bluuebunny/crossref_metadata_2025_split huggingface dataset:
Left Ventricular Mechanical Discoordination in Nonischemic Hearts: Relationship with Left Ventricular Function, Geometry, and Electrical Dyssynchrony
Authors: Shimamoto Shinsaku , Ito Takahide , Nogi Shimpei , Kizawa Shun , Ishizaka Nobukazu 
Published: February 2014

BackgroundMechanical discoordination (MD) is known as a myocardial deformation of opposite strain during ejection, reflecting dyssynchronous electrical activation. We used speckle tracking echocardiography to examine the relationship between MD, left ventricular (LV) function and geometry, as well as electrical dyssynchrony in various nonischemic hearts.Methods and ResultsWe examined 131 subjects (left bundle branch block [LBBB] 27; dilated cardiomyopathy [DCM] without LBBB 33; LV hypertrophy 28; and normal heart 43) using circumferential strain rate analysis. Integration of positive (stretch) and negative (shortening) components during the ejection time was obtained in the mid‐ventricular level for 6 myocardial segments, and MD was quantified as the stretch to shortening ratio (SSR). The SSR in the septal region (anteroseptal and septal segments) was markedly elevated in the LBBB and DCM groups compared with the other groups. With univariate analysis, SSR over the septal region was found to be correlated with QRS duration, LV end‐diastolic dimension, and LV ejection fraction. Multivariate analysis revealed that QRS duration and LV ejection fraction were significant independent determinants of SSR for the septal region.ConclusionsIn nonischemic hearts, electrical dyssynchrony and LV dysfunction may contribute synergistically to MD in the septal region. The finding that non‐LBBB DCM patients exhibited a certain amount of SSR may provide new insight into therapeutic strategies for cardiac resynchronization therapy.
CB1 augments mGluR5 function in medial prefrontal cortical neurons to inhibit amygdala hyperactivity in an arthritis pain model
Authors: Ji Guangchen , Neugebauer Volker 
Published: February 2014

AbstractThe medial prefrontal cortex (mPFC) serves executive control functions and forms direct connections with subcortical areas such as the amygdala. Our previous work showed abnormal inhibition of mPFC pyramidal cells and hyperactivity of amygdala output neurons in an arthritis pain model. To restore mPFC activity and hence control pain‐related amygdala hyperactivity this study focused on CB1 and mGluR5 receptors, which are important modulators of cortical functions. Extracellular single‐unit recordings of infralimbic mPFC pyramidal cells and of amygdala output neurons in the laterocapsular division of the central nucleus (CeLC) were made in anesthetised adult male rats. mPFC neurons were classified as ‘excited’ or ‘inhibited’ based on their response to brief innocuous and noxious test stimuli. After arthritis pain induction, background activity and evoked responses of excited neurons and background activity and inhibition of inhibited neurons decreased. Stereotaxic application of an mGluR5‐positive allosteric modulator (N‐cyclobutyl‐6‐((3‐fluorophenyl)ethynyl) nicotinamide hydrochloride, VU0360172) into the mPFC increased background and evoked activity of excited, but not inhibited, mPFC neurons under normal conditions but not in arthritis. A selective CB1 receptor agonist (arachidonyl‐2‐chloroethylamide) alone had no effect but restored the facilitatory effects of VU0360172 in the pain model. Coactivation of CB1 and mGluR5 in the mPFC inhibited the pain‐related activity increase of CeLC neurons but had no effect under normal conditions. The data suggest that excited mPFC neurons are inversely linked to amygdala output (CeLC) and that CB1 can increase mGluR5 function in this subset of mPFC neurons to engage cortical control of abnormally enhanced amygdala output in pain.
From genes to pain: nerve growth factor and hereditary sensory and autonomic neuropathy type V
Authors: Capsoni Simona 
Published: February 2014

