bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical and mechanical properties of Tunisian women hair
Authors: Sayahi E. , Harizi T. , Msahli S. , Sakli F. 
Published: February 2016

AbstractBackgroundMechanical analysis of human hair may provide the dermatologists with several markers of considerable diagnostic importance. The aim of this study was to analyse the physical and mechanical properties of Tunisian women's hair.MethodsSurface characteristics were determined with scanning electron microscopy (SEM). Mechanical properties were studied using the Miniature Tensile Tester Model 675 (MTT675), and the Fibre Dimensional Analysis Unit Model 765 (FDAS765) of Dia‐Stron, UK, was used to measure the cross‐sectional area.ResultsThe cross‐sectional area, stress at break, strain at break, elastic modulus and total work were 4643.21 ± 817 μm2, 201 ± 11.26 MPa, 47.3 ± 3.6%, 3.1 ± 0.16 GPa, and 9 ± 2.2 mJ, respectively. The effects of the factors ‘hair curliness’ and ‘age’ on the physical and mechanical properties were studied. The cross‐sectional area and the break load are influenced by the factors ‘age’ and ‘curl type’, whereas Young's modulus shows a significant dependency only on the age.ConclusionTunisian women hair presented good mechanical properties as shown by a greater breaking stress and higher breaking strain. Both curl type and age are important factors to consider when evaluating the behaviour of hair.
Efficacy of three different pulpotomy agents in primary molars: a randomized control trial
Authors: Rajasekharan S. , Martens L. C. , Vandenbulcke J. , Jacquet W. , Bottenberg P. , Cauwels R. G. E. C. 
Published: February 2016

AbstractAimTo compare the clinical and radiographic efficacy of Biodentine™, ProRoot® White Mineral Trioxide Aggregate (WMTA) and Tempophore™ as pulpotomy medicaments in the treatment of carious primary molars.MethodologyA parallel‐design, randomized controlled trial was developed. Patients above 3 years of age with carious primary teeth with vital pulps without spontaneous pain or history of swelling were included. Fifty‐eight patients (82 teeth) with a mean age of 4.79 ± 1.23 years were included. The teeth were randomized, blinded and allocated to one of the three groups (Biodentine™, ProRoot® WMTA or Tempophore™) for pulpotomy treatment. All teeth were followed up clinically and radiographically (after 6, 12 and 18 months) by two blinded calibrated investigators. A generalized estimating equation (GEE), Wald chi‐square test and an intention‐to‐treat analysis (ITT) with ‘last carried forward’ approach were performed using Statistical Package for Social Sciences v 21.0 (IBM Corp., Armonk, NK, USA).ResultsForty‐six patients and 69 teeth were available for follow‐up after 18 months. Clinical success (radiographic success in parenthesis) was 95.24% (94.4%), 100% (90.9%) and 95.65% (82.4%) in the Biodentine™, ProRoot® WMTA and Tempophore™ groups, respectively, but the difference was not significant. Pulp canal obliteration was significantly different amongst the experimental groups as the Biodentine™ group exhibited significantly more pulp canal obliteration when compared to the ProRoot® WMTA group at 6 months (P = 0.008) and 18 months (P = 0.003).ConclusionsAfter 18‐month follow‐up, there was no significant difference between Biodentine™ in comparison with ProRoot® WMTA or Tempophore™.
Secukinumab improves patient‐reported psoriasis symptoms of itching, pain, and scaling: results of two phase 3, randomized, placebo‐controlled clinical trials
Authors: Strober Bruce , Sigurgeirsson Bárður , Popp Georg , Sinclair Rodney , Krell James , Stonkus Sigitas , Septe Marcis , Elewski Boni E. , Gottlieb Alice B. , Zhao Yang , Tran Mary H. , Karpov Alexander , McLeod Lori D. , Mordin Margaret , Papavassilis Charis , Nyirady Judit , Lebwohl Mark 
Published: February 2016

