bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standardization of transfusion practice in organ donors using the Digital Intern, an electronic decision support algorithm
Authors: Connor Joseph P. , Cunningham Ashley M. , Raife Thomas , Rose William N. , Medow Joshua E. 
Published: March 2017

BACKGROUNDProspective clinical trials support restrictive thresholds for red blood cell (RBC) transfusion. Nonsurvivable donors are a major source of organs for transplantation. The Digital Intern (DI) is a computer algorithm to standardize donor care that includes a more restrictive transfusion threshold. The impact of standardized and restrictive RBC transfusion in organ donors, as determined by the DI, has not been reported.STUDY DESIGN AND METHODSWe conducted a retrospective cohort study to compare the transfusion practice of the DI (n = 100) to a historic group of physician‐managed donors (n = 90). Transfusion rates, the number of units transfused, and pretransfusion laboratory values were compared between groups. The variability of these parameters was also compared between groups. Finally, the number of transplanted organs per donor in each group was compared.RESULTSThe mean time as a donor was 25.9 ± 15.2 hours and was not different between the groups. In the DI group 19% were transfused compared to 26% in the control group (p = 0.3). The number of units transfused was less in the DI group (1 unit vs. 2 units per transfusion, p = 0.03) and the pretransfusion hematocrit was lower in the DI group (23% vs. 27%, p = 0.01). The variability in the latter two parameters was significantly lower in the DI group. The number of transplanted organs per donor was similar in both groups (3.24 [DI] vs. 3.03 [control], p = 0.37).CONCLUSIONThe DI provides a more standardization transfusion practice in organ donors and reduces blood use without compromising transplantable organs.
A case of anti‐Rd causing fetal anemia
Authors: Rauch Stefan , Ritgen Jochen , Wißkirchen Matthias , Bauerfeind Ursula , Kohne Elisabeth , Weinstock Christof 
Published: March 2017

BACKGROUNDRd (SC4) is a low‐frequency antigen of the Scianna blood group system. Only very few reports on anti‐Rd in pregnancy exist. Mild to moderate hemolytic disease of the newborn caused by anti‐Rd has been reported. This report may add further information on the clinical significance of anti‐Rd for the fetus.CASE REPORTIn a case of severe fetal anemia (hemoglobin concentration, 3.0 g/dL) repeated intrauterine transfusions were required. The strongly positive direct antiglobulin test (DAT) of the fetal red blood cells led to the diagnosis of hemolytic disease. The routine antibody screen was negative, extended testing revealed a maternal anti‐Rd with a titer of 256. Both the newborn and her father were confirmed to carry the SC*01.04 allele.CONCLUSIONAnti‐Rd can cause fetal anemia. Low‐frequency antigens including Rd are normally not present on screening cells. Antibodies directed against low‐frequency antigens will usually not be detected by routine antibody screening in pregnancy. Thus, in cases of fetal anemia the DAT should always be included in the diagnostic workup.
Effectiveness of falls prevention interventions for older adults newly discharged from hospital: a systematic review protocol
Authors: Naseri Chiara , McPhail Steven , Francis-Coad Jacqueline , Haines Terry , Etherton-Beer Christopher , Morris Meg E. , Flicker Leon , Shorr Ronald , Bulsara Max , Netto Julie , Lee Den-Ching , Waldron Nicholas , Boudville Amanda , Hill Anne-Marie 
Published: March 2017

Review objective:
The objective of this review is to synthesize the best available evidence on the effectiveness of falls prevention interventions provided just prior or immediately after discharge from hospital on falls rates and falls injuries among older adults living in the community in the first 6 months after discharge from hospital.
Effectiveness of intrathecal nicardipine on cerebral vasospasm in non-traumatic subarachnoid hemorrhage: a systematic review protocol
Authors: Stuart Daniel , Christian Robin , Uschmann Hartmut 
Published: March 2017

Review question/objective:
The objective of this review is to determine the effectiveness of intrathecal (IT) nicardipine on cerebral vasospasm and its impact on the following outcome measures: mean flow velocities, angiographic and/or clinical vasospasm and infection rates. Specifically, the review question is: What is the effectiveness of IT nicardipine on cerebral vasospasm in adult patients with aneurysmal subarachnoid hemorrhage?
Effectiveness of Mohs micrographic surgery for nonmelanoma skin cancer: a systematic review protocol
Authors: Tokede Oluwatosin , Jadotte Yuri T. , Nkemjika Stanley , Holly Cheryl , Cohen Philip , Schwartz Robert , Watkins Ann , Dellavalle Robert 
Published: March 2017

