bluuebunny/crossref_metadata_2025_split huggingface dataset:
Botulinum Toxin A: Dose-dependent Effect on Reepithelialization and Angiogenesis
Authors: Gugerell Alfred , Kober Johanna , Schmid Melanie , Buchberger Elisabeth , Kamolz Lars-Peter , Keck Maike 
Published: August 2016

Background:
Botulinum (neuro)toxin A (BoNT) is widely used in the field of plastic and reconstructive surgery. Among treatment of pain, hyperhidrosis, or aesthetic purposes, it is also used to enhance wound healing and prevent excessive scar formation. Some clinical data already exist, but only little is known on a cellular level. The aim of this study was to evaluate the effect of BoNT on cells essential for wound healing in vitro. Therefore, primary human keratinocytes and endothelial cells were treated with different concentrations of BoNT and tested on proliferation, migration, and angiogenic behavior.

Methods:
BoNT was exposed to human keratinocytes and endothelial cells in a low (1 IU/mL), medium (10 IU/mL), and high (20 IU/mL) concentrations in cell culture. Proliferation and migration of the 2 cell types were observed and also the angiogenic potential of endothelial cells in vitro.

Results:
BoNT 20 IU/mL negatively influenced proliferation and migration of keratinocytes but not those of endothelial cells. Angiogenesis in vitro was less effective with the highest BoNT concentrations tested. Low concentrations of BoNT supported sprouting of endothelial cells.

Conclusions:
High concentrations of botulinum toxin interfered with wound closure as keratinocytes’ proliferation and migration were deteriorated. Furthermore, BoNT concentrations of 20 IU/mL constrain in vitro vessel formation but do not influence proliferation or migration of endothelial cells.
Utility of preclinical assays to assess stored platelet function
Authors: Francis Richard O. 
Published: August 2016

Purpose of review
Increased use of platelets and the brief shelf life allowed by storage at 22 °C are promoting exploration of new methods to store platelets. As storage may affect the hemostatic efficacy of platelets, it is very important to assess their in-vivo hemostatic efficacy. The potential usefulness of preclinical models in evaluating methods for storing platelets will be discussed.

Recent findings
The use of new technologies to examine the in-vitro characteristics of stored platelet products continues to evolve. Although in-vitro evaluation, coupled with posttransfusion recovery in healthy volunteers and studies in thrombocytopenic patients, are mainstays of evaluating new platelet products, the inclusion of preclinical animal models for the systematic evaluation of the in-vivo hemostatic function of these products would enhance the information gained from these studies.

Summary
The application of novel integrated platforms will be key in realizing advancements in the field of platelet storage. These preclinical models can be applied to rapidly assess the effect of new additive solutions and storage methods on platelet hemostatic function prior to performing human clinical trials.
Matched sibling donor hematopoietic stem cell transplantation for thalassemia
Authors: Issaragrisil Surapol , Kunacheewa Chutima 
Published: August 2016

Purpose of review
Bone marrow transplantation is the only curative treatment for severe thalassemia. Since its successful first report in 1981, more than 4000 patients with this disease worldwide underwent bone marrow transplantation. The purpose of this review is to update the most recent reports of matched sibling donor hematopoietic stem cell transplantation in thalassemia.

Recent findings
Advanced and improved transplant techniques result in the improved outcomes in those transplants from a matched sibling donor with transplant-related mortality less than 5%. Class 3 patients aged at least 7 years and liver enlargement at least 5 cm have a very high risk of graft rejection and regimen-related toxicity. This subset of patients require innovative approaches to overcome the morbidity and mortality. Those include the addition of hydroxyurea, azathioprine, and fludarabine as preconditioning to busulfan, thiotepa, and cyclophosphamide. Novel conditioning consisting of pretransplant immunosuppression with two cycles of fludarabine and dexamethasone followed by reduced intensity conditioning with fludarabine, busulfan, and thymoglobulin has been developed.

