bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing T-cell receptor gene therapy for hematologic malignancies
Authors: Morris Emma C. , Stauss Hans J. 
Published: May 2016

AbstractRecent advances in genetic engineering have enabled the delivery of clinical trials using patient T cells redirected to recognize tumor-associated antigens. The most dramatic results have been seen with T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19, a differentiation antigen expressed in B cells and B lineage malignancies. We propose that antigen expression in nonmalignant cells may contribute to the efficacy of T-cell therapy by maintaining effector function and promoting memory. Although CAR recognition is limited to cell surface structures, T-cell receptors (TCRs) can recognize intracellular proteins. This not only expands the range of tumor-associated self-antigens that are amenable for T-cell therapy, but also allows TCR targeting of the cancer mutagenome. We will highlight biological bottlenecks that potentially limit mutation-specific T-cell therapy and may require high-avidity TCRs that are capable of activating effector function when the concentrations of mutant peptides are low. Unexpectedly, modified TCRs with artificially high affinities function poorly in response to low concentration of cognate peptide but pose an increased safety risk as they may respond optimally to cross-reactive peptides. Recent gene-editing tools, such as transcription activator–like effector nucleases and clustered regularly interspaced short palindromic repeats, provide a platform to delete endogenous TCR and HLA genes, which removes alloreactivity and decreases immunogenicity of third-party T cells. This represents an important step toward generic off-the-shelf T-cell products that may be used in the future for the treatment of large numbers of patients.
Epidemiological studies of burn patients in a burn center in Ghana: any clues for prevention?
Authors: Agbenorku P. , Aboah K. , Akpaloo J. , Amankwa R. , Farhat B. , Turkson E. , Hoyte-Williams P. E. , Klutsey E. E. , Yorke J. 
Published: May 2016

AbstractBackgroundBurn injuries are a serious problem worldwide, with most occurrences in low- and middle-income countries. Depending on the extent of injury, burn victims are faced with the challenges of fitting into society due to complications such as extensive scarring and contractures. The current study seeks to determine whether epidemiological studies of burn patients can provide guidelines to enhance burn prevention among the Ghanaian population.MethodsData from the Burns Registry of the Burns Intensive Care Unit (BICU) of Komfo Anokye Teaching Hospital (KATH) was obtained. Data on sex, age, aetiology, % total body surface area (TBSA), and admission outcomes from May 1, 2009, to April 30, 2013, were retrieved for a total of 487 patients during this period.ResultsData on burn admissions comprising 263 (54.0 %) males and 224 (46.0 %) females were obtained from the Burns Registry. Children 0–10 years were the most affected age group. The yearly mean % TBSA ranged from 24.74 % to 35.07 %. The majority of burns was caused by scalding. Mortality rates ranged from 8.4 % to 32.0 % during the period under review.ConclusionsThe study shows that children of 10 years old and below are the most affected group; this may be due to inattention to these children by parents/caretakers. Safety and safe working environments should be provided at home and workplaces, and promotion of education on burn prevention should be intensified.
Epidemiology of burns and scalds in children presenting to the emergency department of a regional burns unit: a 7-year retrospective study
Authors: Battle Ceri Elisabeth , Evans Vanessa , James Karen , Guy Katherine , Whitley Janet , Evans Phillip Adrian 
Published: May 2016

Abstract

Background
Variation in the incidence and mechanism of thermal injury has been reported in different age groups in children. The aim of this study was to report the incidence, mechanisms, and environmental factors of all burns presentations to the emergency department (ED) of a regional burns centre over a 7-year period.

Methods
A retrospective, chart review study of all burns presentations to the ED of a regional burns centre in South Wales was conducted. All children recorded as having sustained a burn or scald, aged less than 16 years were included in the analysis. Subjects’ demographics were analysed using descriptive statistics, and comparisons were made between patients aged less than 5 and patients aged 5–16 using chi-square test and Mann–Whitney U test.

Results
A total of 1387 cases were included in the final analysis. Scalds were the most common thermal injury with 569 (41.0 %) reported, followed by contact burns in 563 (40.6 %) patients. The patients requiring hospitalisation were significantly younger (2 vs 3 years; p &lt; 0.001) and had a higher rate of non-accidental injury (10 vs 4; p &lt; 0.001). The most commonly injured site in both age groups was a hand or digit.

