bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimized culture methods for isolating small extracellular vesicles derived from human induced pluripotent stem cells
Authors: Luo Ying , Gao Dunqin , Wang Peng , Lou Cheng , Li Tong , Niu Wenhui , Gao Yingtang 
Published: April 2021

AbstractExtracellular vesicles that are derived from stem cells play an important role in the treatment of disease. To obtain high‐quality small extracellular vesicles (sEVs), we optimized the culture conditions of human induced pluripotent stem cells (hiPSCs), the supernatant collection time, and sEVs extraction methods. Firstly, hiPSCs were cultured in extracellular vesicles‐production medium (EVs‐PM) containing different concentrations (0%, 0.25%, 0.5%, 2%, 5%, and 20%) of extracellular vesicle‐depleted knockout serum replacement (ED‐KSR), and the culture supernatants were collected continuously for 5 days. Then, the sEVs were isolated, followed by an evaluation of their characteristics. The survival rates of the hiPSCs lines that were cultured in EVs‐PM containing 0.5% to 20% ED‐KSR were not significantly different (P > 0.05). The survival rates of the hiPSCs in 0.5% ED‐KSR after the culture supernatants were continuously collected for day 1, day 3, and day 5 were not statistically significant (P > 0.05). After 5 days of continuous collection of the supernatant, the hiPSCs expressed some pluripotent markers, while SSEA4 and TRA‐1‐60 expression changed gradually. The sEVs that were extracted by the two methods were all 50–200 nm, double‐layered and oval or round cellular vesicles and expressed the marker proteins CD63, TSG101, and HSP70. The characteristics of sEVs extracted on day 1, day 3, and day 5 were almost identical on morphology, size and the relative quantity of annexin V‐positive subpopulations. The PKH67 staining showed that the sEVs could be endocytosed by HepG2 cells and aggregated in the cytoplasm. The proliferation experiments showed that the sEVs can promote cell proliferation. In Conclusion, the 0.5% ED‐KSR is the optimal concentration, and that the hiPSCs culture supernatant can be continuously collected for 5 days while maintaining high cell viability and some pluripotent characteristics. Both of the methods extraction can be used to obtain biologically active sEVs.
Viral reduction of human blood by ultraviolet A‐photosensitized vitamin K5
Authors: He Yong , Xu Fei , Ibrahim Zina , Feyissa Qinati , Reed Jennifer L. , Vostal Jaroslav G. 
Published: April 2021

AbstractBlood product transfusion can transmit viral pathogens. Pathogen reduction methods for blood products have been developed but, so far, are not available for whole blood. We evaluated if vitamin K5 (VK5) and ultraviolet A (UVA) irradiation could be used for virus inactivation in plasma and whole blood. Undiluted human plasma and whole blood diluted to 20% were spiked with high levels of vaccinia or Zika viruses. Infectious titers were measured by standard TCID50 assay before and after VK5/UVA treatments. Up to 3.6 log of vaccinia and 3.2 log of Zika were reduced in plasma by the combination of 500 μM VK5 and 3 J/cm2 UVA, and 3.1 log of vaccinia and 2.9 log of Zika were reduced in diluted human blood (20%) by the combination of 500 μM VK5 and 70 J/cm2 UVA. At end of whole blood treatment, hemolysis increased from 0.18% to 0.41% but remained below 1% hemolysis, which is acceptable to the Food and Drug Administration for red cell transfusion products. No significant alteration of biochemical parameters of red blood cells occurred with treatment. Our results provide proof of the concept that a viral pathogen reduction method based on VK5/UVA may be developed for whole blood.
Stroke and HIV‐associated neurological complications: A retrospective nationwide study
Authors: Patel Urvish K. , Malik Preeti , Li Yingjie , Habib Anam , Shah Shamik , Lunagariya Abhishek , Jani Vishal , Dhamoon Mandip S. 
Published: April 2021

