bluuebunny/crossref_metadata_2025_split huggingface dataset:
What will be the future of the giant gypsum crystals of Naica mine?
Authors: Forti Paolo 
Published: November 2017

Abstract

The mine caves of Naica (Chihuahua, Mexico) are famous because they host large gypsum crystals. Mine works intersected new caves hosting the largest crystals in the world in the year 2000. From 2006 these caves became the object of a multidisciplinary research project with the goal of inferring their ages, the boundary conditions for their formation and the mechanisms inducing their development. Several other scientific aspects were also considered, including palynology, mineralogy, microbiology, physiology, hydrogeology and astrobiology. From 2006 to 2009, scientists and explorers tried to ensure the complete documentation of these natural wonders because they were expected to be accessible for only a few years. As a result of their location
c.
160 m below the natural groundwater level, they were predicted to be flooded with thermal water as soon as dewatering of the mine ceased. This occurred at the end of 2015, so that the lower part of the mine is already submerged and in the near future the giant crystal caves will also disappear. Theoretically, it is still possible to maintain these incredible wonders for future generations, but this seems highly unlikely. Soon the crystals will be submerged below
c.
150 m of hot water, restarting their incredible slow growth.
Localized Synchrotron Irradiation of Mouse Skin Induces Persistent Systemic Genotoxic and Immune Responses
Authors: Ventura Jessica , Lobachevsky Pavel N. , Palazzolo Jason S. , Forrester Helen , Haynes Nicole M. , Ivashkevich Alesia , Stevenson Andrew W. , Hall Christopher J. , Ntargaras Andreas , Kotsaris Vasilis , Pollakis Gerasimos Ch. , Potsi Gianna , Skordylis Konstantinos , Terzoudi Georgia , Pateras Ioannis S. , Gorgoulis Vassilis G. , Georgakilas Alexandros G. , Sprung Carl N. , Martin Olga A. 
Published: November 2017

AbstractThe importance of nontargeted (systemic) effects of ionizing radiation is attracting increasing attention. Exploiting synchrotron radiation generated by the Imaging and Medical Beamline at the Australian Synchrotron, we studied radiation-induced nontargeted effects in C57BL/6 mice. Mice were locally irradiated with a synchrotron X-ray broad beam and a multiplanar microbeam radiotherapy beam. To assess the influence of the beam configurations and variations in peak dose and irradiated area in the response of normal tissues outside the irradiated field at 1 and 4 days after irradiation, we monitored oxidatively induced clustered DNA lesions (OCDL), DNA double-strand breaks (DSB), apoptosis, and the local and systemic immune responses. All radiation settings induced pronounced persistent systemic effects in mice, which resulted from even short exposures of a small irradiated area. OCDLs were elevated in a wide variety of unirradiated normal tissues. In out-of-field duodenum, there was a trend for elevated apoptotic cell death under most irradiation conditions; however, DSBs were elevated only after exposure to lower doses. These genotoxic events were accompanied by changes in plasma concentrations of macrophage-derived cytokine, eotaxin, IL10, TIMP1, VEGF, TGFβ1, and TGFβ2, along with changes in tissues in frequencies of macrophages, neutrophils, and T lymphocytes. Overall, our findings have implications for the planning of therapeutic and diagnostic radiation treatments to reduce the risk of radiation-related adverse systemic effects. Cancer Res; 77(22); 6389–99. ©2017 AACR.
BAP1 Is a Novel Target in HPV-Negative Head and Neck Cancer
Authors: Liu Xiyou , Kumar Manish , Yang Liangpeng , Molkentine David P. , Valdecanas David , Yu Shiying , Meyn Raymond E. , Heymach John V. , Skinner Heath D. 
Published: November 2017

