bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key residues at the membrane‐distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte‐specific C‐type lectin‐like receptor KACL with its high‐affinity receptor NKp65
Authors: Bauer Björn , Spreu Jessica , Rohe Christina , Vogler Isabel , Steinle Alexander 
Published: December 2014

SummaryKeratinocyte‐associated C‐type lectin (KACL) is a peculiar C‐type lectin‐like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)‐encoded CTLR, respectively. Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub‐region of the mammalian NKC. The reasons for the tight genetic linkage of these dedicated receptor/ligand pairs are unknown, as is the physiological expression of NKp65. Recently, we reported that the CTLR NKp65 and KACL interact with high affinity, resulting in activation of NKp65‐expressing NK‐92MI cells. Here, we address the molecular basis of this high‐affinity interaction by analysing KACL mutants with KACL‐specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK‐92MI‐NKp65 cells. We find that none of the three N‐linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. However, KACL mutants with non‐conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL‐specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65–KACL interaction by OMA1. Accordingly, functional recognition of these KACL mutants by NK‐92M‐NKp65 cells was completely abolished. Arginine 158 and isoleucine 161 located at the membrane‐distal surface of KACL were defined as residues, decisively determining functional KACL–NKp65 interaction that is independent of KACL glycosylation.
Man's best friend: what can pet dogs teach us about non‐Hodgkin's lymphoma?
Authors: Richards Kristy L. , Suter Steven E. 
Published: December 2014

SummaryAnimal models are essential for understanding lymphoma biology and testing new treatments prior to human studies. Spontaneously arising lymphomas in pet dogs represent an underutilized resource that could be used to complement current mouse lymphoma models, which do not adequately represent all aspects of the human disease. Canine lymphoma resembles human lymphoma in many important ways, including characteristic translocations and molecular abnormalities and similar therapeutic responses to chemotherapy, radiation, and newer targeted therapies (e.g. ibrutinib). Given the large number of pet dogs and high incidence of lymphoma, particularly in susceptible breeds, dogs represent a largely untapped resource for advancing the understanding and treatment of human lymphoma. This review highlights similarities in molecular biology, diagnosis, treatment, and outcomes between human and canine lymphoma. It also describes resources that are currently available to study canine lymphoma, advantages to be gained by exploiting the genetic breed structure in dogs, and current and future challenges and opportunities to take full advantage of this resource for lymphoma studies.
The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled
Authors: Osborne Michael J. , Borden Katherine L. B. 
Published: December 2014

SummaryThe eukaryotic translation initiation factor eIF4E is a potent oncogene. Although eIF4E has traditional roles in translation initiation in the cytoplasm, it is also found in the nucleus, suggesting that it has activities beyond its role in protein synthesis. The road less traveled has been taken to study these nuclear activities and to understand their contribution to the oncogenic potential of eIF4E. The molecular features and biological pathways underpinning eIF4E's nuclear mRNA export are described. New classes of eIF4E regulators have been identified and their relevance to cancer shown. The studies presented here reveal the molecular, biophysical, and structural bases for eIF4E regulation. Finally, recent clinical work targeting eIF4E in acute myeloid leukemia patients with ribavirin is discussed. In summary, these findings provide a novel paradigm for eIF4E function and the molecular basis for targeting it in leukemia patients.
Novel immunotherapies for hematologic malignancies
Authors: Nelson Michelle H. , Paulos Chrystal M. 
Published: December 2014

SummaryThe immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise novel strategies that exploit the patient's immune system to kill cancer. We review various forms of immune‐based therapies, which have shown significant promise in patients with hematologic malignancies, including (i) conventional monoclonal therapies like rituximab; (ii) engineered monoclonal antibodies called bispecific T‐cell engagers; (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T‐cell pathways (i.e. PD‐1, CTLA‐4, and IDO); and (iv) adoptive cell transfer therapy with T cells engineered to express chimeric antigen receptors or T‐cell receptors. We also assess the idea of using these therapies in combination and conclude by suggesting multi‐prong approaches to improve treatment outcomes and curative responses in patients.
Protein ubiquitination in lymphoid malignancies
Authors: Yang Yibin , Staudt Louis M. 
Published: December 2014

