bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Single Transmembrane Segment of Minimal Sensor DesK Senses Temperature via a Membrane-Thickness Caliper
Authors: Inda Maria E. , Oliveira Rafael G. , de Mendoza Diego , Cybulski Larisa E. 
Published: August 2016

ABSTRACT

Thermosensors detect temperature changes and trigger cellular responses crucial for survival at different temperatures. The thermosensor DesK is a transmembrane (TM) histidine kinase which detects a decrease in temperature through its TM segments (TMS). Here, we address a key issue: how a physical stimulus such as temperature can be converted into a cellular response. We show that the thickness of
Bacillus
lipid membranes varies with temperature and that such variations can be detected by DesK with great precision. On the basis of genetic studies and measurements of
in vitro
activity of a DesK construct with a single TMS (
m
inimal
s
ensor DesK [MS-DesK]), reconstituted in liposomes, we propose an interplay mechanism directed by a conserved dyad, phenylalanine 8-lysine 10. This dyad is critical to anchor the only transmembrane segment of the MS-DesK construct to the extracellular water-lipid interphase and is required for the transmembrane segment of MS-DesK to function as a caliper for precise measurement of membrane thickness. The data suggest that positively charged lysine 10, which is located in the hydrophobic core of the membrane but is close to the water-lipid interface, pulls the transmembrane region toward the water phase to localize its charge at the interface. Nevertheless, the hydrophobic residue phenylalanine 8, located at the N-terminal extreme of the TMS, has a strong tendency to remain in the lipid phase, impairing access of lysine 10 to the water phase. The outcome of this interplay is a fine-tuned sensitivity to membrane thickness that elicits conformational changes that favor different signaling states of the protein.

IMPORTANCE
The ability to sense and respond to extracellular signals is essential for cell survival. One example is the cellular response to temperature variation. How do cells “sense” temperature changes? It has been proposed that the bacterial thermosensor DesK acts as a molecular caliper measuring membrane thickness variations that would occur as a consequence of temperature changes and activates a pathway to restore membrane fluidity at low temperature. Here, we demonstrated that membrane thickness variations do occur at physiological temperatures by directly measuring
Bacillus
lipid membrane thickness. We also dissected the N-terminal sensing motif of MS-DesK at the molecular-biophysical level and found that the dyad phenylalanine-lysine at the water-lipid phase is critical for achievement of a fine-tuned sensitivity to temperature.
Usefulness of sulfasalazine for patients with refractory-ulcerative colits
Authors: Yoshino Takuya , Sono Makoto , Yazumi Shujiro 
Published: August 2016

BackgroundPatients with refractory-ulcerative colitis (UC) require therapy escalation. Sulfasalazine (SASP) could deliver a high concentration of 5-aminosalicylic acid to the colon. The usefulness of SASP for refractory-UC patients, however, is unclear.AimThe aim was to evaluate the usefulness of SASP for refractory-UC patients.MethodWe retrospectively analysed 36 (11.4%) of 316 patients with refractory-UC who had been treated with SASP. Clinical and endoscopic activities were evaluated with Lichtiger index and Mayo score, respectively. We analysed the induction-remission rate, predictive factors for the efficacy of SASP, and adverse events.ResultsOf 36 refractory-UC patients, 14 (38.9%) were treated with concomitant mesalazine enemas, 10 (27.8%) with azathiopurine, 4 (11.1%) with tacrolimus and 6 (16.7%) with an antitumour necrosis factor-α agent. After initiating SASP treatment, 25 patients (69.4%) achieved clinical remission. In 9 (64.3%) of 14 patients with UC treated with mesalazine enemas, mesalazine enemas could be discontinued with SASP. In all patients treated with tacrolimus, tacrolimus could be discontinued with SASP. Clinical activity score upon the initiation of SASP was significantly lower (p=0.024) and the number of patients treated with thiopurine was significantly higher (p=0.016) in the clinical remission group than in the non-clinical remission group. These factors might be predictive for the efficacy of SASP, although multivariate analysis demonstrated no statistically significant effect. Adverse events occurred in 7 patients (19.4%), and reduction or discontinuation of SASP led to improvement.ConclusionsSASP appears to be more effective for refractory-UC patients with low clinical-activity and/or thiopurine-use.Trial registration numberUMIN000021615; Results.
Rift migration and lateral propagation: evolution of normal faults and sediment-routing systems of the western Corinth rift (Greece)
Authors: Ford Mary , Hemelsdaël Romain , Mancini Marco , Palyvos Nikolaos 
Published: August 2016

