bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital Cell Sorter (DCS): a cell type identification, anomaly detection, and Hopfield landscapes toolkit for single-cell transcriptomics
Authors: Domanskyi Sergii , Hakansson Alex , Bertus Thomas J. , Paternostro Giovanni , Piermarocchi Carlo 
Published: January 2021

Motivation
Analysis of singe cell RNA sequencing (scRNA-seq) typically consists of different steps including quality control, batch correction, clustering, cell identification and characterization, and visualization. The amount of scRNA-seq data is growing extremely fast, and novel algorithmic approaches improving these steps are key to extract more biological information. Here, we introduce: (i) two methods for automatic cell type identification (i.e., without expert curator) based on a voting algorithm and a Hopfield classifier, (ii) a method for cell anomaly quantification based on isolation forest, and (iii) a tool for the visualization of cell phenotypic landscapes based on Hopfield energy-like functions. These new approaches are integrated in a software platform that includes many other state-of-the-art methodologies and provides a self-contained toolkit for scRNA-seq analysis.

Results
We present a suite of software elements for the analysis of scRNA-seq data. This Python-based open source software, Digital Cell Sorter (DCS), consists in an extensive toolkit of methods for scRNA-seq analysis. We illustrate the capability of the software using data from large datasets of peripheral blood mononuclear cells (PBMC), as well as plasma cells of bone marrow samples from healthy donors and multiple myeloma patients. We test the novel algorithms by evaluating their ability to deconvolve cell mixtures and detect small numbers of anomalous cells in PBMC data.

Availability
The DCS toolkit is available for download and installation through the Python Package Index (PyPI). The software can be deployed using the Python import function following installation. Source code is also available for download on Zenodo: DOI 10.5281/zenodo.2533377.

Supplementary information
Supplemental Materials are available at PeerJ online.
Differences in osseointegration rate due to implant surface geometry can be explained by local tissue strains
Authors: Simmons Craig A. , Meguid Shaker A. , Pilliar Robert M. 
Published: July 2002

AbstractExperimental evidence indicates that the surface geometry of bone‐interfacing implants influences the nature and rate of tissues formed around implants. In a previously reported animal model study, we showed that non‐functional, press‐fitted porous‐surfaced implants placed in rabbit femoral condyle sites osseointegrated more rapidly than plasma‐sprayed implants. We hypothesized that the accelerated osseointegration observed with the porous‐surfaced design was the result of this design providing a local mechanical environment that was more favourable for bone formation. In the present study, we tested this hypothesis using finite element analysis and homogenization methods to predict the local strains in the pre‐mineralized tissues formed around porous‐surfaced and plasma‐sprayed implants. We found that, for loading perpendicular to the implant interface, the porous surface structure provided a large region that experienced low distortional and volumetric strains, whereas the plasma‐sprayed implant provided little local strain protection to the healing tissue. The strain protected region, which was within the pores of the sintered porous surface layer, corresponded to the region where the difference in the amount of mineralization between the two implant designs was the greatest. Low distortional and volumetric strains are believed to favour osteogenesis, and therefore the model results provide initial support for the hypothesis that the porous‐surfaced geometry provides a local mechanical environment that favours more rapid bone formation in certain situations. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Flortaucipir (tau) PET in LGI1 antibody encephalitis
Authors: Day Gregory S. , Gordon Brian A. , McCullough Austin , Bucelli Robert C. , Perrin Richard J. , Benzinger Tammie L. S. , Ances Beau M. 
Published: January 2021

AbstractThe contributors to persistent cognitive impairment and hippocampal atrophy in leucine‐rich glioma‐inactivated 1 antibody encephalitis (LGI1) patients are unknown. We evaluated whether tau neuropathology measured with [18F]flortaucipir PET neuroimaging associated with persistent cognitive impairment and hippocampal atrophy in four recovering LGI1 patients (3 men; median age, 67 [37–88] years). Imaging findings in cases were compared with those observed in age‐ and gender‐similar cognitively normal individuals (n = 124) and individuals with early‐symptomatic Alzheimer disease (n = 11). Elevated [18F]flortaucipir retention was observed in the two LGI1 patients with hippocampal atrophy and persistent cognitive impairment, including one with autopsy‐confirmed Alzheimer disease. Tau neuropathology may associate with cognitive complaints and hippocampal atrophy in recovering LGI1 patients.
Heterojunction Perovskite Microrods Prepared by Remote‐Controlled Vacancy Filling and Halide Exchange
Authors: Shahjahan Md , Yuyama Ken‐ichi , Okamoto Takuya , Biju Vasudevanpillai 
Published: January 2021

