bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contain-ed
Authors: Sheoran Amit , Sharma Puneet , Fahmy Sonia , Saxena Vinay 
Published: October 2017

Network Functions Virtualization (NFV) has enabled operators to dynamically place and allocate resources for network services to match workload requirements. However, unbounded end-to-end (e2e) latency of Service Function Chains (SFCs) resulting from distributed Virtualized Network Function (VNF) deployments can severely degrade performance. In particular, SFC instantiations with inter-data center links can incur high e2e latencies and Service Level Agreement (SLA) violations. These latencies can trigger timeouts and protocol errors with latency-sensitive operations.
Traditional solutions to reduce e2e latency involve physical deployment of service elements in close proximity. These solutions are, however, no longer viable in the NFV era. In this paper, we present our solution that bounds the e2e latency in SFCs and inter-VNF control message exchanges by creating micro-service aggregates based on the affinity between VNFs. Our system, Contain-ed, dynamically creates and manages affinity aggregates using light-weight virtualization technologies like containers, allowing them to be placed in close proximity and hence bounding the e2e latency. We have applied Contain-ed to the Clearwater IP Multimedia Subsystem and built a proof-of-concept. Our results demonstrate that, by utilizing application and protocol specific knowledge, affinity aggregates can effectively bound SFC delays and significantly reduce protocol errors and service disruptions.
Enhanced cerebral perfusion during brief exposures to cyclic intermittent hypoxemia
Authors: Liu Xiaoli , Xu Diqun , Hall James R. , Ross Sarah , Chen Shande , Liu Howe , Mallet Robert T. , Shi Xiangrong 
Published: October 2017

Cerebral vasodilation and increased cerebral oxygen extraction help maintain cerebral oxygen uptake in the face of hypoxemia. This study examined cerebrovascular responses to intermittent hypoxemia in eight healthy men breathing 10% O2 for 5 cycles, each 6 min, interspersed with 4 min of room air breathing. Hypoxia exposures raised heart rate ( P < 0.01) without altering arterial pressure, and increased ventilation ( P < 0.01) by expanding tidal volume. Arterial oxygen saturation ([Formula: see text]) and cerebral tissue oxygenation ([Formula: see text]) fell ( P < 0.01) less appreciably in the first bout (from 97.0 ± 0.3% and 72.8 ± 1.6% to 75.5 ± 0.9% and 54.5 ± 0.9%, respectively) than the fifth bout (from 94.9 ± 0.4% and 70.8 ± 1.0% to 66.7 ± 2.3% and 49.2 ± 1.5%, respectively). Flow velocity in the middle cerebral artery ( VMCA) and cerebrovascular conductance increased in a sigmoid fashion with decreases in [Formula: see text] and [Formula: see text]. These stimulus-response curves shifted leftward and upward from the first to the fifth hypoxia bouts; thus, the centering points fell from 79.2 ± 1.4 to 74.6 ± 1.1% ( P = 0.01) and from 59.8 ± 1.0 to 56.6 ± 0.3% ( P = 0.002), and the minimum VMCA increased from 54.0 ± 0.5 to 57.2 ± 0.5 cm/s ( P = 0.0001) and from 53.9 ± 0.5 to 57.1 ± 0.3 cm/s ( P = 0.0001) for the [Formula: see text]- VMCA and [Formula: see text]- VMCA curves, respectively. Cerebral oxygen extraction increased from prehypoxia 0.22 ± 0.01 to 0.25 ± 0.02 in minute 6 of the first hypoxia bout, and remained elevated between 0.25 ± 0.01 and 0.27 ± 0.01 throughout the fifth hypoxia bout. These results demonstrate that cerebral vasodilation combined with enhanced cerebral oxygen extraction fully compensated for decreased oxygen content during acute, cyclic hypoxemia. NEW & NOTEWORTHY Five bouts of 6-min intermittent hypoxia (IH) exposures to 10% O2 progressively reduce arterial oxygen saturation ([Formula: see text]) to 67% without causing discomfort or distress. Cerebrovascular responses to hypoxemia are dynamically reset over the course of a single IH session, such that threshold and saturation for cerebral vasodilations occurred at lower [Formula: see text] and cerebral tissue oxygenation ([Formula: see text]) during the fifth vs. first hypoxia bouts. Cerebral oxygen extraction is augmented during acute hypoxemia, which compensates for decreased arterial O2 content.
Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma
Authors: Byron Sara A. , Tran Nhan L. , Halperin Rebecca F. , Phillips Joanna J. , Kuhn John G. , de Groot John F. , Colman Howard , Ligon Keith L. , Wen Patrick Y. , Cloughesy Timothy F. , Mellinghoff Ingo K. , Butowski Nicholas A. , Taylor Jennie W. , Clarke Jennifer L. , Chang Susan M. , Berger Mitchel S. , Molinaro Annette M. , Maggiora Gerald M. , Peng Sen , Nasser Sara , Liang Winnie S. , Trent Jeffrey M. , Berens Michael E. , Carpten John D. , Craig David W. , Prados Michael D. 
Published: October 2017

