bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the tissue dielectric constant of skin basal cell cancer lesions
Authors: Mayrovitz H. N. , Gildenberg S. R. , Spagna P. , Killpack L. , Altman D. A. 
Published: May 2018

AbstractBackgroundMeasuring tissue dielectric constant (TDC) of cancer tissues to distinguish them from normal or non‐cancerous tissues has been an active area of research that has targeted several different cancer types usually using in vitro specimens. The goal of this study was to determine if and to what extent TDC values measured in vivo at 300 MHz using a simple hand‐held measuring device might differentiate between skin cancer lesions and non‐cancerous skin.Materials and MethodsTriplicate TDC measurements were made in 32 patients who were subsequently diagnosed with skin basal cell carcinoma (BCC) and in 14 patients subsequently diagnosed as having non‐cancerous lesions. Lesion TDC values were compared to contralateral unaffected skin and between lesion types.ResultsA significantly lower TDC value (mean ± SD) of BCC lesions (TDCL) vs TDC values of contralateral non‐affected skin (TDCC) was found (22.4 ± 16.2 vs 38.1 ± 15.2, P < .00001). A similar pattern was found for non‐cancerous lesions with lesion TDC values less than non‐affected skin (14.5 ± 9.0 vs 29.1 ± 9.0, P < .0001). However, TDC values were not statistically different between BCC lesions and non‐cancerous lesions (22.4 ± 16.2 vs 14.5 ± 9.0, P = .096) and calculated TDCL/TDCC ratios between BCC lesions and non‐cancerous lesions also were not significantly different (0.596 ± 0.345 vs 0.501 ± 0.261, P = .364).Conclusions(1) Main results do not support using TDC measurements to differentiate in vivo skin cancer lesions from non‐cancerous lesions. (2) TDC values strongly suggest reduced water content of both cancerous and non‐cancerous lesions. (3) Lesion TDC measurements provide reference values for future studies.
On the measurement of investment types: Heterogeneity in corporate tax elasticities
Authors: Jungmann Hendrik , Loretz Simon 
Published: May 2018

AbstractThis paper contributes to debates about the appropriate characterisation of heterogeneous investment types and to what extent different investment motives affect the responsiveness to corporate taxation. In particular, we employ and refine a methodology to better evaluate the tax elasticity of investment types. Using a combination of both firm‐specific information and sector‐specific information from input–output tables, we discuss how to classify investment as non‐related, horizontal, vertical and complex types. First, we point out to what extent the resulting classification depends on assumptions made by the researcher. Second, we employ an ample set of classifications and find that non‐related investment reacts stronger to corporate taxation, whereas horizontal investment is less responsive, though, significant negative tax semi‐elasticities turn out for the subset of manufacturing industries. To address inherent characteristics of vertical and complex investment, we extend the methodology and find that, by and large, stronger business motives reduce the tax responsiveness of investment to a larger extent. Given the current debates about substantial corporate tax reforms, it is all the more important to recognise that corporate tax effects can vary fundamentally between countries, driven by country‐specific differences in their composition of industries and investment types.
Organizational models for health actions in the field of blood and blood products in Brazilian and Spanish regional contexts
Authors: Souza M. K. B. 
Published: May 2018

Background and objectivesThis article aims to characterize some elements that define the organizational models of healthcare actions in the field of blood and blood products.Materials and methodsThis exploratory and qualitative study was carried out based on a documentary survey complemented by interviews with key informants of hemotherapy services from three regional territories in Spain and Brazil.ResultsIt was evidenced demographic, territorial and organizational characteristics, as well as on instruments, resources and individuals involved in the planning, organization and implementation of services and actions in the area.DiscussionThe demographic characteristics and the territorial distribution showed a direct relation with the variation in the blood supply system, in the service structure and in the involvement of different individuals. The predominance of hospital services was a common feature in the territories studied, especially for transfusion services. Regionalization, centralization and concentration strategies were aimed at implementing the organization models of such services and actions in the territories. The use of planning and information technologies presents variation in the territories studied.ConclusionThe limits of organizational models are determined by the context and restriction of its constituent elements – structure, resources, financing, individuals involved – which compromise to some degree the objectives/purposes of the policy.
Computed tomographic and radiographic bronchial collapse may be a normal characteristic of forced expiration in dogs
Authors: Kim Hyunryung , Kim Young Joo , Lee Hanbin , An Taegeon , Yu Jin , Yoon Hyounglok , An Gayeon , Jung Jaihyun , Chang Jinhwa , Chang Dongwoo 
Published: May 2018

