bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commuting stress process and self‐regulation at work: Moderating roles of daily task significance, family interference with work, and commuting means efficacy
Authors: Zhou Le , Wang Mo , Chang Chu‐Hsiang , Liu Songqi , Zhan Yujie , Shi Junqi 
Published: January 2017

AbstractBased on self‐regulation theories of stress processes, this study proposed a model to examine the within‐person mediation relationship between morning commuting stressors and self‐regulation at work via morning commuting strain. In addition, the study examined the moderating roles of daily task significance, daily family interference with work, and commuting means efficacy in this mediation model. Results from 45 bus commuters’ daily diary data over a period of 15 workdays indicated that the amount of morning commuting stressors experienced by the bus commuters was positively related to their morning commuting strain, which, in turn, had a negative impact on self‐regulation at work. At the within‐person level, daily task significance buffered the negative indirect relationship between morning commuting stressors and self‐regulation at work via morning commuting strain, whereas daily family interference with work in the morning exacerbated this negative indirect relationship. Further, at the between‐person level, commuting means efficacy buffered this negative indirect relationship such that the negative indirect effect was weaker for workers with higher (vs. lower) commuting means efficacy. Theoretical and practical implications of these findings are discussed.
Growing larger with domestication: a matter of physiology, morphology or allocation?
Authors: Milla R. , Matesanz S. 
Published: January 2017

Abstract

Domestication might affect plant size. We investigated whether herbaceous crops are larger than their wild progenitors, and the traits that influence size variation.

We grew six crop plants and their wild progenitors under common garden conditions. We measured the aboveground biomass gain by individual plants during the vegetative stage. We then tested whether photosynthesis rate, biomass allocation to leaves, leaf size and specific leaf area (SLA) accounted for variations in whole‐plant photosynthesis, and ultimately in aboveground biomass.

Despite variations among crops, domestication generally increased the aboveground biomass (average effect +1.38, Cohen's d effect size). Domesticated plants invested less in leaves and more in stems than their wild progenitors. Photosynthesis rates remained similar after domestication. Variations in whole‐plant C gains could not be explained by changes in leaf photosynthesis. Leaves were larger after domestication, which provided the main contribution to increases in leaf area per plant and plant‐level C gain, and ultimately to larger aboveground biomass.

In general, cultivated plants have become larger since domestication. In our six crops, this occurred despite lower investment in leaves, comparable leaf‐level photosynthesis and similar biomass costs of leaf area (i.e. SLA) than their wild progenitors. Increased leaf size was the main driver of increases in aboveground size. Thus, we suggest that large seeds, which are also typical of crops, might produce individuals with larger organs (i.e. leaves) via cascading effects throughout ontogeny. Larger leaves would then scale into larger whole plants, which might partly explain the increases in size that accompanied domestication.
A Non-Stationary Spatial Model for Temperature Interpolation Applied to the State of Rio De Janeiro
Authors: Cunha Marcelo , Gamerman Dani , Fuentes Montserrat , Paez Marina 
Published: January 2017

SummaryWe propose a model for spatial and temporal interpolation and prediction for a set of monthly minimum temperature measurements from 37 stations in the state of Rio de Janeiro, Brazil, from 1961 to 2010. The model is based on a hierarchical specification where data are modelled with a regression structure for the mean and a non-stationary spatial representation for the spatially structured noise term. The regression term is also allowed to contain spatial dependence through coefficients and its covariates. A novel structure is assumed for the spatial non-stationarity, based on a generalization of a currently proposed convolution of stationary models. It allows more flexibility in the model specification and automatically selects the number of model components. This model provides superior performance when compared with two special cases: one stationary, and one non-stationary, provided by a sum of locally stationary processes. The results show a growth in the spread of temperature, with largely urbanized, warmest areas growing warmer, and largely forested, coolest areas growing cooler.
Whole-Genome Sequencing of Invasion-Resistant Cells Identifies Laminin α2 as a Host Factor for Bacterial Invasion
Authors: van Wijk Xander M. , Döhrmann Simon , Hallström Björn M. , Li Shangzhong , Voldborg Bjørn G. , Meng Brandon X. , McKee Karen K. , van Kuppevelt Toin H. , Yurchenco Peter D. , Palsson Bernhard O. , Lewis Nathan E. , Nizet Victor , Esko Jeffrey D. 
Published: January 2017

