bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling tandem AAG8‐MEK inhibition in melanoma cells
Authors: Sun Bing , Kawahara Masahiro , Nagamune Teruyuki 
Published: March 2014

AbstractDrug resistance presents a challenge to the treatment of cancer patients, especially for melanomas, most of which are caused by the hyperactivation of MAPK signaling pathway. Innate or acquired drug‐resistant relapse calls for the investigation of the resistant mechanisms and new anti‐cancer drugs to provide implications for the ultimate goal of curative therapy. Aging‐associated gene 8 (AAG8, encoded by the SIGMAR1 gene) is a chaperone protein profoundly elaborated in neurology. However, roles of AAG8 in carcinogenesis remain unclear. Herein, we discover AAG8 antagonists as new MEK inhibitors in melanoma cells and propose a novel drug combination strategy for melanoma therapy by presenting the experimental evidences. We report that specific antagonism of AAG8, efficiently suppresses melanoma cell growth and migration through, at least in part, the inactivation of the RAS‐CRAF‐MEK signaling pathway. We further demonstrate that melanoma cells that are resistant to AAG8 antagonist harbor refractory CRAF‐MEK activity. MEK acts as a central mediator for anti‐cancer effects and also for the resistance mechanism, leading to our proposal of tandem AAG8‐MEK inhibition in melanoma cells. Combination of AAG8 antagonist and very low concentration of a MEK inhibitor synergistically restricts the growth of drug‐resistant cells. These data collectively pinpoint AAG8 as a potential target and delineate a promising drug combination strategy for melanoma therapy.
Emission Behavior of Secondary Thioamide‐Based Cationic Pincer Platinum(II) Complexes in the Aggregate State
Authors: Honda Hiroya , Ogawa Yasuyuki , Kuwabara Junpei , Kanbara Takaki 
Published: March 2014

AbstractCationic pincer platinum(II) complexes bearing secondary thioamide units showed aggregation‐induced emission (AIE) activity in chloroform/hexane and methanol/water mixtures. Hydrogen bonding of the thioamide units and interionic interactions contributed to the AIE activities.
Active actinidin retains function upon gastro‐intestinal digestion and is more thermostable than the E‐64‐inhibited counterpart
Authors: Grozdanovic Milica M , Ostojic Sanja , Aleksic Ivana , Andjelkovic Uros , Petersen Arnd , Gavrovic‐Jankulovic Marija 
Published: March 2014

AbstractBACKGROUNDActinidin is a cysteine protease and major allergen from kiwi fruit. When purified under specific native conditions, actinidin preparations from fresh kiwi fruit contain both an active and inactive form of this enzyme. In this study, biochemical and immunological properties upon simulated gastro‐intestinal digestion, as well as thermal stability, were investigated for both active and E‐64‐inhibited actinidin.RESULTSActive actinidin retained its primary structure and proteolytic activity after 2 h of simulated gastric digestion, followed by 2 h of intestinal digestion, as assessed by SDS‐PAGE, zymography and mass spectroscopy. Immunological reactivity of active actinidin was also preserved, as tested by immunoelectrophoresis. The E‐64 inhibited actinidin was fully degraded after 1 h of pepsin treatment. Differential scanning calorimetry showed that active actinidin has one transition maximum temperature (Tm) at 73.9°C, whereas in the E‐64–actinidin complex the two actinidin domains unfolded independently, with the first domain having a Tm value of only 61°C.CONCLUSIONActive actinidin is capable of reaching the intestinal mucosa in a proteolytically active and immunogenic state. Inhibitor binding induces changes in the actinidin molecule that go beyond inhibition of proteolytic activity, also influencing the digestion stability and Tm values of actinidin, features important in the characterisation of food allergens. © 2014 Society of Chemical Industry
Tirasemtiv amplifies skeletal muscle response to nerve activation in humans
Authors: Hansen Richard , Saikali Khalil G. , Chou Willis , Russell Alan J. , Chen Michael M. , Vijayakumar Vipin , Stoltz Randall R. , Baudry Stephane , Enoka Roger M. , Morgans David J. , Wolff Andrew A. , Malik Fady I. 
Published: March 2014

