bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial
Authors: Kaufmann Horacio , Vickery Ross , Wang Whedy , Kanodia Jitendra , Shibao Cyndya A. , Norcliffe-Kaufmann Lucy , Haumann Brett , Biaggioni Italo 
Published: October 2021

Abstract
Purpose
In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension.

Methods
A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety.

Results
Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration.

Conclusion
Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure.

Trial registration
NCT02705755 (first posted March 10, 2016).
Biosorption of nickel, cobalt, zinc and copper ions by Serratia marcescens strain 16 in mono and multimetallic systems
Authors: Díaz A. , Marrero J. , Cabrera G. , Coto O. , Gómez J. M. 
Published: October 2021

AbstractThe metallurgical industry is one of the main sources of heavy metal pollution, which represents a severe threat to life. Metals can be removed from aqueous solutions by using microbial biomasses. This paper analyses the heavy metal biosorption capacity ofSerratia marcescensstrain 16 in single and multimetallic systems. The results obtained show that Co(II), Ni(II) and Zn(II) biosorption in monometallic systems is two to three times higher than in the presence of bi-metallic and multimetallic solutions. Fourier transform infrared spectroscopy confirmed that carbonyl, carboxyl and hydroxyl were the main functional groups, as well as the amide bands I and II involved in metal uptake, which are present in external structures of the bacterial cell. The results obtained demonstrated the viability ofS. marcescensstrain 16 as a biosorbent for the design of eco-friendly technologies for the treatment of waste liquor.
How local communities attribute livelihood vulnerabilities to climate change and other causes: a case study in North Vanuatu
Authors: Nef Danny Philipp , Neneth Daniel , Dini Patteson , Abad Carmenza Robledo , Kruetli Pius 
Published: October 2021

AbstractUnderstanding the causal factors of livelihood challenges and associated vulnerabilities is essential for developing viable adaptation strategies. However, clarifying which livelihood challenges can be attributed to which causal factors remains a challenge. In this paper, we used a case study in Vanuatu to show how local populations attribute subsistence challenges to underlying causes. Particularly, we are interested in whether there is a tendency to view climate change as the primary cause, and if so, why. We followed a participatory approach involving local community members and experts at all stages of the study process. For this, we used complementary research methods such as resource mapping, participant observation, and in-depth interviews with local community members and local agriculture experts. The results show that local populations are indeed inclined to attribute problems to external causes, particularly climate change. However, the results also indicate that this external attribution is not definitive. Rather, we find that over the course of participatory reflection, attribution to climate change was supplemented and even replaced by internal causal factors, such as changes in garden practices. Our findings suggest that the initial emphasis on climate change may be related to prevailing narratives that may have influenced individual perceptions of the study participants and created social desirability. If such bias is not recognized, the narratives risk being reified, with potential new insights being overlooked. As a result, local attribution may overstate or understate specific causes, such as climate change.
Intrinsic Defects in B Cell Development and Differentiation, T Cell Exhaustion and Altered Unconventional T Cell Generation Characterize Human Adenosine Deaminase Type 2 Deficiency
Authors: Yap Jin Yan , Moens Leen , Lin Ming-Wei , Kane Alisa , Kelleher Anthony , Toong Catherine , Wu Kathy H.C. , Sewell William A. , Phan Tri Giang , Hollway Georgina E. , Enthoven Karen , Gray Paul E. , Casas-Martin Jose , Wouters Carine , De Somer Lien , Hershfield Michael , Bucciol Giorgia , Delafontaine Selket , Ma Cindy S. , Tangye Stuart G. , Meyts Isabelle 
Published: October 2021

Abstract
Purpose
Deficiency of adenosine deaminase type 2 (ADA2) (DADA2) is a rare inborn error of immunity caused by deleterious biallelic mutations in ADA2. Clinical manifestations are diverse, ranging from severe vasculopathy with lacunar strokes to immunodeficiency with viral infections, hypogammaglobulinemia and bone marrow failure. Limited data are available on the phenotype and function of leukocytes from DADA2 patients. The aim of this study was to perform in-depth immunophenotyping and functional analysis of the impact of DADA2 on human lymphocytes.

Methods
In-depth immunophenotyping and functional analyses were performed on ten patients with confirmed DADA2 and compared to heterozygous carriers of pathogenic ADA2 mutations and normal healthy controls.

