bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody epitope repertoire analysis enables rapid antigen discovery and multiplex serology
Authors: Kamath Kathy , Reifert Jack , Johnston Timothy , Gable Cameron , Pantazes Robert J. , Rivera Hilda N. , McAuliffe Isabel , Handali Sukwan , Daugherty Patrick S. 
Published: March 2020

AbstractThe detection of pathogen-specific antibodies remains a cornerstone of clinical diagnostics. Yet, many test exhibit undesirable performance or are completely lacking. Given this, we developed serum epitope repertoire analysis (SERA), a method to rapidly discover conserved, pathogen-specific antigens and their epitopes, and applied it to develop an assay for Chagas disease caused by the protozoan parasite Trypanosoma cruzi. Antibody binding peptide motifs were identified from 28 Chagas repertoires using a bacterial display random 12-mer peptide library and next-generation sequencing (NGS). Thirty-three motifs were selected and mapped to candidate Chagas antigens. In a blinded validation set (n = 72), 30/30 Chagas were positive, 30/30 non-Chagas were negative, and 1/12 Leishmania sp. was positive. After unblinding, a Leishmania cross-reactive epitope was identified and removed from the panel. The Chagas assay exhibited 100% sensitivity (30/30) and specificity (90/90) in a second blinded validation set including individuals with other parasitic infections. Amongst additional epitope repertoires with unknown Chagas serostatus, assay specificity was 99.8% (998/1000). Thus, the Chagas assay achieved a combined sensitivity and specificity equivalent or superior to diagnostic algorithms that rely on three separate tests to achieve high specificity. NGS-based serology via SERA provides an effective approach to discover antigenic epitopes and develop high performance multiplex serological assays.
Association between dental caries and adverse pregnancy outcomes
Authors: Cho Geum Joon , Kim So-youn , Lee Hoi Chang , Kim Ho Yeon , Lee Kyu-Min , Han Sung Won , Oh Min-Jeong 
Published: March 2020

AbstractPoor oral health is not only associated with diabetes and cardiovascular disease but adverse pregnancy outcomes. However the influence of dental caries on pregnancy is unknown. The aim of this study was to evaluate the association between dental caries and adverse pregnancy outcomes and the effect of treatment for dental caries on adverse pregnancy outcomes. Primiparas who delivered a singleton between January 1, 2010 and December 31, 2014 and underwent both general health examination and oral health examination during a National Korea Health Screening Examination within 1 year of pregnancy were eligible. The data of the women who met the inclusion criteria were linked to the data of their offspring contained within the National Korea Health Screening Program for Infants and Children database. Among 120,622 women who delivered during the study period, 28,623 (23.7%) women had dental caries. Among them, 4,741 (16.6%) women were treated for dental caries after diagnosis. In a multivariable analysis, women with dental caries had an increased risk of delivering large-for-gestational-age infants (odds ratio, 1.15; 95% confidence interval, 1.07, 1.23) compared to those without dental caries. When women with dental caries were divided on the basis of the treatment of dental caries, women with dental caries but no treatment had an increased risk of delivering large-for-gestational-age infants (odds ratio, 1.15; 95% confidence interval, 1.06, 1.24); conversely, there was no increased risk in women with dental caries and treatment compared with those without. Dental caries and its treatment were not associated with preterm birth and preeclampsia. Untreated dental caries was not associated with preterm birth or preeclampsia but with the risk of delivering large-for-gestational-age infants. These whole observation may be attributed to the various characteristics of mothers who develop dental caries are not treated.
Isotopic Nitrogen-15 Labeling of Mice Identified Long-lived Proteins of the Renal Basement Membranes
Authors: Liu Pan , Xie Xinfang , Jin Jing 
Published: March 2020