Review objectives/questions:
The objective of the review is to evaluate the effectiveness of Mohs micrographic surgery on the mortality, recurrence and quality of life of patients with nonmelanoma skin cancers when compared with other treatment modalities.
Specifically, it aims to examine the effectiveness of Mohs micrographic surgery compared with other treatment modalities such as excisional surgery, curettage and electrodessication and radiation therapy, as well as nonsurgical/chemotherapeutic interventions such as topical 5-fluorouracil and imiquimod immunotherapy in the management of nonmelanoma skin cancers.
Effect of educational and support interventions to increase long-term breastfeeding rates in primiparous women: a systematic review protocol
Authors: Meedya Shahla , Fernandez Ritin , Fahy Kathleen 
Published: March 2017

Review question/objective:
The objective of this review is to identify the effects of educational and supportive interventions provided by health professionals on long-term breastfeeding rates at six months and up to two years post partum among primiparous women who intend to breastfeed.
The Malaria TaqMan Array Card Includes 87 Assays for Plasmodium falciparum Drug Resistance, Identification of Species, and Genotyping in a Single Reaction
Authors: Pholwat Suporn , Liu Jie , Stroup Suzanne , Jacob Shevin T. , Banura Patrick , Moore Christopher C. , Huang Fang , Laufer Miriam K. , Houpt Eric , Guler Jennifer L. 
Published: March 2017

ABSTRACT

Antimalarial drug resistance exacerbates the global disease burden and complicates eradication efforts. To facilitate the surveillance of resistance markers in countries of malaria endemicity, we developed a suite of TaqMan assays for known resistance markers and compartmentalized them into a single array card (TaqMan array card, TAC). We included 87 assays for species identification, for the detection of
Plasmodium falciparum
mutations associated with chloroquine, atovaquone, pyrimethamine, sulfadoxine, and artemisinin resistance, and for neutral single nucleotide polymorphism (SNP) genotyping. Assay performance was first optimized using DNA from common laboratory parasite lines and plasmid controls. The limit of detection was 0.1 to 10 pg of DNA and yielded 100% accuracy compared to sequencing. The tool was then evaluated on 87 clinical blood samples from around the world, and the malaria TAC once again achieved 100% accuracy compared to sequencing and in addition detected the presence of mixed infections in clinical samples. With its streamlined protocol and high accuracy, this malaria TAC should be a useful tool for large-scale antimalarial resistance surveillance.
First Report of the Carbapenemase Gene
bla
OXA-499
in Acinetobacter pittii
Authors: D'Souza Roshan , Pinto Naina Adren , Higgins Paul G. , Hwang Insik , Yong Dongeun , Choi Jongrak , Lee Kyoungwon , Chong Yunsop 
Published: March 2017

ABSTRACT

We identified the carbapenemase gene
bla
OXA-499
, a variant of
bla
OXA-143
, from a clinical isolate of
Acinetobacter pittii
for the first time. OXA-499 shared 93.1% amino acid identity with OXA-143, and the gene was located on the chromosome. By cloning the OXA-499-encoding gene into the pWH1266 vector and transforming it into susceptible
Acinetobacter
spp., we were able to show that OXA-499 confers resistance to carbapenems.
Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes
Authors: Flores Anthony R. , Olsen Randall J. , Cantu Concepcion , Pallister Kyler B. , Guerra Fermin E. , Voyich Jovanka M. , Musser James M. 
Published: March 2017