AbstractThere is an increased risk of stroke and other neurological complications in human immunodeficiency virus (HIV) infected patients with no large population‐based studies in the literature. We aim to evaluate the prevalence of stroke, HIV‐associated neurological complications, and identify risk factors associated with poor outcomes of stroke among HIV admissions in the United States. In the nationwide inpatient sample with adult HIV hospitalizations, patients with primary cerebrovascular disease (CeVDs) and HIV‐associated neurological complications were identified by ICD‐9‐CM codes. We performed a retrospective study with weighted analysis to evaluate the prevalence of stroke and neurological complications and outcomes of stroke among HIV patients. We included 1,559,351 HIV admissions from 2003 to 2014, of which 22470 (1.4%) patients had CeVDs (transient ischemic attack [TIA]: 3240 [0.2%], acute ischemic stroke [AIS]: 14895 [0.93%], and hemorrhagic stroke [HS]: 4334 [0.27%]), 7781 (0.49%) had neurosyphilis, 29,925 (1.87%) meningitis, 39,190 (2.45%) cytomegalovirus encephalitis, 4699 (0.29%) toxoplasmosis, 9964 (0.62%) progressive multifocal leukoencephalopathy, and 142,910 (8.94%) epilepsy. There is increased overall prevalence trend for CeVDs (TIA: 0.17%–0.24%; AIS: 0.62%–1.29%; HS: 0.26%–0.31%; pTrend < .0001) from 2003 to 2014. Among HIV admissions, variables associated with AIS were neurosyphilis (odds ratio: 4.38; 95% confidence interval: 3.21–5.97), meningitis (4.87 [4.10–5.79]), and central nervous system tuberculosis (6.72 [3.85–11.71]). Toxoplasmosis [4.27 [2.34–7.76]), meningitis (2.91 [2.09–4.06)], and cytomegalovirus encephalitis (1.62 [1.11–2.37]) were associated with higher odds of HS compared to patients without HS. There was an increasing trend of CeVDs over time among HIV hospitalizations. HIV‐associated neurological complications were associated with the risk of stroke, together with increased mortality, morbidity, disability, and discharge to long‐term care facilities. Further research would clarify stroke risk factors in HIV patients to mitigate adverse outcomes.
Novel polarization‐dependent combiner for wide field‐of‐view glass‐like near‐eye displays
Authors: Yin Kun , He Ziqian , Li Kun , Wu Shin‐Tson 
Published: April 2021

AbstractWe propose a glass‐like wide field of view near‐eye display with a polarization‐dependent combiner (PDC). The novel PDC consists of two polarization volume lenses with strong polarization selectivity. By inserting a PDC to the proposed polarization‐time multiplexing system, we demonstrate an overall horizontal FOV of 50° while maintaining a compact form factor.
Development and validation of a simultaneous analytical method for non‐steroidal therapeutic compounds in cosmetics using liquid chromatography–tandem mass spectrometry
Authors: Woo In Suk , Kim Jun Hyung , Kim You Kyung , Kim Hyung Il , Shin Dong Woo , Kim Jin Ho , Baek Sun Young 
Published: April 2021

AbstractAtopic dermatitis is a typical chronic inflammatory skin disease that affects all age groups and requires basic skin care for treatment. Anti‐inflammatory and antiallergy steroids are the most frequently used treatments but they are limited due to their side effects caused by a weakening of the immune system. Many consumers focus on performance as a criterion for selecting cosmetics. However, steroids have been illegally used to improve the performance of cosmetics, and consumers have been adversely affected by the corresponding side effects. In this paper, we propose a simple and rapid method using liquid chromatography–tandem mass spectrometry to simultaneously analyze ten non‐permitted atopic therapeutic compounds in cosmetic products: chlorpheniramine maleate, ketotifen fumarate, doxepin hydrochloride, azelastine hydrochloride, bufexamac, clotrimazole, tranilast, fusidic acid, tacrolimus, and pimecrolimus. Additionally, the major characteristic fragment ions for tacrolimus, pimecrolimus, and clotrimazole were identified by time‐of‐flight mass spectrometry. The specificity, linearity, limit of detection, limit of quantification, recovery, precision, accuracy, and stability of the proposed method were validated. The limit of detection and quantification were in the ranges of 5.05–203.30 pg/mL and 15.15–609.90 pg/mL, respectively. The proposed analysis method could help improve the safety management of cosmetics.
Feasibility and Effectiveness of Norepinephrine Outside the Intensive Care Setting for Treatment of Hepatorenal Syndrome
Authors: Kwong Allison , Kim W. Ray , Kwo Paul Y. , Wang Uerica , Cheng Xingxing 
Published: April 2021