AbstractTracheobronchomalacia has been diagnosed using radiography or bronchoscopy to confirm bronchial changes in luminal diameter during the respiratory cycle. However, studies in healthy humans suggest that some degree of bronchial collapse may be observed during the normal respiratory cycle. In this analytical study, the luminal diameter of the bronchus to each of the six pulmonary lobes and the mean percentage of expiratory collapse from end inspiratory, end expiratory, and two forced expiratory phases (10 and 15 ml/kg) were determined via computed tomography (CT) and radiography in 22 healthy Beagle dogs. The bronchial collapsibility was significantly greater during the forced expiration than the end expiration (P < 0.001); the same results were observed in dorsal and sagittal CT images and radiographs (P < 0.001). Median collapsibility values associated with 15 ml/kg forced expiratory collapse determined via cross‐sectional CT images were measured as 16.6–45.5% and differed according to the pulmonary lobe. Median collapsibilities on radiography with 15 ml/kg forced expiration were 57.8% and 62.1% in the right cranial lobe and right caudal lobe, respectively. In conclusion, bronchial diameter may change during the respiratory cycle, and some degree of reduction in bronchial diameter may be an incidental finding in healthy dogs. More rigorous criteria are needed with regards to bronchial collapsibility during normal respiration for the diagnosis of bronchomalacia in order to avoid false‐positive diagnoses.
ATP triggers a robust intracellular [Ca2+]‐mediated signalling pathway in human synovial fibroblasts
Authors: Kondo C. , Clark R. B. , Kim T. Y. , Belke D. , Banderali U. , Szerencsei R. T. , Jalloul A. H. , Schnetkamp P. P. M. , Spitzer K. W. , Giles W. R. 
Published: May 2018

New Findings
What is the central question of this study?
What are the main [Ca2+]i signalling pathways activated by ATP in human synovial fibroblasts?

What is the main finding and its importance?
In human synovial fibroblasts ATP acts through a linked G‐protein (Gq) and phospholipase C signalling mechanism to produce IP3, which then markedly enhances release of Ca2+ from the endoplasmic reticulum. These results provide new information for the detection of early pathophysiology of arthritis.

AbstractIn human articular joints, synovial fibroblasts (HSFs) have essential physiological functions that include synthesis and secretion of components of the extracellular matrix and essential articular joint lubricants, as well as release of paracrine substances such as ATP. Although the molecular and cellular processes that lead to a rheumatoid arthritis (RA) phenotype are not fully understood, HSF cells exhibit significant changes during this disease progression. The effects of ATP on HSFs were studied by monitoring changes in intracellular Ca2+ ([Ca2+]i), and measuring electrophysiological properties. ATP application to HSF cell populations that had been enzymatically released from 2‐D cell culture revealed that ATP (10–100 μm), or its analogues UTP or ADP, consistently produced a large transient increase in [Ca2+]i. These changes (i) were initiated by activation of the P2Y purinergic receptor family, (ii) required Gq‐mediated signal transduction, (iii) did not involve a transmembrane Ca2+ influx, but instead (iv) arose almost entirely from activation of endoplasmic reticulum (ER)‐localized inositol 1,4,5‐trisphosphate (IP3) receptors that triggered Ca2+ release from the ER. Corresponding single cell electrophysiological studies revealed that these ATP effects (i) were insensitive to [Ca2+]o removal, (ii) involved an IP3‐mediated intracellular Ca2+ release process, and (iii) strongly turned on Ca2+‐activated K+ current(s) that significantly hyperpolarized these cells. Application of histamine produced very similar effects in these HSF cells. Since ATP is a known paracrine agonist and histamine is released early in the inflammatory response, these findings may contribute to identification of early steps/defects in the initiation and progression of RA.
The role of miRNA regulation in fetal cardiomyocytes, cardiac maturation and the risk of heart disease in adults
Authors: Lock Mitchell C. , Tellam Ross L. , Botting Kimberley J. , Wang Kimberley C. W. , Selvanayagam Joseph B. , Brooks Doug A. , Seed Mike , Morrison Janna L. 
Published: May 2018

