bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caesarean scar ectopic pregnancy: diagnostic challenges and management options
Authors: Jayaram Pradeep M , Okunoye Gbemisola O , Konje Justin 
Published: January 2017

Key content

Incidence of caesarean scar pregnancy (CSP) is increasing because of a rising number of caesarean sections. Prompt diagnosis of the condition is required to reduce associated morbidity.

A high index of suspicion is required for women with a suggestive history of CSP. Ultrasound scan is the diagnostic tool of choice.

Management options include medical, surgical and interventional radiology. Appropriate patient selection is important for optimal results.

Major haemorrhage and hysterectomy are the main risks associated with CSP. Therefore, adequate counselling and availability of surgical expertise and blood transfusion should be part of a comprehensive management strategy.

Learning objectives

Understand the clinical and ultrasound features of CSP and distinguish these from features of other low implantation pregnancies.

Learn about available treatment options and the factors influencing treatment choices.

Be aware of the ethical issues associated with the diagnosis of live CSP.

Ethical issues

Do women planning subsequent pregnancy after a resolved CSP require surgery to close the uterine defect in the scar to prevent recurrent scar ectopic pregnancy?

Should the risk of CSP in a future pregnancy be routinely discussed prior to primary caesarean section?
Metabolic robustness in young roots underpins a predictive model of maize hybrid performance in the field
Authors: de Abreu e Lima Francisco , Westhues Matthias , Cuadros‐Inostroza Álvaro , Willmitzer Lothar , Melchinger Albrecht E. , Nikoloski Zoran 
Published: January 2017

SummaryHeterosis has been extensively exploited for yield gain in maize (Zea mays L.). Here we conducted a comparative metabolomics‐based analysis of young roots from in vitro germinating seedlings and from leaves of field‐grown plants in a panel of inbred lines from the Dent and Flint heterotic patterns as well as selected F1 hybrids. We found that metabolite levels in hybrids were more robust than in inbred lines. Using state‐of‐the‐art modeling techniques, the most robust metabolites from roots and leaves explained up to 37 and 44% of the variance in the biomass from plants grown in two distinct field trials. In addition, a correlation‐based analysis highlighted the trade‐off between defense‐related metabolites and hybrid performance. Therefore, our findings demonstrated the potential of metabolic profiles from young maize roots grown under tightly controlled conditions to predict hybrid performance in multiple field trials, thus bridging the greenhouse–field gap.
Pheochromocytomas and paragangliomas in humans and dogs
Authors: Galac S. , Korpershoek E. 
Published: January 2017

AbstractPheochromocytomas (PCCs) and paragangliomas (PGLs) are described in several species. In humans and dogs they have many similarities: the excessive catecholamine release in hormonally active PCC causes similar clinical signs, the frequency of metastasis is similar, and they are histopathologically almost identical. Surgery is curative when PCC and PGL have not metastasized, while only palliative treatment is possible for patients with metastatic disease. Mutations in succinate dehydrogenase subunit B (SDHB) are associated with metastatic behaviour in human PCC/PGL and the same mutation has been described in dogs. The dog might therefore be a suitable model for study of the pathogenesis of metastatic PCC and PGL in humans. Further molecular studies of common tumourigenic pathways and comparative studies of histopathology of human and canine PCC and PGL are warranted.
PD‐1 expression by canine T cells and functional effects of PD‐1 blockade
Authors: Coy J. , Caldwell A. , Chow L. , Guth A. , Dow S. 
Published: January 2017

AbstractThe co‐inhibitory checkpoint molecule programmed death receptor 1 (PD‐1) can trigger T cell functional exhaustion upon binding to its ligand PD‐L1 expressed on tumour cells or macrophages. PD‐1 blocking antibodies have generated remarkable results in human cancer patients, including inducing durable responses in a number of advanced cancers. Therefore, monoclonal antibodies specific for canine PD‐1 were assessed for T cell binding and induction of functional activation. A total of 5–10% of CD4 T cells and 20–25% of CD8 T cells from healthy dogs expressed PD‐1, and PD‐1 expression was upregulated on T cells from dogs with cancer. Functionally, PD‐1 antibodies significantly enhanced T‐cell activation, as assessed by proliferation and interferon‐gamma (IFN‐γ) production. PD‐1 antibodies also reversed T‐cell suppression induced by canine soluble PD‐L1 and by tumour cells and tumour explant fragments. These findings indicate that PD‐1 antibodies have potential for use in cancer immunotherapy in dogs.
Sigma 2 receptor expression levels in blood and bladder from healthy and bladder cancer cattle
Authors: Russo V. , Inglese C. , Avallone L. , Roperto F. , Abate C. , Zizzo N. , Munday J. S. , Berardi F. , Colabufo N. A. , Roperto S. 
Published: January 2017