Abstract
The active Corinth rift records hanging-wall migration of faulting and slip-rate acceleration. The rift initiated at approximately 5–4 Ma, and older parts are well exposed in the northern Peloponnese. A new correlation of chrono- and lithostratigraphy and structure across the onland central to westernmost rift with offshore data reveals westward rift propagation, as well as northward fault migration. Northward fault migration ended first in the east, with the stabilization of major north-dipping faults that now bound the Gulf. The basin then propagated to the WNW in two stages, each involving the initiation of a new fault that propagated east to SE to link to the stable fault system. Extension rates accelerated in distinct steps as the rift opened to the west. The youngest faults in the westernmost rift are associated with high seismicity and highest geodetic extension due to rapid fault growth and linkage at depth.
The early synrift succession infilled substantial inherited palaeo-relief. Antecedent rivers established vigorous sediment-routing systems that controlled facies distribution throughout rifting, albeit with drainage reorganization during fault-migration events. Multiple deepening events recorded in the stratigraphy can be due to lateral rift propagation. The transition from rift initiation to rift climax is, therefore, diachronous along the rift axis.
Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging
Authors: Tromberg Bruce J. , Zhang Zheng , Leproux Anaïs , O'Sullivan Thomas D. , Cerussi Albert E. , Carpenter Philip M. , Mehta Rita S. , Roblyer Darren , Yang Wei , Paulsen Keith D. , Pogue Brian W. , Jiang Shudong , Kaufman Peter A. , Yodh Arjun G. , Chung So Hyun , Schnall Mitchell , Snyder Bradley S. , Hylton Nola , Boas David A. , Carp Stefan A. , Isakoff Steven J. , Mankoff David 
Published: August 2016

AbstractThe prospective multicenter ACRIN 6691 trial was designed to evaluate whether changes from baseline to mid-therapy in a diffuse optical spectroscopic imaging (DOSI)–derived imaging endpoint, the tissue optical index (TOI), predict pathologic complete response (pCR) in women undergoing breast cancer neoadjuvant chemotherapy (NAC). DOSI instruments were constructed at the University of California, Irvine (Irvine, CA), and delivered to six institutions where 60 subjects with newly diagnosed breast tumors (at least 2 cm in the longest dimension) were enrolled over a 2-year period. Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO2), water (ctH2O), lipid, and TOI (ctHHb × ctH2O/lipid) were acquired on both breasts up to four times during NAC treatment: baseline, 1-week, mid-point, and completion. Of the 34 subjects (mean age 48.4 ± 10.7 years) with complete, evaluable data from both normal and tumor-containing breast, 10 (29%) achieved pCR as determined by central pathology review. The percent change in tumor-to-normal TOI ratio (%TOITN) from baseline to mid-therapy ranged from −82% to 321%, with a median of −36%. Using pCR as the reference standard and ROC curve methodology, %TOITN AUC was 0.60 (95% CI, 0.39–0.81). In the cohort of 17 patients with baseline tumor oxygen saturation (%StO2) greater than the 77% population median, %TOITN AUC improved to 0.83 (95% CI, 0.63–1.00). We conclude that the combination of baseline functional properties and dynamic optical response shows promise for clinical outcome prediction. Cancer Res; 76(20); 5933–44. ©2016 AACR.
White–Black Differences in Cancer Incidence, Stage at Diagnosis, and Survival among Adults Aged 85 Years and Older in the United States
Authors: Krok-Schoen Jessica L. , Fisher James L. , Baltic Ryan D. , Paskett Electra D. 
Published: August 2016

Abstract
Background: Increased life expectancy, growth of minority populations, and advances in cancer screening and treatment have resulted in an increasing number of older, racially diverse cancer survivors. Potential black/white disparities in cancer incidence, stage, and survival among the oldest old (≥85 years) were examined using data from the SEER Program of the National Cancer Institute.
Methods: Differences in cancer incidence and stage at diagnosis were examined for cases diagnosed within the most recent 5-year period, and changes in these differences over time were examined for white and black cases aged ≥85 years. Five-year relative cancer survival rate was also examined by race.
Results: Among those aged ≥85 years, black men had higher colorectal, lung and bronchus, and prostate cancer incidence rates than white men, respectively. From 1973 to 2012, lung and bronchus and female breast cancer incidence increased, while colorectal and prostate cancer incidence decreased among this population. Blacks had higher rates of unstaged cancer compared with whites. The 5-year relative survival rate for all invasive cancers combined was higher for whites than blacks. Notably, whites had more than three times the relative survival rate of lung and bronchus cancer when diagnosed at localized (35.1% vs. 11.6%) and regional (12.2% vs. 3.2%) stages than blacks, respectively.
Conclusions: White and black differences in cancer incidence, stage, and survival exist in the ≥85 population.
Impact: Continued efforts are needed to reduce white and black differences in cancer prevention and treatment among the ≥85 population. Cancer Epidemiol Biomarkers Prev; 25(11); 1517–23. ©2016 AACR.
Complement-Regulatory Proteins CFHR1 and CFHR3 and Patient Response to Anti-CD20 Monoclonal Antibody Therapy
Authors: Rogers Laura M. , Mott Sarah L. , Smith Brian J. , Link Brian K. , Sahin Deniz , Weiner George J. 
Published: August 2016

