bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial Cluster Detection in Mobility Networks: A Copula Approach
Authors: Kim Heeyoung , Duan Rong , Kim Sungil , Lee Jaehwan , Ma Guang-Qin 
Published: August 2018

SummaryIn mobility network capacity planning, characterizing the mobility network traffic is one of the most challenging tasks. Besides the growth trend and multiple periodic temporal patterns for normal traffic, the problem is complicated by the occasionally intense traffic for special events and its dynamic spatial relationships. Identifying the areas that have different traffic patterns compared with their neighbouring areas is a problem of spatial hotspot detection. In the paper, a copula-based method is proposed: using a multivariate extreme value copula, the upper tail dependence of the traffic distributions of neighbouring cell towers is evaluated, and then a cluster of multiple time series (i.e. multiple cell towers) with high upper tail dependence is detected. The method proposed is validated by using synthetic data as well as real mobility traffic data.
Experiencing and Resisting Nonsuicidal Self‐injury Thoughts and Urges in Everyday Life
Authors: Turner Brianna J. , Baglole J. Sebastian , Chapman Alexander L. , Gratz Kim L. 
Published: August 2018

ObjectiveWe used a daily diary to examine (1) the frequency of three types of NSSI thoughts and urges (fleeting thoughts, persistent thoughts, and intense urges), (2) the correlates of NSSI thought and urges within and across days, (3) strategies that aid in resisting NSSI thoughts and urges, and (4) the prospective association of daily NSSI thoughts and urges with NSSI behavior over 12 months.MethodSixty adults (aged 18–35) completed a two‐week daily diary and follow‐ups every 3 months for one year.ResultsFleeting NSSI thoughts were reported on 48% of days, whereas persistent thoughts (11%) and intense urges (17%) were less common. Within days, earlier stress predicted more persistent NSSI thoughts, whereas earlier perceived support predicted less intense NSSI urges. Furthermore, NSSI thoughts and urges were positively associated with same‐day stress and avoidant coping. Problem‐focused coping was associated with greater success resisting same‐day fleeting thoughts and intense urges, as well as success resisting next‐day persistent thoughts. Perceived support was associated with less intense same‐day urges, but also less success resisting these urges. Over the follow‐up, persistent thoughts predicted less frequent NSSI, whereas intense urges predicted more frequent NSSI.ConclusionsNSSI thoughts and urges are commonly experienced and deserve further attention.
The effects of children’s proximity‐seeking to maternal attachment figures during mild stress exposure on mood and physiological responses: An experimental study
Authors: Dujardin Adinda , De Raedt Rudi , Borelli Jessica L. , Braet Caroline , Vos Pieter , Rinck Mike , Bosmans Guy 
Published: August 2018

AbstractIn this study we investigated the effects of seeking versus avoiding proximity to mother on children’s emotional recovery from a stressor. Sixty children 9–12 years underwent a moodinduction procedure and were randomly assigned to seek proximity from or avoid an image of their mothers. The effect of this manipulation on children’s self‐reported negative emotions, skin conductance and heart rate variability (respiratory sinus arhythmia) was assessed. Higher levels of attachment anxiety were linked to more self‐reported sadness when children had to avoid mother, but no evidence for such an effect was found on a physiological level. For avoidant attachment, a similar pattern of results emerged, but both for self‐reported sadness and skin conductance.
Glutamatergic neurons of the paraventricular nucleus are critical contributors to the development of neurogenic hypertension
Authors: Basting Tyler , Xu Jiaxi , Mukerjee Snigdha , Epling Joel , Fuchs Robert , Sriramula Srinivas , Lazartigues Eric 
Published: August 2018