AbstractHereditary sensory and autonomic neuropathy type V (HSAN V) is an autosomal recessive disorder characterized by the loss of deep pain perception. The anomalous pain and temperature sensations are due to the absence of nociceptive sensory innervation. The neurotrophin nerve growth factor (NGF), by binding to tropomyosin receptor A (TrkA) and p75NTR receptors, is essential for the development and survival of sensory neurons, and for pain perception during adulthood. Recently a homozygous missense mutation (R100W) in the NGF gene has been identified in HSAN V patients. Interestingly, alterations in NGF signalling, due to mutations in the NGF TRKA gene, have also been involved in another congenital insensitivity to pain, HSAN IV, characterized not only by absence of reaction to painful stimuli, but also anhidrosis and mental retardation. These symptoms are absent in HSAN V patients. Unravelling the mechanisms that underlie the differences between HSAN IV and V could assist in better understanding NGF biology. This review highlights the recent key findings in the understanding of HSAN V, including insights into the molecular mechanisms of the disease, derived from genetic studies of patients with this disorder.
N‐methylmesoporphyrin IX fluorescence as a reporter of strand orientation in guanine quadruplexes
Authors: Sabharwal Navin C. , Savikhin Victoria , Turek‐Herman Joshua R. , Nicoludis John M. , Szalai Veronika A. , Yatsunyk Liliya A. 
Published: February 2014

Guanine quadruplexes (GQ) are four‐stranded DNA structures formed by guanine‐rich DNA sequences. The formation of GQs inhibits cancer cell growth, although the detection of GQs in vivo has proven difficult, in part because of their structural diversity. The development of GQ‐selective fluorescent reporters would enhance our ability to quantify the number and location of GQs, ultimately advancing biological studies of quadruplex relevance and function. N‐methylmesoporphyrin IX (NMM) interacts selectively with parallel‐stranded GQs; in addition, its fluorescence is sensitive to the presence of DNA, making this ligand a possible candidate for a quadruplex probe. In the present study, we investigated the effect of DNA secondary structure on NMM fluorescence. We found that NMM fluorescence increases by about 60‐fold in the presence of parallel‐stranded GQs and by about 40‐fold in the presence of hybrid GQs. Antiparallel GQs lead to lower than 10‐fold increases in NMM fluorescence. Single‐stranded DNA, duplex, or i‐motif, induce no change in NMM fluorescence. We conclude that NMM shows promise as a ‘turn‐on’ fluorescent probe for detecting quadruplex structures, as well as for differentiating them on the basis of strand orientation.
The crayfish plague pathogen can infect freshwater‐inhabiting crabs
Authors: Svoboda Jiří , Strand David A. , Vrålstad Trude , Grandjean Frédéric , Edsman Lennart , Kozák Pavel , Kouba Antonín , Fristad Rosa F. , Bahadir Koca Seval , Petrusek Adam 
Published: February 2014

Summary

The oomycete Aphanomyces astaci is generally considered a parasite specific to freshwater crayfish, and it has become known as the crayfish plague pathogen. Old experimental work that reported transmission of crayfish plague to the Chinese mitten crab Eriocheir sinensis, and the ability of A. astaci to grow in non‐decapod crustaceans, has never been tested properly.

We re‐evaluated the host range of A. astaci by screening for the presence of A. astaci in two crab species cohabiting with infected crayfish in fresh waters, as well as in other higher crustaceans from such localities. The animals were tested with species‐specific quantitative PCR, and the pathogen determination was confirmed by sequencing of an amplified fragment of the nuclear internal transcribed spacer. Furthermore, we examined microscopically cuticle samples from presumably infected crab individuals for the presence of A. astaci‐like hyphae and checked for the presence of pathogen DNA in such samples.

Screenings of benthopelagic mysids, amphipods and benthic isopods did not suggest infection by A. astaci in non‐decapod crustaceans. In contrast, both studied lake populations of crabs (a native semiterrestrial species Potamon potamios in Turkey, and an invasive catadromous E. sinensis in Sweden) were infected with this parasite according to both molecular and microscopic evidence.

Analyses of polymorphic microsatellite loci demonstrated that A. astaci strains in the crabs and in cohabiting crayfish belonged to the same genotype group, suggesting crayfish as the source for crab infection.

