bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody complementarity determining region design using high-capacity machine learning
Authors: Liu Ge , Zeng Haoyang , Mueller Jonas , Carter Brandon , Wang Ziheng , Schilz Jonas , Horny Geraldine , Birnbaum Michael E , Ewert Stefan , Gifford David K 
Published: November 2019

Abstract

Motivation
The precise targeting of antibodies and other protein therapeutics is required for their proper function and the elimination of deleterious off-target effects. Often the molecular structure of a therapeutic target is unknown and randomized methods are used to design antibodies without a model that relates antibody sequence to desired properties.

Results
Here, we present Ens-Grad, a machine learning method that can design complementarity determining regions of human Immunoglobulin G antibodies with target affinities that are superior to candidates derived from phage display panning experiments. We also demonstrate that machine learning can improve target specificity by the modular composition of models from different experimental campaigns, enabling a new integrative approach to improving target specificity. Our results suggest a new path for the discovery of therapeutic molecules by demonstrating that predictive and differentiable models of antibody binding can be learned from high-throughput experimental data without the need for target structural data.

Availability and implementation
Sequencing data of the phage panning experiment are deposited at NIH’s Sequence Read Archive (SRA) under the accession number SRP158510. We make our code available at https://github.com/gifford-lab/antibody-2019.

Supplementary information
Supplementary data are available at Bioinformatics online.
The Pleasure of Connectivity: Media, Motherhood, and the Digital Maternal Gaze
Authors: Van Cleaf Kara Mary 
Published: November 2019

AbstractBy examining digital representations of motherhood, we can chart the emergence of what I refer to as the “digital maternal gaze,” a style of visual and narrative representation that highlights connections between mother and self, mother and child, and mother and audience. In contrast to the conventional male gaze, in which pleasure is derived from voyeuristic observation, the digital maternal gaze generates and depicts the pleasure that comes from connection and care. In this article I develop a theory of the digital maternal gaze and explore its implication for the subjective experience of mothers, the markets for digital representations of motherhood, and the feminist politics of pleasure-in-connection.
Glucagon-like peptide-1 receptor and sarcoglycan delta genetic variants can affect cardiovascular risk in chronic kidney disease patients under hemodialysis
Authors: Terranegra Annalisa , Arcidiacono Teresa , Macrina Lorenza , Brasacchio Caterina , Pivari Francesca , Mingione Alessandra , Tomei Sara , Mezzavilla Massimo , Silcock Lee , Cozzolino Mario , Palmieri Nicola , Conte Ferruccio , Sirtori Marcella , Rubinacci Alessandro , Soldati Laura , Vezzoli Giuseppe 
Published: November 2019

Abstract

Background
Chronic kidney disease (CKD) patients under hemodialysis show a higher risk of cardiovascular (CV) mortality and morbidity than the general population. This study aims to identify genetic markers that could explain the increased CV risk in hemodialysis.

Methods
A total of 245 CKD patients under hemodialysis were recruited and followed up for 5 years to record CV events. Genetic analysis was performed using single-nucleotide polymorphisms (SNPs) genotyping by Infinium Expanded Multi-Ethnic Genotyping Array (Illumina, San Diego, CA, USA) comparing patients with and without a history of CV events [161 cardiovascular diseases (CVDs) and 84 no CVDs]. The fixation index (Fst) measure was used to identify the most differentiated SNPs, and gene ontology analysis [Protein Analysis THrough Evolutionary Relationships (PANTHER) and Ingenuity Pathway Analysis (IPA)] was applied to define the biological/pathological roles of the associated SNPs. Partitioning tree analysis interrogated the genotype–phenotype relationship between discovered genetic variants and CV phenotypes. Cox regression analysis measured the effect of these SNPs on new CV events during the follow-up (FU).

Results
Fst analysis identified 3218 SNPs that were significantly different between CVD and no CVD. Gene ontology analysis identified two of these SNPs as involved in cardiovascular disease pathways (Ingenuity Pathway) and heart development (Panther) and belonging to 2 different genes: Glucagon-like peptide-1 receptor (GLP1R) and Sarcoglycan delta (SGCD). The phenotype–genotype analysis found a higher percentage of CVD patients carrying the GLP1R rs10305445 allele A (P = 0.03) and lower percentages of CVD patients carrying the SGCD rs145292439 allele A (P = 0.038). Moreover, SGCD rs145292439 was associated with higher levels of high-density lipoprotein (P = 0.015). Cox analysis confirmed the increased frequency of CV events during the 5-year FU in patients carrying GLP1R rs1035445 allele A but it did not show any significant association with SGCD rs145292439.