Abstract
Purpose: This study examined the potential role of the nuclear deubiquitinating enzyme BRCA1-associated protein-1 (BAP1) in radioresistance in head and neck squamous cell cancer (HNSCC).
Experimental Design: We overexpressed, knocked down, and rescued BAP1 expression in six HNSCC cell lines, three human papillomavirus (HPV)–negative and three HPV-positive, and examined the effects on radiosensitivity in vitro and in an HNSCC mouse xenograft model. Radiosensitivity was assessed by clonogenic cell survival and tumor growth delay assays; changes in protein expression were analyzed by immunofluorescence staining and Western blotting. We also analyzed The Cancer Genome Atlas HNSCC database to test for associations between BAP1 expression and outcome in patients.
Results: Overexpression of BAP1 induced radioresistance in both cell lines and xenograft models; conversely, BAP1 knockdown led to increased ubiquitination of histone H2A, which has been implicated in DNA repair. We further found that BAP1 depletion suppressed the assembly of constitutive BRCA1 foci, which are associated with homologous recombination (HR), but had minimal effect on γ-H2AX foci and did not affect proteins associated with nonhomologous end joining, suggesting that BAP1 affects radiosensitivity in HNSCC by modifying HR. Finally, in patients with HNSCC, overexpression of BAP1 was associated with higher failure rates after radiotherapy.
Conclusions: BAP1 can induce radioresistance in HNSCC cells, possibly via deubiquitination of H2Aub and modulation of HR, and was associated with poor outcomes in patients with HNSCC. BAP1 may be a potential therapeutic target in HNSCC. Clin Cancer Res; 24(3); 600–7. ©2017 AACR.
Performance of the Surprise Question Compared to Prediction Models in Hemodialysis Patients: A Prospective Study
Authors: Malhotra Rakesh , Tao Xia , Wang Yuedong , Chen Yuqi , Apruzzese Rebecca H. , Balter Paul , Xiao Qingqing , Usvyat Len A. , Kotanko Peter , Thijssen Stephan 
Published: November 2017

<b><i>Background:</i></b> The surprise question (SQ) (“Would you be surprised if this patient were still alive in 6 or 12 months?”) is used as a mortality prognostication tool in hemodialysis (HD) patients. We compared the performance of the SQ with that of prediction models (PMs) for 6- and 12-month mortality prediction. <b><i>Methods:</i></b> Demographic, clinical, laboratory, and dialysis treatment indicators were used to model 6- and 12-month mortality probability in a HD patients training cohort (<i>n</i> = 6,633) using generalized linear models (GLMs). A total of 10 nephrologists from 5 HD clinics responded to the SQ in 215 patients followed prospectively for 12 months. The performance of PM was evaluated in the validation (<i>n</i> = 6,634) and SQ cohorts (<i>n</i> = 215) using the areas under receiver operating characteristics curves. We compared sensitivities and specificities of PM and SQ. <b><i>Results:</i></b> The PM and SQ cohorts comprised 13,267 (mean age 61 years, 55% men, 54% whites) and 215 (mean age 62 years, 59% men, 50% whites) patients, respectively. During the 12-month follow-up, 1,313 patients died in the prediction model cohort and 22 in the SQ cohort. For 6-month mortality prediction, the GLM had areas under the curve of 0.77 in the validation cohort and 0.77 in the SQ cohort. As for 12-month mortality, areas under the curve were 0.77 and 0.80 in the validation and SQ cohorts, respectively. The 6- and 12-month PMs had sensitivities of 0.62 (95% CI 0.35–0.88) and 0.75 (95% CI 0.56–0.94), respectively. The 6- and 12-month SQ sensitivities were 0.23 (95% CI 0.002–0.46) and 0.35 (95% CI 0.14–0.56), respectively. <b><i>Conclusion:</i></b> PMs exhibit superior sensitivity compared to the SQ for mortality prognostication in HD patients.
Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks
Authors: Ganz Peter , Amarenco Pierre , Goldstein Larry B. , Sillesen Henrik , Bao Weihang , Preston Gregory M. , Welch K. Michael A. 
Published: November 2017

Background and Purpose—
Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes.

Methods—
We conducted a case–cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes. Time to stroke was evaluated by Cox proportional hazards models.