The potential for A. astaci transmission in the opposite direction, from crabs to crayfish, and potential impact of this pathogen on populations of freshwater crabs require further investigations, because of possible consequences for crayfish and freshwater crab conservation and aquaculture.
A reassessment of global bioenergy potential in 2050
Authors: Searle Stephanie , Malins Chris 
Published: February 2014

AbstractMany climate change mitigation strategies rely on strong projected growth in biomass energy, supported by literature estimating high future bioenergy potential. However, expectations to 2050 are highly divergent. Examining the most widely cited studies finds that some assumptions in these models are inconsistent with the best available evidence. By identifying literature‐supported, up‐to‐date assumptions for parameters including crop yields, land availability, and costs, we revise upper‐end estimates of potential biomass availability from dedicated energy crops. Even allowing for the conversion of virtually all ‘unused’ grassland and savannah, we find that the maximum plausible limit to sustainable energy crop production in 2050 would be 40–110 EJ yr−1. Combined with forestry, crop residues, and wastes, the maximum limit to long‐term total biomass availability is 60–120 EJ yr−1 in primary energy. After accounting for current trends in bioenergy allocation and conversion losses, we estimate maximum potentials of 10–20 EJ yr−1 of biofuel, 20–40 EJ yr−1 of electricity, and 10–30 EJ yr−1 of heating in 2050. These findings suggest that many technical projections and aspirational goals for future bioenergy use could be difficult or impossible to achieve sustainably.
Multicenter validation study of anti‐programmed cell death‐1 antibody as a serological marker for type 1 autoimmune hepatitis
Authors: Miyake Yasuhiro , Yamamoto Kazuhide , Matsushita Hiroshi , Abe Masanori , Takahashi Atsushi , Umemura Takeji , Tanaka Atsushi , Nakamuta Makoto , Nakamoto Yasunari , Ueno Yoshiyuki , Saibara Toshiji , Takikawa Hajime , Yoshizawa Kaname , Ohira Hiromasa , Zeniya Mikio , Onji Morikazu , Tsubouchi Hirohito ,   Intractable Hepato‐Biliary Disease Study Group of Japan
Published: February 2014

AimRecently, serum levels of anti‐programmed cell death‐1 (anti‐PD‐1) antibodies have been reported to be useful for the discrimination of type 1 autoimmune hepatitis (AIH) from drug‐induced liver injury (DILI) and to be associated with clinical features of type 1 AIH. This multicenter study aimed to validate the usefulness of serum anti‐PD‐1 antibody as a serological marker for type 1 AIH.MethodsSerum samples before the initiation of corticosteroid treatment were obtained from 71 type 1 AIH patients and 37 DILI patients. Serum levels of anti‐PD‐1 antibodies were measured by indirect enzyme‐linked immunosorbent assay.ResultsSerum levels of anti‐PD‐1 antibodies were higher in type 1 AIH patients than in DILI patients (P < 0.001). The receiver–operator curve analysis showed that serum levels of anti‐PD‐1 antibodies were useful for the discrimination of type 1 AIH from DILI (area under the curve, 0.80). On the other hand, the multivariate Cox proportional hazard model showed that positivity for serum anti‐PD‐1 antibody, probable diagnosis based on the revised scoring system proposed by the International Autoimmune Hepatitis Group, and prothrombin activity of less than 60% were associated with the later normalization of serum transaminase levels. During the clinical course, the disease relapsed more frequently in patients positive for serum anti‐PD‐1 antibody (36% vs 11%).ConclusionThis study suggests that serum anti‐PD‐1 antibody is useful for the diagnosis of type 1 AIH as an auxiliary diagnostic marker, and that serum levels of anti‐PD‐1 antibodies reflect clinical features of type 1 AIH.
Clinical outcome and prognostic factors of patients with hepatocellular carcinoma and extrahepatic metastasis treated with sorafenib
Authors: Kawaoka Tomokazu , Aikata Hiroshi , Kan Hiromi , Fujino Hatsue , Fukuhara Takayuki , Kobayashi Tomoki , Naeshiro Noriaki , Miyaki Daisuke , Hiramatsu Akira , Imamura Michio , Kawakami Yoshiiku , Hyogo Hideyuki , Chayama Kazuaki 
Published: February 2014

