bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparametric biophysical profiling of red blood cells in malaria infection
Authors: Deshmukh Shreya S. , Shakya Bikash , Chen Anna , Durmus Naside Gozde , Greenhouse Bryan , Egan Elizabeth S. , Demirci Utkan 
Published: June 2021

AbstractBiophysical separation promises label-free, less-invasive methods to manipulate the diverse properties of live cells, such as density, magnetic susceptibility, and morphological characteristics. However, some cellular changes are so minute that they are undetectable by current methods. We developed a multiparametric cell-separation approach to profile cells with simultaneously changing density and magnetic susceptibility. We demonstrated this approach with the natural biophysical phenomenon of Plasmodium falciparum infection, which modifies its host erythrocyte by simultaneously decreasing density and increasing magnetic susceptibility. Current approaches have used these properties separately to isolate later-stage infected cells, but not in combination. We present biophysical separation of infected erythrocytes by balancing gravitational and magnetic forces to differentiate infected cell stages, including early stages for the first time, using magnetic levitation. We quantified height distributions of erythrocyte populations—27 ring-stage synchronized samples and 35 uninfected controls—and quantified their unique biophysical signatures. This platform can thus enable multidimensional biophysical measurements on unique cell types.
PD-1 derived CA-170 is an oral immune checkpoint inhibitor that exhibits preclinical anti-tumor efficacy
Authors: Sasikumar Pottayil G. , Sudarshan Naremaddepalli S. , Adurthi Srinivas , Ramachandra Raghuveer K. , Samiulla Dodderi S. , Lakshminarasimhan Anirudha , Ramanathan Anuradha , Chandrasekhar Talapaneni , Dhudashiya Amit A. , Talapati Sumalatha R. , Gowda Nagesh , Palakolanu Sreenivasulareddy , Mani Jiju , Srinivasrao Bandi , Joseph David , Kumar Nigam , Nair Rashmi , Atreya Hanudatta S. , Gowda Nagaraj , Ramachandra Murali 
Published: June 2021

AbstractSmall molecule immune checkpoint inhibitors targeting PD-1 and other pathways may offer advantages including ease of dosing, ability to manage immune-related adverse events (irAEs) due to their shorter pharmacokinetic exposure and opportunity to target more than one pathway for improving efficacy. Here we describe the identification and characterization of CA-170, an amino acid inspired small molecule inhibitor of PD-L1 and VISTA derived from the interface of PD-1 and PD-L1. CA-170 exhibited potent rescue of proliferation and effector functions of T cells inhibited by PD-L1/L2 and VISTA with selectivity over other immune checkpoint proteins as well as a broad panel of receptors and enzymes. Observed blocking of PD-L1 signaling and binding to PD-L1 in the cellular context without preventing the assembly of PD-1:PD-L1 complex support the formation of a defective ternary complex as the mechanism of action of CA-170. Oral administration of CA-170 resulted in increased proliferation and activation of T cells in the tumor, and significant anti-tumor efficacy in a number of immunocompetent mouse tumor models either as a single agent or in combination with approved therapeutics. These results prompted the advancement of CA-170 to human clinical trials.
Placental secretome characterization identifies candidates for pregnancy complications
Authors: Napso Tina , Zhao Xiaohui , Lligoña Marta Ibañez , Sandovici Ionel , Kay Richard G. , George Amy L. , Gribble Fiona M. , Reimann Frank , Meek Claire L. , Hamilton Russell S. , Sferruzzi-Perri Amanda N. 
Published: June 2021