SummaryHuman lymphoid malignancies inherit gene expression networks from their normal B‐cell counterpart and co‐opt them for their own oncogenic purpose, which is usually governed by transcription factors and signaling pathways. These transcription factors and signaling pathways are precisely regulated at multiple steps, including ubiquitin modification. Protein ubiqutination plays a role in almost all cellular events and in many human diseases. In the past few years, multiple studies have expanded the role of ubiquitination in the genesis of diverse lymphoid malignancies. Here, we discuss our current understanding of both proteolytic and non‐proteolytic functions of the protein ubiquitination system and describe how it is involved in the pathogenesis of human lymphoid cancers. Lymphoid‐restricted ubiquitination mechanisms, including ubiquitin E3 ligases and deubiquitinating enzymes, provide great opportunities for the development of targeted therapies for lymphoid cancers.
Peripheral T‐cell and NK cell lymphoproliferative disorders: cell of origin, clinical and pathological implications
Authors: Inghirami Giorgio , Chan Wing C. , Pileri Stefano ,   the AIRC 5xMille consortium ‘Genetics‐driven targeted management of lymphoid malignancies’
Published: December 2014

SummaryT‐cell lymphoproliferative disorders are a heterogeneous group of neoplasms with distinct clinical‐biological properties. The normal cellular counterpart of these processes has been postulated based on functional and immunophenotypic analyses. However, T lymphocytes have been proven to be remarkably capable of modulating their properties, adapting their function in relationship with multiple stimuli and to the microenvironment. This impressive plasticity is determined by the equilibrium among a pool of transcription factors and by DNA chromatin regulators. It is now proven that the acquisition of specific genomic defects leads to the enforcement/activation of distinct pathways, which ultimately alter the preferential activation of defined regulators, forcing the neoplastic cells to acquire features and phenotypes distant from their original fate. Thus, dissecting the landscape of the genetic defects and their functional consequences in T‐cell neoplasms is critical not only to pinpoint the origin of these tumors but also to define innovative mechanisms to re‐adjust an unbalanced state to which the tumor cells have become addicted and make them vulnerable to therapies and targetable by the immune system. In our review, we briefly describe the pathological and clinical aspects of the T‐cell lymphoma subtypes as well as NK‐cell lymphomas and then focus on the current understanding of their pathogenesis and the implications on diagnosis and treatment.
Japanese nurse practitioner practice and outcomes in a nursing home
Authors: Ono M. , Miyauchi S. , Edzuki Y. , Saiki K. , Fukuda H. , Tonai M. , Magilvy J.K. , Murashima S. 
Published: December 2014

AimBy describing the practice of a Japanese nurse practitioner, this descriptive case study discusses role development and outcomes before and after the intervention.BackgroundOne of the first Japanese nurse practitioners intervened at a nursing home during the government‐designated trial period for nurse practitioner practice.ConclusionBecause of the nurse practitioner's meticulous observation and timely care provision to the residents in collaboration with the physician and the other staff in the facility, comparative data showed improvement in daily health status management of every resident and decreased deterioration of residents' health conditions requiring ambulance transfer and hospitalization.
Spring Freeze Effect on Wheat Yield is Modulated by Winter Temperature Fluctuations: Evidence from Meta‐Analysis and Simulating Experiment
Authors: Li X. , Cai J. , Liu F. , Dai T. , Cao W. , Jiang D. 
Published: December 2014

