bluuebunny/crossref_metadata_2025_split huggingface dataset:
Being born large for gestational age is associated with earlier pubertal take‐off and longer growth duration: a longitudinal study
Authors: Di Giovanni Ilaria , Marcovecchio M. Loredana , Chiavaroli Valentina , de Giorgis Tommaso , Chiarelli Francesco , Mohn Angelika 
Published: October 2016

AbstractAimPerinatal factors seem to influence the onset of puberty, but there is limited information on the potential effect of large size at birth on pubertal growth. This study evaluated pubertal growth in children born large for gestational age (LGA) compared to children born appropriate for gestational age (AGA).MethodsLongitudinal growth data collected from 70 children – 40 AGA and 30 LGA – were analysed. The ages at take‐off, peak height velocity, final height and pubertal growth spurts were calculated using the Preece–Baines model I.ResultsLarge for gestational age children showed an earlier age at take‐off compared to AGA children (10.1 ± 1.2 versus 11.0 ± 1.4 years, p = 0.007), whereas the age at peak height velocity and at final height was similar. LGA children showed a longer growth spurt duration (2.5 ± 1 versus 1.5 ± 1.2 years, p < 0.001) and total pubertal duration (5.3 ± 1.2 versus 4.6 ± 1.2 years, p = 0.036) than AGA children. Results were similar when stratified by sex.ConclusionBeing born LGA was associated with an earlier pubertal take‐off and longer growth duration. These unique findings, due to the lack of studies on pubertal growth patterns in LGA children, might lead the way to novel research and a different approach to LGA children at the onset of pubertal growth.
Severe Epstein–Barr virus infection in primary immunodeficiency and the normal host
Authors: Worth Austen J. J. , Houldcroft Charlotte J. , Booth Claire 
Published: October 2016

SummaryEpstein–Barr virus (EBV) infection is ubiquitous in humans, but the majority of infections have an asymptomatic or self‐limiting clinical course. Rarely, individuals may develop a pathological EBV infection with a variety of life threatening complications (including haemophagocytosis and malignancy) and others develop asymptomatic chronic EBV viraemia. Although an impaired ability to control EBV infection has long been recognised as a hallmark of severe T‐cell immunodeficiency, the advent of next generation sequencing has identified a series of Primary Immunodeficiencies in which EBV‐related pathology is the dominant feature. Chronic active EBV infection is defined as chronic EBV viraemia associated with systemic lymphoproliferative disease, in the absence of immunodeficiency. Descriptions of larger cohorts of patients with chronic active EBV in recent years have significantly advanced our understanding of this clinical syndrome. In this review we summarise the current understanding of the pathophysiology and natural history of these diseases and clinical syndromes, and discuss approaches to the investigation and treatment of severe or atypical EBV infection.
The expanding role of the clinical haematologist in the new world of advanced therapy medicinal products
Authors: Lowdell Mark W. , Thomas Amy 
Published: October 2016

SummaryAdvanced therapy medicinal products (ATMPs) represent the current pinnacle of ‘patient‐specific medicines’ and will change the nature of medicine in the near future. They fall into three categories; somatic cell‐therapy products, gene therapy products and cells or tissues for regenerative medicine, which are termed ‘tissue engineered’ products. The term also incorporates ‘combination products’ where a human cell or tissue is combined with a medical device. Plainly, many of these new medicines share similarities with conventional haematological stem cell transplant products and donor lymphocyte infusions as well as solid organ grafts and yet ATMPs are regulated as medicines and their development has remained predominantly in academic settings and within specialist centres. However, with the advent of commercialisation of dendritic cell vaccines, chimeric antigen receptor (CAR)‐T cells and genetically modified autologous haematopoietic stem cells to cure single gene‐defects in β‐thalassaemia and haemophilia, the widespread availability of these therapies needs to be accommodated. Uniquely to ATMPs, the patient or an allogeneic donor is regularly part of the manufacturing process. All of the examples given above require procurement of blood, bone marrow or an apheresate from a patient as a starting material for manufacture. This can only occur in a clinical facility licensed for the procurement of human cells for therapeutic use and this is likely to fall to haematology departments, either as stem cell transplant programmes or as blood transfusion departments, to provide under a contract with the company that will manufacture and supply the final medicine. The resource implications associated with this can impact on all haematology departments, not just stem cell transplant units, and should not be under‐estimated.
Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer
Authors: Loeb Stacy , Shin Sanghyuk S. , Broyles Dennis L. , Wei John T. , Sanda Martin , Klee George , Partin Alan W. , Sokoll Lori , Chan Daniel W. , Bangma Chris H. , van Schaik Ron H.N. , Slawin Kevin M. , Marks Leonard S. , Catalona William J. 
Published: October 2016

