bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered modulation of lamin A/C‐HDAC2 interaction and p21 expression during oxidative stress response in HGPS
Authors: Mattioli Elisabetta , Andrenacci Davide , Garofalo Cecilia , Prencipe Sabino , Scotlandi Katia , Remondini Daniel , Gentilini Davide , Di Blasio Anna Maria , Valente Sergio , Scarano Emanuela , Cicchilitti Lucia , Piaggio Giulia , Mai Antonello , Lattanzi Giovanna 
Published: August 2018

AbstractDefects in stress response are main determinants of cellular senescence and organism aging. In fibroblasts from patients affected by Hutchinson–Gilford progeria, a severe LMNA‐linked syndrome associated with bone resorption, cardiovascular disorders, and premature aging, we found altered modulation of CDKN1A, encoding p21, upon oxidative stress induction, and accumulation of senescence markers during stress recovery. In this context, we unraveled a dynamic interaction of lamin A/C with HDAC2, an histone deacetylase that regulates CDKN1A expression. In control skin fibroblasts, lamin A/C is part of a protein complex including HDAC2 and its histone substrates; protein interaction is reduced at the onset of DNA damage response and recovered after completion of DNA repair. This interplay parallels modulation of p21 expression and global histone acetylation, and it is disrupted by LMNAmutations leading to progeroid phenotypes. In fact, HGPS cells show impaired lamin A/C‐HDAC2 interplay and accumulation of p21 upon stress recovery. Collectively, these results link altered physical interaction between lamin A/C and HDAC2 to cellular and organism aging. The lamin A/C‐HDAC2 complex may be a novel therapeutic target to slow down progression of progeria symptoms.
Phase I dose‐escalation trial of Sym004, an anti‐EGFR antibody mixture, in Japanese patients with advanced solid tumors
Authors: Kojima Takashi , Yamazaki Kentaro , Kato Ken , Muro Kei , Hara Hiroki , Chin Keisho , Goddemeier Thomas , Kuffel Stefan , Watanabe Morihiro , Doi Toshihiko 
Published: August 2018

Sym004 is a 1:1 mixture of two antibodies targeting non‐overlapping epitopes of the epidermal growth factor receptor that antagonizes ligand binding and induces receptor downregulation. In preclinical models, it has superior antitumor activity to cetuximab and panitumumab. Japanese adults aged ≥20 years with an Eastern Cooperative Oncology Group status of 0/1 and life expectancy ≥3 months were eligible. Patients in Part A (dose escalation) had refractory or recurrent late‐stage solid tumors and received Sym004 6 mg/kg/wk (n = 3), 9 mg/kg loading/6 mg/kg/wk (n = 6), 12 mg/kg/wk (n = 6), or 18 mg/kg biweekly (n = 6). Patients in expansion Part B (n = 30) had esophageal squamous cell carcinoma and received Sym004 at the dose recommended from Part A. Fifty‐one patients received Sym004. No dose‐limiting toxicities were observed in Part A. A dose of 12 mg/kg/wk was selected for Part B. All patients in Part B experienced treatment‐related adverse events, most commonly dermatitis acneiform (76.7%). Eighteen grade ≥3 treatment‐related adverse events and five serious adverse events occurred (cardiac arrest, lung infection, interstitial lung disease, toxic skin eruption, blood creatinine increase). Two patients had treatment‐related adverse events resulting in death (cardiac arrest and blood creatinine increase). Five patients in Part B had a best overall response of partial response, 12 stable diseases and 12 disease progression (1 not evaluable). The objective response rate was 16.7% (95% CI: 5.6%‐34.7%). Sym004 therapy was well tolerated with no dose‐limiting toxicities at any dose studied. Evidence of antitumor activity was seen in patients with esophageal squamous cell carcinoma. ClinicalTrials.gov Identifier: NCT01955473.
Long‐term clinical outcome of single implants inserted flaplessly or conventionally
Authors: Naeini Emitis N. , Dierens Melissa , Atashkadeh Mandana , De Bruyn Hugo 
Published: August 2018