Abstract
Purpose: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generation sequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma.
Experimental Design: We conducted a prospective genomics-informed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome sequencing and tumor RNA sequencing were performed to identify molecular targets for potential matched therapy. A multidisciplinary molecular tumor board issued treatment recommendations based on the genomic results, blood–brain barrier penetration of the indicated therapies, drug–drug interactions, and drug safety profiles. Feasibility of generating genomics-informed treatment recommendations within 35 days of surgery was assessed.
Results: Of the 20 patients enrolled in the study, 16 patients had sufficient tumor tissue for analysis. Exome sequencing was completed for all patients, and RNA sequencing was completed for 14 patients. Treatment recommendations were provided within the study's feasibility time frame for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor board recommendations. Two patients reached 12-month progression-free survival, both adhering to treatments based on the molecular profiling results. One patient remained on treatment and progression free 21 months after surgery, 3 times longer than the patient's previous time to progression. Analysis of matched nonenhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations.
Conclusions: Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system–penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma. Clin Cancer Res; 24(2); 295–305. ©2017 AACR.
See related commentary by Wick and Kessler, p. 256
Circulating Tumor Cells from Different Vascular Sites Exhibit Spatial Heterogeneity in Epithelial and Mesenchymal Composition and Distinct Clinical Significance in Hepatocellular Carcinoma
Authors: Sun Yun-Fan , Guo Wei , Xu Yang , Shi Yin-Hong , Gong Zi-Jun , Ji Yuan , Du Min , Zhang Xin , Hu Bo , Huang Ao , Chen George G. , Lai Paul B.S. , Cao Ya , Qiu Shuang-Jian , Zhou Jian , Yang Xin-Rong , Fan Jia 
Published: October 2017

Abstract
Purpose: The spatial heterogeneity of phenotypic and molecular characteristics of CTCs within the circulatory system remains unclear. Herein, we mapped the distribution and characterized biological features of CTCs along the transportation route in hepatocellular carcinoma (HCC).
Experimental Design: In 73 localized HCC patients, blood was drawn from peripheral vein (PV), peripheral artery (PA), hepatic veins (HV), infrahepatic inferior vena cava (IHIVC), and portal vein (PoV) before tumor resection. Epithelial and mesenchymal transition (EMT) phenotype in CTCs were analyzed by a 4-channel immunofluorescence CellSearch assay and microfluidic quantitative RT-PCR. The clinical significance of CTCs from different vascular sites was evaluated.
Results: The CTC number and size gradient between tumor efferent vessels and postpulmonary peripheral vessels was marked. Tracking the fate of CTC clusters revealed that CTCs displayed an aggregated–singular-aggregated manner of spreading. Single-cell characterization demonstrated that EMT status of CTCs was heterogeneous across different vascular compartments. CTCs were predominantly epithelial at release, but switched to EMT-activated phenotype during hematogeneous transit via Smad2 and β-catenin related signaling pathways. EMT activation in primary tumor correlated with total CTC number at HV, rather than epithelial or EMT-activated subsets of CTCs. Follow-up analysis suggested that CTC and circulating tumor microemboli burden in hepatic veins and peripheral circulation prognosticated postoperative lung metastasis and intrahepatic recurrence, respectively.
Conclusions: The current data suggested that a profound spatial heterogeneity in cellular distribution and biological features existed among CTCs during circulation. Multivascular measurement of CTCs could help to reveal novel mechanisms of metastasis and facilitate prediction of postoperative relapse or metastasis pattern in HCC. Clin Cancer Res; 24(3); 547–59. ©2017 AACR.
Allogeneic Human Double Negative T Cells as a Novel Immunotherapy for Acute Myeloid Leukemia and Its Underlying Mechanisms
Authors: Lee JongBok , Minden Mark D. , Chen Weihsu C. , Streck Elena , Chen Branson , Kang Hyeonjeong , Arruda Andrea , Ly Dalam , Der Sandy D. , Kang Sohyeong , Achita Paulina , D'Souza Cheryl , Li Yueyang , Childs Richard W. , Dick John E. , Zhang Li 
Published: October 2017