AbstractThe kidney is comprised of highly complex structures that rely on self-maintenance for their functions, and tissue repair and regeneration in renal diseases. We devised a proteomics assay to measure the turnover of individual proteins in mouse kidney. Mice were metabolically labeled with a specially formulated chow containing nitrogen-15 (15N) with the absence of normal 14N atoms. Newly synthesized proteins with 15N contents were distinguished from their 14N counterparts by mass spectrometry. In total, we identified over 4,000 proteins from the renal cortex with a majority of them contained only 15N. About 100 proteins had both 14N- and 15N-contents. Notably, the long-lived proteins that had large 14N/15N ratios were mostly matrix proteins. These included proteins such as type IV and type VI collagen, laminin, nidogen and perlecan/HSPG2 that constitute the axial core of the glomerular basement membrane (GBM). In contrast, the surface lamina rara proteins such as agrin and integrin had much shorter longevity, suggesting their faster regeneration cycle. The data illustrated matrix proteins that constitute the basement membranes in the renal cortex are constantly renewed in an ordered fashion. In perspective, the global profile of protein turnover is usefully in understanding the protein-basis of GBM maintenance and repair.
A live-cell super-resolution technique demonstrated by imaging germinosomes in wild-type bacterial spores
Authors: Breedijk R. M. P. , Wen J. , Krishnaswami V. , Bernas T. , Manders E. M. M. , Setlow P. , Vischer N. O. E. , Brul S. 
Published: March 2020

AbstractTime-lapse fluorescence imaging of live cells at super-resolution remains a challenge, especially when the photon budget is limited. Current super-resolution techniques require either the use of special exogenous probes, high illumination doses or multiple image acquisitions with post-processing or combinations of the aforementioned. Here, we describe a new approach by combining annular illumination with rescan confocal microscopy. This optics-only technique generates images in a single scan, thereby avoiding any potential risks of reconstruction related artifacts. The lateral resolution is comparable to that of linear structured illumination microscopy and the axial resolution is similar to that of a standard confocal microscope. As a case study, we present super-resolution time-lapse imaging of wild-type Bacillus subtilis spores, which contain low numbers of germination receptor proteins in a focus (a germinosome) surrounded by an autofluorescent coat layer. Here, we give the first evidence for the existence of germinosomes in wild-type spores, show their spatio-temporal dynamics upon germinant addition and visualize spores coming to life.
Gene editing and CRISPR in the clinic: current and future perspectives
Authors: Hirakawa Matthew P. , Krishnakumar Raga , Timlin Jerilyn A. , Carney James P. , Butler Kimberly S. 
Published: March 2020

AbstractGenome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases which require cell modification in vivo. However, in vivo use of CRISPR technologies can be confounded by problems such as off-target editing, inefficient or off-target delivery, and stimulation of counterproductive immune responses. Current research addressing these issues may provide new opportunities for use of CRISPR in the clinical space. In this review, we examine the current status and scientific basis of clinical trials featuring ZFNs, TALENs, and CRISPR-based genome editing, the known limitations of CRISPR use in humans, and the rapidly developing CRISPR engineering space that should lay the groundwork for further translation to clinical application.
Evidence from high-mass X-ray binaries that Galactic WR components of WR+O binaries end their life with a supernova explosion
Authors: Vanbeveren D. , Mennekens N. , van den Heuvel E. P. J. , Van Bever J. 
Published: March 2020

Context. Theoretical population number studies of binaries with at least one black hole (BH) component obviously depend on whether or not BHs receive a (natal) kick during their formation.
Aims. Several observational facts seem to indicate that BHs do indeed receive a kick during their formation. In the present paper, we discuss additional evidence of this.
Methods. The progenitors of wind-fed high-mass X-ray binaries (HMXB) with a BH component (BH HMXB) are WR+OB binaries where the Wolf–Rayet (WR) star will finally collapse and form the BH. Starting from the observed population of WR+OB binaries in the solar neighborhood, we predict the population of wind-fed BH HMXBs as a function of the BH-natal kick.
Results. The simulations reveal that when WR stars collapse into a BH with a zero or low kick, we should expect 100 or more wind-fed BH HMXBs in the solar neighborhood, whereas only one is observed (Cyg X-1). We consider this as evidence that either WR components in binaries end their life as a neutron star or that they collapse into BHs, both accompanied by a supernova explosion imparting significant (natal) kicks.
Ist die Hormontherapie bei Hodenhochstand noch zeitgemäß?
Authors: Schröder Annette 
Published: March 2020