AbstractBackgroundFlapless implant surgery is mostly performed using guided surgical protocols, however, long‐term studies on free‐handed flapless surgery for single implants are lacking.PurposeThis prospective study evaluates bone level changes, peri‐implant health, and complications of solitary implants placed using a conventional flap (F) or flaplessly (FL) after 6‐9 years.Materials and MethodsFifty‐three single TiUnite Brånemark implants were originally inserted in 49 patients using an one‐stage delayed loading protocol with flap (n = 27, F) or flaplessly (n = 26, FL) based on available bone volume and surgeon's decision‐making. Thirty‐six patients with 37 implants participated in the prospective follow‐up investigation 6‐9 years later whereby survival, bone level changes, peri‐implant health, and complications were assessed.ResultsAfter 88 months (range 76‐107), all implants were survived. For F and FL combined, the overall average radiographic bone level was above the first implant thread, 1.26 mm apical of the implant‐abutment junction (SD 1.08; 0‐4.9) and statistically comparable. Bone loss from time of loading was 0.49 mm (SD 1.1; −1.3 to 2.8) for F and −0.89 mm (SD 1.0; −2.8 to 0.7) for FL (P < .01), suggesting regrowth of bone in FL due to initial countersinking. One implant (2.7%) had a probing depth above 5 mm.ConclusionFree‐handed flapless implant surgery for single implants with neighboring teeth is a predictable long‐term treatment provided when there is sufficient bone volume.
Retrospective radiographic observational study of 1692 Straumann tissue‐level dental implants over 10 years: I. Implant survival and loss pattern
Authors: Kim Seungmin , Jung Ui‐Won , Cho Kyoo‐Sung , Lee Jung‐Seok 
Published: August 2018

AbstractBackgroundImplant dentistry is progressing based on extensive scientific results including preclinical and clinical studies. Researchers and clinicians have focused on implant designs and surface characteristics, which has resulted in various features being developed and introduced for enhancing osseointegration and reducing complications.PurposeThe purpose of this study was to determine the cumulative survival rates of Straumann tissue‐level dental implants over a 10‐year period and identify the patterns of implant loss at a single research institution.Materials and MethodsIn total, 1692 implants were installed in 881 patients who visited the Department of Periodontology, Dental Hospital, Yonsei University, Seoul from January 2003 to December 2009. Cases in which the implant was completely removed were defined as implant failures. Electronic or paper charts and radiographs were used to determine whether the implants failed. The survival rate of implants was analyzed using lifetime tables and Kaplan‐Meier survival estimates. Log‐rank test and Cox regression with shared frailty were used to analyze the risk factors and the types of implant failure.ResultsThe 10‐year cumulative survival rates were 98.23% and 95.70% at the implant and patient levels, respectively. Before installing a prosthesis (defined as the early stage), 13 implants in 10 patients were removed, while eight implants in seven patients were removed after completing a prosthesis (defined as the late stage). The cumulative survival rate was related to the implant diameter, length, site, and insertion torque. Most implant failures within 1 year were attributable to osseointegration failure. There were several cases of failure in the late stage without apparent marginal bone loss.ConclusionStraumann tissue‐level dental implants showed low failure rates and can be considered a useful long‐term treatment option. The length, placement site, and insertion torque might affect implant survival.
Fetal alcohol spectrum disorder in Australia: What is the current state of affairs?
Authors: Reid Natasha 
Published: August 2018

AbstractThe term fetal alcohol spectrum disorder (FASD) is used to describe a wide range of difficulties that individuals who are exposed to alcohol prenatally can face. FASD is a significant public health concern that is currently under‐recognised and consequently, under‐diagnosed in Australia. A new Commonwealth FASD Strategy (2018–2028) is being developed and the Australian Government has announced significant funding for the expansion of FASD prevention, diagnostic and intervention services around Australia. Therefore, it is timely to consider what the current state of affairs regarding FASD in Australia is and describe areas for future research and service delivery.
Interleukin‐1 receptor antagonist as a biomarker of sepsis in neutropenic haematological patients
Authors: Intke Carina , Korpelainen Sini , Hämäläinen Sari , Vänskä Matti , Koivula Irma , Jantunen Esa , Pulkki Kari , Juutilainen Auni 
Published: August 2018

