bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood use in hematologic malignancies: a nationwide overview in Sweden between 2000 and 2010
Authors: Zhao Jingcheng , Rydén Jenny , Wikman Agneta , Norda Rut , Stanworth Simon J. , Hjalgrim Henrik , Edgren Gustaf 
Published: December 2017

BACKGROUNDPatients with hematologic malignancies receive large numbers of blood transfusions, and transfusion practices for this patient group are increasingly being scrutinized by randomized controlled trials. However, no studies so far have presented current transfusion statistics on a population level for this patient group.STUDY DESIGN AND METHODSA retrospective descriptive study was conducted that was based on the Scandinavian Donations and Transfusions Database (SCANDAT2), which includes data on all blood donations and transfusions in Sweden and Denmark since the 1960s. Incident cases of hematologic malignancies were identified in the Swedish Cancer Register between 2000 and 2010. Cases were divided into nine patient groups based on diagnosis.RESULTSA total of 28,693 patients were included in the cohort. Overall, the transfusion pattern varied depending on diagnosis and age. Patients with aggressive and acute diagnoses generally received more transfusions with immediate decline in transfusion incidence after diagnosis, whereas chronic diagnoses generally maintained more stable, but lower, transfusion incidence. In general, patients with leukemia received more transfusions than patients with lymphoma, and patients with acute leukemia as well as patients that had undergone allogeneic stem cell transplantations received the most transfusions. Within 2 years after diagnosis, patients with acute myeloid leukemia diagnosed at ages 0 to 65 years received on average between 30 to 40 red blood cell transfusions and platelet transfusions, respectively, corresponding to direct material costs close to 200,000 SEK (23,809 USD).CONCLUSIONResults from this population‐based overview of blood use in hematologic malignancies showed high variability depending on diagnosis and age.
Blood donor deferral for men who have sex with men: still room to move
Authors: Haire Bridget , Whitford Kate , Kaldor John M. 
Published: December 2017

BACKGROUNDLike a number of other countries, Australia mandates that a man who has had sex with men is deferred from donation until 12 months has elapsed since the sexual activity. This review examined whether this deferral period is justified by current evidence.STUDY DESIGN AND METHODSDatabases (Medline, EMBASE, Scopus) were searched using terms “blood donation” and “gay” or “MSM” and “HIV risk” from the mid‐1980s to the present to investigate the history of donor deferral policy and its rationale in Australia.RESULTSGay and bisexual men in Australia face a higher risk of human immunodeficiency virus and other blood‐borne viruses (BBVs) than other populations. All blood donations, however, are tested for BBVs, and with current testing technologies the window period during which infection may be present but not detected is now less than 1 week. While there is a moral imperative to maintain blood safety, there is also a moral imperative to ensure that differential treatment of population groups with regard to donation eligibility is scientifically justified. Potential social harms that may flow from a dissonance between deferral policy and its evidence base include loss of trust and increased nonadherence to policy.CONCLUSIONSA 12‐month deferral for gay and bisexual men exceeds what is required to maintain blood safety. This disparity potentially causes social harm without any additional benefit to public health. Reducing the deferral period to 3 months will not increase health risk to recipients and may have the social benefit of increasing inclusiveness.
Rebamipide suppresses TNF‐α production and macrophage infiltration in the conjunctiva
Authors: Tajima Kazuki , Hattori Takaaki , Takahashi Hiroki , Katahira Haruki , Narimatsu Akitomo , Kumakura Shigeto , Goto Hiroshi 
Published: December 2017

AbstractPurposeTo evaluate the anti‐inflammatory effect of rebamipide during corneal epithelial wound healing using a mouse wound repair model.MethodsA 2‐mm circular disc of the central cornea was demarcated in the right eye of C57BL/6 mice and the epithelium removed. Rebamipide 2% eyedrop was instilled onto the wounded eye 5 times a day (n = 26). Phosphate‐buffered saline (PBS) was used in the control group (n = 26). Corneal and conjunctival IL‐1β and TNF‐α levels were measured at 6 h and 24 h postinjury by ELISA. The wounded area was evaluated by fluorescein staining at 24 h postinjury. Macrophage infiltration was assessed immunohistochemically, and TNF‐α secretion from macrophages was examined in vitro.ResultsConjunctival IL‐1β and corneal IL‐1β levels were not significantly different between PBS‐treated and rebamipide‐treated groups. However, conjunctival TNF‐α level was significantly lower in the rebamipide‐treated group compared with the PBS‐treated group. Macrophage migration into the conjunctiva, but not into the cornea, was suppressed by rebamipide treatment. In addition, TNF‐α secretion from cultured macrophages was suppressed by rebamipide in a concentration‐dependent manner. Rebamipide treatment significantly accelerated corneal epithelial wound healing at 24 h postinjury.ConclusionsIn a mouse corneal epithelial wound model, rebamipide suppressed TNF‐α secretion and macrophage infiltration in the conjunctiva, which might have contributed to accelerated corneal epithelial wound healing in the first 24 h following injury.
Optic neuritis in dogs: 96 cases (1983‐2016)
Authors: Smith Sara M. , Westermeyer Hans D. , Mariani Christopher L. , Gilger Brian C. , Davidson Michael G. 
Published: December 2017

