Consideration should be given to a trained or certified MBSR instructor to teach the intervention.
Draft Genome Sequence of
Magnetospirillum
sp. Strain 15-1, a Denitrifying Toluene Degrader Isolated from a Planted Fixed-Bed Reactor
Authors: Meyer-Cifuentes Ingrid , Fiedler Stefan , Müller Jochen A. , Kappelmeyer Uwe , Mäusezahl Ines , Heipieper Hermann J. 
Published: August 2017

ABSTRACT

Here, we report the draft genome sequence of
Magnetospirillum
sp. 15-1. This strain was isolated from a planted fixed-bed reactor based on its ability to degrade toluene under anaerobic conditions. The genome assembly consists of 5.4 Mb in 28 contigs and 5,095 coding sequences containing the genes involved in anaerobic toluene degradation.
Discovery and Validation of a Six-Marker Serum Protein Signature for the Diagnosis of Active Pulmonary Tuberculosis
Authors: De Groote Mary A. , Sterling David G. , Hraha Thomas , Russell Theresa M. , Green Louis S. , Wall Kirsten , Kraemer Stephan , Ostroff Rachel , Janjic Nebojsa , Ochsner Urs A. 
Published: August 2017

ABSTRACT

New non-sputum biomarker tests for active tuberculosis (TB) diagnostics are of the highest priority for global TB control. We performed in-depth proteomic analysis using the 4,000-plex SOMAscan assay on 1,470 serum samples from seven countries where TB is endemic. All samples were from patients with symptoms and signs suggestive of active pulmonary TB that were systematically confirmed or ruled out for TB by culture and clinical follow-up. HIV coinfection was present in 34% of samples, and 25% were sputum smear negative. Serum protein biomarkers were identified by stability selection using L1-regularized logistic regression and by Kolmogorov-Smirnov (KS) statistics. A naive Bayes classifier using six host response markers (HR6 model), including SYWC, kallistatin, complement C9, gelsolin, testican-2, and aldolase C, performed well in a training set (area under the sensitivity-specificity curve [AUC] of 0.94) and in a blinded verification set (AUC of 0.92) to distinguish TB and non-TB samples. Differential expression was also highly significant (
P
< 10
−20
) for previously described TB markers, such as IP-10, LBP, FCG3B, and TSP4, and for many novel proteins not previously associated with TB. Proteins with the largest median fold changes were SAA (serum amyloid protein A), NPS-PLA2 (secreted phospholipase A2), and CA6 (carbonic anhydrase 6). Target product profiles (TPPs) for a non-sputum biomarker test to diagnose active TB for treatment initiation (TPP#1) and for a community-based triage or referral test (TPP#2) have been published by the WHO. With 90% sensitivity and 80% specificity, the HR6 model fell short of TPP#1 but reached TPP#2 performance criteria. In conclusion, we identified and validated a six-marker signature for active TB that warrants diagnostic development on a patient-near platform.
Comparative Genomics Study of Staphylococcus epidermidis Isolates from Orthopedic-Device-Related Infections Correlated with Patient Outcome
Authors: Post Virginia , Harris Llinos G. , Morgenstern Mario , Mageiros Leonardos , Hitchings Matthew D. , Méric Guillaume , Pascoe Ben , Sheppard Samuel K. , Richards R. Geoff , Moriarty T. Fintan 
Published: August 2017

ABSTRACT

Staphylococcus epidermidis
has emerged as an important opportunistic pathogen causing orthopedic-device-related infections (ODRI). This study investigated the association of genome variation and phenotypic features of the infecting
S. epidermidis
isolate with the clinical outcome for the infected patient.
S. epidermidis
isolates were collected from 104 patients with ODRI. Their clinical outcomes were evaluated, after an average of 26 months, as either “cured” or “not cured.” The isolates were tested for antibiotic susceptibility and biofilm formation. Whole-genome sequencing was performed on all isolates, and genomic variation was related to features associated with “cured” and “not cured.” Strong biofilm formation and aminoglycoside resistance were associated with a “not-cured” outcome (
P
= 0.031 and
P
< 0.001, respectively). Based on gene-by-gene analysis, some accessory genes were more prevalent in isolates from the “not-cured” group. These included the biofilm-associated
bhp
gene, the antiseptic resistance
qacA
gene, the cassette chromosome recombinase-encoding genes
ccrA
and
ccrB
, and the IS
256
-like transposase gene. This study identifies biofilm formation and antibiotic resistance as associated with poor outcome in
S. epidermidis
ODRI. Whole-genome sequencing identified specific genes associated with a “not-cured” outcome that should be validated in future studies. (The study has been registered at ClinicalTrials.gov with identifier NCT02640937.)
Sorafenib Impedes Rift Valley Fever Virus Egress by Inhibiting Valosin-Containing Protein Function in the Cellular Secretory Pathway
Authors: Brahms Ashwini , Mudhasani Rajini , Pinkham Chelsea , Kota Krishna , Nasar Farooq , Zamani Rouzbeh , Bavari Sina , Kehn-Hall Kylene 
Published: August 2017