ABSTRACTIntroduction: In this study we tested the hypothesis that tirasemtiv, a selective fast skeletal muscle troponin activator that sensitizes the sarcomere to calcium, could amplify the response of muscle to neuromuscular input in humans. Methods: Healthy men received tirasemtiv and placebo in a randomized, double‐blind, 4‐period, crossover design. The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot. The force–frequency relationship of tibialis anterior dorsiflexion was assessed after dosing. Results: Tirasemtiv increased force produced by the tibialis anterior in a dose‐, concentration‐, and frequency‐dependent manner with the largest increases [up to 24.5% (SE 3.1), P < 0.0001] produced at subtetanic nerve stimulation frequencies (10 Hz). Conclusions: The data confirm that tirasemtiv amplifies the response of skeletal muscle to nerve input in humans. This outcome provides support for further studies of tirasemtiv as a potential therapy in conditions marked by diminished neuromuscular input. Muscle Nerve 50: 925–931, 2014
Preparation and Characterization of Preyssler‐type Phosphotungstic Acid, H15–n[P5W30O110Mn+], with Different Encapsulated Cations (M = Na, Ca, Bi, Eu, Y, or Ce), and their Thermal Stability and Acid Catalyst Properties
Authors: Takahashi Keita , Sano Tsuneji , Sadakane Masahiro 
Published: March 2014

AbstractPreyssler‐type phosphotungstic acid, H15–n[P5W30O110Mn+], with different encapsulated cations (M = Ca2+, Bi3+, Eu3+, Y3+, Ce3+) were prepared and characterized using 31P NMR and IR spectroscopy, acid‐base titration, and elemental analyses. The pKa value of an internal proton of Ca‐encapsulated derivative, [P5W30O110CaHin]12–, was estimated to be 5.9. Their thermal stabilities and acid catalyst properties were compared with a parent Na‐encapsulated Preyssler‐type phoshotungstic acid, H14[P5W30O110Na]. Thermal stability of the Preyssler‐type molecule was increased by exchanging the encapsulated Na+ with Bi3+, Eu3+, or Ce3+, with keeping their high acidic properties.
On the lifetimes of evaporating droplets
Authors: Stauber J. M. , Wilson S. K. , Duffy B. R. , Sefiane K. 
Published: March 2014

AbstractThe complete description of the lifetime of a droplet on a solid substrate evaporating in a ‘stick–slide’ mode is obtained. The unexpectedly subtle relationship between the lifetime of such a droplet and the lifetimes of initially identical droplets evaporating in the extreme modes (namely the constant contact radius and constant contact angle modes) is described and summarised in an appropriate master diagram. In particular, it is shown that the lifetime of a droplet is not, in general, constrained by the lifetimes of the extreme modes.
Evaluating the impact of the Baby-Friendly Hospital Initiative on breast-feeding rates: a multi-state analysis
Authors: Hawkins Summer Sherburne , Stern Ariel Dora , Baum Christopher F , Gillman Matthew W 
Published: March 2014

AbstractObjectiveTo evaluate the impact of the Baby-Friendly Hospital Initiative (BFHI) on breast-feeding initiation and duration overall and according to maternal education.DesignQuasi-experimental study using data from five states (Alaska, Maine, Nebraska, Ohio, Washington) that participated in the Pregnancy Risk Assessment Monitoring System from 1999 to 2009. Using differences-in-differences models that included year and hospital fixed effects, we compared rates of breast-feeding initiation and duration (any and exclusive breast-feeding for ≥4 weeks) before and after BFHI accreditation between mothers who gave birth in hospitals that were accredited or became accredited and mothers from matched non-BFHI facilities. We stratified analyses into lower and higher education groups.SettingThirteen BFHI hospitals and nineteen matched non-BFHI facilities across five states in the USA.SubjectsMothers (n 11 723) who gave birth in BFHI hospitals and mothers (n 13 604) from nineteen matched non-BFHI facilities.ResultsAlthough we did not find overall differences in breast-feeding initiation between birth facilities that received BFHI accreditation compared with non-Baby-Friendly facilities (adjusted coefficient = 0·024; 95 % CI −0·00, 0·51), breast-feeding initiation increased by 3·8 percentage points among mothers with lower education who delivered in Baby-Friendly facilities (P = 0·05), but not among mothers with higher education (adjusted coefficient = 0·002; 95 % CI −0·04, 0·05). BFHI accreditation also increased exclusive breast-feeding for ≥4 weeks by 4·5 percentage points (P = 0·02) among mothers with lower education who delivered in BFHI facilities.ConclusionsBy increasing breast-feeding initiation and duration among mothers with lower education, the BFHI may reduce socio-economic disparities in breast-feeding.
The Spatial Hearing Questionnaire: Data From Individuals With Normal Hearing
Authors: Perreau Ann E. , Spejcher Bryn , Ou Hua , Tyler Richard 
Published: March 2014

