bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, Tolerability, and Pharmacokinetics of Intravenous Doses of PF‐07304814, a Phosphate Prodrug Protease Inhibitor for the Treatment of SARS‐CoV‐2, in Healthy Adult Participants
Authors: Zhu Tong , Pawlak Sylvester , Toussi Sima S. , Hackman Frances , Thompson Kimberly , Song Wei , Salageanu Joanne , Winter Erica , Shi Haihong , Winton Jennifer , Binks Michael 
Published: October 2022

AbstractStudies on targeted antivirals for treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the cause of the ongoing pandemic, are limited. PF‐07304814 (lufotrelvir) is the phosphate prodrug of PF‐00835231, a protease inhibitor targeting the 3C‐like protease of SARS‐CoV‐2. This phase 1 study evaluated the safety, tolerability, and pharmacokinetics (PK) of single ascending intravenous doses of lufotrelvir (continuous 24‐hour infusion of 50, 150, 500, or 700 mg) versus placebo in healthy volunteers (2 interleaving cohorts: 1, n = 8; 2, n = 7). Each dosing period was separated by a washout interval (≥5 days). Treatment‐emergent adverse events, PK, and biomarker concentrations were estimated from plasma/urine samples. Lufotrelvir was administered to 15 volunteers (mean [SD] age 39.7 [11.8] years). No serious adverse events, discontinuations, or deaths were reported. Mean maximum observed concentration of PF‐00835231 (active moiety; 97.0 ng/mL to 1288 ng/mL) were observed between median time to maximum concentration of 14 to 16 hours after the start of the lufotrelvir infusion. Near‐maximum plasma concentrations of PF‐00835231 were observed ≈6 hours after infusion start and sustained until infusion end. PF‐00835231 plasma concentrations declined rapidly after infusion end (mean terminal half‐life: 500 mg, 2.0 hours; 700 mg, 1.7 hours). Approximately 9%–11% of the dose was recovered in urine as PF‐00835231 across doses. A continuous, single‐dose, 24‐hour infusion of lufotrelvir (50–700 mg) was rapidly converted to PF‐00835231 (active moiety), with dose‐proportional PK exposures and no significant safety concerns. A daily, 24‐hour continuous infusion of 270 to 350 mg is expected to maintain PF‐00835231 concentration at steady state/above effective antiviral concentrations. Further studies exploring lufotrelvir efficacy in patients with coronavirus disease 2019 are ongoing.
Kibria‐Lukmantype estimator for gamma regression model
Authors: Shewa Gladys Amos , Ugwuowo Fidelis Ifeayi 
Published: October 2022

SummaryThe gamma regression model explores the relationship between a skewed response variable and one or more independent variables. The method of maximum likelihood is popularly adopted to model the relationship. However, the method performance drops when linear dependency exists among the predictors (multicollinearity). In this article, we develop a new method to account for multicollinearity in gamma regression model. The proposed estimator theoretically dominates the existing estimators. The simulation studies and real‐life application supports the theoretical findings.
Multiplexed Single‐Nucleus RNA Sequencing Using Lipid‐Oligo Barcodes
Authors: Zhang Qi , Kim Seong Won , Gorham Joshua M. , DeLaughter Daniel M. , Ward Tarsha , Seidman Christine E. , Seidman Jonathan G. 
Published: October 2022

AbstractThis protocol describes a robust pipeline for simultaneously analyzing multiple samples by single‐nucleus (sn)RNA‐seq. cDNA obtained from each single sample are labeled with the same lipid‐coupled oligonucleotide barcode (10X Genomics). Nuclei from as many as 12 individual samples can be pooled together and simultaneously processed for cDNA library construction and subsequent DNA sequencing. While previous protocols using lipid‐coupled oligonucleotide barcodes were optimized for analysis of samples consisting of viable cells, this protocol is optimized for analyses of quick‐frozen cell samples. The protocol ensures efficient recovery of nuclei both by incorporating high sucrose buffered solutions and by including a tracking dye (trypan blue) during nuclei isolation. The protocol also describes a procedure for removing single nuclei ‘artifacts’ by removing cell debris prior to single nuclear fractionation. This protocol informs the use of computational tools for filtering poorly labeled nuclei and assigning sample identity using barcode unique molecular identifier (UMI) read counts percentages. The computational pipeline is applicable to either cultured or primary, fresh or frozen cells, regardless of their cell types and species. Overall, this protocol reduces batch effects and experimental costs while enhancing sample comparison. © 2022 Wiley Periodicals LLC.Basic Protocol 1: Labeling cells with lipid oligo barcodes and generating multiplexed single‐nucleus RNA‐seq librariesBasic Protocol 2: Bioinformatic deconvolution of the multiplexed snRNAseq libraries
Exploring Epigenomic Datasets by ChIPseeker
Authors: Wang Qianwen , Li Ming , Wu Tianzhi , Zhan Li , Li Lin , Chen Meijun , Xie Wenqin , Xie Zijing , Hu Erqiang , Xu Shuangbin , Yu Guangchuang 
Published: October 2022

