bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose‐intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma: a randomized phase II study
Authors: Ishida Takashi , Jo Tatsuro , Takemoto Shigeki , Suzushima Hitoshi , Uozumi Kimiharu , Yamamoto Kazuhito , Uike Naokuni , Saburi Yoshio , Nosaka Kisato , Utsunomiya Atae , Tobinai Kensei , Fujiwara Hiroshi , Ishitsuka Kenji , Yoshida Shinichiro , Taira Naoya , Moriuchi Yukiyoshi , Imada Kazunori , Miyamoto Toshihiro , Akinaga Shiro , Tomonaga Masao , Ueda Ryuzo 
Published: March 2015

SummaryThis multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti‐CC chemokine receptor 4 antibody, to mLSG15, a dose‐intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma (ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (%CR); secondary endpoints included the overall response rate (ORR) and safety. The %CR and ORR in the mLSG15‐plus‐mogamulizumab arm (n = 29) were 52% [95% confidence interval (CI), 33–71%] and 86%, respectively; the corresponding values in the mLSG15 arm (n = 24) were 33% (95% CI, 16–55%) and 75%, respectively. Grade ≥ 3 treatment‐emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15‐plus‐mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15‐plus‐mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher %CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887.
Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long‐Standing Model
Authors: Leão Anderson H.F.F. , Sarmento‐Silva Aldair J. , Santos José R. , Ribeiro Alessandra M. , Silva Regina H. 
Published: March 2015

AbstractThe administration of reserpine to rodents was one of the first models used to investigate the pathophysiology and screening for potential treatments of Parkinson's disease (PD). The reserpine model was critical to the understanding of the role of monoamine system in the regulation of motor and affective disorders, as well as the efficacy of current PD treatments, such as L‐DOPA and dopamine agonists. Nevertheless, with the introduction of toxin‐induced and genetic models of PD, reserpine became underused. The main rationale to this drawback was the supposed absence of reserpine construct validity with PD. Here, we highlight classical and recent experimental findings that support the face, pharmacological, and construct validity of reserpine PD model and reason against the current rationale for its underuse. We also aim to shed a new perspective upon the model by discussing the main challenges and potentials for the reserpine model of PD.
STAT-5 is activated constitutively in T cells, B cells and monocytes from patients with primary Sjögren's syndrome
Authors: Pertovaara M , Silvennoinen O , Isomäki P 
Published: March 2015

Summary
The expression and phosphorylation of signal transducer and activator of transcription-1 (STAT-1) have been shown to be markedly increased in the salivary gland epithelial cells of patients with primary Sjögren's syndrome (pSS). The present aim was to investigate the activation status of different STAT proteins in peripheral blood (PB) lymphocytes and monocytes, and their correlations with clinical parameters in patients with pSS. To this end, PB samples were drawn from 16 patients with active pSS and 16 healthy blood donors, and the phosphorylation of STAT-1, -3, -4, -5 and -6 proteins was studied in T cells, B cells and monocytes using multi-colour flow cytometry. In addition, mRNA expression of STAT molecules in PB mononuclear cells (PBMC) was studied with quantitative reverse transcriptase–polymerase chain reaction (RT–PCR). Basal phosphorylation of STAT-5 was found to be significantly higher in PB T cells, B cells and monocytes in patients with pSS than in healthy controls. The expression of STAT-5 mRNA was not increased in PBMC. pSTAT-5 levels in B cells and monocytes showed a significant correlation with serum immunoglobulin (Ig)G levels and anti-SSB antibody titres. Constitutive STAT-5 activation in monocytes and CD4+ T cells was associated with purpura. There were no major differences in the activation of other STATs between pSS patients and healthy controls. In conclusion, STAT-5 is activated constitutively in PB leucocytes in patients with pSS, and basal STAT-5 phosphorylation seems to associate with hypergammaglobulinaemia, anti-SSB antibody production and purpura.
Vitamin D and insulin resistance
Authors: Wallace Ian R. , Wallace Helen J. , McKinley Michelle C. , Bell Patrick M. , Hunter Steven J. 
Published: March 2015