Abstract
Purpose: To explore the potential of ex vivo expanded healthy donor–derived allogeneic CD4 and CD8 double-negative cells (DNT) as a novel cellular immunotherapy for leukemia patients.
Experimental Design: Clinical-grade DNTs from peripheral blood of healthy donors were expanded and their antileukemic activity and safety were examined using flow cytometry–based in vitro killing assays and xenograft models against AML patient blasts and healthy donor–derived hematopoietic cells. Mechanism of action was investigated using antibody-mediated blocking assays and recombinant protein treatment assays.
Results: Expanded DNTs from healthy donors target a majority (36/46) of primary AML cells, including 9 chemotherapy-resistant patient samples in vitro, and significantly reduce the leukemia load in patient-derived xenograft models in a DNT donor–unrestricted manner. Importantly, allogeneic DNTs do not attack normal hematopoietic cells or affect hematopoietic stem/progenitor cell engraftment and differentiation, or cause xenogeneic GVHD in recipients. Mechanistically, DNTs express high levels of NKG2D and DNAM-1 that bind to cognate ligands preferentially expressed on AML cells. Upon recognition of AML cells, DNTs rapidly release IFNγ, which further increases NKG2D and DNAM-1 ligands’ expression on AML cells. IFNγ pretreatment enhances the susceptibility of AML cells to DNT-mediated cytotoxicity, including primary AML samples that are otherwise resistant to DNTs, and the effect of IFNγ treatment is abrogated by NKG2D and DNAM-1–blocking antibodies.
Conclusions: This study supports healthy donor–derived allogeneic DNTs as a therapy to treat patients with chemotherapy-resistant AML and also reveals interrelated roles of NKG2D, DNAM-1, and IFNγ in selective targeting of AML by DNTs. Clin Cancer Res; 24(2); 370–82. ©2017 AACR.
Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients
Authors: Schimrigk Sebastian , Marziniak Martin , Neubauer Christine , Kugler Eva Maria , Werner Gudrun , Abramov-Sommariva Dimitri 
Published: October 2017

Treatment of neuropathic pain (NP) symptoms associated with multiple sclerosis (MS) is frequently insufficient. Yet, cannabis is still rarely offered for treatment of pain. This clinical trial aimed at showing the positive benefit-risk ratio of dronabinol. Two hundred forty MS patients with central NP entered a 16-weeks placebo-controlled phase-III study followed by a 32-weeks open-label period. One hundred patients continued therapy for overall up to 119 weeks. Primary endpoint was change of pain intensity on the 11-point Numerical Rating Scale over a 16-weeks treatment period. Safety was assessed on the basis of adverse reactions (ARs), signs of dependency and abuse. Pain intensity during 16-weeks dronabinol and placebo treatment was reduced by 1.92 and 1.81 points without significant difference in between (<i>p</i> = 0.676). Although the proportion of patients with ARs was higher under dronabinol compared to placebo (50.0 vs. 25.9%), it decreased during long-term use of dronabinol (26%). No signs of drug abuse and only one possible case of dependency occurred. The trial results demonstrate that dronabinol is a safe long-term treatment option.
Jean-Martin Charcot (1825–1893): A Treatment Approach Gone Astray?
Authors: Walusinski Olivier 
Published: October 2017

Jean-Martin Charcot’s reputation remains that of a physician who took little interest in treatments for the neurological diseases he did much to identify. After reviewing the limited number of medicinal remedies of slight effectiveness at Charcot’s disposal, we analyze in this review the numerous therapeutic tests that he conducted: vibratory medicine for Parkinson’s disease, treatment of tabes by suspension technique, metallotherapy and moral ­treatment for hysteria. Understanding that he fully and completely adhered to the far-reaching heredity-based theories of his day makes it possible to perceive his natural and fundamental pessimism. By drawing on both ­ancestral traditions and innovative approaches, Charcot “combined genius with charlatanism” in a surprising way: he demonstrated genius in the area of nosology, and a sort of charlatanism in the area of treatments.
Neuropsychological Training of Attention Improves MS-Related Fatigue: Results of a Randomized, Placebo-Controlled, Double-Blind Pilot Study
Authors: Flachenecker Peter , Meissner Heike , Frey Rebecca , Guldin Wolfgang 
Published: October 2017

