bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance of pre‐existing DNA methylation states through recurring excess‐light stress
Authors: Ganguly Diep R. , Crisp Peter A. , Eichten Steven R. , Pogson Barry J. 
Published: April 2018

AbstractThe capacity for plant stress priming and memory and the notion of this being underpinned by DNA methylation‐mediated memory is an appealing hypothesis for which there is mixed evidence. We previously established a lack of drought‐induced methylome variation inArabidopsis thaliana(Arabidopsis); however, this was tied to only minor observations of physiological memory. There are numerous independent observations demonstrating that photoprotective mechanisms, induced by excess‐light stress, can lead to robust programmable changes in newly developing leaf tissues. Although key signalling molecules and transcription factors are known to promote this priming signal, an untested question is the potential involvement of chromatin marks towards the maintenance of light stress acclimation, or memory. Thus, we systematically tested our previous hypothesis of a stress‐resistant methylome using a recurring excess‐light stress, then analysing new, emerging, and existing tissues. The DNA methylome showed negligible stress‐associated variation, with the vast majority attributable to stochastic differences. Yet, photoacclimation was evident through enhanced photosystem II performance in exposed tissues, and nonphotochemical quenching and fluorescence decline ratio showed evidence of mitotic transmission. Thus, we have observed physiological acclimation in new and emerging tissues in the absence of substantive DNA methylome changes.
Transarterial chemoembolization in children to treat unresectable hepatocellular carcinoma
Authors: Weiss Krista E. , Sze Daniel Y. , Rangaswami Arun A. , Esquivel Carlos O. , Concepcion Waldo , Lebowitz Edward A. , Kothary Nishita , Lungren Matthew P. 
Published: April 2018

AbstractChildren with unresectable HCC have a dismal prognosis and few approved treatment options. TACE is an effective treatment option for adults with HCC, but experience in children is very limited. Retrospective analysis was performed of 8 patients aged 4‐17 years (4 male, mean 12.5 years) who underwent TACE for unresectable HCC. Response to TACE was evaluated by change in AFP, RECIST and tumor volume, PRETEXT, and transplantation eligibility by UCSF and Milan criteria. Post‐procedure mean follow‐up was 8.2 years. Mean overall change in tumor volume for the 8 patients was 51%. Percent change in AFP ranged from a decrease of 100% to an increase of 89.3%, with a mean change of −49.6%. Two patients did not undergo resection or transplantation and died of progressive disease. Six patients underwent orthotopic liver transplantation with mean first TACE‐to‐transplant interval of 141 days (range 11‐514). Following transplantation, 5 patients were alive at the end of the follow‐up period and one died of recurrent disease. Based on our initial experience, TACE for children with unresectable HCC appears to be a safe and effective method for managing hepatic tumor burden and for downstaging and bridging to liver transplantation.
Evaluation of the molecular lipid organization in millimeter‐sized stratum corneum by synchrotron X‐ray diffraction
Authors: Suzuki T. , Uchino T. , Hatta I. , Miyazaki Y. , Kato S. , Sasaki K. , Kagawa Y. 
Published: April 2018

AbstractBackgroundThe aim of this study was to investigate whether the lamellar and lateral structure of intercellular lipid of stratum corneum (SC) can be evaluated from millimeter‐sized SC (MSC) by X‐ray diffraction.Materials and MethodsA 12 mm × 12 mm SC sheet from hairless mouse was divided into 16 pieces measuring 3 mm × 3 mm square. From another sheet, 4 pieces of ultramillimeter‐sized SC (USC:1.5 mm × 1.5 mm square) were prepared. Small and wide‐angle X‐ray diffraction (SAXD and WAXD) measurements were performed on each piece. For MSC and USC, changes in the lamellar and lateral structure after the application of d‐limonene were measured.ResultsThe intensity of SAXD peaks due to the lamellar phase of long periodicity phase (LPP) and WAXD peaks due to the lateral hydrocarbon chain‐packing structures varied in MSC and USC pieces, although over the 12 mm × 12 mm SC sheet. These results indicated that the intercellular lipid components and their proportion appeared nearly uniform. Application of d‐limonene on MSC and USC piece with strong peaks in SAXD and the WAXD resulted in the disappearance of peaks due to the lamellar phase of LPP and decrease in peak intensity for the lateral hydrocarbon chain‐packing structures. These changes are consistent with normal‐sized sample results.ConclusionWe found that the selection of a sample piece with strong diffraction peaks due to the lamellar and lateral structure enabled evaluation of the SC structure in small‐sized samples by X‐ray diffraction.
Enhanced immunity in intradermal vaccination by novel hollow microneedles
Authors: Ogai N. , Nonaka I. , Toda Y. , Ono T. , Minegishi S. , Inou A. , Hachiya M. , Fukamizu H. 
Published: April 2018