Vasoconstrictors are the treatment of choice for hepatorenal syndrome (HRS). We evaluate the real‐life effectiveness of a sequential vasoconstrictor regimen of midodrine–octreotide followed by norepinephrine in a nonintensive care unit (non‐ICU) setting in the United States, where terlipressin is not available. The diagnosis of HRS and definitions of response to therapy were based on 2015 guidelines from the International Club of Ascites. In adult patients with HRS without partial or full response to oral midodrine and subcutaneous octreotide, norepinephrine was administered at a starting dose of 5 mcg/minute, with a goal to achieve a mean arterial pressure (MAP) of 10 mm Hg above baseline. We assessed predictors of response and treatment outcomes. A total of 61 patients were administered midodrine and octreotide for the treatment of HRS, with a 28% response rate. The median MELD‐Na (Model for End‐Stage Liver Disease–sodium) score was 30 (interquartile range [IQR] 24‐35). Responders were more likely to have alcohol‐related liver disease and lower Acute‐on‐Chronic Liver Failure (ACLF) grade. Of the nonresponders, 20 were then administered norepinephrine, of whom 45% achieved full or partial response. Achieving an MAP increase of ≥10 mm Hg was associated with a greater probability of response. Patients who responded to norepinephrine experienced improved transplant‐free survival at 90 days (88% versus 27%; P = 0.02); 5 of 20 patients experienced norepinephrine treatment–related adverse events, namely arrhythmias. Norepinephrine can be effectively used in a non‐ICU setting as rescue therapy in patients who have not responded to midodrine and octreotide. Based on these data, we propose a practical stepwise algorithm for vasoconstrictor therapy to manage HRS in situations where terlipressin is not an option.
A note on eigenvalue bounds for non‐compact manifolds
Authors: Keller Matthias , Liu Shiping , Peyerimhoff Norbert 
Published: April 2021

AbstractIn this article we prove upper bounds for the Laplace eigenvalues below the essential spectrum for strictly negatively curved Cartan–Hadamard manifolds. Our bound is given in terms of k2 and specific geometric data of the manifold. This applies also to the particular case of non‐compact manifolds whose sectional curvature tends to , where no essential spectrum is present due to a theorem of Donnelly/Li. The result stands in clear contrast to Laplacians on graphs where such a bound fails to be true in general.
The effect of the reformed nurse staffing policy on employment of nurses in Korea
Authors: Kim Jinhyun , Kim Sungjae , Lee Eunhee , Kwon Hyunjeong , Lee Jayon , Bae Hyunji 
Published: April 2021

AbstractAimThis study aims to analyse the employment effect of reformed nurse staffing policy which is the “Integrated Nursing and Care Service” scheme that was introduced by the Korean government.DesignEconomic evaluation study focusing on employment effect.MethodAn input–output model was used to estimate the employment‐inducing effect of the new staffing policy. The analysed data of 26,381 beds, of 400 hospitals that are participated in the Integrated Nursing and Care Service scheme were retrieved from the Korean National Health Insurance claims database.ResultsThe job‐creation effect of the new staffing policy was estimated to be 48.5 persons per USD 1 million expenditure, which means 28,154 persons were employed when USD 580.15 million expenditures was paid to the hospitals by the National Health Insurance Service. In addition, the policy had an employment‐inducing effect which is as high as 3.09~6.07 times higher than that of similar industries and all industries.
An ultra‐high affinity protein–protein interface displaying sequence‐robustness
Authors: Møller Marie Sofie , Olesen Sita Vaag , André Ingemar 
Published: April 2021

