bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Lesions
Authors: Tak Won Young , Lin Shi-Ming , Wang Yijun , Zheng Jiasheng , Vecchione Aldo , Park Soo Young , Chen Min Hua , Wong Stephen , Xu Ruocai , Peng Cheng-Yuan , Chiou Yi-You , Huang Guan-Tarn , Cai Jianqiang , Abdullah Basri Johan Jeet , Lee June Sung , Lee Jae Young , Choi Jong-Young , Gopez-Cervantes Julieta , Sherman Morris , Finn Richard S. , Omata Masao , O'Neal Michael , Makris Lukas , Borys Nicholas , Poon Ronnie , Lencioni Riccardo 
Published: October 2017

Abstract
Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.
Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.
Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76–1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41–0.96; P &lt; 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.
Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73–83. ©2017 AACR.
Functional Genomics Approach Identifies Novel Signaling Regulators of TGFα Ectodomain Shedding
Authors: Wilson Jennifer L. , Kefaloyianni Eirini , Stopfer Lauren , Harrison Christina , Sabbisetti Venkata S. , Fraenkel Ernest , Lauffenburger Douglas A. , Herrlich Andreas 
Published: October 2017

AbstractEctodomain shedding of cell-surface precursor proteins by metalloproteases generates important cellular signaling molecules. Of importance for disease is the release of ligands that activate the EGFR, such as TGFα, which is mostly carried out by ADAM17 [a member of the A-disintegrin and metalloprotease (ADAM) domain family]. EGFR ligand shedding has been linked to many diseases, in particular cancer development, growth and metastasis, as well as resistance to cancer therapeutics. Excessive EGFR ligand release can outcompete therapeutic EGFR inhibition or the inhibition of other growth factor pathways by providing bypass signaling via EGFR activation. Drugging metalloproteases directly have failed clinically because it indiscriminately affected shedding of numerous substrates. It is therefore essential to identify regulators for EGFR ligand cleavage. Here, integration of a functional shRNA genomic screen, computational network analysis, and dedicated validation tests succeeded in identifying several key signaling pathways as novel regulators of TGFα shedding in cancer cells. Most notably, a cluster of genes with NFκB pathway regulatory functions was found to strongly influence TGFα release, albeit independent of their NFκB regulatory functions. Inflammatory regulators thus also govern cancer cell growth–promoting ectodomain cleavage, lending mechanistic understanding to the well-known connection between inflammation and cancer.Implications: Using genomic screens and network analysis, this study defines targets that regulate ectodomain shedding and suggests new treatment opportunities for EGFR-driven cancers. Mol Cancer Res; 16(1); 147–61. ©2017 AACR.
Higher Adiposity Is Associated With Slower Cognitive Decline in Hypertensive Patients: Secondary Analysis of the China Stroke Primary Prevention Trial
Authors: Zhang Jun , Tang Genfu , Xie Haiqun , Wang Binyan , He Mingli , Fu Jia , Shi Xiuli , Zhang Chengguo , Huo Yong , Xu Xiping , Wang Kai 
Published: October 2017

Background
Obesity is a risk factor for many diseases. However, the potential association between adiposity and cognitive decline in hypertensive patients is inconclusive. We performed a secondary data analysis of the CSPPT (China Stroke Primary Prevention Trial) to examine whether adiposity is correlated with longitudinal cognitive performance in hypertensive adults.

Methods and Results

The analysis included 16 791 patients in the
CSPPT
who received at least 2 cognitive assessments by the Mini‐Mental State Examination (
MMSE
) during the follow‐up (median, 4.5 years; interquartile range, 4.2–4.8 years). Outcomes included changes in
MMSE
scores and cognitive impairment (defined as
MMSE
score less than education‐specific cutoff point). A marked reduction in
MMSE
scores at the final (compared with at the 1‐year) follow‐up was apparent in both men (n=4838; mean [
SD
] score, 0.41 [3.62]) and women (n=7190; mean [SD] score, 1.07 [4.61]; both
P
<0.001). Analysis using a mixed‐effects model revealed an association between higher body mass index with less
MMSE
decline, even after controlling for demographics and comorbidities (men, β=0.0134 [
SE
, 0.0036]; women, β=0.0133 [SE, 0.0034]; both
P
<0.001). A total of 1037 men (15.3%) and 3317 women (33.1%) developed cognitive impairment. In multivariable Cox regression analyses, being obese in men (11.3% versus 18.0%; hazard ratio, 0.75; 95% confidence interval, 0.60–0.94) and women (30.1% versus 36.5%; hazard ratio, 0.82; 95% confidence interval, 0.74–0.91) was a protective factor against cognitive impairment compared with normal body mass index.