AbstractAnion exchange reaction tunes the band gap of halide perovskites, which proceeds by the migration of the ions through the halide vacancies. This study reports the preparation of the heterojunction perovskite microrods by optically controlled localized halide vacancy filling, and halide exchange leading to color tuning in the MAPbBr3 microrod crystals. The exchange reaction is homogeneously suppressed by treating the crystal with a halide precursor solution, whereas the reaction is locally inhibited at the specific site of a crystal by filling the halide vacancies using a tightly focused beam of a near‐infrared laser. By controlling the density of halide vacancies at the specific site of the crystal, the rate of nonradiative recombination of charge carriers in the crystal is controlled. This halide vacancy filling by the remote‐controlled reaction helps to locally control the crystal quality and photoluminescence for designing perovskite‐based high‐quality photovoltaic and optoelectronic devices.
A Micropatterned Human‐Specific Neuroepithelial Tissue for Modeling Gene and Drug‐Induced Neurodevelopmental Defects
Authors: Sahni Geetika , Chang Shu‐Yung , Meng Jeremy Teo Choon , Tan Jerome Zu Yao , Fatien Jean Jacques Clement , Bonnard Carine , Utami Kagistia Hana , Chan Puck Wee , Tan Thong Teck , Altunoglu Umut , Kayserili Hülya , Pouladi Mahmoud , Reversade Bruno , Toh Yi‐Chin 
Published: January 2021

AbstractThe generation of structurally standardized human pluripotent stem cell (hPSC)‐derived neural embryonic tissues has the potential to model genetic and environmental mediators of early neurodevelopmental defects. Current neural patterning systems have so far focused on directing cell fate specification spatio‐temporally but not morphogenetic processes. Here, the formation of a structurally reproducible and highly‐organized neuroepithelium (NE) tissue is directed from hPSCs, which recapitulates morphogenetic cellular processes relevant to early neurulation. These include having a continuous, polarized epithelium and a distinct invagination‐like folding, where primitive ectodermal cells undergo E‐to‐N‐cadherin switching and apical constriction as they acquire a NE fate. This is accomplished by spatio‐temporal patterning of the mesoendoderm, which guides the development and self‐organization of the adjacent primitive ectoderm into the NE. It is uncovered that TGFβ signaling emanating from endodermal cells support tissue folding of the prospective NE. Evaluation of NE tissue structural dysmorphia, which is uniquely achievable in the model, enables the detection of apical constriction and cell adhesion dysfunctions in patient‐derived hPSCs as well as differentiating between different classes of neural tube defect‐inducing drugs.
Modularly Programmable Nanoparticle Vaccine Based on Polyethyleneimine for Personalized Cancer Immunotherapy
Authors: Nam Jutaek , Son Sejin , Park Kyung Soo , Moon James J. 
Published: January 2021

AbstractNanoparticles (NPs) can serve as a promising vaccine delivery platform for improving pharmacological property and codelivery of antigens and adjuvants. However, NP‐based vaccines are generally associated with complex synthesis and postmodification procedures, which pose technical and manufacturing challenges for tailor‐made vaccine production. Here, modularly programmed, polyethyleneimine (PEI)‐based NP vaccines are reported for simple production of personalized cancer vaccines. Briefly, PEI is conjugated with neoantigens by facile coupling chemistry, followed by electrostatic assembly with CpG adjuvants, leading to the self‐assembly of nontoxic, sub‐50 nm PEI NPs. Importantly, PEI NPs promote activation and antigen cross‐presentation of antigen‐presenting cells and cross‐priming of neoantigen‐specific CD8+ T cells. Surprisingly, after only a single intratumoral injection, PEI NPs with optimal PEGylation elicit as high as ≈30% neoantigen‐specific CD8+ T cell response in the systemic circulation and sustain elevated CD8+ T cell response over 3 weeks. PEI‐based nanovaccines exert potent antitumor efficacy against pre‐established local tumors as well as highly aggressive metastatic tumors. PEI engineering for modular incorporation of neoantigens and adjuvants offers a promising strategy for rapid and facile production of personalized cancer vaccines.
Mitochondrial Damage‐Induced Innate Immune Activation in Vascular Smooth Muscle Cells Promotes Chronic Kidney Disease‐Associated Plaque Vulnerability
Authors: Bi Xianjin , Du Changhong , Wang Xinmiao , Wang Xue‐Yue , Han Wenhao , Wang Yue , Qiao Yu , Zhu Yingguo , Ran Li , Liu Yong , Xiong Jiachuan , Huang Yinghui , Liu Mingying , Liu Chi , Zeng Chunyu , Wang Junping , Yang Ke , Zhao Jinghong 
Published: January 2021