AbstractAlterations in maternal physiological adaptation during pregnancy lead to complications, including abnormal birthweight and gestational diabetes. Maternal adaptations are driven by placental hormones, although the full identity of these is lacking. This study unbiasedly characterized the secretory output of mouse placental endocrine cells and examined whether these data could identify placental hormones important for determining pregnancy outcome in humans. Secretome and cell peptidome analyses were performed on cultured primary trophoblast and fluorescence-activated sorted endocrine trophoblasts from mice and a placental secretome map was generated. Proteins secreted from the placenta were detectable in the circulation of mice and showed a higher relative abundance in pregnancy. Bioinformatic analyses showed that placental secretome proteins are involved in metabolic, immune and growth modulation, are largely expressed by human placenta and several are dysregulated in pregnancy complications. Moreover, proof-of-concept studies found that secreted placental proteins (sFLT1/MIF and ANGPT2/MIF ratios) were increased in women prior to diagnosis of gestational diabetes. Thus, placental secretome analysis could lead to the identification of new placental biomarkers of pregnancy complications.
Prioritization of candidate causal genes for asthma in susceptibility loci derived from UK Biobank
Authors: Valette Kim , Li Zhonglin , Bon-Baret Valentin , Chignon Arnaud , Bérubé Jean-Christophe , Eslami Aida , Lamothe Jennifer , Gaudreault Nathalie , Joubert Philippe , Obeidat Ma’en , van den Berge Maarten , Timens Wim , Sin Don D. , Nickle David C. , Hao Ke , Labbé Catherine , Godbout Krystelle , Côté Andréanne , Laviolette Michel , Boulet Louis-Philippe , Mathieu Patrick , Thériault Sébastien , Bossé Yohan 
Published: June 2021

AbstractTo identify candidate causal genes of asthma, we performed a genome-wide association study (GWAS) in UK Biobank on a broad asthma definition (n = 56,167 asthma cases and 352,255 controls). We then carried out functional mapping through transcriptome-wide association studies (TWAS) and Mendelian randomization in lung (n = 1,038) and blood (n = 31,684) tissues. The GWAS reveals 72 asthma-associated loci from 116 independent significant variants (PGWAS < 5.0E-8). The most significant lung TWAS gene on 17q12-q21 is GSDMB (PTWAS = 1.42E-54). Other TWAS genes include TSLP on 5q22, RERE on 1p36, CLEC16A on 16p13, and IL4R on 16p12, which all replicated in GTEx lung (n = 515). We demonstrate that the largest fold enrichment of regulatory and functional annotations among asthma-associated variants is in the blood. We map 485 blood eQTL-regulated genes associated with asthma and 50 of them are causal by Mendelian randomization. Prioritization of druggable genes reveals known (IL4R, TSLP, IL6, TNFSF4) and potentially new therapeutic targets for asthma.
All-electrical creation and control of spin-galvanic signal in graphene and molybdenum ditelluride heterostructures at room temperature
Authors: Hoque Anamul Md. , Khokhriakov Dmitrii , Zollner Klaus , Zhao Bing , Karpiak Bogdan , Fabian Jaroslav , Dash Saroj P. 
Published: June 2021

AbstractThe ability to engineer new states of matter and control their spintronic properties by electric fields is at the heart of future information technology. Here, we report a gate-tunable spin-galvanic effect in van der Waals heterostructures of graphene with a semimetal of molybdenum ditelluride at room temperature due to an efficient spin-charge conversion process. Measurements in different device geometries with control over the spin orientations exhibit spin-switch and Hanle spin precession behavior, confirming the spin origin of the signal. The control experiments with the pristine graphene channels do not show any such signals. We explain the experimental spin-galvanic signals by theoretical calculations considering the spin-orbit induced spin-splitting in the bands of the graphene in the heterostructure. The calculations also reveal an unusual spin texture in graphene heterostructure with an anisotropic out-of-plane and in-plane spin polarization. These findings open opportunities to utilize graphene-based heterostructures for gate-controlled spintronic devices.
Perceived global increase in algal blooms is attributable to intensified monitoring and emerging bloom impacts
Authors: Hallegraeff Gustaaf M. , Anderson Donald M. , Belin Catherine , Bottein Marie-Yasmine Dechraoui , Bresnan Eileen , Chinain Mireille , Enevoldsen Henrik , Iwataki Mitsunori , Karlson Bengt , McKenzie Cynthia H. , Sunesen Inés , Pitcher Grant C. , Provoost Pieter , Richardson Anthony , Schweibold Laura , Tester Patricia A. , Trainer Vera L. , Yñiguez Aletta T. , Zingone Adriana 
Published: June 2021