AimThe purpose of this study was to assess the clinical outcome and identify prognostic factors following treatment of patients with advanced hepatocellular carcinoma (HCC) and extrahepatic metastasis with sorafenib.MethodsSixty‐one HCC patients with extrahepatic metastasis who were treated with sorafenib were enrolled in this retrospective cohort study.ResultsThe median survival time (MST) of all patients was 11 months. The median time to radiological progression was 4.2 months. The response rates (complete response [CR] + partial response [PR]) by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were 3.0% and 8.0%, respectively, while the disease control rates (CR + PR + stable disease) were 49% and 49%, respectively. Multivariate analysis identified T factor (intrahepatic tumor stage, T 0–2), response to disease control and des‐γ‐carboxy prothrombin (<2600 mAU/mL) as significant and independent determinants of survival. Intrahepatic tumor stage before treatment allows stratification of prognosis of patients treated with sorafenib. Four T0 patients remained alive. The MST of patients with T1 (n = 6), T2 (n = 10), T3 (n = 23) and T4 (n = 18) of intrahepatic tumor stage was 20, 23, 7 and 5 months, respectively. Among the progressive disease group, patients with T0–2 intrahepatic tumor stage had better prognosis than patients with T3–4.ConclusionIn HCC patients with extrahepatic metastasis who are treated with sorafenib, intrahepatic tumor stage was a significant and independent prognostic factor.
Factors affecting the success rate of buccal infiltration anaesthesia in the mandibular molar region
Authors: Kwon H. , Shin Y. , Cho S.‐Y. , Park S.‐H. , Jung I.‐Y. 
Published: February 2014

AbstractAimTo compare the anaesthetic efficacy of mandibular second premolar infiltration (SP) with that of mandibular first molar infiltration (FM) in inducing pulpal anaesthesia in the mandibular first molar. To further investigate the mechanisms of action that underlie mandibular infiltration, gender‐related differences in the anaesthetic efficacy were also assessed.MethodologyA total of 29 adult subjects randomly received two sets of SP and FM injections using one cartridge (1.7 mL) of 4% articaine and 1 : 100 000 adrenaline at two separate appointments. The responses of the teeth were assessed using an electronic pulp tester over a 30‐min period. A comparison of the anaesthetic success between the SP and FM infiltration routes was analysed using the McNemar's test. Gender‐related differences in the anaesthetic success of infiltration routes were assessed using the Fisher's exact test.ResultsFor the second premolar and the first and second molar teeth, the success rates of SP were 72.4%, 62.1% and 48.3%, whereas the success rates of FM were 75.9%, 51.7% and 55.1%, respectively. There were no significant differences between the success rates of SP and FM or between the rates obtained for each tooth. Significant gender‐related differences were observed for the second premolar (P < 0.01) and the first molar (P < 0.05) using FM. However, a significant difference was observed only for the second premolar using SP (P < 0.05).ConclusionsThe differences in the injection sites did not affect the anaesthetic success rates for the mandibular second premolar and molar teeth. However, articaine buccal infiltration produced a higher anaesthetic success rate in the second premolar and first molar teeth of Korean female patients.
T helper subsets & regulatory T cells: rethinking the paradigm in the clinical context of solid organ transplantation
Authors: Askar M. 
Published: February 2014

SummaryRecent years have witnessed remarkable expansion in the knowledge of how various immune/inflammatory cells and T helper (Th) cell subsets, including Th1, Th2, Th9, Th17, Th22, follicular T helper (Tfh) and Treg subpopulations, reciprocally regulate each other. This review highlights current understanding of the Th subsets paradigm, who are the old school players, who are the new kids on the block and how does each come to play in different clinical contexts in solid organ transplantation. The article commences with a brief overview of the development and characteristic cytokine profiles of individual members of the paradigm. However, the main focus of this review is on the current understanding of the Th subset paradigm, and how these unique subpopulations impact host responses towards solid organ allografts. More specifically, it will highlight the recent findings that implicate the paradigm in transplantation. The interplay among different subsets is discussed collectively in the clinical context of pretransplant immunological risk factors such as alloimmunization as well as post‐transplant immunological consequences such as rejection. Accumulating evidence suggests that Th17 cells play a role in the development of chronic allograft injury in transplantation of various organs. In vitro, tacrolimus suppressed Th1 and Th2 cells but not Th17 cells. Animal studies suggest that regulatory T cells (Treg)‐based therapies could be effective as mechanisms of long‐term drug‐free transplant tolerance in humans. Indeed, a dual role for TGF‐β and Foxp3 in induced tolerance has been proposed, in which TGF‐β stimulates Foxp3 expression and is associated with the induction of Treg‐facilitating acquisition of tolerance. Exploiting Th subsets' regulatory functions could potentially offer opportunities for immunological interventions in solid organ transplantation.
Photovoltaic Properties of Multiferroic BiFeO3/BiCrO3 Heterostructures
Authors: Chakrabartty Joyprokash , Nechache Riad , Li Shun , Nicklaus Mischa , Ruediger Andreaus , Rosei Federico 
Published: February 2014

