bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of covariate‐specific time‐dependent ROC curves in the presence of missing biomarkers
Authors: Li Shanshan , Ning Yang 
Published: April 2015

SummaryCovariate‐specific time‐dependent ROC curves are often used to evaluate the diagnostic accuracy of a biomarker with time‐to‐event outcomes, when certain covariates have an impact on the test accuracy. In many medical studies, measurements of biomarkers are subject to missingness due to high cost or limitation of technology. This article considers estimation of covariate‐specific time‐dependent ROC curves in the presence of missing biomarkers. To incorporate the covariate effect, we assume a proportional hazards model for the failure time given the biomarker and the covariates, and a semiparametric location model for the biomarker given the covariates. In the presence of missing biomarkers, we propose a simple weighted estimator for the ROC curves where the weights are inversely proportional to the selection probability. We also propose an augmented weighted estimator which utilizes information from the subjects with missing biomarkers. The augmented weighted estimator enjoys the double‐robustness property in the sense that the estimator remains consistent if either the missing data process or the conditional distribution of the missing data given the observed data is correctly specified. We derive the large sample properties of the proposed estimators and evaluate their finite sample performance using numerical studies. The proposed approaches are illustrated using the US Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset.
Scheduling the Stork: Media Portrayals of Women's and Physicians’ Reasons for Elective Cesarean Delivery
Authors: Campo‐Engelstein Lisa , Howland Lauren E. , Parker Wendy M. , Burcher Paul 
Published: April 2015

AbstractBackgroundMedia interest in cesarean delivery has grown in recent years driven both by rising cesarean delivery rates and the decision by the American College of Obstetrics and Gynecology (ACOG) to permit elective cesarean (EC) delivery.MethodsA content analysis of United States newspaper and magazine articles from 2000 to 2013 (n = 131 articles) was completed to understand how the news media portrays ECs.ResultsThe majority of articles (71.8%) emphasized reasons to support women having an EC, while 38.2 percent of the articles exhibited themes of physician support for ECs. Relatively few articles mentioned reasons against ECs either from the women's perspective (11.5%) or the practitioners’ (3.8%). The most common themes given for women choosing ECs were convenience/scheduling (48.9%), avoidance of pain or fear of labor (29.8%), and physical harm to women from vaginal birth (17.6%). Doctors’ perspectives were less prevalent in the media than women's perspectives, but when mentioned they were almost exclusively in support of ECs for reasons including avoiding malpractice (28.2%), avoiding physical harm to the woman or baby (16.8%), and timing/scheduling (14.5%).DiscussionMedia coverage suggests ECs are widely accepted by both women and doctors, with women choosing an EC mainly for convenience/scheduling and fear. However, 43 percent of doctors surveyed by ACOG said they were not willing to perform the procedure, and surveys report that mothers rarely request an EC.
Feasibility of a ward‐based psychological intervention to improve staff and patient relationships in psychiatric rehabilitation settings
Authors: Berry Katherine , Haddock Gillian , Kellett Stephen , Roberts Chris , Drake Richard , Barrowclough Christine 
Published: April 2015

ObjectivesRecent inquiries highlight the anti‐therapeutic nature of inpatient psychiatric care. We aim to assess the feasibility and potential efficacy of a ward‐based psychological intervention to improve staff–patient relationships in psychiatric rehabilitation settings.MethodsA single‐blind cluster randomized design compared the intervention with treatment as usual (TAU) on measures of relationships, staff well‐being, and patient functioning. Assessments were carried out at baseline and at 6 months.ResultsFifty‐one patients and 85 staff were recruited across 10 wards. Fifteen patients and 11 staff were lost to follow‐up, with primary reason being ward discharge. Uptake to the intervention was variable but on average lower than anticipated (mean number of sessions 3.5, range 0–11). Despite this lower than anticipated uptake, compared with TAU, patients in the intervention arm felt significantly less criticized by their key workers and reported improvements in ward atmosphere. Staff in the intervention arm also reported significantly lower levels of depersonalization post‐intervention. Although trend level data favoured the intervention group, in this relatively small feasibility study, we were not able to demonstrate statistically significant differences between the groups in terms of staff perceptions of relationships, staff stress, and longer‐term patient outcomes.ConclusionsThis psychologically informed ward‐based intervention shows potential in improving relationships, although findings and feasibility may be enhanced if further measures are put into place to ensure that all members of the team attend intervention sessions on a more frequent basis. Loss at follow‐up due to discharge also needs to be factored into future power calculations.Practitioner points

It is feasible to implement and trial a ward‐based psychological intervention (team‐based formulation) in long‐stay psychiatric settings using a cluster randomized design.