ZusammenfassungDie Hormontherapie wurde über Jahrzehnte (zumindest in Europa) als integraler Bestandteil der Behandlung des Hodenhochstandes angesehen. Die Datenlage ist jedoch ausgesprochen kontrovers. Die Induktion des Deszensus gelang in vielen Studien und laut einer großen Metaanalyse nur in ca. 20 % der Fälle, einzelne kleinere Studien beschreiben bessere Ergebnisse. Auch die potenzielle Verbesserung der Fertilität wird in einigen Studien als erwiesen angegeben, andere beschreiben gegenteilige Ergebnisse.Inzwischen wurde die Hormontherapie aus den meisten internationalen Leitlinien vollends entfernt und wird auch in Deutschland nur noch für wenige Indikationen empfohlen. Bez. der Induktion des Deszensus hat die Hormontherapie aufgrund der vielfach dokumentierten unzureichenden Wirksamkeit keinen hohen Stellenwert mehr, lediglich mit dem Ziel der potenziellen Fertilitätsverbesserung bei bilateralem Hodenhochstand wird sie noch mit einer gewissen Zurückhaltung empfohlen.In Anbetracht der widersprüchlichen Datenlage fällt es schwer, die Hormontherapie aktuell noch zu empfehlen.
The affordances and challenges of wearable technologies for training public service interpreters
Authors: Eser Oktay , Lai Miranda , Saltan Fatih 
Published: March 2020

Abstract
Interpreter training has evolved from traditional face-to-face classroom settings to alternative modes of delivery such as online and blended learning because of the rise in information and communication technology. The limited body of literature shows that the most documented pedagogical application of interpreter training delivery is via virtual learning environments such as Moodle and Blackboard. To enrich the literature on technology use in interpreter training, a pilot project was conducted in which participant students and trainers accessed a three-dimensional virtual environment using wearable technology (i.e., three-dimensional virtual reality glasses) and students practiced interpreting using a prerecorded animated dialogue. A virtual reality platform was built using Unity 3D and run on Android to host the piloted dialogue, with a view to adding dialogues in the future to develop it into a healthcare interpreting training platform. Qualitative data collected through observations and semi-structured interviews were analyzed. The results show that using wearable devices in interpreter training has the potential to create immersive simulated environments for auto­nomous learning and to improve interpreter training when used with instructional support. However, challenges including physiological effects, level of authenticity, and the need for equipment support warrant further exploration and refinement of its pedagogical application in the future.
Availability of information for dosing commonly used medications in special ICU populations
Authors: Eastman Candice , Erstad Brian L 
Published: March 2020

Abstract

Purpose
Medication product labeling was reviewed to determine if sufficient information is available to appropriately calculate dosing regimens for special intensive care unit (ICU) populations, including patients at extremes of body habitus and patients receiving hemodialysis, continuous renal replacement therapy (CRRT), or extracorporeal membrane oxygenation (ECMO).

Methods
The labeling of the 100 most commonly used injectable medications in the adult ICUs of an academic medical center in Arizona were evaluated. Any information related to adult weight-based dosing, weight descriptors, dosing of patients at extremes of weight (body mass index of &lt;18.5 or &gt;40 kg/m2), and dosing of patients receiving hemodialysis, CRRT, or ECMO was extracted from Food and Drug Administration–approved product labeling. Information was ranked for dosing usefulness on a scale of 0 to 3; an information usefulness score of 2 or greater was considered minimally adequate for dosing special ICU populations.

Results
Among the 100 medications evaluated, the labeling of 47 provided information on weight-based dosing, with the labeling of 30% referring to a specific weight descriptor. The labeling of 15 medications had information on dosing for patients at extremes of body habitus: underweight (3 medications), obesity (12 medications), and extreme obesity (2 medications), with the labeling of 8 medications receiving an information usefulness score of ≥2 (2, 6, and 1 medication in the respective categories). Among the 42 medications whose labeling provided hemodialysis-related dosing information, the labeled information of 52% was assigned a usefulness score of ≥2; among the 3 medications with CRRT-related dosing information, the labeling of 1 received a score of ≥2. ECMO-related dosing information was available for 2 medications, with 1 score of ≥2 assigned.

Conclusion
Information in the product labeling of injectable medications commonly used in the ICU is limited and generally inadequate for calculating an appropriate dose for special ICU populations.
PolishEM: image enhancement in FIB–SEM
Authors: Fernandez Jose-Jesus , Torres Teobaldo E , Martin-Solana Eva , Goya Gerardo F , Fernandez-Fernandez Maria-Rosario 
Published: March 2020

Abstract

Summary
We have developed a software tool to improve the image quality in focused ion beam–scanning electron microscopy (FIB–SEM) stacks: PolishEM. Based on a Gaussian blur model, it automatically estimates and compensates for the blur affecting each individual image. It also includes correction for artifacts commonly arising in FIB–SEM (e.g. curtaining). PolishEM has been optimized for an efficient processing of huge FIB–SEM stacks on standard computers.