SummaryVitamin D is a steroid hormone, which in active form binds to the vitamin D receptor. Expression of the vitamin D receptor in diverse cell types (pancreatic islet cells, myocytes, hepatocytes and adipocytes) raises the suspicion that vitamin D may be involved in multiple cellular processes, including the response to insulin. Insulin resistance is a characteristic feature of type 2 DM, and its attenuation may reduce the incidence of type 2 DM and cardiovascular disease. In observational studies, low serum 25‐hydroxyvitamin D (25‐OHD) concentrations are associated with an increased risk of type 2 DM. It has been suggested that increasing serum 25‐OHD concentrations may have beneficial effects on glucose and insulin homeostasis. However, cross‐sectional and interventional studies of vitamin D supplementation provide conflicting results and demonstrate no clear beneficial effect of vitamin D on insulin resistance. These studies are complicated by inclusion of different patient cohorts, different 25‐OHD assays and different doses and preparations of vitamin D. Any possible association may be confounded by alterations in PTH, 1,25‐dihydroxyvitamin D or tissue vitamin D concentrations. We identified 39 studies via MEDLINE and PUBMED. We review the evidence from 10 studies (seven observational and three interventional) examining vitamin D and type 2 DM incidence, and 29 studies (one prospective observational, 12 cross‐sectional and 16 interventional trials) examining vitamin D and insulin resistance. Based on this data, it is not possible to state that vitamin D supplementation has any effect on type 2 DM incidence or on insulin resistance. Data from the multiple ongoing randomized controlled trials of vitamin D supplementation due to report over the next few years should help to clarify this area.
Maternal vitamin D supplementation during pregnancy prevents vitamin D deficiency in the newborn: an open‐label randomized controlled trial
Authors: Rodda C.P. , Benson J.E. , Vincent A.J. , Whitehead C.L. , Polykov A. , Vollenhoven B. 
Published: March 2015

SummaryObjectiveTo determine whether maternal vitamin D supplementation, in the vitamin D deficient mother, prevents neonatal vitamin D deficiency.DesignOpen‐label randomized controlled trial.SettingMetropolitan Melbourne, Australia, tertiary hospital routine antenatal outpatient clinic.ParticipantsSeventy‐eight women with singleton pregnancies with vitamin D deficiency/insufficiency (serum 25‐OH Vit D < 75 nmol/l) at their first antenatal appointment at 12–16‐week gestation were recruited.InterventionParticipants were randomized to vitamin D supplementation (2000–4000 IU cholecalciferol) orally daily until delivery or no supplementation.Main outcome measuresThe primary outcome was neonatal serum 25‐OH vit D concentration at delivery. The secondary outcome was maternal serum 25‐OH vit D concentration at delivery.ResultsBaseline mean maternal serum 25‐OH vit D concentrations were similar (P = 0·9) between treatment (32 nmol/l, 95% confidence interval 26–39 nmol/l) and control groups (33 nmol/l, 95% CI 26–39 nmol/l). Umbilical cord serum 25‐OH vit D concentrations at delivery were higher (P < 0·0001) in neonates of treatment group mothers (81 nmol/l, 95% CI; 70–91 nmol/l) compared with neonates of control group mothers (42 nmol/l, 95% CI; 34–50 nmol/l) with a strongly positive correlation between maternal serum 25‐OH Vit D and umbilical cord serum 25‐OH vit D concentrations at delivery (Spearman rank correlation coefficient 0·88; P < 0·0001). Mean maternal serum 25‐OH Vit D concentrations at delivery were higher (P < 0·0001) in the treatment group (71 nmol/l, 95% CI; 62–81 nmol/l) compared with the control group (36 nmol/l, 95% CI; 29–42 nmol/l).ConclusionVitamin D supplementation of vitamin D deficient pregnant women prevents neonatal vitamin D deficiency.
An analysis of different therapeutic options in patients with Cushing's syndrome due to bilateral macronodular adrenal hyperplasia: a single‐centre experience
Authors: Albiger N.M. , Ceccato F. , Zilio M. , Barbot M. , Occhi G. , Rizzati S. , Fassina A. , Mantero F. , Boscaro M. , Iacobone M. , Scaroni C. 
Published: March 2015