Abstract
Purpose: Anti-CD20 mAb therapies, including rituximab and obinutuzumab (GA101), are common treatments for follicular lymphoma. In an effort to better understand the role of complement in mAb action, we recently performed germline SNP profiling on 142 follicular lymphoma patients and found rs3766404 genotype correlated with patient response to rituximab. To assess the role of three SNP-associated complement-regulatory proteins (CFH, CFHR1, and CFHR3) in clinical response to anti-CD20 mAb, we studied two cohorts of patients treated with anti-CD20 mAb.
Experimental Design: Cohorts included the Iowa/Mayo Lymphoma SPORE observational cohort of subjects with a new diagnosis of follicular lymphoma treated with rituximab and the GAUSS prospective randomized trial cohort of follicular lymphoma subjects randomized to receive single-agent rituximab or obinutuzumab. Circulating protein expression was measured for CFH, CFHR1, and CFHR3 and correlated to clinical outcome.
Results: rs3766404 genotype correlated with expression of the related downstream genes CFHR1 and CFHR3. Loss of CFHR1 expression correlated with inferior patient outcome in the observational cohort, but not in the GAUSS cohort. Loss of CFHR3 correlated with superior event-free survival in GAUSS subjects treated with obinutuzumab, but not rituximab.
Conclusions: We conclude that the relationship between complement-regulatory proteins CFHR1 and CFHR3 and response to anti-CD20 mAb therapy varies based on the specific anti-CD20 mAb used. We propose that CFHR3 is a candidate biomarker for obinutuzumab response. Further studies are needed to validate these findings and to better understand how complement pathways and complement-regulatory proteins impact on the efficacy of anti-CD20 mAb therapy. Clin Cancer Res; 23(4); 954–61. ©2016 AACR.
Key insights to understand the immunogenicity of FVIII products
Authors: Goudemand Jenny , Peyvandi Flora , Lacroix-Desmazes Sébastien 
Published: August 2016

SummaryThe treatment of haemophilia has made significant progress in recent decades, and patients are now being treated safely with great clotting products. However, inhibitor development remains the largest problem, particularly in children. Consequently, the haemostasis that was obtained with traditional clotting factors is not being achieved. Moreover, inhibitor complications translate into adult life and there are an increasing number of situations where adult patients with an inhibitor require major surgery but the clinician is faced with the knowledge that required haemostasis levels are difficult to achieve. Therefore, it is of upmost importance to consider factors relating to inhibitor development, and to determine how inhibitors can be prevented and/or eliminated. Of the various factors at play with regard to inhibitor development, it is important to consider the immunogenicity of factor VIII (FVIII) products, and this topic is the focus of the current paper.
Contemporary issues in the management of von Willebrand disease
Authors: Königs Christoph , James Andra , Federici Augusto 
Published: August 2016

SummaryVon Willebrand disease (VWD) is the most common inherited bleeding disorder. Bleeding scores in VWD, focused in particular on mucosal bleeding, can be very useful in the diagnosis and validation of different types of treatment. The results of an extended prospective study with a large amount of information on clinical phenotype and implications in treatment are reviewed in this article. Treatment of mucosal and joint bleeding in severe VWD remains difficult in some patients. Due to the lack of data on the use of prophylaxis in these patients it is difficult to establish optimal treatment regimens. An overview of the literature, with a focus on the ongoing PRO.WILL study, is provided here. Furthermore, understanding the changes in von Willebrand factor (VWF) levels during pregnancy is very important for establishing the optimal management strategy for pregnancy and delivery in women with VWD. A recently published prospective observational cohort study in women with and without VWD during the postpartum period provides important data that should allow the improvement of postpartum treatment protocols.
Do consumo de marcação à marcação do consumo: #riachuelo e a moda midiatizada
Authors: Souza Lívia Silva de 
Published: August 2016