AbstractChronic kidney disease (CKD) is associated with accelerated atherosclerosis progression and high incidence of cardiovascular events, hinting that atherosclerotic plaques in CKD may be vulnerable. However, its cause and mechanism remain obscure. Here, it is shown that apolipoprotein E‐deficient (ApoE−/−) mouse with CKD (CKD/ApoE−/− mouse) is a useful model for investigating the pathogenesis of plaque vulnerability, and premature senescence and phenotypic switching of vascular smooth muscle cells (VSMCs) contributes to CKD‐associated plaque vulnerability. Subsequently, VSMC phenotypes in patients with CKD and CKD/ApoE−/− mice are comprehensively investigated. Using multi‐omics analysis and targeted and VSMC‐specific gene knockout mice, VSMCs are identified as both type‐I‐interferon (IFN‐I)‐responsive and IFN‐I‐productive cells. Mechanistically, mitochondrial damage resulting from CKD‐induced oxidative stress primes the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway to trigger IFN‐I response in VSMCs. Enhanced IFN‐I response then induces VSMC premature senescence and phenotypic switching in an autocrine/paracrine manner, resulting in the loss of fibrous cap VSMCs and fibrous cap thinning. Conversely, blocking IFN‐I response remarkably attenuates CKD‐associated plaque vulnerability. These findings reveal that IFN‐I response in VSMCs through immune sensing of mitochondrial damage is essential for the pathogenesis of CKD‐associated plaque vulnerability. Mitigating IFN‐I response may hold promise for the treatment of CKD‐associated cardiovascular diseases.
Dual‐Targeting Peptide‐Guided Approach for Precision Delivery and Cancer Monitoring by Using a Safe Upconversion Nanoplatform
Authors: Zha Shuai , Chau Ho‐Fai , Chau Wai Yin , Chan Lai Sheung , Lin Jun , Lo Kwok Wai , Cho William Chi‐Shing , Yip Yim Ling , Tsao Sai Wah , Farrell Paul J. , Feng Liang , Di Jin Ming , Law Ga‐Lai , Lung Hong Lok , Wong Ka‐Leung 
Published: January 2021

AbstractUsing Epstein‐Barr virus (EBV)‐induced cancer cells and HeLa cells as a comparative study model, a novel and safe dual‐EBV‐oncoproteins‐targeting pH‐responsive peptide engineering, coating, and guiding approach to achieve precision targeting and treatment strategy against EBV‐associated cancers is introduced. Individual functional peptide sequences that specifically bind to two overexpressed EBV‐specific oncoproteins, EBNA1 (a latent cellular protein) and LMP1 (a transmembrane protein), are engineered in three different ways and incorporated with a pH‐sensitive tumor microenvironment (TME)‐cleavable linker onto the upconversion nanoparticles (UCNP) NaGdF4:Yb3+, Er3+@NaGdF4 (UCNP‐Pn, n = 5, 6, and 7). A synergistic combination of the transmembrane LMP1 targeting ability and the pH responsiveness of UCNP‐Pn is found to give specific cancer differentiation with higher cellular uptake and accumulation in EBV‐infected cells, thus a lower dose is needed and the side effects and health risks from treatment would be greatly reduced. It also gives responsive UC signal enhancement upon targeted dual‐protein binding and shows efficacious EBV cancer inhibition in vitro and in vivo. This is the first example of simultaneous imaging and inhibition of two EBV latent proteins, and serves as a blueprint for next‐generation peptide‐guided precision delivery nanosystem for the safe monitoring and treatment against one specific cancer.
Small Molecules with Controllable Molecular Weights Passivate Surface Defects in Air‐Stable p‐i‐n Perovskite Solar Cells
Authors: Hsu Hsiang‐Lin , Jiang Bing‐Huang , Lan Jie‐Min , Wu Chien‐Hsin , Jeng Ru‐Jong , Chen Chih‐Ping 
Published: January 2021