AbstractBackgroundThe intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity.MethodsWe fabricated a hollow microneedle unit made of poly‐glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure ID delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either ID delivery with microneedles or SC administration with a 27‐G stainless needle of graded vaccine doses.ResultsThe unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to ID distribution. Histologically, a wedge‐shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination.ConclusionsThe microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of ID delivery as an immunogenic option to enhance vaccination efficacy.
Extracorporeal photopheresis in the treatment of acute graft‐versus‐host disease: a single‐center experience
Authors: Niittyvuopio Riitta , Juvonen Eeva , Heiskanen Jouni , Lindström Vesa , Nihtinen Anne , Sahlstedt Leila , Volin Liisa 
Published: April 2018

BACKGROUNDSteroid‐refractory acute graft‐versus‐host disease (aGVHD) is a serious complication after hematopoietic stem cell transplantation. The long‐term outcome of the patients is poor. Various immunosuppressive agents have been proposed as the second‐line therapy but none of them has turned out more effective than the others. Extracorporeal photopheresis (ECP) is a treatment option that does not predispose the patients to severe side effects of the immunosuppressive drugs.STUDY DESIGN AND METHODSWe analyzed the treatment results of ECP in 52 patients with steroid‐refractory or steroid‐dependent aGVHD. Eighty‐one percent of the patients suffered from a severe, Grade III or IV, aGVHD. ECP was started alone as the second‐line treatment in 23 patients and in combination with an immunosuppressive drug in 18 patients. Eleven patients received ECP as the third‐line or later treatment.RESULTSA total of 62% of the patients responded, with 48% achieving complete response. In the patients with complete or partial response, the probabilities of survival at 4 years were 54 and 17%, respectively. The outcome of nonresponders was poor. The 1‐year overall survivals of the patients with ECP as the second‐line treatment either alone or in combination with an immunosuppressive drug or as the third‐line treatment were 51, 28, and 18%, respectively. In multivariate analysis, starting ECP no later than 10 days after the start of the first‐line treatment correlated with a good response and a consequent survival benefit.CONCLUSIONExtracorporeal photopheresis is an effective and well‐tolerated treatment that should be considered as a second‐line treatment for aGVHD.
Casein kinase 2 inhibition impairs spontaneous and oxytocin‐induced contractions in late pregnant mouse uterus
Authors: Suhas K. S. , Parida Subhashree , Gokul Chandrasekaran , Srivastava Vivek , Prakash E. , Chauhan Sakshi , Singh Thakur Uttam , Panigrahi Manjit , Telang Avinash G. , Mishra Santosh K. 
Published: April 2018

New Findings
What is the central question of this study?
Does the inhibition of the protein kinase casein kinase 2 (CK2) alter the uterine contractility?

What is the main finding and its importance?
Inhibition of CK2 impaired the spontaneous and oxytocin‐induced contractility in late pregnant mouse uterus. This finding suggests that CK2 is a novel pathway mediating oxytocin‐induced contractility in the uterus and thus opens up the possibility for this class of drugs to be developed as a new class of tocolytics.

