bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health‐Literacy‐Sensitive Diabetes Self‐Management Interventions: A Systematic Review and Meta‐Analysis
Authors: Kim Su Hyun , Lee Anna 
Published: April 2016

ABSTRACTBackgroundLow health literacy is a potential barrier to self‐management among patients with diabetes. A variety of strategies for low health literacy have been proposed for diabetes self‐management interventions, but interventions accommodating low health literacy have been heterogeneous in terms of content and have produced mixed results.AimTo systematically review health‐literacy‐sensitive diabetes management interventions, with a focus on identifying strategies for accommodating patients with low health literacy, and to examine the efficacy of these interventions to improve health outcomes.MethodsPubMed, CINAHL, and EMBASE were searched for intervention studies published between January 2000 and January 2015. Two authors separately identified full‐texts according to the inclusion criteria and assessed study quality using the quantitative components of the Mixed Methods Appraisal Tool. The final list of studies to be analyzed was made through discussion. The meta‐analysis was conducted using a random effects model.ResultsThirteen studies were selected from the 490 studies found in our initial search. We identified a range of strategies for accommodating those with low health literacy in diabetes self‐management interventions, which encompassed four domains: written communication, spoken communication, empowerment, and language/cultural consideration. Using at least one of the spoken communication strategies led to positive cognitive/psychological, self‐care, and health outcomes. We found that, overall, health‐literacy‐sensitive diabetes management interventions were effective in reducing HbA1C level in the meta‐analysis.Linking Evidence to ActionHealthcare providers should consider active implementation of strategies for accommodating people with low health literacy in diabetes self‐management interventions. The routine use of spoken communication strategies would be necessary to achieve the best health outcomes in diabetes self‐management interventions. More research is needed to determine the individual effects of the key strategies that improve health and reduce health disparity.
Use dependence of peripheral nociceptive conduction in the absence of tetrodotoxin‐resistant sodium channel subtypes
Authors: Hoffmann Tal , Kistner Katrin , Nassar Mohammed , Reeh Peter W. , Weidner Christian 
Published: April 2016

Key points
This study examines conduction in peripheral nerves and its use dependence in tetrodotoxin‐resistant (TTXr) sodium channel (Nav1.8, Nav1.9) knockout and wildtype animals.
We observed use‐dependent decreases of single fibre and compound action potential amplitude in peripheral mouse C‐fibres (wildtype). This matches the previously published hypothesis that increased Na/K‐pump activity is not the underlying mechanism for use‐dependent changes of neural conduction.
Knocking out TTXr sodium channels influences use‐dependent changes of conductive properties (action potential amplitude, latency, conduction safety) in the order Nav1.8 KO > Nav1.9KO > wildtype.
This is most likely explained by different subsets of presumably (relatively) Nav1.7‐rich conducting fibres in knockout animals as compared to wildtypes, in combination with reduced per‐pulse sodium influx.
AbstractUse dependency of peripheral nerves, especially of nociceptors, correlates with receptive properties. Slow inactivation of voltage‐gated sodium channels has been discussed to be the underlying mechanism – pointing to a receptive class‐related difference of sodium channel equipment. Using electrophysiological recordings of single unmyelinated cutaneous fibres and their compound action potential (AP), we evaluated use‐dependent changes in mouse peripheral nerves, and the contribution of the tetrodotoxin‐resistant (TTXr) sodium channels Nav1.8 and Nav1.9 to these changes. Nerve fibres were electrically stimulated using single or double pulses at 2 Hz. Use‐dependent changes of latency, AP amplitude, and duration as well as the fibres’ ability to follow the stimulus were evaluated. AP amplitudes substantially diminished in used fibres from C57BL/6 but increased in Nav1.8 knockout (KO) mice, with Nav1.9 KO in between. Activity‐induced latency slowing was in contrast the most pronounced in Nav1.8 KOs and the least in wildtype mice. The genotype was also predictive of how long fibres could follow the double pulsed stimulus with wildtype fibres blocking first and Nav1.8 KO fibres enduring the longest. In contrast, changes in spike duration were less pronounced and displayed no significant tendency. Thus, all major measures of peripheral nerve accommodation (amplitude, latency and durability) depended on genotype. All use‐dependent changes appeared in the order NaV1.8 KO > NaV1.9 KO > wildtype, which is most likely explained by the relative contribution of Nav1.7 varying in the same order and the amounts of per‐pulse sodium influx expected in the opposite order.
Microglia across the lifespan: from origin to function in brain development, plasticity and cognition
Authors: Tay Tuan Leng , Savage Julie C. , Hui Chin Wai , Bisht Kanchan , Tremblay Marie‐Ève 
Published: April 2016