AbstractObjectiveTo characterize ocular and neurologic findings, causes, and treatment outcomes of dogs with optic neuritis.ProcedureMedical records from dogs with a diagnosis of optic neuritis at North Carolina State University, College of Veterinary Medicine, Veterinary Hospital between 1983 and 2016 were reviewed.ResultsNinety‐six cases (20 unilateral, 76 bilateral), comprised of 38 males and 58 females with a mean age of 6.1 ± 3.0 years (range 0.5‐13), were identified. Seventy‐four cases were presented for vision loss, and 42 had other concurrent neurologic abnormalities. Funduscopic findings included optic nerve head elevation (n = 92), peripapillary retinal edema or separation (n = 37), retinal hemorrhage or dilation of retinal vasculature (n = 23), and multiple inflammatory foci in the peripapillary region (n = 13). Retrobulbar optic neuritis was diagnosed in four cases. The final diagnoses included the following: multifocal meningoencephalitis of unknown etiology (MUE,n = 35), isolated optic neuritis (I‐ON,n = 42), neoplasia (n = 10), microbial infection (n = 6), orbital inflammation (n = 2), and suspected ivermectin toxicosis (n = 1). Dogs with I‐ONwere more commonly male, and medium‐to‐large breed, when compared to dogs withMUE. Follow‐up was available in 72 cases, 50 of which remained blind, 10 had partial visual improvement, and 12 were assessed as having normal vision in the affected eye(s).ConclusionOptic neuritis was most commonly associated with multifocalMUEor was isolated as the sole neurologic finding, with a similar incidence between the two groups. Findings suggest that a clinical syndrome of isolated optic neuritis, distinct from multifocalMUE, occurs in dogs.
Low Energy Availability Is Difficult to Assess but Outcomes Have Large Impact on Bone Injury Rates in Elite Distance Athletes
Authors: Heikura Ida A. , Uusitalo Arja L.T. , Stellingwerff Trent , Bergland Dan , Mero Antti A. , Burke Louise M. 
Published: December 2017

We aimed to (a) report energy availability (EA), metabolic/reproductive function, bone mineral density, and injury/illness rates in national/world-class female and male distance athletes and (b) investigate the robustness of various diagnostic criteria from the Female Athlete Triad (Triad), Low Energy Availability in Females Questionnaire, and relative energy deficiency in sport (RED-S) tools to identify risks associated with low EA. Athletes were distinguished according to benchmarks of reproductive function (amenorrheic [n = 13] vs. eumenorrheic [n = 22], low [lowest quartile of reference range; n = 10] versus normal testosterone [n = 14]), and EA calculated from 7-day food and training diaries (< or >30 kcal·kg−1 fat-free mass·day−1). Sex hormones (p < .001), triiodothyronine (p < .05), and bone mineral density (females, p < .05) were significantly lower in amenorrheic (37%) and low testosterone (40%; 15.1 ± 3.0 nmol/L) athletes, and bone injuries were ∼4.5-fold more prevalent in amenorrheic (effect size = 0.85, large) and low testosterone (effect size = 0.52, moderate) groups compared with others. Categorization of females and males using Triad or RED-S tools revealed that higher risk groups had significantly lower triiodothyronine (female and male Triad and RED-S: p < .05) and higher number of all-time fractures (male Triad: p < .001; male RED-S and female Triad: p < .01) as well as nonsignificant but markedly (up to 10-fold) higher number of training days lost to bone injuries during the preceding year. Based on the cross-sectional analysis, current reproductive function (questionnaires/blood hormone concentrations) appears to provide a more objective and accurate marker of optimal energy for health than the more error-prone and time-consuming dietary and training estimation of EA. This study also offers novel findings that athlete health is associated with EA indices.
The Effect of Small-Sided Game Formats on Physical and Technical Performance in Wheelchair Basketball
Authors: Mason Barry S. , van der Slikke Rienk M.A. , Hutchinson Michael J. , Berger Monique A.M. , Goosey-Tolfrey Victoria L. 
Published: December 2017

