bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms
Authors: Ramberger Melanie , Berretta Antonio , Tan Jeanne M M , Sun Bo , Michael Sophia , Yeo Tianrong , Theorell Jakob , Bashford-Rogers Rachael , Paneva Sofija , O’Dowd Victoria , Dedi Neesha , Topia Sarfaraj , Griffin Robert , Ramirez-Franco Jorge , El Far Oussama , Baulac Stéphanie , Leite Maria I , Sen Arjune , Jeans Alexander , McMillan David , Marshall Diane , Anthony Daniel , Lightwood Daniel , Waters Patrick , Irani Sarosh R 
Published: March 2020

Abstract
Autoantibodies against leucine-rich glioma inactivated 1 (LGI1) are found in patients with limbic encephalitis and focal seizures. Here, we generate patient-derived monoclonal antibodies (mAbs) against LGI1. We explore their sequences and binding characteristics, plus their pathogenic potential using transfected HEK293T cells, rodent neuronal preparations, and behavioural and electrophysiological assessments in vivo after mAb injections into the rodent hippocampus. In live cell-based assays, LGI1 epitope recognition was examined with patient sera (n = 31), CSFs (n = 11), longitudinal serum samples (n = 15), and using mAbs (n = 14) generated from peripheral B cells of two patients. All sera and 9/11 CSFs bound both the leucine-rich repeat (LRR) and the epitempin repeat (EPTP) domains of LGI1, with stable ratios of LRR:EPTP antibody levels over time. By contrast, the mAbs derived from both patients recognized either the LRR or EPTP domain. mAbs against both domain specificities showed varied binding strengths, and marked genetic heterogeneity, with high mutation frequencies. LRR-specific mAbs recognized LGI1 docked to its interaction partners, ADAM22 and ADAM23, bound to rodent brain sections, and induced internalization of the LGI1-ADAM22/23 complex in both HEK293T cells and live hippocampal neurons. By contrast, few EPTP-specific mAbs bound to rodent brain sections or ADAM22/23-docked LGI1, but all inhibited the docking of LGI1 to ADAM22/23. After intrahippocampal injection, and by contrast to the LRR-directed mAbs, the EPTP-directed mAbs showed far less avid binding to brain tissue and were consistently detected in the serum. Post-injection, both domain-specific mAbs abrogated long-term potentiation induction, and LRR-directed antibodies with higher binding strengths induced memory impairment. Taken together, two largely dichotomous populations of LGI1 mAbs with distinct domain binding characteristics exist in the affinity matured peripheral autoantigen-specific memory pools of individuals, both of which have pathogenic potential. In human autoantibody-mediated diseases, the detailed characterization of patient mAbs provides a valuable method to dissect the molecular mechanisms within polyclonal populations.
On the Behaviour of
p
-Adic Scaled Space Filling Curve Indices for High-Dimensional Data
Authors: Bradley Patrick Erik , Jahn Markus Wilhelm 
Published: March 2020

Abstract
Space filling curves are widely used in computer science. In particular, Hilbert curves and their generalizations to higher dimension are used as an indexing method because of their nice locality properties. This article generalizes this concept to the systematic construction of $p$-adic versions of Hilbert curves based on special affine transformations of the $p$-adic Gray code and develops a scaled indexing method for data taken from high-dimensional spaces based on these new curves, which with increasing dimension is shown to be less space consuming than the optimal standard static Hilbert curve index. A measure is derived, which allows to assess the local sparsity of a dataset, and is tested on some real-world data.
Case report of successful low-dose, ultra-slow infusion thrombolysis of prosthetic mitral valve thrombosis in a high risk patient after redo-mitral valve replacement
Authors: Kapos Ioannis , Fuchs Tobias , Tanner Felix C 
Published: March 2020

Abstract

Background
An increase in transvalvular pressure gradient of prosthetic valve should always raise suspicion for obstructive valve thrombosis. A multimodality diagnostic approach including transthoracic echocardiography, transoesophageal echocardiography (TOE), cinefluoroscopy, or computed tomography (CT) is necessary for a prompt diagnosis. The management of mechanical prosthetic valve thrombosis (PVT) is high risk in any therapeutic option taken. Emergency valve replacement is recommended for critically ill patients. Fibrinolysis is an alternative for patients with contraindication to surgery or if surgery is not immediately available.