Developing psychological formulations with frontline ward staff around patients’ needs has the potential to improve staff‐patient relationships.

The small sample size and loss of data at follow‐up may have limited the power of the study to detect the full range of treatment effects.

Larger trials are needed to assess the reliability and generalizability of our findings across different wards.
Potent anti‐inflammatory effects of the narrow spectrum kinase inhibitor RV1088 on rheumatoid arthritis synovial membrane cells
Authors: To Wing S , Aungier Susan R , Cartwright Alison J , Ito Kazuhiro , Midwood Kim S 
Published: April 2015

Background and PurposeTo investigate whether a narrow spectrum kinase inhibitor RV1088, which simultaneously targets specific MAPKs, Src and spleen tyrosine kinase (Syk), is more effective at inhibiting inflammatory signalling in rheumatoid arthritis (RA) than single kinase inhibitors (SKIs).Experimental Approachelisas were used to determine the efficacy of RV1088, clinically relevant SKIs and the pharmaceutical Humira on pro‐inflammatory cytokine production by activated RA synovial fibroblasts, primary human monocytes and macrophages, as well as spontaneous cytokine synthesis by synovial membrane cells from RA patients. In human macrophages, RNAi knockdown of individual kinases was used to reveal the effect of inhibition of kinase expression on cytokine synthesis.Key ResultsRV1088 reduced TNF‐α, IL‐6 and IL‐8 production in all individual activated cell types with low, nM, IC50s. SKIs, and combinations of SKIs, were significantly less effective than RV1088. RNAi of specific kinases in macrophages also caused only modest inhibition of pro‐inflammatory cytokine production. RV1088 was also significantly more effective at inhibiting IL‐6 and IL‐8 production by monocytes and RA synovial fibroblasts compared with Humira. Finally, RV1088 was the only inhibitor that was effective in reducing TNF‐α, IL‐6 and IL‐8 synthesis in RA synovial membrane cells with low nM IC50s.Conclusions and ImplicationsThis study demonstrates potent anti‐inflammatory effect of RV1088, highlighting that distinct signalling pathways drive TNF‐α, IL‐6 and IL‐8 production in the different cell types found in RA joints. As such, targeting numerous signalling pathways simultaneously using RV1088 could offer a more powerful method of reducing inflammation in RA than targeting individual kinases.
A Peptide Inhibitor Derived from the Conserved Ectodomain Region of DENV Membrane (M) Protein with Activity Against Dengue Virus Infection
Authors: Panya Aussara , Sawasdee Nunghathai , Junking Mutita , Srisawat Chatchawan , Choowongkomon Kiattawee , Yenchitsomanus Pa‐thai 
Published: April 2015

Dengue virus (DENV) infection is a public health problem worldwide; thus, the development of a vaccine and anti‐DENV drugs is urgently needed. It has been observed that low levels of viremia in DENV‐infected individuals are associated with mild disease outcomes; therefore, reduction of DENV load should offer therapeutic benefits. Disruption of protein–protein interactions on the surface of DENV by a peptide that mimics part of its structural protein may affect stability of the virion structure and inhibit viral entry into host cells. To test this hypothesis, we generated a novel peptide inhibitor that mimics the conserved ectodomain region of DENV membrane (M) protein, MLH40 peptide, for DENV inhibition assays. MLH40 inhibited all four serotypes of the virus (DENV1–4) at half maximal inhibition concentration of 24–31 μm. MLH40 at 100 μm blocked DENV2 attachment to cells by 80%. The inhibitory activity of MLH40 against DENV was consistently observed with different cell types, including Vero, A549, and Huh7 cells. Prediction of MLH40 binding by a molecular docking program indicated that its N‐terminal loop may interact with DENV envelope (E) proteins and alter their dimer conformation. Thus, MLH40 may serve as a lead‐peptide inhibitor for the development of an anti‐DENV drug.
Phylogeny of the Alismatales (Monocotyledons) and the relationship of Acorus (Acorales?)
Authors: Petersen Gitte , Seberg Ole , Cuenca Argelia , Stevenson Dennis W. , Thadeo Marcela , Davis Jerrold I. , Graham Sean , Ross T. Gregory 
Published: April 2015