AbstractGlobal trends in the occurrence, toxicity and risk posed by harmful algal blooms to natural systems, human health and coastal economies are poorly constrained, but are widely thought to be increasing due to climate change and nutrient pollution. Here, we conduct a statistical analysis on a global dataset extracted from the Harmful Algae Event Database and Ocean Biodiversity Information System for the period 1985–2018 to investigate temporal trends in the frequency and distribution of marine harmful algal blooms. We find no uniform global trend in the number of harmful algal events and their distribution over time, once data were adjusted for regional variations in monitoring effort. Varying and contrasting regional trends were driven by differences in bloom species, type and emergent impacts. Our findings suggest that intensified monitoring efforts associated with increased aquaculture production are responsible for the perceived increase in harmful algae events and that there is no empirical support for broad statements regarding increasing global trends. Instead, trends need to be considered regionally and at the species level.
Horizontal circulation across density surfaces contributes substantially to the long-term mean northern Atlantic Meridional Overturning Circulation
Authors: Zhang Rong , Thomas Matthew 
Published: June 2021

AbstractThe Greenland Sea is often viewed as the northern terminus of the Atlantic Meridional Overturning Circulation. It has also been proposed that the shutdown of open-ocean deep convection in the Labrador or Greenland Seas would substantially weaken the Atlantic Meridional Overturning Circulation. Here we analyze Robust Diagnostic Calculations conducted in a high-resolution global coupled climate model constrained by observed hydrographic climatology to provide a holistic picture of the long-term mean Atlantic Overturning Circulation at northern high latitudes. Our results suggest that the Arctic Ocean, not the Greenland Sea, is the northern terminus of the mean Atlantic Overturning Circulation; open-ocean deep convection, in either the Labrador or Greenland Seas, contributes minimally to the mean Atlantic Overturning Circulation, hence it would not necessarily be substantially weakened by a shutdown of open-ocean deep convection; horizontal circulation across sloping isopycnals contributes substantially (more than 40%) to the maximum mean northeastern subpolar Atlantic Overturning Circulation.
Streamer‐to‐precursor transition in N2–SF6 mixtures under positive repetitive submicrosecond pulses
Authors: Zhao Zheng , Dai Zhifeng , Sun Anbang , Li Jiangtao 
Published: June 2021

AbstractThe evolution of discharge dynamics in N2–SF6 mixtures under long‐term repetitive submicrosecond pulses is investigated based on pulse‐sequence resolved electrical and optical diagnostics. The effects of gas pressure, pulse repetition frequency (PRF), and SF6 concentration on discharge evolutions are determined. The number of applied pulses before breakdown is shown to non‐linearly decrease with increasing PRF for all included gas pressures and SF6 concentrations. A higher SF6 concentration is favourable for increasing relative insulation capability under repetitive pulses. Unexpected complexities of discharge evolutions under repetitive pulses are reported for the first time for the discharge mechanism transition when a strong electronegative gas is introduced. A pulse‐to‐pulse progressive streamer (first discharge)‐to‐precursor (before breakdown) transition is observed in an N2–SF6 mixture under positive repetitive pulses and is less dependent on gas pressure than traditional scenarios. The formation of a precursor section is jointly supported by electrical and optical signatures. The discharge mechanism transition and the detour phenomenon under repetitive pulses are discussed based on the effects of space charges on the spatial distribution of the electric field strength.
Milky Way spiral arms from open clusters in Gaia EDR3
Authors: Castro-Ginard A. , McMillan P. J. , Luri X. , Jordi C. , Romero-Gómez M. , Cantat-Gaudin T. , Casamiquela L. , Tarricq Y. , Soubiran C. , Anders F. 
Published: June 2021

Context. The physical processes driving the formation of Galactic spiral arms are still under debate. Studies using open clusters favour the description of the Milky Way spiral arms as long-lived structures following the classical density wave theory. Current studies comparing the Gaia DR2 field stars kinematic information of the solar neighbourhood to simulations, find a better agreement with short-lived arms with a transient behaviour.
Aims. Our aim is to provide an observational, data-driven view of the Milky Way spiral structure and its dynamics using open clusters as the main tracers, and to contrast it with simulation-based approaches. We used the most complete catalogue of Milky Way open clusters, with astrometric Gaia EDR3 updated parameters, estimated astrophysical information, and radial velocities, to revisit the nature of the spiral pattern of the Galaxy.
Methods. We used a Gaussian mixture model to detect overdensities of open clusters younger than 30 Myr that correspond to the Perseus, Local, Sagittarius, and Scutum spiral Arms, respectively. We used the birthplaces of the open cluster population younger than 80 Myr to trace the evolution of the different spiral arms and compute their pattern speed. We analysed the age-distribution of the open clusters across the spiral arms to explore the differences in the rotational velocity of stars and spiral arms.
Results. We are able to increase the range in Galactic azimuth where present-day spiral arms are described, better estimating its parameters by adding 264 young open clusters to the 84 high-mass star-forming regions used so far, thus increasing the number of tracers by 314%. We used the evolution of the open clusters from their birth positions to find that spiral arms nearly co-rotate with field stars at any given radius, discarding a common spiral pattern speed for the spiral arms explored.
Conclusions. The derivation of different spiral pattern speeds for the different spiral arms disfavours classical density waves as the main drivers for the formation of the Milky Way spiral structure, and it is in better agreement with simulation-based approaches that tend to favour transient spirals. The increase in the number of known open clusters, as well as in their derived properties, allows us to use them as effective spiral structure tracers and homogenise the view from open clusters and field stars on the nature of the Galactic spiral arms.
Reproduction number for an age of infection structured model
Authors: Barril Carles , Calsina Àngel , Cuadrado Sílvia , Ripoll Jordi 
Published: June 2021