Conclusions
Higher adiposity is independently associated with slower cognitive decline in Chinese hypertensive adults.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00794885
CSPPT
.
Mortality and Disability According to Baseline Blood Pressure in Acute Ischemic Stroke Patients Treated by Thrombectomy: A Collaborative Pooled Analysis
Authors: Maïer Benjamin , Gory Benjamin , Taylor Guillaume , Labreuche Julien , Blanc Raphaël , Obadia Michael , Abrivard Marie , Smajda Stanislas , Desilles Jean‐Philippe , Redjem Hocine , Ciccio Gabriele , Lukaszewicz Anne Claire , Turjman Francis , Riva Roberto , Labeyrie Paul Emile , Duhamel Alain , Blacher Jacques , Piotin Michel , Lapergue Bertrand , Mazighi Mikael , Decroix Jean‐Pierre , Wang Adrien , Evrard Serge , Tchikviladzé Maya , Bourdin Frederic , Gonzalez‐Valcarcel Jaime , Di Maria Federico , Pico Fernando , Rakotoharinandrasana Haja , Tassan Philippe , Poll Roxanna , Corabianu Ovide , de Broucker Thomas , Smadja Didier , Alamowitch Sonia , Ille Olivier , Manchon Eric , Garcia Pierre‐Yves 
Published: October 2017

Background

High blood pressure (
BP
) is associated with worse clinical outcomes in the setting of acute ischemic stroke, but the optimal blood pressure target is still a matter of debate. We aimed to study the association between baseline
BP
and mortality in acute ischemic stroke patients treated by mechanical thrombectomy.

Methods and Results

A total of 1332 acute ischemic stroke patients treated by mechanical thrombectomy were enrolled (from January 2012 to June 2016) in the
ETIS
(Endovascular Treatment in Ischemic Stroke) registry. Linear and polynomial logistic regression models were used to assess the association between
BP
and mortality and functional outcome at 90 days. Highest mortality was found at lower and higher baseline systolic blood pressure (
SBP
) values following a J‐ or U‐shaped relationship, with a nadir at 157 mm Hg (95% confidence interval 143‐170). When
SBP
values were categorized in 10–mm Hg increments, the odds ratio for all‐cause mortality was 3.78 (95% confidence interval 1.50‐9.55) for
SBP
<110 mm Hg and 1.81 (95% confidence interval 1.01‐3.36) for
SBP
≥180 mm Hg using
SBP
≥150 to 160 mm Hg as reference. The rate of favorable outcome was the highest at low
SBP
values and lowest at high
SBP
values, with a nonlinear relationship; in unplanned exploratory analysis, an optimal threshold
SBP
≥177 mm Hg was found to predict unfavorable outcome (adjusted odds ratio 0.47; 95% confidence interval 0.31‐0.70).

Conclusion

In acute ischemic stroke patients treated by mechanical thrombectomy, baseline
SBP
is associated with all‐cause mortality and favorable outcome. In contrast to mortality, favorable outcome rate was the highest at low
SBP
values and lowest at high
SBP
values. Further studies are warranted to confirm these findings.
Circulatory Dynamics During Pulmonary Vein Isolation Using the Second‐Generation Cryoballoon
Authors: Kajiyama Takatsugu , Miyazaki Shinsuke , Watanabe Tomonori , Yamao Kazuya , Kusa Shigeki , Igarashi Miyako , Nakamura Hiroaki , Hachiya Hitoshi , Iesaka Yoshito 
Published: October 2017

Background
Circulatory dynamics change during pulmonary vein (PV) isolation using cryoballoons. This study sought to investigate the circulatory dynamics during cryoballoon‐based PV isolation procedures and the contributing factors.