AbstractA phylogenetic analysis of the early branching lineages of the monocotyledons is performed using data from two plastid genes (rbcL and matK), five mitochondrial genes (atp1, ccmB, cob, mttB and nad5) and morphology. The complete matrix includes 93 terminals representing Acorus, the 14 families currently recognized within Alismatales, and numerous lineages of monocotyledons and other angiosperms. Total evidence analysis results in an almost completely resolved strict consensus tree, but all data partitions, genomic as well as morphological, are incongruent. The effects of RNA editing and potentially processed paralogous sequences are explored and discussed. Despite a decrease in incongruence length differences after exclusion of edited sites, the major data partitions remain significantly incongruent. The 14 families of Alismatales are all found to be monophyletic, but Acorus is found to be included in Alismatales rather than being the sister group to all other monocotyledons. The placement is strongly supported by the mitochondrial data, atp1 in particular, but it cannot be explained as an artifact caused by patterns of editing or by sampling of processed paralogues.
The long‐term outcome of transvaginal anterior levatorplasty for intractable rectovaginal fistula
Authors: Maeda K. , Koide Y. , Hanai T. , Sato H. , Masumori K. , Matsuoka H. , Katsuno H. 
Published: April 2015

AbstractAimSeveral procedures have been described for rectovaginal fistula with a wide range of success, but there is little information on the long‐term outcome. The aim of the present study was to investigate the long‐term outcome after transvaginal anterior levatorplasty (ALP) for intractable rectovaginal fistula.MethodData of 16 consecutive patients undergoing transvaginal ALP with fistulectomy and closure of the rectum and vagina between 1998 and 2011 were prospectively recorded and retrospectively investigated to study the long‐term outcome.ResultsBirth injury (n = 7), low anterior resection for rectal cancer (n = 3), pouch surgery for ulcerative colitis (n = 2) and a procedure for prolapse and haemorrhoids (n = 2) were the main causes of the fistula. Nine patients had a covering stoma before surgery. All patients underwent ALP, with a covering stoma in two patients. Infection occurred in one patient and wound rupture after surgery in another patient. These patients underwent reoperation by ALP. All fistulae had healed at a median follow‐up of 84 (8–193) months after initial surgery or stoma closure.ConclusionTransvaginal ALP is effective for the treatment of mid or low rectovaginal fistula. The results show that a graft is not necessary regardless of whether or not previous surgery has been performed.
Features of developmental coordination disorder in active childhood epilepsy: a population‐based study
Authors: Reilly Colin , Atkinson Patricia , Das Krishna B , Chin Richard F , Aylett Sarah E , Burch Victoria , Gillberg Christopher , Scott Rod C , Neville Brian G R 
Published: April 2015

AimsTo provide data on parent‐reported features of developmental coordination disorder (DCD) and describe neurobehavioural comorbidity in children with epilepsy and DCD.MethodEighty‐five (74% of those eligible) children (44 males, 41 females; age range 5–15y) with active childhood epilepsy (an epileptic seizure in the last year and/or currently taking antiepileptic drugs) in a population‐based cohort underwent comprehensive multidisciplinary assessment. The DCD Questionnaire (DCD‐Q) was completed by parents (n=69) of children with an IQ>34, of whom 56 did not have cerebral palsy (CP), and were considered for a diagnosis of DCD.ResultsOf those considered for a DCD diagnosis, 16 (29%) met DSM‐IV‐TR criteria whereas 34 (61%) scored in the at‐risk range on the DCD‐Q. The sensitivity of the DCD‐Q was 100% (95% CI 76–100) and specificity was 55% (95% CI 39–70). Significant predictors of higher scores on the DCD‐Q included the presence of autism spectrum disorder, CP, and early seizure onset. Increasing age and IQ were independently associated with higher DCD‐Q scores. Intellectual disability, attention‐deficit–hyperactivity disorder, academic underachievement, and specific memory problems were the most common neurobehavioural difficulties in those with both DCD and epilepsy.InterpretationParent‐reported symptoms of DCD are very common in childhood epilepsy. The DCD‐Q has good sensitivity but lower specificity in this population.
Determinants of Secondary Pulmonary Hypertension in Patients with Takotsubo Cardiomyopathy
Authors: Izumo Masaki , Shiota Maiko , Nalawadi Smruti , Das Jayanta , Dohad Sohail , Kuwahara Eiji , Fukuoka Yoko , Siegel Robert J , Shiota Takahiro 
Published: April 2015

