bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and characteristics of naturally occurring sofosbuvir resistance‐associated variants in patients with hepatitis C virus genotype 1b infection
Authors: Ito Jun , Suda Goki , Yamamoto Yoshiya , Nagasaka Atsushi , Furuya Ken , Kumagai Kenichi , Kikuchi Hideaki , Miyagishima Takuto , Kobayashi Tomoe , Kimura Megumi , Yamasaki Kazushi , Umemura Machiko , Izumi Takaaki , Tsunematsu Seiji , Sato Fumiyuki , Tsukuda Yoko , Terashita Katsumi , Nakai Masato , Sho Takuya , Natsuizaka Mitsuteru , Morikawa Kenichi , Ogawa Koji , Sakamoto Naoya ,   for the NORTE Study Group
Published: February 2016

AimSofosbuvir (SOF), a nucleotide analog pro‐drug, targets hepatitis C virus (HCV) NS5B polymerase and shows potential for treating HCV infection, given its high efficacy and good barrier to resistance. However, in addition to the rare resistant‐associated variant (RAV) of non‐structural protein NS5B S282T, several new potential RAVs of SOF have been reported, especially related to HCV genotype 1b. However, the prevalence and characteristics of these RAVs have not been clarified.MethodsWe analyzed the prevalence of variants in the NS3/NS5A/NS5B regions in 96 patients treated with simeprevir (SMV) combination therapy, and the prevalence of RAVs in patients showing treatment failure was determined by direct‐ or deep‐sequencing methods. Associations between these potential RAVs and clinical factors were also analyzed.ResultsPrevalence of NS5B RAV C316N was high (46.9%, 45/96), whereas that of NS5B L159F was relatively low (1.04%, 1/96); however, deep sequencing showed that 30.0% of patients with C316N also had NS5B RAV L159F. Additionally, there was no significant relationship between the existence of potential NS5B and NS5A or NS3 RAVs. However, the presence of NS5B C316N was significantly associated with an HCV core amino acid 91 substitution. No significant difference was detected between each RAV and sustained virological response in simeprevir combination therapy.ConclusionWe provide clear evidence of the high prevalence of two potential naturally occurring NS5B RAVs (C316N and L159F) in Japan. It may be important to pay particular attention to these new potential RAVs, especially when using SOF‐based therapy in patients with RAVs due to previous direct‐acting antiviral therapy failure.
Effect of emulsifier type on physicochemical properties of water‐in‐oil emulsions for confectionery applications
Authors: Mazo Rivas Juan Camilo , Schneider Yvonne , Rohm Harald 
Published: February 2016

SummaryIn a first step of designing tailored confectionery masses using water‐in‐oil emulsions, a parameter screening on emulsion rheology and stability was carried out. The experimental set‐up included cocoa butter as continuous phase and the variation of the disperse phase (water, or 50% sucrose in water), two volume fraction levels and the type of emulsifier (lecithin, polyglycerol polyricinoleate (PGPR), ammonium phosphatide (YN) and blends of lecithin or YN with PGPR). Emulsions were characterised by microscopy, laser diffraction, analytical centrifugation and shear rheology. Results show multimodal droplet size distributions in lecithin‐ or YN‐stabilised emulsions, and droplets which tend to form aggregates and an internal network responsible for shear thinning. PGPR emulsions are characterised by monomodal droplet size distributions and smaller droplets without networking tendency. They exhibit Newtonian flow behaviour and a much higher stability against phase separation. In emulsifier blends, PGPR is mainly responsible for the modulation of physical properties of the emulsions.
The role of polysaccharides on the stability of colloidal particles of beer
Authors: Martinez Amezaga Nancy Maria J. , Benítez Elisa I. , Sosa Gladis L. , Peruchena Nélida M. , Lozano Jorge E. 
Published: February 2016

SummaryThis study aimed at understanding the influence of beer colloidal composition and size on physical stability of the colloidal suspensions in beer before filtration. The percentages of retention during filtration indicate that colloidal particles consist principally of polysaccharides (97.04%) and smaller amounts of proteins (2.87%) and polyphenols (0.22). The viscosity of a colloidal dispersion can be modelled as the sum of a hard‐sphere contribution and a colloidal force contribution. The colloidal force contribution is determined from the volume fraction of particles, the viscosity colloidal dispersion and the beer viscosity without particles. The volume fraction of particles could be estimated from the particle density and the total solid present in the beer. The fitting parameters of the correlation between the particles volume fraction and the colloidal force viscosity could explain the low stability of the colloidal particles of beer. This last determination is more specific than the simple viscosity of beer and could help to improve the prediction of the filtration flow.
Aggression on inpatient units: Clinical characteristics and consequences
Authors: Renwick Laoise , Stewart Duncan , Richardson Michelle , Lavelle Mary , James Karen , Hardy Claire , Price Owen , Bowers Len 
Published: February 2016