AbstractMicroglia are the only immune cells that permanently reside in the central nervous system (CNS) alongside neurons and other types of glial cells. The past decade has witnessed a revolution in our understanding of their roles during normal physiological conditions. Cutting‐edge techniques revealed that these resident immune cells are critical for proper brain development, actively maintain health in the mature brain, and rapidly adapt their function to physiological or pathophysiological needs. In this review, we highlight recent studies on microglial origin (from the embryonic yolk sac) and the factors regulating their differentiation and homeostasis upon brain invasion. Elegant experiments tracking microglia in the CNS allowed studies of their unique roles compared with other types of resident macrophages. Here we review the emerging roles of microglia in brain development, plasticity and cognition, and discuss the implications of the depletion or dysfunction of microglia for our understanding of disease pathogenesis. Immune activation, inflammation and various other conditions resulting in undesirable microglial activity at different stages of life could severely impair learning, memory and other essential cognitive functions. The diversity of microglial phenotypes across the lifespan, between compartments of the CNS, and sexes, as well as their crosstalk with the body and external environment, is also emphasised. Understanding what defines particular microglial phenotypes is of major importance for future development of innovative therapies controlling their effector functions, with consequences for cognition across chronic stress, ageing, neuropsychiatric and neurological diseases.
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Renal extracellular vesicles: from physiology to clinical application
Authors: Morrison E. E. , Bailey M. A. , Dear J. W. 
Published: April 2016

AbstractUrinary extracellular vesicles (uEVs) are released from all regions of the kidney's nephron and from other cells that line the urinary tract. Extracellular vesicles retain proteomic and transcriptomic markers specific to their cell of origin and so represent a potential reservoir for kidney disease biomarker discovery. Exosomes, a subtype of uEVs, are distinguished from other vesicles by features related to their biogenesis within cells: mature multi‐vesicular bodies fuse with the cellular membrane to liberate exosomes into the extracellular space. uEVs represent a novel cell signalling mechanism because they can be shuttled to a recipient cell and, through a number of proposed mechanisms, affect the recipient cell's proteome and function. Here we review the current evidence for uEV signalling along the nephron, their role in health and disease of the kidney, and their potential for clinical translation as biomarkers and therapeutics.
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The acquisition of mechano‐electrical transducer current adaptation in auditory hair cells requires myosin VI
Authors: Marcotti Walter , Corns Laura F. , Goodyear Richard J. , Rzadzinska Agnieszka K. , Avraham Karen B. , Steel Karen P. , Richardson Guy P. , Kros Corné J. 
Published: April 2016

Key points
The transduction of sound into electrical signals occurs at the hair bundles atop sensory hair cells in the cochlea, by means of mechanosensitive ion channels, the mechano‐electrical transducer (MET) channels.
The MET currents decline during steady stimuli; this is termed adaptation and ensures they always work within the most sensitive part of their operating range, responding best to rapidly changing (sound) stimuli.
In this study we used a mouse model (Snell's waltzer) for hereditary deafness in humans that has a mutation in the gene encoding an unconventional myosin, myosin VI, which is present in the hair bundles.
We found that in the absence of myosin VI the MET current fails to acquire its characteristic adaptation as the hair bundles develop.
We propose that myosin VI supports the acquisition of adaptation by removing key molecules from the hair bundle that serve a temporary, developmental role.
AbstractMutations in Myo6, the gene encoding the (F‐actin) minus end‐directed unconventional myosin, myosin VI, cause hereditary deafness in mice (Snell's waltzer) and humans. In the sensory hair cells of the cochlea, myosin VI is expressed in the cell bodies and along the stereocilia that project from the cells’ apical surface. It is required for maintaining the structural integrity of the mechanosensitive hair bundles formed by the stereocilia. In this study we investigate whether myosin VI contributes to mechano‐electrical transduction. We report that Ca2+‐dependent adaptation of the mechano‐electrical transducer (MET) current, which serves to keep the transduction apparatus operating within its most sensitive range, is absent in outer and inner hair cells from homozygous Snell's waltzer mutant mice, which fail to express myosin VI. The operating range of the MET channels is also abnormal in the mutants, resulting in the absence of a resting MET current. We found that cadherin 23, a component of the hair bundle's transient lateral links, fails to be downregulated along the length of the stereocilia in maturing Myo6 mutant mice. MET currents of heterozygous littermates appear normal. We propose that myosin VI, by removing key molecules from developing hair bundles, is required for the development of the MET apparatus and its Ca2+‐dependent adaptation.
Genome Sequence of the Tick-Borne Pathogen
Rickettsia raoultii
Authors: El Karkouri Khalid , Mediannikov Oleg , Robert Catherine , Raoult Didier , Fournier Pierre-Edouards 
Published: April 2016