Methods and Results

This study retrospectively included 35 atrial fibrillation patients who underwent PV isolation with 28‐mm second‐generation cryoballoons and single 3‐minute freeze techniques. Blood pressures were continuously monitored via arterial lines. The left ventricular function was evaluated with intracardiac echocardiography throughout the procedure in 5 additional patients. Overall, 126 cryoapplications without interrupting freezing were analyzed. Systolic blood pressure (
SBP
) significantly increased during freezing (138.7±28.0 to 148.0±27.2 mm Hg,
P
<0.001) and sharply dropped (136.3±26.0 to 95.0±17.9 mm Hg,
P
<0.001) during a mean of 21.0±8.0 seconds after releasing the occlusion during thawing. In the multivariate analyses, the left
PV
s (
P
=0.008) and lower baseline
SBP
(
P
<0.001) correlated with a larger
SBP
rise, whereas a higher baseline
SBP
(
P
<0.001), left
PV
s (
P
=0.017), lower balloon nadir temperature (
P
=0.027), and female sex (
P
=0.045) correlated with larger
SBP
drops. These changes were similarly observed regardless of preprocedural atropine administration and the target
PV
order.
PV
occlusions without freezing exhibited no
SBP
change.
PV
antrum freezing without occlusions similarly increased the
SBP
, but the
SBP
drop was significantly smaller than that with occlusions (
P
<0.001). The
SBP
drop time‐course paralleled the left ventricular ejection fraction increase (66.8±8.1% to 79.3±6.7%,
P
<0.001) and systemic vascular resistance index decrease (2667±1024 to 1937±513 dynes‐sec/cm
2
per m
2
,
P
=0.002).

Conclusions

With second‐generation cryoballoon‐based PV isolation,
SBP
significantly increased during freezing owing to atrial tissue freezing and dropped sharply after releasing the occlusion, presumably because of the peripheral vascular resistance decrease mainly by circulating chilled blood.
Bosutinib Attenuates Inflammation via Inhibiting Salt-Inducible Kinases in Experimental Model of Intracerebral Hemorrhage on Mice
Authors: Ma Li , Manaenko Anatol , Ou Yi-Bo , Shao An-Wen , Yang Shu-Xu , Zhang John H. 
Published: October 2017

Background and Purpose—
Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. Pronounced inflammation plays a significant role in the development of the secondary brain injury after ICH. Recently, SIK-2 (salt-inducible kinase-2) was identified as an important component controlling inflammatory response. Here we sought to investigate the role of SIK-2 in post-ICH inflammation and potential protective effects of SIK-2 inhibition after ICH.

Methods—
Two hundred and ninety-three male CD-1 mice were used. ICH was induced via injection of 30 μL of autologous blood. Recombinant SIK-2 was administrated 1 hour after ICH intracerebroventricularly. SIK-2 small interfering RNA was injected intracerebroventricularly 24 hours before ICH. Bosutinib, a clinically approved tyrosine kinase inhibitor with affinity to SIK-2, was given intranasally 1 hour or 6 hours after ICH. Effects of treatments were evaluated by neurological tests and brain water content calculation. Molecular pathways were investigated by Western blots and immunofluorescence studies.

Results—
Endogenous SIK-2 was expressed in microglia and neurons. SIK-2 expression was reduced after ICH. Exogenous SIK-2 aggravated post-ICH inflammation, leading to brain edema and the neurobehavioral deficits. SIK-2 inhibition attenuated post-ICH inflammation, reducing brain edema and ameliorating neurological dysfunctions. Bosutinib inhibited SIK-2–attenuating ICH-induced brain damage. Protective effects of Bosutinib were mediated, at least partly, by CRTC3 (cyclic amp-response element binding protein-regulated transcription coactivator 3)/cyclic amp-response element binding protein/NF-κB (nuclear factor-κB) pathway.

Conclusions—
SIK-2 participates in inflammation induction after ICH. SIK-2 inhibition via Bosutinib or small interfering RNA decreased inflammation, attenuating brain injury. SIK-2 effects are, at least partly, mediated by CRTC3-cyclic amp-response element binding protein-NF-κB signaling pathway.
Dietary Sodium to Potassium Ratio and Risk of Stroke in a Multiethnic Urban Population
Authors: Willey Joshua , Gardener Hannah , Cespedes Sandino , Cheung Ying K. , Sacco Ralph L. , Elkind Mitchell S.V. 
Published: October 2017

Background and Purpose—
There is growing evidence that increased dietary sodium (Na) intake increases the risk of vascular diseases, including stroke, at least in part via an increase in blood pressure. Higher dietary potassium (K), seen with increased intake of fruits and vegetables, is associated with lower blood pressure. The goal of this study was to determine the association of a dietary Na:K with risk of stroke in a multiethnic urban population.