Case summary
A 52-year-old woman presented with symptoms and signs of cardiac congestion. On laboratory, brain natriuretic peptide was elevated and international normalized ratio (INR) was in subtherapeutic range. She underwent a mitral valve replacement with mechanical prosthesis 7 months before, because of a significant residual regurgitation after repair on the same year. TOE revealed severe stenosis of the prosthesis with immobile anterior disc but there was no mass present. CT revealed a minor lesion at the hinge points of the prosthesis without involvement of the ring, suggestive for thrombus. The initial fruitless management with intravenous (i.v) heparin in high therapeutic range was followed by a successful ‘low-dose, ultra-slow’ fibrinolysis.

Discussion
CT may help differentiate thrombus vs. pannus. The acute onset of symptoms, inadequate anticoagulation, and restricted leaflet motion increased the suspicion for PVT. The current European guidelines propose normal dose fibrinolysis. We performed ‘low-dose, ultra-slow’ fibrinolysis due to lower bleeding risk with successful results. Low dose should be considered as alternative to normal dose fibrinolysis or urgent surgery.
Implementing Package of Essential Non-communicable Disease Interventions in the Republic of Moldova—a feasibility study
Authors: Laatikainen Tiina , Inglin Laura , Collins Dylan , Ciobanu Angela , Curocichin Ghenadie , Salaru Virginia , Zatic Tatiana , Anisei Angela , Chiosa Diana , Munteanu Maria , Alexa Zinaida , Farrington Jill 
Published: March 2020

Abstract

Background
The aim of this study is to determine the feasibility of implementing and evaluating the World Health Organization Package of Essential Non-communicable Disease Interventions (WHO PEN) approach in primary healthcare in the Republic of Moldova.

Methods
According to our published a priori methods, 20 primary care clinics were randomized to 10 intervention and 10 control clinics. The intervention consisted of implementation of adapted WHO PEN guidelines and structured training for health workers; the control clinics continued with usual care. Data were gathered from paper-based patient records in July 2017 and August 2018 resulting in a total of 1174 and 995 patients in intervention and control clinics at baseline and 1329 and 1256 at follow-up. Pre-defined indicators describing assessment of risk factors and total cardiovascular risk, prescribing medications and treatment outcomes were calculated. Differences between baseline and follow-up as well as between intervention and control clinics were calculated using logistic and linear regression models and by assessing interaction effects.

Results
Improvements were seen in recording smoking status, activity to measure HbA1c among diabetes patients and achieving control in hypertension treatment. Improvement was also seen in identification of patients with hypertension or diabetes. Less improvement or even deterioration was seen in assessing total risk or prescribing statins for high-risk patients.

Conclusions
It is feasible to evaluate the quality and management of patients with non-communicable diseases in low-resource settings from routine data. Modest improvements in risk factor identification and management can be achieved in a relatively short period of time.
Sensitivity analysis of gravity gradient inversion of the Moho depth—a case example for the Amazonian Craton
Authors: Haas Peter , Ebbing Jörg , Szwillus Wolfgang 
Published: March 2020

SUMMARYWe present a novel approach for linearized gravity inversion to estimate the Moho depth, which allows the use of any gravitational component instead of the vertical gravity component only. The inverse problem is solved with the Gauss–Newton algorithm and the gravitational field of the undulating Moho depth is calculated with tesseroids. Hereby, the density contrast can be laterally variable by using information from seismological regionalization. Our approach is illustrated with a synthetic example, which we use to explore different regularization parameters. The vertical gravity gradient gzz provides the most reasonable results with appropriate parameters. As a case example, we invert for the Moho depth of the Amazonian Craton and its surroundings. The results are constrained by estimates from active seismic measurements. Our new Moho depth model correlates to tectonic domains and is in agreement with previous models. The estimated density contrasts of the tectonic domains agree well with the lithospheric architecture and show with 300–450 kg m–3 lower density contrasts for continental domains, whereas the oceans reveal a density contrast of 450–500 kg m–3. The wider range of estimated density contrast for the continent reflects uncertainties in Precambrian Fold Belts that arise from its small gravity signal. Our results demonstrate that a variable density contrast at the Moho depth is a valuable enhancement for gravity inversion.
A single Rayleigh mode may exist with multiple values of phase-velocity at one frequency
Authors: Forbriger Thomas , Gao Lingli , Malischewsky Peter , Ohrnberger Matthias , Pan Yudi 
Published: March 2020