ABSTRACT

Rickettsia raoultii
is a tick-associated spotted fever group (SFG) organism, causing scalp eschar and neck lymphadenopathy after tick bite (SENLAT) in humans. We report here the genome sequence of
R. raoultii
strain Khabarovsk
T
(CSUR R3
T
, ATCC VR-1596
T
), which was isolated from a
Dermacentor silvarum
tick collected in Russia.
Draft Genome Sequence of the Spore-Forming Probiotic Strain
Bacillus coagulans
Unique IS-2
Authors: Upadrasta Aditya , Pitta Swetha , Madempudi Ratna Sudha 
Published: April 2016

ABSTRACT

Bacillus coagulans
Unique IS-2 is a potential spore-forming probiotic that is commercially available on the market. The draft genome sequence presented here provides deep insight into the beneficial features of this strain for its safe use as a probiotic for various human and animal health applications.
Draft Genome Sequences of 63
Pseudomonas aeruginosa
Isolates Recovered from Cystic Fibrosis Sputum
Authors: Spilker Theodore , LiPuma John J. 
Published: April 2016

ABSTRACT

Here, we report the draft genome sequences of 63
Pseudomonas aeruginosa
isolates, recovered in culture of sputum from 15 individuals with cystic fibrosis (CF) receiving care in a single CF care center over a 13-year period. These sequences add value to studies of within-host evolution of bacterial pathogens during chronic infection.
Genome Sequence of the Endophytic Bacterium
Bacillus thuringiensis
Strain KB1, a Potential Biocontrol Agent against Phytopathogens
Authors: Jeong Haeyoung , Jo Sung Hee , Hong Chi Eun , Park Jeong Mee 
Published: April 2016

ABSTRACT

Bacillus thuringiensis
is the most widely known microbial pesticide used in agricultural applications. Herein, we report a draft genome sequence of the endophytic bacterium
Bacillus thuringiensis
strain KB1, which exhibits antagonism against phytopathogens.
Complete Genome Sequence of
Lactobacillus rhamnosus
Strain BPL5 (CECT 8800), a Probiotic for Treatment of Bacterial Vaginosis
Authors: Chenoll Empar , Codoñer Francisco M. , Martinez-Blanch Juan F. , Ramón Daniel , Genovés Salvador , Menabrito Marco 
Published: April 2016

ABSTRACT

Lactobacillus rhamnosus
BPL5 (CECT 8800), is a probiotic strain suitable for the treatment of bacterial vaginosis. Here, we report its complete genome sequence deciphered by PacBio single-molecule real-time (SMRT) technology. Analysis of the sequence may provide insight into its functional activity.
Draft Genome Sequence of a Biocontrol Rhizobacterium,
Chryseobacterium kwangjuense
Strain KJ1R5, Isolated from Pepper (
Capsicum annuum
)
Authors: Jeong Jin-Ju , Park Hongjae , Park Byeong Hyeok , Mannaa Mohamed , Sang Mee Kyung , Choi In-Geol , Kim Ki Deok 
Published: April 2016

ABSTRACT

Strain KJ1R5 of the rhizobacterium
Chryseobacterium kwangjuense
is an effective biocontrol agent against Phytophthora blight of pepper caused by a destructive soilborne oomycete,
Phytophthora capsici
. Here, we present the draft genome sequence of strain KJ1R5, which contains genes related to biocontrol, plant growth promotion, and environmental stress adaptation.
Complete Genome Sequence of an NADC30-Like Strain of Porcine Reproductive and Respiratory Syndrome Virus in China
Authors: Ji Guobiao , Li Yingying , Tan Feifei , Zhuang Jinshan , Li Xiangdong , Tian Kegong 
Published: April 2016

ABSTRACT
The most recently emergent porcine reproductive and respiratory syndrome virus strains in China are characterized by 393 nucleotide deletions in the nonstructural protein 2 (NSP2) region and are known as NADC30-like strains. Here, we report the complete genome sequence of the NADC30-like HNjz15 strain that was isolated in 2015.
EOLE
Authors: Perais Arthur , Seznec André 
Published: April 2016