AbstractIn many aspects of life, epigenetics, or the altering of phenotype without changes in sequences, play an essential role in biological function. A vast number of epigenomic datasets are emerging as a result of the advent of next‐generation sequencing. Annotation, comparison, visualization, and interpretation of epigenomic datasets remain key aspects of computational biology. ChIPseeker is a Bioconductor package for performing these analyses among variable epigenomic datasets. The fundamental functions of ChIPseeker, including data preparation, annotation, comparison, and visualization, are explained in this article. ChIPseeker is a freely available open‐source package that may be found at https://www.bioconductor.org/packages/ChIPseeker. © 2022 Wiley Periodicals LLC.Basic Protocol 1: ChIPseeker and epigenomic dataset preparationBasic Protocol 2: Annotation of epigenomic datasetsBasic Protocol 3: Comparison of epigenomic datasetsBasic Protocol 4: Visualization of annotated resultsBasic Protocol 5: Functional analysis of epigenomic datasetsBasic Protocol 6: Genome‐wide and locus‐specific distribution of epigenomic datasetsBasic Protocol 7: Heatmaps and metaplots of epigenomic datasets
Making spaces for collaborative action and learning: Reflections on teacher‐led decolonising initiatives from a professional learning network in England
Authors: Glowach Terra , Mitchell Rafael , Bennett Tryphosa , Donaldson Lydia , Jefferson Jo , Panford Lisa , Saleh Amy , Smee Kate , Wells‐Dion Bathsheba , Hemmings Evie 
Published: October 2022

AbstractThis article draws on the experiences of teachers and teacher educators within the “Bristol Decolonising Network”, an informal professional learning network based in South West England, to share examples of teacher‐led decolonising/antiracist initiatives. The seven vignettes presented cover a range of subject areas across the English Secondary school curriculum, with varying rationales, foci, forms and intended outcomes. For this Special Issue, we look across these cases to consider links between teacher‐led decolonising and antiracist initiatives and professional learning. We suggest that professional learning is both a condition for, and outcome of, teachers' engagement in such work; and that extending collaboration beyond hierarchical and institutional boundaries is a key enabler for progress on this agenda.
High‐content video flow cytometry with digital cell filtering for label‐free cell classification by machine learning
Authors: Liu Chao , Wang Zhuo , Jia Junkun , Liu Qiao , Su Xuantao 
Published: October 2022

AbstractRecent development of imaging flow cytometry (IFC) has enabled the measurements of single cells with high throughput, where fluorescent labels provide specificity for cellular diagnosis. The fluorescent labels may disturb the cell functions, and the requirements for high‐throughput measurements limit the cell image quality. Here, we develop the high‐content video flow cytometry (VFC) that measures unlabeled single cells with a rate of approximately 1000 cells per minute. For the obtained big data, the frame of interest (FOI) is automatically prepared by a digital cell filtering technique with machine learning. Cervical carcinoma cell lines (Caski, HeLa and C33‐A cells) are differentiated with an accuracy of 91.5%, 90.5%, and 90.5% by deep learning in a three‐way classification, respectively. The high‐content VFC not only provides high‐quality images of single cells with high throughput and rewinding, but also performs automatic digital cell filtering and label‐free cell classification that may have clinical applications.
Pals1a and aPKCλ are not essential for Schwann cell migration, division or myelination in zebrafish
Authors: Boueid Marie‐José , Mikdache Aya , Lesport Emilie , Delespierre Brigitte , Loisel‐Duwattez Julien , Degerny Cindy , Tawk Marcel 
Published: October 2022