ObjectiveTo examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study.Materials and MethodsThe study population included 728 men, with prostate‐specific antigen (PSA) levels of 2–10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi‐site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI‐based multivariable predictive model, and created a nomogram.ResultsOf 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap‐corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision‐curve analysis.ConclusionUsing PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis.
Impact of suboptimal neoadjuvant chemotherapy on peri‐operative outcomes and survival after robot‐assisted radical cystectomy: a multicentre multinational study
Authors: Hinata Nobuyuki , Hussein Ahmed Aly , George Saby , Trump Donald L. , Levine Ellis G. , Omar Kawa , Dasgupta Prokar , Khan Muhammad Shamim , Hosseini Abolfazl , Wiklund Peter , Guru Khurshid A. 
Published: October 2016

ObjectivesTo evaluate the effect of suboptimal dosing on the outcomes of patients who received neoadjuvant chemotherapy (NAC) and robot‐assisted radical cystectomy (RARC).Patients and MethodsWe retrospectively reviewed 336 consecutive patients with urothelial carcinoma of the bladder who were treated with NAC and RARC at three academic institutions. Outcomes were compared among three groups: patients who received optimal NAC; patients who received suboptimal NAC; and those who did not receive NAC. To adjust for potential baseline differences between the three groups, propensity‐score‐based matching was performed. The suboptimal dose group was defined as those who received <3 cycles of cisplatin‐based chemotherapy, received a decreased dosage, or those not treated with cisplatin. Primary outcomes analysed were recurrence‐free survival (RFS) and overall survival (OS). Secondary outcomes were peri‐operative complications and readmissions after RARC.ResultsAfter propensity‐score matching, 69 patients in the cohort received optimal‐dose NAC, 41 received suboptimal NAC and 69 did not receive NAC. Complication rates and readmission rates did not differ significantly among the three groups. On multivariable analysis, suboptimal NAC and no NAC were independent predictors of worse RFS (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.2–5.7, P = 0.01 and HR 2.4, 95% CI 1.28–5.16, P = 0.01) and worse OS (HR 4.5, 95% CI 1.6–15.0, P < 0.01 and HR 4.9, 95% CI 1.9–15.6, P < 0.01) in patients who received NAC and RARC. Failure to achieve pathological complete response (ypT0N0) was also an independent predictor of worse RFS (HR 6.6, 95% CI 1.3–20.9; P = 0.02) and OS (HR 4.9, 95% CI 1.8–15.3; P = 0.02).ConclusionOptimal NAC resulted in a better RFS and OS when compared with suboptimal or no NAC. Suboptimal and no NAC were associated with worse OS and RFS. These findings will facilitate improved patient counseling and treatment selection.
Adjuvant radiation therapy is associated with better oncological outcome compared with salvage radiation therapy in patients with pN1 prostate cancer treated with radical prostatectomy
Authors: Tilki Derya , Preisser Felix , Tennstedt Pierre , Tober Patrick , Mandel Philipp , Schlomm Thorsten , Steuber Thomas , Huland Hartwig , Schwarz Rudolf , Petersen Cordula , Graefen Markus , Ahyai Sascha 
Published: October 2016