ABSTRACT

To understand the role of glycosaminoglycans in bacterial cellular invasion, xylosyltransferase-deficient mutants of Chinese hamster ovary (CHO) cells were created using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-
cas9
) gene targeting. When these mutants were compared to the pgsA745 cell line, a CHO xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. Bacterial invasion of pgsA745 cells by group B Streptococcus (GBS), group A
Streptococcus
, and
Staphylococcus aureus
was markedly reduced compared to the invasion of wild-type cells, but newly generated CRISPR-
cas9
mutants were only resistant to GBS. Invasion of pgsA745 cells was not restored by transfection with xylosyltransferase, suggesting that an additional mutation conferring panresistance to multiple bacteria was present in pgsA745 cells. Whole-genome sequencing and transcriptome sequencing (RNA-Seq) uncovered a deletion in the gene encoding the laminin subunit α2 (
Lama2
) that eliminated much of domain L4a. Silencing of the long
Lama2
isoform in wild-type cells strongly reduced bacterial invasion, whereas transfection with human
LAMA2
cDNA significantly enhanced invasion in pgsA745 cells. The addition of exogenous laminin-α2β1γ1/laminin-α2β2γ1 strongly increased bacterial invasion in CHO cells, as well as in human alveolar basal epithelial and human brain microvascular endothelial cells. Thus, the L4a domain in laminin α2 is important for cellular invasion by a number of bacterial pathogens.

IMPORTANCE
Pathogenic bacteria penetrate host cellular barriers by attachment to extracellular matrix molecules, such as proteoglycans, laminins, and collagens, leading to invasion of epithelial and endothelial cells. Here, we show that cellular invasion by the human pathogens group B
Streptococcus
, group A
Streptococcus
, and
Staphylococcus aureus
depends on a specific domain of the laminin α2 subunit. This finding may provide new leads for the molecular pathogenesis of these bacteria and the development of novel antimicrobial drugs.
Physical and cultural determinants of postpartum pelvic floor support and symptoms following vaginal delivery: a protocol for a mixed-methods prospective cohort study
Authors: Nygaard Ingrid E , Clark Erin , Clark Lauren , Egger Marlene J , Hitchcock Robert , Hsu Yvonne , Norton Peggy , Sanchez-Birkhead Ana , Shaw Janet , Sheng Xiaoming , Varner Michael 
Published: January 2017

IntroductionPelvic floor disorders (PFDs), including pelvic organ prolapse (POP), stress and urgency urinary incontinence, and faecal incontinence, are common and arise from loss of pelvic support. Although severe disease often does not occur until women become older, pregnancy and childbirth are major risk factors for PFDs, especially POP. We understand little about modifiable factors that impact pelvic floor function recovery after vaginal birth. This National Institutes of Health (NIH)-funded Program Project, ‘Bridging physical and cultural determinants of postpartum pelvic floor support and symptoms following vaginal delivery’, uses mixed-methods research to study the influences of intra-abdominal pressure, physical activity, body habitus and muscle fitness on pelvic floor support and symptoms as well as the cultural context in which women experience those changes.Methods and analysisUsing quantitative methods, we will evaluate whether pelvic floor support and symptoms 1 year after the first vaginal delivery are affected by biologically plausible factors that may impact muscle, nerve and connective tissue healing during recovery (first 8 weeks postpartum) and strengthening (remainder of the first postpartum year). Using qualitative methods, we will examine cultural aspects of perceptions, explanations of changes in pelvic floor support, and actions taken by Mexican-American and Euro-American primipara, emphasising early changes after childbirth. We will summarise project results in a resource toolkit that will enhance opportunities for dialogue between women, their families and providers, and across lay and medical discourses. We anticipate enrolling up to 1530 nulliparous women into the prospective cohort study during the third trimester, following those who deliver vaginally 1 year postpartum. Participants will be drawn from this cohort to meet the project's aims.Ethics and disseminationThe University of Utah and Intermountain Healthcare Institutional Review Boards approved this study. Data are stored in a secure password-protected database. Papers summarising the primary results and ancillary analyses will be published in peer-reviewed journals.
Functioning and health-related quality of life following injury in older people: a systematic review
Authors: Brown Katherine , Cameron Ian D , Keay Lisa , Coxon Kristy , Ivers Rebecca 
Published: January 2017