AbstractObjectiveThe study aim was to compare the performance of interleukin‐1 receptor antagonist (IL‐1Ra) to C‐reactive protein (CRP) and procalcitonin (PCT) in early prediction of the clinical course of febrile neutropenia.MethodsThe study population consisted of 86 consecutive patients with febrile neutropenia who received intensive chemotherapy for haematological malignancy between November 2009 and November 2012 at the adult haematology ward of Kuopio University Hospital. Twenty‐three (27%) patients had acute myeloid leukaemia and 63 (73%) patients were autologous stem cell transplant recipients. IL‐1Ra, CRP and procalcitonin were measured at the onset of fever (d0), on day 1 (d1) and on day 2 (d2).ResultsEight patients developed severe sepsis, including three patients with septic shock. Eighteen patients had bacteraemia. After the onset of febrile neutropenia Youden´s indices (with their 95% confidence intervals) to identify severe sepsis were for IL‐1Ra on d0 0.57 (0.20‐0.71) and on d1 0.65 (0.28‐0.78), for CRP on d0 0.41 (0.04‐0.61) and on d1 0.47 (0.11‐0.67) and for PCT on d0 0.39 (0.05‐0.66) and on d1 0.52 (0.18‐0.76).ConclusionsIn haematological patients, IL‐1Ra has a comparable capacity with CRP and PCT to predict severe sepsis at the early stages of febrile neutropenia.
Neuroscience without borders: Preserving the history of neuroscience
Authors: Lorusso Lorenzo , Piccolino Marco , Motta Saba , Gasparello Anna , Barbara Jean‐Gaël , Bossi‐Régnier Laura , Shepherd Gordon M. , Swanson Larry , Magistretti Pierre , Everitt Barry , Molnár Zoltán , Brown Richard E. 
Published: August 2018

AbstractOver the last 50 years, neuroscience has enjoyed a spectacular development, with many discoveries greatly expanding our knowledge of brain function. Despite this progress, there has been a disregard for preserving the history of these discoveries. In many European countries, historic objects, instruments, and archives are neglected, while libraries and museums specifically focusing on neuroscience have been closed or drastically cut back. To reverse this trend, the Federation of European Neuroscience Societies (FENS) has organized a number of projects, including (a) the History of Neuroscience online projects, (b) the European Brain Museum Project (EBM), (c) the History online library, (d) theFENSmeeting History Corner, (e) history lectures in historic venues, and (f) a series of history seminars in various European venues. These projects aim to stimulate research in, and increase awareness of, the history of European neuroscience. Our seminars have attracted large audiences of students, researchers, and the general public, who have supported our initiatives for the preservation of the history of neuroscience for future generations and for the promotion of interest in the history of neuroscience. It is therefore urgent to develop new methods for preserving our history, not only in Europe but also in the rest of the world, and to increase greatly teaching and research in this important aspect of our scientific and cultural legacy.
The role of environmental factors in allergy: A critical reappraisal
Authors: Gilles Stefanie , Akdis Cezmi , Lauener Roger , Schmid‐Grendelmeier Peter , Bieber Thomas , Schäppi Georg , Traidl‐Hoffmann Claudia 
Published: August 2018

AbstractAllergies are usually referred to as type I hypersensitivity reactions against innocuous environmental antigens, characterized by a Th2/IgE‐dominated inflammation. They can manifest themselves in various organs, such as skin, gastrointestinal and respiratory tract, and comprise diseases as diverse as allergic rhinitis and conjunctivitis, bronchial asthma, oral allergy syndrome, food allergy, urticaria and atopic eczema, but also anaphylactic shock. Within the last decades, there was a significant global increase in allergy prevalence, which has been mostly attributed to changes in environment and lifestyle. But which, among all factors discussed, are the most relevant, and what are the mechanisms by which these factors promote or prevent the development of allergic diseases? To answer this, it is necessary to go back to the two key questions that have occupied allergy researchers for the last decades: Firstly, what makes an allergen an allergen? Secondly, why are more and more individuals affected? Within the last decade, we have made considerable progress in answering these questions. This review gives an overview over scientific progress in the field, summarizes latest findings and points out future prospective and research needs.
Methods for measurement of root canal curvature: a systematic and critical review
Authors: Hartmann R. C. , Fensterseifer M. , Peters O. A. , de Figueiredo J. A. P. , Gomes M. S. , Rossi‐Fedele G. 
Published: August 2018