Summary
Bone marrow transplantation in young low-risk (class 1 and 2) patients should be performed as soon as possible. For class 3 severe thalassemia, novel conditioning regimens have been developed to overcome graft rejection and regimen-related toxicity. Hematopoietic stem cell transplantation in adults who have been well chelated should be offered with clinical trials.
Loss of a Candidate Biliary Atresia Susceptibility Gene, add3a, Causes Biliary Developmental Defects in Zebrafish
Authors: Tang Vivian , Cofer Zenobia C. , Cui Shuang , Sapp Valerie , Loomes Kathleen M. , Matthews Randolph P. 
Published: August 2016

ABSTRACTObjectives:Biliary atresia (BA) is a progressive fibroinflammatory cholangiopathy affecting the bile ducts of neonates. Although BA is the leading indication for pediatric liver transplantation, the etiology remains elusive. Adducin 3 (ADD3) and X‐prolyl aminopeptidase 1 (XPNPEP1) are 2 genes previously identified in genome‐wide association studies as potential BA susceptibility genes. Using zebrafish, we investigated the importance of ADD3 and XPNPEP1 in functional studies.Methods:To determine whether loss of either gene leads to biliary defects, we performed morpholino antisense oligonucleotide (MO) knockdown studies targeting add3a and xpnpep1 in zebrafish. Individuals were assessed for decreases in biliary function and the presence of biliary defects. Quantitative polymerase chain reaction was performed on pooled 5 days postfertilization larvae to assess variations in transcriptional expression of genes of interest.Results:Although both xpnpep1 and add3a are expressed in the developing zebrafish liver, only knockdown of add3a produced intrahepatic defects and decreased biliary function. Similar results were observed in homozygous add3a mutants. MO‐mediated knockdown of add3a also showed higher mRNA expression of hedgehog (Hh) targets. Inhibition of Hh signaling rescued biliary defects caused by add3a knockdown. Combined knockdown of add3a and glypican‐1 (gpc1), another mediator of Hh activity that is also a BA susceptibility gene, resulted in more severe biliary defects than knockdown of either alone.Conclusions:Our results support previous studies identifying ADD3 as a putative genetic risk factor for BA susceptibility. Our results also provide evidence that add3a may be affecting the Hh pathway, an important factor in BA pathogenesis.
Translating Neurodevelopmental Care Policies Into Practice: The Experience of Neonatal ICUs in France—The EPIPAGE-2 Cohort Study
Authors: Pierrat Veronique , Coquelin Anaëlle , Cuttini Marina , Khoshnood Babak , Glorieux Isabelle , Claris Olivier , Durox Mélanie , Kaminski Monique , Ancel Pierre-Yves , Arnaud Catherine 
Published: August 2016

Objectives:
To describe the implementation of neurodevelopmental care for newborn preterm infants in neonatal ICUs in France in 2011, analyze changes since 2004, and investigate factors associated with practice.

Design:
Prospective national cohort study of all births before 32 weeks of gestation.

Setting:
Twenty-five French regions.

Participants:
All neonatal ICUs (n = 66); neonates surviving at discharge (n = 3,005).

Interventions:
None.

Measurements and Main Results:
Neurodevelopmental care policies and practices were assessed by structured questionnaires. Proportions of neonates initiating kangaroo care during the first week of life and those whose mothers expressed breast milk were measured as neurodevelopmental care practices. Multilevel logistic regression analyses were used to investigate relationships between kangaroo care or breast-feeding practices and unit policies, taking into account potential confounders. Free visiting policies, bed availability for parents, and kangaroo care encouragement significantly improved between 2004 and 2011 but with large variabilities between units. Kangaroo care initiation varied from 39% for neonates in the most restrictive units to 68% in less restrictive ones (p < 0.001). Individual factors associated with kangaroo care initiation were gestational age (odds ratio, 5.79; 95% CI, 4.49–7.48 for babies born at 27–31 wk compared with babies born at 23–26 wk) and, to a lesser extent, single pregnancy, birthweight above the 10th centile, and mother’s employment before pregnancy. At unit level, policies and training in neurodevelopmental care significantly influenced kangaroo care initiation (odds ratio, 3.5; 95% CI, 1.8–7.0 for Newborn Individualized Developmental Care and Assessment Program implementation compared with no training). Breast milk expression by mothers was greater in units with full-time availability professionals trained for breast-feeding support (60% vs 73%; p < 0.0001).