Key points
Recurrent periods of over‐excitation in the paraventricular nucleus (PVN) of the hypothalamus could contribute to chronic over‐activation of this nucleus and thus enhanced sympathetic drive.
Stimulation of the PVN glutamatergic population utilizing channelrhodopsin‐2 leads to an immediate frequency‐dependent increase in baseline blood pressure.
Partial lesions of glutamatergic neurons of the PVN (39.3%) result in an attenuated rise in blood pressure following Deoxycorticosterone acetate (DOCA)‐salt treatment and reduced index of sympathetic activity.
These data suggest that stimulation of PVN glutamatergic neurons is sufficient to cause autonomic dysfunction and drive the increase in blood pressure during hypertension.
AbstractNeuro‐cardiovascular dysregulation leads to increased sympathetic activity and neurogenic hypertension. The paraventricular nucleus (PVN) of the hypothalamus is a key hub for blood pressure (BP) control, producing or relaying the increased sympathetic tone in hypertension. We hypothesize that increased central sympathetic drive is caused by chronic over‐excitation of glutamatergic PVN neurons. We tested how stimulation or lesioning of excitatory PVN neurons in conscious mice affects BP, baroreflex and sympathetic activity. Glutamatergic PVN neurons were unilaterally transduced with channelrhodopsin‐2 using an adeno‐associated virus (CamKII‐ChR2‐eYFP‐AAV2) in wildtype mice (n = 7) to assess the impact of acute stimulation of excitatory PVN neurons selectively on resting BP in conscious mice. Stimulation of the PVN glutamatergic population resulted in an immediate frequency‐dependent (2, 10 and 20 Hz) increase in BP from baseline by ∼9 mmHg at 20 Hz stimulation (P < 0.001). Additionally, in vGlut2‐cre mice glutamatergic neurons of the PVN were bilaterally lesioned utilizing a cre‐dependent caspase (AAV2‐flex‐taCASP3‐TEVp). Resting BP and urinary noradrenaline (norepinephrine) levels were then recorded in conscious mice before and after DOCA‐salt hypertension. Partial lesions of glutamatergic neurons of the PVN (39.3%, P < 0.05) resulted in an attenuated rise in BP following DOCA‐salt treatment (P < 0.05 at 7 day time point, n = 8). Noradrenaline levels as an index of sympathetic activity between the lesion and wildtype groups showed a significant reduction after DOCA‐salt treatment in the lesioned animals (P < 0.05). These experiments suggest that stimulation of PVN glutamatergic neurons is sufficient to cause autonomic dysfunction and drive the increase in BP.
Experimental Infection of
Tadarida brasiliensis
with
Pseudogymnoascus destructans
, the Fungus That Causes White-Nose Syndrome
Authors: Verant Michelle L. , Meteyer Carol U. , Stading Benjamin , Blehert David S. 
Published: August 2018

White-nose syndrome (WNS) is a fungal disease that is causing severe declines of bat populations in North America. Identifying ways to reduce the impacts of this disease is a priority but is inhibited by the lack of an experimental animal model that does not require the use of wild-caught bat species already impacted by WNS. We tested whether
Tadarida brasiliensis
, one of the most abundant species of bats in the Americas, could serve as a suitable animal model for WNS research. While
T. brasiliensis
bats were susceptible to experimental infection with the fungus under conditions that induced hibernation, the species exhibited limited pathology diagnostic for WNS. These results indicate that
T. brasiliensis
is not likely a suitable experimental model for WNS research. However, the recovery of viable WNS-causing fungus from experimentally infected bats indicates a potential for this species to contribute to the spread of the pathogen where it coexists with other species of bats affected by WNS.
The PedS2/PedR2 Two-Component System Is Crucial for the Rare Earth Element Switch in Pseudomonas putida KT2440
Authors: Wehrmann Matthias , Berthelot Charlotte , Billard Patrick , Klebensberger Janosch 
Published: August 2018

The function of lanthanides for methanotrophic and methylotrophic bacteria is gaining increasing attention, while knowledge about the role of rare earth elements (REEs) in nonmethylotrophic bacteria is still limited. The present study investigates the recently described differential expression of the two PQQ-EDHs of
P. putida
in response to lanthanides. We demonstrate that a specific TCS is crucial for their inverse regulation and provide evidence for a dual regulatory function of the LuxR-type response regulator involved. Thus, our study represents the first detailed characterization of the molecular mechanism underlying the REE switch of PQQ-EDHs in a nonmethylotrophic bacterium and stimulates subsequent investigations for the identification of additional genes or phenotypic traits that might be coregulated during REE-dependent niche adaptation.
Half bolus dose of intravenous abciximab is safe and effective in the setting of acute stroke endovascular treatment
Authors: Delgado Fernando , Oteros Rafael , Jimenez-Gomez Elvira , Bravo Rey Isabel , Bautista María Dolores , Valverde Moyano Roberto 
Published: August 2018