AbstractBackgroundSecukinumab is a human interleukin‐17A antagonist indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The objective of this analysis was to measure the treatment response on psoriasis‐related itching, pain, and scaling via the Psoriasis Symptom Diary (PSD)©.MethodsERASURE (n = 738) and FIXTURE (n = 1306) were double‐blind, multicenter phase 3 studies in adults randomized to secukinumab (300, 150 mg, n = 1144) or placebo (n = 574) (administered at Weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks) or a biologic active control (FIXTURE only). Patient‐reported itching, pain, and scaling were assessed during the first 12 weeks of treatment using the PSD.The results reported here are limited to subjects in the secukinumab and placebo treatment groups who completed the PSD. The proportions of subjects achieving prespecified responses (improvement:reduction of at least 2.2 points for itching, 2.2 points for pain, or 2.3 points for scaling) were compared for secukinumab versus placebo.ResultsOverall, 39% of subjects completed the PSD at baseline and Week 12 (n = 453 secukinumab; 225 placebo). Subjects treated with secukinumab achieved significantly greater improvements in itching, pain, and scaling at Week 12 versus placebo (all P < 0.0001) and had significantly greater proportions of itching, pain, and scaling responders at Week 12 versus placebo (all P < 0.05).ConclusionSecukinumab significantly improves patient‐reported itching, pain, and scaling in adults with moderate to severe psoriasis compared with placebo.
Glycosylated haemoglobin assessment in diabetic patients with acute coronary syndromes
Authors: Snir A. , Dabin B. , Hyun K. , Yamen E. , Ryan M. , Aliprandi‐Costa B. , Brieger D. 
Published: February 2016

BackgroundGuidelines for the management of acute coronary syndromes (ACS) advocate for maintaining adequate long‐term glycaemic control in diabetic patients. Glycosylated haemoglobin (HbA1c) measurement is commonly used to monitor long‐term glycaemic control in diabetes.AimsTo evaluate the frequency and clinical predictors of in‐hospital HbA1c measurement in diabetic patients presenting with ACS and the relationship between HbA1c assessment and mortality following discharge.MethodsThis registry‐based cohort study included 1743 diabetic patients from 33 representative hospitals across Australia with a final diagnosis of ACS. Independent predictors of HbA1c assessment were evaluated using a multivariable logistic generalised estimating equations analysis. The association between HbA1c assessment and mortality following discharge was evaluated using Cox proportional hazard analysis.ResultsSeven hundred and fourteen (41%) patients had HbA1c assessment during admission. Frequency of assessment varied markedly between hospitals (7.7–87.6%). HbA1c assessment was significantly more frequent in hospitals with catheterisation laboratories. Frequency of assessment was not associated with location of hospital (rural vs urban) or hospital capacity. Independent clinical predictors of HbA1c assessment across participating hospitals were younger age, ST‐Elevation Myocardial Infarction, cardiac catheterisation and coronary artery bypass surgery during admission. HbA1c assessment was associated with higher rates of coronary catheterisation, revascularisation and receipt of evidence‐based medicines but not with mortality during 6 months following discharge (hazard ratio, 0.48; 95% confidence interval, 0.19–1.18).ConclusionFrequency of HbA1c assessment varies markedly between hospitals, and most diabetic patients admitted for ACS in Australia do not receive assessment of pre‐admission glycaemic control. HbA1c assessment was associated with better evidence driven medical care.
The epidemiology of in‐hospital cardiac arrests in Australia and New Zealand
Authors: Fennessy G. , Hilton A. , Radford S. , Bellomo R. , Jones D. 
Published: February 2016

BackgroundThe epidemiology of in‐hospital cardiac arrests (IHCA) in Australia and New Zealand (ANZ) has not been systematically assessed.AimTo conduct a systematic review of the frequency, characteristics and outcomes of adult IHCA in ANZ.MethodsMedline search for studies published in 1964–2014 using MeSH terms ‘arrest AND hospital AND Australia’, ‘arrest AND hospital AND New Zealand’, ‘inpatient AND arrest AND Australia’ and ‘inpatient AND arrest AND New Zealand’.ResultsWe screened 934 studies, analysed 50 and included 30. Frequency of IHCA ranged from 1.31 to 6.11 per 1000 admissions in 4 population studies and 0.58 to 4.59 per 1000 in 16 cohort studies. The frequency was 4.11 versus 1.32 per 1000 admissions in hospitals with rapid response system (RRS) compared with those without (odds ratio: 0.32; 95% confidence interval 0.28‐0.37; P < 0.001). On aggregate, the initial cardiac rhythm was ventricular tachycardia/fibrillation in 31.4% (range 19.0–48.8%) in 10 studies reporting such data. On aggregate, IHCA were witnessed in 80.2% cases (three studies) and monitored patients in 53.4% cases (four studies). Details of life support were poorly documented. On aggregate, return of spontaneous circulation occurred in 46.0% of patients. Overall, 74.6% (range 59.4–77.5%) died in‐hospital but survival was higher among monitored or younger patients, in those with a shockable rhythm, or during working hours.ConclusionIHCA are uncommon in ANZ and three quarters die in‐hospital. However, their frequency varies markedly across institutions and may be affected by the presence of RRS. Where reported, the long‐term outcomes survivors appear to have acceptable neurological outcomes.
Fostering of advanced mutualism with gut microbiota by Immunoglobulin A
Authors: Sutherland Duncan B. , Suzuki Keiichiro , Fagarasan Sidonia 
Published: February 2016