AbstractMyocardial infarction is a primary contributor towards the global burden of cardiovascular disease. Rather than repairing the existing damage of myocardial infarction, current treatments only address the symptoms of the disease and reducing the risk of a secondary infarction. Cardiac regenerative capacity is dependent on cardiomyocyte proliferation, which concludes soon after birth in humans and precocial species such as sheep. Human fetal cardiac tissue has some ability to repair following tissue damage, whereas a fully matured human heart has minimal capacity for cellular regeneration. This is in contrast to neonatal mice and adult zebrafish hearts, which retain the ability to undergo cardiomyocyte proliferation and can regenerate cardiac tissue after birth. In mice and zebrafish models, microRNAs (miRNAs) have been implicated in the regulation of genes involved in cardiac cell cycle progression and regeneration. However, the significance of miRNA regulation in cardiomyocyte proliferation for humans and other large mammals, where the timing of heart development in relation to birth is similar, remains unclear. miRNAs may be valuable targets for therapies that promote cardiac repair after injury. Therefore, elucidating the role of specific miRNAs in large animals, where heart development closely resembles that of humans, remains vitally important for identifying therapeutic targets that may be translated into clinical practice focused on tissue repair.
Genome Sequence of
Geothermobacter
sp. Strain HR-1, an Iron Reducer from the Lō‘ihi Seamount, Hawai’i
Authors: Smith Hillary , Abuyen Karla , Tremblay Jason , Savalia Pratixaben , Pérez-Rodríguez Ileana , Emerson David , Tully Benjamin , Amend Jan 
Published: May 2018

ABSTRACT

Geothermobacter
sp. strain HR-1 was isolated from the Lō‘ihi Seamount vent system in the Pacific Ocean at a depth of 1,000 m. Reported here is its 3.84-Mb genome sequence.
Draft Genome Sequences of Enterococcus mundtii Strains Isolated from Beef Slaughterhouses in Kenya
Authors: Wambui Joseph , Stevens Marc , Njage Patrick Murigu Kamau , Wüthrich Daniel , Egli Adrian , Stephan Roger , Tasara Taurai 
Published: May 2018

ABSTRACT

We present here draft genome sequences of
Enterococcus mundtii
strains K7-EM, P2-EM, C11-EM, and H18-EM, which were isolated from slaughterhouse equipment, carcasses, and personnel of small- and medium-sized beef slaughterhouses in Kenya.
Nsp1α of Porcine Reproductive and Respiratory Syndrome Virus Strain BB0907 Impairs the Function of Monocyte-Derived Dendritic Cells via the Release of Soluble CD83
Authors: Chen Xi , Bai Juan , Liu Xuewei , Song Zhongbao , Zhang Qiaoya , Wang Xianwei , Jiang Ping 
Published: May 2018

ABSTRACT
Porcine reproductive and respiratory syndrome virus (PRRSV), a virulent pathogen of swine, suppresses the innate immune response and induces persistent infection. One mechanism used by viruses to evade the immune system is to cripple the antigen-processing machinery in monocyte-derived dendritic cells (MoDCs). In this study, we show that MoDCs infected by PRRSV express lower levels of the major histocompatibility complex (MHC)-peptide complex proteins TAP1 and ERp57 and are impaired in their ability to stimulate T cell proliferation and increase their production of CD83. Neutralization of sCD83 removes the inhibitory effects of PRRSV on MoDCs. When MoDCs are incubated with exogenously added sCD83 protein, TAP1 and ERp57 expression decreases and T lymphocyte activation is impaired. PRRSV nonstructural protein 1α (Nsp1α) enhances CD83 promoter activity. Mutations in the ZF domain of Nsp1α abolish its ability to activate the CD83 promoter. We generated recombinant PRRSVs with mutations in Nsp1α and the corresponding repaired PRRSVs. Viruses with Nsp1α mutations did not decrease levels of TAP1 and ERp57, impair the ability of MoDCs to stimulate T cell proliferation, or increase levels of sCD83. We show that the ZF domain of Nsp1α stimulates the secretion of CD83, which in turn inhibits MoDC function. Our study provides new insights into the mechanisms of immune suppression by PRRSV.