Availability and implementation
PolishEM has been developed in C. GPL source code and binaries for Linux, OSX and Windows are available at http://www.cnb.csic.es/%7ejjfernandez/polishem.

Supplementary information
Supplementary data are available at Bioinformatics online.
DHH Students’ Phoneme Repetition Awareness in Sentence Reading
Authors: Li Degao , Lin Kuan 
Published: March 2020

Abstract
To examine deaf and hard-of-hearing (DHH) students’ awareness of phoneme repetition in Chinese sentence reading, two experiments were conducted in the self-paced, moving-window reading paradigm. The materials comprised sentences in which Chinese characters that sequentially followed each other shared similar spelling initials and finals in Experiments 1 and 2, respectively. In comparison to hearing participants, DHH participants were more likely to find it more time-consuming to read sentences with, as opposed to without, phoneme repetitions. However, their difficulty in phonological processing seemed to be linked to their weakness at syntactic skilfulness, thus having a negative influence on their reading performance. It is concluded that Chinese DHH college students have developed a phoneme repetition awareness which is different from how hearing college students are aware of phoneme repetitions in Chinese sentence reading. It is implicated that DHH students are able to develop their own skills of phonological information processing in sentence reading as a result of many practices.
Correlation of magnetic resonance imaging and post-ablation endoscopy to detect oesophageal thermal injury in patients after atrial fibrillation ablation: MRI-EDEL-study
Authors: Halbfass Philipp , Lehmkuhl Lukas , Foldyna Borek , Berkovitz Artur , Sonne Kai , Nentwich Karin , Ene Elena , Fochler Franziska , Hörning Frank , Matveeva Anna , Lüsebrink Ulrich , Deneke Thomas 
Published: March 2020

Abstract

Aims
To correlate oesophageal magnetic resonance imaging (MRI) abnormalities with ablation-induced oesophageal injury detected in endoscopy.

Methods and results
Ablation-naïve patients with atrial fibrillation (AF), who underwent ablation using a contact force sensing irrigated radiofrequency ablation catheter, received a cardiac MRI on the day of ablation, and post-ablation oesophageal endoscopy (OE) 1 day after ablation. Two MRI expert readers recorded presence of abnormal oesophageal tissue signal intensities, defined as increased oesophageal signal in T2-fat-saturated (T2fs), short-tau inversion-recovery (STIR), or late gadolinium enhancement (LGE) sequences. Oesophageal endoscopy was performed by experienced operators. Finally, we correlated the presence of any affection with endoscopically detected oesophageal thermal lesions (EDEL). Among 50 consecutive patients (age 67 ± 7 years, 60% male), who received post-ablation MRI and OE, complete MRI data were available in 44 of 50 (88%) patients. In OE, 7 of 50 (14%) presented with EDEL (Category 1 lesion: erosion n = 3, Category 2 lesion: ulcer n = 4). Among those with EDEL, 6 of 7 (86%) patients presented with increased signal intensities in all three MRI sequences, while only 2 of 37 (5%) showed hyperintensities in all three MRI sequences and negative endoscopy. Correspondingly, sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for MRI (increased signal in T2fs, STIR, and LGE) were 86%, 95%, 75%, and 97%, respectively.

Conclusion
Increased signal intensity in T2fs, STIR, and LGE represents independent markers of EDEL. In particular, the combination of all three has the highest diagnostic value. Hence, MRI may represent an accurate, non-invasive method to exclude acute oesophageal injury after AF ablation (NPV: 97%).
Cost-effectiveness of remote monitoring of implantable cardioverter-defibrillators in France: a meta-analysis and an integrated economic model derived from randomized controlled trials
Authors: Sequeira Saannya , Jarvis Christopher I , Benchouche Akram , Seymour Jerome , Tadmouri Abir 
Published: March 2020

Abstract

Aims
Cost-effectiveness data on the remote monitoring (RM) of implantable cardioverter-defibrillators (ICDs) compared to the current standard of care (SC) remains limited. This meta-analysis was performed to assess the economic burden, and to develop an integrated economic model evaluating the efficiency of the RM strategy vs. SC in the context of French healthcare.