SummaryImmunoglobulin A (IgA), the most abundantly secreted antibody isotype in mammals, not only provides direct immune protection to neonates via maternal milk but also helps program the infant immune system by regulating the microbiota. IgA continues to maintain dynamic interactions with the gut microbiota throughout life and this influences immune system homeostasis as well as other physiological processes. The secretory IgA produced independently of T‐cell selection are commonly referred to as natural or innate antibodies. Our studies have shown that innate‐IgA, while effective at excluding microorganisms from the gut, does not promote mutualism with the microbiota in the same way as adaptive‐IgA that is selected in T cell‐dependent germinal center reactions. Adaptive‐IgA fosters more advanced mutualism with the microbiota than innate‐IgA by selecting and diversifying beneficial microbial communities. In this review, we suggest that the diversified microbiota resulting from adaptive‐IgA pressure was pivotal in promoting ecological adaptability and speciation potential of mammals.
Targeting plasma cells: are we any closer to a panacea for diseases of antibody‐secreting cells?
Authors: Low Michael , Infantino Simona , Grigoriadis George , Tarlinton David 
Published: February 2016

SummaryAntibody‐secreting cells (ASCs) are critical for a functional and effective adaptive immune system. In a number of illnesses, however, these same cells contribute to the underlying disease state leading to significant morbidity and mortality. While therapeutic targeting of antibody‐secreting cells has progressed significantly over the last two decades, many of these conditions remain major health problems. In this review, we will discuss current and potential therapeutic targeting of ASCs in the context of the known biology of these cells.
Immunogenicity of therapeutic recombinant immunotoxins
Authors: Mazor Ronit , Onda Masanori , Pastan Ira 
Published: February 2016

SummaryRecombinant immunotoxins (RITs) are chimeric proteins designed to treat cancer. They are made up of an Fv or Fab that targets an antigen on a cancer cell fused to a 38‐kDa portion of Pseudomonas exotoxin A (PE38). Because PE38 is a bacterial protein, it is highly immunogenic in patients with solid tumors that have normal immune systems, but much less immunogenic in patients with hematologic malignancies where the immune system is suppressed. RITs have shown efficacy in refractory hairy cell leukemia and in some children with acute lymphoblastic leukemia, but have been much less effective in solid tumors, because neutralizing antibodies develop and prevent additional treatment cycles. In this paper we will (i) review data from clinical trials describing the immunogenicity of PE38 in different patient populations; (ii) review results from clinical trials using different immunosuppressive drugs; and (iii) describe our efforts to make new less‐immunogenic RITs by identifying and removing T‐ and B‐cell epitopes to hide the RIT from the immune system.
Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site
Authors: Kiefer Jonathan D. , Neri Dario 
Published: February 2016

SummaryThe activation of the immune system for a selective removal of tumor cells represents an attractive strategy for the treatment of metastatic malignancies, which cannot be cured by existing methodologies. In this review, we examine the design and therapeutic potential of immunocytokines and bispecific antibodies, two classes of bifunctional products which can selectively activate the immune system at the tumor site. Certain protein engineering aspects, such as the choice of the antibody format, are common to both classes of therapeutic agents and can have a profound impact on tumor homing performance in vivo of individual products. However, immunocytokines and bispecific antibodies display different mechanisms of action. Future research activities will reveal whether an additive of even synergistic benefit can be obtained from the judicious combination of these two types of biopharmaceutical agents.
Sweeping antibody as a novel therapeutic antibody modality capable of eliminating soluble antigens from circulation
Authors: Igawa Tomoyuki , Haraya Kenta , Hattori Kunihiro 
Published: February 2016

