bluuebunny/crossref_metadata_2025_split huggingface dataset:
L‐Fucose production by engineered Escherichia coli
Authors: Liu Jing‐Jing , Lee Jae Won , Yun Eun Ju , Jung Sang‐Min , Seo Jin‐Ho , Jin Yong‐Su 
Published: December 2018

AbstractL‐Fucose (6‐deoxy‐L‐galactose) is a major constituent of glycans and glycolipids in mammals. Fucosylation of glycans can confer unique functional properties and may be an economical way to manufacture L‐fucose. Research can extract L‐fucose directly from brown algae, or by enzymatic hydrolysis of L‐fucose‐rich microbial exopolysaccharides. However, these L‐fucose production methods are not economical or scalable for various applications. We engineered an Escherichia coli strain to produce L‐fucose. Specifically, we modified the strain genome to eliminate endogenous L‐fucose and lactose metabolism, produce 2′‐fucosyllactose (2′‐FL), and to liberate L‐fucose from 2′‐FL. This E. coli strain produced 16.7 g/L of L‐fucose with productivity of 0.1 g·L−1·h−1 in a fed‐batch fermentation. This study presents an efficient one‐pot biosynthesis strategy to produce a monomeric form of L‐fucose by microbial fermentation, making large‐scale industrial production of L‐fucose feasible.
Interaction of cell culture process parameters for modulating mAb afucosylation
Authors: Nguyen Dang Anh , Mun Melissa , Rose Christopher M. , Ahyow Patrick , Meier Angela , Sandoval Wendy , Yuk Inn H. 
Published: December 2018

AbstractThe extent of afucosylation, which refers to the absence of core fucose on Fc glycans, can correlate positively with the antibody‐dependent cellular cytotoxicity (ADCC) activity of a monoclonal antibody (mAb). Therefore, it is important to maintain consistent afucosylation during cell culture process scale‐up in bioreactors for a mAb with ADCC activity. However, there is currently a lack of understanding about the impact of partial pressure of carbon dioxide (pCO2)—a parameter that can vary with bioreactor scale—on afucosylation. Using a small‐scale (3 L) bioreactor model that can modulate pCO
2 levels through modified configurations and gassing strategies, we identified three cell culture process parameters that influence afucosylation of a mAb produced by a recombinant Chinese Hamster Ovary (CHO) cell line: pCO
2, media hold duration (at 37°C), and manganese. These three‐independent parameters demonstrated a synergistic effect on mAb afucosylation; increase in pCO
2, media hold duration, and manganese consistently increased afucosylation. Our investigations into the underlying mechanisms through proteomic analysis indicated that the synergistic interactions downregulated pathways related to guanosine diphosphate‐fucose synthesis and fucosylation, and upregulated manganese transport into the CHO cells. These new findings highlight the importance of considering potential differences in culture environment and operations across bioreactor scales, and understanding the impact of their interactions on product quality.
Three‐dimensional nanofibrous polystyrene scaffolds modify macrophage phenotypes and activate macrophage angiogenic potential
Authors: Olkowski Radosław , Czarnowska Elżbieta , Wojasiński Michał , Niderla‐Bielińska Justyna , Ciach Tomasz , Ratajska Anna 
Published: December 2018