We study the basic reproduction number (R0) in an epidemic model where infected individuals are initially asymptomatic and structured by the time since infection. At the beginning of an epidemic outbreak the computation of R0 relies on limited data based mostly on symptomatic cases, since asymptomatic infected individuals are not detected by the surveillance system. R0 has been widely used as an indicator to assess the dissemination of infectious diseases. Asymptomatic individuals are assumed to either become symptomatic after a fixed period of time or they are removed (recovery or disease-related death). We determine R0 understood as the expected secondary symptomatic cases produced by a symptomatic primary case through a chain of asymptomatic infections. R0 is computed directly by interpreting the model ingredients and also using a more systematic approach based on the next-generation operator. Reported Covid-19 cases data during the first wave of the pandemic in Spain are used to fit the model and obtain both values of R0 before and after the severe lockdown imposed in March 2020. The results confirm that SARS-CoV-2 was expanding within the population before the lockdown whereas the virus spreading was controlled two weeks after the lockdown.
In memoriam Carles Perelló, emeritus professor at UAB, recently deceased and scientific father/grandfather of the authors.
Eyelid Malposition after Blepharoplasty: An Ounce of Prevention
Authors: Williams Katherine J. , Allen Richard C. 
Published: June 2021

AbstractUpper and lower eyelid blepharoplasty are common procedures performed to provide a more youthful and rejuvenated appearance. However, this seemingly straightforward procedure may result in lid malpositions, frustrating the patient and surgeon alike, which ultimately require further treatment. We review preoperative assessment pearls to avoid these lid malpositions, as well as options for treating any postoperative complications related to lid position. Many of the techniques discussed in this article, in addition to many other oculoplastic procedures, are available to view in Dr. Richard C. Allen's operative video library at: http://webeye.ophth.uiowa.edu/eyeforum/video/plastics/.
An Atypical Case of Mild COVID-19 Infection with Severe Guillain-Barré Syndrome as Neurological Manifestation
Authors: Behera Debasis , Behera Ruchi Rekha , Jagaty Suman Kumar , Das Rekha , Venkataram Rajesh , Subhankar Saswat , Samal Vikram 
Published: June 2021

Abstract
Introduction More than 80 million people have been infected with coronavirus disease 2019 (COVID-19) infection worldwide till date with more than 17,00000 fatalities. Although COVID-19 commonly affects respiratory system in the form of cough and dyspnea, a neurotropic presentation has been described in one-third of patients.
Objective We report an atypical case of COVID-19 with mild symptoms who presented to our hospital with features suggestive of severe Guillain-Barré syndrome (GBS).
Discussion The mechanisms by which severe acute respiratory syndrome coronavirus 2 causes neurologic damage are multifactorial, including direct damage to specific receptors, cytokine-mediated injury, secondary hypoxia, and retrograde travel along nerve fibers. The pathogenesis of GBS secondary to COVID-19 is not yet well understood. It is hypothesized that viral illnesses-related GBS could be mediated due to autoantibodies or direct neurotoxic effects of viruses.
Conclusion In this ongoing era of pandemic, it is very important for the clinicians to be aware of association of GBS with COVID-19, as early diagnosis and treatment of this complication could have gratifying results. It is also very important to differentiate GBS from critical illness neuropathy and respiratory distress secondary to COVID-19 itself, as treatment to the above conditions is quite different and inability to correctly diagnose could lead to significant increase in morbidity and mortality.
The relationship between net promoter score and insurers’ profitability: an empirical analysis at the customer level
Authors: Jahnert Jonas R. , Schmeiser Hato 
Published: June 2021