Results
The median age of the patients was 10 years (mean 20.7 years, range 1–44 years). Four out of ten patients were on treatment with steroids and/or etanercept or other immunosuppressives. We confirmed a defect in terminal B cell differentiation in DADA2 and reveal a block in B cell development in the bone marrow at the pro-B to pre-B cell stage. We also show impaired differentiation of CD4+ and CD8+ memory T cells, accelerated exhaustion/senescence, and impaired survival and granzyme production by ADA2 deficient CD8+ T cells. Unconventional T cells (i.e. iNKT, MAIT, Vδ2+ γδT) were diminished whereas pro-inflammatory monocytes and CD56bright immature NK cells were increased. Expression of the IFN-induced lectin SIGLEC1 was increased on all monocyte subsets in DADA2 patients compared to healthy donors. Interestingly, the phenotype and function of lymphocytes from healthy heterozygous carriers were often intermediate to that of healthy donors and ADA2-deficient patients.

Conclusion
Extended immunophenotyping in DADA2 patients shows a complex immunophenotype. Our findings provide insight into the cellular mechanisms underlying some of the complex and heterogenous clinical features of DADA2. More research is needed to design targeted therapy to prevent viral infections in these patients with excessive inflammation as the overarching phenotype.
Tabu search for a parallel-machine scheduling problem with periodic maintenance, job rejection and weighted sum of completion times
Authors: Krim Hanane , Zufferey Nicolas , Potvin Jean-Yves , Benmansour Rachid , Duvivier David 
Published: October 2021

AbstractWe consider in this work a bicriteria scheduling problem on two different parallel machines with a periodic preventive maintenance policy. The two objectives considered involve minimization of job rejection costs and weighted sum of completion times. They are handled through a lexicographic approach, due to a natural hierarchy among the two objectives in the applications considered. The main contributions of this paper are first to present a new problem relevant to practice, second, to develop a mixed-integer-linear-program model for the problem, and third, to introduce two generalizable tabu-search metaheuristics relying on different neighborhood structures and solution spaces. Computational results for 120 instances (generated from a real case) are reported to empirically demonstrate the effectiveness of the proposed metaheuristics.
New Tour on the Subdifferential of Supremum via Finite Sums and Suprema
Authors: Hantoute A. , López-Cerdá M. A. 
Published: October 2021

AbstractThis paper provides new characterizations for the subdifferential of the pointwise supremum of an arbitrary family of convex functions. The main feature of our approach is that the normal cone to the effective domain of the supremum (or to finite-dimensional sections of it) does not appear in our formulas. Another aspect of our analysis is that it emphasizes the relationship with the subdifferential of the supremum of finite subfamilies, or equivalently, finite weighted sums. Some specific results are given in the setting of reflexive Banach spaces, showing that the subdifferential of the supremum can be reduced to the supremum of a countable family.
Are sustainability-oriented investors different? Evidence from equity crowdfunding
Authors: Hornuf Lars , Stenzhorn Eliza , Vintis Tim 
Published: October 2021

AbstractIn this article, we examine how investor motives affect investment behavior in equity crowdfunding. In particular, we compare the investment behavior of sustainability-oriented with ordinary crowd investors on six leading equity crowdfunding platforms in Austria and Germany and investigate whether they suffer from a default shock that was recently identified by Dorfleitner et al. (2019). In general, we find evidence of a default shock in equity crowdfunding that occurs immediately after the event or if investors experience more than two insolvencies. Moreover, we find that sustainability-oriented investors pledge larger amounts of money and invest in more campaigns than ordinary crowd investors. The results also suggest that sustainability-oriented crowd investors care about non-financial returns, as they react more sensitively after experiencing a default in their equity crowdfunding portfolios, which indicates that they suffer beyond the pure financial loss. These findings contribute to recent literature on equity crowdfunding, socially responsible investing, and how individual investment motives and personal experiences affect investment decisions.
Physical Representation Learning and Parameter Identification from Video Using Differentiable Physics
Authors: Kandukuri Rama Krishna , Achterhold Jan , Moeller Michael , Stueckler Joerg 
Published: October 2021

AbstractRepresentation learning for video is increasingly gaining attention in the field of computer vision. For instance, video prediction models enable activity and scene forecasting or vision-based planning and control. In this article, we investigate the combination of differentiable physics and spatial transformers in a deep action conditional video representation network. By this combination our model learns a physically interpretable latent representation and can identify physical parameters. We propose supervised and self-supervised learning methods for our architecture. In experiments, we consider simulated scenarios with pushing, sliding and colliding objects, for which we also analyze the observability of the physical properties. We demonstrate that our network can learn to encode images and identify physical properties like mass and friction from videos and action sequences. We evaluate the accuracy of our training methods, and demonstrate the ability of our method to predict future video frames from input images and actions.
In Vitro Evaluation of Biologically Derived Hydroxyapatite Coatings Manufactured by High Velocity Suspension Spraying
Authors: Blum M. , Sayed M. , Mahmoud E. M. , Killinger A. , Gadow R. , Naga S. M. 
Published: October 2021