Conclusions
Scalds and contact burns were the most commonly reported thermal injury in children aged less than 16. Common mechanisms were hot beverages, hobs and hair straighteners, highlighting further burn prevention strategies are needed and good-quality prospective studies that investigate the effectiveness of such strategies.
NECAP2 controls clathrin coat recruitment to early endosomes for fast endocytic recycling
Authors: Chamberland John P. , Antonow Lauren T. , Dias Santos Michel , Ritter Brigitte 
Published: May 2016

ABSTRACT
Endocytic recycling returns receptors to the plasma membrane following internalization and is essential to maintain receptor levels on the cell surface, re-sensitize cells to extracellular ligands and for continued nutrient uptake. Yet, the protein machineries and mechanisms that drive endocytic recycling remain ill-defined. Here, we establish that NECAP2 regulates the endocytic recycling of EGFR and transferrin receptor. Our analysis of the recycling dynamics revealed that NECAP2 functions in the fast recycling pathway that directly returns cargo from early endosomes to the cell surface. In contrast, NECAP2 does not regulate the clathrin-mediated endocytosis of these cargos, the degradation of EGFR or the recycling of transferrin along the slow, Rab11-dependent recycling pathway. We show that protein knockdown of NECAP2 leads to enlarged early endosomes and causes the loss of the clathrin adapter AP-1 from the organelle. Through structure-function analysis, we define the protein-binding interfaces in NECAP2 that are crucial for AP-1 recruitment to early endosomes. Together, our data identify NECAP2 as a pathway-specific regulator of clathrin coat formation on early endosomes for fast endocytic recycling.
Chromatibody, a novel non-invasive molecular tool to explore and manipulate chromatin in living cells
Authors: Jullien Denis , Vignard Julien , Fedor Yoann , Béry Nicolas , Olichon Aurélien , Crozatier Michèle , Erard Monique , Cassard Hervé , Ducommun Bernard , Salles Bernard , Mirey Gladys 
Published: May 2016

ABSTRACT
Chromatin function is involved in many cellular processes, its visualization or modification being essential in many developmental or cellular studies. Here, we present the characterization of chromatibody, a chromatin-binding single-domain, and explore its use in living cells. This non-intercalating tool specifically binds the heterodimer of H2A–H2B histones and displays a versatile reactivity, specifically labeling chromatin from yeast to mammals. We show that this genetically encoded probe, when fused to fluorescent proteins, allows non-invasive real-time chromatin imaging. Chromatibody is a dynamic chromatin probe that can be modulated. Finally, chromatibody is an efficient tool to target an enzymatic activity to the nucleosome, such as the DNA damage-dependent H2A ubiquitylation, which can modify this epigenetic mark at the scale of the genome and result in DNA damage signaling and repair defects. Taken together, these results identify chromatibody as a universal non-invasive tool for either in vivo chromatin imaging or to manipulate the chromatin landscape.
Dipeptidyl peptidase-IV inhibitors used in type-2 diabetes inhibit a phospholipase C: a case of promiscuous scaffolds in proteins
Authors: Chakraborty Sandeep , Rendón-Ramírez Adela , Ásgeirsson Bjarni , Dutta Mouparna , Ghosh Anindya S. , Oda Masataka , Venkatramani Ravindra , Rao Basuthkar J. , Dandekar Abhaya M. , Goñi Félix M. 
Published: May 2016