O consumo midiatizado caracteriza-se pela crescente relevância da mídia na formação de práticas de consumo (Trindade e Perez, 2014). Na circulação nas redes digitais, tais práticas se manifestam de formas singulares, na passagem de uma sociedade do consumo de marcação (Douglas e Isherwood, 2013) para uma sociedade centrada no consumidor, que cria sentidos nos seus usos e na marcação de seu consumo. Aqui, dirigimos nosso olhar para a marca de moda Riachuelo, a partir dos usos da hashtag #riachuelo na rede social Instagram.
Characterization of Proliferating Lesion‐Resident Cells During All Stages of Atherosclerotic Growth
Authors: Lhoták Šárka , Gyulay Gabriel , Cutz Jean‐Claude , Al‐Hashimi Ali , Trigatti Bernardo L. , Richards Carl D. , Igdoura Suleiman A. , Steinberg Gregory R. , Bramson Jonathan , Ask Kjetil , Austin Richard C. 
Published: August 2016

Background
Monocyte recruitment leads to accumulation of macrophage foam cells and contributes to atherosclerotic lesion growth. Recent studies have reported that lesion‐resident macrophages can proliferate and represent a major cellular component during lesion development. This study was designed to assess whether the rate of macrophage proliferation changes during well‐established stages of lesion growth and to characterize other populations of proliferating cells within these lesions.

Methods and Results

Using murine models of atherosclerosis (
Apoe

−/−

and

LDL
r

−/−

mice) and human coronary artery lesions, in situ proliferation of lesion‐resident cells at different stages of growth was assessed by staining for Ki67 and bromodeoxyuridine (BrdU). In early lesions, close to half of all actively growing macrophages were proliferating in situ. BrdU pulse labeling allowed for accurate identification of in situ proliferating macrophages compared to those derived from monocyte recruitment. Local macrophage proliferation declined as lesions advanced. Interestingly, intimal inflammatory cell infiltrates containing proliferating T lymphocytes were identified during the active phase of lesion growth and correlated with apoptotic cell death. Inflammatory cell infiltrates were completely resolved in advanced lesions and replaced with the necrotic core.

Conclusions
Our findings indicate that atherosclerotic lesions contain locally proliferating macrophages primarily during early and intermediate stages of lesion growth. Furthermore, T‐lymphocyte‐enriched inflammatory cell infiltrates represent a novel subset of proliferating cells within the atherosclerotic lesion that correlate with apoptosis and precede the necrotic core. These findings have novel implications in understanding the pathogenesis of atherosclerosis and may implicate proliferating T lymphocytes as a contributing factor to lesion progression and stability.
Circulating MicroRNA‐188, ‐30a, and ‐30e as Early Biomarkers for Contrast‐Induced Acute Kidney Injury
Authors: Sun Shi‐qun , Zhang Tuo , Ding Ding , Zhang Wei‐feng , Wang Xiao‐lei , Sun Zhe , Hu Liu‐hua , Qin Sheng‐ying , Shen Ling‐hong , He Ben 
Published: August 2016

Background

Contrast‐induced acute kidney injury (
CI
‐
AKI
) is typically defined by an increase in serum creatinine after intravascular administration of contrast medium. Because creatinine is an unreliable indicator of acute changes in kidney function, we assessed whether circulating micro
RNA
s (mi
RNA
s) could serve as biomarkers for early detection of
CI
‐
AKI
.

Methods and Results

Using a rat model of
CI
‐
AKI
, we first evaluated the mi
RNA
profile of rat plasma and kidney. Three mi
RNA
species with >1.5‐fold increase in plasma samples of
CI
‐
AKI
rats, including mi
RNA
‐188, mi
RNA
‐30a, and mi
RNA
‐30e, were selected as candidate mi
RNA
s. Quantitative real‐time polymerase chain reaction showed that these candidate mi
RNA
s peaked in concentration around 4 hours after contrast medium exposure and were relatively renal‐specific. We compared the plasma levels of these candidate mi
RNA
s in 71 patients who underwent coronary angiography or percutaneous coronary intervention and developed
CI
‐
AKI
with those of 71 matched controls. The plasma levels of the 3 candidate mi
RNA
s were significantly elevated in the
CI
‐
AKI
group as compared to the control group. Receiver operating characteristic analysis showed that these mi
RNA
s significantly distinguished patients with
CI
‐
AKI
from those without
CI
‐
AKI
. Mi
RNA
composites were highly accurate for
CI
‐
AKI
prediction, as shown in maximized specificity by treble‐positive mi
RNA
composite or maximized Youden index by any‐positive mi
RNA
composite. Moreover, the selected mi
RNA
s changes were associated with Mehran Risk Scores.