<b><i>Background:</i></b> Attentional deficits may be pathophysiologically relevant in MS-associated fatigue. <b><i>Patients and Methods:</i></b> Thirty MS patients with fatigue and attentional deficits in neuropsychological testing participated in this randomized, placebo-controlled, double-blind trial. The intervention group (IG; <i>n</i> = 14) was treated with 10 h of computerized, specific neuropsychological training performing simple reaction time tasks, whereas the control group (CG; <i>n</i> = 16) also runs through computerized, but unspecific neuropsychological training using tasks without time components. The subjective feeling of fatigue was assessed with the Würzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS) questionnaire, and testing of alertness was used as an objective measure at baseline and after the 2-week study period. <b><i>Results:</i></b> Reaction times of alertness were significantly decreased in IG but not CG after 2 weeks. The subjective feeling of fatigue was ameliorated in both groups but more pronounced in IG. Effect sizes were below 0.7 for alertness and WEIMuS scores in CG but large and clinically meaningful in IG for both measures. <b><i>Conclusions:</i></b> Our pilot study suggests that neuropsychological training of attention may improve both measures of fatigue. The parallel improvement of attentional deficits and subjective fatigue after specific neuropsychological training support previous findings that fatigue may be at least partially caused by impaired intensity of attention.
<b>A note on the population status and threats on two endemic and Endangered species of <I>Garcinia</I> of Agasthyamalai Biosphere Reserve, Tamil Nadu, India</b>
Authors: Manikandan G. , Ramasubbu R. 
Published: October 2017

The genus Garcinia comprises c. 35 species in India many of which are endemic and economically important with immense medicinal properties. The two species viz., Garcinia imberti and G. travancorica are lesser-known endemic medium-sized straight-stemmed trees with horizontal branches. The trees are distributed in the restricted forest areas (700–1,500 m) of Agasthyamalai Biosphere Reserve. Both the species are dioecious trees and have male and female flowers in two different individuals, sometimes at a distance of a few kilometers from each other. A large number of mature individuals of these species have been over-exploited from Agasthyamalai Biosphere Reserve and therefore a few mature individuals and seedlings alone exist. The populations were severely fragmented and exist in a few locations of natural forest areas. The number of mature individuals recorded in G. imbertI and G. travancorica was 127±14 and 112±14 respectively in the entire distributional areas. There was an extreme fluctuation observed every year in the case of flowering and fruiting and also in the number of individuals due to the disturbance in the forest ecosystem. Both species have been included under IUCN threatened category and therefore they need effective conservation measures.
Impact of CD14 Polymorphisms on Anti-Apolipoprotein A-1 IgG-Related Coronary Artery Disease Prediction in the General Population
Authors: Antiochos Panagiotis , Marques-Vidal Pedro , Virzi Julien , Pagano Sabrina , Satta Nathalie , Hartley Oliver , Montecucco Fabrizio , Mach François , Kutalik Zoltan , Waeber Gerard , Vollenweider Peter , Vuilleumier Nicolas 
Published: October 2017

Objective—
We aimed to determine whether autoantibodies against apoA-1 (apolipoprotein A-1; anti-apoA-1 IgG) predict incident coronary artery disease (CAD), defined as adjudicated incident myocardial infarction, angina, percutaneous coronary revascularization, or bypass grafting, in the general population. We further investigated whether this association is modulated by a functional CD14 receptor single nucleotide polymorphism.