AbstractAggression and violence are widespread in UK Mental Health Trusts, and are accompanied by negative psychological and physiological consequences for both staff and other patients. Patients who are younger, male, and have a history of substance use and psychosis diagnoses are more likely to display aggression; however, patient factors are not solely responsible for violence, and there are complex circumstances that lead to aggression. Indeed, patient–staff interactions lead to a sizeable portion of aggression and violence on inpatient units, thus they cannot be viewed without considering other forms of conflict and containment that occur before, during, and after the aggressive incident. For this reason, we examined sequences of aggressive incidents in conjunction with other conflict and containment methods used to explore whether there were particular profiles to aggressive incidents. In the present study, 522 adult psychiatric inpatients from 84 acute wards were recruited, and there were 1422 incidents of aggression (verbal, physical against objects, and physical). Cluster analysis revealed that aggressive incident sequences could be classified into four separate groups: solo aggression, aggression–rule breaking, aggression–medication, and aggression–containment. Contrary to our expectations, we did not find physical aggression dominant in the aggression–containment cluster, and while verbal aggression occurred primarily in solo aggression, physical aggression also occurred here. This indicates that the management of aggression is variable, and although some patient factors are linked with different clusters, these do not entirely explain the variation.
Activity‐Related Postlesional Vestibular Reorganization
Authors: DIERINGER NORBERT 
Published: February 2016

AbstractThe synaptic convergence patterns of semicircular canal and macular afferent nerve inputs onto second‐order vestibular neurons reorganize in adult frogs after a change in the activity of vestibular nerve afferent fibers. Axotomized afferent nerve fibers become silent after a vestibular nerve lesion, and second‐order vestibular target neurons become disfacilitated. These changes initiate an activity‐related process that was studied in detail in vitro two months after a section of the ramus anterior (RA) of N. VIII. The postlesional reaction results in an expansion of signals, preferentially from intact, remaining afferent nerve fibers, but also from excitatory commissural and spinal ascending fibers. This process of expansion takes weeks, is graded in its extent, and reversible in case of a nerve regeneration, but is not competitive, i.e., the synaptic contacts from axotomized afferent nerve fibers are maintained without a change in their efficacy.Postlesional synaptic reorganization in the brainstem is restricted to the operated side, underlies the improved responsiveness of disfacilitated second‐order vestibular neurons, but also their altered spatial response tuning. The functional consequences of this reorganization were studied in vivo two months after RA nerve section by recording abducens nerve responses during linear or angular accelerations. The vector orientations of best responses of the abducens nerve of chronic RA frogs evoked by linear or angular acceleration differed from the vector orientations of controls. In chronic RA frogs, linear acceleration evoked contralesional abducens nerve responses that originated from the utricle on the intact side and from the lagena, a vertical macular organ in frogs. Such an inadequate lagenar response component was absent in controls and in the ipsilesional abducens nerve of chronic RA frogs. Similar differences were detected in the direction of abducens nerve responses of chronic RA frogs during angular acceleration. Thus, compensatory vestibulo‐ocular reflexes of chronic RA frogs became more symmetric in gain, but less precise in direction.
Commentary: The devastating effects of ignoring child maltreatment in psychiatry – a commentary on Teicher and Samson 2016
Authors: van der Kolk Bessel 
Published: February 2016

