bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxoplasmosis Among 38 751 Hematopoietic Stem-cell Transplant Recipients: A Systematic Review of Disease Prevalence and a Compilation of Imaging and Autopsy Findings
Authors: Contopoulos-Ioannidis Despina G. , Cho Stephanie M. , Bertaina Alice , Leung Ann N. , Fischbein Nancy , Lanzman Bryan , Schwenk Hayden T. , Montoya Jose G. 
Published: March 2021

Background.
Toxoplasmosis in hematopoietic stem-cell transplant (HSCT) recipients can be life threatening if not promptly diagnosed and treated.

Methods.
We performed a systematic review (PubMed last search March 29, 2020) of toxoplasmosis among HSCT recipients and calculated the toxoplasmosis prevalence across studies. We also created a compilation list of brain imaging, chest imaging, and autopsy findings of toxoplasmosis among HSCT recipients.

Results.
We identified 46 eligible studies (47 datasets) with 399 toxoplasmosis cases among 38 751 HSCT recipients. There was large heterogeneity in the reported toxoplasmosis prevalence across studies, thus formal meta-analysis was not attempted. The median toxoplasmosis prevalence among 38 751 HSCT recipients was 2.14% (range 0%–66.67%). Data on toxoplasmosis among at-risk R+HSCT recipients were more limited (25 studies; 2404 R+HSCT recipients [6.2% of all HSCT recipients]), although the median number of R+HSCT recipients was 56.79% across all HSCT recipients. The median toxoplasmosis prevalence across studies among 2404 R+HSCT was 7.51% (range 0%–80%) versus 0% (range 0%–1.23%) among 7438 R–HSCT. There were limited data to allow meaningful analyses of toxoplasmosis prevalence according to prophylaxis status of R+HSCT recipients.

Conclusions.
Toxoplasmosis prevalence among HSCT recipients is underestimated. The majority of studies report toxoplasmosis prevalence among all HSCT recipients rather than only among the at-risk R+HSCT recipients. In fact, the median toxoplasmosis prevalence among all R+//R– HSCT recipients is 3.5-fold lower compared with the prevalence among only the at-risk R+HSCT recipients and the median prevalence among R+HSCT recipients is 7.51-fold higher than among R–HSCT recipients. The imaging findings of toxoplasmosis among HSCT recipients can be atypical. High index of suspicion is needed in R+HSCT recipients with fever, pneumonia, or encephalitis.
An Integrated Clinical and Genetic Prediction Model for Tacrolimus Levels in Pediatric Solid Organ Transplant Recipients
Authors: Min Sandar , Papaz Tanya , Lambert A. Nicole , Allen Upton , Birk Patricia , Blydt-Hansen Tom , Foster Bethany J. , Grasemann Hartmut , Hamiwka Lorraine , Litalien Catherine , Ng Vicky , Berka Noureddine , Campbell Patricia , Daniel Claude , Saw Chee Loong , Tinckam Kathryn , Urschel Simon , Van Driest Sara L. , Parekh Rulan , Mital Seema 
Published: March 2021

Background.
There are challenges in achieving and maintaining therapeutic tacrolimus levels after solid organ transplantation (SOT). The purpose of this genome-wide association study was to generate an integrated clinical and genetic prediction model for tacrolimus levels in pediatric SOT.

Methods.
In a multicenter prospective observational cohort study (2015–2018), children <18 years old at their first SOT receiving tacrolimus as maintenance immunosuppression were included (455 as discovery cohort; 322 as validation cohort). Genotyping was performed using a genome-wide single nucleotide polymorphism (SNP) array and analyzed for association with tacrolimus trough levels during 1-y follow-up.

Results.
Genome-wide association study adjusted for clinical factors identified 25 SNPs associated with tacrolimus levels; 8 were significant at a genome-wide level (P < 1.025 × 10−7). Nineteen SNPs were replicated in the validation cohort. After removing SNPs in strong linkage disequilibrium, 14 SNPs remained independently associated with tacrolimus levels. Both traditional and machine learning approaches selected organ type, age at transplant, rs776746, rs12333983, and rs12957142 SNPs as the top predictor variables for dose-adjusted 36- to 48-h posttacrolimus initiation (T1) levels. There was a significant interaction between age and organ type with rs776476*1 SNP (P < 0.05). The combined clinical and genetic model had lower prediction error and explained 30% of the variation in dose-adjusted T1 levels compared with 18% by the clinical and 12% by the genetic only model.