ABSTRACT

Studies of the human pathogen group A
Streptococcus
(GAS) define the carrier phenotype to be an increased ability to adhere to and persist on epithelial surfaces and a decreased ability to cause disease. We tested the hypothesis that a single amino acid change (Arg135Gly) in a highly conserved sensor kinase (LiaS) of a poorly defined GAS regulatory system contributes to a carrier phenotype through increased pilus production. When introduced into an
emm
serotype-matched invasive strain, the carrier allele (the gene encoding the LiaS protein with an arginine-to-glycine change at position 135 [
liaS
R135G
]) recapitulated a carrier phenotype defined by an increased ability to adhere to mucosal surfaces and a decreased ability to cause disease. Gene transcript analyses revealed that the
liaS
mutation significantly altered transcription of the genes encoding pilus in the presence of bacitracin. Elimination of pilus production in the isogenic carrier mutant decreased its ability to colonize the mouse nasopharynx and to adhere to and be internalized by cultured human epithelial cells and restored the virulence phenotype in a mouse model of necrotizing fasciitis. We also observed significantly reduced survival of the isogenic carrier mutant compared to that of the parental invasive strain after exposure to human neutrophils. Elimination of pilus in the isogenic carrier mutant increased the level of survival after exposure to human neutrophils to that for the parental invasive strain. Together, our data demonstrate that the carrier mutation (
liaS
R135G
) affects pilus expression. Our data suggest new mechanisms of pilus gene regulation in GAS and that the invasiveness associated with pilus gene regulation in GAS differs from the enhanced invasiveness associated with increased pilus production in other bacterial pathogens.
Perforin Expression by CD8 T Cells Is Sufficient To Cause Fatal Brain Edema during Experimental Cerebral Malaria
Authors: Huggins Matthew A. , Johnson Holly L. , Jin Fang , N′Songo Aurelie , Hanson Lisa M. , LaFrance Stephanie J. , Butler Noah S. , Harty John T. , Johnson Aaron J. 
Published: March 2017

ABSTRACTHuman cerebral malaria (HCM) is a serious complication ofPlasmodium falciparuminfection. The most severe outcomes for patients include coma, permanent neurological deficits, and death. Recently, a large-scale magnetic resonance imaging (MRI) study in humans identified brain swelling as the most prominent predictor of fatal HCM. Therefore, in this study, we sought to define the mechanism controlling brain edema through the use of the murine experimental cerebral malaria (ECM) model. Specifically, we investigated the ability of CD8 T cells to initiate brain edema during ECM. We determined that areas of blood-brain barrier (BBB) permeability colocalized with a reduction of the cerebral endothelial cell tight-junction proteins claudin-5 and occludin. Furthermore, through small-animal MRI, we analyzed edema and vascular leakage. Using gadolinium-enhanced T1-weighted MRI, we determined that vascular permeability is not homogeneous but rather confined to specific regions of the brain. Our findings show that BBB permeability was localized within the brainstem, olfactory bulb, and lateral ventricle. Concurrently with the initiation of vascular permeability, T2-weighted MRI revealed edema and brain swelling. Importantly, ablation of the cytolytic effector molecule perforin fully protected against vascular permeability and edema. Furthermore, perforin production specifically by CD8 T cells was required to cause fatal edema during ECM. We propose that CD8 T cells initiate BBB breakdown through perforin-mediated disruption of tight junctions. In turn, leakage from the vasculature into the parenchyma causes brain swelling and edema. This results in a breakdown of homeostatic maintenance that likely contributes to ECM pathology.
CRISPR-Cas and Contact-Dependent Secretion Systems Present on Excisable Pathogenicity Islands with Conserved Recombination Modules
Authors: Carpenter Megan R. , Kalburge Sai S. , Borowski Joseph D. , Peters Molly C. , Colwell Rita R. , Boyd E. Fidelma 
Published: March 2017

ABSTRACT

Pathogenicity islands (PAIs) are mobile integrated genetic elements that contain a diverse range of virulence factors. PAIs integrate into the host chromosome at a tRNA locus that contains their specific bacterial attachment site,
attB
, via integrase-mediated site-specific recombination generating
attL
and
attR
sites. We identified conserved recombination modules (integrases and
att
sites) previously described in choleragenic
Vibrio cholerae
PAIs but with novel cargo genes. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated proteins (Cas proteins) and a type VI secretion system (T6SS) gene cluster were identified at the
Vibrio
pathogenicity island 1 (VPI-1) insertion site in 19
V. cholerae
strains and contained the same recombination module. Two divergent type I-F CRISPR-Cas systems were identified, which differed in Cas protein homology and content. The CRISPR repeat sequence was identical among all
V. cholerae
strains, but the CRISPR spacer sequences and the number of spacers varied.
In silico
analysis suggests that the CRISPR-Cas systems were active against phages and plasmids. A type III secretion system (T3SS) was present in 12
V. cholerae
strains on a 68-kb island inserted at the same tRNA-serine insertion site as VPI-2 and contained the same recombination module. Bioinformatics analysis showed that two divergent T3SSs exist among the strains examined. Both the CRISPR and T3SS islands excised site specifically from the bacterial chromosome as complete units, and the cognate integrases were essential for this excision. These data demonstrated that identical recombination modules that catalyze integration and excision from the chromosome can acquire diverse cargo genes, signifying a novel method of acquisition for both CRISPR-Cas systems and T3SSs.