Methods and results
Randomized controlled trials, comparing RM to SC in patients implanted with ICDs with or without resynchronization therapy (±CRT-D), were identified through a systematic search of scientific literature databases dating from 2005. Seventeen trials (10 229 patients) reporting data on clinical outcomes, quality of life, cost, and/or utility, either as primary or secondary endpoints were identified. Compared to SC, RM resulted in significant reductions in annual costs per patient for direct healthcare costs (seven studies, difference in means −276.1, 95% standard error [SE]: 66.0, I2 = 76.3%) and for labour costs (two studies, difference in means −11.3, 95% SE: 1.4, I2 = 96.3%). A three-state Markov Model showed that RM resulted in cost-savings of €4142 per patient over a 5-year time horizon, with a quality-adjusted life year (QALY) gain of 0.29. The incremental cost-effectiveness ratio was −14 136 €/QALY, in favour of RM. Furthermore, probabilistic sensitivity analyses confirmed that the RM strategy was dominant over SC in 70% of cases.

Conclusion
Our economic model demonstrates that once implemented, RM of ICD ± CRT-D patients would result in increased effectiveness for lower costs over a 5-year period, compared to the current SC in France.
Chitinolytic proteins secreted by Cellulosimicrobium sp. NTK2
Authors: Niki Daisuke , Higashitani Akari , Osada Haruki , Bito Tomohiro , Shimizu Katsuhiko , Arima Jiro 
Published: March 2020

ABSTRACT
Cellulosimicrobium sp. NTK2 (NTK2 strain) was isolated as a chitinolytic bacterium from mature compost derived from chitinous waste. The growth of the NTK2 strain was enhanced by supplementation of the culture medium with 2% crystalline chitin. Approximately 70% of the supplemented crystalline chitin was degraded during cultivation. Whole genome analysis of the NTK2 strain identified eight chitinases and two chitin-binding proteins. The NTK2 strain secreted two bacterial extracellular solute-binding proteins, three family 18 glycosyl hydrolases and one lytic polysaccharide monooxygenase specifically in the presence of crystalline chitin. A chitinolytic enzyme with a molecular mass of 29 kDa on SDS-PAGE under native conditions was also secreted. This chitinolytic enzyme exhibited the largest band upon zymography but could not be identified. In an attempt to identify all the chitinases secreted by the NTK2 strain, we expressed recombinant versions of the proteins exhibiting chitinolytic activity in Escherichia coli. Our results suggest that the 29 kDa protein belonging to family 19 glycosyl hydrolase was expressed specifically in the presence of 2% crystalline chitin.
Bordetella pertussis Induces Interferon Gamma Production by Natural Killer Cells, Resulting in Chemoattraction by Respiratory Epithelial Cells
Authors: den Hartog Gerco , Schijf Marcel A , Berbers Guy A M , van der Klis Fiona R M , Buisman Anne-Marie 
Published: March 2020

Abstract

Background
Whooping cough is caused by infection of the airways with Bordetella pertussis (Bp). As interferon gamma (IFN-γ) is essential for protective immunity against Bp, we investigated how IFN-γ is induced by Bp or the virulence antigens filamentous hemagglutinin adhesin, pertactin, or pertussis toxin, and how IFN-γ contributes to local immune responses in humans.

Methods
Peripheral blood mononuclear cells (PBMCs) from healthy donors and/or respiratory epithelial cells were stimulated with soluble antigens or inactivated intact Bp and the presence or absence of blocking antibodies or chemokines. Supernatants and cells were analyzed for IFN-γ and chemokine production, and lymphocyte migration was tested using epithelial supernatants.

Results
The soluble antigens failed to induce IFN-γ production, whereas inactivated Bp induced IFN-γ production. Natural killer (NK) cells were the main source of IFN-γ production, which was enhanced by interleukin 15. Epithelial–PBMC co-cultures showed robust IFN-γ–dependent CXCL9 and CXCL10 production by the epithelial cells following stimulation with IFN-γ and Bp. The epithelial-derived chemokines resulted in CXCR3-dependent recruitment of NK and T cells.

Conclusions
Inactivated Bp, but not antigens, induced potent IFN-γ production by NK cells, resulting in chemoattraction of lymphocytes toward the respiratory epithelium. These data provide insight into the requirements for IFN-γ production and how IFN-γ enhances local immune responses to prevent Bp-mediated disease.