Conclusions
This study identified GLP1R rs10305445 and SCGD rs145292439 as potential genetic markers that may explain the higher risk of CVD in hemodialysis patients.
Structure Fault Tolerance of Recursive Interconnection Networks
Authors: Sabir Eminjan , Meng Jixiang 
Published: November 2019

Abstract
Motivated by effects caused by structure link faults in networks, we study the following graph theoretical problem. Let $T$ be a connected subgraph of a graph $G$ except for $K_{1}$. The $T$-structure edge-connectivity $\lambda (G;T)$ (resp. $T$-substructure edge-connectivity $\lambda ^s(G;T)$) of $G$ is the minimum cardinality of a set of edge-disjoint subgraphs $\mathcal{F}=\{T_{1},T_{2},...,T_{m}\}$ (resp. $\mathcal{F}=\{T_{1}^{^{\prime}},T_{2}^{^{\prime}},...,T_{m}^{^{\prime}}\}$) such that $T_{i}$ is isomorphic to $T$ (resp. $T_{i}^{^{\prime}}$ is a connected subgraph of $T$) for every $1 \le i \le m $, and $E(\mathcal{F})$’s removal leaves the remaining graph disconnected. In this paper, we determine both $\lambda (G;T)$ and $\lambda ^{s}(G;T)$ for $(1)$ the hypercube $Q_{n}$ and $T\in \{K_{1,1},K_{1,2},K_{1,3},P_{4},Q_{1},Q_{2},Q_{3}\}$; $(2)$ the $k$-ary $n$-cube $Q^{k}_{n}$$(k\ge 3)$ and $T\in \{K_{1,1},K_{1,2},K_{1,3},Q^{3}_{1},Q^{4}_{1}\}$; $(3)$ the balanced hypercube $BH_{n}$ and $T\in \{K_{1,1},K_{1,2},BH_{1}\}$. We also extend some results in Lin, C.-K., Zhang, L., Fan, J. and Wang, D. (2016, Structure connectivity and substructure connectivity of hypercubes. Theor. Comput. Sci., 634, 97–107) and Lv, Y., Fan, J., Hsu, D.F. and Lin, C.-K. (2018, Structure connectivity and substructure connectivity of $k$-ary $n$-cubes. Inf. Sci., 433, 115–124).
Distinct Cutoff Values of Adalimumab Trough Levels Are Associated With Different Therapeutic Outcomes in Patients With Inflammatory Bowel Disease
Authors: Park Sang Hyoung , Al-Bawardy Badr , Aniwan Satimai , Kane Sunanda V , Coelho-Prabhu Nayantara , Papadakis Konstantinos A , Kisiel John B , Bruining David H , Faubion William A , Raffals Laura E , Pardi Darrell S , Tremaine William J , Stephens Michael C , Tung Jeanne , Khanna Sahil , Willrich Maria Alice V , Loftus Edward V 
Published: November 2019

Abstract

Background and Aims
We aimed to evaluate the relationship of serum adalimumab trough levels (ATL) with disease activity of inflammatory bowel disease (IBD) patients in a large, well-characterized referral center-based cohort.

Methods
We compared serum ATL between those with clinical, biochemical, or endoscopic/radiologic disease activity and those without.

Results
A total of 236 patients with IBD were included. Higher cutoff levels were associated with endoscopic and/or radiologic responses (cutoff value: 5.3 mcg/mL, P = 0.003) compared with improvement in C-reactive protein (cutoff value: 4.3 mcg/mL, P = 0.031).

Conclusions
Higher cutoff ATL was associated with endoscopic and/or radiologic response.
R2 prime (R2′) magnetic resonance imaging for post-myocardial infarction intramyocardial haemorrhage quantification
Authors: Rossello Xavier , Lopez-Ayala Pedro , Fernández-Jiménez Rodrigo , Oliver Eduardo , Galán-Arriola Carlos , de Molina-Iracheta Antonio , Agüero Jaume , López Gonzalo J , Lobo-Gonzalez Manuel , Vílchez-Tschischke Jean Paul , Fuster Valentin , Sánchez-González Javier , Ibanez Borja 
Published: November 2019

Abstract

Aims
To assess whether R2* is more accurate than T2* for the detection of intramyocardial haemorrhage (IMH) and to evaluate whether T2′ (or R2′) is less affected by oedema than T2* (R2*), and thus more suitable for the accurate identification of post-myocardial infarction (MI) IMH.

