bluuebunny/crossref_metadata_2025_split huggingface dataset:
Affinity-matured variants derived from nimotuzumab keep the original fine specificity and exhibit superior biological activity
Authors: Tundidor Yaima , Ponce Luis F. , Chao Lisset , Solozábal Joaquín , Hust Michael , Dübel Stefan , Rojas Gertrudis 
Published: January 2020

AbstractNimotuzumab is a humanized monoclonal antibody against the Epidermal Growth Factor Receptor with a long history of therapeutic use, recognizing an epitope different from the ones targeted by other antibodies against the same antigen. It is also distinguished by much less toxicity resulting in a better safety profile, which has been attributed to its lower affinity compared to these other antibodies. Nevertheless, the ideal affinity window for optimizing the balance between anti-tumor activity and toxic effects has not been determined. In the current work, the paratope of the phage-displayed nimotuzumab Fab fragment was evolved in vitro to obtain affinity-matured variants. Soft-randomization of heavy chain variable region CDRs and phage selection resulted in mutated variants with improved binding ability. Two recombinant antibodies were constructed using these variable regions, which kept the original fine epitope specificity and showed moderate affinity increases against the target (3-4-fold). Such differences were translated into a greatly enhanced inhibitory capacity upon ligand-induced receptor phosphorylation on tumor cells. The new antibodies, named K4 and K5, are valuable tools to explore the role of affinity in nimotuzumab biological properties, and could be used for applications requiring a fine-tuning of the balance between binding to tumor cells and healthy tissues.
Electrical impedance as an indicator of microalgal cell health
Authors: Sui Jianye , Foflonker Fatima , Bhattacharya Debashish , Javanmard Mehdi 
Published: January 2020

AbstractSeparating specific cell phenotypes from a heterotypic mixture is a critical step in many research projects. Traditional methods usually require a large sample volume and a complex preparation process that may alter cell property during the sorting process. Here we present the use of electrical impedance as an indicator of cell health and for identifying specific microalgal phenotypes. We developed a microfluidic platform for measuring electrical impedance at different frequencies using the bacterium-sized green algaPicochlorumSE3. The cells were cultured under different salinity conditions and sampled at four different time points. Our results demonstrate the utility of electrical impedance as an indicator of cell phenotype by providing results that are consistent with known changes in cell size and physiology. Outliers in the cell data distribution are particularly useful because they represent phenotypes that have the ability to maintain size and/or membrane ionic permeability under prolonged salt stress. This suggests that our device can be used to identify and sort desired (e.g., experimentally evolved, mutant) cell phenotypes based on their electrical impedance properties.
Pterosaurs ate soft-bodied cephalopods (Coleoidea)
Authors: Hoffmann R. , Bestwick J. , Berndt G. , Berndt R. , Fuchs D. , Klug C. 
Published: January 2020

AbstractDirect evidence of successful or failed predation is rare in the fossil record but essential for reconstructing extinct food webs. Here, we report the first evidence of a failed predation attempt by a pterosaur on a soft-bodied coleoid cephalopod. A perfectly preserved, fully grown soft-tissue specimen of the octobrachian coleoid Plesioteuthis subovata is associated with a tooth of the pterosaur Rhamphorhynchus muensteri from the Late Jurassic Solnhofen Archipelago. Examination under ultraviolet light reveals the pterosaur tooth is embedded in the now phosphatised cephalopod soft tissue, which makes a chance association highly improbable. According to its morphology, the tooth likely originates from the anterior to middle region of the upper or lower jaw of a large, osteologically mature individual. We propose the tooth became associated with the coleoid when the pterosaur attacked Plesioteuthis at or near the water surface. Thus, Rhamphorhynchus apparently fed on aquatic animals by grabbing prey whilst flying directly above, or floating upon (less likely), the water surface. It remains unclear whether the Plesioteuthis died from the pterosaur attack or survived for some time with the broken tooth lodged in its mantle. Sinking into oxygen depleted waters explains the exceptional soft tissue preservation.
Effect of Amoxicillin in combination with Imipenem-Relebactam against Mycobacterium abscessus
Authors: Lopeman Rose C. , Harrison James , Rathbone Daniel L. , Desai Maya , Lambert Peter A. , Cox Jonathan A. G. 
Published: January 2020