IMPORTANCE
This work demonstrated the presence of CRISPR-Cas systems and T3SSs on PAIs. Our work showed that similar recombination modules can associate with different cargo genes and catalyze their incorporation into bacterial chromosomes, which could convert a strain into a pathogen with very different disease pathologies. Each island had the ability to excise from the chromosome as distinct, complete units for possible transfer. Evolutionary analysis of these regions indicates that they were acquired by horizontal transfer and that PAIs are the units of transfer. Similar to the case for phage evolution, PAIs have a modular structure where different functional regions are acquired by identical recombination modules.
Considerations for effective science communication
Authors: Cooke Steven J. , Gallagher Austin J. , Sopinka Natalie M. , Nguyen Vivian M. , Skubel Rachel A. , Hammerschlag Neil , Boon Sarah , Young Nathan , Danylchuk Andy J. 
Published: March 2017

It is increasingly common for scientists to engage in sharing science-related knowledge with diverse knowledge users—an activity called science communication. Given that many scientists now seek information on how to communicate effectively, we have generated a list of 16 important considerations for those interested in science communication: (1) Define what science communication means to you and your research; (2) Know—and listen to—your target audience; (3) Consider a diverse but coordinated communication portfolio; (4) Draft skilled players and build a network; (5) Create and seize opportunities; (6) Be creative when you communicate; (7) Focus on the science in science communication; (8) Be an honest broker; (9) Understand the science of science communication; (10) Think like an entrepreneur; (11) Don’t let your colleagues stop you; (12) Integrate science communication into your research program; (13) Recognize how science communication enhances your science; (14) Request science communication funds from grants; (15) Strive for bidirectional communication; and (16) Evaluate, reflect, and be prepared to adapt. It is our ambition that the ideas shared here will encourage readers to engage in science communication and increase the effectiveness of those already active in science communication, stimulating them to share their experiences with others.
The BTK Inhibitor Ibrutinib (PCI-32765) Overcomes Paclitaxel Resistance in ABCB1- and ABCC10-Overexpressing Cells and Tumors
Authors: Zhang Hui , Patel Atish , Wang Yi-Jun , Zhang Yun-Kai , Kathawala Rishil J. , Qiu Long-Hui , Patel Bhargav A. , Huang Li-Hua , Shukla Suneet , Yang Dong-Hua , Ambudkar Suresh V. , Fu Li-Wu , Chen Zhe-Sheng 
Published: March 2017

AbstractPaclitaxel is one of the most widely used antineoplastic drugs in the clinic. Unfortunately, the occurrence of cellular resistance has limited its efficacy and application. The ATP-binding cassette subfamily B member 1 (ABCB1/P-glycoprotein) and subfamily C member 10 (ABCC10/MRP7) are the major membrane protein transporters responsible for the efflux of paclitaxel, constituting one of the most important mechanisms of paclitaxel resistance. Here, we demonstrated that the Bruton tyrosine kinase inhibitor, ibrutinib, significantly enhanced the antitumor activity of paclitaxel by antagonizing the efflux function of ABCB1 and ABCC10 in cells overexpressing these transporters. Furthermore, we demonstrated that the ABCB1 or ABCC10 protein expression was not altered after treatment with ibrutinib for up to 72 hours using Western blot analysis. However, the ATPase activity of ABCB1 was significantly stimulated by treatment with ibrutinib. Molecular docking analysis suggested the binding conformation of ibrutinib within the large cavity of the transmembrane region of ABCB1. Importantly, ibrutinib could effectively enhance paclitaxel-induced inhibition on the growth of ABCB1- and ABCC10-overexpressing tumors in nude athymic mice. These results demonstrate that the combination of ibrutinib and paclitaxel can effectively antagonize ABCB1- or ABCC10-mediated paclitaxel resistance that could be of great clinical interest. Mol Cancer Ther; 16(6); 1021–30. ©2017 AACR.
Global Longitudinal Strain by Echocardiography Predicts Long-Term Risk of Cardiovascular Morbidity and Mortality in a Low-Risk General Population
Authors: Biering-Sørensen Tor , Biering-Sørensen Sofie Reumert , Olsen Flemming Javier , Sengeløv Morten , Jørgensen Peter Godsk , Mogelvang Rasmus , Shah Amil M. , Jensen Jan Skov 
Published: March 2017