AbstractBackgroundSchwann cells (SCs) are specialized glial cells of the peripheral nervous system that produce myelin and promote fast action potential propagation. In order to myelinate, SCs engage in a series of events that include migration and division along axons, followed by extensive cytoskeletal rearrangements that ensure axonal ensheathment and myelination. SCs are polarized and extend their processes along an abaxonal‐adaxonal axis. Here, we investigate the role of the apical polarity proteins, Pals1a, and aPKCλ, in SC behavior during zebrafish development.ResultsWe analyzed zebrafish nok and has mutants deficient for pals1a and aPKCλ function respectively. Using live imaging, transmission electron microscopy and whole mount immunostaining, we show that SCs can migrate and divide appropriately, exhibit normal radial sorting, express myelin markers and ensheath axons on time in has and nok mutants.ConclusionsPals1a and aPKCλ are not essential for SC migration, division or myelination in zebrafish.
Zebrafish Galectin 3 binding protein is the target antigen of the microglial 4C4 monoclonal antibody
Authors: Rovira Mireia , Miserocchi Magali , Montanari Alice , Hammou Latifa , Chomette Laura , Pozo Jennifer , Imbault Virginie , Bisteau Xavier , Wittamer Valérie 
Published: October 2022

AbstractBackgroundTwo decades ago, the fish‐specific monoclonal antibody 4C4 was found to be highly reactive to zebrafish microglia, the macrophages of the central nervous system. This has resulted in 4C4 being widely used, in combination with available fluorescent transgenic reporters to identify and isolate microglia. However, the target protein of 4C4 remains unidentified, which represents a major caveat. In addition, whether the 4C4 expression pattern is strictly restricted to microglial cells in zebrafish has never been investigated.ResultsHaving demonstrated that 4C4 is able to capture its native antigen from adult brain lysates, we used immunoprecipitation/mass‐spectrometry, coupled to recombinant expression analyses, to identify its target. The cognate antigen was found to be a paralog of Galectin 3 binding protein (Lgals3bpb), known as MAC2‐binding protein in mammals. Notably, 4C4 did not recognize other paralogs, demonstrating specificity. Moreover, our data show that Lgals3bpb expression, while ubiquitous in microglia, also identifies leukocytes in the periphery, including populations of gut and liver macrophages.ConclusionsThe 4C4 monoclonal antibody recognizes Lgals3bpb, a predicted highly glycosylated protein whose function in the microglial lineage is currently unknown. Identification of Lgals3bpb as a new pan‐microglia marker will be fundamental in forthcoming studies using the zebrafish model.
Using successional drivers to understand spatiotemporal dynamics in intertidal mudflat communities
Authors: Norris Gregory S. , Gerwing Travis G. , Hamilton Diana J. , Barbeau Myriam A. 
Published: October 2022

AbstractElucidating factors (“drivers”) that influence succession after disturbance can explain ecological phenomena, including why communities vary spatiotemporally. To gain insight on drivers related to habitat availability, species availability, and species performance during succession, we conducted two field experiments on infaunal communities in intertidal mudflats, one on each of the Atlantic and Pacific coasts of Canada, that had disturbances of different type, size, and frequency. Related to habitat availability drivers, we observed that disturbance type and size, which differed between experiments, did not change end patterns of succession; however, disturbance frequency, directly assessed in one experiment, did. Dispersal of species from surrounding mudflat and water column (species availability) was the primary driver of succession, whereas local interactions between species after colonization (species performance drivers) did not have a detectable effect. We suggested that ample space and resources diffused competition and predation effects, and so species replacements did not occur in our systems, resulting in a lack of “traditional” successional dynamics as observed in other ecosystems. Our findings that community composition in intertidal mudflats is strongly influenced by species availability on two different coasts suggest that this driver may be key to variation in intertidal mudflat communities elsewhere.
The thioredoxin system: Balancing redox responses in immune cells and tumors
Authors: Muri Jonathan , Kopf Manfred 
Published: October 2022