AbstractProtein–protein interactions are crucial in biology and play roles in for example, the immune system, signaling pathways, and enzyme regulation. Ultra‐high affinity interactions (Kd <0.1 nM) occur in these systems, however, structures and energetics behind stability of ultra‐high affinity protein–protein complexes are not well understood. Regulation of the starch debranching barley limit dextrinase (LD) and its endogenous cereal type inhibitor (LDI) exemplifies an ultra‐high affinity complex (Kd of 42 pM). In this study the LD–LDI complex is investigated to unveil how robust the ultra‐high affinity is to LDI sequence variation at the protein–protein interface and whether alternative sequences can retain the ultra‐high binding affinity. The interface of LD–LDI was engineered using computational protein redesign aiming at identifying LDI variants predicted to retain ultra‐high binding affinity. These variants present a very diverse set of mutations going beyond conservative and alanine substitutions typically used to probe interfaces. Surface plasmon resonance analysis of the LDI variants revealed that high affinity of LD–LDI requires interactions of several residues at the rim of the protein interface, unlike the classical hotspot arrangement where key residues are found at the center of the interface. Notably, substitution of interface residues in LDI, including amino acids with functional groups different from the wild‐type, could occur without loss of affinity. This demonstrates that ultra‐high binding affinity can be conferred without hotspot residues, thus making complexes more robust to mutational drift in evolution. The present mutational analysis also demonstrates how energetic coupling can emerge between residues at large distances at the interface.
Comparison of the short‐term operative, Oncological, and Functional Outcomes between two types of robot‐assisted total mesorectal excision for rectal cancer: Da Vinci versus Micro Hand S surgical robot
Authors: Jiang Juan , Zhu Shaihong , Yi Bo , Li Jianmin 
Published: April 2021

AbstractObjectiveThis study aimed to evaluate the difference of two various robotic technology applied in R‐ Total mesorectal excision (TME).MethodsFrom May 2017 to December 2018, consecutive patients with rectal cancer who underwent da Vinci R‐TME or Micro Hand S R‐TME were enrolled. The comparative study was conducted on Short‐term Operative, Oncological, and Functional Outcomes between two type of R‐TME.Results47 patients underwent da Vinci R‐TME, and 43 patients underwent Micro Hand S R‐TME. No difference occured between two groups in TME completeness, CRM, DRM, CRM involvement and DRM involvement, operative time, blood loss, protective ileostomy, conversion rate, number of retrieved lymph nodes, Comprehensive Complication Index (CCI), International Prostate Symptom Score (IPSS) or Wexner scores. However, the setup time in the Micro Hand S group was longer.ConclusionsIn the present study, both da Vinci R‐TME and Micro Hand S R‐TME achieve excellent TME quality with acceptable morbidity and postoperative function.
The effect of corporate environmental responsibility and religiosity on corporate cash holding decisions and profitability: Evidence from the United States' policies for sustainable development
Authors: Tsendsuren Chuluunbat , Yadav Prayag L. , Han Seung Hun , Mun Seongjae 
Published: April 2021

AbstractWe use religious background as a proxy for local risk‐taking attitudes and investigate whether geographical variation in religion affects corporate environmental responsibility (CER) with regards to corporate cash policies and profitability. We conjecture that the presence of environmentally conscious firms would be higher in areas with more Catholics relative to Protestants. Study data comprises of the largest publicly traded U.S.‐listed firms of Newsweek's green rankings of 2015–2016. We use green scores and the concentration of Catholic to Protestant population ratio as proxies for CER and religiosity, respectively. We provide robust evidence that corporate environmental practices attenuate the demand for precautionary cash reserves to protect firms from unforeseeable risks. Furthermore, environmentally conscious firms located in high risk‐taking areas gain financial stability and improve profitability, strengthening their CER. The findings provide contributions to risk management literature and document the importance of firms' efforts to harmonize social behavior for sustainable financial policies.
Predictability of Localized Plasmonic Responses in Nanoparticle Assemblies
Authors: Roccapriore Kevin M. , Ziatdinov Maxim , Cho Shin Hum , Hachtel Jordan A. , Kalinin Sergei V. 
Published: April 2021