Conclusions:
Dissemination of neurodevelopmental practices occurred between 2004 and 2011, but large variabilities between units persist. Practices increased in units with supportive policies. Specific neurodevelopmental care training with multifaceted interventions strengthened the implementation of policies.
Donor Characteristics of Pancreas Transplantation in Australia and New Zealand: A Cohort Study 1984-2014
Authors: Peng Xi (Alex) , Kelly Patrick J. , Mulley William R. , Pleass Henry , Pilmore Helen , Webster Angela C. 
Published: August 2016

Background
The aim of this study was to audit the characteristics of pancreas donors over time in Australia and New Zealand. Pancreas transplantation was introduced in Australian and New Zealand in 1984.

Methods
We analyzed data from the Australia and New Zealand Islet and Pancreas Transplant Registry, 1984 to 2014. We investigated the variation of donor characteristics of sex, age, body mass index, smoking status, blood group, multiple organ donation, cytomegalovirus status, terminal creatinine, hypertension, and cause of death for pancreas transplantation over time. We used χ2 test (Fisher test when necessary) or analysis of variance to test difference for categorical or continuous characteristics, respectively.

Results
There were 628 pancreas donors from 1984 to 2014. Donor body mass index (from 21.9 to 24.0, P < 0.001) and age (from 23.9 to 28.5, P = 0.02) have both increased while terminal creatinine has decreased (86.3 to 73.3, P = 0.01) from 1995 to 2014. In the meantime, the proportions of donors with hypertension (from 19% to 1%, P < 0.001) and who were smokers (from 54% to 15%, P < 0.001) have decreased. Profile of cause of donor death has also changed over time (P = 0.06) with increase in cerebral hypoxia/ischemia (from 3% to 17%) and reductions in intracranial hemorrhage (27% to 13%).

Conclusions
Many donor characteristics have changed over time. The most significant changes appear to reflect changes in the general population, rather than changes in donor selection.
Dissection of molecular assembly dynamics by tracking orientation and position of single molecules in live cells
Authors: Mehta Shalin B. , McQuilken Molly , Riviere Patrick La , Occhipinti Patricia , Verma Amitabh , Oldenbourg Rudolf , Gladfelter Amy S. , Tani Tomomi 
Published: August 2016

AbstractRegulation of order, such as orientation and conformation, drives the function of most molecular assemblies in living cells, yet remains difficult to measure accurately through space and time. We built an instantaneous fluorescence polarization microscope, which simultaneously images position and orientation of fluorophores in living cells with single-molecule sensitivity and a time resolution of 100ms. We developed image acquisition and analysis methods to track single particles that interact with higher-order assemblies of molecules. We tracked the fluctuations in position and orientation of molecules from the level of an ensemble of fluorophores down to single fluorophores. We tested our systemin vitrousing fluorescently labeled DNA and F-actin in which the ensemble orientation of polarized fluorescence is known. We then tracked the orientation of sparsely labeled F-actin network at the leading edge of migrating human keratinocytes, revealing the anisotropic distribution of actin filaments relative to the local retrograde flow of the F-actin network. Additionally, we analyzed the position and orientation of septin-GFP molecules incorporated in septin bundles in growing hyphae of a filamentous fungus. Our data indicate that septin-GFP molecules undergo positional fluctuations within, ∼350nm of the binding site and angular fluctuations within ∼30°of the central orientation of the bundle. By reporting position and orientation of molecules while they form dynamic higher-order structures, our approach can provide new insights into how micron-scale ordered assemblies emerge from nanoscale molecules in living cells.Significance StatementIn living cells, the 3D architecture of molecular assemblies such as chromosomes, lipid bilayers, and the cytoskeleton is regulated through the interaction among their component molecules. Monitoring the position and orientation of constituent molecules is important for understanding the mechanisms that govern the structure and function of these assemblies. We have developed an instantaneous fluorescence polarization microscope to track the position and orientation of fluorescently labeled particles, including single molecules, which form micron-scale macromolecular assemblies in living cells. Our imaging approach is broadly applicable to the study of dynamic molecular interactions that underpin the function of micron-scale assemblies in living cells.
Cleavage modification did not alter early blastomere fates during bryozoan evolution
Authors: Vellutini Bruno C. , Martín-Durán José M. , Hejnol Andreas 
Published: August 2016