Purpose: To examine the effects of different small-sided games (SSGs) on physical and technical aspects of performance in wheelchair basketball (WB) players. Design: Observational cohort study. Methods: Fifteen highly trained WB players participated in a single 5v5 (24-s shot clock) match and three 3v3 SSGs (18-s shot clock) on a (1) full court, (2) half-court, and (3) modified-length court. During all formats, players’ activity profiles were monitored using an indoor tracking system and inertial measurement units. Physiological responses were monitored via heart rate and rating of perceived exertion. Technical performance, that is, ball handling, was monitored using video analysis. Repeated-measures analysis of variance and effect sizes (ESs) were calculated to determine the statistical significance and magnitude of any differences between game formats. Results: Players covered less distance and reached lower peak speeds during half-court (P ≤ .0005; ES ≥ very large) compared with all other formats. Greater distances were covered, and more time was spent performing moderate- and high-speed activity (P ≤ .008; ES ≥ moderate) during full court compared with all other formats. Game format had little bearing on physiological responses, and the only differences in technical performance observed were in relation to 5v5. Players spent more time in possession, took more shots, and performed more rebounds in all 3v3 formats compared with 5v5 (P ≤ .028; ES ≥ moderate). Conclusions: Court dimensions affect the activity profiles of WB players during 3v3 SSGs yet had little bearing on technical performance when time pressures (shot clocks) were constant. These findings have important implications for coaches to understand which SSG format may be most suitable for physically and technically preparing WB players.
Validity and Reliability of a Digital Inclinometer to Assess Knee Joint Position Sense in an Open Kinetic Chain
Authors: Romero-Franco Natalia , Montaño-Munuera Juan Antonio , Fernández-Domínguez Juan Carlos , Jiménez-Reyes Pedro 
Published: December 2017

Context: New methods are being validated to easily evaluate the knee joint position sense (JPS) due to its role in the sports movement and the risk of injury. However, no studies to date have considered the open kinetic chain (OKC) technique, despite the biomechanical differences compared with closed kinetic chain movements. Objective: To analyze the validity and reliability of a digital inclinometer to measure the knee JPS in the OKC movement. Design: The validity and intertester and intratester reliability of a digital inclinometer for measuring knee JPS were evaluated. Setting: Sports research laboratory. Participants: A total of 18 athletes (11 males and 7 females; 28.4 [6.6] y; 71.9 [14.0] kg; 1.77 [0.09] m; 22.8 [3.2] kg/m2) voluntary participated in this study. Main Outcomes Measures: Absolute angular error (AAE), relative angular error (RAE), and variable angular error (VAE) of knee JPS in an OKC. Results: Intraclass correlation coefficient (ICC) and standard error of the mean (SEM) were calculated to determine the validity and reliability of the inclinometer. Data showed excellent validity of the inclinometer to obtain proprioceptive errors compared with the video analysis in JPS tasks (AAE: ICC = .981, SEM = 0.08; RAE: ICC = .974, SEM = 0.12; VAE: ICC = .973, SEM = 0.07). Intertester reliability was also excellent for all the proprioceptive errors (AAE: ICC = .967, SEM = 0.04; RAE: ICC = .974, SEM = 0.03; VAE: ICC = .939, SEM = 0.08). Similar results were obtained for intratester reliability (AAE: ICC = .861, SEM = 0.1; RAE: ICC = .894, SEM = 0.1; VAE: ICC = .700, SEM = 0.2). Conclusions: The digital inclinometer is a valid and reliable method to assess the knee JPS in OKC. Sport professionals may evaluate the knee JPS to monitor its deterioration during training or improvements throughout the rehabilitation process.
Gibberish in Communicating Written Physical Activity Information: Making Strides at Derailing a Perpetual Problem
Authors: Thomas Jafrā D. , Cardinal Bradley J. 
Published: December 2017

The majority of physical activity resources are too difficult to be easily read and understood by most U.S. adults. Attempts to ensure that such resources are written in the most accessible manner possible have been advanced (e.g., 2010 U.S.National Action Plan to Improve Health Literacy). For this study, physical activity educational resources were collected through the Internet (N = 163), and their reading grade levels were analyzed. Over 50% of the resources were written at an unsatisfactory level, with the observed reading grade level being greater than eighth-grade (M = 8.98,SD = 2.92,p < .001, 95% CI [8.53, 9.43]), the maximum recommended. Suggestions for future research and publicly engaged sociology of sport praxis are discussed, with a focus on increasing the equity of written physical activity educational resources.
Superhuman AI for heads-up no-limit poker: Libratus beats top professionals
Authors: Brown Noam , Sandholm Tuomas 
Published: December 2017

Libratus versus humans
Pitting artificial intelligence (AI) against top human players demonstrates just how far AI has come. Brown and Sandholm built a poker-playing AI called Libratus that decisively beat four leading human professionals in the two-player variant of poker called heads-up no-limit Texas hold'em (HUNL). Over nearly 3 weeks, Libratus played 120,000 hands of HUNL against the human professionals, using a three-pronged approach that included precomputing an overall strategy, adapting the strategy to actual gameplay, and learning from its opponent.