Aim and backgroundThere is growing evidence around the impact of injury and recovery trajectories but little focuses on older people, despite rising burden. The aim of this review was to describe the evidence for postinjury functioning and health-related quality of life (HRQoL) in older people.MethodA systematic search of three databases and an extensive search of the grey literature was carried out on prospective injury outcome studies in older people (age ≥65 years) that used a generic health status outcome measure. The search results were reported using PRISMA reporting guidelines, and risk of bias was assessed using a modification of the Quality in Prognosis Studies tool.ResultsThere was limited evidence on functioning and HRQoL postinjury in older people. There were 367 studies identified, with 13 eligible for inclusion. Most focused on hip fracture or traumatic brain injury. Older people appeared to have poorer postinjury functioning and HRQoL compared with younger adults or preinjury levels. Poor preinjury function, pre-existing conditions and increasing age were associated with poorer outcomes, whereas preinjury-independent living was associated with better outcomes.DiscussionThe studies were heterogeneous, limiting synthesis. There was a lack of evidence around the impact of injury on older people in terms of paid work and unpaid work. It was unclear if existing injury outcome guidelines are appropriate for older people.ConclusionsFurther research is required on older people's postinjury course, outcomes and determinants. This will require standardised methodologies and qualitative studies. The findings will inform clinical care, policy development, health and compensation systems.
Patency of the vein of Labbé after venous stenting of the transverse and sigmoid sinuses
Authors: Raper Daniel M S , Ding Dale , Chen Ching-Jen , Buell Thomas J , Crowley R Webster , Liu Kenneth C 
Published: January 2017

BackgroundVenous sinus stenting is an emerging treatment for patients with idiopathic intracranial hypertension and evidence of venous stenosis. Stents placed across the transverse and sigmoid sinuses often cover the vein of Labbé (VOL), a major anastomotic vein draining the cerebral hemisphere. The patency of the VOL after stenting and its clinical implications are poorly understood.MethodsA retrospective analysis was performed of a prospectively collected database of patients undergoing venous sinus stenting. Pre- and post-stent angiography were compared to assess changes in VOL patency, clinical and radiographic outcomes.ResultsThe study cohort comprised 56 patients. The stent covered the VOL in 92.9% of cases. Thirty-two cases with VOL coverage had evaluable angiograms immediately after stent placement. Among these, VOL filled normally in 75.0%, exhibited diminished caliber with normal transit time in 3.1%, filled sluggishly in 18.8%, and was occluded in 3.1%. Follow-up was assessed in patients with at least 3 months' angiographic follow-up (46 patients, mean 7.2 months). Of these, normal filling was seen in 71.7%, diminished caliber in 26.1%, and sluggish filling in 2.2% of cases. Neither stent coverage of the VOL nor its patency immediately after stenting or at follow-up correlated with stent-adjacent stenosis. There were no neurological sequelae from coverage of the VOL or alteration of its drainage pattern.ConclusionsIn the majority of venous stenting cases involving the transverse and sigmoid sinuses, the VOL remains widely patent. Complete VOL occlusion rarely occurs after stenting and may not result in clinical sequelae. Stent coverage of the VOL should not deter the therapeutic use of venous sinus stenting.
Horse: anaesthetic management for open castration of a Belgian draught horse with interventricular septum defect, aortic regurgitation and ventricular premature depolarisations
Authors: Cerasoli Ilaria , Melis Sanne , van Loon Gunther , De Clercq Dominique , Brunsting Julie , Schauvliege Stijn 
Published: January 2017

A 2 years and 11 months old Belgian draught horse stallion with a membranous ventricular septal defect, severe aortic regurgitation, mild left ventricular enlargement and ventricular premature depolarisations was anaesthetised to perform open castration. A balanced anaesthetic approach, involving intravenous use of romifidine (80 µg/kg), morphine (0.1 mg/kg) and lidocaine (1 mg/kg) for premedication, followed by induction of anaesthesia with ketamine (2.2 mg/kg) and midazolam (0.06 mg/kg) and maintenance with isoflurane, lidocaine CRI (50 µg/kg/min) and intratesticular lidocaine 2 per cent (10 ml in each testicle) was used to optimise the cardiovascular stability and enhance the safety of the procedure. A multimodal analgesic approach was provided, aiming to reduce the amount of isoflurane required to maintain a surgical plane of anaesthesia. A smooth and uneventful recovery was obtained. The present case report describes an anaesthetic protocol that could be applied in similar cases.
Identification of CCR2 and CD180 as Robust Pharmacodynamic Tumor and Blood Biomarkers for Clinical Use with BRD4/BET Inhibitors
Authors: Yeh Tammie C. , O'Connor Greg , Petteruti Philip , Dulak Austin , Hattersley Maureen , Barrett J. Carl , Chen Huawei 
Published: January 2017