Despite the numerous studies over the past 30 years that have clarified the devastating effects of child maltreatment on mental and physical health, the role of trauma within the caregiving system remains unrecognized both in our diagnostic systems and in our dominant treatment paradigms. Research of people with histories of caregiver abuse and neglect consistently demonstrates problems with concentration, anger, panic, depression, food intake, drugs, and sleep, as well as decreased Heart RateVariability, higher levels of stress hormones, and reduced or impaired immune response. Their relationship between documented brain changes and psychopathology is complex.Traumatic life experiences during childhood and adolescence are far more common than expected. The Centers for Disease Control and Prevention estimates that child maltreatment may be the most costly public health issue in the United States, Eradicating child abuse in America would reduce the overall rate of depression by more than half, alcoholism by two‐thirds, and suicide, serious drug abuse, and domestic violence by three quarters. It would also have a significantly positive effect on workplace performance, and vastly decrease the need for incarceration. The current practice of applying multiple distinct comorbid diagnoses to traumatized children prevents a comprehensive treatment approach. Approaching their problems from a framework of memories of discreet traumatic ignores the fact that the damage affects the brain's neural circuitry and goes well beyond dealing with discrete painful events. Our great challenge is to learn to utilize the brain's neuroplasticity to reorganize defective brain circuits.
Commentary: Thinking outside the box about children's sleep – a commentary on Gregory and Sadeh (2016)
Authors: Stores Gregory 
Published: February 2016

AbstractThis commentary is intended to supplement the accompanying review of sleep problems in childhood psychiatric disorders by Gregory and Sadeh. A number of considerations are outlined because of their relevance to both clinical practice and research concerning assessment and treatment of sleep disturbance in children in general and especially those with psychiatric and/or neurological conditions. These considerations (which illustrate the importance of combined medical and psychological involvement) are as follows: the importance of screening for sleep disturbance which otherwise may well be overlooked; the need to specify sleep disorders rather than simply nonspecific sleep problems as this will guide choice of appropriate advice and treatment; the risk of sleep disorders being misdiagnosed because of clinicians' unfamiliarity with the sleep disorders field; the possibility that a child's sleep disturbance is of multiple aetiology; a wide range of treatments for disturbed sleep is now described from which a choice is possible given an accurate diagnosis; sleep problems may be intensified if a child's condition is complicated by intellectual disability but the same principles of assessment and management apply as in other children in the expectation that treatment can be effective.
Prognostic role of 25‐hydroxyvitamin D in patients with liver metastases from colorectal cancer treated with radiofrequency ablation
Authors: Facciorusso Antonio , Del Prete Valentina , Muscatiello Nicola , Crucinio Nicola , Barone Michele 
Published: February 2016

AbstractBackground and AimVitamin D is implicated in the etiology of several neoplastic diseases, but its relationship with colorectal cancer survival is still unclear. Aim of this study was to determine whether vitamin D levels influence survival outcomes in colorectal cancer liver metastases patients treated with percutaneous radiofrequency ablation.MethodsWe measured 25‐hydroxyvitamin D levels in 143 patients with 215 colorectal liver metastases who underwent radiofrequency ablation between 1999 and 2011 at our institution. The influence of 25‐hydroxyvitamin D levels on overall survival and time to recurrence was evaluated in univariate and multivariate Cox analyses.ResultsMedian age was 68 years (range 41–85), and median number of nodules was 2 (1–3) with a median maximum diameter of 26 mm (10–48). Median survival was 44 months (36–62), and survival rate was 91.4%, 46.5%, and 42.2% at 1, 4, and 5 years in the whole cohort. Median survival was 65 months (52–74) if 25‐hydroxyvitamin D >20 ng/mL and 34 months (24–41) if ≤20 ng/mL (P < 0.001). In the whole cohort, median time to recurrence was 34 months (26–47), 50 months (36–62) in the case of 25‐hydroxyvitamin D >20 ng/mL and 24 months (20–32) if ≤20 ng/mL (P < 0.001). Nodule size and 25‐hydroxyvitamin D resulted as significant predictors of both overall survival and time to recurrence in multivariate analysis.ConclusionsOur study provides support for the use of 25‐hydroxyvitamin D as a new predictor of outcome for colorectal liver metastases patients.
Association Between Anthropometric Measures and Long‐Term Survival in Frail Older Women: Observations from the Women's Health Initiative Study
Authors: Zaslavsky Oleg , Rillamas‐Sun Eileen , LaCroix Andrea Z. , Woods Nancy F. , Tinker Lesley F. , Zisberg Anna , Shadmi Efrat , Cochrane Barbara , Edward Beatrice J. , Kritchevsky Stephen , Stefanick Marcia L. , Vitolins Mara Z. , Wactawski‐Wende Jean , Zelber‐Sagi Shira 
Published: February 2016