AbstractThe protein kinase casein kinase 2 (CK2) is a ubiquitously expressed serine or threonine kinase known to phosphorylate a number of substrates. The aim of this study was to assess the effect of CK2 inhibition on spontaneous and oxytocin‐induced uterine contractions in 19 day pregnant mice. The CK2 inhibitor CX‐4945 elicited a concentration‐dependent relaxation in late pregnant mouse uterus. CX‐4945 and another selective CK2 inhibitor, apigenin, also inhibited the oxytocin‐induced contractile response in late pregnant uterine tissue. Apigenin also blunted the prostaglandin F2α response, but CX‐4945 did not. Casein kinase 2 was located in the lipid raft fractions of the cell membrane, and disruption of lipid rafts was found to reverse its effect. The results of the present study suggest that CK2, located in lipid rafts of the cell membrane, is an active regulator of spontaneous and oxytocin‐induced uterine contractions in the late pregnant mouse.
Impaired modulation of postjunctional α1‐ but not α2‐adrenergic vasoconstriction in contracting forearm muscle of postmenopausal women
Authors: Kruse Nicholas T. , Hughes William E. , Ueda Kenichi , Hanada Satoshi , Feider Andrew J. , Iwamoto Erika , Bock Joshua M. , Casey Darren P. 
Published: April 2018

Key points
Contraction‐mediated blunting of postjunctional α‐adrenergic vasoconstriction (functional sympatholysis) is attenuated in skeletal muscle of ageing males, brought on by altered postjunctional α1‐ and α2‐adrenergic receptor sensitivity. The extent to which postjunctional α‐adrenergic vasoconstriction occurs in the forearms at rest and during exercise in postmenopausal women remains unknown.
The novel findings indicate that contraction‐mediated blunting of α1‐ (via intra‐arterial infusion of phenylephrine) but not α2‐adrenergic (via intra‐arterial infusion of dexmedetomidine) vasoconstriction was attenuated in postmenopausal women compared to young women.
Additional important findings revealed that postjunctional α‐adrenergic vasoconstrictor responsiveness at rest does not appear to be affected by age in women.
Collectively, these results contribute to our understanding of local neurovascular control at rest and during exercise with age in women.
AbstractContraction‐mediated blunting of postjunctional α‐adrenergic vasoconstriction (functional sympatholysis) is attenuated in older males; however, direct confirmation of this effect remains unknown in postmenopausal women (PMW). The present study examined whether PMW exhibit augmented postjunctional α‐adrenergic receptor vasoconstriction at rest and during forearm exercise compared to young women (YW). Eight YW (24 ± 1 years) and eight PMW (65 ± 1 years) completed a series of randomized experimental trials: (1) at rest, (2) under high flow (adenosine infusion) conditions and (3) during 6 min of forearm exercise at relative (20% of maximum) and absolute (7 kg) intensities. Phenylephrine (α1‐agonist) or dexmedetomidine (α2‐agonist) was administered during the last 3 min of each trial to elicit α‐adrenergic vasoconstriction. Forearm vascular conductance (FVC) was calculated from blood flow and blood pressure. Vasoconstrictor responsiveness was identified as the change in FVC (%) during α‐adrenergic agonist infusions from baseline (resting trial) or from steady‐state conditions (high flow and exercise trials). During resting and high flow trials, the %FVC during α1‐ and α2‐agonist stimulation was similar between YW and PMW. During exercise, α1‐mediated vasoconstriction was blunted in YW vs. PMW at relative (−6 ± 2% vs. −15 ± 3%) and absolute (−4 ± 2% vs. −14 ± 5%) workloads, such that blood flow and FVC were lower in PMW (P < 0.05 for all). Conversely, α2‐mediated vasoconstriction was similar between YW and PMW at relative (−22 ± 3% vs. −22 ± 4%; P > 0.05) and absolute (−19 ± 3% vs. ‐18 ± 4%; P > 0.05) workloads. Collectively, these findings demonstrate that despite similar α‐adrenergic vasoconstrictor responsiveness at rest, PMW have a decreased ability to attenuate α1‐adrenergic vasoconstriction in contracting skeletal muscle.
Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae of Sequence Type 36
Authors: Feng Yu , Lu Yang , Yao Zhihong , Zong Zhiyong 
Published: April 2018

ABSTRACT

Sequence type 36 (ST36)
Klebsiella pneumoniae
is distributed worldwide. We found an ST36
K. pneumoniae
clinical isolate that was carbapenem resistant, carried
bla
KPC-2
, had mucoid regulator gene
rmpA
, and exhibited high virulence. The finding suggests the emergence of carbapenem-resistant hypervirulent
K. pneumoniae
of ST36, and surveillance of carbapenem-resistant hypervirulent
K. pneumoniae
is required.
Failure and post-failure analysis of submarine mass movements using geomorphology and geomechanical concepts
Authors: Locat Jacques 
Published: April 2018