IMPORTANCE
PRRSV has a severe impact on the swine industry throughout the world. Understanding the mechanisms by which PRRSV infection suppresses the immune system is essential for a robust and sustainable swine industry. Here, we demonstrated that PRRSV infection manipulates MoDCs by interfering with their ability to produce proteins in the MHC-peptide complex. The virus also impairs the ability of MoDCs to stimulate cell proliferation, due in large part to the enhanced release of soluble CD83 from PRRSV-infected MoDCs. The viral nonstructural protein 1 (Nsp1) is responsible for upregulating CD83 promoter activity. Amino acids in the ZF domain of Nsp1α (L5-2A, rG45A, G48A, and L61-6A) are essential for CD83 promoter activation. Viruses with mutations at these sites no longer inhibit MoDC-mediated T cell proliferation. These findings provide novel insights into the mechanism by which the adaptive immune response is suppressed during PRRSV infection.
Kynurenine pathway is altered in patients with SLE and associated with severe fatigue
Authors: Åkesson Karolina , Pettersson Susanne , Ståhl Sara , Surowiec Izabella , Hedenström Mattias , Eketjäll Susanna , Trygg Johan , Jakobsson Per-Johan , Gunnarsson Iva , Svenungsson Elisabet , Idborg Helena 
Published: May 2018

ObjectiveFatigue has been reported as the most disturbing symptom in a majority of patients with SLE. Depression is common and often severe. Together these symptoms cause significant morbidity and affect patients with otherwise relatively mild disease. Tryptophan and its metabolites in the kynurenine pathway are known to be important in several psychiatric conditions, for example, depression, which are often also associated with fatigue. We therefore investigated the kynurenine pathway in patients with SLE and controls.MethodsIn a cross-sectional design plasma samples from 132 well-characterised patients with SLE and 30 age-matched and gender-matched population-based controls were analysed by liquid chromatography tandem mass spectrometry to measure the levels of tryptophan and its metabolites kynurenine and quinolinic acid. Fatigue was measured with Fatigue Severity Scale and depression with Hospital Anxiety and Depression Scale. SLE disease activity was assessed with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).ResultsThe kynurenine/tryptophan ratio, as a measure of indoleamine 2,3-dioxygenase (IDO) activity, was increased in patients with SLE. Patients with active disease (SLEDAI ≥6) showed lower tryptophan levels compared with controls (54 µM, SD=19 vs 62 µM, SD=14, p=0.03), although patients with SLE overall did not differ compared with controls. Patients with SLE had higher levels of tryptophan metabolites kynurenine (966 nM, SD=530) and quinolinic acid (546 nM, SD=480) compared with controls (kynurenine: 712 nM, SD=230, p=0.0001; quinolinic acid: 380 nM, SD=150, p=0.001). Kynurenine, quinolinic acid and the kynurenine/tryptophan ratio correlated weakly with severe fatigue (rs=0.34,rs=0.28 andrs=0.24, respectively) but not with depression.ConclusionsMetabolites in the kynurenine pathway are altered in patients with SLE compared with controls. Interestingly, fatigue correlated weakly with measures of enhanced tryptophan metabolism, while depression did not. Drugs targeting enzymes in the kynurenine pathway, for example, IDO inhibitors or niacin (B12) supplementation, which suppresses IDO activity, merit further investigation as treatments in SLE.
Erythrocyte-bound C4d in combination with complement and autoantibody status for the monitoring of SLE
Authors: Merrill Joan T , Petri Michelle A , Buyon Jill , Ramsey-Goldman Rosalind , Kalunian Kenneth , Putterman Chaim , Conklin John , Furie Richard A , Dervieux Thierry 
Published: May 2018

BackgroundWe examined the usefulness of erythrocyte-bound C4d (EC4d) to monitor disease activity in SLE.MethodsData and blood samples were collected from three different studies, each of which included longitudinal evaluations using the Physicians Global Assessment (PGA) of disease activity and the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI), which was assessed without anti-double-stranded DNA (dsDNA) and low complement C3/C4 (clinical SELENA-SLEDAI). EC4d levels were determined using flow cytometry; other laboratory measures included antibodies to dsDNA, C3 and C4 proteins. Relationships between clinical SELENA-SLEDAI, PGA and the laboratory measures were analysed using linear mixed effect models.ResultsThe three studies combined enrolled 124 patients with SLE (mean age 42 years, 97% women, 31% Caucasians and 34% African-Americans) followed for an average of 5 consecutive visits (range 2–13 visits). EC4d levels and low C3/C4 status were significantly associated the clinical SELENA-SLEDAI or PGA in each of the three study groups (p<0.05). Multivariate analysis revealed that EC4d levels (estimate=0.94±0.28) and low complement C3/C4 (estimate=1.24±0.43) were both independently and significantly associated with the clinical SELENA-SLEDAI (p<0.01) and PGA. EC4d levels were also associated with the clinical SELENA-SLEDAI (estimate: 1.20±0.29) and PGA (estimate=0.19±0.04) among patients with chronically low or normal C3/C4 (p<0.01). Anti-dsDNA titres were generally associated with disease activity.ConclusionThese data support the association of EC4d with disease activity regardless of complement C3/C4 status and its usefulness in monitoring SLE disease. Additional studies will be required to support these validation data.
The Limits of SDP Relaxations for General-Valued CSPs
Authors: Thapper Johan , Živný Stanislav 
Published: May 2018