Results—

There was no association between time to stroke and lipoprotein-associated phospholipase A
2
, monocyte chemoattractant protein-1, resistin, matrix metalloproteinase-9, N-terminal fragment of pro-B-type natriuretic peptide, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, or soluble CD40 ligand. In adjusted analyses, osteopontin (hazard ratio per SD change, 1.362;
P
<0.0001), neopterin (hazard ratio, 1.137;
P
=0.0107), myeloperoxidase (hazard ratio, 1.177;
P
=0.0022), and adiponectin (hazard ratio, 1.207;
P
=0.0013) were independently associated with outcome strokes. After adjustment for the Stroke Prognostic Instrument-II and treatment, osteopontin, neopterin, and myeloperoxidase remained independently associated with outcome strokes. The addition of these 3 biomarkers to Stroke Prognostic Instrument-II increased the area under the receiver operating characteristic curve by 0.023 (
P
=0.015) and yielded a continuous net reclassification improvement (29.1%;
P
<0.0001) and an integrated discrimination improvement (42.3%;
P
<0.0001).

Conclusions—
Osteopontin, neopterin, and myeloperoxidase were independently associated with the risk of recurrent stroke and improved risk classification when added to a clinical risk algorithm.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique Identifier: NCT00147602.
Direct Mechanical Intervention Versus Bridging Therapy in Stroke Patients Eligible for Intravenous Thrombolysis
Authors: Bellwald Sebastian , Weber Ralph , Dobrocky Tomas , Nordmeyer Hannes , Jung Simon , Hadisurya Jeffrie , Mordasini Pasquale , Mono Marie-Luise , Stracke Christian P. , Sarikaya Hakan , Bernasconi Corrado , Berger Klaus , Arnold Marcel , Chapot René , Gralla Jan , Fischer Urs 
Published: November 2017

Background and Purpose—
Randomized controlled trials have shown that mechanical thrombectomy (MT) plus best medical treatment improves outcome in stroke patients with large-vessel occlusion in the anterior circulation. Whether direct MT is equally effective as bridging thrombolysis (intravenous thrombolysis plus MT) in intravenous thrombolysis eligible patients remains unclear.

Methods—
We compared clinical and radiological outcomes at 3 months in 249 bridging patients with 111 patients receiving direct MT for large-vessel occlusion anterior circulation stroke from 2 prospective registries (study period Essen: June 2012 to August 2013, Bern February 2009 to August 2014). We matched all patients from the direct MT group who would have qualified for intravenous thrombolysis with controls from the bridging group, using multivariate and propensity score methods. Subgroup analyses for internal carotid artery occlusions were performed.

Results—

Baseline characteristics did not differ between the direct MT group and bridging cohort, except for higher rates of coronary heart disease (
P
=0.029) and shorter intervals from onset to endovascular therapy (
P
<0.001) in the MT group. Functional outcome, mortality, and intracerebral hemorrhage did not differ, neither in univariate nor after multivariate and propensity score matching. However, in patients with internal carotid artery occlusion, mortality in the direct cohort was significantly lower.

Conclusions—
In this matched-pair analysis, there was no difference in outcome in patients with large-vessel occlusion anterior circulation stroke treated with direct MT compared with those treated with bridging thrombolysis; however, mortality in patients with internal carotid artery occlusion treated with direct MT was significantly lower than after bridging thrombolysis. Randomized trials comparing direct MT with bridging therapy are needed.
Fingolimod Protects Against Ischemic White Matter Damage by Modulating Microglia Toward M2 Polarization via STAT3 Pathway
Authors: Qin Chuan , Fan Wen-Hui , Liu Qian , Shang Ke , Murugan Madhuvika , Wu Long-Jun , Wang Wei , Tian Dai-Shi 
Published: November 2017

Background and Purpose—
White matter (WM) ischemic injury, a major neuropathological feature of cerebral small vessel diseases, is an important cause of vascular cognitive impairment in later life. The pathogenesis of demyelination after WM ischemic damage are often accompanied by microglial activation. Fingolimod (FTY720) was approved for the treatment of multiple sclerosis for its immunosuppression property. In this study, we evaluated the neuroprotective potential of FTY720 in a WM ischemia model.