AbstractThe assessment of root canal curvature is essential for clinical and research purposes. This systematic review presents an overview of the published techniques for the measurement of root canal curvature features using imaging and to provide a critique of their clinical application. A database search in PubMed, PubMed Central, Embase, Scopus, EBSCO Dentistry & Oral Sciences Source and Virtual Health Library was conducted, using appropriate key words to identify measurement methods for root canal curvatures. The search strategy retrieved 10594 records in total, and 31 records fulfilled the inclusion criteria. From 2D image acquisitions, eleven studies measured exclusively the angle of curvature, an additional thirteen measured other curvature features (level, height, radius, length and shape). Seven reports described methods from 3D imaging (CBCT, μCT). Root canal curvatures should be measured, for clinical proposes, to facilitate endodontic treatment planning, and in research, to reduce the risk of selection bias. This review has revealed that there are many methods described in the literature; however, no consensus exists on which method should be used. Some of the methodologies have potential clinical translation, whereas others are suitable for research purpose only, as they require a specific software or radiographic exposure in the mesiodistal direction.
Effect of midwife‐led care on birth outcomes of primiparas
Authors: Jiang Xiu‐Min , Chen Qi‐Yan , Guo Sheng‐Bin , Jin Li‐Zhu , Huang Xin‐Xin , Liu Xiu‐Wu , Hong Jin‐Xiu , Qu Hai‐Bin , Hu Rong‐Fang 
Published: August 2018

AbstractBackgroundThe high caesarean section rate is a prominent public health problem in China.AimThis study aimed to determine the effects of midwife‐led care during labour on birth outcomes for healthy primiparas.DesignRandomized controlled trial.SettingThe Obstetrics Department of Fujian Provincial Maternity and Child Health Hospital.MethodsA total of 666 primiparas in labour were randomly divided into an intervention and control group (333 in each group). The intervention group received a midwife‐led model of care during labour.ResultsData from 648 cases (331 intervention group and 317 control group) were analysed. The intervention group was less likely to experience caesarean section, postpartum haemorrhage, opiate analgesia, vaginal examinations, neonatal asphyxia, and neonatal hospitalization and was more likely to experience shorter length of labour and vaginal birth than the control group (all, P < 0.05). No differences were found in the number of artificial rupture of membranes and oxytocin use (P > 0.05).ConclusionsMidwife‐led care can reduce the caesarean section rate, promote normal birth, improve birth outcomes, and promote maternal and child health.
Human CD8 T‐cell activation in acute and chronic chikungunya infection
Authors: Dias Cinthia Nóbrega de Sousa , Gois Bruna Macêdo , Lima Viviane Silva , Guerra‐Gomes Isabel Cristina , Araújo Josélio Maria Galvão , Gomes Juliana de Assis Silva , Araújo Demétrius Antônio Machado , Medeiros Isac Almeida , Azevedo Fátima de Lourdes Assunção Araújo de , Veras Robson Cavalcanti , Janebro Daniele Idalino , Amaral Ian Porto Gurgel do , Keesen Tatjana Souza Lima 
Published: August 2018

SummaryThere is a need for more detailed elucidation of T‐cell immunity in chikungunya infection. CD8 T cells are one of main actors against viruses. Here, we analysed CD8+ T lymphocytes from patients in the acute and chronic phases of chikungunya disease (CHIKD). Our results demonstrate that CD8+ T cells expressed higher ex vivo granzyme B, perforin and CD107A expression in patients in the acute phase of CHIKD compared with healthy individuals and higher ex vivo expression of CD69, interleukin‐17A, interleukin‐10 and CD95 ligand, and co‐expression of CD95/CD95 ligand. These results elucidate the importance of these lymphocytes, demonstrating immune mechanisms mediated in human chikungunya infection.
The dynamics of simian immunodeficiency virus after depletion of CD8+ cells
Authors: Cardozo Erwing Fabian , Apetrei Cristian , Pandrea Ivona , Ribeiro Ruy M. 
Published: August 2018