AbstractThis paper examines the relationship between customer satisfaction and profitability at the level of the individual customer. In many industries, investigations detect a positive, decreasing relationship between customer satisfaction and firm profitability. The insurance industry has rarely been the object of such investigations. Pooser and Browne (2018) started this discussion by examining U.S. insurers at the firm level. We provide reasons why the positive satisfaction–profitability relationship might be reversed, particularly in the case of the insurance industry. We conduct an array of OLS regressions with customer-level data. Our results reveal a strong positive relationship between customer satisfaction and profitability. The effect is considerably large and also robust when investigating the effect of several customer characteristics on this relationship. We recommend that the increase in profitability is induced by a strong positive correlation between customer satisfaction and premium income, while satisfaction is not associated with the combined ratio.
The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients
Authors: Pyfrom Sarah , Paneru Bam , Knox James J. , Cancro Michael P. , Posso Sylvia , Buckner Jane H. , Anguera Montserrat C. 
Published: June 2021

SignificancePathogenic autoantibodies are a feature of systemic lupus erythematosus (SLE), of which 85% of patients are women. Multiple X chromosomes increase the risk for SLE, suggesting an important role for X-linked gene expression for the female sex bias. X-chromosome inactivation (XCI) regulates X-linked gene expression on the inactive X. This study examines XCI maintenance across multiple human B cell subsets from healthy individuals and SLE patients. Importantly, we found that both pediatric and adult SLE patient B cells have significant reductions with epigenetic modifications on the inactive X and aberrant X-linked gene expression. Our findings will be instrumental for future investigations of disease mechanisms underlying the female bias of SLE and abnormal autoantibody production in B cells.
Selective filtering of excitatory inputs to nucleus accumbens by dopamine and serotonin
Authors: Christoffel Daniel J. , Walsh Jessica J. , Hoerbelt Paul , Heifets Boris D. , Llorach Pierre , Lopez Ricardo C. , Ramakrishnan Charu , Deisseroth Karl , Malenka Robert C. 
Published: June 2021

Significance
Dopamine (DA) and serotonin (5-HT) release in the nucleus accumbens (NAc) influence motivated behaviors, yet the mechanisms by which they modulate NAc activity are unclear. Here, we report that DA selectively reduced excitatory postsynaptic currents (EPSCs) from paraventricular thalamus (PVT) inputs, whereas 5-HT reduced EPSCs from PVT, ventral hippocampus (vHip), and basolateral amygdala (BLA) inputs but not medial prefrontal cortex (mPFC) inputs. Mimicking the input-specific effect of DA via optogenetic inhibition of the PVT promoted cocaine-conditioned place preference, while inhibition of the mPFC blocked the enhancement of sociability induced by (±)3,4-methylenedioxymethamphetamine (MDMA). Together, these results suggest that these input-specific effects on NAc excitatory transmission contribute to the distinct modulation of behavior that is generated by release of DA and 5-HT.
Filtration of 2-particles suspension in a porous medium
Authors: Kuzmina L I , Osipov Yu V , Astakhov M D 
Published: June 2021

Abstract
Abstract During the construction of underground storage of hazardous waste, it is necessary to create waterproof walls in the ground. The grout is filtered in the rock, fills the pores and, when hardened, creates a reliable barrier to groundwater. A one-dimensional model of the flow of inhomogeneous particles in a porous medium is considered. The retained particles profiles formed during deep bed filtration are studied. It is shown that when filtering a 2-particle suspension, the deposit is distributed unevenly. The profile of large retained particles is always monotonous, and the profile of small retained particles is nonmonotonic. The monotonicity of the total deposit profile depends on the model parameters. The shape of non-monotonic profiles is time-dependent. At short times, the profile decreases monotonously. At some point, a maximum appears on the profile graph, which shifts from the inlet to the output with increasing time. When the maximum point reaches the outlet, the profile becomes monotonically increasing. With a further increase in time, the retention profiles remain monotonically increasing. Analytical solutions for a filtration model with particles of three or more different types are unknown. Analysis of the retention profiles of the polydisperse suspension requires further study.