Methods and results
Reperfused anterior MI was performed in 20 pigs, which were sacrificed at 120 min, 24 h, 4 days, and 7 days. At each time point, cardiac magnetic resonance (CMR) T2- and T2*-mapping scans were recorded, and myocardial tissue samples were collected to quantify IMH and myocardial water content. After normalization by the number of red blood cells in remote tissue, histological IMH increased 5.2-fold, 10.7-fold, and 4.1-fold at Days 1, 4, and 7, respectively. The presence of IMH was correlated more strongly with R2* (r = 0.69; P = 0.013) than with T2* (r = −0.50; P = 0.085). The correlation with IMH was even stronger for R2′ (r = 0.72; P = 0.008). For myocardial oedema, the correlation was stronger for R2* (r = −0.63; P = 0.029) than for R2′ (r = −0.50; P = 0.100). Multivariate linear regressions confirmed that R2* values were significantly explained by both IMH and oedema, whereas R2′ values were mostly explained by histological IMH (P = 0.024) and were little influenced by myocardial oedema (P = 0.262).

Conclusion
Using CMR mapping with histological validation in a pig model of reperfused MI, R2′more accurately detected IMH and was less influenced by oedema than R2* (and T2*). Further studies are needed to elucidate whether R2′ is also better suited for the characterization of post-MI IMH in the clinical setting.
Consolidated quality improvements following benchmarking with cardiothoracic surgery registries—a systematic review
Authors: de By Theo M M H , Muslem Rahatullah , Caliskan Kadir , Bortolussi Giacomo , Philipsen Tine , Friberg Örjan , Bogers Ad J J C , Pagano Domenico 
Published: November 2019

Abstract

The influence of registries in medicine is large. However, there has been no systematic assessment conducted to quantify the impact of benchmarking with registries focused on cardiothoracic surgery. Numerous publications conclude that registry participation leads to improvement of outcomes for patients. A large number of registries provide evidence sub-structured by statistics that show decreases in morbidity and mortality in the participants’ clinical units. Many authors praise the benchmarking method making use of databases of registries as having a positive effect on outcome of care. However, studies proving the direct causal relation between the use of cardiothoracic surgery-oriented registries and improvement of clinical in-hospital outcomes are extremely scarce. We aimed to analyse the causal relation between the use of cardiothoracic surgery-oriented registries and improvement of clinical outcomes. In a systematic literature review, publications demonstrating the use of registry data to obtain consolidated quality improvements were selected. After analysis of 2990 scientific publications, 6 studies filled the inclusion criteria. The selected studies acknowledged that benchmarking of data against registries was used for a focused and methodologically organized improvement in cardiothoracic departments. In conjunction with the impact of the applied methods on healthcare, their results demonstrate quantifiable enhanced local outcomes over time.
Carotenoids produced by halophilic bacterial strains on mural paintings and laboratory conditions
Authors: Cojoc L R , Enache M I , Neagu S E , Lungulescu M , Setnescu R , Ruginescu R , Gomoiu I 
Published: November 2019

ABSTRACT
Due to the presence of efflorescences and improper microclimate conditions for conservation, pink-pigmented areas were reported in two historic monuments in Northern and Central part of Romania. The aims of the present study were to find the nature of pink pigments observed on the pictorial layer, original and infilling mortar, to investigate the presence of carotenoids both on mural paintings and in the isolated halophilic bacterial strains and to preliminary characterize and identify the producing strains. Their role in the aesthetical biodeterioration of historic monuments was also pointed out. Obtained Raman spectra of the pink pigments extracted both from the isolated bacterial cultures (molecularly identified as mostly related to Halobacillus hunanensis and Halobacillus naozhouensis) and from the mural painting samples contain diagnostic bands of carotenoids. These results were confirmed by FTIR spectroscopy. The strong Raman signal of bacterial carotenoids detected on mural painting indicated their potential use as biomarker molecules in the evaluation of contamination and state of conservation of mural paintings and lithic monuments. Our results contribute to opening a new direction in cultural heritage restoration to assess the conservation status on the basis of interdisciplinary research, starting with spectroscopic methods (Raman, FTIR) and confirmed by microbiological analysis.
Effects of Density Control and Fertilization on Log Wood Quality from a Douglas-fir Stand in Western Oregon, USA
Authors: Kantavichai Rapeepan , Turnblom Eric C , Lowell Eini C 
Published: November 2019