Methods—
Chronic WM ischemic injury model was induced by bilateral carotid artery stenosis. Cognitive function, WM integrity, microglial activation, and potential pathway involved in microglial polarization were assessed after bilateral carotid artery stenosis.

Results—
Disruption of WM integrity was characterized by demyelination in the corpus callosum and disorganization of Ranvier nodes using Luxol fast blue staining, immunofluorescence staining, and electron microscopy. In addition, radial maze test demonstrated that working memory performance was decreased at 1-month post–bilateral carotid artery stenosis–induced injury. Interestingly, FTY720 could reduce cognitive decline and ameliorate the disruption of WM integrity. Mechanistically, cerebral hypoperfusion induced microglial activation, production of associated proinflammatory cytokines, and priming of microglial polarization toward the M1 phenotype, whereas FTY720 attenuated microglia-mediated neuroinflammation after WM ischemia and promoted oligodendrocytogenesis by shifting microglia toward M2 polarization. FTY720’s effect on microglial M2 polarization was largely suppressed by selective signal transducer and activator of transcription 3 (STAT3) blockade in vitro, revealing that FTY720-enabled shift of microglia from M1 to M2 polarization state was possibly mediated by STAT3 signaling.

Conclusions—
Our study suggested that FTY720 might be a potential therapeutic drug targeting brain inflammation by skewing microglia toward M2 polarization after chronic cerebral hypoperfusion.
Circulating Endothelial Markers in Retinal Vasculopathy With Cerebral Leukoencephalopathy and Systemic Manifestations
Authors: Pelzer Nadine , Bijkerk Roel , Reinders Marlies E.J. , van Zonneveld Anton Jan , Ferrari Michel D. , van den Maagdenberg Arn M.J.M. , Eikenboom Jeroen , Terwindt Gisela M. 
Published: November 2017

Background and Purpose—

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a monogenic small vessel disease, caused by C-terminal truncating
TREX1
mutations, that can be considered a model for stroke and vascular dementia. The pathophysiology of RVCL-S is largely unknown, but systemic endothelial involvement has been suggested, leading to pathology in the brain and other highly vascularized organs. Here, we investigated circulating endothelial markers to confirm endothelial involvement and identify biomarkers for disease activity.

Methods—
We measured circulating levels of von Willebrand factor (VWF) antigen, VWF propeptide, and angiopoietin-2 in members of 3 Dutch RVCL-S families and matched unrelated healthy controls. Stratified analyses based on symptomatology and age were performed.

Results—

We found elevated levels of VWF antigen, VWF propeptide, and angiopoietin-2 in
TREX1
mutation carriers (n=31) compared with family members without a
TREX1
mutation (n=33) and unrelated healthy controls (n=31; Kruskal–Wallis test
P
<0.001 for all comparisons). Effects were most pronounced in mutation carriers with clinical manifestations aged ≥40 years (Mann–Whitney
U
test
P
<0.001 for all comparisons). Compared with healthy controls, levels of VWF antigen (
P
=0.02) and angiopoietin-2 (
P
=0.04) were also elevated in mutation carriers aged <40 years. All 3 markers showed moderate correlations with markers of kidney and liver disease and inflammation (ie, systemic symptoms of RVCL-S).

Conclusions—
Our results confirm an important role of the endothelium in RVCL-S pathophysiology. VWF antigen, VWF propeptide, and angiopoietin-2 might serve as early biomarkers of disease activity. Our findings might also help to understand the pathophysiology of common neurovascular disorders, such as stroke.
Unruptured Brain Arteriovenous Malformations
Authors: Singfer Uri , Hemelsoet Dimitri , Vanlangenhove Peter , Martens Frederic , Verbeke Luc , Van Roost Dirk , Defreyne Luc 
Published: November 2017

Background and Purpose—
In light of evidence from ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), neurovascular specialists had to reconsider deliberate treatment of unruptured brain arteriovenous malformations (uBAVMs). Our objective was to determine the outcomes of uBAVM treated with primary embolization using ethylene vinyl alcohol (ONYX).