Abstract

Access to submarine slopes is usually limited and it is often difficult to rely on deep cores or
in situ
measurements to determine the geotechnical characteristics of the sediments involved in a slide when carrying out back-analyses of submarine mass movements and their consequences. The approach presented here uses geomorphology and basic geomechanical concepts to reduce uncertainties in slope stability and mobility analyses. It shows how geomorphology can be used to select the geomechanical input parameters required in failure and post-failure analyses. Typical parameters derived from such analyses are related to the strength of the material, the pore water pressure at the time of failure, and the rheological properties of post-failure debris or mud flows.
Charting the Algorithmic Complexity of Waypoint Routing
Authors: Amiri Saeed Akhoondian , Foerster Klaus-Tycho , Jacob Riko , Schmid Stefan 
Published: April 2018

Modern computer networks support interesting new routing models in which traffic flows from a source sto a destination t can be flexibly steered through a sequence of waypoints, such as (hardware) middleboxes or (virtualized) network functions (VNFs), to create innovative network services like service chains or segment routing. While the benefits and technological challenges of providing such routing models have been articulated and studied intensively over the last years, less is known about the underlying algorithmic traffic routing problems.
The goal of this paper is to provide the network community with an overview of algorithmic techniques for waypoint routing and also inform about limitations due to computational hardness. In particular, we put the waypoint routing problem into perspective with respect to classic graph theoretical problems. For example, we find that while computing a shortest path from a source s to a destination t is simple (e.g., using Dijkstra's algorithm), the problem of finding a shortest route from s to t via a single waypoint already features a deep combinatorial structure.
Thoughts and Recommendations from the ACM SIGCOMM 2017 Reproducibility Workshop
Authors: Saucez Damien , Iannone Luigi 
Published: April 2018

Ensuring the reproducibility of results is an essential part of experimental sciences, including computer networking. Unfortunately, as highlighted recently, a large portion of research results are hardly, if not at all, reproducible, raising reasonable lack of conviction on the research carried out around the world.
Recent years have shown an increasing awareness about reproducibility of results as an essential part of research carried out by members of the ACM SIGCOMM community. To address this important issue, ACM has introduced a new policy on results and artifacts review and badging. The policy defines the terminology to be used to assess results and artifacts but does not specify the review process or how to make research reproducible.
During SIGCOMM'17 a side workshop has been organized with the specific purpose to tackle this issue. The objective being to trigger discussion and activity in order to craft recommendations on how to introduce incentives for authors to share their artifacts, and the details on how to use them, as well as defining the process to be used.
This editorial overviews the workshop activity and summarizes the main discussions and outcomes.
A Survey on Artifacts from CoNEXT, ICN, IMC, and SIGCOMM Conferences in 2017
Authors: Flittner Matthias , Mahfoudi Mohamed Naoufal , Saucez Damien , Wählisch Matthias , Iannone Luigi , Bajpai Vaibhav , Afanasyev Alex 
Published: April 2018

Reproducibility of artifacts is a cornerstone of most scientific publications. To improve the current state and strengthen ongoing community efforts towards reproducibility by design, we conducted a survey among the papers published at leading ACM computer networking conferences in 2017: CoNEXT, ICN, IMC, and SIGCOMM.
The objective of this paper is to assess the current state of artifact availability and reproducibility based on a survey. We hope that it will serve as a starting point for further discussions to encourage researchers to ease the reproduction of scientific work published within the SIGCOMM community. Furthermore, we hope this work will inspire program chairs of future conferences to emphasize reproducibility within the ACM SIGCOMM community as well as will strengthen awareness of researchers.
CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia
Authors: Ajiro Masahiko , Sakai Hiroyuki , Onogi Hiroshi , Yamamoto Makoto , Sumi Eriko , Sawada Teruo , Nomura Takashi , Kabashima Kenji , Hosoya Takamitsu , Hagiwara Masatoshi 
Published: April 2018