The long term side effects of any newly introduced drug is a subject of intense research, and often raging controversies. One such example is the dipeptidyl peptidase-IV (DPP4) inhibitor used for treating type 2 diabetes, which is inconclusively implicated in increased susceptibility to acute pancreatitis. Previously, based on a computational analysis of the spatial and electrostatic properties of active site residues, we have demonstrated that phosphoinositide-specific phospholipase C (PI-PLC) from Bacillus cereus is a prolyl peptidase using in vivo experiments. In the current work, we first report the inhibition of the native activity of PI-PLC by two DPP4 inhibitors - vildagliptin (LAF-237) and K-579. While vildagliptin inhibited PI-PLC at micromolar concentrations, K-579 was a potent inhibitor even at nanomolar concentrations. Subsequently, we queried a comprehensive, non-redundant set of 5000 human proteins (50% similarity cutoff) with known structures using serine protease (SPASE) motifs derived from trypsin and DPP4. A pancreatic lipase and a gastric lipase are among the proteins that are identified as proteins having promiscuous SPASE scaffolds that could interact with DPP4 inhibitors. The presence of such scaffolds in human lipases is expected since they share the same catalytic mechanism with PI-PLC. However our methodology also detects other proteins, often with a completely different enzymatic mechanism, that have significantly congruent domains with the SPASE motifs. The reported elevated levels of serum lipase, although contested, could be rationalized by inhibition of lipases reported here. In an effort to further our understanding of the spatial and electrostatic basis of DPP4 inhibitors, we have also done a comprehensive analysis of all 76 known DPP4 structures liganded to inhibitors till date. Also, the methodology presented here can be easily adopted for other drugs, and provide the first line of filtering in the identification of pathways that might be inadvertently affected due to promiscuous scaffolds in proteins.
Attainment of Metasubject and Personal Results by Means of Learning Kit «Primary School of XXI Century» Training
Authors: Соловьёв  , Solovev Yakov 
Published: May 2016

The article defines the pedagogical potential of teaching materials “Primary school in the XXI century”, which can be used to achieve highquality
educational outcomes, gives the author’s approach to the methods and technologies of training for requirements realization of the Federal
State Educational Standard of Primary Education of the second generation with regard to formation of metasubject results. This article is
intended to help elementary school teachers in the choice of training resources.
Teaching Younger Schoolchildren to Differentiate and Apply Forms of Words and Conjugate Word
Authors: Рывкина  , Ryvkina L. 
Published: May 2016

The article considers the formation methodology of one of the most important skill, which should master a primary schoolchild, - morphemic
analysis of a word. Acquisition of this basic skills by a primary schoolchild gives him an opportunity not only to choose the right spelling of the
word part, but also to extend his vocabulary. It also forms practical skills of the word-formative activity.
Structure and tensile properties evaluation of
samples produced by Fused Deposition Modeling
Authors: Gajdoš Ivan , Slota Ján , Spišák Emil , Jachowicz Tomasz , Tor-Swiatek Aneta 
Published: May 2016

Abstract
This paper presents the result of a study evaluating
the influence of alternative path generation strategy
on structure and some mechanical properties of parts
produced by Fused Deposition Modeling (FDM) technology.
Several scientific investigations focused on resolving
issues in FDM parts by modifying a path generation strategy
to optimize its mechanical properties. In this study,
an alternative strategy was proposed with the intention of
minimizing internal voids and, thus, to improve mechanical
properties. Polycarbonate samples made by this alternative
path generation strategy were subjected to tensile
strength test and metro-tomography structure evaluation.
The results reveal that the structure observed on
build models differs from a structure expected from path
generation predicted by software Insight 9.1. This difference
affected the tensile strength of samples.
Synaptic and extrasynaptic traces of long-term memory: the ID molecule theory
Authors: Legéndy Charles R. 
Published: May 2016

AbstractIt is generally assumed at the time of this writing that memories are stored in the form of synaptic weights. However, it is now also clear that the synapses are not permanent; in fact, synaptic patterns undergo significant change in a matter of hours. This means that to implement the long survival of distant memories (for several decades in humans), the brain must possess a molecular backup mechanism in some form, complete with provisions for the storage and retrieval of information. It is found below that the memory-supporting molecules need not contain a detailed description of mental entities, as had been envisioned in the ‘memory molecule papers’ from 50 years ago, they only need to contain unique identifiers of various entities, and that this can be achieved using relatively small molecules, using a random code (‘ID molecules’). In this paper, the logistics of information flow are followed through the steps of storage and retrieval, and the conclusion reached is that the ID molecules, by carrying a sufficient amount of information (entropy), can effectively control the recreation of complex multineuronal patterns. In illustrations, it is described how ID molecules can be made to revive a selected cell assembly by waking up its synapses and how they cause a selected cell assembly to ignite by sending slow inward currents into its cells. The arrangement involves producing multiple copies of the ID molecules and distributing them at strategic locations at selected sets of synapses, then reaching them through small noncoding RNA molecules. This requires the quick creation of entropy-rich messengers and matching receptors, and it suggests that these are created from each other by small-scale transcription and reverse transcription.
Interrater Reliability of the 6-Minute Walk Test in Women With Hip Fracture
Authors: Overgaard Jan Arnholtz , Larsen Camilla Marie , Holtze Steffen , Ockholm Kenneth , Kristensen Morten Tange 
Published: May 2016