ObjectiveTo analyse the comparative effectiveness of no treatment (NT) or salvage radiation therapy (sRT) at biochemical recurrence (BCR) vs adjuvant radiation therapy (aRT) in patients with lymph node (LN)‐positive prostate cancer (PCa) after radical prostatectomy (RP).Patients and MethodsA total of 773 patients with LN‐positive PCa at RP, with or without additional radiation therapy (RT), in the period 2005–2013, were retrospectively analysed. Cox regression analysis was used to assess factors influencing BCR and metastasis‐free survival (MFS). Propensity score‐matched analyses were performed.ResultsThe median follow‐up for the entire patient group was 33.8 months. Four‐year BCR‐free and MFS rates were 43.3% and 86.6%, respectively, for all patients. In multivariate analysis, NT/sRT (n = 505) was an independent risk factor for BCR and metastasis compared with aRT (n = 213). The superiority of aRT was confirmed after propensity score matching. The 4‐year MFS in the matched cohort was 82.5% vs 91.8% for the NT/sRT and aRT groups, respectively (P = 0.02). Early sRT (pre‐RT prostate‐specific antigen [PSA] ≤0.5 ng/mL) compared with sRT at PSA >0.5 ng/mL was significantly associated with a lower risk of metastasis.ConclusionPatients with LN‐positive PCa who received aRT had a significantly better oncological outcome than patients with NT/sRT, independent of tumour characteristics. Patients with early sRT had higher rates of response and better MFS than patients with pre‐RT PSA >0.5 ng/mL.
Antioxidants from black and green tea: from dietary modulation of oxidative stress to pharmacological mechanisms
Authors: Peluso Ilaria , Serafini Mauro 
Published: October 2016

The consumption of tea (Camellia sinensis) has been correlated with a low incidence of chronic pathologies, such as cardiovascular disease and cancer, in which oxidative stress plays a critical role. Tea catechins and theaflavins are, respectively, the bioactive phytochemicals responsible for the antioxidant activity of green tea (GT) and black tea (BT). In addition to their redox properties, tea catechins and theaflavins could have also pharmacological activities, such as the ability to lower glucose, lipid and uric acid (UA) levels. These activities are mediated by pharmacological mechanisms such as enzymatic inhibition and interaction with transporters. Epigallocatechin gallate is the most active compound at inhibiting the enzymes involved in cholesterol and UA metabolism (hydroxy‐3‐methyl‐glutaryl‐CoA reductase and xanthine oxidase respectively) and affecting glucose transporters. The structural features of catechins that significantly contribute to their pharmacological effect are the presence/absence of the galloyl moiety and the number and positions of the hydroxyl groups on the rings. Although the inhibitory effects on α‐glucosidase, maltase, amylase and lipase, multidrug resistance 1, organic anion transporters and proton‐coupled folate transport occur at higher concentrations than those apparent in the circulation, these effects could be relevant in the gut. In conclusion, despite the urgent need for further research in humans, the regular consumption of moderate quantities of GT and BT can effectively modulate their antioxidant capacity, mainly in people subjected to oxidative stress, and could improve the metabolism of glucose, lipid and UA.Linked ArticlesThis article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc
Sleep Complaints and the 24‐h Melatonin Level in Individuals with Smith–Magenis Syndrome: Assessment for Effective Intervention
Authors: Spruyt Karen , Braam Wiebe , Smits Marcel , Curfs Leopold MG 
Published: October 2016