AbstractThe thioredoxin (TRX) system is an important contributor to cellular redox balance and regulates cell growth, apoptosis, gene expression, and antioxidant defense in nearly all living cells. Oxidative stress, the imbalance between reactive oxygen species (ROS) and antioxidants, can lead to cell death and tissue damage, thereby contributing to aging and to the development of several diseases, including cardiovascular and allergic diseases, diabetes, and neurological disorders. Targeting its activity is also considered as a promising strategy in the treatment of cancer. Over the past years, immunologists have established an essential function of TRX for activation, proliferation, and responses in T cells, B cells, and macrophages. Upon activation, immune cells rearrange their redox system and activate the TRX pathway to promote proliferation through sustainment of nucleotide biosynthesis, and to support inflammatory responses in myeloid cells by allowing NF‐κB and NLRP3 inflammasome responses. Consequently, targeting the TRX system may therapeutically be exploited to inhibit immune responses in inflammatory conditions. In this review, we summarize recent insights revealing key roles of the TRX pathway in immune cells in health and disease, and lessons learnt for cancer therapy.
Dithienylethene‐Containing Cyclometalated Platinum(II) Complexes with Tunable Photochromic and Photophysical Properties
Authors: Fung Tony Ho‐Ching , Ng Maggie , Wu Nathan Man‐Wai , Yam Vivian Wing‐Wah 
Published: October 2022

AbstractA series of cyclometalated platinum(II) complexes with a dithienylethene‐containing N^C and an ancillary O^O ligand have been synthesized and characterized. All the complexes, [Pt(thpy‐DTE)(dtpd)] (1), [Pt(CF3‐thpy‐DTE)(dtpd)] (2) and [Pt(Me‐thpy‐DTE)(dtpd)] (3), exhibit photochromism that can be triggered by photoexcitation at 420 nm into the metal‐to‐ligand charge transfer (MLCT)/intraligand charge transfer (ILCT) band at the visible region, which is accompanied with colour changes from yellow to green, as well as the quenching of red phosphorescence originated from the emissive triplet intraligand (3IL) excited state. The photophysical and photochromic properties can be readily tuned by varying the ligands. Moreover, the fatigue resistance and thermal irreversibility of this series of complexes have also been demonstrated by the representative complex 1 with persistence of the photochromic activity after six photoswitching cycles and a thermal decay half‐live of 4.8 days even at 308 K.
Synthesis of 3‐Oxatricyclo[7.2.0.01,5]undeca‐7,10‐dienes through Intramolecular Photocycloaddition Reactions of Alkenes to 1,8 a‐Position of Naphthalene Ring
Authors: Maeda Hajime , Kubo Yuta , Nakashima Ryota , Mizuno Kazuhiko , Furuyama Taniyuki , Segi Masahito 
Published: October 2022

AbstractBenzene solutions of 1‐(5‐aryl‐2‐oxapent‐4‐enyl)‐2‐cyanonaphthalenes 6 were irradiated with a high‐pressure mercury lamp for 20 h to give 3‐oxatricyclo[7.2.0.01,5]undecadienes 7 in good yields. In all cases, the trans isomer was preferentially obtained. Sensitization and quenching experiments showed that the reaction proceeds via an excited singlet state. When a dichloromethane solution of 6 was irradiated for only 1 h, an eight‐membered ring compound 8 was obtained as an intermediate. When the obtained 8 was irradiated, the final product 7 was produced. The long wavelength absorption of 6 originates from the 2‐cyanonaphthalene chromophore, indicating that the reaction is initiated by photoexcitation of the naphthalene ring. In addition, the fluorescence of 6 was intramolecularly quenched, and a weak intramolecular exciplex emission was observed at 400–550 nm. In this reaction, after photoexcitation of 6, a [2+2] photocycloadduct is formed at the 1,8a‐position of the naphthalene ring via an intramolecular singlet exciplex, followed by thermal ring‐opening and 4π disrotatory ring‐closure leads to 7.
Migraine in university students: A systematic review and meta‐analysis
Authors: Flynn Orla , Fullen Brona M. , Blake Catherine 
Published: October 2022