ObjectivesTo evaluate the association between currently recommended guidelines and commonly used clinical criteria for body mass index (BMI), waist circumference (WC), and waist‐to‐hip ratio (WHR) and all‐cause mortality in frail older women.DesignLongitudinal prospective cohort study.SettingWomen's Health Initiative (WHI)—Observational Study.ParticipantsA sample of women aged 65–84 with complete data to characterize frailty in the third year of WHI follow‐up (N = 11,070).MeasurementsFrailty phenotype was determined using the modified Fried criteria. Information on anthropometric measures (BMI, WC, WHR) was collected in clinical examinations. Cox proportional hazards models were used to estimate the effect of BMI, WC, and WHR on mortality adjusted for demographic characteristics and health behaviors.ResultsOver a mean follow‐up of 11.5 years, there were 2,911 (26%) deaths in the sample. Women with a BMI from 25.0 to 29.9 kg/m2 (hazard rate ratio (HR) = 0.80, 95% confidence interval (CI) = 0.73–0.88) and those with a BMI from 30.0 to 34.9 kg/m2 (HR = 0.79, 95% CI = 0.71–0.88) had lower mortality than those with a BMI from 18.5 to 24.9 kg/m2. Women with a WHR greater than 0.8 had higher mortality (HR = 1.16, 95% CI = 1.07–1.26) than those with a WHR of 0.8 or less. No difference in mortality was observed according to WC. Stratifying according to chronic morbidity or smoking status or excluding women with early death and unintentional weight loss did not substantially change these findings.ConclusionIn frail, older women, having a BMI between 25.0 and 34.9 kg/m2 or a WHR of 0.8 or less was associated with lower mortality. Currently recommended healthy BMI guidelines should be reevaluated for frail older women.
Elder‐Clowning in Long‐Term Dementia Care: Results of a Pilot Study
Authors: Kontos Pia , Miller Karen‐Lee , Colobong Romeo , Palma Lazgare Luis I. , Binns Malcolm , Low Lee‐Fay , Surr Claire , Naglie Gary 
Published: February 2016

ObjectivesTo assess the effects of elder‐clowning on moderate to severe behavioral and psychological symptoms of dementia (BPSD) in nursing home residents with dementia, primarily of the Alzheimer's type.DesignBefore‐and‐after study.SettingNursing home.ParticipantsNursing home residents with moderate to severe BPSD, as defined according to a Neuropsychiatric Inventory—Nursing Home version (NPI‐NH) score of 10 or greater (N = 23), and their care aides.InterventionA pair of elder‐clowns visited all residents twice weekly (~10 minutes per visit) for 12 weeks. They used improvisation, humor, empathy, and expressive modalities such as song, musical instruments, and dance to individualize resident engagement.MeasurementsPrimary outcomes were BPSD measured using the the NPI‐NH, quality of life measured using Dementia Care Mapping (DCM), and nursing burden of care measured using the Modified Nursing Care Assessment Scale (M‐NCAS). Secondary outcomes were occupational disruptiveness measured using the NPI‐NH, agitation measured using the Cohen Mansfield Agitation Inventory (CMAI), and psychiatric medication use.ResultsOver 12 weeks, NPI‐NH scores declined significantly (t22 = −2.68, P = .01), and DCM quality‐of‐life scores improved significantly (F1,50 = 23.09, P < .001). CMAI agitation scores decreased nominally, but the difference was not statistically significant (t22 = −1.86, P = .07). Occupational disruptiveness score significantly improved (t22 = −2.58, P = .02), but there was no appreciable change in M‐NCAS scores of staff burden of care.ConclusionResults suggest that elder‐clowning reduced moderate to severe BPSD of nursing home residents with dementia, primarily of the Alzheimer's type. Elder‐clowning is a promising intervention that may improve Alzheimer's disease care for nursing home residents.
Fluid‐fluxed melting and melt loss in a syntectonic contact metamorphic aureole from the Variscan eastern Pyrenees
Authors: Aguilar C. , Liesa M. , Reche J. , Powell R. 
Published: February 2016