It has been shown that for a general-valued constraint language Γ the following statements are equivalent: (1) any instance of VCSP(Γ) can be solved to
optimality
using a
constant level
of the Sherali-Adams LP hierarchy, (2) any instance of VCSP(Γ) can be solved to optimality using the
third level
of the Sherali-Adams LP hierarchy, and (3) the support of Γ satisfies the “
bounded width condition
” (i.e., it contains weak near-unanimity operations of all arities).

We show that if the support of Γ violates the bounded width condition then not only is VCSP(Γ) not solved by a constant level of the Sherali-Adams LP hierarchy, but it also requires linear levels of the Lasserre SDP hierarchy (also known as the sum-of-squares SDP hierarchy). For Γ corresponding to linear equations in an Abelian group, this result follows from existing work on inapproximability of Max-CSPs. By a breakthrough result of Lee, Raghavendra, and Steurer [STOC’15], our result implies that for any Γ whose support violates the bounded width condition no SDP relaxation of polynomial size solves VCSP(Γ).
We establish our result by proving that various reductions preserve exact solvability by the Lasserre SDP hierarchy (up to a constant factor in the level of the hierarchy). Our results hold for general-valued constraint languages (i.e., sets of functions on a fixed finite domain that take on rational or infinite values) and thus also hold in notable special cases of { 0, ∞ }-valued languages (CSPs), {0, 1}-valued languages (Min-CSPs/Max-CSPs), and Q-valued languages (finite-valued CSPs).
Comprehensive Profiling of DNA Repair Defects in Breast Cancer Identifies a Novel Class of Endocrine Therapy Resistance Drivers
Authors: Anurag Meenakshi , Punturi Nindo , Hoog Jeremy , Bainbridge Matthew N. , Ellis Matthew J. , Haricharan Svasti 
Published: May 2018

Abstract
Purpose: This study was undertaken to conduct a comprehensive investigation of the role of DNA damage repair (DDR) defects in poor outcome ER+ disease.
Experimental Design: Expression and mutational status of DDR genes in ER+ breast tumors were correlated with proliferative response in neoadjuvant aromatase inhibitor therapy trials (discovery dataset), with outcomes in METABRIC, TCGA, and Loi datasets (validation datasets), and in patient-derived xenografts. A causal relationship between candidate DDR genes and endocrine treatment response, and the underlying mechanism, was then tested in ER+ breast cancer cell lines.
Results: Correlations between loss of expression of three genes: CETN2 (P &lt; 0.001) and ERCC1 (P = 0.01) from the nucleotide excision repair (NER) and NEIL2 (P = 0.04) from the base excision repair (BER) pathways were associated with endocrine treatment resistance in discovery dataset, and subsequently validated in independent patient cohorts. Complementary mutation analysis supported associations between mutations in NER and BER genes and reduced endocrine treatment response. A causal role for CETN2, NEIL2, and ERCC1 loss in intrinsic endocrine resistance was experimentally validated in ER+ breast cancer cell lines, and in ER+ patient-derived xenograft models. Loss of CETN2, NEIL2, or ERCC1 induced endocrine treatment resistance by dysregulating G1–S transition, and therefore, increased sensitivity to CDK4/6 inhibitors. A combined DDR signature score was developed that predicted poor outcome in multiple patient cohorts.
Conclusions: This report identifies DDR defects as a new class of endocrine treatment resistance drivers and indicates new avenues for predicting efficacy of CDK4/6 inhibition in the adjuvant treatment setting. Clin Cancer Res; 24(19); 4887–99. ©2018 AACR.