Conclusions.
Our study highlights the importance of incorporating age, organ type, and genotype in predicting tacrolimus levels and lays the groundwork for developing an individualized age and organ-specific genotype-guided tacrolimus dosing algorithm.
Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance
Authors: Coku Jorida , Booth David M. , Skoda Jan , Pedrotty Madison C. , Vogel Jennifer , Liu Kangning , Vu Annette , Carpenter Erica L. , Ye Jamie C. , Chen Michelle A. , Dunbar Peter , Scadden Elizabeth , Nakamaru-Ogiso Eiko , Li Yimei , Goldsmith Kelly C. , Patrick Reynolds C. , Hajnoczky Gyorgy , Hogarty Michael D. 
Published: March 2021

ABSTRACTMost cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptotic programs. We isolated mitochondria from neuroblastoma cell lines obtained from children at diagnosis and after relapse following failed therapy, and profiled responses to tBid and Bim, death effectors activated by therapeutic stress. Mitochondria from post-relapse models had markedly attenuated cytochrome c release (surrogate for apoptotic commitment) in comparison with patient-matched diagnostic models. Mitochondrial DNA content, size, and shape did not differ consistently. However, we used electron microscopy to identify reduced endoplasmic reticulum-mitochondria contacts (ERMCs) as correlated with therapy resistance. ERMCs form microdomains for the transfer of Ca2+to mitochondria. We confirmed reduced Ca2+transfer in resistant cells, with restoration by re-opposing ERMCs via genetically-encoded linkers. However, reduced Ca2+transfer was not present in all ERMC-reduced cancers with therapy resistance, supporting Ca2+-independent mechanisms. Genetically or biochemically reducing ERMCs in therapy sensitive tumors phenocopied resistance, validating these inter-organelle contacts as physiologic regulators of apoptosis. Our work confirms the importance of ERMCs in stress signaling and provides a previously unrecognized mechanism for cancer cell resistance that is not exclusive to other contributors.
Sandalwood, an Indian medicinal plant attenuates the microbial growth and influence up/down regulation of the metabolites
Authors: Parveen Romana , Shamsi Tooba Naz , Fatima Sadaf 
Published: March 2021

AbstractThe methanolic extract of sandalwood (SwME) was prepared by soxhlet apparatus and the antibacterial assay was performed. Further, the metabolite profiling of SwME and lysates ofE. coliandE. coligrown in the presence of SwME was generated. SwME showed maximum inhibition againstE. coli(MTCC 443) i.e. 82.71%, and minimal againstB. subtilis(MTCC 736) i.e. 26.82%. The metabolome profiles ofE. coliand SwME were generated using gas chromatography-mass spectrometry (GC-MS) technique. Comparative studies were done to understand to what extent metabolite modifications differ between SwME,E. colilysate and theE. colistrain grown in presence of extract. Result revealed 23 peaks with major compounds present inE. coliwere 9-Octadecenoic Acid (Z)-, Methyl Ester (26.85%), Hexadecanoic Acid, methyl ester (20.5%) and Hexadecanoic acid, trimethylsilyl ester (15.79%). WhenE. coliwas grown in the presence of SwME, GC-MS analysis showed 25 peaks with major compounds such as 9-Octadecenoic Acid, Methyl Ester (21.97%), Hexadecanoic Acid, Methyl Ester (17.03%), and Hexadecanoic Acid, Trimethylsilyl Ester (14.96%). Correlating the metabolic profiles with the changes occurring is essential to progression their comprehension and in the development of new approaches to identify the metabolomics regulation inE. coliin response to SwME.
Single Image-based Vignetting Correction for Improving the Consistency of Neural Activity Analysis in 2-Photon Functional Microscopy
Authors: Li Dong , Wang Guangyu , Werner René , Xie Hong , Guan Ji-Song , Hilgetag Claus C. 
Published: March 2021