Abstract
Purpose: Cervical cancer is one of the leading causes of cancer-related deaths among women worldwide. The purpose of this study is to assess the therapeutic effect of the newly developed cyclin-dependent kinase 9 (CDK9) inhibitor FIT-039 on cervical neoplasia induced by human papillomavirus (HPV) infection.
Experimental Design: We examined FIT-039 for its effect on HPV gene expression in HPV+ cervical cancer cells. Primary keratinocytes monolayer and organotypic raft culture models were used to evaluate HPV viral replication and cervical intraepithelial neoplasia (CIN) phenotypes. Preclinical pharmacokinetics and toxicity tests for FIT-039 were also conducted. Finally, the anti-HPV effect of FIT-039 was further examined in vivo, using HPV+ cervical cancer xenografts.
Results: FIT-039 inhibits HPV replication and expression of E6 and E7 viral oncogenes, restoring tumor suppressors p53 and pRb in HPV+ cervical cancer cells. The therapeutic effect of FIT-039 was demonstrated in CIN model of an organotypic raft culture, where FIT-039 suppressed HPV18-induced dysplasia/hyperproliferation with reduction in viral load. FIT-039 also repressed growth of HPV16+, but not HPV− cervical cancer xenografts without any significant adverse effects. Safety and pharmacokinetics of FIT-039 were confirmed for systemic and topical routes.
Conclusions: The CDK9 inhibitor FIT-039 showed potent anti-HPV activity without significant toxicity in preclinical studies. Thus, FIT-039 is expected to be a novel therapeutic for CIN to prevent cervical cancer. Clin Cancer Res; 24(18); 4518–28. ©2018 AACR.
Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population
Authors: Li Yanping , Pan An , Wang Dong D. , Liu Xiaoran , Dhana Klodian , Franco Oscar H. , Kaptoge Stephen , Di Angelantonio Emanuele , Stampfer Meir , Willett Walter C. , Hu Frank B. 
Published: April 2018

Background:
Americans have a shorter life expectancy compared with residents of almost all other high-income countries. We aim to estimate the impact of lifestyle factors on premature mortality and life expectancy in the US population.

Methods:

Using data from the Nurses’ Health Study (1980–2014; n=78 865) and the Health Professionals Follow-up Study (1986–2014, n=44 354), we defined 5 low-risk lifestyle factors as never smoking, body mass index of 18.5 to 24.9 kg/m
2
, ≥30 min/d of moderate to vigorous physical activity, moderate alcohol intake, and a high diet quality score (upper 40%), and estimated hazard ratios for the association of total lifestyle score (0–5 scale) with mortality. We used data from the NHANES (National Health and Nutrition Examination Surveys; 2013–2014) to estimate the distribution of the lifestyle score and the US Centers for Disease Control and Prevention WONDER database to derive the age-specific death rates of Americans. We applied the life table method to estimate life expectancy by levels of the lifestyle score.

Results:
During up to 34 years of follow-up, we documented 42 167 deaths. The multivariable-adjusted hazard ratios for mortality in adults with 5 compared with zero low-risk factors were 0.26 (95% confidence interval [CI], 0.22–0.31) for all-cause mortality, 0.35 (95% CI, 0.27–0.45) for cancer mortality, and 0.18 (95% CI, 0.12–0.26) for cardiovascular disease mortality. The population-attributable risk of nonadherence to 5 low-risk factors was 60.7% (95% CI, 53.6–66.7) for all-cause mortality, 51.7% (95% CI, 37.1–62.9) for cancer mortality, and 71.7% (95% CI, 58.1–81.0) for cardiovascular disease mortality. We estimated that the life expectancy at age 50 years was 29.0 years (95% CI, 28.3–29.8) for women and 25.5 years (95% CI, 24.7–26.2) for men who adopted zero low-risk lifestyle factors. In contrast, for those who adopted all 5 low-risk factors, we projected a life expectancy at age 50 years of 43.1 years (95% CI, 41.3–44.9) for women and 37.6 years (95% CI, 35.8–39.4) for men. The projected life expectancy at age 50 years was on average 14.0 years (95% CI, 11.8–16.2) longer among female Americans with 5 low-risk factors compared with those with zero low-risk factors; for men, the difference was 12.2 years (95% CI, 10.1–14.2).

Conclusions:
Adopting a healthy lifestyle could substantially reduce premature mortality and prolong life expectancy in US adults.