AbstractThe passivation of surface defects at the interfaces and grain boundaries of perovskites has great potential to improve the optoelectronic properties of related devices. In this study, the small molecules LG0.5, LG1.5, and LG2.5—having precise and controllable molecular weights (various generations synthesized through click reactions) and featuring urethane, urea, and malonamide functionalities—are synthesized, and their ability to passivate the defects of perovskites are evaluated. X‐ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, and time‐resolved photoluminescence spectroscopy are used to observe the interactions between the perovskites and these molecules. The embedding of LG0.5 promotes the growth of large‐grain perovskite crystals, leading to increases in the intensities of the UV–vis absorption and photoluminescence spectral signals of the perovskite as well as longer carrier lifetimes. A power conversion efficiency of almost 20% for a p‐i‐n perovskite solar cell having the layer structure indium tin oxide/NiOx/CH3NH3PbI3 (with LG0.5)/[6,6]‐phenyl C61 butyric acid methyl ester/bathocuproine/Ag is observed. This device (without encapsulation) exhibits excellent air‐stability, retaining 89.8% of its initial performance after storage in an ambient environment (25 °C, 40% humidity) for over 120 d.
Evaluating high‐resolution optical and thermal reflectance of maize interseeded with cover crops across spatial scales using remotely sensed imagery
Authors: Brooker Aaron , Renner Karen , Price Richard F. , Basso Bruno 
Published: January 2021

AbstractWe evaluated the optical and thermal reflectance of maize (Zea mays L.) interseeded with cover crops using remotely sensed canopy temperature and multispectral imagery. In 2017 and 2018 annual ryegrass (Lolium multiflorum Lam.), crimson clover (Trifolium incarnatum L.), oilseed radish (Raphanus sativus L.), and a mixture of annual ryegrass and crimson clover were interseeded in maize at V3 and V6 at three different cover crop seeding rates in small research plots at two experimental farm sites within the network of Michigan State University. The same cover crop species were interseeded in maize at V3 and V6 at a single seeding rate in on‐farm replicated strip trials and also a full‐scale field trial at five locations in Michigan. Canopy temperature and multispectral reflectance were remotely measured 10–12 times throughout each season at all sites using fixed wing aircraft at 1‐m spatial resolution. Optical and thermal reflectance were also measured remotely using an unmanned aerial vehicle (UAV) with 2‐cm spatial resolution three times during the growing season at the small plot sites. Normalized difference vegetation index (NDVI) and normalized difference red‐edge (NDRE) were calculated for each of the experimental sites. No significant differences were detected between the interseeded treatments and control with regards to the optical and thermal reflectance and maize grain yield. Variability at field scale was due to inherent differences and not caused by the interseeding treatments.
Silicon uptake and translocation in low‐silica rice mutants investigated by isotope fractionation
Authors: Zhou Jingjie , Sun Yan , Xiao Han , Ma Qingxu , Si Linlin , Ni Liang , Wu Lianghuan 
Published: January 2021

AbstractSilicon (Si) alleviates biotic and abiotic stress in plants and many studies have been conducted in Si uptake by the roots. However, there is limited information about Si translocation during grain filling and the Si transport pathways regulating plant Si uptake. In the present study, we performed a 2‐yr field trial on the wild‐type rice (Oryza sativa L.) varieties Oochikara and Taichung‐65 and their corresponding mutants lsi1 and lsi2. We used multi‐collector, inductively coupled plasma mass spectrometry to evaluate Si isotope fractionation by the Lsi1 and Lsi2 transporters. The qualitative isotope fractionation caused by Lsi1 and Lsi2 (δ30SiLsi1 and δ30SiLsi2) were −2.95 and −2.61‰, respectively, in 2016 and −1.35 and −1.67‰, respectively, in 2017, indicating that transporter Lsi1 and Lsi2 preferentially absorbed 28Si rather than 30Si. Moreover, there was net 28Si enrichment in the mutants, indicating that except for Lsi1 and Lsi2, other Si transport pathways belong to ion channels and electrogenic pumps occur in rice. The unexpected observed decrease in 30Si from the husk to the grain suggests xylem‐to‐phloem Si transfer during grain filling. Hence, Si isotope fractionation is a useful tool to investigate plant Si uptake and translocation.
Relating through Oppression: Longitudinal Relations between Parental Racial Socialization, School Racial Climate, Oppressed Minority Ideology, and Empathy in Black Male Adolescents’ Prosocial Development
Authors: Bañales Josefina , Lozada Fantasy T. , Channey Jozet , Jagers Robert J. 
Published: January 2021