AbstractHigh-resolution functional 2-photon microscopy of neural activity is a cornerstone technique in current neuroscience, enabling, for instance, the image-based analysis of relations of the organization of local neuron populations and their temporal neural activity patterns. Interpreting local image intensity as a direct quantitative measure of neural activity presumes, however, a consistent within- and across-image relationship between the image intensity and neural activity, which may be subject to interference by illumination artifacts. In particular, the so-called vignetting artifact - the decrease of image intensity towards the edges of an image - is, at the moment, widely neglected in the context of functional microscopy analyses of neural activity, but potentially introduces a substantial center-periphery bias of derived functional measures. In the present report, we propose a straightforward protocol for single image-based vignetting correction. Using immediate-early-gene-based 2-photon microscopic neural image data of the mouse brain, we show the necessity of correcting both image brightness and contrast to improve within- and across-image intensity consistency and demonstrate the plausibility of the resulting functional data.
Atorvastatin effectively inhibits late replicative cycle steps of SARS-CoV-2in vitro
Authors: Zapata-Cardona María I. , Flórez-Álvarez Lizdany , Zapata-Builes Wildeman , Guerra-Sandoval Ariadna L. , Guerra-Almonacid Carlos M. , Hincapié-García Jaime , Rugeles María T. , Hernandez Juan C. 
Published: March 2021

AbstractIntroductionSARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused a pandemic of historic proportions and continues to spread worldwide. Currently, there is no effective therapy against this virus. This article evaluated thein vitroantiviral effect of Atorvastatin against SARS-CoV-2 and also identified the interaction affinity between Atorvastatin and three SARS-CoV-2 proteins, usingin silicostructure-based molecular docking approach.Materials and methodsThe antiviral activity of Atorvastatin against SARS-CoV-2 was evaluated by three different treatment strategies using a clinical isolate of SARS-CoV-2. The interaction of Atorvastatin with Spike, RNA-dependent RNA polymerase (RdRp) and 3C-like protease (3CLpro) was evaluated by molecular docking.ResultsAtorvastatin showed anti-SARS-CoV-2 activity of 79%, 54.8%, 22.6% and 25% at 31.2, 15.6, 7.9, and 3.9 µM, respectively, by pre-post-treatment strategy. In addition, atorvastatin demonstrated an antiviral effect of 26.9% at 31.2 µM by pre-infection treatment. This compound also inhibited SARS-CoV-2 in 66.9%, 75%, 27.9% and 29.2% at concentrations of 31.2, 15.6, 7.9, and 3.9 µM, respectively, by post-infection treatment. The interaction of atorvastatin with SARS-CoV-2 Spike, RdRp and 3CL protease yielded a binding affinity of −8.5 Kcal/mol, −6.2 Kcal/mol, and −7.5 Kcal/mol, respectively.ConclusionOur study demonstrated thein vitroanti-SARS-CoV-2 activity of Atorvastatin, mainly against the late steps of the viral replicative cycle. A favorable binding affinity with viral proteins by bioinformatics methods was also shown. Due to its low cost, availability, well-established safety and tolerability, and the extensive clinical experience of atorvastatin, it could prove valuable in reducing morbidity and mortality from COVID-19.ImportanceThe COVID-19 pandemic constitutes the largest global public health crisis in a century, with enormous health and socioeconomic challenges. Therefore, it is necessary to search for specific antivirals against its causative agent (SARS-CoV-2). In this sense, the use of existing drugs may represent a useful treatment option in terms of safety, cost-effectiveness, and timeliness. Atorvastatin is widely used to prevent cardiovascular events. This compound modulates the synthesis of cholesterol, a molecule necessary in different stages of the viral replicative cycle. Our study demonstrated the antiviral potential of atorvastatin against SARS-CoV-2, using anin vitromodel. Furthermore, the ability of Atorvastatin to directly interfere with three viral targets (Spike, RdRp and 3CL protease) was demonstrated by bioinformatic methods. This compound is a well-studied, low-cost, and generally well-tolerated drug, so it could be a promising antiviral for the treatment of COVID-19.
FGFR inhibitor mediated dismissal of SWI/SNF complexes from YAP-dependent enhancers induces adaptive therapeutic resistance
Authors: Li Yihao , Qiu Xintao , Wang Xiaoqing , Liu Hui , Geck Renee C. , Tewari Alok K. , Xiao Tengfei , Font-Tello Alba , Lim Klothilda , Jones Kristen L. , Morrow Murry , Vadhi Raga , Kao Pei-Lun , Jaber Aliya , Yerrum Smitha , Xie Yingtian , Chow Kin-Hoe , Cejas Paloma , Nguyen Quang-Dé , Long Henry W. , Liu X. Shirley , Toker Alex , Brown Myles 
Published: March 2021