Abstract3D scaffolds represent an attractive substrate for studying macrophage activation and modification since they mimic extracellular matrix (ECM). However, macrophage response to such materials, particularly with respect to angiogenic potential is still poorly recognized. Therefore, we investigated the effect of 3D nanofibrous polystyrene scaffolds (NPSs) versus tissue culture polystyrene (TCPS) on THP‐1‐derived macrophages in various environmental conditions, for example, standard (m0), pro‐inflammatory (m1), or anti‐inflammatory (m2) with respect to pro‐angiogenic potential. There were no differences in the expression of TNF‐α and IL‐10 mRNAs and respective proteins in cells cultured on NPSs compared with flat polystyrene (TCPS), however, NPSs induced an increased VEGF production by macrophages cultured in m0 and m1 media. Cells cultured in m1, and m2 conditions secreted elevated amounts of TNF‐α and IL‐10, respectively, irrespective of substrate surface geometry. Each macrophage population contains large, medium, and small cells. Moreover, there were significant differences in the proportion of large to small macrophages depending on the medium composition, that is, in m0, m1, and m2 media these proportions were 1:4, 1:3, and 1:10, respectively. The ultrastructure and the immunoexpression of TNF‐α and IL‐10 were analyzed under a confocal microscope. The results demonstrated differences in cell ultrastructure and suggested that the larger cells were pro‐inflammatory macrophages, while the smaller cells were anti‐inflammatory macrophages. In conclusion, NPSs activate macrophage pro‐angiogenic potential. In addition, an increase in the proportion of pro‐inflammatory macrophages relative to anti‐inflammatory ones in a given population favors this potential.
Feeling and body investigators (FBI): ARFID division—An acceptance‐based interoceptive exposure treatment for children with ARFID
Authors: Zucker Nancy L. , LaVia Maria C. , Craske Michelle G. , Foukal Martha , Harris Adrianne A. , Datta Nandini , Savereide Erik , Maslow Gary R. 
Published: December 2018

AbstractObjectiveIndividuals with Avoidant Restrictive Food Intake Disorder (ARFID) experience impairing health consequences from insufficient nutritional variety and/or quantity. Early medical conditions and/or somatic symptoms such as abdominal pain may lead some with ARFID to experience somatic sensations as aversive. As such, food avoidance may be part of a broader behavioral repertoire aimed at suppressing bodily sensations. Avoiding these necessary and informative signals (e.g., growls of hunger) may subvert the emergence of healthy self‐awareness and self‐regulation. Teaching children with ARFID to engage adaptively with bodily sensations may help decrease aversiveness, increase self‐awareness, and increase approach behaviors.MethodDrawing from interventions for panic disorder and irritable bowel syndrome, we developed an acceptance‐based interoceptive exposure treatment for young children with ARFID, Feeling and Body Investigators (FBI)‐ARFID Division. Using playful cartoons and developmentally sensitive exposures, we teach young children how to map interoceptive sensations onto meanings (e.g., emotions) and actions (e.g., if I feel nervous, I'll hold someone's hand).ResultsWe present a case study of a 4‐year old child with lifelong poor appetite/food indifference.DiscussionSome individuals with ARFID may avoid food to avoid internal sensations. Developmentally appropriate interoceptive exposures may decrease ARFID symptoms while increasing more general self‐regulation skills.
Could repetitive negative thinking interfere with corrective learning? The example of anorexia nervosa
Authors: Reilly Erin E. , Lavender Jason M. , Berner Laura A. , Brown Tiffany A. , Wierenga Christina E. , Kaye Walter H. 
Published: December 2018

AbstractIdentifying processes that may interfere with corrective learning during treatments for anorexia nervosa (AN) may help to improve the effectiveness of existing interventions. We propose that certain cognitive processes characteristic of the AN temperament may help explain previous findings in AN suggesting difficulty updating previously learned associations and learning from feedback. Specifically, we hypothesize that engagement in repetitive negative thinking (RNT), including worry and rumination, could interfere with corrective learning that is critical to the success of behavioral treatments. In doing so, we draw from existing work in anxiety and mood disorders linking RNT to the maintenance of symptoms and poorer response to cognitive‐behavioral treatments. Next, we outline hypothesized mechanisms through which engagement in RNT before, during, and after exposure to aversive stimuli could interfere with learning in AN. We then provide recommendations for how these hypothesized associations could be tested in future research. Although prior work has suggested that RNT processes are common among individuals with AN, this work has been primarily descriptive in nature. We propose that extending this work through direct examination of the impact of active engagement in RNT on corrective learning could aid in identifying AN maintenance processes that could be explicitly targeted in treatment.
The ultraviolet B inflammation model: Postinflammatory hyperpigmentation and validation of a reduced UVB exposure paradigm for inducing hyperalgesia in healthy subjects
Authors: Siebenga Pieter S. , van Amerongen Guido , Klaassen Erica S. , de Kam Marieke L. , Rissmann Robert , Groeneveld Geert Jan 
Published: December 2018