Background and Purpose:
The 6-minute walk test (6MWT) is widely used as a clinical outcome measure. However, the reliability of the 6MWT is unknown in individuals who have recently experienced a hip fracture. The aim of this study was to evaluate the relative and absolute interrater reliability of the 6MWT in individuals with hip fracture.

Methods:
Two senior physical therapy students independently examined a convenience sample of 20 participants in a randomized order. Their assessments were separated by 2 days and followed the guidelines of the American Thoracic Society. Hip fracture-related pain was assessed with the Verbal Ranking Scale.

Results:
Participants (all women) with a mean (standard deviation) age of 78.1 (5.9) years performed the test at a mean of 31.5 (5.8) days postsurgery. Of the participants, 10 had a cervical fracture and 10 had a trochanteric fracture. Excellent interrater reliability (intraclass correlation coefficient [ICC2.1] = 0.92; 95% confidence interval, 0.81-0.97) was found, and the standard error of measurement and smallest real difference were calculated to be 21.4 and 59.4 m, respectively. Bland-Altman plots revealed no significant difference (mean of 3.2 [31.5] m, P = .83) between the 2 raters, and no heteroscedasticity was observed (r = −0.196, P = .41). By contrast, participants walked an average of 21.7 (22.5) m longer during the second trial (P = .002). Participants with moderate hip fracture-related pain walked a shorter distance than those with no or light pain during the first test (P = .04), but this was not the case during the second test (P = .25).

Conclusion:
The interrater reliability of the 6MWT is excellent, and changes of more than 21.4 m (group level) and 59.4 m (individual participants with hip fracture) indicate a real change in the 6MWT. Measuring hip fracture-related pain during testing is recommended for individuals with hip fracture who undergo the 6MWT.
Phenotypic Consequences of a Spontaneous Loss of Heterozygosity in a Common Laboratory Strain of Candida albicans
Authors: Ciudad Toni , Hickman Meleah , Bellido Alberto , Berman Judith , Larriba Germán 
Published: May 2016

Abstract
By testing the susceptibility to DNA damaging agents of several Candida albicans mutant strains derived from the commonly used laboratory strain, CAI4, we uncovered sensitivity to methyl methanesulfonate (MMS) in CAI4 and its derivatives, but not in CAF2-1. This sensitivity is not a result of URA3 disruption because the phenotype was not restored after URA3 reintroduction. Rather, we found that homozygosis of a short region of chromosome 3R (Chr3R), which is naturally heterozygous in the MMS-resistant-related strains CAF4-2 and CAF2-1, confers MMS sensitivity and modulates growth polarization in response to MMS. Furthermore, induction of homozygosity in this region in CAF2-1 or CAF4-2 resulted in MMS sensitivity. We identified 11 genes by SNP/comparative genomic hybridization containing only the a alleles in all the MMS-sensitive strains. Four candidate genes, SNF5, POL1, orf19.5854.1, and MBP1, were analyzed by generating hemizygous configurations in CAF2-1 and CAF4-2 for each allele of all four genes. Only hemizygous MBP1a/mbp1b::SAT1-FLIP strains became MMS sensitive, indicating that MBP1a in the homo- or hemizygosis state was sufficient to account for the MMS-sensitive phenotype. In yeast, Mbp1 regulates G1/S genes involved in DNA repair. A second region of homozygosis on Chr2L increased MMS sensitivity in CAI4 (Chr3R homozygous) but not CAF4-2 (Chr3R heterozygous). This is the first example of sign epistasis in C. albicans.
A DEGRADAÇÃO E FRAGILIDADE DOS SOLOS NO SUDOESTE DE GOIÁS: O CASO DA BACIA HIDROGRÁFICA DO RIBEIRÃO DA PICADA
Authors: Estevam-Alves Régia , Francisca-de-Souza Luzia , Maria-de-Souza Valéria , Ferreira-Queiroz Thales Augusto , Vieira-Lima Jéssica 
Published: May 2016