Recent work in the field of value prediction (VP) has shown that given an efficient confidence estimation mechanism, prediction validation could be removed from the out-of-order engine and delayed until commit time. As a result, a simple recovery mechanism—pipeline squashing—can be used, whereas the out-of-order engine remains mostly unmodified.
Yet, VP and validation at commit time require additional ports on the physical register file, potentially rendering the overall number of ports unbearable. Fortunately, VP also implies that many single-cycle ALU instructions have their operands predicted in the front-end and can be executed in-place, in-order. Similarly, the execution of single-cycle instructions whose result has been predicted can be delayed until commit time since predictions are validated at commit time.
Consequently, a significant number of instructions—10% to 70% in our experiments—can bypass the out-of-order engine, allowing for a reduction of the issue width. This reduction paves the way for a truly practical implementation of VP. Furthermore, since VP in itself usually increases performance, our resulting {Early—Out-of-Order—Late} Execution architecture, EOLE, is often more efficient than a baseline VP-augmented 6-issue superscalar while having a significantly narrower 4-issue out-of-order engine.
Binding of Released Bim to Mcl-1 is a Mechanism of Intrinsic Resistance to ABT-199 which can be Overcome by Combination with Daunorubicin or Cytarabine in AML Cells
Authors: Niu Xiaojia , Zhao Jianyun , Ma Jun , Xie Chengzhi , Edwards Holly , Wang Guan , Caldwell J. Timothy , Xiang Shengyan , Zhang Xiaohong , Chu Roland , Wang Zhihong J. , Lin Hai , Taub Jeffrey W. , Ge Yubin 
Published: April 2016

Abstract
Purpose: To investigate the molecular mechanism underlying intrinsic resistance to ABT-199.
Experimental Design: Western blots and real-time RT-PCR were used to determine levels of Mcl-1 after ABT-199 treatment alone or in combination with cytarabine or daunorubicin. Immunoprecipitation of Bim and Mcl-1 were used to determine the effect of ABT-199 treatment on their interactions with Bcl-2 family members. Lentiviral short hairpin RNA knockdown of Bim and CRISPR knockdown of Mcl-1 were used to confirm their role in resistance to ABT-199. JC-1 assays and flow cytometry were used to determine drug-induced apoptosis.
Results: Immunoprecipitation of Bim from ABT-199–treated cell lines and a primary patient sample demonstrated decreased association with Bcl-2, but increased association with Mcl-1 without corresponding change in mitochondrial outer membrane potential. ABT-199 treatment resulted in increased levels of Mcl-1 protein, unchanged or decreased Mcl-1 transcript levels, and increased Mcl-1 protein half-life, suggesting that the association with Bim plays a role in stabilizing Mcl-1 protein. Combining conventional chemotherapeutic agent cytarabine or daunorubicin with ABT-199 resulted in increased DNA damage along with decreased Mcl-1 protein levels, compared with ABT-199 alone, and synergistic induction of cell death in both AML cell lines and primary patient samples obtained from AML patients at diagnosis.
Conclusions: Our results demonstrate that sequestration of Bim by Mcl-1 is a mechanism of intrinsic ABT-199 resistance and supports the clinical development of ABT-199 in combination with cytarabine or daunorubicin for the treatment of AML. Clin Cancer Res; 22(17); 4440–51. ©2016 AACR.
EGFR Fusions as Novel Therapeutic Targets in Lung Cancer
Authors: Konduri Kartik , Gallant Jean-Nicolas , Chae Young Kwang , Giles Francis J. , Gitlitz Barbara J. , Gowen Kyle , Ichihara Eiki , Owonikoko Taofeek K. , Peddareddigari Vijay , Ramalingam Suresh S. , Reddy Satyanarayan K. , Eaby-Sandy Beth , Vavalà Tiziana , Whiteley Andrew , Chen Heidi , Yan Yingjun , Sheehan Jonathan H. , Meiler Jens , Morosini Deborah , Ross Jeffrey S. , Stephens Philip J. , Miller Vincent A. , Ali Siraj M. , Lovly Christine M. 
Published: April 2016