AbstractBackgroundPain models are commonly used in drug development to demonstrate analgesic activity in healthy subjects and should therefore not cause long‐term adverse effects. The ultraviolet B (UVB) model is a model for inflammatory pain in which three times the minimal erythema dose (3MED) is typically applied to induce sensitization. Based on reports of long‐lasting postinflammatory hyperpigmentation (PIH) associated with 3MED, it was decided to investigate the prevalence of PIH among subjects who were previously exposed to 3MED at our research centre. In addition, re‐evaluation of the UVB inflammation model using a reduced exposure paradigm (2MED) was performed in healthy subjects.MethodsIn the first study, all 142 subjects previously exposed to 3MED UVB were invited for a clinical evaluation of PIH. In the second study, 18 healthy subjects were exposed to 2MED UVB, and heat pain detection threshold (PDT) and PIH were evaluated.ResultsIn total, 78 of the 142 subjects responded. The prevalence of PIH among responders was 53.8%. In the second study, we found a significant and stable difference in PDT between UVB‐exposed and control skin 3 hr after irradiation; 13 hr post‐irradiation, the least squares mean estimate of the difference in PDT ranged from −2.6°C to −4.5°C (p < 0.0001). Finally, the prevalence of PIH was lower in the 2MED group compared to the 3MED group.ConclusionsThe 3MED model is associated with a relatively high prevalence of long‐lasting PIH. In contrast, 2MED exposure produces stable hyperalgesia and has a lower risk of PIH and is therefore recommended for modelling inflammatory pain.SignificancePostinflammatory hyperpigmentation is an unwanted long‐term side effect associated with the UVB inflammation model using the 3× minimal erythema dose (3MED) paradigm. In contrast, using a 2MED paradigm results in hyperalgesia that is stable for 36 hr and has a lower risk of inducing postinflammatory hyperpigmentation.
Spinal cord stimulation for chronic refractory pain: Long‐term effectiveness and safety data from a multicentre registry
Authors: Brinzeu Andrei , Cuny Emmanuel , Fontaine Denys , Mertens Patrick , Luyet Pierre‐Philippe , Van den Abeele Carine , Djian Marie‐Christine ,   on behalf of the French SCS Study Group
Published: December 2018

AbstractBackgroundSpinal cord stimulation (SCS) is an established therapy for refractory neuropathic pain. To ascertain the balance between treatment benefits and risks, the French National Authority for Health requested a post‐market registry for real‐world evaluation of the long‐term effectiveness and safety of the therapy.MethodsA total of 402 patients undergoing implantation with a Medtronic SCS device as either a primo‐implant (n = 264) or replacement implant (n = 138) were enrolled across 28 representative sites in France. Outcome measures at 2 years included pain intensity, satisfaction with treatment, improvement of pain relief and daily life activity, willingness to undergo the treatment again and use of pain treatments. A patient was considered a responder if, compared to baseline, predominant pain reduction was ≥50%.ResultsAt the 2‐year follow‐up visit, predominant pain intensity for primo‐implant patients had decreased from baseline (p < 0.001), with responder rates of 55%, 36% and 67% for the lower limbs, back and upper limbs, respectively. Most patients acknowledged an improvement in pain relief (89%) and daily life activity (82%) were satisfied with treatment (91%) and willing to undergo the treatment again (93%). A significant decrease (p < 0.01) in the proportion of patients receiving pain treatment was observed for all drug and non‐drug treatments. Reported adverse events were in line with the literature. Pain intensity at 2 years was comparable for patients in the replacement group, supporting the long‐term stability and effectiveness of SCS.ConclusionReal‐world evaluation of the use of spinal cord stimulation under the recommendations of the French Health Authority shows that two years after the first implantation of an SCS device close to 60% of the patients retain a significant pain reduction and 74% show improvement in pain scores [of at least 30%] with significant decreases in drug and non‐drug pain treatments.SignificanceThis observational, prospective study in a real‐life setting followed a large cohort of patients suffering from chronic pain and implanted with SCS devices in France. The study assessed the long‐term effectiveness and safety of SCS therapy in a representative sample of implanting sites in France.
Confinement effects on DNA hybridization in electrokinetic micro‐ and nanofluidic systems
Authors: Downs Alex M. , McCallum Christopher , Pennathur Sumita 
Published: December 2018