AbstractInfections caused by Mycobacterium abscessus are increasing in prevalence in cystic fibrosis patients. This opportunistic pathogen′s intrinsic resistance to most antibiotics has perpetuated an urgent demand for new, more effective therapeutic interventions. Here we report a prospective advance in the treatment of M. abscessus infection; increasing the susceptibility of the organism to amoxicillin, by repurposing the β-lactamase inhibitor, relebactam, in combination with the front line M. abscessus drug imipenem. We establish by multiple in vitro methods that this combination works synergistically to inhibit M. abscessus. We also show the direct competitive inhibition of the M. abscessus β-lactamase, BlaMab, using a novel assay, which is validated kinetically using the nitrocefin reporter assay and in silico binding studies. Furthermore, we reverse the susceptibility by overexpressing BlaMab in M. abscessus, demonstrating relebactam-BlaMab target engagement. Finally, we highlight the in vitro efficacy of this combination against a panel of M. abscessus clinical isolates, revealing the therapeutic potential of the amoxicillin-imipenem-relebactam combination.
Removal of Refractory Dissolved Organic Carbon in the Amundsen Sea, Antarctica
Authors: Fang Ling , Lee SangHoon , Lee Shin-Ah , Hahm Doshik , Kim Guebuem , Druffel Ellen R. M. , Hwang Jeomshik 
Published: January 2020

AbstractThe removal mechanism of refractory deep-ocean dissolved organic carbon (deep-DOC) is poorly understood. The Amundsen Sea Polynya (ASP) serves as a natural test basin for assessing the fate of deep-DOC when it is supplied with a large amount of fresh-DOC and exposed to strong solar radiation during the polynya opening in austral summer. We measured the radiocarbon content of DOC in the water column on the western Amundsen shelf. The radiocarbon content of DOC in the surface water of the ASP reflected higher primary production than in the region covered by sea ice. The radiocarbon measurements of DOC, taken two years apart in the ASP, were different, suggesting rapid cycling of DOC. The increase in DOC concentration was less than expected from the observed increase in radiocarbon content from those at the greatest depths. Based on a radiocarbon mass balance, we show that deep-DOC is consumed along with fresh-DOC in the ASP. Our observations imply that water circulation through the surface layer, where fresh-DOC is produced, may play an important role in global DOC cycling.
Photocatalytic Degradation of Wastewater by Molecularly Imprinted Ag2S-TiO2 with High-selectively
Authors: Liu Xian , Zhu Lei , Wang Xun , Meng Xide 
Published: January 2020

AbstractThe molecular imprinting technique is a new method for preparing molecularly imprinted polymers (MIPs) with specific molecular recognition sites for individual target molecules. In this study, Ag2S-MIP-TiO2 nanocomposite was synthesized by a sol-gel-deposition method with ethyl p-hydroxybenzoate as an imprinting molecule. The obtained powder was characterized by XRD and other analytical methods. The results show that the obtained Ag2S-MIP-TiO2 nanocomposite demonstrates better catalytic performance than pure anatase TiO2. The degradation efficiency of ethyl p-hydroxybenzoate during 1.5 h of the photocatalytic reaction is 92.22%, which is 42% higher than pure TiO2. The selectivity factor for the treatment of ethyl p-hydroxybenzoate compared to phenol using Ag2S-MIP-TiO2 reached 3.571, which is 72% higher than pure TiO2.
Guided migration analyses at the single-clone level uncover cellular targets of interest in tumor-associated myeloid-derived suppressor cell populations
Authors: Duarte-Sanmiguel Silvia , Shukla Vasudha , Benner Brooke , Moore Jordan , Lemmerman Luke , Lawrence William , Panic Ana , Wang Shipeng , Idzkowski Nicholas , Guio-Vega Gina , Higuita-Castro Natalia , Ghadiali Samir , Carson William E. , Gallego-Perez Daniel 
Published: January 2020

AbstractMyeloid-derived suppressor cells (MDSCs) are immune cells that exert immunosuppression within the tumor, protecting cancer cells from the host’s immune system and/or exogenous immunotherapies. While current research has been mostly focused in countering MDSC-driven immunosuppression, little is known about the mechanisms by which MDSCs disseminate/infiltrate cancerous tissue. This study looks into the use of microtextured surfaces, coupled with in vitro and in vivo cellular and molecular analysis tools, to videoscopically evaluate the dissemination patterns of MDSCs under structurally guided migration, at the single-cell level. MDSCs exhibited topographically driven migration, showing significant intra- and inter-population differences in motility, with velocities reaching ~40 μm h−1. Downstream analyses coupled with single-cell migration uncovered the presence of specific MDSC subpopulations with different degrees of tumor-infiltrating and anti-inflammatory capabilities. Granulocytic MDSCs showed a ~≥3-fold increase in maximum dissemination velocities and traveled distances, and a ~10-fold difference in the expression of pro- and anti-inflammatory markers. Prolonged culture also revealed that purified subpopulations of MDSCs exhibit remarkable plasticity, with homogeneous/sorted subpopulations giving rise to heterogenous cultures that represented the entire hierarchy of MDSC phenotypes within 7 days. These studies point towards the granulocytic subtype as a potential cellular target of interest given their superior dissemination ability and enhanced anti-inflammatory activity.
Slow sand filtration of raw wastewater using biochar as an alternative filtration media
Authors: Kaetzl Korbinian , Lübken Manfred , Nettmann Edith , Krimmler Stefan , Wichern Marc 
Published: January 2020