Background—
Global longitudinal strain (GLS) is prognostic of adverse cardiovascular outcomes in various patient populations, but the prognostic utility of GLS for long-term cardiovascular morbidity and mortality in the general population is unknown.

Methods and Results—

A total of 1296 participants in a general population study underwent a health examination, including echocardiography measurement of GLS. The primary end point was the composite of incident heart failure, acute myocardial infarction, or cardiovascular death. During a median follow-up of 11 years, 149 (12%) participants were diagnosed with heart failure, acute myocardial infarction, or cardiovascular death. Lower GLS was associated with a higher risk of the composite end point (hazard ratio, 1.12; 95% confidence interval, 1.08–1.17;
P
<0.001 per 1% decrease), an association that persisted after multivariable adjustment for age, sex, heart rate, hypertension, systolic blood pressure, left ventricular ejection fraction, left ventricular mass index, left ventricular dimension, deceleration time, left atrium dimension,
E
/
e
′, and pro B-type natriuretic peptide (hazard ratio, 1.05; 95% confidence interval, 1.00–1.11;
P
=0.045 per 1% decrease). GLS provided incremental prognostic information beyond the Framingham Risk Score, the Systemic Coronary Evaluation risk chart, and the modified American College of Cardiology/American Heart Association Pooled Cohort Equation for the composite outcome and incident heart failure. Sex modified the relationship between GLS and outcome such that after multivariable adjustment, GLS was an independent predictor of outcomes in men but not in women (hazard ratio, 1.14; 95% confidence interval, 1.06–1.24;
P
=0.001, and hazard ratio, 0.99; 95% confidence interval, 0.92–1.07;
P
=0.81, respectively;
P
for interaction =0.032).

Conclusions—
In the general population, GLS provides independent and incremental prognostic information regarding long-term risk of cardiovascular morbidity and mortality. GLS seems to be a stronger prognosticator in men than in women.
Cerebral Aneurysm Morphology Before and After Rupture
Authors: Skodvin Torbjørn Øygard , Johnsen Liv-Hege , Gjertsen Øivind , Isaksen Jørgen Gjernes , Sorteberg Angelika 
Published: March 2017

Background and Purpose—
Using postrupture morphology to predict rupture risk of an intracranial aneurysm may be inaccurate because of possible morphological changes at or around the time of rupture. The present study aims at comparing morphology from angiograms obtained prior to and just after rupture and to evaluate whether postrupture morphology is an adequate surrogate for rupture risk.

Methods—
Case series of 29 aneurysms from a nationwide retrospective data collection. Two neuroradiologists who were blinded to pre- versus postrupture images assessed predefined morphological parameters independently and reached consensus regarding all measurements. Prerupture morphology and respective changes after rupture were quantified and linked to risk factors and to the risk of rupture according to the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, site of aneurysm) and unruptured intracranial aneurysm treatment (UIAT) scores.

Results—

All 1-dimensional parameter medians were significantly larger after rupture, except neck diameter. Number of aneurysms with daughter sacs was 9 (31%) before and 17 (59%) after rupture (
P
=0.005). Aneurysm growth from the images prior to and just after rupture increased with the time elapsed between images. Aneurysms in patients with hypertension were significantly larger at diagnosis. Prerupture morphology did not differ in relation to smoke status. Clinical risk factors were not significantly associated with morphological change.

Conclusions—
The changes in aneurysm morphology observed after rupture reflect the compound effect of time with successive growth and formation of irregularities and the impact of rupture per se. Postrupture morphology should not be considered an adequate surrogate for the prerupture morphology in the evaluation of rupture risk.