ABSTRACT
There is an urgent need for therapeutic development to combat infections caused by Rift Valley fever virus (RVFV), which causes devastating disease in both humans and animals. In an effort to repurpose drugs for RVFV treatment, our previous studies screened a library of FDA-approved drugs. The most promising candidate identified was the hepatocellular and renal cell carcinoma drug sorafenib. Mechanism-of-action studies indicated that sorafenib targeted a late stage in virus infection and caused a buildup of virions within cells. In addition, small interfering RNA (siRNA) knockdown studies suggested that nonclassical targets of sorafenib are important for the propagation of RVFV. Here we extend our previous findings to identify the mechanism by which sorafenib inhibits the release of RVFV virions from the cell. Confocal microscopy imaging revealed that glycoprotein Gn colocalizes and accumulates within the endoplasmic reticulum (ER) and the transport of Gn from the Golgi complex to the host cell membrane is reduced. Transmission electron microscopy demonstrated that sorafenib caused virions to be present inside large vacuoles inside the cells. p97/valosin-containing protein (VCP), which is involved in membrane remodeling in the secretory pathway and a known target of sorafenib, was found to be important for RVFV egress. Knockdown of VCP resulted in decreased RVFV replication, reduced Gn Golgi complex localization, and increased Gn ER accumulation. The intracellular accumulation of RVFV virions was also observed in cells transfected with siRNA targeting VCP. Collectively, these data indicate that sorafenib causes a disruption in viral egress by targeting VCP and the secretory pathway, resulting in a buildup of virions within dilated ER vesicles.

IMPORTANCE
In humans, symptoms of RVFV infection mainly include a self-limiting febrile illness. However, in some cases, infected individuals can also experience hemorrhagic fever, neurological disorders, liver failure, and blindness, which could collectively be lethal. The ability of RVFV to expand geographically outside sub-Saharan Africa is of concern, particularly to the Americas, where native mosquito species are capable of virus transmission. Currently, there are no FDA-approved therapeutics to treat RVFV infection, and thus, there is an urgent need to understand the mechanisms by which the virus hijacks the host cell machinery to replicate. The significance of our research is in identifying the cellular target of sorafenib that inhibits RVFV propagation, so that this information can be used as a tool for the further development of therapeutics used to treat RVFV infection.
Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon
Authors: Akiyama Hisashi , Ramirez Nora-Guadalupe Pina , Gibson Gregory , Kline Christopher , Watkins Simon , Ambrose Zandrea , Gummuluru Suryaram 
Published: August 2017

ABSTRACTA hallmark of human immunodeficiency virus type 1 (HIV-1) infectionin vivois chronic immune activation concomitant with type I interferon (IFN) production. Although type I IFN induces an antiviral state in many cell types, HIV-1 can replicatein vivovia mechanisms that have remained unclear. We have recently identified a type I IFN-inducible protein, CD169, as the HIV-1 attachment factor on dendritic cells (DCs) that can mediate robust infection of CD4+T cells intrans. Since CD169 expression on macrophages is also induced by type I IFN, we hypothesized that type I IFN-inducible CD169 could facilitate productive HIV-1 infection in myeloid cells incisand CD4+T cells intransand thus offset antiviral effects of type I IFN. In support of this hypothesis, infection of HIV-1 or murine leukemia virus Env (MLV-Env)-pseudotyped HIV-1 particles was enhanced in IFN-α-treated THP-1 monocytoid cells, and this enhancement was primarily dependent on CD169-mediated enhancement at the virus entry step, a phenomenon phenocopied in HIV-1 infections of IFN-α-treated primary monocyte-derived macrophages (MDMs). Furthermore, expression of CD169, a marker of type I IFN-induced immune activationin vivo, was enhanced in lymph nodes from pigtailed macaques infected with simian immunodeficiency virus (SIV) carrying HIV-1 reverse transcriptase (RT-SHIV), compared to uninfected macaques, and interestingly, there was extensive colocalization of p27gagand CD169, suggesting productive infection of CD169+myeloid cellsin vivo. While cell-free HIV-1 infection of IFN-α-treated CD4+T cells was robustly decreased, initiation of infection intransvia coculture with CD169+IFN-α-treated DCs restored infection, suggesting that HIV-1 exploits CD169 incisand intransto attenuate a type I IFN-induced antiviral state.IMPORTANCEHIV-1 infection in humans causes immune activation characterized by elevated levels of proinflammatory cytokines, including type I interferons (IFN). Although type I IFN induces an antiviral state in many cell typesin vitro, HIV-1 can replicatein vivovia mechanisms that have remained unclear. In this study, we tested the hypothesis that CD169, a type I IFN-inducible HIV-1 attachment factor, offsets antiviral effects of type I IFN. Infection of HIV-1 was rescued in IFN-α-treated myeloid cells via upregulation of CD169 and a subsequent increase in CD169-dependent virus entry. Furthermore, extensive colocalization of viral Gag and CD169 was observed in lymph nodes of infected pigtailed macaques, suggesting productive infection of CD169+cellsin vivo. Treatment of dendritic cell (DC)-T cell cocultures with IFN-α upregulated CD169 expression on DCs and rescued HIV-1 infection of CD4+T cells intrans, suggesting that HIV-1 exploits CD169 to attenuate type I IFN-induced restrictions.
Structure-Based Design of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses to a Conserved Epitope
Authors: Pierce Brian G. , Boucher Elisabeth N. , Piepenbrink Kurt H. , Ejemel Monir , Rapp Chelsea A. , Thomas William D. , Sundberg Eric J. , Weng Zhiping , Wang Yang 
Published: August 2017