AbstractThe efficiency of anaerobic biofilters (AnBF) as low-cost wastewater treatment systems was investigated. Miscanthus-biochar was used as filtration media and compared with sand as a common reference material. Raw sewage from a municipal wastewater treatment plant was stored in a sedimentation tank for two days to allow pre-settlement of wastewater particles. Subsequently, wastewater was treated by AnBFs at 22 °C room temperature at a hydraulic loading rate of 0.05 m∙h−1 with an empty bed contact time of 14.4 h and a mean organic loading rate of 509 ± 173 gCOD∙m−3∙d−1. Mean removal of chemical oxygen demand (COD) of biochar filters was with 74 ± 18% significantly higher than of sand filters (61 ± 12%). In contrast to sand filters with a mean reduction of 1.18 ± 0.31 log-units, E. coli removal through biochar was with 1.35 ± 0.27 log-units significantly higher and increased with experimental time. Main removal took place within the schmutzdecke, a biologically active dirt layer that develops simultaneously on the surface of filter beds. Since the E. coli contamination of both filter materials was equal, the higher removal efficiency of biochar filters is probably a result of an improved biodegradation within deeper zones of the filter bed. Overall, performance of biochar filters was better or equal compared to sand and have thus demonstrated the suitability of Miscanthus-biochar as filter media for wastewater treatment.
Pathogenomics and Evolutionary Epidemiology of Multi-Drug Resistant Clinical Klebsiella pneumoniae Isolated from Pretoria, South Africa
Authors: Mbelle Nontombi Marylucy , Feldman Charles , Sekyere John Osei , Maningi Nontuthuko Excellent , Modipane Lesedi , Essack Sabiha Yusuf 
Published: January 2020

AbstractAntibiotic-resistantKlebsiella pneumoniaeis increasingly being implicated in invasive infections worldwide with high mortalities. Forty-two multidrug resistant (MDR)K. pneumoniaeisolates were collected over a 4-month period. Antimicrobial susceptibility was determined using Microscan. The evolutionary epidemiology, resistome, virulome and mobilome of the isolates were characterised using whole-genome sequencing and bioinformatics analysis. All isolates contained theblaCTX-Mgene, whilst 41/42(97%) containedblaTEM, 36/42(86%) containedblaOXAand 35/42(83%) harbouredblaSHVgenes. Other resistance genes found includedblaLEN,aac(6′)-lb-cr,qnrA,qnrB,qnrS,oqxAB,aad,aph,dfr,sul1,sul2,fosA, andcatgenes. Fluoroquinolone and colistin resistance-conferring mutations inparC,gyrAB,pmrAB,phoPQ andkpnEF were identified. TheblaLENgene, rarely described worldwide, was identified in four isolates. The isolates comprised diverse sequence types, the most common being ST152 in 7/42(17%) isolates; clone-specific O and K capsule types were identified. Diverse virulence genes that were not clone-specific were identified in all but one isolate. IncF, IncH and IncI plasmid replicons and two novel integrons were present. TheblaCTX-M-15andblaTEM-1genes were bracketed by Tn3 transposons, ISEc9, a resolvase and IS91 insertion sequence. There were 20 gene cassettes in 14 different cassette arrays, with thedfrAandaadAgene cassettes being the most frequent. Phylogenetic analysis demonstrated that the isolates were evolutionarily associated with strains from both South Africa and abroad. These findings depict the rich resistome, mobilome and virulome repertoire in clinicalK. pneumoniaestrains, which are mainly transmitted by clonal, multiclonal and horizontal means in South Africa.
Identification of a novel uterine leiomyoma GWAS locus in a Japanese population
Authors: Sakai Kensuke , Tanikawa Chizu , Hirasawa Akira , Chiyoda Tatsuyuki , Yamagami Wataru , Kataoka Fumio , Susumu Nobuyuki , Terao Chikashi , Kamatani Yoichiro , Takahashi Atsushi , Momozawa Yukihide , Hirata Makoto , Kubo Michiaki , Fuse Nobuo , Takai-Igarashi Takako , Shimizu Atsushi , Fukushima Akimune , Kadota Aya , Arisawa Kokichi , Ikezaki Hiroaki , Wakai Kenji , Yamaji Taiki , Sawada Norie , Iwasaki Motoki , Tsugane Shoichiro , Aoki Daisuke , Matsuda Koichi 
Published: January 2020

AbstractUterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P = 6.12 × 10−25 with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma.
Mud volcanoes and the presence of PAHs
Authors: Remizovschi Alexei , Carpa Rahela , Forray Ferenc L. , Chiriac Cecilia , Roba Carmen-Andreea , Beldean-Galea Simion , Andrei Adrian-Ștefan , Szekeres Edina , Baricz Andreea , Lupan Iulia , Rudi Knut , Coman Cristian 
Published: January 2020

AbstractA mud volcano (MV) is a naturally hydrocarbon-spiked environment, as indicated by the presence of various quantities of PAHs and aromatic isotopic shifts in its sediments. Recurrent expulsion of various hydrocarbons consolidates the growth of hydrocarbonoclastic bacterial communities in the areas around MVs. In addition to the widely-known availability of biologically malleable alkanes, MVs can represent hotbeds of polyaromatic hydrocarbons (PAHs), as well - an aspect that has not been previously explored. This study measured the availability of highly recalcitrant PAHs and the isotopic signature of MV sediments both by GC-MS and δ13C analyses. Subsequently, this study highlighted both the occurrence and distribution of putative PAH-degrading bacterial OTUs using a metabarcoding technique. The putative hydrocarbonoclastic taxa incidence are the following: Enterobacteriaceae (31.5%), Methylobacteriaceae (19.9%), Bradyrhizobiaceae (16.9%), Oxalobacteraceae (10.2%), Comamonadaceae (7.6%) and Sphingomonadaceae (5.5%). Cumulatively, the results of this study indicate that MVs represent polyaromatic hydrocarbonoclastic hotbeds, as defined by both natural PAH input and high incidence of putative PAH-degrading bacterial OTUs.
Sarcopenia index based on serum creatinine and cystatin C is associated with 3-year mortality in hospitalized older patients
Authors: Tang Tianjiao , Zhuo Yan , Xie Lingling , Wang Haozhong , Yang Ming 
Published: January 2020

AbstractTo investigate the association of the sarcopenia index (SI, serum creatinine value/cystatin C value × 100) with 3-year mortality and readmission among older inpatients, we reanalyzed a prospective study in the geriatric ward of a teaching hospital in western China. Older inpatients aged ≥ 60 years with normal kidney function were included. Survival status and readmission information were assessed annually during the 3-year follow-up. We applied Cox regression models to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) of sarcopenia for predicting mortality and readmission. We included 248 participants (mean age: 81.2 ± 6.6 years). During the follow-up, 57 participants (23.9%) died, whereas 179 participants (75.2%) were readmitted at least one time. The SI was positively correlated with body mass index (BMI) (r = 0.214, p = 0.001), calf circumference (CC) (r = 0.253, p < 0.001), handgrip strength (r = 0.244, p < 0.001), and gait speed (r = 0.221, p < 0.001). A higher SI was independently associated with a lower risk of 3-year all-cause mortality after adjusting for potential confounders (HR per 1-SD = 0.80, 95% CI: 0.63–0.97). The SI was not significantly associated with readmission (HR per 1-SD = 0.97, 95% CI: 0.77–1.25). In conclusion, the SI is associated with 3-year all-cause mortality but not readmission in a study population of hospitalized older patients.
Unique natural killer cell subpopulations are associated with exacerbation risk in chronic obstructive pulmonary disease
Authors: Osterburg Andrew R. , Lach Laura , Panos Ralph J. , Borchers Michael T. 
Published: January 2020

AbstractChronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide. COPD is frequently punctuated by acute exacerbations that are precipitated primarily by infections, which increase both morbidity and mortality and inflates healthcare costs. Despite the significance of exacerbations, little understanding of immune function in COPD exacerbations exists. Natural killer (NK) cells are important effectors of innate and adaptive immune responses to pathogens and NK cell function is altered in smokers and COPD. Using high-dimensional flow cytometry, we phenotyped peripheral blood NK cells from never smokers, smokers, and COPD patients and employed a non-supervised clustering algorithm to define and detect changes in NK cell populations. We identified greater than 1,000 unique NK cell subpopulations across patient groups and describe 13 altered NK populations in patients who experienced prior exacerbations. Based upon cluster sizes and associated fluorescence data, we generated a logistic regression model to predict patients with a history of exacerbations with high sensitivity and specificity. Moreover, highly enriched NK cell subpopulations implicated in the regression model exhibited enhanced effector functions as defined by in vitro cytotoxicity assays. These novel data reflect the effects of smoking and disease on peripheral blood NK cell phenotypes, provide insight into the potential immune pathophysiology of COPD exacerbations, and indicate that NK cell phenotyping may be a useful and biologically relevant marker to predict COPD exacerbations.
Anaerobic Threshold Biophysical Characterisation of the Four Swimming
Techniques
Authors: Carvalho Diogo Duarte , Soares Susana , Zacca Rodrigo , Sousa João , Marinho Daniel Almeida , Silva António José , Vilas-Boas João Paulo , Fernandes Ricardo J. 
Published: January 2020

AbstractThe anaerobic threshold (AnT) seems to be not only a physiologic boundary but
also a transition after which swimmers technique changes, modifying their
biomechanical behaviour. We expanded the AnT concept to a biophysical construct
in the four conventional swimming techniques. Seventy-two elite swimmers
performed a 5×200 m incremental protocol in their preferred
swimming technique (with a 0.05 m·s−1
increase and a 30 s interval between steps). A capillary blood samples
were collected from the fingertip and stroke rate (SR) and length (SL)
determined for the assessment of [La], SR and SL vs. velocity inflexion points
(using the interception of a pair of linear and exponential regression curves).
The [La] values at the AnT were 3.3±1.0, 3.9±1.1, 2.9±1
.34 and 4.5±1.4 mmol·l−1
(mean±SD) for front crawl, backstroke, breaststroke and butterfly, and
its corresponding velocity correlated highly with those at SR and SL inflection
points (r=0.91–0.99, p<0.001). The agreement analyses
confirmed that AnT represents a biophysical boundary in the four competitive
swimming techniques and can be determined individually using [La] and/or
SR/SL. Blood lactate increase speed can help characterise
swimmers’ anaerobic behaviour after AnT and between competitive swimming
techniques.
Diabetesberatung zum Hybrid-AID-System bei Typ-1-Diabetes: neue Perspektiven und Therapieempfehlungen
Authors: Biester Torben , Bratina Natasa , Lange Karin , Biester Sarah , Remus Kerstin , Thomas Andreas , Danne Thomas , Kordonouri Olga 
Published: January 2020

ZusammenfassungKontinuierliche Glukosemonitoringsysteme (CGM) haben inzwischen eine so hohe Messqualität erreicht, dass automatisierte therapeutische Entscheidungen und eine bedarfsgerechte automatisierte Insulinzufuhr möglich geworden sind. Dazu werden CGM und Insulinpumpen zu einem „AID-System“ (Automated Insulin Delivery) zusammengeführt. Ein Algorithmus errechnet dabei kontinuierlich aus den gemessenen Glukosewerten unter Berücksichtigung individueller Nutzerdaten die Insulindosis. Idealerweise verringert sich damit der Einfluss des „Human-Faktors“, d. h. die notwendige manuelle Steuerung der Insulinabgabe durch den Nutzer. Seit 2016 steht in den USA, seit 2018 in einigen europäischen Ländern und seit 2019 in Deutschland ein Hybrid-AID für Personen mit Typ-1-Diabetes zur Verfügung. Der Begriff „Hybrid“ bezeichnet dabei die automatische adaptive Zufuhr des nahrungsunabhängigen, basalen Insulinanteils und die manuelle Abgabe des Insulinbolus zu den Mahlzeiten. Derzeit setzen ca. 200 000 Personen mit Diabetes weltweit ein solches System ein.Dieses, aber auch zukünftige Systeme zur vollautomatischen Insulinabgabe setzen voraus, dass die Nutzer ihr AID-System verstehen und in ungewöhnlichen oder kritischen Situationen sachgerecht reagieren können. Damit ist eine qualifizierte Schulung gerade zu diesen neuen Technologien aus unserer Sicht unverzichtbar. Nutzer können nur dann von den Vorteilen des Systems profitieren, wenn sie verstehen, weshalb ein automatisierter Modus verlassen wird, und sie im manuellen Modus sicher und korrekt handeln können. In diesem Beitrag werden relevante Aspekte und zentrale Herausforderungen bei der Schulung zum Hybrid-AID System MiniMed 670G dargestellt.