AbstractStereotypic cleavage patterns play a crucial role in cell fate determination by precisely positioning early embryonic blastomeres. Although misplaced cell divisions can alter blastomere fates and cause embryonic defects, cleavage patterns have changed several times during animal evolution. Here, we analyze the evolutionary transition from spiral cleavage – a stereotypic pattern remarkably conserved in many protostomes – to the biradial cleavage of bryozoans. We characterize the cell lineage, MAPK signaling and expression of several developmental genes in the bryozoanMembranipora membranacea, and found that the fate and the genes expressed in the early bryozoan blastomeres are similar to their putative homologous blastomeres in spiral-cleaving embryos. The data indicate that cleavage geometry evolved independent from other developmental traits during the transition from spiral to biradial cleavage in the bryozoan lineage, revealing that stereotypic cleavage patterns can be evolutionarily modified without major changes to the molecular identity and fate of embryonic blastomeres.
Investigations of human myosin VI targeting using optogenetically-controlled cargo loading
Authors: French Alexander R. , Sosnick Tobin R. , Rock Ronald S. 
Published: August 2016

AbstractMyosins play countless critical roles in the cell, each requiring it to be activated at a specific location and time. To control myosin VI with this specificity, we created a novel optogenetic tool for activating myosin VI by fusing the light-sensitiveAvena sativaphototropin1 LOV2 domain to a peptide from Dab2 (LOVDab), a myosin VI cargo protein. Our approach harnesses the native targeting and activation mechanism of myosin VI, allowing direct inferences on myosin VI function. LOVDab robustly recruits human full length myosin VI to various organellesin vivoand hinders peroxisome motion in a light-controllable manner. LOVDab also activates myosin VI in anin vitrogliding filament assay. Our data suggest that protein and lipid cargoes cooperate to activate myosin VI, allowing myosin VI to integrate Ca2+, lipid, and protein cargo signals in the cell to deploy in a site-specific manner.Significance StatementMyosins are a broad class of motor proteins that generate force on actin filaments and fulfill contractile, transport, and anchoring roles. Myosin VI, the only myosin to walk toward the pointed end of actin filaments, is implicated in cancer metastasis and deafness. Intriguingly, myosin VI may play both transport and anchoring roles, depending upon where it is activated in the cell. Here we develop an optogenetic tool for studying myosin VI activation with high spatial and temporal resolution. Our approach photoactivates unmodified myosin VI through its native cargo pathway, enabling investigation of motor function and activation partners with minimal perturbation. This approach allows us to detect how and where myosin VI integrates multiple protein and second messenger signals to activate.
Dopaminergic drugs decrease loss aversion in Parkinson’s disease with but not without depression
Authors: Timmer Monique H.M. , Sescousse Guillaume , Esselink Rianne A.J. , Piray Payam , Cools Roshan 
Published: August 2016

AbstractDepression, a common non-motor symptom of Parkinson’s disease (PD), is accompanied by impaired decision making and an enhanced response to aversive outcomes. Current strategies to treat depression in PD include dopaminergic medication. However, their use can be accompanied by detrimental side effects, such as enhanced risky choice. The mechanisms underlying dopamine-induced increases in risky choice are unclear. In the current study we adopt a clinical-neuroeconomic approach to investigate the effects of dopaminergic medication on loss aversion during risky choice in depressed and non-depressed PD. Twenty-three healthy controls, 21 depressed and 22 non-depressed PD patients were assessed using a well-established gambling task measuring loss aversion during risky choice. Patients were tested on two occasions, after taking their normal dopaminergic medication (ON) and after withdrawal of their medication (OFF). Dopaminergic medication decreased loss aversion to a greater extent in depressed than non-depressed PD patients. Moreover, we show that the degree to which dopaminergic medication decreases loss aversion correlated with current depression severity and with drug effects on depression scores. These findings demonstrate that dopamine-induced changes in loss aversion depend on the presence of depressive symptoms in PD.Significance statementDopaminergic medication that is used to treat motor and non-motor symptoms in patients with Parkinson’s disease is known to contribute to risky decision-making. The underlying mechanisms are unclear. The present study demonstrates that dopaminergic medication in Parkinson’s disease decreases loss aversion during risky choice, but only in depressed and not in non-depressed patients with Parkinson’s disease. These results advance our understanding of the mechanisms underlying dopamine-induced risky choice, while also identifying depression as an important factor that confers vulnerability to such dopamine-induced risky choice.Conflict of InterestThe authors declare no competing financial interests.
Development of vaccines against pertussis caused by Bordetella holmesii using a mouse intranasal challenge model
Authors: Saito Momoko , Odanaka Keita , Otsuka Nao , Kamachi Kazunari , Watanabe Mineo 
Published: August 2016