Abstract
This study aimed to investigate the effects of juvenile spacing (precommercial thinning), thinning, and fertilization on Douglas-fir butt log (first 4.9 m) and second log (4.9–10 m) quality attributes: juvenile wood percentage, heartwood percentage, rings per inch, specific gravity, and modulus of elasticity. A 41-year-old, 36.6 m site index Douglas-fir stand in western Oregon, USA was selected as the first stand to explore. Nine common silviculture pathway treatments of juvenile spacing, thinning, and fertilization were applied to independent 0.404-hectare plots. Ninety-nine trees were felled and disks cut at five heights along the stem. Wood properties were measured and calculated from the disks for log quality attributes. There was no effect of silvicultural treatments on log heartwood percentage, but significant effects on other log quality attributes were observed. Juvenile wood percentage and rings per inch declined with stand density control and fertilization treatment. Responses to thinning and fertilization in log specific gravity depend on juvenile spacing. Also, thinning and juvenile spacing were shown to have impacts on log modulus of elasticity.
Estimating temporal changes in seismic velocity using a Markov chain Monte Carlo approach
Authors: Taylor G , Hillers G 
Published: November 2019

SUMMARYWe present a new method for estimating time-series of relative seismic velocity changes (dv/v) within the Earth. Our approach is a Markov chain Monte Carlo (MCMC) technique that seeks to construct the full posterior probability distribution of the dv/v variations. Our method provides a robust, computationally efficient way to compute dv/v time-series that can incorporate information about measurement uncertainty, and any prior constraints that may be available. We demonstrate the method with a synthetic experiment, and then apply the MCMC algorithm to three data examples. In the first two examples we reproduce dv/v time-series associated with the response to the 2010 M 7.2 El Mayor-Cucapah earthquake at two sites in southern California, that have been studied in previous literature. In the San Jacinto fault zone environment we reproduce the dv/v signature of a deep creep slip sequence triggered by the El Mayor-Cucapah event, that is superimposed on a strong seasonal signal. At the Salton Sea Geothermal Field we corroborate the previously observed drop-and-recovery in seismic velocity caused by ground shaking related to the El Mayor-Cucapah event. In a third, new example we compute a month long velocity change time-series at hourly resolution at Piñon Flat, California. We observe a low amplitude variation in seismic velocity with a dominant frequency of 1 cycle per day, as well as a second transient signal with a frequency of 1.93 cycles per day. We attribute the 1-d periodicity in the dv/v variation to the combined effects of the diurnal tide and solar heating. The frequency of the signal at 1.93 cycles per day matches that of the lunar (semi-diurnal) tide. Analysis of the uncertainties in the Piñon Flat time-series shows that the error contains a signal with a frequency of 1 cycle per day. We attribute this variation to seismic noise produced by freight trains operating within the Coachella Valley. By demonstrating the applicability of the MCMC method in these examples, we show that it is well suited to tackle problems involving large data volumes that are typically associated with modern seismic experiments.
Geometry of Bäcklund transformations II: Monge–Ampère invariants
Authors: Hu Yuhao 
Published: November 2019

Abstract
This article is concerned with the question: For which pairs of hyperbolic Euler–Lagrange systems in the plane does there exist a rank-$1$ Bäcklund transformation relating them? We express some obstructions to such existence in terms of the local invariants of the Euler–Lagrange systems. In addition, we discover a class of Bäcklund transformations relating two hyperbolic Euler–Lagrange systems of distinct types.
How the presentation of patient information and decision-support advisories influences opioid prescribing behavior: A simulation study
Authors: Hussain Mustafa I , Nelson Ariana M , Yeung Brent G , Sukumar Lauren , Zheng Kai 
Published: November 2019

Abstract

Objective
The United States faces an opioid crisis. Integrating prescription drug monitoring programs into electronic health records offers promise to improve opioid prescribing practices. This study aimed to evaluate 2 different user interface designs for prescription drug monitoring program and electronic health record integration.

Materials and Methods
Twenty-four resident physicians participated in a randomized controlled experiment using 4 simulated patient cases. In the conventional condition, prescription opioid histories were presented in tabular format, and computerized clinical decision support (CDS) was provided via interruptive modal dialogs (ie, pop-ups). The alternative condition featured a graphical opioid history, a cue to visit that history, and noninterruptive CDS. Two attending pain specialists judged prescription appropriateness.

Results
Participants in the alternative condition wrote more appropriate prescriptions. When asked after the experiment, most participants stated that they preferred the alternative design to the conventional design.