Este artículo presenta una reflexión sobre la degradación del punto de vista de la fragilidad ambiental del suelo, presentando como área de estudio la cuenca hidrográfica del Ribeirão da Picada/GO. Para eso, se ha elaborado la fragilidad potencial y emergente de esta cuenca utilizando información y datos sobre el clima, el suelo, la declividad, erosividad y el uso de la tierra. Además, fue hecha una revisión de la literatura sobre el tema de la degradación y metodologías de la tierra utilizadas en la preparación de la fragilidad del medio ambiente. Los resultados mostraron que la preparación de la fragilidad ambiental permite conocer las características del entorno de las cuencas hidrográficas, lo que permite identificar los más propensos a las áreas de degradación. ABSTRACTThis paper presents a reflection on the degradation of soils from the environmental fragility point of view, having as area of study the watershed of Ribeirao da Picada/GO. For this purpose, the potential and emerging fragility of that watershed has been established by using information and data on climate, soils, slope, rainfall erosivity and land use. In addition, there was a literature review on the issue of land degradation and methodologies used to establish the environmental fragility.The results showed us that the preparation of the environmental fragility makes it possible to know the characteristics of the watershed environment, allowing the identification of areas that are more prone to degradation.RESUMOEste trabalho apresenta uma reflexão sobre a degradação dos solos do ponto de vista da fragilidade ambiental, tendo como área de estudo a Bacia Hidrográfica do Ribeirão da Picada/GO. Para isso elaborou-se a fragilidade potencial e emergente dessa bacia hidrográfica utilizando informações e dados sobre o clima, os solos, a declividade, erosividade e o uso da terra. Além disso, fez-se uma revisão bibliográfica acerca da questão da degradação dos solos e de metodologias utilizadas para elaboração de fragilidade ambiental. Os resultados mostraram que a elaboração da fragilidade ambiental possibilita conhecer as características do ambiente da bacia hidrográfica, permitindo identificar quais as áreas mais propensas à degradação.
Outcomes of endoscopic suturectomy with postoperative helmet therapy in bilateral coronal craniosynostosis
Authors: Rottgers S. Alex , Lohani Subash , Proctor Mark R. 
Published: May 2016

OBJECTIVE
Historically, bilateral frontoorbital advancement (FOA) has been the keystone for treatment of turribrachycephaly caused by bilateral coronal synostosis. Early endoscopic suturectomy has become a popular technique for treatment of single-suture synostosis, with acceptable results and minimal perioperative morbidity. Boston Children's Hospital has adopted this method of treating early-presenting cases of bilateral coronal synostosis.

METHODS
A retrospective review of patients with bilateral coronal craniosynostosis who were treated with endoscopic suturectomy between 2005 and 2012 was completed. Patients were operated on between 1 and 4 months of age. Hospital records were reviewed for perioperative morbidity, length of stay, head circumference and cephalic indices, and the need for further surgery.

RESULTS
Eighteen patients were identified, 8 males and 10 females, with a mean age at surgery of 2.6 months (range 1–4 months). Nine patients had syndromic craniosynostosis. The mean duration of surgery was 73.3 minutes (range 50–93 minutes). The mean blood loss was 40 ml (range 20–100 ml), and 2 patients needed a blood transfusion. The mean duration of hospital stay was 1.2 days (range 1–2 days). There was 1 major complication in the form of a CSF leak. The mean follow-up was 37 months (range 6–102 months). Eleven percent of nonsyndromic patients required a subsequent FOA; 55.6% of syndromic patients underwent FOA. The head circumference percentiles and cephalic indices improved significantly.

CONCLUSIONS
Early endoscopic suturectomy successfully treats the majority of patients with bilateral coronal synostosis, and affords a short procedure time, a brief hospital stay, and an expedited recovery. Close follow-up is needed to detect patients who will require a secondary FOA due to progressive suture fusion or resynostosis of the released coronal sutures.