PurposeAlthough a number of questionnaires are available to assess hearing aid benefit and general hearing disability, relatively few investigate spatial hearing ability in more complex listening situations. The aim of this study was to document the performance of individuals with normal hearing using the Spatial Hearing Questionnaire (SHQ; Tyler, Perreau, & Ji, 2009) and to compare performance with published data from cochlear implant (CI) users.MethodFifty-one participants with normal hearing participated. All participants completed the 24-item SHQ. Also, a factor analysis and reliability tests were performed.ResultsPerformance on the SHQ was high (87%) for the participants with normal hearing. Subjective ratings varied across different listening situations: Understanding speech in quiet (98%) was rated higher than sound localization (84%) and understanding speech in a background of noise (85%). Compared with previously published data (Tyler, Perreau, & Ji, 2009), listeners with normal hearing rated their spatial hearing ability significantly better than bilateral and unilateral CI users. Results confirmed that the SHQ is a reliable measure of spatial hearing ability for listeners with normal hearing.ConclusionsOverall, results indicated that the SHQ is able to capture expected differences between individuals with normal hearing and CI users. These new data can be used as targets following the provision of hearing devices.
Effects of gum chewing on postoperative bowel motility after caesarean section: a meta‐analysis of randomised controlled trials
Authors: Zhu Y‐P , Wang W‐J , Zhang S‐L , Dai B , Ye D‐W 
Published: March 2014

BackgroundGum chewing has been reported to enhance bowel motility and reduce postoperative ileus (POI). However, the efficacy remains imprecise for women following caesarean section.ObjectivesTo summarise and evaluate the current evidence for postoperative gum chewing on the recovery of bowel function following caesarean section.Search strategyWe searched studies from the following electronic databases: PubMed, EMBASE, SCOPUS and Cochrane Library from inception to 30 May 2013.Selection criteriaWe included randomised controlled trials (RCTs) of women after caesarean section; these RCTs should compared gum chewing with no gum chewing and reported on at least one of the outcomes: time to flatus, time to bowel sound, time to passing stool and length of hospital stay (LOS).Data collection and analysisStudy outcomes were presented as mean differences (for continuous data) with 95% confidence interval (95% CI). The risk of bias in the study results was assessed using the assessment tool from the Cochrane Handbook.Main resultsSix RCTs including 939 women were included in our meta‐analysis. The pooled results demonstrated that gum chewing is superior to no gum chewing with a reduction of 6.42 hours (95% CI −7.55 to −5.29) for time to first flatus, 3.62 hours (95% CI −6.41 to −0.83) for time to first bowel sound, 6.58 hours (95% CI −10.10 to −3.07) for time to first stool and 5.94 hours (95% CI −9.39 to −2.49) for LOS. In addition, no evidence emerged for any side effects caused by gum chewing.ConclusionsThe current evidence suggests that gum chewing is associated with early recovery of bowel motility and shorter LOS for women after caesarean section. This safe and inexpensive intervention should be included in routine postoperative care following a caesarean section.
Novel Y‐chromosome polymorphisms in Chinese domestic yak
Authors: Li R. , Wang S.‐Q. , Xu S.‐Y. , Huang J.‐P. , Wang F.‐Q. , Ma Z.‐J. , Dang R.‐H. , Lan X.‐Y. , Chen H. , Lei C.‐Z. 
Published: March 2014

SummaryY‐chromosome‐specific haplotypes (Y‐haplotypes) constructed using single nucleotide polymorphisms (Y‐SNPs) in the MSY (male‐specific region of the Y‐chromosome) are valuable in population genetic studies. But sequence variants in the yak MSY region have been poorly characterized so far. In this study, we screened a total of 16 Y‐chromosome‐specific gene segments from the ZFY, SRY, UTY, USP9Y, AMELY and OFD1Y genes to identify Y‐SNPs in domestic yaks. Six novel Y‐SNPs distributed in the USP9Y (g.223C>T), UTY19 (g.158A>C and g.169C>T), AMELY2 (g.261C>T), OFD1Y9 (g.165A>G) and SRY4 (g.104G>A) loci, which can define three Y‐haplotypes (YH1, YH2 and YH3) in yaks, were discovered. YH1 was the dominant and presumably most ancient haplotype based on the comparison of UTY19 locus with other bovid species. Interestingly, we found informative UTY19 markers (g.158A>C and g.169C>T) that can effectively distinguish the three yak Y‐haplotypes. The nucleotide diversity was 1.7 × 10−4 ± 0.3 × 10−4, indicating rich Y‐chromosome diversity in yaks. We identified two highly divergent lineages (YH1 and YH2 vs. YH3) that share similar frequencies (YH1 + YH2: 0.82–0.89, YH3: 0.11–0.18) among all three populations. In agreement with previous mtDNA studies, we supported the hypothesis that the two highly divergent lineages (YH1 and YH2 vs. YH3) derived from a single gene pool, which can be explained by the reunion of at least two paternal populations with the divergent lineages already accumulated before domestication. We estimated a divergence time of 408 110 years between the two divergent lineages, which is consistent with the data from mitochondrial DNA in yaks.
Review article: permanent drug withdrawal is desirable and achievable for autoimmune hepatitis
Authors: Czaja A. J. 
Published: March 2014