AbstractOpen‐system behaviour through fluid influx and melt loss can produce a variety of migmatite morphologies and mineral assemblages from the same protolith composition. This is shown by different types of granulite facies migmatite from the contact aureole of the Ceret gabbro–diorite stock in the Roc de Frausa Massif (eastern Pyrenees). Patch, stromatic and schollen migmatites are identified in the inner contact aureole, whereas schollen migmatites and residual melanosomes are found as xenoliths inside the gabbro–diorite. Patch and schollen migmatites record D1 and D2 structures in folded melanosome and mostly preserve the high‐T D2 in granular or weakly foliated leucosome. Stromatic migmatites and residual melanosomes only preserve D2. The assemblage quartz–garnet–biotite–sillimanite–cordierite±K‐feldspar–plagioclase is present in patch and schollen migmatites, whereas stromatic migmatites and residual melanosomes contain a sub‐assemblage with no sillimanite and/or K‐feldspar. A decrease in
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Fe (molar Fe/(Fe + Mg)) in garnet, biotite and cordierite is observed from patch migmatites through schollen and stromatic migmatites to residual melanosomes. Whole‐rock compositions of patch, schollen and stromatic migmatites are similar to those of non‐migmatitic rocks from the surrounding area. These metasedimentary rocks are interpreted as the protoliths of the migmatites. A decrease in the silica content of migmatites from 63 to 40 wt% SiO2 is accompanied by an increase in Al2O3 and MgO+FeO and by a depletion in alkalis. Thermodynamic modelling in the NCKFMASHTO system for the different types of migmatite provides peak metamorphic conditions ~7–8 kbar and 840 °C. A nearly isothermal decompression history down to 5.5 kbar was followed by isobaric cooling from 840 °C through 690 °C to lower temperatures. The preservation of granulite facies assemblages and the variation in mineral assemblages and chemical composition can be modelled by ongoing H2O‐fluxed melting accompanied by melt loss. The fluids were probably released by the crystallizing gabbro–diorite, infiltrating the metasedimentary rocks and fluxing melting. Release of fluids and melt loss were probably favoured by coeval deformation (D2). The amount of melt remaining in the system varied considerably among the different types of migmatite. The whole‐rock compositions of the samples, the modelled compositions of melts at the solidus at 5.5 kbar and the residues show a good correlation.
High glucose‐induced oxidative stress represses sirtuin deacetylase expression and increases histone acetylation leading to neural tube defects
Authors: Yu Jingwen , Wu Yanqing , Yang Peixin 
Published: February 2016

AbstractAberrant epigenetic modifications are implicated in maternal diabetes‐induced neural tube defects (NTDs). Because cellular stress plays a causal role in diabetic embryopathy, we investigated the possible role of the stress‐resistant sirtuin (SIRT) family histone deacetylases. Among the seven sirtuins (SIRT1‐7), pre‐gestational maternal diabetes in vivo or high glucose in vitro significantly reduced the expression of SIRT 2 and SIRT6 in the embryo or neural stem cells, respectively. The down‐regulation of SIRT2 and SIRT6 was reversed by superoxide dismutase 1 (SOD1) over‐expression in the in vivo mouse model of diabetic embryopathy and the SOD mimetic, tempol and cell permeable SOD, PEGSOD in neural stem cell cultures. 2,3‐dimethoxy‐1,4‐naphthoquinone (DMNQ), a superoxide generating agent, mimicked high glucose‐suppressed SIRT2 and SIRT6 expression. The acetylation of histone 3 at lysine residues 56 (H3K56), H3K14, H3K9, and H3K27, putative substrates of SIRT2 and SIRT6, was increased by maternal diabetes in vivo or high glucose in vitro, and these increases were blocked by SOD1 over‐expression or tempol treatment. SIRT2 or SIRT6 over‐expression abrogated high glucose‐suppressed SIRT2 or SIRT6 expression, and prevented the increase in acetylation of their histone substrates. The potent sirtuin activator (SRT1720) blocked high glucose‐increased histone acetylation and NTD formation, whereas the combination of a pharmacological SIRT2 inhibitor and a pan SIRT inhibitor mimicked the effect of high glucose on increased histone acetylation and NTD induction. Thus, diabetes in vivo or high glucose in vitro suppresses SIRT2 and SIRT6 expression through oxidative stress, and sirtuin down‐regulation‐induced histone acetylation may be involved in diabetes‐induced NTDs.
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The mechanism underlying pre‐gestational diabetes‐induced neural tube defects (NTDs) is still elusive. Our study unravels a new epigenetic mechanism in which maternal diabetes‐induced oxidative stress represses sirtuin deacetylase 2 (SIRT2) and 6 (SIRT6) expression leading to histone acetylation and gene expression. SIRT down‐regulation mediates the teratogenicity of diabetes leading to (NTD) formation. The study provides a mechanistic basis for the development of natural antioxidants and SIRT activators as therapeutics for diabetic embryopathy.