AbstractHow cancer cells adapt to evade the therapeutic effects of drugs targeting oncogenic drivers is poorly understood. Here we report an epigenetic mechanism leading to the adaptive resistance of triple-negative breast cancer (TNBC) to fibroblast growth factor receptor (FGFR) inhibitors. Prolonged FGFR inhibition suppresses the function of BRG1-dependent chromatin remodeling leading to an epigenetic state that derepresses YAP-associated enhancers. These chromatin changes induce the expression of several amino acid transporters resulting in increased intracellular levels of specific amino acids that reactivate mTORC1. Collectively, these findings reveal a novel feedback loop involving an epigenetic state transition and metabolic reprogramming that leads to adaptive therapeutic resistance.
Utilization of recycled polyester nonwovens as sorbent for oil spill cleanups
Authors: Subramoniapillai Viju , Thilagavathi G. 
Published: March 2021

Purpose
The most widely recycled plastic in the world is recycled polyethylene terephthalate (rPET). To minimize the environmental related issues associated with synthetic fibers, several researchers have explored the potential use of recycled polyester fibers in developing various technical textile products. This study aims to develop needle-punched nonwoven fabrics from recycled polyester fibers and investigate its suitability in oil spill cleanup process.

Design/methodology/approach
According to Box and Behnken factorial design, 15 different needle-punched nonwoven fabrics from recycled polyester fibers were prepared by changing the parameters, namely, needle punch density, needle penetration depth and fabric areal weight. Several featured parameters such as oil sorption, oil retention, oil sorption kinetics, wettability and reusability performance were systematically elucidated.

Findings
The maximum oil sorption of recycled nonwoven polyester is found to be 24.85 g/g and 20.58 g/g for crude oil and vegetable oil, respectively. The oil retention is about 93%–96% in case of crude oil, whereas 87%–91% in case of vegetable oil. Recycled polyester nonwoven possesses good hydrophobic–oleophilic properties with static contact angle of 138° against water, whereas 0° against crude oil and vegetable oil. The reusability test results indicate that recycled polyester nonwoven fabric can be used several times because of its reusability features.

Originality/value
There is no detailed study on the oil sorption features of needle-punched nonwoven fabrics developed from recycled polyester fibers. This study is expected to help in developing fabrics for oil spill cleanups.
The earlier the better? Nesting timing and reproductive success in subalpine cavity‐nesting bees
Authors: Wong Lydia H. , Forrest Jessica R. K. 
Published: March 2021

Abstract

Reproductive timing can affect an organism's production of offspring and its offspring's success, both of which contribute to its overall fitness. In seasonal environments, the timing of reproductive activity may be restricted to short periods of the year owing to numerous potential selective pressures such as variation in daylength, weather, food availability, predation or competition.

We documented the relationships between reproductive timing and individual reproductive success (total reproductive output and offspring success) in subalpine populations of five cavity‐nesting solitary bee species. We also examined the relationships between bee reproductive success and environmental variables that are likely ultimate drivers of bee phenology in subalpine environments (i.e. seasonality of floral resource abundance and temperature).

Over 6 years, we recorded solitary bee nesting timing, egg production and offspring success using artificial nesting structures (‘trap‐nests’) established at multiple study sites. We also quantified floral resources and recorded temperature throughout growing seasons.

Bees nesting earlier in the season exhibited greater reproductive success. Reproductive output generally increased with floral abundance, although this relationship was weak and only significant for some bee species. Elevated temperatures were associated with increased nest construction rate, but not with greater reproductive output. These contrasting effects of temperature may have been driven by the negative relationship between temperature and bee longevity. Bees who nested for shorter durations of time (a proxy for longevity) produced fewer offspring, and individuals exhibiting the shortest nesting durations were also those that began nesting late in the season.