SummaryBackgroundAutoimmune hepatitis can be rendered treatment‐free, but the difficulty, frequency and risks associated with the pursuit of this outcome are unclear.AimTo describe the frequency that autoimmune hepatitis can be rendered treatment‐free, identify the features that characterise these patients, examine the pathogenic pathways that may sustain or terminate the disease and indicate management protocols that can obtain this result.MethodsStudies cited in Pub Med from 1972–2014 for autoimmune hepatitis, treatment, relapse, remission and outcome were selected.ResultsThe frequency of a treatment‐free state varies from 19% to 40% in patients observed for ≥3 years after drug withdrawal. Complete laboratory resolution and reversion to normal liver tissue prior to drug withdrawal favours this response. The development of cirrhosis during therapy may increase treatment‐dependence. Persistent liver damage and the generation of neo‐antigens during the apoptosis of hepatocytes may perpetuate the disease. Genetic and age‐related effects on the vigour of the immune response may also contribute. Reversion to normal liver tissue is achieved in only 22% of patients during conventional corticosteroid therapy, and the emerging pharmacological and biological interventions may improve this frequency. A management strategy designed to achieve a treatment‐free state accommodates all candidates for this outcome, and it can be modified to a long‐term maintenance strategy as warranted by the clinical response.ConclusionsPermanent drug withdrawal is a treatment outcome that is desirable and achievable in patients with autoimmune hepatitis. Normalisation of liver tests and liver tissue during treatment enhances this occurrence.
Effects of Wind Energy Development on Nesting Ecology of Greater Prairie‐Chickens in Fragmented Grasslands
Authors: MCNEW LANCE B. , HUNT LYLA M. , GREGORY ANDREW J. , WISELY SAMANTHA M. , SANDERCOCK BRETT K. 
Published: March 2014

AbstractWind energy is targeted to meet 20% of U.S. energy needs by 2030, but new sites for development of renewable energy may overlap with important habitats of declining populations of grassland birds. Greater Prairie‐Chickens (Tympanuchus cupido) are an obligate grassland bird species predicted to respond negatively to energy development. We used a modified before–after control–impact design to test for impacts of a wind energy development on the reproductive ecology of prairie‐chickens in a 5‐year study. We located 59 and 185 nests before and after development, respectively, of a 201 MW wind energy facility in Greater Prairie‐Chicken nesting habitat and assessed nest site selection and nest survival relative to proximity to wind energy infrastructure and habitat conditions. Proximity to turbines did not negatively affect nest site selection (β = 0.03, 95% CI = −1.2–1.3) or nest survival (β = −0.3, 95% CI = −0.6–0.1). Instead, nest site selection and survival were strongly related to vegetative cover and other local conditions determined by management for cattle production. Integration of our project results with previous reports of behavioral avoidance of oil and gas facilities by other species of prairie grouse suggests new avenues for research to mitigate impacts of energy development.Efectos del Desarrollo de la Energía Eólica sobre la Ecología de Anidación de Gallinas de la Gran Pradera en Pastizales Fragmentados
Use of Multispecies Occupancy Models to Evaluate the Response of Bird Communities to Forest Degradation Associated with Logging
Authors: CARRILLO‐RUBIO EDUARDO , KÉRY MARC , MORREALE STEPHEN J. , SULLIVAN PATRICK J. , GARDNER BETH , COOCH EVAN G. , LASSOIE JAMES P. 
Published: March 2014