SummaryHuman immunodeficiency virus infection is still one of the most important causes of morbidity and mortality in the world, with a disproportionate human and economic burden especially in poorer countries. Despite many years of intense research, an aspect that still is not well understood is what (immune) mechanisms control the viral load during the prolonged asymptomatic stage of infection. Because CD8+ T cells have been implicated in this control by multiple lines of evidence, there has been a focus on understanding the potential mechanisms of action of this immune effector population. One type of experiment used to this end has been depleting these cells with monoclonal antibodies in the simian immunodeficiency virus‐macaque model and then studying the effect of that depletion on the viral dynamics. Here we review what these experiments have told us. We emphasize modeling studies to interpret the changes in viral load observed in these experiments, including discussion of alternative models, assumptions and interpretations, as well as potential future experiments.
Modifying clonal selection theory with a probabilistic cell
Authors: Hodgkin Philip D. 
Published: August 2018

SummaryProblem‐solving strategies in immunology currently utilize a series of ad hoc, qualitative variations on a foundation of Burnet's formulation of clonal selection theory. These modifications, including versions of two‐signal theory, describe how signals regulate lymphocytes to make important decisions governing self‐tolerance and changes to their effector and memory states. These theories are useful but are proving inadequate to explain the observable genesis and control of heterogeneity in cell types, the nonlinear passage of cell fate trajectories and how the input from multiple environmental signals can be integrated at different times and strengths. Here, I argue for a paradigm change to place immune theory on a firmer philosophical and quantitative foundation to resolve these difficulties. This change rejects the notion of identical cell subsets and substitutes the concept of a cell as comprised of autonomous functional mechanical components subject to stochastic variations in construction and operation. The theory aims to explain immunity in terms of cell population dynamics, dictated by the operation of cell machinery, such as randomizing elements, division counters, and fate timers. The effect of communicating signals alone and in combination within this system is determined with a cellular calculus. A series of models developed with these principles can resolve logical cell fate and signaling paradoxes and offer a reinterpretation for how self‐non‐self discrimination and immune response class are controlled.
Insight into treatment ofHIVinfection from viral dynamics models
Authors: Hill Alison L. , Rosenbloom Daniel I. S. , Nowak Martin A. , Siliciano Robert F. 
Published: August 2018

SummaryThe odds of living a long and healthy life withHIVinfection have dramatically improved with the advent of combination antiretroviral therapy. Along with the early development and clinical trials of these drugs, and new field of research emerged calledviral dynamics, which uses mathematical models to interpret and predict the time‐course of viral levels during infection and how they are altered by treatment. In this review, we summarize the contributions that virus dynamics models have made to understanding the pathophysiology of infection and to designing effective therapies. This includes studies of the multiphasic decay of viral load when antiretroviral therapy is given, the evolution of drug resistance, the long‐term persistence latently infected cells, and the rebound of viremia when drugs are stopped. We additionally discuss new work applying viral dynamics models to new classes of investigational treatment forHIV, including latency‐reversing agents and immunotherapy.
Factors influencing refusing of flu vaccination among pregnant women in Italy: Healthcare workers’ role
Authors: Prospero Emilia , Galmozzi Sara , Paris Valentina , Felici Gessica , Barbadoro Pamela , D'Alleva Antonella , Zocco Gemma , Ciavattini Andrea 
Published: August 2018

BackgroundPregnant women are at increased risk of influenza complications. Influenza vaccine provides them a substantial protection.ObjectiveThe aim of this study was to investigate determinants associated with non‐adherence to influenza vaccine recommendations in pregnant women in Italy.MethodsA cross‐sectional study has been carried out among pregnant women attending their follow‐up visit in some mother and child services in a Region of Italy from October 2016 to January 2017. The study protocol was approved by the local research Ethics. A self‐administered close‐ended questionnaire has been administered to the pregnant women. Differences in background, socio‐demographic characteristics, knowledge and attitudes towards flu vaccine were tested in vaccinated and unvaccinated women. Multivariate analysis was performed to control for confounding factors.ResultsThree hundred and sixty‐six women answered the survey (97% response rate) and 96.1% (348) declared of being unvaccinated against influenza during the 2016‐2017 influenza season. Frequent reasons for refusing vaccination were drugs objection and concerns about vaccines’ effects. According to the refusal attitude, influenza knowledge was low in the group. Moreover, analysis showed that low adherence to vaccination is associated to lacking promotion of vaccination to pregnant women carried out by healthcare workers (P < 0.005).ConclusionsHealthcare workers have a key role in assisting women during the gestational period, so their active involvement in vaccination promotion is essential. It is necessary to improve health care workers’ knowledge about vaccine relevance in protecting pregnancy and their communication skills to properly inform pregnant women.