AbstractBackgroundMigraine is a complex, neurobiological disorder usually presenting as a unilateral, moderate to severe headache accompanied by sensory disturbances. Migraine prevalence has risen globally, affecting 14% of individuals and 16% of students and carries many negative impacts in both cohorts. With no recent meta‐analysis of global migraine prevalence or associated factors in students, this systematic review and meta‐analysis were conducted.Databases and data treatmentThe review was registered with PROSPERO (CRD42020167927). Electronic databases (n = 12) were searched for cross‐sectional studies (1988 to August 2021, IHS criteria). Ninety‐two articles were meta‐analysed and 103 were narratively reviewed. The risk of bias was assessed using an established tool.ResultsThe risk of bias ranged from low to moderate. Migraine pooled prevalence (R‐Studio) was demonstrated at 19% (95% CI, 16%–22%,p < 0.001, I^2 98%): females 23% (95% CI, 19%–27%,p < 0.001), males 12% (95% CI, 9%–15%,p < 0.001). Gender (p < 0.0001), geographical region (p = 0.01), migraine types (p = 0.0002) and prevalence timeframes (p = 0.02) may be influencing the substantial heterogeneity. Migraine triggers were primarily behavioural and environmental and treatments were predominantly pharmaceutical. Impacts ranged from academic performance impairment to psychological co‐morbidities.ConclusionsThis study offers the most comprehensive overview of migraine prevalence and associated factors in university students. Migraine prevalence in university students has increased and has many negative effects. Enhancing migraine recognition and management at university may have positive implications for an improved educational experience, as well as for the burden migraine currently incurs, both in university and beyond.SignificanceThis global systematic review and meta‐analysis of 92 studies and narrative review of 103 studies provide the most comprehensive synthesis to date of migraine prevalence and associated factors in university students. Pooled prevalence has increased to 19%. The significant heterogeneity demonstrated is influenced by gender, geographical region, migraine type and prevalence timeframes. Students manage migraines primarily with pharmaceuticals. Further studies conducted in low and middle‐income countries, following headache protocols and reporting frequency of treatment‐seeking and medication usage are warranted.
Experiencing Buddhist practices promotes nonbelievers’ preference for future rewards in intertemporal choices
Authors: Wang Ziyi , Chen Cheng , Mo Jian , Lu Fan , Ma Jiatao , Chen Chuansheng , He Guibing 
Published: October 2022

AbstractReligious individuals often prefer future rewards more in intertemporal decision‐making than nonreligious individuals, but the reasons behind this preference remain under‐investigated. Focusing on decision‐making in Buddhist culture, the current study aimed to examine three potential mechanisms: Buddhist practices, self‐control and belief in future‐oriented concepts. In five studies, we consistently found that nonbelievers’ preference ratings for Larger and Later (LL) options increased after visiting a temple (Study 1, n = 99) or participating in Buddha name chanting (Studies 2–5, n = 314). We also found in Studies 3 and 4 that this effect was mediated by the individual's level of self‐control, but no evidence was found to support the mediation of belief in future‐oriented concepts. These results contribute to the work attesting to the effect of religious practices on individuals (especially nonbelievers). They also provide a mechanism (self‐control) for the positive correlation between individuals’ religiousness and preference for future rewards in intertemporal decision‐making.
The fear of confession? High Catholic collective narcissism and low secure identification with Catholics predict increased pedophilia myth acceptance
Authors: Marchlewska Marta , Górska Paulina , Molenda Zuzanna , Lipowska Katarzyna , Malinowska Katarzyna 
Published: October 2022

AbstractOver the past 30 years, the Catholic Church has been rocked by a series of child sexual abuse scandals worldwide. Some of the religious officials suggested that the children are partly to blame for being sexually abused by priests. We assumed that such convictions (i.e., pedophilia myth acceptance) should be associated with a defensive commitment to one's religious group, captured by religious collective narcissism. In two studies conducted among Polish participants (Study 1, longitudinal, n = 719; Study 2, cross‐sectional, n = 357), we found that pedophilia myth acceptance was positively predicted by Catholic narcissism but negatively by secure identification with Catholics. We additionally demonstrated that the effect of Catholic narcissism on pedophilia myth acceptance was mediated by a siege mentality with respect to the religious in‐group. We discuss the role of different types of group commitment in predicting in‐group criticism and prejudice against underaged victims of sexual abuse.