AbstractThis investigation aims to study a novel biologically derived coating applied on Ti alloy substrates. Obtained from a low-cost fish bone resource, a nanocrystalline hydroxyapatite has been synthesized and converted to an organic suspension. Coating was then manufactured by a high-velocity suspension flame spray process. The microstructure, phase composition, coating thickness, and roughness of hydroxyapatite (HA)-coated samples were studied. The results indicated the presence of both hydroxyapatite and β-tricalcium phosphate phases and the final coating layer was uniform and dense. In vitro bioactivity and biodegradability of the HA/Ti composite samples were estimated by immersion in simulated body fluid. Remarkable reductions in Ca2+ and PO43− ion concentrations were observed as well as low weight loss percentage and a slight variation in the pH value, indicating the generation of an apatite layer on the surface of all studied samples. Scanning electron microscopy, energy-dispersive x-ray analysis, and inductively coupled plasma–optical emission spectrometry confirm these results. Thus biological derived HA coatings are a promising candidate to enhance bioactivity and biodegradability of bone implants. To demonstrate feasibility on commercial medical components, a medical screw was coated and evaluated.
The effects of increased dopamine-levels on attentional control during reading and reading comprehension
Authors: Swart Elise K. , Sikkema-de Jong Maria T. 
Published: October 2021

AbstractThe aim of the present study was to gain insight into the neurobiological processes, particularly the dopaminergic processes, underlying attentional control during reading and reading comprehension. In order to test the effects of increased levels of dopamine (DA) in the brain, female university students (N = 80), half of them being carriers of the DRD4-7R allele and half of them not, participated in a double-blind placebo-controlled within-subjects experiment in which they were orally administered levodopa or a placebo before reading a text. After reading the text, participants reported on their attentional control during reading and completed comprehension questions. Pharmacologically increasing DA levels in the brain negatively influenced reading comprehension. This effect was moderate (ηp2 = .13). No interaction effects of condition and DRD4 genotype were found, for either attentional control or reading comprehension. Exploratory analyses showed that increased DA levels in the brain positively influenced fluctuations in attentional control, but only in a group of slow readers. No effects of increased DA were found for the two other attentional control measures used in the present study and no effects of increased DA on attentional control were found for fast readers. Results are discussed from the perspective of the inverted U-shape theory and the possible dopamine-related mechanisms.
A Review of the Neoproterozoic Global Glaciations and a Biotic Cause of Them
Authors: Casado Juan 
Published: October 2021

AbstractIn the Neoproterozoic Era, the Earth experienced two broad intervals of global glaciation, commonly known as Snowball Earth. There was also a rapid diversification of life, with the evolution of most of the eukaryotic lineages. Here, salient evidence for the Neoproterozoic global glaciations, including the carbon isotope record, is reinterpreted, and an alternative explanation for the causes of glaciation is proposed. The proliferation of life could have led to increases in atmospheric O2levels and concomitant decreases in CO2and CH4. Coupled biochemical and geochemical changes would have led to global cooling and glaciation. This so-called biotic hypothesis of the Snowball Earth is consistent with the most salient features of the reported evidence and explains the consecutive episodes of global glaciation.
Outpatient antimicrobial stewardship programs in pediatric institutions in 2020: Status, needs, barriers
Authors: El Feghaly Rana E. , Monsees Elizabeth A. , Burns Alaina , Wirtz Ann , Lee Brian R. , Hersh Adam L. , Newland Jason G. 
Published: October 2021