AbstractDesign of nanoscale structures with desired optical properties is a key task for nanophotonics. Here, the correlative relationship between local nanoparticle geometries and their plasmonic responses is established using encoder‐decoder neural networks. In the im2spec network, the relationship between local particle geometries and local spectra is established via encoding the observed geometries to a small number of latent variables and subsequently decoding into plasmonic spectra; in the spec2im network, the relationship is reversed. Surprisingly, these reduced descriptions allow high‐veracity predictions of local responses based on geometries for fixed compositions and surface chemical states. Analysis of the latent space distributions and the corresponding decoded and closest (in latent space) encoded images yields insight into the generative mechanisms of plasmonic interactions in the nanoparticle arrays. Ultimately, this approach creates a path toward determining configurations that yield the spectrum closest to the desired one, paving the way for stochastic design of nanoplasmonic structures.
Chiral hydrodynamics in strong external magnetic fields
Authors: Ammon Martin , Grieninger Sebastian , Hernandez Juan , Kaminski Matthias , Koirala Roshan , Leiber Julian , Wu Jackson 
Published: April 2021

AbstractWe construct the general hydrodynamic description of (3+1)-dimensional chiral charged (quantum) fluids subject to a strong external magnetic field with effective field theory methods. We determine the constitutive equations for the energy-momentum tensor and the axial charge current, in part from a generating functional. Furthermore, we derive the Kubo formulas which relate two-point functions of the energy-momentum tensor and charge current to 27 transport coefficients: 8 independent thermodynamic, 4 independent non-dissipative hydrodynamic, and 10 independent dissipative hydrodynamic transport coefficients. Five Onsager relations render 5 more transport coefficients dependent. We uncover four novel transport effects, which are encoded in what we call the shear-induced conductivity, the two expansion-induced longitudinal conductivities and the shear-induced Hall conductivity. Remarkably, the shear-induced Hall conductivity constitutes a novel non-dissipative transport effect. As a demonstration, we compute all transport coefficients explicitly in a strongly coupled quantum fluid via holography.
Traversability of multi-boundary wormholes
Authors: Al Balushi Abdulrahim , Wang Zhencheng , Marolf Donald 
Published: April 2021

Abstract
We generalize the Gao-Jafferis-Wall construction of traversable two-sided wormholes to multi-boundary wormholes. In our construction, we take the background spacetime to be multi-boundary black holes in AdS3. We work in the hot limit where the dual CFT state in certain regions locally resembles the thermofield double state. Furthermore, in these regions, the hot limit makes the causal shadow exponentially small. Based on these two features of the hot limit, and with the three-boundary wormhole as our main example, we show that traversability between any two asymptotic regions in a multi-boundary wormhole can be triggered using a double-trace deformation. In particular, the two boundary regions need not have the same temperature and angular momentum. We discuss the non-trivial angular dependence of traversability in our construction, as well as the effect of the causal shadow region.
Fusion of conformal defects in four dimensions
Authors: Söderberg Alexander 
Published: April 2021

AbstractWe consider two conformal defects close to each other in a free theory, and study what happens as the distance between them goes to zero. This limit is the same as zooming out, and the two defects have fused to another defect. As we zoom in we find a non-conformal effective action for the fused defect. Among other things this means that we cannot in general decompose the two-point correlator of two defects in terms of other conformal defects. We prove the fusion using the path integral formalism by treating the defects as sources for a scalar in the bulk.
Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
Authors: Dumanski Jan P. , Halvardson Jonatan , Davies Hanna , Rychlicka-Buniowska Edyta , Mattisson Jonas , Moghadam Behrooz Torabi , Nagy Noemi , Węglarczyk Kazimierz , Bukowska-Strakova Karolina , Danielsson Marcus , Olszewski Paweł , Piotrowski Arkadiusz , Oerton Erin , Ambicka Aleksandra , Przewoźnik Marcin , Bełch Łukasz , Grodzicki Tomasz , Chłosta Piotr L. , Imreh Stefan , Giedraitis Vilmantas , Kilander Lena , Nordlund Jessica , Ameur Adam , Gyllensten Ulf , Johansson Åsa , Józkowicz Alicja , Siedlar Maciej , Klich-Rączka Alicja , Jaszczyński Janusz , Enroth Stefan , Baran Jarosław , Ingelsson Martin , Perry John R. B. , Ryś Janusz , Forsberg Lars A. 
Published: April 2021

AbstractEpidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer’s disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a “genetic wasteland”, and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.