SUMMARYOther than commonly assumed in seismology, the phase velocity of Rayleigh waves is not necessarily a single-valued function of frequency. In fact, a single Rayleigh mode can exist with three different values of phase velocity at one frequency. We demonstrate this for the first higher mode on a realistic shallow seismic structure of a homogeneous layer of unconsolidated sediments on top of a half-space of solid rock (LOH). In the case of LOH a significant contrast to the half-space is required to produce the phenomenon. In a simpler structure of a homogeneous layer with fixed (rigid) bottom (LFB) the phenomenon exists for values of Poisson’s ratio between 0.19 and 0.5 and is most pronounced for P-wave velocity being three times S-wave velocity (Poisson’s ratio of 0.4375). A pavement-like structure (PAV) of two layers on top of a half-space produces the multivaluedness for the fundamental mode. Programs for the computation of synthetic dispersion curves are prone to trouble in such cases. Many of them use mode-follower algorithms which loose track of the dispersion curve and miss the multivalued section. We show results for well established programs. Their inability to properly handle these cases might be one reason why the phenomenon of multivaluedness went unnoticed in seismological Rayleigh wave research for so long. For the very same reason methods of dispersion analysis must fail if they imply wave number kl(ω) for the lth Rayleigh mode to be a single-valued function of frequency ω. This applies in particular to deconvolution methods like phase-matched filters. We demonstrate that a slant-stack analysis fails in the multivalued section, while a Fourier–Bessel transformation captures the complete Rayleigh-wave signal. Waves of finite bandwidth in the multivalued section propagate with positive group-velocity and negative phase-velocity. Their eigenfunctions appear conventional and contain no conspicuous feature.
Linking the performance of a data-limited empirical catch rule to life-history traits
Authors: Fischer Simon H , De Oliveira José A A , Kell Laurence T 
Published: March 2020

AbstractWorldwide, the majorities of fish stocks are data-limited and lack fully quantitative stock assessments. Within ICES, such data-limited stocks are currently managed by setting total allowable catch without the use of target reference points. To ensure that such advice is precautionary, we used management strategy evaluation to evaluate an empirical rule that bases catch advice on recent catches, information from a biomass survey index, catch length frequencies, and MSY reference point proxies. Twenty-nine fish stocks were simulated covering a wide range of life histories. The performance of the rule varied substantially between stocks, and the risk of breaching limit reference points was inversely correlated to the von Bertalanffy growth parameter k. Stocks with k&gt;0.32 year−1 had a high probability of stock collapse. A time series cluster analysis revealed four types of dynamics, i.e. groups with similar terminal spawning stock biomass (collapsed, BMSY, 2BMSY, 3BMSY). It was shown that a single generic catch rule cannot be applied across all life histories, and management should instead be linked to life-history traits, and in particular, the nature of the time series of stock metrics. The lessons learnt can help future work to shape scientific research into data-limited fisheries management and to ensure that fisheries are MSY compliant and precautionary.
Comparative digestibility of polysaccharide-complexed zinc and zinc sulfate in diets for gestating and lactating sows
Authors: Holen Julia P , Johnston Lee J , Urriola Pedro E , Garrett Jack E , Shurson Gerald C 
Published: March 2020