AbstractObjective:To assess current resources, interventions, and obstacles of pediatric outpatient antimicrobial stewardship programs (ASP).Design:Cross-sectional study.Setting:Institutions from the Sharing Antimicrobial Reports for Pediatric Stewardship OutPatient collaborative (SHARPS-OP).Participants:Antimicrobial stewardship leaders from the above institutions.Methods:An investigator-developed survey was deployed online in September 2020 to antimicrobial stewardship leaders in SHARPS-OP institutions. The survey was divided into 4 sections: (1) basic information, (2) status of pediatric outpatient ASP in the institutions including financial support, (3) outpatient ASP interventions undertaken by the institutions, and (4) needs and SHARPS-OP collaborative goals.Results:Of 56 invited institutions, 45 participated, achieving an 80% response rate. Only 5 sites (11%) had allocated financial support for an outpatient ASP, compared to 42 (95.6%) for their inpatient ASP. The most widely used outpatient ASP interventions included antimicrobial guidance (57.8%), education (46.7%), and quality improvement projects (37.8%). Time was identified as the biggest barrier to expanding outpatient ASPs (91.1%), followed by financial support (53.3%), development of meaningful reports (51.1%), and administrative support (44.4%). Important goals of the collaborative included seeking learning opportunities and developing clear metrics for pediatric outpatient ASP benchmarking. Program needs included securing operational support (35.8%) and strengthening data analysis (31.6%).Conclusions:Very few pediatric institutions with robust inpatient ASPs have devoted time and financial support to advance outpatient efforts. To promote appropriate antibiotic prescribing in the outpatient arena, time and resource funding by administrative leaders are necessary to develop a robust, sustainable stewardship infrastructure.
Characteristics of Ionospheric Storm on October 13, 2016 at the Greenwich Meridian
Authors: Wan Qingtao , Ma Guanyi , Maruyama Takashi , Li Jinghua , Wang Xiaolan , Lu Weijun 
Published: October 2021

AbstractAn ionospheric positive disturbance during a moderate geomagnetic storm on October 13, 2016 was studied with total electron content (TEC) from a chain of GNSS receivers and F2 layer peak parameters from two ionosondes at the Greenwich meridian. During a slow decrease of Dst, a large enhancement of the daytime TEC was observed from high to middle latitudes successively while there was small disturbance observed in low latitudes. The occurrence of TEC peak delayed with decreasing latitude. Similarly, positive disturbance of hmF2 and foF2 was recorded and their onsets were earlier in high latitude than middle latitude. These observations indicated that the ionospheric positive disturbance propagated equatorward which denied the dominant effect of prompt penetration eastward electric field (PPEF). Using the latitudinal and temporal variations of TEC peaks, the propagation velocity of the disturbance was estimated and found to decrease with decreasing latitude. Two available Fabry‐Perot interferometers (FPI) at the meridian W of the Greenwich showed that nighttime equatorward wind in middle latitude increased significantly after the storm sudden commencement (SSC), while no change of that was observed in low latitude. The coincidence of the directional and latitudinal features between the ionospheric disturbance and the wind observation suggested the impact of the positive storm was most likely the equatorward wind surge which raised the ionosphere to higher altitude where lower chemical loss led to increase of electron density in the daytime.
First High‐Resolution Benthic Habitat Map From the Greenland Shelf (Disko Bay Pilot Study)
Authors: Krawczyk D. W. , Zinglersen K. B. , Al‐Hamdani Z. , Yesson C. , Blicher M. E. , Arboe N. H. , Jensen J. B. , Wagnholt J. N. , Hansen F. , Rödel L.‐G. 
Published: October 2021

AbstractA healthy ocean where marine habitats and ecosystems are mapped and protected is one of the UN's Sustainable Development Goals to sustainably use marine resources. Our study presents the first high‐resolution benthic habitat map from Greenland integrating analyses of multibeam bathymetry and backscatter data, and ground‐truth data including video sled, drop camera and day grab. The pilot area of 30 × 20 km is located on the continental shelf in central Disko Bay, West Greenland and all data were collected in a single, 10‐day survey. Multibeam bathymetry data were gridded to a 10 × 10 m resolution, whereas backscatter mosaic was built from a 1 × 1 m grid cell to obtain higher resolution manifestation of seafloor properties. Ground‐truth data consisted of 14 video transects, 17 drop camera deployments, and 17 sediment samples. Our results were verified with the published shallow seismic and vibrocore data from the Disko Bay region to link the geological background with the sedimentary environment. We distinguished five physical habitats in the area, based on the distribution of sediment types, water depth with general water masses and morphology. In addition, numerous gas seeps alongside pockmarks were observed in the area, as well as recent iceberg ploughmarks. The identified habitats were associated with two basic communities of benthic fauna, linked primarily to the distribution of sediments and representing hard bottom habitats (sessile fauna) and soft bottom habitats (shrimp/polychaetes). Our study is the first step toward mapping the entire seafloor of Disko Bay to provide a scientific context for the management of seafloor and marine resources.