Methods—
Stroke-free participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were followed-up for incident stroke. Baseline food frequency questionnaires were analyzed for Na and K intake. We estimated the hazard ratios and 95% confidence intervals for the association of Na:K with incident total stroke using multivariable Cox proportional hazards models.

Results—
Among 2570 participants with dietary data (mean age, 69±10 years; 64% women; 21% white; 55% Hispanic; 24% black), the mean Na:K ratio was 1.22±0.43. Over a mean follow-up of 12 years, there were 274 strokes. In adjusted models, a higher Na:K ratio was associated with increased risk for stroke (hazard ratio, 1.6; 95% confidence interval, 1.2–2.1) and specifically ischemic stroke (hazard ratio, 1.6; 95% confidence interval, 1.2–2.1).

Conclusions—
Na:K intake is an independent predictor of stroke risk. Further studies are required to understand the joint effect of Na and K intake on risk of cardiovascular disease.
Neuronal SIRT1 (Silent Information Regulator 2 Homologue 1) Regulates Glycolysis and Mediates Resveratrol-Induced Ischemic Tolerance
Authors: Koronowski Kevin B. , Khoury Nathalie , Saul Isabel , Loris Zachary B. , Cohan Charles H. , Stradecki-Cohan Holly M. , Dave Kunjan R. , Young Juan I. , Perez-Pinzon Miguel A. 
Published: October 2017

Background and Purpose—
Resveratrol, at least in part via SIRT1 (silent information regulator 2 homologue 1) activation, protects against cerebral ischemia when administered 2 days before injury. However, it remains unclear if SIRT1 activation must occur, and in which brain cell types, for the induction of neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol-induced ischemic tolerance and sought to characterize the metabolic pathways regulated by neuronal Sirt1 at the cellular level in the brain.

Methods—
We assessed infarct size and functional outcome after transient 60 minute middle cerebral artery occlusion in control and inducible, neuronal-specific SIRT1 knockout mice. Nontargeted primary metabolomics analysis identified putative SIRT1-regulated pathways in brain. Glycolytic function was evaluated in acute brain slices from adult mice and primary neuronal-enriched cultures under ischemic penumbra-like conditions.

Results—

Resveratrol-induced neuroprotection from stroke was lost in neuronal
Sirt1
knockout mice. Metabolomics analysis revealed alterations in glucose metabolism on deletion of neuronal
Sirt1
, accompanied by transcriptional changes in glucose metabolism machinery. Furthermore, glycolytic ATP production was impaired in acute brain slices from neuronal
Sirt1
knockout mice. Conversely, resveratrol increased glycolytic rate in a SIRT1-dependent manner and under ischemic penumbra-like conditions in vitro.

Conclusions—
Our data demonstrate that resveratrol requires neuronal SIRT1 to elicit ischemic tolerance and identify a novel role for SIRT1 in the regulation of glycolytic function in brain. Identification of robust neuroprotective mechanisms that underlie ischemia tolerance and the metabolic adaptations mediated by SIRT1 in brain are crucial for the translation of therapies in cerebral ischemia and other neurological disorders.
Description of Ektaphelenchus oleae n. sp. (Rhabditida: Ektaphelenchinae) from Iran
Authors: Miraeiz Esmaeil , Heydari Ramin , Adeldoost Yaser , Ye Weimin 
Published: October 2017

Ektaphelenchus oleae n. sp. is described and illustrated based on morphological and molecular data from the rhizosphere of an olive tree (Olea europium) from the suburbs of Gorgan, Golestan Province, in northern Iran. The new species is characterised by females 441-652 μm long, stylet 15-19 μm long with wide lumen without basal swelling, labial region set off by a clear constriction, appearing bowl-like, four incisures in lateral field, excretory pore always located posterior to median bulb and anterior to hemizonid, post-uterine sac 43-73 μm long, conoid tail, and the presence of four pairs of male subventral caudal papillae. The new species is typologically similar to species belonging to three genera: Anomyctus, Ektaphelenchus and Seinura, by a combination of morphological characters, e.g., head with expanded lips, forming a small bowl-like structure, stylet without knobs or swellings at the base, short conical tail and a vestigial anus and rectum in most individuals. Molecular analysis of the new species was performed using sequences of SSU and LSU ribosomal DNA genes.
Does Security Increase Secularity? Evidence from the British Household Panel Survey on the Relationship between Income and Religious Service Attendance
Authors: Storm Ingrid 
Published: October 2017