BackgroundAlthough takotsubo cardiomyopathy (TTC) has been reported to have a favorable outcome, many complications may occur in the acute phase. Heart failure is the most common clinical complication in patients with TTC. We aimed to investigate determinants of secondary pulmonary hypertension (PH) in patients with TTC.MethodsThis study consisted of 55 patients with TTC. Detailed echocardiographic measurements were taken, including pulmonary artery systolic pressure (PASP). PH was identified PASP >35 mmHg. The severity of mitral regurgitation (MR) was evaluated by measuring effective regurgitant orifice area (EROA). Follow‐up echocardiography was performed in 45 patients (81.8%) within 4 weeks after initial presentation.ResultsAll patients were stratified into PH or no PH (NPH) group (average PASP: 46.2 ± 6.7 vs. 29.8 ± 3.3 mmHg, P < 0.001); 25 patients (45.5%) were categorized into the PH group. Left ventricular (LV) volume, LV ejection fraction, and troponin I levels did not significantly differ between the two groups. Age and EROA were significantly greater in PH group than NPH group (age; 74.6 ± 9.1 vs. 63.5 ± 17.7, EROA; 0.22 ± 0.17 vs. 0.03 ± 0.05 cm2, all P < 0.01). The multivariate analysis revealed that age and EROA were independent predictors for PH in patients with TTC (all P < 0.001). PASP was significantly improved at follow‐up compared to those at initial presentation (35.8 ± 8.4 vs. 30.3 ± 7.9 mmHg, P < 0.01).ConclusionAge and the severity of MR were independent predictors for secondary PH in patients with TTC.
Influence of native and alien Prunus species and light conditions on performance of the leaf beetle Gonioctena quinquepunctata
Authors: Mąderek Ewa , Łukowski Adrian , Giertych Marian J. , Karolewski Piotr 
Published: April 2015

AbstractThe polyphagous beetle Gonioctena quinquepunctata Fabricius (Coleoptera: Chrysomelidae) is a serious leaf pest of the native European bird cherry, Prunus padus L., and the invasive alien black cherry, Prunus serotina Ehrh. (Rosaceae). In the shade, leaf damage is extensive in both species, whereas in full light, it is extensive in P. padus, but very low in P. serotina. We determined the influence of Prunus species and light conditions on differences in performance of both sexes of this folivore. In a laboratory experiment in which larvae were fed with leaves of a single species grown under particular light conditions, we measured larval, pupal, and adult mass, efficiency of conversion of ingested food (ECI), duration of development, total food eaten, and relative growth rate. In the field, we observed differences in beetle mass on shrubs of the two species growing under various light conditions. From the field observations, we hypothesised that leaves of the invasive P. serotina are not an equally good food source as leaves of P. padus for G. quinquepunctata, and the preference of these beetles for shaded shrubs is most favourable for their growth and development. Under laboratory conditions, we found that the beetle growth rate was not affected significantly by Prunus species or light conditions, despite the significant effect of light condition on the structure and chemical composition of Prunus seedlings. The lower ECI value for larvae feeding on sunlit leaves was compensated for by their higher level of consumption. In the field, adult insect mass was higher on P. padus than on P. serotina, and higher on sunlit shrubs of both species than on shaded ones. Under natural conditions, the mass of adult insects is probably also affected by other factors, such as predators and competition among folivores.
Clear advantages for fall armyworm larvae from feeding on maize relative to its ancestor Balsas teosinte may not be reflected in their mother's host choice
Authors: Bernal Julio S. , Melancon Joseph E. , Zhu‐Salzman Keyan 
Published: April 2015