AbstractSpatial confinement, within cells or micro‐ and nanofabricated devices, impacts the conformation and binding kinetics of biomolecules. Understanding the role of spatial confinement on molecular behavior is important for comprehending diverse biological phenomena, as well as for designing biosensors. Specifically, the behavior of molecular binding under an applied electric field is of importance in the development of electrokinetic biosensors. Here, we investigate whether confinement of DNA oligomers in capillary electrophoresis impacts the binding kinetics of the DNA. To infer the role of confinement on hybridization dynamics, we perform capillary electrophoresis measurements on DNA oligomers within micro‐ and nanochannels, then apply first‐order reaction dynamics theory to extract kinetic parameters from electropherogram data. We find that the apparent dissociation constants at the nanoscale (i.e., within a 100 nm channel) are lower than at the microscale (i.e., within a 1 μm channel), indicating stronger binding with increased confinement. This confirms, for the first time, that confinement‐based enhancement of DNA hybridization persists under application of an electric field.
Multiple infection of cells changes the dynamics of basic viral evolutionary processes
Authors: Wodarz Dominik , Levy David N. , Komarova Natalia L. 
Published: December 2018

AbstractThe infection of cells by multiple copies of a given virus can impact viral evolution in a variety of ways, yet some of the most basic evolutionary dynamics remain underexplored. Using computational models, we investigate how infection multiplicity affects the fixation probability of mutants, the rate of mutant generation, and the timing of mutant invasion. An important insight from these models is that for neutral and disadvantageous phenotypes, rare mutants initially enjoy a fitness advantage in the presence of multiple infection of cells. This arises because multiple infection allows the rare mutant to enter more target cells and to spread faster, while it does not accelerate the spread of the resident wild-type virus. The rare mutant population can increase by entry into both uninfected and wild-type-infected cells, while the established wild-type population can initially only grow through entry into uninfected cells. Following this initial advantageous phase, the dynamics are governed by drift or negative selection, respectively, and a higher multiplicity reduces the chances that mutants fix in the population. Hence, while increased infection multiplicity promotes the presence of neutral and disadvantageous mutants in the short-term, it makes it less likely in the longer term. We show how these theoretical insights can be useful for the interpretation of experimental data on virus evolution at low and high multiplicities. The dynamics explored here provide a basis for the investigation of more complex viral evolutionary processes, including recombination, reassortment, as well as complementary/inhibitory interactions.
Alkoxy(tetraaryl)silicates bearing 9,10‐disilatriptycene skeleton
Authors: Ishida Shintaro , Takiguchi Minori , Iwamoto Takeaki 
Published: December 2018

AbstractAs anionic five‐coordinate silicon species (five‐coordinate silicates) exhibit high reactivity and unique fluxional behavior, their structure and property have received substantial attention. We report herein synthesis, structure, and fluxional behavior of alkoxy(tetraaryl)silicates having the 9,10‐disilatriptycene skeleton (6− and 7−). The molecular structure of the cryptate salt [Li(crypt‐222)]+7− shows that the five‐coordinate silicon adopts a distorted trigonal bipyramidal structure with oxygen atom occupying an equatorial position. In the 1H and 13C{1H} NMR spectra of [Li(crypt‐222)]+7−, a set of signals due to o‐phenylene blades in 7− was observed at room temperature, which indicates fluxional behavior of 7− on the NMR timescale. Computational study suggests that the observed process proceeds via a 120° rotation of bidentate ligand around the Si‐Si axis that consists of two sequential Berry pseudorotations.
AHNS Series – Do you know your guidelines?: Assessment and management of malnutrition in patients with head and neck cancer: Review of the NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines)
Authors: Gill Amarbir , Givi Babak , Moore Michael G. 
Published: December 2018