AbstractWe hypothesized that the digestibility of a zinc polysaccharide complex is greater than zinc sulfate when sows consume high fiber diets containing corn dried distillers grains with solubles (DDGS). Gilts and sows (n = 32) were blocked according to parity and assigned randomly to one of four dietary treatments (n = 8 sows per treatments). Dietary treatments consisted of: 1) Control (ConZnSO4)—corn–soybean meal-based diet + 100 ppm supplemental Zn from ZnSO4; 2) Control PSZn (ConPSZn)—corn–soybean meal-based diet + 100 ppm supplemental Zn from Zn polysaccharide complex; 3) DDGS/ZnSO4—corn–soybean meal–40% DDGS gestation diet and a 30% DDGS lactation diet, with each containing 100 ppm supplemental Zn from ZnSO4; 4) DDGS/PSZn—corn–soybean meal–40% DDGS gestation diet and a 30% DDGS lactation diet, with each containing 100 ppm supplemental Zn from Zn polysaccharide complex. A fifth dietary treatment was imposed using a subset of sows (n = 20) to determine basal Zn losses in gestating and lactating sows fed corn–soybean meal-based diets containing no supplemental Zn. Nutrient balance experiments were conducted in both gestation and lactation to evaluate the digestibility of Zn sources of the four dietary treatments and to determine basal Zn losses when no supplemental Zn was provided. The statistical model included fixed effects of diet, Zn source, and their interaction, and random effects of parity. Estimated endogenous losses of Zn were used to adjust apparent total tract digestibility (ATTD) to true total tract digestibility (TTTD) of Zn in the four dietary treatment balance periods. There were no differences in Zn concentrations of urine, plasma, colostrum, or milk samples among treatments at any time of the experiment (P &gt; 0.05). Gestating sows fed DDGS/PSZn had improved (P &lt; 0.05) ATTD, TTTD, and overall retention of Zn compared with both Control treatments, with the DDGS/ZnSO4 treatment responses being intermediate. Lactating sows consuming diets without DDGS and supplemented with Zn polysaccharide complex had the greatest (P &lt; 0.05) ATTD, TTTD, and retention of Zn, which were opposite to responses observed in gestation. Furthermore, ATTD, TTTD, and Zn retention for lactating sows consuming DDGS/PSZn were less (P &lt; 0.05) than all other treatments. Overall, zinc digestibility of ZnSO4 and PSZn appears to be differentially influenced by the stage of the reproductive cycle and presence of dietary fiber from DDGS.
Increasing the ratio of SID lysine to metabolizable energy improves pig performance during a viral challenge
Authors: Jasper Jessica E , Mendoza Omarh F , Shull Caleb M , Schweer Wesley P , Schwartz Kent J , Gabler Nicholas K 
Published: March 2020

AbstractPorcine reproductive and respiratory syndrome virus (PRRSV) compromises pig performance. However, increasing standardized ileal digestible Lys per Mcal metabolizable energy (SID Lys:ME) above requirement has been shown to mitigate reduced performance seen during a porcine reproductive and respiratory syndrome (PRRS) virus challenge. The objective of this study was to evaluate the effects of increasing the dietary SID Lys:ME from 100% National Research Council (NRC) requirement to 120% of the requirement in vaccinated (vac+; modified live vaccine Ingelvac PRRS) and non-vaccinated (vac−; no PRRS vaccine) grower pigs subjected to a PRRSV challenge. In addition, the dietary formulation approach to achieve the 120% ratio by increasing Lys relative to energy (HL) or diluting energy in relation to Lys (LE) was evaluated. This allowed us to test the hypothesis that pigs undergoing a health challenge would have the ability to eat to their energy needs. Within vaccine status, 195 mixed-sex pigs, vac+ (35.2 ± 0.60 kg body weight [BW]) and vac− (35.2 ± 0.65 kg BW) were randomly allotted to one of three dietary treatments (2.67, 3.23, or 3.22 g SID Lys:ME) for a 42-d PRRS virus challenge study representing 100%, 120%, and 120% of NRC requirement, respectively. Pigs were randomly allotted across two barns, each containing 24 pens with 7 to 10 pigs per pen (8 pens per diet per vaccine status). On day post-inoculation 0, both barns were inoculated with PRRSV and started on experimental diets. Within vaccine status, weekly and overall challenge period pig performance were assessed. In both vac+ (P &lt; 0.05) and vac− (P &lt; 0.05) pigs, the HL and LE diets increased end BW and overall average daily gain (ADG) ADG compared with pigs fed the control diet (P &lt; 0.05). Overall, average daily feed intake (ADFI) during the challenge period was greater (P &lt; 0.05) for pigs fed the LE diet compared with pigs fed control and HL treatments, regardless of vaccine status (20% and 17% higher ADFI than the control in vac+ and vac− pigs, respectively). The HL vac+ pigs had the greatest gain to feed (G:F) compared with the control and LE pigs (0.438 vs. 0.394 and 0.391 kg/kg, respectively; P &lt; 0.01). Feed efficiency was not impacted (P &gt; 0.10) by treatment in the vac− pigs. In summary, PRRSV-challenged grower pigs consumed feed to meet their energy needs as indicated by the increase in ADFI when energy was diluted in the (LE) diet, compared with control pigs. In both PRRS vac+ and vac− pigs subsequently challenged with PRRSV, regardless of formulation approach, fed 120% SID Lys:ME diets resulted in enhanced overall growth performance.
Landscape genetics of wolverines (Gulo gulo): scale-dependent effects of bioclimatic, topographic, and anthropogenic variables
Authors: Balkenhol Niko , Schwartz Michael K , Inman Robert M , Copeland Jeffrey P , Squires John S , Anderson Neil J , Waits Lisette P 
Published: March 2020