AbstractThe expression of sigma‐2 receptor (S2R) was assayed in blood and bladder samples from healthy cattle and in blood and bladder of cattle with deltapapillomavirus‐associated urothelial tumors. Samples of bladder from cattle with neoplasia had significantly higher S2R than samples of bladder from healthy cattle (95% CI 0.31–0.82, P < 0.05). In addition, significantly higher S2R was detected in the blood of cattle with bladder cancer than blood from healthy cattle (95% CI 0.22–0.41, P < 0.05). The results provide evidence that increased expression of SR2 in blood could be useful as circulating biomarker for bladder cancer in cattle. PGRMC1 protein levels were also found to be increased in blood and bladder from cattle with cancer and increased expression of PGRMC1 transcripts was detected by quantitative real time PCR in samples from cattle neoplasia. Furthermore, electron microscopy revealed phagophores and numerous autophagosomes, ultrastructural hallmark of autophagy.
Immature platelets do not reliably predict platelet recovery in patients with intensive chemotherapy or stem cell transplantation
Authors: Meintker L. , Fritsch J. D. , Ringwald J. , Krause S. W. 
Published: January 2017

Background and ObjectivesIt has been reported that immature platelets may indicate imminent platelet (PLT) recovery following intensive chemotherapy and/or haematopoietic stem cell transplantation with the perspective to withhold unnecessary transfusions. The objective of our prospective study was to test immature PLTs as measured by two haematology analysers to predict PLT recovery.Material and MethodsThis study monitored 51 courses of severe thrombocytopenia after chemotherapy in 35 adult haematology/oncology patients starting at a PLT count <70 × 109/l until PLT recovery (>20 × 109/l) or discharge from hospital. Immature platelets as measured by immature platelet fraction (IPF) (Sysmex XE‐5000) and retPLT (Abbott CD‐Sapphire) as well as reticulocyte and leucocyte count were evaluated regarding their usefulness to predict PLT recovery. Furthermore, the influence of platelet concentrate (PC) transfusions upon IPF and retPLT was assessed.ResultsWith beginning of thrombocytopenia, most patients demonstrated elevated IPF% (median 8·6%) and retPLT% (median 6·8%). These elevated values significantly dropped after transfusions of PCs. IPF and retPLT values during nadir and at imminent PLT recovery were largely overlapping and receiver operating characteristics analysis demonstrated poor separation between both clinical situations. A reasonable cut‐off could not be established to prospectively predict imminent PLT recovery for either of the parameters investigated.ConclusionMeasurements of IPF and retPLT lack predictive power regarding imminent PLT recovery in patients with severe thrombocytopenia following intensive chemotherapy. Decisions regarding prophylactic PC transfusions should not be based on these parameters.
ACOUSTICAL STANDARDS NEWS
Authors: Stremmel Neil B. , Struck Christopher J. 
Published: January 2017

American National Standards (ANSI Standards) developed by Accredited Standards Committees S1, S2, S3, S3/SC 1, and S12 in the areas of acoustics, mechanical vibration and shock, bioacoustics, animal bioacoustics, and noise, respectively, are published by the Acoustical Society of America (ASA). In addition to these standards, ASA publishes a catalog of Acoustical American National Standards. To receive a copy of the latest Standards catalog, please contact Neil Stremmel.
Comments are welcomed on all material in Acoustical Standards News.
This Acoustical Standards News section in JASA and other information on the Standards Program of the Acoustical Society of America are available via the ASA home page: http://acousticalsociety.org.
Feasibility and Impact of High-Intensity Walking Training in Frail Older Adults
Authors: Danilovich Margaret K. , Conroy David E. , Hornby T. George 
Published: January 2017