ABSTRACTBordetella holmesii is recognized as the third causative agent of pertussis (whooping cough) in addition to Bordetella pertussis and Bordetella parapertussis. Pertussis caused by B. holmesii is not rare around the world. However, to date, there is no effective vaccine against B. holmesii. We examined the protective potency of pertussis vaccines available in Japan and vaccines prepared from B. holmesii. A murine model of respiratory infection was exploited to evaluate protective potency. No Japanese commercial pertussis vaccines were effective against B. holmesii. In contrast, a wBH vaccine and an aBH vaccine prepared from B. holmesii were both protective. Passive immunization with sera from mice immunized with aBH vaccine established protection against B. holmesii, indicating that B. holmesii‐specific serum antibodies might play an important role in protection. Immuno‐proteomic analysis with sera from mice immunized with aBH vaccine revealed that the sera recognized a BipA‐like protein of B. holmesii. An aBH vaccine prepared from a BipA‐like protein‐deficient mutant strain did not have a protective effect against B. holmesii. Taken together, our results suggest that the BipA‐like protein plays an important role in the protective efficacy of aBH vaccine.
Day‐surgery approach for incision and drainage of an abscess
Authors: Balakumar Ramkishan , Samuel Nehemiah , Jackson Andrew , Butterworth Joanne , Shiwani Muhammad H. 
Published: August 2016

AimThe treatment for an abscess is usually incision and drainage in the emergency theatre. These cases are considered a low priority, and therefore, their procedure is often delayed, resulting in longer inpatient stay. Recent guidelines have recommended a day‐surgery approach for these cases.Patients and MethodsAn abscess pathway was created to allow patients to go home and return the following morning to be operated first on the emergency list and subsequently discharged by nurses. The process was audited before (retrospectively) and after (prospectively) the introduction of the pathway. It looked at clinically‐well adults presenting with a superficial uncomplicated abscess.ResultsA total of 40 and 35 patients were included for the preliminary and subsequent audit cycle, respectively. The introduction of the pathway reduced the mean inpatient stay from 29.3 to 13.8 h, reduced the preoperative waiting times from 12.5 to 4.3 h and resulted in only 26 per cent of patients waiting more than 6 h compared with 68 per cent prior to its introduction. Inpatient hospital costs per patient (calculated at £250/bed/day for non‐clinical services) were mean cost to £312.50 and £27.78 per patient, respectively, saving £284.72 per patient.ConclusionThe abscess pathway has reduced preoperative waiting times and total inpatient stay significantly, without compromising patient safety.
Rapid Identification and Comparison of Compounds with Antioxidant Activity in Coreopsis tinctoria Herbal Tea by High‐Performance Thin‐Layer Chromatography Coupled with DPPH Bioautography and Densitometry
Authors: Lam Shing‐Chung , Lam Sio‐Fong , Zhao Jing , Li Shao‐Ping 
Published: August 2016

AbstractA simple and efficient method based on high‐performance thin‐layer chromatography coupled with 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) bioautography (HPTLC‐DPPH) was established for the screening and comparison of antioxidants in different parts of Coreopsis tinctoria herbal tea from different origins and other related herbal tea materials, which used Chrysanthemum morifolium cv. “Gongju” and “Hangju” in this study. Scanning densitometry after DPPH derivatization was applied for the determination of antioxidant capacities of isolated compounds in each sample. It is considered that ethanol extracts of C. tinctoria had stronger antioxidant activity and more characteristic bands than those of 2 compared samples, C. morifolium cv. “Gongju” and “Hangju.” Chemometric analysis results showed that the combination of hierarchical clustering analysis and principal component analysis based on determined antioxidant capacities could be used for the discrimination of different parts of C. tinctoria and C. morifolium. Results showed that 7 compounds made up the major contributions of antioxidant activity in C. tinctoria, including okanin, isookanin, marein, flavanomarein, 5,7,3′,5′‐tetrahydroxyflavanone‐7‐O‐glucoside, 3,5‐dicaffeoylquinic acid, and chlorogenic acid. Therefore, 7 compounds were identified as major antioxidant biomarkers for quality control of C. tinctoria. Results demonstrated that the established method could be applied for the identification of C. tinctoria, and were beneficial for the bioactivity‐based quality control of C. tinctoria.