AbstractConsistent with an increasing number of comparisons between crop plants and their wild ancestors, a previous study showed that in the field, maize [Zea mays ssp. mays L. (Poaceae)] suffers more herbi‐vory by larvae of Spodoptera frugiperda JE Smith (Lepidoptera: Noctuidae) than its ancestor Balsas teosinte (Zea mays ssp. parviglumis Iltis & Doebley). This study addressed plausible causes of the differing herbivory levels between maize and Balsas teosinte, specifically whether host plant selection by adult females is biased for either host plant depending on larval performance—i.e., the preference‐performance hypothesis—or risk of mortality by parasitoids and predators—i.e., the natural enemy‐free space hypothesis. Field observations showed that performance of S. frugiperda larvae was superior on maize compared with Balsas teosinte, a result partially explainable by the greater toughness of teosinte compared with maize tissue, but not by a difference in inhibition of protein digestion by larvae. Additional field observations showed that the mortality risk of S. frugiperda larvae is higher on Balsas teosinte, as indicated by higher parasitism (ca. four‐fold) and predation (ca. three‐fold) rates on the teosinte compared with maize. However, laboratory observations showed that S. frugiperda females did not discriminate between maize and Balsas teosinte for oviposition. Overall, the study's results were consistent with prior observations that direct and indirect defenses of maize against S. frugiperda larvae were weakened with domestication. In contrast, the results were inconsistent with predictions of the preference‐performance and natural enemy‐free space hypotheses, because selection of maize or Balsas teosinte plants by S. frugiperda females was independent of their offspring's performance and risk of mortality by natural enemies. On the one hand, this study's results partially explained differing herbivory levels between a crop and its wild ancestor, and on the other hand they suggested that host selection by S. frugiperda may be mediated by larval dispersal behavior and host choices.
Role of vasoactive intestinal peptide in the light input to the circadian system
Authors: Vosko Andrew , van Diepen Hester C. , Kuljis Dika , Chiu Andrew M. , Heyer Djai , Terra Huub , Carpenter Ellen , Michel Stephan , Meijer Johanna H. , Colwell Christopher S. 
Published: April 2015

AbstractThe neuropeptide vasoactive intestinal peptide (VIP) is expressed at high levels in a subset of neurons in the ventral region of the suprachiasmatic nucleus (SCN). While VIP is known to be important for the synchronization of the SCN network, the role of VIP in photic regulation of the circadian system has received less attention. In the present study, we found that the light‐evoked increase in electrical activity in vivo was unaltered by the loss of VIP. In the absence of VIP, the ventral SCN still exhibited N‐methyl‐d‐aspartate‐evoked responses in a brain slice preparation, although the absolute levels of neural activity before and after treatment were significantly reduced. Next, we used calcium imaging techniques to determine if the loss of VIP altered the calcium influx due to retinohypothalamic tract stimulation. The magnitude of the evoked calcium influx was not reduced in the ventral SCN, but did decline in the dorsal SCN regions. We examined the time course of the photic induction of Period1 in the SCN using in situ hybridization in VIP‐mutant mice. We found that the initial induction of Period1 was not reduced by the loss of this signaling peptide. However, the sustained increase in Period1 expression (after 30 min) was significantly reduced. Similar results were found by measuring the light induction of cFOS in the SCN. These findings suggest that VIP is critical for longer‐term changes within the SCN circuit, but does not play a role in the acute light response.
Action observation with kinesthetic illusion can produce human motor plasticity
Authors: Nojima Ippei , Koganemaru Satoko , Kawamata Toshio , Fukuyama Hidenao , Mima Tatsuya 
Published: April 2015

AbstractAfter watching sports, people often feel as if their sports skills might have been improved, even without any actual training. On some occasions, this motor skill learning through observation actually occurs. This phenomenon may be due to the fact that both action and action observation (AO) can activate shared cortical areas. However, the neural basis of performance gain through AO has not yet been fully clarified. In the present study, we used transcranial magnetic stimulation to investigate whether primary motor cortex (M1) plasticity is a physiological substrate of AO‐induced performance gain and whether AO itself is sufficient to change motor performance. The excitability of M1, especially that of its intracortical excitatory circuit, was enhanced after and during AO with kinesthetic illusion but not in interventions without this illusion. Moreover, behavioral improvement occurred only after AO with kinesthetic illusion, and a significant correlation existed between the performance gain and the degree of illusion. Our findings indicated that kinesthetic illusion is an essential component of the motor learning and M1 plasticity induced by AO, and this insight may be useful for the strategic rehabilitation of stroke patients.