Approach and Results—

In a prospectively studied, population-based cohort of 5220 subjects (mean age 52.6±10.7 years, 47.4% males), followed over a median period of 5.6 years, subjects positive versus negative for anti-apoA-1 IgG presented a total CAD rate of 3.9% versus 2.8% (
P
=0.077) and a nonfatal CAD rate of 3.6% versus 2.3% (
P
=0.018), respectively. After multivariate adjustment for established cardiovascular risk factors, the hazard ratios of anti-apoA-1 IgG for total and nonfatal CAD were: hazard ratio=1.36 (95% confidence interval, 0.94–1.97;
P
=0.105) and hazard ratio=1.53 (95% confidence interval, 1.03–2.26;
P
=0.034), respectively. In subjects with available genetic data for the C260T
rs2569190
single nucleotide polymorphism in the CD14 receptor gene (n=4247), we observed a significant interaction between anti-apoA-1 IgG and
rs2569190
allele status with regards to CAD risk, with anti-apoA-1 IgG conferring the highest risk for total and nonfatal CAD in non-TT carriers, whereas being associated with the lowest risk for total and nonfatal CAD in TT homozygotes (
P
for interaction =0.011 and
P
for interaction =0.033, respectively).

Conclusions—
Anti-apoA-1 IgG are independent predictors of nonfatal incident CAD in the general population. The strength of this association is dependent on a functional polymorphism of the CD14 receptor gene, a finding suggesting a gene–autoantibody interaction for the development of CAD.
Avian Sensor Packages for Meteorological Measurements
Authors: Thomas Rick M. , MacKenzie A. Rob , Reynolds S. James , Sadler Jonathan P. , Cropley Ford , Bell Simon , Dugdale Stephen J. , Chapman Lee , Quinn Andrew , Cai Xiaoming 
Published: October 2017

Abstract
The increasing miniaturization of accurate, reliable meteorological sensors and logging systems allows the deployment of sensor packages on lightweight airborne platforms. Here, we demonstrate the safe and humane use of avian species (white-tailed and Spanish imperial eagles) to carry a prototype miniature sensor package to measure temperature with a 5-Hz response and ±0.2°C resolution. This technique could allow sensor deployment above complex urban terrain, where such data are urgently required. Recent meteorological work has been facilitated by using unmanned aerial vehicles (UAVs), but their use within, and adjacent to, urban areas is heavily controlled. The package contains a wind speed sensor, a GPS, a pressure altimeter, and accelerometers. Four flight tests were conducted in a steep valley (glen) at a remote Scottish location that provided contrasting vertical temperature profiles. The glen was instrumented with additional meteorological equipment at the bird launch and landing sites. Vertical temperature profile data from the raptors indicated the success of this approach with absolute temperatures and lapse rates consistent with those measured by the weather stations. Movement and airspeed data aided the interpretation of finescale temperature profiles in complex terrain. As well as the potential for meteorological sensing, this work is of interest to the avian ecology and behavior communities and to aerodynamicists interested in developing airborne robotics to mimic aspects of bird flight. These sensors are being miniaturized further for deployment on other bird species in urban areas for rapid, repeatable, and reliable measurements, with the potential to fulfill a measurement niche above the urban canopy.
A 65-yr Climatology of Unusual Tracks of Tropical Cyclones in the Vicinity of China’s Coastal Waters during 1949–2013
Authors: Zhang Xuerong , Li Ying , Zhang Da-Lin , Chen Lianshou 
Published: October 2017

AbstractDespite steady improvements in tropical cyclone (TC) track forecasts, it still remains challenging to predict unusual TC tracks (UNTKs), such as the tracks of sharp turning or looping TCs, especially after they move close to coastal waters. In this study 1059 UNTK events associated with 564 TCs are identified from a total of 1320 TCs, occurring in the vicinity of China’s coastal waters, during the 65-yr period of 1949–2013, using the best-track data archived at the China Meteorological Administration’s Shanghai Typhoon Institute. These UNTK events are then categorized into seven types of tracks—sharp westward turning (169), sharp eastward turning (86), sharp northward turning (223), sharp southward turning (46), looping (153), rotating (199), and zigzagging (183)—on the basis of an improved UNTK classification scheme. Results show significant annual variability of unusual tracking TCs, ranging between 2 and 18 per year, many of which experience more than one UNTK event in the same or different UNTK types during their life spans. The monthly distribution of the UNTK events resembles that of TCs, with more occurring in June–November. An analysis of their spatial distributions reveals that all of the UNTK events tend to take place in the areas to the south of 30°N, most frequently in the South China Sea and to the east of the Philippines. The results suggest that more attention be paid to the improved understanding and prediction of UNTK events so that the current positive trend in TC track forecast accuracy can continue for many years to come.