Science
, this issue p.
418
Roles of Staphylococcus aureus Mnh1 and Mnh2 Antiporters in Salt Tolerance, Alkali Tolerance, and Pathogenesis
Authors: Vaish Manisha , Price-Whelan Alexa , Reyes-Robles Tamara , Liu Jun , Jereen Amyeo , Christie Stephanie , Alonzo Francis , Benson Meredith A. , Torres Victor J. , Krulwich Terry A. 
Published: December 2017

ABSTRACT

Staphylococcus aureus
has three types of cation/proton antiporters. The type 3 family includes two
m
ultisubunit
N
a
+
/
H
+
(Mnh) antiporters, Mnh1 and Mnh2. These antiporters are clusters of seven hydrophobic membrane-bound protein subunits. Mnh antiporters play important roles in maintaining cytoplasmic pH in prokaryotes, enabling their survival under extreme environmental stress. In this study, we investigated the physiological roles and catalytic properties of Mnh1 and Mnh2 in
S. aureus
. Both Mnh1 and Mnh2 were cloned separately into a pGEM3Z+ vector in the antiporter-deficient KNabc
Escherichia coli
strain. The catalytic properties of the antiporters were measured in everted (inside out) vesicles. The Mnh1 antiporter exhibited a significant exchange of Na
+
/H
+
cations at pH 7.5. Mnh2 showed a significant exchange of both Na
+
/H
+
and K
+
/H
+
cations, especially at pH 8.5. Under elevated salt conditions, deletion of the
mnhA1
gene resulted in a significant reduction in the growth rate of
S. aureus
in the range of pH 7.5 to 9. Deletion of
mnhA2
had similar effects but mainly in the range of pH 8.5 to 9.5. Double deletion of
mnhA1
and
mnhA2
led to a severe reduction in the
S. aureus
growth rate mainly at pH values above 8.5. The effects of functional losses of both antiporters in
S. aureus
were also assessed via their support of virulence in a mouse
in vivo
infection model. Deletion of the
mnhA1
gene led to a major loss of
S. aureus
virulence in mice, while deletion of
mnh2
led to no change in virulence.

IMPORTANCE
This study focuses on the catalytic properties and physiological roles of Mnh1 and Mnh2 cation/proton antiporters in
S. aureus
and their contributions under different stress conditions. The Mnh1 antiporter was found to have catalytic activity for Na
+
/H
+
antiport, and it plays a significant role in maintaining halotolerance at pH 7.5 while the Mnh2 antiporter has catalytic antiporter activities for Na
+
/H
+
and K
+
/H
+
that have roles in both osmotolerance and halotolerance in
S. aureus
. Study of
S. aureus
with a single deletion of either
mnhA1
or
mnhA2
was assessed in an infection model of mice. The result shows that
mnhA1
, but not
mnhA2
, plays a major role in
S. aureus
virulence.
Multiple Structures Disclose the Secretins' Secrets
Authors: Filloux Alain , Voulhoux Romé 
Published: December 2017

ABSTRACT
Bacterial secretins are outer membrane proteins that provide a path for secreted proteins to access the cell exterior/surface. They are one of the core components of secretion machines and are found in type II and type III secretion systems (T2SS and T3SS, respectively). The secretins comprise giant ring-shaped homo-oligomers whose precise atomic organization was only recently deciphered thanks to spectacular developments in cryo-electron microscopy (cryo-EM) imaging techniques.
The Host Factor AUF1 p45 Supports Flavivirus Propagation by Triggering the RNA Switch Required for Viral Genome Cyclization
Authors: Friedrich Susann , Engelmann Susanne , Schmidt Tobias , Szczepankiewicz Grit , Bergs Sandra , Liebert Uwe G. , Kümmerer Beate M. , Golbik Ralph P. , Behrens Sven-Erik 
Published: December 2017