Material security has been associated with lower religious attendance both between and within countries and has been proposed as one of the mechanisms causing long term religious decline in economically developed countries. Using a British panel study, this article examines (a) whether change to household incomes can incite individual religious change and (b) whether religion can buffer against the stress of economic loss.
The main trend in Britain is that of religious stability or decline, and income change does nothing to reverse this trend. Increases in household income are associated with religious disengagement, but income reduction has no effect on religious attendance. However, religious activity may still act as a ‘buffer’ by improving and maintaining life satisfaction in the face of economic loss.
A contribution to the knowledge of the subfamily Panagaeinae Hope, 1838 from Africa. Part 3. Revision of the Craspedophorus strachani and C. brevicollis groups (Coleoptera: Carabidae)
Authors: HÄCKEL MARTIN 
Published: October 2017

Revised are Afrotropical species of the Craspedophorus strachani and C. brevicollis groups. New taxa are C. dicranulothorax n. sp. (Cameroon), C. lemariei n. sp. (Gabon), C. phenacoides n. sp. (Cameroon), C. ruficroides n. sp. (Guinea), C. cuneatus rotundatus n. ssp. (Cameroon, central Africa), C. ruficroides thomsoni n. ssp. (Cameroon, central Africa, Gabon), C. strachani bamendanus n. ssp. (Cameroon), C. tetrastigma morettoi n. ssp. (west Africa) and C. brevicollis beninensis n. ssp. (Benin). C. ruficrus (Laferté-Sénectere, 1851) and C. gabonicus (Thomson, 1858) are considered nomina dubia, because their original descriptions do not provide enough information to allow linking the names to any known specimens. To correct the situation, the authorship of C. ruficrus is ascribed to the first reviser, Chaudoir (1861) [as a valid name (sp. resurr.)], who designated a lectotype and provided an adequate redescription; the invalid name C. gabonicus (Thomson) sensu Chaudoir (1861) is synonymized with C. muata (Harold, 1883). The status of the following species is changed to subspecies: C. grossus (Hope, 1842) is demoted to ssp. of C. strachani (Hope, 1842), C. paromius Basilewsky, 1987 is demoted to ssp. of C. cuneatus (Alluaud, 1915) and C. milzi Duvivier, 1891 is demoted to ssp. of C. tetrastigma (Laferté). C. strachani depressus Burgeon, 1930 is synonymized with C. tetrastigma milzi Duvivier, 1891 and C. chevalieri jokoanus Basilewsky, 1987 is synonymized with C. chevalieri (Alluaud, 1915). C. strachani and C. brevicollis groups sensu Chaudoir 1879 are redefined. C. latemaculatus Alluaud, 1930 is removed from C. reflexus group Häckel 2016 and transferred to C. strachani group nov.
Gust Factors: Meteorologically Stratified Climatology, Data Artifacts, and Utility in Forecasting Peak Gusts
Authors: Harris Austin R. , Kahl Jonathan D. W. 
Published: October 2017

AbstractGust factors in Milwaukee, Wisconsin, are investigated using Automated Surface Observing System (ASOS) wind measurements from 2007 to 2014. Wind and gust observations reported in the standard hourly ASOS dataset are shown to contain substantial bias caused by sampling and reporting protocols that restrict the reporting of gusts to arbitrarily defined “gusty” periods occurring during small subsets of each hour. The hourly ASOS gust reports are found to be inadequate for describing the gust characteristics of the site and ill suited for the study of gust factors. A gust-factor climatology was established for Milwaukee using the higher-resolution, 1-min version of the ASOS dataset. The mean gust factor is 1.74. Stratified climatologies demonstrate that Milwaukee gust factors vary substantially with meteorological factors, with wind speed and wind direction exerting the strongest controls. A variety of modified gust-factor models were evaluated in which the peak wind gust is estimated by multiplying a gust factor by the observed, rather than forecast, wind speed. Errors thus obtained are entirely attributable to utility of the gust factor in forecasting peak gusts, having eliminated any error associated with the wind speed forecast. Results show that gust-factor models demonstrate skill in estimating peak gusts and improve with the use of meteorologically stratified gust factors.