Abstract
Here, we report that novel epidermal growth factor receptor (EGFR) gene fusions comprising the N-terminal of EGFR linked to various fusion partners, most commonly RAD51, are recurrent in lung cancer. We describe five patients with metastatic lung cancer whose tumors harbored EGFR fusions, four of whom were treated with EGFR tyrosine kinase inhibitors (TKI) with documented antitumor responses. In vitro, EGFR–RAD51 fusions are oncogenic and can be therapeutically targeted with available EGFR TKIs and therapeutic antibodies. These results support the dependence of EGFR-rearranged tumors on EGFR-mediated signaling and suggest several therapeutic strategies for patients whose tumors harbor this novel alteration.
Significance: We report for the first time the identification and therapeutic targeting of EGFR C-terminal fusions in patients with lung cancer and document responses to the EGFR inhibitor erlotinib in 4 patients whose tumors harbored EGFR fusions. Findings from these studies will be immediately translatable to the clinic, as there are already several approved EGFR inhibitors. Cancer Discov; 6(6); 601–11. ©2016 AACR.
See related commentary by Paik, p. 574.
This article is highlighted in the In This Issue feature, p. 561
Thrombin-Activatable Fibrinolysis Inhibitor in Chronic Thromboembolic Pulmonary Hypertension
Authors: Yaoita Nobuhiro , Satoh Kimio , Satoh Taijyu , Sugimura Koichiro , Tatebe Shunsuke , Yamamoto Saori , Aoki Tatsuo , Miura Masanobu , Miyata Satoshi , Kawamura Takeshi , Horiuchi Hisanori , Fukumoto Yoshihiro , Shimokawa Hiroaki 
Published: April 2016

Objective—
The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) remains to be elucidated. Thrombin-activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis. It remains to be elucidated whether TAFI is directly involved in the pathogenesis of CTEPH. We examined potential involvement of TAFI in the pathogenesis of CTEPH in humans.

Approach and Results—

We enrolled 68 consecutive patients undergoing right heart catheterization in our hospital, including those with CTEPH (n=27), those with pulmonary arterial hypertension (n=22), and controls (non–pulmonary hypertension, n=19). Whole blood clot lysis assay showed that the extent of clot remaining after 4 hours was significantly higher in CTEPH compared with pulmonary arterial hypertension or controls (41.9 versus 26.5 and 24.6%, both
P
<0.01). Moreover, plasma levels of TAFI were significantly higher in CTEPH than in pulmonary arterial hypertension or controls (19.4±4.2 versus 16.1±4.5 or 16.3±3.3 μg/mL, both
P
<0.05), which remained unchanged even after hemodynamic improvement by percutaneous transluminal pulmonary angioplasty. Furthermore, the extent of clot remaining after 4 hours was significantly improved with CPI-2KR (an inhibitor of activated TAFI) or prostaglandin E
1
(an inhibitor of activation of platelets). Importantly, plasma levels of TAFI were significantly correlated with the extent of clot remaining after 4 hours. In addition, the extent of clot remaining after 4 hours was improved with an activated TAFI inhibitor.

Conclusions—
These results indicate that plasma levels of TAFI are elevated in patients with CTEPH and are correlated with resistance to clot lysis in those patients.
The Novel Oral Syk Inhibitor, Bl1002494, Protects Mice From Arterial Thrombosis and Thromboinflammatory Brain Infarction
Authors: van Eeuwijk Judith M.M. , Stegner David , Lamb David J. , Kraft Peter , Beck Sarah , Thielmann Ina , Kiefer Friedemann , Walzog Barbara , Stoll Guido , Nieswandt Bernhard 
Published: April 2016

Objective—
Ischemic stroke, which is mainly caused by thromboembolic occlusion of brain arteries, is the second leading cause of death and disability worldwide with limited treatment options. The platelet collagen receptor glycoprotein VI (GPVI) is a key player in arterial thrombosis and a critical determinant of stroke outcome, making its signaling pathway an attractive target for pharmacological intervention. The spleen tyrosine kinase (Syk) is an essential signaling mediator downstream of not only GPVI but also other platelet and immune cell receptors. We sought to assess whether Syk might be an effective antithrombotic target.

Approach and Results—
We demonstrate that mice lacking Syk in platelets specifically are protected from arterial thrombus formation and ischemic stroke but display unaltered hemostasis. Furthermore, we show that mice treated with the novel, selective, and orally bioavailable Syk inhibitor BI1002494 were protected in a model of arterial thrombosis and had smaller infarct sizes and a significantly better neurological outcome 24 hours after transient middle cerebral artery occlusion, also when BI1002494 was administered therapeutically, that is, after ischemia.

Conclusions—
These results provide direct evidence that pharmacological Syk inhibition might provide a safe therapeutic strategy to prevent arterial thrombosis and to limit infarct progression in acute stroke.