Methods—
Patients with uBAVM who met the inclusion criteria of ARUBA and were treated with primary Onyx embolization were assigned to this retrospective study. The primary outcome was the modified Rankin Scale score. Secondary outcomes were stroke or death because of uBAVM or intervention and uBAVM obliteration.

Results—
Sixty-one patients (mean age, 38 years) were included. The median observation period was 60 months. Patients were treated by embolization alone (41.0%), embolization and radiosurgery (57.4%), or embolization and excision (1.6%). Occlusion was achieved in 44 of 57 patients with completed treatment (77.2%). Forty-seven patients (77.1%) had no clinical impairment at the end of observation (modified Rankin Scale score of <2). Twelve patients (19.7%) reached the outcome of stroke or death because of uBAVM or intervention. Treatment-related mortality was 6.6% (4 patients).

Conclusions—
In uBAVM, Onyx embolization alone or combined with stereotactic radiosurgery achieves a high occlusion rate. Morbidity remains a challenge, even if it seems lower than in the ARUBA trial.
Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation
Authors: Jin Rong , Xiao Adam Y. , Chen Rui , Granger D. Neil , Li Guohong 
Published: November 2017

Background and Purpose—
Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses.

Methods—
Focal cerebral ischemia was induced in C57BL/6 mice by a 60-minute transient middle cerebral artery occlusion. Animals were treated with anti-CD147 function–blocking antibody (αCD147) or isotype control antibody. Blood–brain barrier permeability, thrombus formation, and microvascular patency were assessed 24 hours after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia.

Results—
CD147 expression was rapidly increased in ischemic brain endothelium after transient middle cerebral artery occlusion. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after transient middle cerebral artery occlusion. The neuroprotective effects were associated with (1) prevented blood–brain barrier damage, (2) decreased intravascular fibrin and platelet deposition, which in turn reduced thrombosis and increased cerebral perfusion, and (3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced NF-κB (nuclear factor κB) activation, MMP-9 (matrix metalloproteinase-9) activity, and PAI-1 (plasminogen activator inhibitor-1) expression in brain microvascular endothelial cells.

Conclusions—
Inhibition of CD147 ameliorates acute ischemic stroke by reducing thromboinflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thromboinflammatory disorders.
Conundrums in Indology
Authors: Slaje Walter 
Published: November 2017

A Śarabha is generally understood as an eight-legged monster, surpassing even elephants and lions in strength. A closer inspection of the sources reveals that the evidence for such a one-sided determination is entirely lacking. The notion of a Śarabha has a complex history. Its earliest attestation as a monster occurs only in late strata of the Mahābhārata. Despite this fact, the monstrous nature of a Śarabha was projected in an anachronistic manner indiscriminately onto other literatures as well. Starting, however, from the Atharvaveda, all texts previous to, or uninfluenced by, the Smārta tradition – in particular Buddhist, but also Jain ones –, keep to a different conception, one of an ordinary animal. The present article deals with the original zoological identity of the Śarabha as Mārkhor (Capra falconeri Wagn.) and with the misconceptions that motivated its gradual development into a monster.
Christians in Iraq: The Transition from Religious to Secular Identity
Authors: Teule Herman G.B. 
Published: November 2017

In the Middle Eastern societies, Christians traditionally define themselves as religious communities or churches. This is a continuation of the Ottoman millet system, where religion determined the place one had in society and the patriarch was responsible for the insertion of his community into the state. It not only preserves the traditional ecclesiastical divisions based on dogmatic divergences and church politics but also transposes them to the political field.
For a few decades, many lay politicians in Syria considered this system as detrimental to Christian interests. They developed the idea of a common ethnic identity for all churches using Syriac. New political circumstances in Iraq made it possible to give a political translation of this idea by the creation of Christian political parties, defending common ethnic minority rights. Despite some positive results, attempts at creating unity failed, not only because a lack of unanimity about certain political choices but also about the idea of ethnic identity itself.