AbstractIncreasing climatic variability is projected to affect large‐scale atmospheric circulation, triggers and exacerbates more extreme weather events, including winter warming and more frequent extreme low temperatures in spring. Historical data from 1961–2000 indicate these temperature fluctuations may seriously affect grain yield of winter wheat crops. In this study, a field air temperature control system (FATC) was used to simulate the winter warming, spring cold and freezing events in the field experiment in 2010–2011 to explore their impacts on growth and yield of winter wheat. Eight elite wheat varieties released during 1961–2000 were included and four temperature scenarios were applied, including late spring freeze alone, winter warming + late spring freeze, early spring cold + late spring freeze and the normal temperature condition as control. Winter warming combined with late spring freeze significantly decreased tiller survival rate, leaf photosynthetic rate and leaf growth in wheat plants, and reduced the spike number and kernel number per spike, and the final grain yield. In contrast, the wheat plants experienced early spring cold had higher tiller survival rate, leaf photosynthetic capacity and sugar accumulation and improved tolerance to the late spring freeze, resulting in less yield loss, as compared with those without experiencing early spring cold. Both the meta‐analyses and the field experimental data demonstrated that the effects of later spring freeze stress on wheat yield were exacerbated by winter warming but were extenuated by early spring cold events. Therefore, it is important to consider the characteristics of temperature fluctuations during winter to spring for precise evaluation of climate change effects on wheat production.
Discharged Energy Properties of SrO–PbO–Na2O–Nb2O5–SiO2 Glass‐Ceramics with Different Crystallization Time
Authors: Zhang Qingmeng , Li Chang , Liu Hongwei , Tang Qun , Liu Jinfeng , Li Hongtao , Wang Meng , Xie Weiping , Du Jun 
Published: December 2014

Discharged energy properties of PbO–SrO–Na2O–Nb2O5–SiO2 glass‐ceramics with crystallization time from 1 to 1000 min were investigated by measuring their hysteresis loops (described as quasi‐static measuring method) and pulse‐discharge current‐time curves (described as dynamic measuring method). The results show the same trend for both measuring methods: With the increment of crystallization time, the discharged energy density increases gradually, while the energy efficiency decreases. The highest energy efficiencies were obtained in the sample with crystallization time of 1 min, which are 96.3% and 82.4%, corresponding quasi‐static and dynamic measurement, respectively. The reduction of energy efficiency with crystallization time is attributed to combined effect of ferroelectric polarization and interfacial polarization, and part of the corresponding energy could not release in the pulse‐discharge process.
A randomized controlled trial of the effectiveness of a postnatal psychoeducation programme on self‐efficacy, social support and postnatal depression among primiparas
Authors: Shorey Shefaly , Chan Sally Wai Chi , Chong Yap Seng , He Hong‐Gu 
Published: December 2014

AbstractAimTo examine the effectiveness of a postnatal psychoeducation programme in enhancing maternal self‐efficacy and social support and reducing postnatal depression among primiparas.BackgroundPrimiparas experience various challenges during the early postnatal period with low self‐efficacy, depression and lack of social support. Support in the form of postnatal educational programmes is needed to improve these outcomes of primiparas.DesignA randomized controlled two‐group pre‐test–post‐test design was adopted.MethodsData were collected from June–December 2012 in a public hospital in Singapore from 122 primiparas, who were randomly assigned to the intervention (n = 61) or control group (n = 61). The intervention group received postnatal psychoeducation programme and routine care while the control group received routine care only. The Maternal Parental Self‐Efficacy scale, Perinatal Infant Care Social Support scale and Edinburgh Postnatal Depression Scale were used to measure outcomes of maternal parental self‐efficacy, social support and postnatal depression. The mean percentage changes of all three outcome variables from baseline to 6 and 12 weeks postpartum between groups were used when performing repeated measures multivariate analysis of covariance.ResultsThe intervention group had significantly higher scores of maternal parental self‐efficacy and social support and lower scores of postnatal depression at 6 and 12 weeks postpartum when compared with the control group.ConclusionThe postnatal psychoeducation programme was effective in improving maternal outcomes and hence could be introduced as routine care with ongoing evaluation in the postnatal period. Future studies could focus on the effects of this programme on other populations.Trial registration no: ISRCTN15886353.
The Thriving of Older People Assessment Scale: validity and reliability assessments
Authors: Bergland Ådel , Kirkevold Marit , Sandman Per‐Olof , Hofoss Dag , Edvardsson David 
Published: December 2014