ABSTRACT
In previous studies, we showed that the cellular RNA-binding protein AUF1 supports the replication process of the flavivirus West Nile virus. Here we demonstrate that the protein also enables effective proliferation of dengue virus and Zika virus, indicating that AUF1 is a general flavivirus host factor. Further studies demonstrated that the AUF1 isoform p45 significantly stimulates the initiation of viral RNA replication and that the protein's RNA chaperone activity enhances the interactions of the viral 5′UAR and 3′UAR genome cyclization sequences. Most interestingly, we observed that AUF1 p45 destabilizes not only the 3′-terminal stem-loop (3′SL) but also 5′-terminal stem-loop B (SLB) of the viral genome. RNA structure analyses revealed that AUF1 p45 increases the accessibility of defined nucleotides within the 3′SL and SLB and, in this way, exposes both UAR cyclization elements. Conversely, AUF1 p45 does not modulate the fold of stem-loop A (SLA) at the immediate genomic 5′ end, which is proposed to function as a promoter of the viral RNA-dependent RNA polymerase (RdRp). These findings suggest that AUF1 p45, by destabilizing specific stem-loop structures within the 5′ and 3′ ends of the flaviviral genome, assists genome cyclization and concurrently enables the RdRp to initiate RNA synthesis. Our study thus highlights the role of a cellular RNA-binding protein inducing a flaviviral RNA switch that is crucial for viral replication.

IMPORTANCE
The genus
Flavivirus
within the
Flaviviridae
family includes important human pathogens, such as dengue, West Nile, and Zika viruses. The initiation of replication of the flaviviral RNA genome requires a transformation from a linear to a cyclized form. This involves considerable structural reorganization of several RNA motifs at the genomic 5′ and 3′ ends. Specifically, it needs a melting of stem structures to expose complementary 5′ and 3′ cyclization elements to enable their annealing during cyclization. Here we show that a cellular RNA chaperone, AUF1 p45, which supports the replication of all three aforementioned flaviviruses, specifically rearranges stem structures at both ends of the viral genome and in this way permits 5′-3′ interactions of cyclization elements. Thus, AUF1 p45 triggers the RNA switch in the flaviviral genome that is crucial for viral replication. These findings represent an important example of how cellular (host) factors promote the propagation of RNA viruses.
Antagonism of the Protein Kinase R Pathway in Human Cells by Rhesus Cytomegalovirus
Authors: Child Stephanie J. , Hickson Sarah E. , Bayer Avraham , Malouli Daniel , Früh Klaus , Geballe Adam P. 
Published: December 2017

ABSTRACT
While cytomegalovirus (CMV) infections are often limited in host range by lengthy coevolution with a single host species, a few CMVs are known to deviate from this rule. For example, rhesus macaque CMV (RhCMV), a model for human CMV (HCMV) pathogenesis and vaccine development, can replicate in human cells, as well as in rhesus cells. Both HCMV and RhCMV encode species-specific antagonists of the broadly acting host cell restriction factor protein kinase R (PKR). Although the RhCMV antagonist of PKR, rTRS1, has very limited activity against human PKR, here, we show it is essential for RhCMV replication in human cells because it prevents human PKR from phosphorylating the translation initiation factor eIF2α, thereby allowing continued translation and viral replication. Although rTRS1 is necessary for RhCMV replication, it is not sufficient to rescue replication of HCMV lacking its own PKR antagonists in human fibroblasts. However, overexpression of rTRS1 in human fibroblasts enabled HCMV expressing rTRS1 to replicate, indicating that elevated levels or early expression of a weak antagonist can counteract a resistant restriction factor like human PKR. Exploring potential mechanisms that might allow RhCMV to replicate in human cells revealed that RhCMV makes no less double-stranded RNA than HCMV. Rather, in human cells, RhCMV expresses rTRS1 at levels 2 to 3 times higher than those of the HCMV-encoded PKR antagonists during HCMV infection. These data suggest that even a modest increase in expression of this weak PKR antagonist is sufficient to enable RhCMV replication in human cells.

IMPORTANCE
Rhesus macaque cytomegalovirus (RhCMV) offers a valuable model for studying congenital human cytomegalovirus (HCMV) pathogenesis and vaccine development. Therefore, it is critical to understand variations in how each virus infects and affects its host species to be able to apply insights gained from the RhCMV model to HCMV. While HCMV is capable only of infecting cells from humans and very closely related species, RhCMV displays a wider host range, including human as well as rhesus cells. RhCMV expresses an antagonist of a broadly acting antiviral factor present in all mammalian cells, and its ability to counter both the rhesus and human versions of this host factor is a key component of RhCMV's ability to cross species barriers. Here, we examine the molecular mechanisms that allow this RhCMV antagonist to function against a human restriction factor.