ABSTRACT
Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as well as a bivalent immunogen with two copies of the epitope on the E2 surface. We solved the X-ray structure of a cyclic immunogen in complex with the HCV1 antibody and confirmed preservation of the epitope conformation and the HCV1 interface. Mice vaccinated with our designed immunogens produced robust antibody responses to epitope I, and their serum could neutralize HCV. Notably, the cyclic designs induced greater epitope-specific responses and neutralization than the native peptide epitope. Beyond successfully designing several novel HCV immunogens, this study demonstrates the principle that neutralizing anti-HCV antibodies can be induced by epitope-based, engineered vaccines and provides the basis for further efforts in structure-based design of HCV vaccines.

IMPORTANCE
Hepatitis C virus is a leading cause of liver disease and liver cancer, with approximately 3% of the world's population infected. To combat this virus, an effective vaccine would have distinct advantages over current therapeutic options, yet experimental vaccines have not been successful to date, due in part to the virus's high sequence variability leading to immune escape. In this study, we rationally designed several vaccine immunogens based on the structure of a conserved epitope that is the target of broadly neutralizing antibodies.
In vivo
results in mice indicated that these antigens elicited epitope-specific neutralizing antibodies, with various degrees of potency and breadth. These promising results suggest that a rational design approach can be used to generate an effective vaccine for this virus.
Adenovirus Core Protein VII Downregulates the DNA Damage Response on the Host Genome
Authors: Avgousti Daphne C. , Della Fera Ashley N. , Otter Clayton J. , Herrmann Christin , Pancholi Neha J. , Weitzman Matthew D. 
Published: August 2017

ABSTRACT
Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier to successful infection. The adenovirus genome is packaged with protein VII, a virally encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by the cellular DNA damage machinery. We showed that protein VII localizes to host chromatin during infection, leading us to hypothesize that protein VII may affect DNA damage responses on the cellular genome. Here we show that protein VII at cellular chromatin results in a significant decrease in accumulation of phosphorylated H2AX (γH2AX) following irradiation, indicating that protein VII inhibits DDR signaling. The oncoprotein SET was recently suggested to modulate the DDR by affecting access of repair proteins to chromatin. Since protein VII binds SET, we investigated a role for SET in DDR inhibition by protein VII. We show that knockdown of SET partially rescues the protein VII-induced decrease in γH2AX accumulation on the host genome, suggesting that SET is required for inhibition. Finally, we show that knockdown of SET also allows ATM to localize to incoming viral genomes bound by protein VII during infection with a mutant lacking early region E4. Together, our data suggest that the protein VII-SET interaction contributes to DDR evasion by adenovirus. Our results provide an additional example of a strategy used by adenovirus to abrogate the host DDR and show how viruses can modify cellular processes through manipulation of host chromatin.

IMPORTANCE
The DNA damage response (DDR) is a cellular network that is crucial for maintaining genome integrity. DNA viruses replicating in the nucleus challenge the resident genome and must overcome cellular responses, including the DDR. Adenoviruses are prevalent human pathogens that can cause a multitude of diseases, such as respiratory infections and conjunctivitis. Here we describe how a small adenovirus core protein that localizes to host chromatin during infection can globally downregulate the DDR. Our study focuses on key players in the damage signaling pathway and highlights how viral manipulation of chromatin may influence access of DDR proteins to the host genome.