SummaryAimsIndividuals with Smith–Magenis syndrome (SMS) are reported to have a disrupted circadian rhythm. Our aim was to examine problematic sleeping in those attending our sleep clinic for the first time.MethodsAt intake, caregivers of 50 children and nine adults with SMS were surveyed about the sleep pattern and potential melatonin administration. Sampling of salivary melatonin levels was performed.ResultsAt intake, exogenous melatonin was used by 16 children (27.1% of sample; 56.3% male) with mean age 6.8 ± 2.8 years, whereas 34 children (57.6%; 7.5 ± 4.8 years old; 64.7% male) and nine adults (15.3%; 36.8 ± 15.3 years old; 44.4% male) were not taking melatonin at intake. Participants were reported to have problems with night waking and early awakenings regardless of melatonin administration. Overall, moderate to high levels of salivary melatonin at noon were found in individuals with SMS. In particular, children with SMS showed a disrupted melatonin pattern. Furthermore, the endogenous melatonin level, age, and gender may potentially interact, yielding the severity range of sleep disturbances reported in SMS.ConclusionTreatment of sleep problems in SMS is complex, and our findings may support person‐centered sleep and medication management. Future clinical trials including larger groups may shed light on such approaches.
Vitamin D in hematological disorders and malignancies
Authors: Kulling Paige M. , Olson Kristine C. , Olson Thomas L. , Feith David J. , Loughran Thomas P. 
Published: October 2016

AbstractCommonly known for its critical role in calcium homeostasis and bone mineralization, more recently vitamin D has been implicated in hematological cancer pathogenesis and shows promise as an anti‐cancer therapy. Serum levels of 25(OH)D3, the precursor to the active form of vitamin D, calcitriol, are frequently lower in patients with hematological disease compared to healthy individuals. This often correlates with worse disease outcome. Furthermore, diseased cells typically highly express the vitamin D receptor, which is required for many of the anti‐cancer effects observed in multiple in vivo and in vitro cancer models. In abnormal hematological cells, vitamin D supplementation promotes apoptosis, induces differentiation, inhibits proliferation, sensitizes tumor cells to other anti‐cancer therapies, and reduces the production of pro‐inflammatory cytokines. Although the dosage of vitamin D required to achieve these effects may induce hypercalcemia in humans, analogs and combinatorial treatments have been developed to circumvent this side effect. Vitamin D and its analogs are well tolerated in clinical trials, and thus, further investigation into the use of these agents in the clinic is warranted. Here, we review the current literature in this field.
Dependence of Asian honeybee on deciduous woody plants for pollen resource during spring to mid‐summer in northern Japan
Authors: Fujiwara Ayumi , Washitani Izumi 
Published: October 2016

AbstractApis cerana japonica Radoszkowski, endemic to Japan, is known to be one of the most important pollinators for wild plants and crops, such as buckwheat, in cool to warm temperate Japan. To determine the degree of dependence of A. cerana japonica on forest resources, we analyzed pollen brought back to nests in a typical “Satoyama” landscape with relatively high deciduous forest coverage in northern Japan. We divided the landscape elements of the study area into three types: deciduous forest, conifer plantation and open land according to landcover digital data, and each pollen taxon was assigned to one of these three types of landscape elements. We collected total pollen loads of 15.75 g (total of colonies A and B) in May (spring), 1.57 g (total of colonies A and C) in June (early summer), 19.03 g (total of colonies A, B and C) in July (mid‐summer) and 45.61 g (total of colonies A, B and D) in September (autumn). Deciduous forests are the most important foraging habitats for A. cerana japonica in the “Satoyama” landscape especially from spring to mid‐summer when mass flowering of tall trees and shrubs species provides rich floral resources for developing bee colonies. On the other hand, the bees frequently foraged from herbaceous plant species in autumn when flowering of tree species reduces and herbaceous plant species have flowering peaks. In turn, the bees provide pollination services to a number of wild flowers blooming in various forest layers ranging from the canopy to the understory layer.
Crystal structure of a crustacean hyperglycemic hormone (CHH) precursor suggests structural variety in the C‐terminal regions of CHH superfamily members
Authors: Tsutsui Naoaki , Sakamoto Tatsuya , Arisaka Fumio , Tanokura Masaru , Nagasawa Hiromichi , Nagata Koji 
Published: October 2016