BackgroundA stent is often necessary for the treatment of stroke. In such cases,it is essential for the patient to have antiplatelet therapy. There are several methods of antiaggregation, such as oral loading doses of aspirin and clopidogrel, intravenous aspirin, or intravenous glycoprotein IIb/IIIa receptor antagonists, such as abciximab. The aim of this study was to evaluate the incidence of symptomatic intracerebral hematoma (sICH) associated with our antiplatelet protocol: intravenous abciximab bolus at half the dose (0125 mg/kg) at the time of the stenting procedure; oral aspirin (150 mg) and clopidogrel (75 mg) daily added the next day after CT shows no significant hematoma.Materials and methodsRetrospective review of our database of endovascular management of large acute vessel occlusion treated with intravenous abciximab between January 2015 and March 2018. Demographics data, material, drugs, and complications were registered. Fisher tests were used to compare the incidence of sICH in the literature where abciximab 0.25 mg/kg plus maintenance doses are often administrated.ResultsIntravenous abciximab was administered to 99 patients. No sICH was observed. According to the European Cooperative Acute Stroke Study Scale, there were 8 cases of hemorrhagic infarction 1, 5 cases of hemorrhagic infarction 2, 4 cases of parenchymal hemorrhage 1, and no cases of parenchymal hemorrhage 2. A comparison between sICH with conventional antiplatelet doses based on the literature showed a statistically significant difference favoring our protocol.ConclusionIn the endovascular treatment of acute ischemic stroke, a bolus dose of 0125 mg/kg of abciximab with no maintenance doses, followed by 150 mg of aspirin and 75 mg of clopidogrel orally the next day, is safe and effective.
Treatment strategies for recurrent and residual aneurysms after Woven Endobridge implantation
Authors: Kabbasch Christoph , Goertz Lukas , Siebert Eberhard , Herzberg Moriz , Hamisch Christina , Mpotsaris Anastasios , Dorn Franziska , Liebig Thomas 
Published: August 2018

BackgroundWoven Endobridge (WEB) embolization is a safe and efficient technique for endovascular treatment of intracranial aneurysms. However, the management of aneurysm recurrence after WEB placement has not been well described to date. We present our multicenter experience of endovascular retreatment of aneurysm recurrence after WEB implantation.MethodsThis is a multicenter study of patients who underwent endovascular retreatment after WEB implantation in three German tertiary care centers. Treatment strategies, complications, and angiographic outcome were retrospectively assessed.ResultsAmong 122 aneurysms treated with the WEB device, 15 were retreated. Of these, six were initially treated with the WEB only, two were pretreated by coiling, and seven large aneurysms were treated in a multimodality approach. Ten were true aneurysm remnants and five were neck remnants. The reasons for retreatment were WEB migration (n=6), initial incomplete occlusion (n=5), and WEB compression (n=4). Retreatment strategies included coiling (n=4), stent-assisted coiling (n=7), flow diversion (n=3), and placement of an additional WEB (n=1). All procedures were technically successful and there were no procedure-related complications. Among 11 patients available for follow-up after retreatment, three were retreated again. At last angiographic follow-up, available in 11/15 cases at a median of 23 months, complete occlusion was obtained in eight cases and neck remnants in three.ConclusionsThis pilot study shows that endovascular retreatment of recurrent or residual aneurysms after WEB implantation can be done safely and can achieve adequate occlusion rates.
AptimaTrichomonas vaginalisassay elucidates significant underdiagnosis of trichomoniasis among women in Brazil according to an observational study
Authors: Bruni Mirian Pinheiro , Freitas da Silveira Mariangela , Stauffert Dulce , Bicca Guilherme Lucas de Oliveira , Caetano dos Santos Carolina , da Rosa Farias Nara Amélia , Golparian Daniel , Unemo Magnus 
Published: August 2018