To investigate the impact of high-intensity walking training (HIWT) on prefrail and frail older adults, five assisted living residents underwent a supervised 12-session intervention. The intervention consisted of 30 min of HIWT at 70–80% of heart rate reserve or ratings of 15 to 17 (hard to very hard) on the Borg Rating of Perceived Exertion scale. Training included walking at fast speeds, multi-directions, stairs, and outdoor surfaces with and without an assistive device. Training significantly reduced frailty using the SHARE-FI (p = .008), increased fast gait speed (p = .01), improved 6-min walk test distance (p = .03), and enhanced Berg Balance Scale scores (p = .03). There were no adverse events and all participants reached target training intensity in all 12 sessions. Participants viewed the walking intervention as highly satisfactory (9.6/10 on a Likert scale) and 100% recommended that the assisted living facility should offer HIWT as part of routine programming.
Candida albicans
Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions
Authors: Wagener Jeanette , MacCallum Donna M. , Brown Gordon D. , Gow Neil A. R. 
Published: January 2017

ABSTRACT

The opportunistic human fungal pathogen
Candida albicans
can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid
l
-arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host’s arginase activity to prevent the conversion of
l
-arginine to nitric oxide. We report here that
C. albicans
blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the
C. albicans
-induced arginase activity with the arginase-specific substrate inhibitor
N
ω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that
C. albicans
influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore,
C. albicans
modulates
l
-arginine metabolism in macrophages during an infection, potentiating its own survival.

IMPORTANCE
The availability and metabolism of amino acids are increasingly recognized as crucial regulators of immune functions. In acute infections, the conversion of the “conditionally essential” amino acid
l
-arginine by the inducible nitric oxide synthase to nitric oxide is a resistance factor that is produced by the host to fight pathogens. Manipulation of these host defense mechanisms by the pathogen can be key to successful host invasion. We show here that the human opportunistic fungal pathogen
Candida albicans
influences
l
-arginine availability for nitric oxide production by induction of the substrate-competing host enzyme arginase-1. This led to a reduced production of nitric oxide and, moreover, reduced eradication of the fungus by human macrophages. We demonstrate that blocking of host arginase-1 activity restored nitric oxide production and increased the killing potential of macrophages. These results highlight the therapeutic potential of
l
-arginine metabolism in fungal diseases.
A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria
Authors: Yang Yunpeng , Zhang Lu , Huang He , Yang Chen , Yang Sheng , Gu Yang , Jiang Weihong 
Published: January 2017

ABSTRACT

Catabolite control protein A (CcpA) is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR) and carbon catabolite activation (CCA), two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt) consensus site that is called a catabolite response element (
cre
) within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named
cre
var
, has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA). It was found that the length of the intervening spacer of
cre
var
can affect CcpA binding affinity, and moreover, the core palindromic sequence of
cre
var
is the key structure for regulation. Such a variable architecture of
cre
var
shows potential importance for CcpA’s diverse and fine regulation. A total of 103 potential
cre
var
sites were discovered in solventogenic
Clostridium acetobutylicum
, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs), and 30 sites were confirmed to be bound by CcpA. These 30
cre
var
sites are associated with 27 genes involved in many important pathways. Also of significance, the
cre
var
sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria.

IMPORTANCE
In Gram-positive bacteria, the global regulator CcpA controls a large number of important physiological and metabolic processes. Although a typical consensus CcpA-binding site,
cre
, has been identified, it remains poorly explored for the diversity of CcpA-mediated catabolite regulation. Here, we discovered a novel flexible CcpA-binding site architecture (
cre
var
) that is highly variable in both length and base composition but follows certain principles, providing new insights into how CcpA can differentially recognize a variety of target genes to form a complicated regulatory network. A comprehensive search further revealed the wide distribution of
cre
var
sites in Gram-positive bacteria, indicating it may have a universal function. This finding is the first to characterize such a highly flexible transcription factor-binding site architecture, which would be valuable for deeper understanding of CcpA-mediated global catabolite regulation in bacteria.
Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization
Authors: De Oliveira David M. P. , Hartley-Tassell Lauren , Everest-Dass Arun , Day Christopher J. , Dabbs Rebecca A. , Ve Thomas , Kobe Bostjan , Nizet Victor , Packer Nicolle H. , Walker Mark J. , Jennings Michael P. , Sanderson-Smith Martina L. 
Published: January 2017