SummaryContextBilateral macronodular adrenal hyperplasia (BMAH) is a rare form of Cushing's syndrome (CS). A variety of in vivo tests to identify aberrant receptor expression have been proposed to guide medical treatment. Unilateral adrenalectomy (UA) may be effective in selected patients, but little is known about recurrence during follow‐up.ObjectiveTo describe a series of patients with BMAH and CS treated by different approaches, with a particular focus on the benefit of UA.Design and patientsWe retrospectively assessed 16 patients with BMAH and CS (11 females, five males), analysing the in vivo cortisol response to different provocative tests. Twelve of the 16 patients underwent UA and were monitored over the long term.ResultsBased on in vivo test results, octreotide LAR or propranolol was administered in one case of food‐dependent CS and two patients with a positive postural test. A significant improvement in biochemical values was seen in all patients but with limited clinical response. UA was performed in 12 patients, producing long‐term remission in three (106 ± 28 months; range: 80–135), recurrence in eight (after 54 ± 56 months; range 12–180) and persistence in one other. Four patients subsequently underwent contralateral adrenalectomy for overt CS, one received ketoconazole, and four other patients remain under observation for subclinical CS.ConclusionsMedical treatment based on cortisol response to provocative tests had a limited role in our patients, whereas UA was useful in some of them. Although recurrence is likely, the timing of onset is variable and close follow‐up is mandatory to identify it.
Sebaceous induction in dermatofibroma: a common feature of dermatofibromas on the shoulder
Authors: Zeidi Majid , North Jeffrey P. 
Published: March 2015

BackgroundDermatofibroma (DF) has multiple histopathological variants and overlying acanthosis, hyperkeratosis and hyperpigmentation are often present. We have frequently observed sebaceous induction in DFs on the shoulder and wanted to assess if this is a site‐specific finding.MethodsWe prospectively collected 100 DFs and assessed for sebaceous induction, the histopathologic pattern of the DF and any associated‐epidermal changes. We retrospectively searched for DFs with sebaceous induction to assess the anatomic site of the biopsy.ResultsIn the 100 prospectively collected DFs, 49% occurred on the lower extremities, 39% on the upper extremities, 10% on the trunk and 2% on the head. Sebaceous induction was present in 16 DFs, 81% of which occurred on or near the shoulder. The most common variant was fibrocollagenous DF (64%), including in DFs with sebaceous induction. The retrospective search for DFs with sebaceous induction found 19 cases in which 95% occurred on the shoulder area. Sclerotic pattern DFs were most common in this retrospective cohort (47%), and seborrheic keratosis‐like hyperplasia occurred in 100% of these cases.ConclusionDFs occurring on the shoulder have a high incidence of sebaceous induction with seborrheic keratosis‐like epidermal hyperplasia and a fibrocollagenous or sclerotic pattern.
Parental social consequences of having a child with cerebral palsy in Denmark
Authors: Michelsen Susan I , Flachs Esben M , Madsen Mette , Uldall Peter 
Published: March 2015

AimTo analyse the social situation of parents who have a child with cerebral palsy (CP).MethodThis was a population‐based longitudinal study with linkage to public registries. Parents of children withCP(n=3671) identified in the DanishCPRegistry were compared with 17 983 parents of children withoutCP. Employment, income, cohabitation status, and presence of additional children were factors analysed during a follow‐up period of 28 years. We followed parents from before their child was born and up to the age of 43 years of the child.ResultsMothers of children withCPunder the age of 10 were less often employed: odds ratio [OR] of employment at age 5y 0.45 (95% confidence interval [CI] 0.36–0.57), but only 11% left the labour market. Mothers of children withoutCPhad higher incomes: ratio full‐time working 1.11 (95%CI1.07–1.15). The risk of not living together was not increased among parents of children withCP: at age 5 yearsOR1.04 (95%CI0.84–1.28). Parents of children withCPas the first born postponed or more seldom had subsequent children: hazard ratio [HR] 0.75 (95%CI0.68–0.83).InterpretationThe Danish welfare system seems to have succeeded in keeping parents in the labour market and living together with their child. Special attention needs to be paid to the financial situation of families with children withCPunder 10 years of age.
Cognition in children with neurofibromatosis type 1: data from a population‐based study
Authors: Lehtonen Annukka , Garg Shruti , Roberts Stephen A , Trump Dorothy , Evans D Gareth , Green Jonathan , Huson Susan M 
Published: March 2015