ObjectivesTrichomonas vaginalis (TV) infection is the most common non-viral STI globally and can result in adverse pregnancy outcomes and exacerbated HIV acquisition/transmission. Nucleic acid amplification tests (NAATs) are the most sensitive diagnostic tests, with high specificity, but TV NAATs are rarely used in Brazil. We investigated the TV prevalence and compared the performance of the US Food and Drug Association-cleared Aptima TV assay with microscopy (wet mount and Gram-stained) and culture for TV detection in women in Pelotas, Brazil in an observational study.MethodsFrom August 2015 to December 2016, 499 consecutive asymptomatic and symptomatic sexually active women attending a Gynaecology and Obstetrics Outpatient Clinic were enrolled. Vaginal fluid and swab specimens were collected and wet mount microscopy, Gram-stained microscopy, culture and the Aptima TV assay performed.ResultsThe median age of enrolled women was 36.5 years (range: 15–77). The majority were white, had a steady sexual partner and low levels of education. The TV detection rate was 4.2%, 2.4%, 1.2% and 0% using the Aptima TV assay, culture, wet mount microscopy and Gram-stained microscopy, respectively. The sensitivity of culture and wet mount microscopy was only 57.1% (95% CI 36.5 to 75.5) and 28.6% (95% CI 13.8 to 50.0), respectively.ConclusionsA 4.2% positivity rate ofT. vaginaliswas found among women in Pelotas, Brazil and the routine diagnostic test (wet mount microscopy) and culture had low sensitivities. More sensitive diagnostic tests (NAATs) and enhanced testing of symptomatic and asymptomatic at-risk women are crucial to mitigate the transmission of TV infection, TV-associated sequelae and enhanced HIV acquisition and transmission.
Human Papilloma Virus Specific Immunogenicity and Dysfunction of CD8+ T Cells in Head and Neck Cancer
Authors: Krishna Sri , Ulrich Peaches , Wilson Eric , Parikh Falguni , Narang Pooja , Yang Shanshan , Read Amelia K. , Kim-Schulze Seunghee , Park Jin G. , Posner Marshall , Wilson Sayres Melissa A. , Sikora Andrew , Anderson Karen S. 
Published: August 2018

AbstractHuman papillomavirus subtype 16 (HPV16) is the primary cause of an increasing number of head and neck squamous cell carcinomas (HNSCC), providing strong rationale for T-cell immune therapies against HPV+ HNSCC. Here we assess immunogenicity of HPV16-specific CD8+ T cells (CTL) and characterize HPV-specific mechanisms of T-cell dysfunction. We identified 16 strong and 29 moderately immunogenic CTL-epitopes from HPV16 E2, E6, and E7 antigens restricted by 12 common HLA class I alleles. E2-specific CTL-reactivity was higher in patients with HPV+ HNSCC than in healthy controls (&gt;3-fold; P = 0.026). Patient-derived E2, E6, and E7 peripheral CTLs exhibited heterogeneity in dysfunctional phenotypes. Immunogenomic analyses of 119 HNSCC transcriptomes revealed high T-cell infiltration and dysfunction in HPV+ HNSCC and correlation of HPV antigen expression with T-cell exhaustion gene signatures. Indoleamine 2,3-dioxygenase (IDO-1) was strongly expressed in HPV+ HNSCC versus HPV− HNSCC (P = 0.001) and correlated with E7 expression (R2 = 0.84; P = 0.033). Combination treatment with PD-1 blockade and IDO-1 inhibition overcame profound CTL-dysfunction, enhancing HPV+ HNSCC sensitivity to CTL-cytotoxicity in vitro (up to 10-fold in E7-CTLs, P = 0.011). Our findings implicate mechanisms of T-cell escape in HPV+ HNSCC, wherein high tumoral HPV-antigen load results in high expression of immune dysfunction genes on tumor cells (e.g., IDO-1), and dysfunction of HPV-specific CTLs (e.g., E7, E2-CTLs). The HPV16 CTL-epitopes identified in this study, in combination with blockade of HPV+ HNSCC-specific PD-1/IDO-1 checkpoints, may be useful for targeted immunotherapy.Significance: This study evaluates the HPV antigen T-cell immunogenicity role of inhibitory receptors and other exhaustion markers in the cytotoxic function of HPV antigen-specific CTLs and identifies combined inhibition of PD-1/IDO-1 as a strategy to enhance CTL targeting of HPV+ HNSCC. Cancer Res; 78(21); 6159–70. ©2018 AACR.
Intrathecal Viral Vector Delivery of Trastuzumab Prevents or Inhibits Tumor Growth of Human HER2-Positive Xenografts in Mice
Authors: Rothwell William T. , Bell Peter , Richman Laura K. , Limberis Maria P. , Tretiakova Anna P. , Li Mingyao , Wilson James M. 
Published: August 2018