AbstractThis article is a part of the “Do you know your guidelines” series by the Education Committee of the American Head and Neck Society. The aim is to summarize the core principles outlined by the NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) on management of malnutrition in patients with head and neck cancer. We outline the current recommendations from the National Comprehensive Cancer Network® (NCCN®) for the screening and management of malnutrition, including indications for nutritional supplementation and placement of a nasogastric or gastrostomy tube. We also include a brief review of the available literature on additional screening tools, alternative guidelines, as well as an update on the emerging data surrounding the use of immune‐enhancing nutrition.
Lateral cervical approach for open laryngeal surgery: Technical notes
Authors: Spriano Giuseppe , Mercante Giuseppe , Anelli Andrea , Cristalli Giovanni , Ferreli Fabio 
Published: December 2018

AbstractBackgroundTransoral minimally invasive techniques for laryngeal cancer have been proposed to preserve healthy tissues. The aim of this study was to describe a minimally invasive procedure for all laryngectomies with/without neck dissection using a lateral cervical approach.MethodsA monolateral or bilateral neck incision at the level of the anterior border of the sterno‐cleido‐mastoid muscle is performed in accordance with the side of the neck dissection. The harvesting of an anterior myocutaneous (AMC) cervical flap, including skin, platysma, fascia superficialis, anterior jugular veins, homohyoid and sternohyoid muscles is performed. A neck dissection is executed through the same skin incision. Contraindication is represented by extralaryngeal spread with the involvement of the strap muscles. Supra‐hyoid, sternohyoid, and homohyoid muscles and hyoid bone are preserved.ConclusionOpen partial/total laryngectomies through a lateral cervical approach are feasible and safe. This surgical access with an AMS cervical flap allows to simultaneously perform neck dissections and the removal of the entire laryngeal specimen.
High pretreatment neutrophil‐to‐lymphocyte ratio as a predictor of poor survival prognosis in head and neck squamous cell carcinoma: Systematic review and meta‐analysis
Authors: Yang Lin , Huang Yu , Zhou Lie , Dai Yuhong , Hu Guangyuan 
Published: December 2018

AbstractBackgroundThe prognostic roles of neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) have been reported in head and neck squamous cell carcinoma (HNSCC), but their results remain controversial.MethodsA total of 25 literatures with 28 cohorts involving 6847 HNSCC patients were included. The hazard ratio (HR) was pooled with 95% confidence interval (CI) using fixed‐effects or random‐effects models.ResultsHigh pretreatment NLR predicted poor overall survival (OS: HR = 1.68; 95% CI = 1.39‐2.03; P < .001), disease‐free survival (DFS: HR = 1.76; 95% CI = 1.42‐2.17; P < .001), progression‐free survival (PFS: HR = 1.53; 95% CI = 1.09‐2.14; P = .014), and cancer‐specific survival (CSS: HR = 1.45; 95% CI = 1.23‐1.71; P < .001) in HNSCC. However, the association between PLR and OS or DFS was not statistically significant.ConclusionThe NLR can serve as a potential prognostic biomarker for patients with HNSCC.
Prognostic and clinicopathological significance of CTTN/cortactin alterations in head and neck squamous cell carcinoma: Systematic review and meta‐analysis
Authors: Ramos‐García Pablo , González‐Moles Miguel Ángel , Ayén Ángela , González‐Ruiz Lucía , Ruiz‐Ávila Isabel , Gil‐Montoya José Antonio 
Published: December 2018

AbstractBackgroundTo evaluate the prognostic significance of CTTN/cortactin alterations in head and neck squamous cell carcinoma (HNSCC).Material and methodsWe searched PubMed, Embase, Web of Science, and Scopus for studies published before May 2018. We conducted a meta‐analysis to quantify the impact of CTTN/cortactin alterations on clinicopathological and survival variables.ResultsEighteen studies (1633 patients) met inclusion criteria. Quantitative evaluation revealed a strong association of CTTN/cortactin alterations with N+ status (P < .001), higher T status (P < .001), advanced clinical stage (P < .001), high histological grade (P = .001), and lower overall survival (OS) (P < .001). We found heterogeneity in T status, histological grade, and OS and observed small‐study effects on N status and OS. In subgroup analyses, a significant association of CTTN amplification and cortactin overexpression with the above variables was preserved. The strongest association between CTTN/cortactin alterations and a worse outcome was observed in the subgroups of Asian patients and pharyngolaryngeal squamous cell carcinomas.Conclusions
CTTN/cortactin alterations should be evaluated to predict the HNSCC prognosis.