AbstractPurpose: AZD5153 is a novel BRD4/BET inhibitor with a distinctive bivalent bromodomain binding mode. To support its clinical development, we identified pharmacodynamic (PD) biomarkers for use in clinical trials to establish target engagement.Experimental Design: CCR2 and CD180 mRNAs, initially identified from whole transcriptome profiling, were further evaluated by quantitative PCR in hematologic cell lines, xenografts, and whole blood from rat, healthy volunteers, and patients with cancer. MYC and HEXIM1 mRNAs were also evaluated.Results: RNA-sequencing data showed consistent decreases in CCR2/CD180 expression across multiple hematologic cell lines upon AZD5153 treatment. Evaluation of dose dependence in MV4,11 cells confirmed activity at clinically relevant concentrations. In vivo downregulation of CCR2/CD180 mRNAs (&gt;80%) was demonstrated in MV4,11 and KMS-11 xenograft tumors at efficacious AZD5153 doses. Consistent with in vitro rat blood data, an in vivo rat study confirmed greater inhibition of CCR2/CD180 mRNA in whole blood versus MYC at an efficacious dose. Finally, in vitro treatment of whole blood from healthy volunteers and patients with cancer demonstrated, in contrast to MYC, almost complete downregulation of CCR2/CD180 at predicted clinically achievable concentrations.Conclusions: Our data strongly support the use of CCR2 and CD180 mRNAs as whole blood PD biomarkers for BRD4 inhibitors, especially in situations where paired tumor biopsies are unavailable. In addition, they can be used as tumor-based PD biomarkers for hematologic tumors. MYC mRNA is useful as a hematologic tumor-based biomarker but suboptimal as a whole blood biomarker. Utility of HEXIM1 mRNA may be limited to higher concentrations. Clin Cancer Res; 23(4); 1025–35. ©2017 AACR.
Dasatinib Changes Immune Cell Profiles Concomitant with Reduced Tumor Growth in Several Murine Solid Tumor Models
Authors: Hekim Can , Ilander Mette , Yan Jun , Michaud Erin , Smykla Richard , Vähä-Koskela Markus , Savola Paula , Tähtinen Siri , Saikko Leena , Hemminki Akseli , Kovanen Panu E. , Porkka Kimmo , Lee Francis Y.F. , Mustjoki Satu 
Published: January 2017

Abstract
Dasatinib, a broad-range tyrosine kinase inhibitor, induces rapid mobilization of lymphocytes and clonal expansion of cytotoxic cells in leukemia patients. Here, we investigated whether dasatinib could induce beneficial immunomodulatory effects in solid tumor models. The effects on tumor growth and on the immune system were studied in four different syngeneic mouse models (B16.OVA melanoma, 1956 sarcoma, MC38 colon, and 4T1 breast carcinoma). Both peripheral blood (PB) and tumor samples were immunophenotyped during treatment. Although in vitro dasatinib displayed no direct cytotoxicity to B16 melanoma cells, a significant decrease in tumor growth was observed in dasatinib-treated mice compared with vehicle-treated group. Further, dasatinib-treated melanoma-bearing mice had an increased proportion of CD8+ T cells in PB, together with a higher amount of tumor-infiltrating CD8+ T cells. Dasatinib-mediated antitumor efficacy was abolished when CD4+ and CD8+ T cells were depleted with antibodies. Results were confirmed in sarcoma, colon, and breast cancer models, and in all cases mice treated daily with dasatinib had a significant decrease in tumor growth. Detailed immunophenotyping of tumor tissues with CyTOF indicated that dasatinib had reduced the number of intratumoral regulatory T cells in all tumor types. To conclude, dasatinib is able to slow down the tumor growth of various solid tumor models, which is associated with the favorable blood/tumor T-cell immunomodulation. The assessment of synergistic combinatorial therapies with other immunomodulatory drugs or targeted small-molecule oncokinase inhibitors is warranted in future clinical trials. Cancer Immunol Res; 5(2); 157–69. ©2017 AACR.
Temporally Distinct PD-L1 Expression by Tumor and Host Cells Contributes to Immune Escape
Authors: Noguchi Takuro , Ward Jeffrey P. , Gubin Matthew M. , Arthur Cora D. , Lee Sang Hun , Hundal Jasreet , Selby Mark J. , Graziano Robert F. , Mardis Elaine R. , Korman Alan J. , Schreiber Robert D. 
Published: January 2017