AbstractAimTo explore construct validity and reliability of the Thriving of Older People Assessment Scale.BackgroundThe concept of thriving emphasizes person–environment interaction in relation to well‐being. The Thriving of Older People Assessment Scale has been developed and evaluated as a self‐report and proxy scale based on the theory of thriving.DesignCross‐sectional survey design.MethodThe Thriving of Older People Assessment Scale was completed by a sample of 259 residents, 146 family members and 52 staff from 13 long‐term care facilities in Norway and Sweden. Data were collected between April 2010–December 2011. Exploratory factor analysis was applied to explore construct validity in terms of factor structure and dimensionality of the 32‐item scale in relation to the thriving theory. Reliability was explored through internal consistency estimation using Cronbach's alpha and through homogeneity evaluation using corrected item‐total correlations.ResultsExploratory factor analysis resulted in five factors (subscales) that corresponded meaningfully with the thriving theory and were labelled 1: Resident' attitudes towards being in long‐term care; 2: Quality of care and caregivers; 3: Resident engagement and peer relationships; 4: Keeping in touch with people and places; and 5: Quality of the physical environment. The scale had satisfactory internal consistency and homogeneity estimates.ConclusionThe 32‐item Thriving of Older People Assessment Scale can be regarded as construct valid and reliable. Its factor structure corresponded logically to the thriving theory and its factors showed satisfactory internal consistency and homogeneity. Nevertheless, the TOPAS would benefit from further testing in other populations and contexts.
A randomized controlled trial examining the effectiveness of a STOMA psychosocial intervention programme on the outcomes of colorectal patients with a stoma: study protocol
Authors: Lim Siew Hoon , Chan Sally Wai‐Chi , Lai Jiunn Herng , He Hong‐Gu 
Published: December 2014

AbstractAimsTo report a study protocol that evaluates the effects of a psychosocial intervention on patients with a newly formed stoma.BackgroundWith the loss of a significant body function and distorted body image, stoma patients experience physical, psychological and social challenges. Nurses have an important role in helping patients’ make a smooth transition to living with their stoma. Limited studies have examined the effects of psychosocial interventions on improving stoma‐related health outcomes.DesignA randomized controlled trial is planned.MethodsEighty‐four patients with newly formed stoma in a tertiary hospital in Singapore (Research Ethics Committee approval obtained in January 2013) will be recruited. Participants will be randomly assigned to either a control group who receive routine care or an intervention group who receive STOMA psychosocial intervention besides routine care. Outcome variables include stoma care self‐efficacy, days to stoma proficiency, length of hospital stay, acceptance of stoma, anxiety and depression and quality of life. Data will be collected at four time points: before randomization and intervention (baseline), on the day of discharge (mid‐intervention), at 4 weeks after discharge (postintervention 1) and at 4 months after discharge (postintervention 2).DiscussionThis study will develop a psychosocial intervention programme, which may improve patients’ stoma‐related outcomes. The findings will provide direction to health professionals about education and the type of support that could be offered to patients concerning stoma care in the hospital setting, which will eventually improve their quality of life.
Unrivalled specialization in a pollination network from South Africa reveals that specialization increases with latitude only in the Southern Hemisphere
Authors: Pauw Anton , Stanway Rosanne 
Published: December 2014

AbstractAimWe aimed to produce the first complete pollination network for Africa to test (1) whether South African plants are unusually specialized in their interactions with pollinators, and (2) whether the South African data conform with global patterns of specialization.LocationCederberg, Cape Floristic Region, South Africa (32°04′31.52″ S, 19°04′ 48.42″ E; elevation 320 m).MethodsWe sampled all plant–pollinator interactions within a 1‐ha plot to assemble a network of 62 plant species linked to 217 pollinators species by 10,314 visits. We calculated the standardized Kullback–Leibler distance (d′) as an estimate of plant and animal specialization, and standardized two‐dimensional Shannon entropy (ΔH2′) as an estimate of network‐wide specialization. We compared these metrics with those calculated for 58 other networks from across the world.ResultsIn a global context, the South African plant species had an unusually high number of interaction partners (mean = 6.32) while the animal species had unusually few (mean = 1.81). Animal diversity was high relative to plant diversity (network asymmetry = 0.56). Nevertheless, the South African plants, pollinators and network overall were more specialized than any previously studied community (weighted mean d′ plants = 0.824 and animals = 0.807, community ΔH2′ = 0.834), suggesting functional specialization. Overall, specialization was found to increase sharply with latitude in the Southern Hemisphere, whereas no relationship was found in the Northern Hemisphere.Main conclusionsThe findings that South African plants have a high diversity of pollinators and that specialization of pollination networks increases with latitude in the Southern Hemisphere only are in contradiction to expectations derived from earlier literature. Long‐term climatic stability in the Southern Hemisphere might have allowed phenotypic and functional specialization to manifest and persist.
Digital Plethysmography and Arginine Metabolism in Prehypertension—Effect of Nebivolol Therapy
Authors: Kandavar Ramprasad , Fernandez Camilo , Sander Gary E. , Kim Catherine , Velaga Santhosh , Sukhanov Sergiy , Delafontaine Patrice , Egan Peter , Roffidal Louise E. , Giles Thomas D. 
Published: December 2014