We report a power conversion efficiency of ~0.01% in multistacking of BiFeO3/BiCrO3 bilayer thin films used as active layers in a photovoltaic (PV) device. The films were epitaxially deposited by pulse laser deposition onto (100) oriented CaRuO3‐coated LaAlO3 substrates and were subsequently illuminated with 1 sun (AM 1.5). The fill factor is determined to be 0.31%, a remarkable value for ferroelectric‐ and multiferroic‐based PV devices. Our results demonstrate that photocurrent density and photovoltage can be tuned by varying the thickness and number of respective bilayers in the improvement of PV properties of multiferroic heterostructures. The maximum photocurrent is generated at an optimal multilayer thickness of 60 nm, with its origin being mainly ascribed to the contribution of ferroelectric polarization.
Incremental Value of Larger Interventricular Conduction Time in Improving Cardiac Resynchronization Therapy Outcome in Patients with Different QRS Duration
Authors: D'ONOFRIO ANTONIO , BOTTO GIANLUCA , MANTICA MASSIMO , LA ROSA CONCETTO , OCCHETTA ERALDO , VERLATO ROBERTO , MOLON GIULIO , AMMENDOLA ERNESTO , VILLANI GIOVANNI Q. , BONGIORNI MARIA GRAZIA , BIANCHI VALTER , GELMINI GIAN PAOLO , VALSECCHI SERGIO , CIARDIELLO CARMINE 
Published: February 2014

Interventricular Electrical DelayIntroductionThe left ventricular (LV) pacing site and the magnitude of the electrical delay within the LV, as expressed by prolonged QRS duration, are major determinants of cardiac resynchronization therapy (CRT) efficacy. We investigated the incremental value of positioning the LV lead in areas of late activation in order to enhance the response to CRT in patients with different degrees of QRS complex lengthening.Methods and ResultsThis analysis was performed on 301 heart failure patients who received a CRT defibrillator. On implantation, the right ventricular (RV)‐to‐LV interval was measured as the delay between local activations recorded through the RV and LV leads in the final position. After 1 year, 171 (57%) patients displayed reverse LV remodeling, as measured by a ≥15% reduction in the LV end‐systolic volume. Both the RV‐to‐LV interval and its percentage value corrected for the QRS duration were significantly associated with a positive response to CRT. An RV‐to‐LV interval >80 milliseconds and an RV‐to‐LV interval/QRS >58% yielded the best prediction of reverse remodeling. Although the response to CRT decreased with shorter QRS duration in the overall population, patients with an RV‐to‐LV interval >80 milliseconds showed a response rate >65% in all QRS subgroups.ConclusionA longer RV‐to‐LV interval is associated with reverse LV remodeling after CRT. On implantation attempts could be made to maximize it when selecting the LV lead position, especially in patients with shorter QRS duration, and thus less likely to respond positively to CRT.
Weakened purifying selection leads to elevated mutation load under environmental sex determination
Authors: Freedberg S. , Debenport S. J. 
Published: February 2014

AbstractIn many gonochoristic taxa, sex is influenced by developmental environment, a system that can lead to temporal fluctuations in offspring sex ratio. Demographic models suggest that only short‐lived species with environmental sex determination (ESD) are negatively impacted by sex‐ratio fluctuations, yet these models fail to account for the potential mutation load associated with reductions in genetically effective population sizes. In this study, we developed a series of individual‐based simulation models that explore the fixation rates of mildly deleterious alleles under different sex‐determining systems and examine the impacts of variation in lifespan and offspring sex ratio. Populations with ESD exhibited increases in fixation rates in both short‐ and long‐lived populations, but substantial increases were limited to populations characterized by a combination of high sex‐ratio variation and short lifespan. Fixation rates were negatively associated with effective population size, indicating that purifying selection operates less efficiently under ESD relative to genotypic sex determination. Reductions in effective population size could be attributed to both intragenerational forces (unequal sex ratio) and intergenerational forces (variable census population sizes). Levels of temporal sex‐ratio variation calculated from wild populations of ESD species were capable of yielding large increases in fixation rates, although this relationship was strongly mediated by lifespan. Our results may help to explain the limited phylogenetic distribution of ESD in short‐lived taxa.