AbstractForest degradation is arguably the greatest threat to biodiversity, ecosystem services, and rural livelihoods. Therefore, increasing understanding of how organisms respond to degradation is essential for management and conservation planning. We were motivated by the need for rapid and practical analytical tools to assess the influence of management and degradation on biodiversity and system state in areas subject to rapid environmental change. We compared bird community composition and size in managed (ejido, i.e., communally owned lands) and unmanaged (national park) forests in the Sierra Tarahumara region, Mexico, using multispecies occupancy models and data from a 2‐year breeding bird survey. Unmanaged sites had on average higher species occupancy and richness than managed sites. Most species were present in low numbers as indicated by lower values of detection and occupancy associated with logging‐induced degradation. Less than 10% of species had occupancy probabilities >0.5, and degradation had no positive effects on occupancy. The estimated metacommunity size of 125 exceeded previous estimates for the region, and sites with mature trees and uneven‐aged forest stand characteristics contained the highest species richness. Higher estimation uncertainty and decreases in richness and occupancy for all species, including habitat generalists, were associated with degraded young, even‐aged stands. Our findings show that multispecies occupancy methods provide tractable measures of biodiversity and system state and valuable decision support for landholders and managers. These techniques can be used to rapidly address gaps in biodiversity information, threats to biodiversity, and vulnerabilities of species of interest on a landscape level, even in degraded or fast‐changing environments. Moreover, such tools may be particularly relevant in the assessment of species richness and distribution in a wide array of habitats.Uso de Modelos de Ocupación para Múltiples Especies para Evaluar la Respuesta de las Comunidades de Aves a la Degradación de Bosques Asociada con la Tala
Plasma cell myeloma with unusual morphology–A series of 6 cases
Authors: Gupta Ruchi , Hussain Naushad , Rahman Khaliqur , Nityanand Soniya 
Published: March 2014

AbstractMorphological variants of plasma cells have been described in cases of Plasma cell neoplasm. Presence of these atypical forms poses difficulty in morphological diagnosis and demands the use of ancillary techniques to ascertain the nature of these atypical cells. We hereby report a series of 6 such cases where the bone marrow examination showed plasma cells with atypical morphology, leading to varied differential diagnosis; however immunophenotyping by flow cytometry in adjunct to serum electrophoresis, immunofixation and free light chain assays confirmed the diagnosis.
Role of oxidative stress and autoimmunity in onset and progression of vitiligo
Authors: Laddha Naresh C. , Dwivedi Mitesh , Mansuri Mohmmad Shoab , Singh Mala , Gani Amina R. , Yeola Asmita P. , Panchal Vipul N. , Khan Fazal , Dave Darshana J. , Patel Ananddeep , Madhavan Shajil E. , Gupta Richa , Marfatia Zarna , Marfatia Yogesh S. , Begum Rasheedunnisa 
Published: March 2014

AbstractVitiligo is an acquired depigmentation disorder characterized by the loss of functional melanocytes from the epidermis. Two major theories of vitiligo pathogenesis include autoimmunity and oxidative stress‐mediated toxicity in melanocytes. The present study aimed to evaluate both the hypotheses in vitiligo patients and to investigate their role in the disease onset and progression. Antimelanocyte antibody levels and lipid peroxidation (LPO) levels were evaluated in 427 patients and 440 controls; antithyroid peroxidase (TPO) antibody levels were estimated in 102 patients and 72 controls. Patients showed a significant increase in LPO and antimelanocyte antibody levels compared to controls. Antimelanocyte antibody and LPO levels were higher in active vitiligo compared to stable. Only 9.8% of patients showed the presence of anti‐TPO antibodies in their circulation. Oxidative stress may be the initial triggering event to precipitate vitiligo in Gujarat population, which is exacerbated by contributing autoimmune factors together with oxidative stress.
Anatomical distribution analysis reveals lack of Langerin+ dermal dendritic cells in footpads and tail of C57BL/6 mice
Authors: Voisin Benjamin , Mairhofer David Gabriel , Chen Suzie , Stoitzner Patrizia , Mueller Christopher George , Flacher Vincent 
Published: March 2014

AbstractEpidermal Langerhans cells (LCs) and dermal dendritic cells (dDCs) capture cutaneous antigens and present them to T‐cells in lymph nodes (LNs). The function of LCs and Langerin+ dDCs was extensively studied in the mouse, but their anatomical repartition is unknown. Here, we found LCs in back skin, footpads and tail skin of C57BL/6, BALB/c, 129/Sv and CBA/J mice. Langerin+ dDCs were readily observed in back skin of all strains, but only in footpads and tail of BALB/c and CBA/J mice. Similarly, while LCs were equally present in all LNs and strains, Langerin+ dDCs were found in popliteal LNs (draining footpads) only in BALB/c and CBA/J mice. The sciatic LNs, which we identified as the major tail‐draining lymphoid organ, were devoid of Langerin+ dDCs in all strains. Thus, functionally different DCs reside in different skin areas, with variations among mouse strains, implying a potential impact on the cutaneous immune reaction.