Prehypertension is an important phenotype for cardiovascular risk and development of established hypertension. To better understand the early circulatory changes in this group, the authors studied 34 patients with prehypertension (blood pressure 120–139/80–89 mm Hg) using digital plethysmography for measurement of blood flow and reactive hyperemic index (RHI). Arterial augmentation index (AI) was also measured. Because prehypertension is associated with endothelial dysfunction and decreased availability of nitric oxide (NO), indices of arginine metabolism (l‐arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, and l‐citrulline) were measured. Nebivolol (5 mg/d), a vasodilating β1‐antagonist with β3‐agonist activity, was studied in a double‐blind fashion for 8 weeks. Nebivolol increases the bioavailability of NO. Prehypertension was associated with normal RHI and baseline digital blood flow. AI was abnormal and associated with diastolic blood pressure. ADMA concentration was increased at baseline. After 8 weeks of nebivolol therapy, RHI, ADMA, symmetric dimethylarginine, and AI showed no significant change, but digital blood flow and l‐citrulline levels were significantly increased. Prehypertension is associated with increased ADMA and evidence of increased arterial stiffness and preserved RHI. Nebivolol therapy is associated with digital vasodilation and increased NO production, as depicted by increased levels of l‐citruline and mean digital blood flow.
Comparing Clinical Effectiveness and Drug Toxicity With Hydrochlorothiazide and Chlorthalidone Using Two Potency Ratios in a Managed Care Population
Authors: Saseen Joseph J. , Ghushchyan Vahram , Nair Kavita V. 
Published: December 2014

This study compared the clinical effectiveness and drug toxicity of chlorthalidone and hydrochlorothiazide. Electronic health records and claims data were used to identify patients initially prescribed chlorthalidone or hydrochlorothiazide. A total of 214 patients prescribed chlorthalidone 25 mg were matched with 428 patients prescribed hydrochlorothiazide 25 mg (1:1 potency ratio) and 214 patients prescribed hydrochlorothiazide 50 mg (1:2 potency ratio). Mean systolic blood pressure/diastolic blood pressure values at least 30 days after initial prescription were lower with chlorthalidone (132.2/74 mm Hg) compared with hydrochlorothiazide 25 mg (137.0/77.5 mm Hg) and hydrochlorothiazide 50 mg (138.6/78.5 mm Hg) (P<.05 for all comparisons). Goal systolic blood pressure/diastolic blood pressure values were achieved in a higher percentage of patients prescribed chlorthalidone (45.0%/78.3%) than with either hydrochlorothiazide 25 mg (32.1%/63.9%) or hydrochlorothiazide 50 mg (32.8%/68.9%) (P<.05 for all comparisons). Mean serum potassium was 3.94 mEq/L with chlorthalidone 25 mg, 4.13 mEq/L with hydrochlorothiazide 25 mg (P<.01 vs chlorthalidone), and 3.96 mEq/L with hydrochlorothiazide 50 mg. These findings indicate that chlorthalidone 25 mg is associated with a better antihypertensive response than hydrochlorothiazide 25 mg or 50 mg, without clinically significant differences in serum potassium.