AbstractThis research explored whether Black male adolescents’ (N = 453; Mage = 13.72, SD = 1.33) perceptions of parental racial socialization (i.e., behavioral racial socialization) and school racial climate (i.e., equitable school racial climate) were associated with prosocial outcomes (i.e., prosocial behaviors and positive relations with others) across three waves of adolescence. This study also explored whether youth’s beliefs about the extent to which Black individuals and other marginalized communities are united by experiences of oppression (i.e., oppressed minority ideology) and empathy mediated these associations. Structural equation modeling indicated that parental behavioral racial socialization at Wave 1 and positive relations with others at Wave 3 were positively linked through youth’s oppressed minority ideology and empathy at Wave 2. Thus, Black male adolescents who relate to other marginalized communities through a shared experience of oppression and feel empathy towards others’ lives possess skills that translate their lessons about race and racism into positive relations with others.
Mortality from silicosis in Brazil: Temporal trends in the period 1980–2017
Authors: Algranti Eduardo , Saito Cézar A. , Carneiro Ana P. S. , Bussacos Marco A. 
Published: January 2021

AbstractBackgroundSilicosis is the most prevalent pneumoconiosis in Brazil. We aimed to estimate mortality rates and temporal trends for silicosis, and to identify areas of highest mortality.MethodsRecords of silicosis as the underlying (1980–2017) or contributory (2000–2017) cause of death in adults aged 20 years and older were retrieved from the Brazilian Mortality Database. Age‐standardized mortality rates (ASMR) were calculated. The annual trend in ASMR was analyzed by joinpoint regression. Mortality rates per 100,000 person‐years were calculated for each municipality. We analyzed temporal trends in municipalities where similar activities with exposure to silica were performed.ResultsThere were 3164 death records (96.6% men) distributed over 14% of the municipalities. Mean age of death was 59.2 (SD 15.1) and mean ASMR was 0.085/100,000 (confidence interval 0.080–0.091). Joinpoint regression showed a significant increase in ASMR from 1980 to 2006 and a significant decrease after 2006 driven by a decline in deaths of individuals younger than 70 years. The highest mortality rate was 21.83/100,000 person‐years, in a municipality with small mining operations for gems. Gold mining municipalities showed the highest composite death rate, 4.0/100,000 person‐years. Tuberculosis was the main cause of death when silicosis was a contributing cause.ConclusionsIn contrast with developed countries, silicosis mortality in Brazil increased to 2006 and subsequently started to drop, mostly from a plateau or decrease in deaths occurring in municipalities which regulated economic activities. However, this decrease did not occur in the older age group nor in the unregulated sector, the latter being the main challenge for exposure control and surveillance.
Increased β‐site APP cleaving enzyme 1‐mediated insulin receptor cleavage in type 2 diabetes mellitus with cognitive impairment
Authors: Bao Hong , Liu Yiming , Zhang Mengguo , Chen Zuolong , Zhang Weiwei , Ge Yuhao , Kang Dongmei , Gao Feng , Shen Yong 
Published: January 2021

AbstractIntroductionPatients with type 2 diabetes mellitus (T2DM) are at a high risk of cognitive impairment, with insulin resistance playing a pivotal role. β‐site amyloid precursor protein cleaving enzyme 1 (BACE1) is considered a predictor of Alzheimer's disease. However, the potential roles of BACE1 in insulin resistance and the risk of cognitive impairment in T2DM remain unclear.MethodsWe measured plasma BACE1 levels, BACE1 cleavage activities for Swedish mutant amyloid precursor protein (APPsw) and insulin receptor β subunit (INSR‐β), and soluble INSR (sINSR) levels in a clinical cohort study.ResultsT2DM patients with or without cognitive impairment exhibited elevated plasma BACE1 levels and BACE1 enzymatic activities for APPsw and INSR‐β, and sINSR levels. Moreover, the glycemic status correlated with elevated BACE1 levels and BACE1‐mediated INSR cleavage, which was associated with insulin resistance.DiscussionThe elevated BACE1 levels in T2DM may contribute to increasing the cognitive impairment risk through both amyloidogenesis and insulin resistance.