ABSTRACT

Streptococcus pyogenes
(group A streptococcus [GAS]) is responsible for over 500,000 deaths worldwide each year. The highly virulent M1T1 GAS clone is one of the most frequently isolated serotypes from streptococcal pharyngitis and invasive disease. The oral epithelial tract is a niche highly abundant in glycosylated structures, particularly those of the ABO(H) blood group antigen family. Using a high-throughput approach, we determined that a strain representative of the globally disseminated M1T1 GAS clone 5448 interacts with numerous, structurally diverse glycans. Preeminent among GAS virulence factors is the surface-expressed M protein. M1 protein showed high affinity for several terminal galactose blood group antigen structures. Deletion mutagenesis shows that M1 protein mediates glycan binding via its B repeat domains. Association of M1T1 GAS with oral epithelial cells varied significantly as a result of phenotypic differences in blood group antigen expression, with significantly higher adherence to those cells expressing H antigen structures compared to cells expressing A, B, or AB antigen structures. These data suggest a novel mechanism for GAS attachment to host cells and propose a link between host blood group antigen expression and M1T1 GAS colonization.

IMPORTANCE
There has been a resurgence in group A streptococcal (GAS) invasive disease, which has been paralleled by the emergence of the highly virulent M1T1 GAS clone. Intensive research has focused on mechanisms that contribute to the invasive nature of this serotype, while the mechanisms that contribute to host susceptibility to disease and bacterial colonization and persistence are still poorly understood. The M1T1 GAS clone is frequently isolated from the throat, an environment highly abundant in blood group antigen structures. This work examined the interaction of the M1 protein, the preeminent GAS surface protein, against a wide range of host-expressed glycan structures. Our data suggest that susceptibility to infection by GAS in the oral tract may correlate with phenotypic differences in host blood group antigen expression. Thus, variations in host blood group antigen expression may serve as a selective pressure contributing to the dissemination and overrepresentation of M1T1 GAS.
Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: protocol detailing observations in a whole of population cohort
Authors: Daniels Benjamin , Lord Sarah J , Kiely Belinda E , Houssami Nehmat , Haywood Philip , Lu Christine Y , Ward Robyn L , Pearson Sallie-Anne 
Published: January 2017

BackgroundThe management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2-targeted therapies in Australia.Methods/designOur ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2-targeted therapies to undertake this research.Ethics and disseminationEthics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments.
Are first rib fractures a marker for other life-threatening injuries in patients with major trauma? A cohort study of patients on the UK Trauma Audit and Research Network database
Authors: Sammy Ian Ayenga , Chatha Hridesh , Lecky Fiona , Bouamra Omar , Fragoso-Iñiguez Marisol , Sattout Abdo , Hickey Michael , Edwards John E 
Published: January 2017

BackgroundFirst rib fractures are considered indicators of increased morbidity and mortality in major trauma. However, this has not been definitively proven. With an increased use of CT and the potential increase in detection of first rib fractures, re-evaluation of these injuries as a marker for life-threatening injuries is warranted.MethodsPatients sustaining rib fractures between January 2012 and December 2013 were investigated using data from the UK Trauma Audit and Research Network. The prevalence of life-threatening injuries was compared in patients with first rib fractures and those with other rib fractures. Multivariate logistic regression was performed to determine the association between first rib fractures, injury severity, polytrauma and mortality.ResultsThere were 1683 patients with first rib fractures and 8369 with fractures of other ribs. Life-threatening intrathoracic and extrathoracic injuries were more likely in patients with first rib fractures. The presence of first rib fractures was a significant predictor of injury severity (Injury Severity Score >15) and polytrauma, independent of mechanism of injury, age and gender with an adjusted OR of 2.64 (95% CI 2.33 to 3.00) and 2.01 (95% CI 1.80 to 2.25), respectively. Risk-adjusted mortality was the same in patients with first rib fractures and those with other rib fractures (adjusted OR 0.97, 95% CI 0.79 to 1.19).ConclusionFirst rib fractures are a marker of life-threatening injuries in major trauma, though they do not independently increase mortality. Management of patients with first rib fractures should focus on identification and treatment of associated life-threatening injuries.