Overall, bees who initiated nesting early and sustained activity for a long duration had the highest reproductive output. This work documents the relationship between reproductive phenology and fitness in wild insect populations and highlights the ways in which organisms can cope with the challenges of living in seasonal and highly variable environments.
THE RISK OF AUSTERITY CO‐PRODUCTION IN CITY‐REGIONAL GOVERNANCE IN ENGLAND
Authors: Habermehl Victoria , Perry Beth 
Published: March 2021

AbstractThis article examines the risk of what we term ‘austerity co‐production’, a weak form of collaborative governance shaped by resource scarcity and fragmented, multiple forms of expertise. Despite the hope that co‐production has radical potential to solve governance challenges across city‐regions, not enough attention has been paid to the institutional contexts in which co‐production is developed. We argue this institutional context is crucial in shaping how co‐production comes to ground and the conditions it reproduces. We draw on a critical case study of metropolitan policymaking in Greater Manchester, England, to examine the gap between imagined and actual institutional contexts for co‐production. We develop a framework that can be applied in different policy areas to assess the potential implementation of co‐production in city‐regional governance. Whilst the promise of co‐production remains, we conclude that austerity co‐production risks operating as an already‐existing default solution to urban problems that constrains more innovative approaches to the governance and politics of the city‐region.
Curcumin induces ferroptosis in non‐small‐cell lung cancer via activating autophagy
Authors: Tang Xin , Ding Hui , Liang Maoli , Chen Xing , Yan Yuxia , Wan Nansheng , Chen Qianqian , Zhang Jing , Cao Jie 
Published: March 2021

AbstractBackgroundEmerging studies showed curcumin can inhibit glioblastoma and breast cancer cells via regulating ferroptosis. However, the role of ferroptosis in the inhibitory effect of curcumin on non‐small‐cell lung cancer (NSCLC) remains unclear.MethodsCell counting kit‐8 (CCK‐8) assay was used to measure the viability of A549 and H1299 cells under different conditions. Cell proliferation was examined by Ki67 immunofluorescence. The morphological changes of cells and tumor tissues were observed by optical microscope and hematoxylin and eosin (H&E) staining. Intracellular reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and iron contents were determined by corresponding assay kit. The related protein expression levels were detected by western blot and immunohistochemistry. Transmission electron microscope was used to observe ultrastructure changes of A549 and H1299 cells.ResultsCurcumin inhibited tumor growth and cell proliferation, but promoted cell death. Characteristic changes of ferroptosis were observed in curcumin group, including iron overload, GSH depletion and lipid peroxidation. Meanwhile, the protein level of ACSL4 was higher and the levels of SLC7A11 and GPX4 were lower in curcumin group than that in control group. Incubation of ferroptosis inhibitors ferrostatin‐1 (Fer‐1) or knockdown of iron‐responsive element‐binding protein 2 (IREB2) notably weakened curcumin‐induced anti‐tumor effect and ferroptosis in A549 and H1299 cells. Further investigation suggested that curcumin induced mitochondrial membrane rupture and mitochondrial cristae decrease, increased autolysosome, increased the level of Beclin1 and LC3, and decreased the level of P62. Curcumin‐induced autophagy and subsequent ferroptosis were both alleviated with autophagy inhibitor chloroquine (CQ) or siBeclin1.ConclusionCurcumin induced ferroptosis via activating autophagy in NSCLC, which enhanced the therapeutic effect of NSCLC.
BiT age: A transcriptome‐based aging clock near the theoretical limit of accuracy
Authors: Meyer David H. , Schumacher Björn 
Published: March 2021

AbstractAging clocks dissociate biological from chronological age. The estimation of biological age is important for identifying gerontogenes and assessing environmental, nutritional, or therapeutic impacts on the aging process. Recently, methylation markers were shown to allow estimation of biological age based on age‐dependent somatic epigenetic alterations. However, DNA methylation is absent in some species such as Caenorhabditis elegans and it remains unclear whether and how the epigenetic clocks affect gene expression. Aging clocks based on transcriptomes have suffered from considerable variation in the data and relatively low accuracy. Here, we devised an approach that uses temporal scaling and binarization of C. elegans transcriptomes to define a gene set that predicts biological age with an accuracy that is close to the theoretical limit. Our model accurately predicts the longevity effects of diverse strains, treatments, and conditions. The involved genes support a role of specific transcription factors as well as innate immunity and neuronal signaling in the regulation of the aging process. We show that this binarized transcriptomic aging (BiT age) clock can also be applied to human age prediction with high accuracy. The BiT age clock could therefore find wide application in genetic, nutritional, environmental, and therapeutic interventions in the aging process.