SummaryMonoclonal antibodies have become a general modality in therapeutic development, and a variety of monoclonal antibodies targeting soluble antigens have been developed. However, even with infinite binding affinity to an antigen, a conventional antibody can bind to the antigen only once and results in an increase in total plasma antigen concentration in vivo. This antibody‐mediated antigen accumulation generally occurs because the clearance from circulation of an antibody–antigen complex is much slower than that of a free antigen. This limitation has recently been overcome by sweeping antibodies, which are capable of actively eliminating soluble antigens from circulation. A sweeping antibody incorporates two antibody engineering technologies: one is variable region engineering to enable the antibody to bind to an antigen in plasma and dissociate from the antigen in endosome (after which the antigen undergoes lysosomal degradation), and the other is constant region engineering to increase the cellular uptake of the antibody–antigen complex into endosome. By enhancing the elimination of soluble antigens from circulation, sweeping antibodies can therapeutically target soluble antigens that conventional antibodies cannot. This review discusses the features, engineering technologies, advantages, and applications of sweeping antibodies that target soluble antigens.
Harnessing T cells to fight cancer with BiTE® antibody constructs – past developments and future directions
Authors: Klinger Matthias , Benjamin Jonathan , Kischel Roman , Stienen Sabine , Zugmaier Gerhard 
Published: February 2016

SummaryBispecific T‐cell engager (BiTE®) antibody constructs represent a novel immunotherapy that bridges cytotoxic T cells to tumor cells, thereby inducing target cell‐dependent polyclonal T‐cell activation and proliferation, and leading to apoptosis of bound tumor cells. Anti‐CD19 BiTE® blinatumomab has demonstrated clinical activity in Philadelphia chromosome (Ph)‐negative relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) eventually resulting in conditional approval by the U.S. Food and Drug Administration in 2014. This drug is currently further developed in pediatric and Ph+ r/r, as well as in minimal residual disease‐positive ALL, and might also offer clinical benefit for patients with non‐Hodgkin's lymphoma, especially for those with aggressive forms like diffuse large B‐cell lymphoma. Another BiTE® antibody construct in hemato‐oncology designated AMG 330 targets CD33 on acute myeloid leukemia blast cells. After showing promising ex vivo activity, this drug candidate has recently entered phase 1 clinical development, and has further indicated potential for combination with checkpoint inhibitors. In solid tumor indications, three BiTE® antibody constructs have been tested in phase 1 studies so far: anti‐EpCAM BiTE® AMG 110, anti‐CEA BiTE® MEDI‐565/AMG 211, and anti‐PSMA BiTE® BAY2010112/AMG 212. Pertinent questions comprise how to maximize BiTE® penetration and T‐cell infiltration of the tumor while simultaneously minimizing any adverse events, which is currently explored by a continuous intravenous infusion approach. Thus, BiTE® antibody constructs will hopefully provide new treatment options for patients in several indications with high unmet medical need.
Stable long‐term cultures of self‐renewing B cells and their applications
Authors: Kwakkenbos Mark J. , van Helden Pauline M. , Beaumont Tim , Spits Hergen 
Published: February 2016

SummaryMonoclonal antibodies are essential therapeutics and diagnostics in a large number of diseases. Moreover, they are essential tools in all sectors of life sciences. Although the great majority of monoclonal antibodies currently in use are of mouse origin, the use of human B cells to generate monoclonal antibodies is increasing as new techniques to tap the human B cell repertoire are rapidly emerging. Cloned lines of immortalized human B cells are ideal sources of monoclonal antibodies. In this review, we summarize our studies to the regulation of the replicative life span, differentiation, and maturation of B cells that led to the development of a platform that uses immortalization of human B cells by in vitro genetic modification for antibody development. We describe a number of human antibodies that were isolated using this platform and the application of the technique in other species. We also discuss the use of immortalized B cells as antigen‐presenting cells for the discovery of tumor neoantigens.
Discovery and bio‐optimization of human antibody therapeutics using the XenoMouse® transgenic mouse platform
Authors: Foltz Ian N. , Gunasekaran Kannan , King Chadwick T. 
Published: February 2016