AimThis study aimed to investigate the core cognitive deficits in children with neurofibromatosis type 1 (NF1).MethodThe study recruited 49 children with NF1 (25 males, 24 females; mean age 11y 9mo [SD 3y 2mo]), 19 healthy siblings of children with NF1 (sibling comparisons; mean age 12y 7mo [SD 2y 7mo], 9 males, 10 females) and 29 healthy children from the community (community comparisons; mean age 11y [SD 2y 7mo], 12 males, 17 females). Participants completed a battery of cognitive tests including tests of intelligence, academic achievement, attention, visuoperceptual functioning, visual learning, executive functioning, and non‐verbal working memory tests.ResultsOur study, using a population‐based sample, confirmed previous findings from studies using variable sampling methods. Children with NF1 had significantly lower Full‐scale IQs (p=0.04) and lower academic achievement (p=0.026–0.005) than their siblings. Compared with their siblings, they also had significantly poorer visuospatial processing (p=0.007), visual associate learning (p=0.014), non‐verbal working memory (p=0.023), and executive function (p<0.001). Data from the community comparisons were not included because they were subject to significant selection bias.InterpretationPopulation‐based frequencies for cognitive deficits in children with NF1 are similar to the frequencies in non‐population based samples. This study highlights the heterogeneous nature of cognitive problems in children with NF1 and the need for monitoring and support at school.
Accuracy of Echocardiographic Cardiac Index Assessment in Subjects with Preserved Left Ventricular Ejection Fraction
Authors: Maeder Micha T. , Karapanagiotidis Sofie , Dewar Elizabeth M. , Kaye David M. 
Published: March 2015

IntroductionWe aimed to determine the accuracy of the echocardiographic assessment of cardiac index (CI) in subjects with preserved left ventricular ejection fraction (LVEF).MethodsThirty‐three subjects with LVEF >50%, normal sinus rhythm, and a broad spectrum of hemodynamic profiles underwent echocardiography immediately followed by right heart catheterization. As gold standards, CI was assessed using thermodilution [CI (TD)] and the Fick method [CI (F)]. Echocardiographic CI was assessed by four methods: from the left ventricular outflow tract (LVOT) velocity time integral and the LVOT diameter as measured [CI (LVOTm)] as well as estimated from body surface area [CI (LVOTe)], and from stroke volume indices assessed using the biplane [CI (BP)] and monoplane [CI (MP)] methods.ResultsThe mean CI (TD), CI (F), CI (LVOTm), CI (LVOTe), CI (BP), and CI (MP) were 3.0 ± 0.9, 3.1 ± 0.7, 2.8 ± 0.6, 3.3 ± 0.6, 2.0 ± 0.6, and 2.2 ± 0.7 L/min/m2. There were modest correlations between CI (TD) and CI (F) and all four noninvasive measures of CI with r2 values ranging from 0.09 to 0.30. CI (LVOTm) underestimated CI (TD) and CI (F) by 0.3 and 0.3 L/min/m2, CI (LVOTe) overestimated CI (TD) and CI (F) by 0.3 and 0.2 L/min/m2, and CI (BP) and CI (MP) underestimated CI (TD) and CI (F) by 1.1 and 1.1 L/min/m2 and 0.9 and 0.9 L/min/m2, respectively, with large limits of agreement for all comparisons.ConclusionsIn subjects with nondilated left ventricles with preserved LVEF, flow‐ or volume‐based measures of CI by 2D echocardiography may not accurately reflect CI (TD) and CI (F). Further larger studies are required to verify our findings and to evaluate the accuracy of contrast and 3D echocardiography in this setting.
Mating status regulates post‐mating refractory period in Striacosta albicosta females
Authors: Konopka Joanna K. , McNeil Jeremy N. 
Published: March 2015