AbstractClimate change can have particularly severe consequences for high-elevation species that are well-adapted to long-lasting snow conditions within their habitats. One such species is the wolverine, Gulo gulo, with several studies showing a strong, year-round association of the species with the area defined by persistent spring snow cover. This bioclimatic niche also predicts successful dispersal paths for wolverines in the contiguous United States, where the species shows low levels of genetic exchange and low effective population size. Here, we assess the influence of additional climatic, vegetative, topographic, and anthropogenic, variables on wolverine genetic structure in this region using a multivariate, multiscale, landscape genetic approach. This approach allows us to detect landscape-genetic relationships both due to typical, small-scale genetic exchange within habitat, as well as exceptional, long-distance dispersal among habitats. Results suggest that a combination of snow depth, terrain ruggedness, and housing density, best predict gene flow in wolverines, and that the relative importance of variables is scale-dependent. Environmental variables (i.e., isolation-by-resistance, IBR) were responsible for 79% of the explained variation at small scales (i.e., up to ~230 km), and 65% at broad scales (i.e., beyond ~420 km). In contrast, a null model based on only space (i.e., isolation-by-distance, IBD) accounted only for 17% and 11% of the variation at small and broad scales, respectively. Snow depth was the most important variable for predicting genetic structures overall, and at small scales, where it contributed 43% to the variance explained. At broad spatial scales, housing density and terrain ruggedness were most important with contributions to explained variation of 55% and 25%, respectively. While the small-scale analysis most likely captures gene flow within typical wolverine habitat complexes, the broad-scale analysis reflects long-distance dispersal across areas not typically inhabited by wolverines. These findings help to refine our understanding of the processes shaping wolverine genetic structure, which is important for maintaining and improving functional connectivity among remaining wolverine populations.
Bayes-Raking: Bayesian Finite Population Inference with Known Margins
Authors: Si Yajuan , Zhou Peigen 
Published: March 2020

AbstractRaking is widely used for categorical data modeling and calibration in survey practice but faced with methodological and computational challenges. We develop a Bayesian paradigm for raking by incorporating the marginal constraints as a prior distribution via two main strategies: (1) constructing solution subspaces via basis functions or the projection matrix and (2) modeling soft constraints. The proposed Bayes-raking estimation integrates the models for the margins, the sample selection and response mechanism, and the outcome as a systematic framework to propagate all sources of uncertainty. Computation is done via Stan, and codes are ready for public use. Simulation studies show that Bayes-raking can perform as well as raking with large samples and outperform in terms of validity and efficiency gains, especially with a sparse contingency table or dependent raking factors. We apply the new method to the longitudinal study of well-being study and demonstrate that model-based approaches significantly improve inferential reliability and substantive findings as a unified survey inference framework.