The crustacean hyperglycemic hormone (CHH) is one of the major hormones in crustaceans, and peptides belonging to the CHH superfamily have been found in diverse ecdysozoans. Although the basic function of CHH is to control energy metabolism, it also plays various roles in crustacean species, such as in molting and vitellogenesis. Here, we present the crystal structure of Pej‐SGP‐I‐Gly, a partially active precursor of CHH from the kuruma prawn Marsupenaeus japonicus, which has an additional Gly residue in place of the C‐terminal amide group of the mature Pej‐SGP‐I. The 1.6‐angstrom crystal structure showed not only the common CHH superfamily scaffold comprising three α‐helices, three disulfide bridges, and a hydrophobic core but also revealed that the C‐terminal part has a variant backbone fold that is specific to Pej‐SGP‐I‐Gly. The α‐helix 4 of Pej‐SGP‐I‐Gly was much longer than that of molt‐inhibiting hormone (Pej‐MIH) from the same species, and as a result, the following C‐terminal helix, corresponding to α‐helix 5 in MIH, was not formed. Unlike monomeric Pej‐MIH, Pej‐SGP‐I‐Gly forms a homodimer in the crystal structure via its unique α‐helix 4. The unexpected dissimilar folds between Pej‐SGP‐I‐Gly and Pej‐MIH appear to be the result of their distinct C‐terminal amino acid sequences. Variations in amino acid sequences and lengths and the resulting variety of backbone folds allow the C‐terminal and sterically adjoining regions to confer different hormonal activities in diverse CHH superfamily members.DatabaseStructural data are available in the PDB under the accession number 5B5I.
Insecticidal activity of a recombinant knottin peptide from Loxosceles intermedia venom and recognition of these peptides as a conserved family in the genus
Authors: Matsubara F. H. , Meissner G. O. , Herzig V. , Justa H. C. , Dias B. C. L. , Trevisan‐Silva D. , Gremski L. H. , Gremski W. , Senff‐Ribeiro A. , Chaim O. M. , King G. F. , Veiga S. S. 
Published: October 2016

AbstractLoxosceles intermedia venom comprises a complex mixture of proteins, glycoproteins and low molecular mass peptides that act synergistically to immobilize envenomed prey. Analysis of a venom‐gland transcriptome from L. intermedia revealed that knottins, also known as inhibitor cystine knot peptides, are the most abundant class of toxins expressed in this species. Knottin peptides contain a particular arrangement of intramolecular disulphide bonds, and these peptides typically act upon ion channels or receptors in the insect nervous system, triggering paralysis or other lethal effects. Herein, we focused on a knottin peptide with 53 amino acid residues from L. intermedia venom. The recombinant peptide, named U2‐sicaritoxin‐Li1b (Li1b), was obtained by expression in the periplasm of Escherichia coli. The recombinant peptide induced irreversible flaccid paralysis in sheep blowflies. We screened for knottin‐encoding sequences in total RNA extracts from two other Loxosceles species, Loxosceles gaucho and Loxosceles laeta, which revealed that knottin peptides constitute a conserved family of toxins in the Loxosceles genus. The insecticidal activity of U2‐SCTX‐Li1b, together with the large number of knottin peptides encoded in Loxosceles venom glands, suggests that studies of these venoms might facilitate future biotechnological applications of these toxins.
An integration of mixed VND and VNS: the case of the multivehicle covering tour problem
Authors: Kammoun Manel , Derbel Houda , Ratli Mostapha , Jarboui Bassem 
Published: October 2016

AbstractThe multivehicle covering tour problem (m‐CTP) is a transportation problem with different kinds of locations, where a set of locations must be visited while another set must be close enough to planned routes. Given two sets of vertices V and W, where V represents the set of vertices that may be visited and W is a set of vertices that must be covered by up to m vehicles, the m‐CTP problem is to minimize vehicle routes on a subset of V including T, which represents the subset of vertices that must be visited through the use of potential locations in V. The variant of m‐CTP without a route‐length constraint is treated in this paper. To tackle this problem, we propose a variable neighborhood search heuristic based on variable neighborhood descent method. Experiments were conducted using the datasets based on traveling salesman problem library instances.