AbstractIn polyandrous insect species, males may transfer substances to reduce sperm competition by affecting female sexual receptivity. In this study, we determined the incidence of polyandry in females of Western bean cutworm (WBC), Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), and investigated the influence of both previous female and male mating history on the duration of mating, the female refractory period, and subsequent calling behavior of females under controlled laboratory conditions. The mating status of WBC males influenced mating duration, with copulations involving previously mated males taking longer, possibly related to the time required to produce an ejaculate. The duration of the female refractory period and the onset time of recalling during the scotophase were both affected by female mating history, but not by that of the males. Females had a shorter refractory period and resumed calling activity earlier after their second and third matings than after their first mating. The earlier onset of calling by previously mated females could reduce competition with virgin females and their shorter refractory period could explain the high incidence of polyandry observed in nature.
Direct effect of ozone pollution on aphids: revisiting the evidence at individual and population scales
Authors: Telesnicki Marta C. , Martínez‐Ghersa M. Alejandra , Arneodo Joel D. , Ghersa Claudio M. 
Published: March 2015

AbstractMost of our knowledge about the consequences of tropospheric ozone pollution on aphid–plant interaction assumes the absence of a direct effect of ozone on aphids. However, the biological effects of ozone encompass changes in reactive oxygen species signalling, oxidative stress accumulation, and the immune response of both plants and animals. The main objective of this work was to evaluate the direct effect of ozone on Metopolophium dirhodum (Walker) aphids (Hemiptera: Aphididae), linking mechanisms that operate at individual scale (oxidative stress parameters and aphid‐bacteria symbiosis persistence) with their consequences at population scale (mortality, dispersion, and population growth). Two experiments were conducted in open‐top chambers with three contrasting ozone exposure regimes (6 h at 0.5 ± 0.3, 50 ± 5, or 150 ± 10 p.p.b.) and artificial diets to evaluate the direct effect of ozone on aphids. Exposure of aphids to ozone increased insect mortality compared to the control treatment. However, the populations established from the surviving insects of each treatment increased similarly. Consistently, aphid symbiosis with Buchnera aphidicola Munson et al. (Proteobacteria) and Hamiltonella defensa Moran et al. (Enterobacteriaceae) persisted in all treatments. Ozone also affected aphid behaviour. The proportion of insects dispersing from diet cages was lower in the ozone treatments than in the control treatment. In addition, lipid peroxidation was higher at 150 p.p.b. than at 50 p.p.b. treatment, although not different from that in the control. The reduction in aphid dispersion coupled with increased mortality suggests that direct exposure to ozone could lower aphid efficiency as virus vectors. These results could be partially associated with mechanisms operating at individual scale (accumulation of oxidative damage). Overall, these experiments encourage reconsidering the impact of the direct effects of ozone on aphids when assessing the consequences of this component of global change on plant–aphid interactions.
Musical expertise is related to neuroplastic changes of multisensory nature within the auditory cortex
Authors: Pantev Christo , Paraskevopoulos Evangelos , Kuchenbuch Anja , Lu Yao , Herholz Sibylle C. 
Published: March 2015

AbstractRecent neuroscientific evidence indicates that multisensory integration does not only occur in higher level association areas of the cortex as the hierarchical models of sensory perception assumed, but also in regions traditionally thought of as unisensory, such as the auditory cortex. Nevertheless, it is not known whether expertise‐induced neuroplasticity can alter the multisensory processing that occurs in these low‐level regions. The present study used magnetoencephalography to investigate whether musical training may induce neuroplastic changes of multisensory processing within the human auditory cortex. Magnetoencephalography data of four different experiments were used to demonstrate the effect of long‐term and short‐term musical training on the integration of auditory, somatosensory and visual stimuli in the auditory cortex. The cross‐sectional design of three of the experiments allowed us to infer that long‐term musical training is related to a significantly different way of processing multisensory information within the auditory cortex, whereas the short‐term training design of the fourth experiment allowed us to causally infer that multisensory music reading training affects the multimodal processing within the auditory cortex.