Abstract
Breast cancer brain metastases are a deadly sequela of primary breast tumors that overexpress human epidermal growth factor receptor 2 (HER2); median survival for patients with these tumors is 10 to 13 months from the time of diagnosis. Current treatments for HER2-positive breast cancer brain metastases are invasive, toxic, and largely ineffective. Here, we have developed an adeno-associated virus serotype 9 (AAV9) vector to express the anti-HER2 monoclonal antibody trastuzumab (Herceptin) in vivo. A single prophylactic intrathecal administration of AAV9.trastuzumab vector in a novel orthotopic Rag1−/− murine xenograft model of HER2-positive breast cancer brain metastases significantly increased median survival, attenuated brain tumor growth, and preserved both the HER2 antigen specificity and the natural killer cell–associated mechanism of action of trastuzumab. When administered as a tumor treatment, AAV9.trastuzumab increased median survival. Dose-escalation studies revealed that higher doses of AAV9.trastuzumab resulted in smaller tumor volumes. Our results indicate that intrathecal AAV9.trastuzumab may provide significant antitumor activity in patients with HER2-positive breast cancer brain metastases.
Significance: Intrathecal delivery of trastuzumab via adeno-associated virus has the potential to become a novel, integral part of adjuvant therapy for patients with HER2-positive breast cancer brain metastases. Cancer Res; 78(21); 6171–82. ©2018 AACR.
Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem–like Cells
Authors: Högström Jenny , Heino Sarika , Kallio Pauliina , Lähde Marianne , Leppänen Veli-Matti , Balboa Diego , Wiener Zoltán , Alitalo Kari 
Published: August 2018

Abstract
The homeobox transcription factor PROX1 is induced by high Wnt/β-catenin activity in intestinal adenomas and colorectal cancer, where it promotes tumor progression. Here we report that in LGR5+ colorectal cancer cells, PROX1 suppresses the Notch pathway, which is essential for cell fate in intestinal stem cells. Pharmacologic inhibition of Notch in ex vivo 3D organoid cultures from transgenic mouse intestinal adenoma models increased Prox1 expression and the number of PROX1-positive cells. Notch inhibition led to increased proliferation of the PROX1-positive colorectal cancer cells, but did not affect their ability to give rise to PROX1-negative secretory cells. Conversely, PROX1 deletion increased Notch target gene expression and NOTCH1 promoter activity, indicating reciprocal regulation between PROX1 and the Notch pathway in colorectal cancer. PROX1 interacted with the nucleosome remodeling and deacetylase (NuRD) complex to suppress the Notch pathway. Thus, our data suggests that PROX1 and Notch suppress each other and that PROX1-mediated suppression of Notch mediates its stem cell function in colorectal cancer.
Significance: These findings address the role of the PROX1 homeobox factor as a downstream effector of Wnt/β-catenin singling in colorectal cancer stem cells and show that PROX1 inhibits the Notch pathway and helps to enforce the stem cell phenotype and inhibit differentiation. Cancer Res; 78(20); 5820–32. ©2018 AACR.
Emerin Deregulation Links Nuclear Shape Instability to Metastatic Potential
Authors: Reis-Sobreiro Mariana , Chen Jie-Fu , Novitskaya Tatiana , You Sungyong , Morley Samantha , Steadman Kenneth , Gill Navjot Kaur , Eskaros Adel , Rotinen Mirja , Chu Chia-Yi , Chung Leland W.K. , Tanaka Hisashi , Yang Wei , Knudsen Beatrice S. , Tseng Hsian-Rong , Rowat Amy C. , Posadas Edwin M. , Zijlstra Andries , Di Vizio Dolores , Freeman Michael R. 
Published: August 2018

Abstract
Abnormalities in nuclear shape are a well-known feature of cancer, but their contribution to malignant progression remains poorly understood. Here, we show that depletion of the cytoskeletal regulator, Diaphanous-related formin 3 (DIAPH3), or the nuclear membrane–associated proteins, lamin A/C, in prostate and breast cancer cells, induces nuclear shape instability, with a corresponding gain in malignant properties, including secretion of extracellular vesicles that contain genomic material. This transformation is characterized by a reduction and/or mislocalization of the inner nuclear membrane protein, emerin. Consistent with this, depletion of emerin evokes nuclear shape instability and promotes metastasis. By visualizing emerin localization, evidence for nuclear shape instability was observed in cultured tumor cells, in experimental models of prostate cancer, in human prostate cancer tissues, and in circulating tumor cells from patients with metastatic disease. Quantitation of emerin mislocalization discriminated cancer from benign tissue and correlated with disease progression in a prostate cancer cohort. Taken together, these results identify emerin as a mediator of nuclear shape stability in cancer and show that destabilization of emerin can promote metastasis.
Significance: This study identifies a novel mechanism integrating the control of nuclear structure with the metastatic phenotype, and our inclusion of two types of human specimens (cancer tissues and circulating tumor cells) demonstrates direct relevance to human cancer.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/21/6086/F1.large.jpg. Cancer Res; 78(21); 6086–97. ©2018 AACR.