SummarySince the late 1990s, the use of transgenic animal platforms has transformed the discovery of fully human therapeutic monoclonal antibodies. The first approved therapy derived from a transgenic platform – the epidermal growth factor receptor antagonist panitumumab to treat advanced colorectal cancer – was developed using XenoMouse® technology. Since its approval in 2006, the science of discovering and developing therapeutic monoclonal antibodies derived from the XenoMouse® platform has advanced considerably. The emerging array of antibody therapeutics developed using transgenic technologies is expected to include antibodies and antibody fragments with novel mechanisms of action and extreme potencies. In addition to these impressive functional properties, these antibodies will be designed to have superior biophysical properties that enable highly efficient large‐scale manufacturing methods. Achieving these new heights in antibody drug discovery will ultimately bring better medicines to patients. Here, we review best practices for the discovery and bio‐optimization of monoclonal antibodies that fit functional design goals and meet high manufacturing standards.
Increased Night Temperatures During Cotton's Early Reproductive Stage Affect Leaf Physiology and Flower Bud Carbohydrate Content Decreasing Flower Bud Retention
Authors: Loka D. A. , Oosterhuis D. M. 
Published: February 2016

AbstractHigher than optimum temperatures during cotton's (Gossypium hirsutum L.) growing season is a common occurrence in cotton‐growing areas around the world with negative consequences on productivity. According to climate projections, night temperatures are expected to increase more than day temperatures. The objective of this study was to monitor and record the effects of higher than optimum night temperatures during cotton's early reproductive stage on physiological (photosynthesis, respiration and membrane damage) and biochemical (leaf adenosine triphosphate (ATP) levels, as well as glutathione reductase (GR) content and soluble carbohydrate concentrations of the leaf subtending the flower buds. Number, dry weight, carbohydrate concentrations and GR levels of flower buds were also measured at the end of the experiment. Growth chamber experiments were conducted using cotton cultivar ST 5288 B2RF and treatments consisted of normal day/night temperatures (32/24 °C) and high night temperatures (32/30 °C) for 7 days at squaring (approximately 4 weeks after planting). The results indicated that high night temperatures had an immediate effect on leaf respiration rates and membrane damage by significantly increasing them compared to the control and a similar pattern was observed on leaf photosynthesis and ATP levels that were markedly decreased. Leaf GR levels were also substantially increased under conditions of high night temperatures, in contrast to flower bud GR content which remained unaffected. High night temperatures had a significant effect on leaf carbohydrate concentrations resulting in significant decreases in hexose, sucrose and starch levels. Nevertheless, flower bud sucrose content was substantially increased under conditions of high night temperatures, while hexose content was decreased and starch concentrations remained unaffected. A detrimental effect of elevated night temperatures on the number of flower buds per plant and on the dry weight of flower buds was observed, and it was concluded that high night temperatures had a negative effect on cotton flower bud production due to disruptions on flower bud carbohydrate metabolism as a result of the insufficient GR response.
Functional TRPV2 and TRPV4 channels in human cardiac c‐kit+ progenitor cells
Authors: Che Hui , Xiao Guo‐Sheng , Sun Hai‐Ying , Wang Yan , Li Gui‐Rong 
Published: February 2016

AbstractThe cellular physiology and biology of human cardiac c‐kit+ progenitor cells has not been extensively characterized and remains an area of active research. This study investigates the functional expression of transient receptor potential vanilloid (TRPV) and possible roles for this ion channel in regulating proliferation and migration of human cardiac c‐kit+ progenitor cells. We found that genes coding for TRPV2 and TRPV4 channels and their proteins are significantly expressed in human c‐kit+ cardiac stem cells. Probenecid, an activator of TRPV2, induced an increase in intracellular Ca2+ (Ca2+i), an effect that may be attenuated or abolished by the TRPV2 blocker ruthenium red. The TRPV4 channel activator 4α‐phorbol 12‐13‐dicaprinate induced Ca2+i oscillations, which can be inhibited by the TRPV4 blocker RN‐1734. The alteration of Ca2+i by probenecid or 4α‐phorbol 12‐13‐dicprinate was dramatically inhibited in cells infected with TRPV2 short hairpin RNA (shRNA) or TRPV4 shRNA. Silencing TRPV2, but not TRPV4, significantly reduced cell proliferation by arresting cells at the G0/G1 boundary of the cell cycle. Cell migration was reduced by silencing TRPV2 or TRPV4. Western blot revealed that silencing TRPV2 decreased expression of cyclin D1, cyclin E, pERK1/2 and pAkt, whereas silencing TRPV4 only reduced pAkt expression. Our results demonstrate for the first time that functional TRPV2 and TRPV4 channels are abundantly expressed in human cardiac c‐kit+ progenitor cells. TRPV2 channels, but not TRPV4 channels, participate in regulating cell cycle progression; moreover, both TRPV2 and TRPV4 are involved in migration of human cardiac c‐kit+ progenitor cells.