Conclusions
How patient information and CDS are presented appears to have a significant influence on opioid prescribing behavior.
Impact of early weaning on small intestine, metabolic, immune and endocrine system development, growth and body composition in artificially reared lambs
Authors: McCoard Sue A , Cristobal-Carballo Omar , Knol Frederik W , Heiser Axel , Khan Muhammed A , Hennes Nina , Johnstone Peter , Lewis Sarah , Stevens David R 
Published: November 2019

Abstract
AbstractThis study evaluated the effect of early weaning (EW) of artificially reared lambs using a restricted milk replacer (MR) feeding and step-down weaning system on the short- and long-term effects on growth, feed intake, selected blood metabolites and hormones, body composition, and small intestine development. Mixed-sex twin-born 2 to 5 d old lambs were randomly allocated to individual pens and fed MR at 20% of initial individual BW in week 1 and 15% in week 2 followed by weaning off MR by the end of week 4 (EW; n = 16) or week 6 (Control; Ctrl, n = 16) using a step-down procedure. Concentrate starter and fiber diets were offered ad libitum to week 9, then gradually removed over a 10-d period. All lambs were managed as a single group on pasture from weeks 6 to 16 of the trial. Feed intake was recorded daily in the first 6 wk, and BWs recorded weekly. At weeks 2, 4, 6, and 8, and pre- and postclostridial vaccination at week 8, blood samples were collected for analysis of selected blood metabolites, IGF-1, and immune function. Body composition was evaluated in eight animals per group at weeks 4 and 16 after euthanasia, and duodenal samples collected for histomorphometric evaluation. Early weaned lambs had lower DM, ME, CP, and NDF intake than Ctrl lambs at 21, 15, 21, and 36 d of rearing, respectively (P &lt; 0.001), driven by lower intakes of MR from day 15 (P &lt; 0.001) as per the experimental design, and lower total DMI of fiber (P = 0.001) from 21 to 42 d of rearing. Lamb BW tended (P = 0.097) to be lower in EW than Ctrl lambs from 5 to 10 wk of rearing, with lower ADG in EW lambs from weeks 3 to 6 (P = 0.041). Early weaning had negligible effects on duodenal morphology, organ, and carcass weights at weeks 4 and 16. Plasma metabolites (urea nitrogen, triglycerides, NEFA, glucose, and total protein) were similar between groups, while β-hydroxybutyrate was greater in EW than Ctrl lambs at weeks 4 and 6 (P = 0.018) but not week 8 indicative of early rumen development. Serum IGF-1 tended to be lower in EW than Ctrl lambs from weeks 2 to 6 only (P = 0.065). All lambs developed antibody responses postvaccination and there was no effect of treatment (P = 0.528). The results of this study illustrate that artificially reared lambs can be weaned off MR by 4 or 6 wk of rearing without compromising growth, small intestine morphology, major organ development, and body composition, nor immune function at either 4 (preweaning) or 16 (postweaning) wk of age.
Inter-unit variability of multi-leaf collimator parameters for IMRT and VMAT treatment planning: a multi-institutional survey
Authors: Isono Masaru , Akino Yuichi , Mizuno Hirokazu , Tanaka Yoshihiro , Masai Norihisa , Yamamoto Toshijiro 
Published: November 2019

Abstract
Modern treatment machines have shown small inter-unit variability regarding beam data. Recently, vendor-provided average beam data, such as the Representative Beam Data (RBD) of the TrueBeam (Varian Medical Systems, Palo Alto, CA, USA), has been used for modeling of the Eclipse (Varian Medical Systems) treatment planning system. However, RBD does not provide multi-leaf collimator (MLC) parameters, such as MLC leaf transmission factor (LTF) and dosimetric leaf gap (DLG). We performed a web-based multi-institutional survey to investigate these parameters as well as the measurement protocols and customization of the parameters for intensity-modulated radiotherapy (IMRT) and/or volumetric modulated radiotherapy (VMAT) commissioning. We collected 69 sets of linear accelerator (linac) data from 58 institutions. In order to measure MLC parameters, most institutions used farmer-type ionization chambers with a sensitive volume of 0.6 cm3, water phantoms, source surface distance of 90 cm with 10 cm depth, and a vendor-provided plan. The LTF showed small inter-unit variabilities, although the DLG showed large variations. For optimization of the parameters for IMRT/VMAT calculations, DLG values were upwardly adjusted at many institutions, whereas the LTF values were modestly changed. We clarified that MLC parameters were measured under the same conditions at more than half of the facilities. Most institutions customized parameters in a similar manner for IMRT/VMAT. The median measured and customized values obtained in our study will be valuable to verify MLC installation accuracy and to shorten the iterative processes of finding the optimal values.