Conclusions

Plasma levels of candidate mi
RNA
s significantly distinguished patients with
CI
‐
AKI
from those without
CI
‐
AKI
. Thus, mi
RNA
s are potential biomarkers for early detection of
CI
‐
AKI
.
Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy
Authors: Austein Friederike , Riedel Christian , Kerby Tina , Meyne Johannes , Binder Andreas , Lindner Thomas , Huhndorf Monika , Wodarg Fritz , Jansen Olav 
Published: August 2016

Background and Purpose—
Computed tomographic perfusion represents an interesting physiological imaging modality to select patients for reperfusion therapy in acute ischemic stroke. The purpose of our study was to determine the accuracy of different commercial perfusion CT software packages (Philips (A), Siemens (B), and RAPID (C)) to predict the final infarct volume (FIV) after mechanical thrombectomy.

Methods—
Single-institutional computed tomographic perfusion data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and FIV were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. FIV was measured at follow-up imaging between days 1 and 8 after stroke.

Results—

In 118 successfully recanalized patients (TICI 2b/3), a moderately to strongly positive correlation was observed between ischemic core and FIV. The highest accuracy and best correlation are shown in early and fully recanalized patients (Pearson
r
for A=0.42, B=0.64, and C=0.83;
P
<0.001). Bland–Altman plots and boxplots demonstrate smaller ranges in package C than in A and B. Significant differences were found between the packages about over- and underestimation of the ischemic core. Package A, compared with B and C, estimated more than twice as many patients with a malignant stroke profile (
P
<0.001). Package C best predicted hypoperfusion volume in nonsuccessfully recanalized patients.

Conclusions—
Our study demonstrates best accuracy and approximation between the results of a fully automated software (RAPID) and FIV, especially in early and fully recanalized patients. Furthermore, this software package overestimated the FIV to a significantly lower degree and estimated a malignant mismatch profile less often than other software.
Association Between Serum Phosphate Levels and Stroke Risk in Patients Undergoing Hemodialysis
Authors: Yamada Shunsuke , Tsuruya Kazuhiko , Taniguchi Masatomo , Tokumoto Masanori , Fujisaki Kiichiro , Hirakata Hideki , Fujimi Satoru , Kitazono Takanari 
Published: August 2016

Background and Purpose—
The contribution of serum phosphate levels to stroke risk in dialysis patients remains unclear. The present study aimed to elucidate the respective association between serum phosphate levels and the risk of brain hemorrhage or infarction in patients undergoing hemodialysis.

Methods—
A total of 3437 patients undergoing hemodialysis were followed up for a median of 3.9 years. The primary outcome was the occurrence of brain hemorrhage or infarction. Patients were divided into 4 groups based on their baseline serum phosphate levels (Q1–Q4). Stroke risk was estimated using a Cox proportional hazards model.

Results—

During the follow-up period, 75 patients experienced brain hemorrhage and 139 experienced brain infarction. The risk of brain hemorrhage was significantly higher in the highest (Q4) compared with the lowest quartile (Q1) as the reference value (multivariate-adjusted hazard ratio [95% confidence intervals]: Q1, 1.00; Q2, 1.76 [0.79–4.18]; Q3, 1.99 [0.92–4.67]; and Q4, 2.74 [1.27–6.47];
P
=0.077 for trend; hazard ratio for every 1 mmol/L increase in serum phosphate level, 2.07 [1.10–3.81];
P
=0.025). In contrast, the risk of brain infarction was significantly higher in Q1 (
P
=0.045) compared with Q3 as the reference value (Q1, 1.65 [1.01–2.73]; Q2, 1.35 [0.82–2.25]; Q3, 1.00; and Q4, 1.30 [0.77–2.20]).

Conclusions—
Higher serum phosphate levels were associated with an increased risk of brain hemorrhage, whereas low levels were associated with an increased risk of brain infarction in hemodialysis patients. These results suggest the importance of managing serum phosphate levels within an appropriate range in hemodialysis patients.

Clinical Trial Registration—

URL:
http://www.umin.ac.jp/
. Unique identifier: UMIN000000556.