Abstract
Antibody blockade of programmed death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy. Using CRISPR/Cas9-induced loss-of-function approaches and overexpression gain-of-function techniques, we confirmed that PD-L1 on tumor cells is key to promoting tumor escape. In addition, the capacity of PD-L1 to suppress antitumor responses was inversely proportional to tumor cell antigenicity. PD-L1 expression on host cells, particularly tumor-associated macrophages (TAM), was also important for tumor immune escape. We demonstrated that induction of PD-L1 on tumor cells was IFNγ-dependent and transient, but PD-L1 induction on TAMs was of greater magnitude, only partially IFNγ dependent, and was stable over time. Thus, PD-L1 expression on either tumor cells or host immune cells could lead to tumor escape from immune control, indicating that total PD-L1 expression in the immediate tumor microenvironment may represent a more accurate biomarker for predicting response to PD-1/PD-L1 blockade therapy, compared with monitoring PD-L1 expression on tumor cells alone. Cancer Immunol Res; 5(2); 106–17. ©2017 AACR.
Sheet-Like Remodeling of the Transverse Tubular System in Human Heart Failure Impairs Excitation-Contraction Coupling and Functional Recovery by Mechanical Unloading
Authors: Seidel Thomas , Navankasattusas Sutip , Ahmad Azmi , Diakos Nikolaos A. , Xu Weining David , Tristani-Firouzi Martin , Bonios Michael J. , Taleb Iosif , Li Dean Y. , Selzman Craig H. , Drakos Stavros G. , Sachse Frank B. 
Published: January 2017

Background:
Cardiac recovery in response to mechanical unloading by left ventricular assist devices (LVADs) has been demonstrated in subgroups of patients with chronic heart failure (HF). Hallmarks of HF are depletion and disorganization of the transverse tubular system (t-system) in cardiomyocytes. Here, we investigated remodeling of the t-system in human end-stage HF and its role in cardiac recovery.

Methods:
Left ventricular biopsies were obtained from 5 donors and 26 patients with chronic HF undergoing implantation of LVADs. Three-dimensional confocal microscopy and computational image analysis were applied to assess t-system structure, density, and distance of ryanodine receptor clusters to the sarcolemma, including the t-system. Recovery of cardiac function in response to mechanical unloading was assessed by echocardiography during turndown of the LVAD.

Results:

The majority of HF myocytes showed remarkable t-system remodeling, particularly sheet-like invaginations of the sarcolemma. Circularity of t-system components was decreased in HF versus controls (0.37±0.01 versus 0.46±0.02;
P
<0.01), and the volume/length ratio was increased in HF (0.36±0.01 versus 0.25±0.02 µm
2
;
P
<0.0001). T-system density was reduced in HF, leading to increased ryanodine receptor–sarcolemma distances (0.96±0.05 versus 0.64±0.1 µm;
P
<0.01). Low ryanodine receptor–sarcolemma distances at the time of LVAD implantation predicted high post-LVAD left ventricular ejection fractions (
P
<0.01) and ejection fraction increases during unloading (
P
<0.01). Ejection fraction in patients with pre-LVAD ryanodine receptor–sarcolemma distances >1 µm did not improve after mechanical unloading. In addition, calcium transients were recorded in field-stimulated isolated human cardiomyocytes and analyzed with respect to local t-system density. Calcium release in HF myocytes was restricted to regions proximal to the sarcolemma. Local calcium upstroke was delayed (23.9±4.9 versus 10.3±1.7 milliseconds;
P
<0.05) and more asynchronous (18.1±1.5 versus 8.9±2.2 milliseconds;
P
<0.01) in HF cells with low t-system density versus cells with high t-system density.

Conclusions:
The t-system in end-stage human HF presents a characteristic novel phenotype consisting of sheet-like invaginations of the sarcolemma. Our results suggest that the remodeled t-system impairs excitation-contraction coupling and functional recovery during chronic LVAD unloading. An intact t-system at the time of LVAD implantation may constitute a precondition and predictor for functional cardiac recovery after mechanical unloading.