bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering Social Stratification: Intersectional Inequalities in Work and Family Life Courses by Gender and Race
Authors: Fasang Anette Eva , Aisenbrey Silke 
Published: November 2021

Abstract
Enduring and accumulated advantages and disadvantages in work and family lives remain invisible in studies focusing on single outcomes. Further, single outcome studies tend to conflate labor market inequalities related to gender, race, and family situation. We combine an intersectional and quantitative life course perspective to analyze parallel work and family lives for Black and White men and women aged 22–44. Results using sequence analysis and data from the National Longitudinal Survey of Youth (NLSY79) show that White men enjoy privileged opportunities to combine work and family life and elicit specific gendered and racialized constraints for Black men and women and White women. Black women experience the strongest interdependence between work and family life: events in their work lives constrain and condition their family lives and vice versa. For Black men, stable partnerships and career success mutually support and sustain each other over the life course. In contrast, for Black women, occupational success goes along with the absence of stable partnerships. Precarious and unstable employment is associated with early single parenthood for all groups supporting instability spillovers between life domains that are most prevalent among Black women, followed by Black men. The findings highlight a sizeable group of resourceful Black single mothers who hold stable middle-class jobs and have often gone unnoticed in previous research. We conclude that economic interventions to equalize opportunities in education, employment, and earnings, particularly early in life, are more promising for reducing intersectional inequalities in work-family life courses than attempting to intervene in family lives.
Electing between equitable remedies
Authors: Islam Carl 
Published: November 2021

Abstract
Carl Islam explains the operation of the principle of election, and concludes that in a breach of fiduciary duty claim, before an election between equitable remedies must be made by the claimant beneficiary, the judge should first consider the duties and powers of the defendant fiduciary. Because that exercise is inseparable from determination of breach, the author further submits that the exercise should be undertaken by the judge at the same time, i.e. at trial, before making a finding about breach.
Cerebrovascular response to exercise interacts with individual genotype and amyloid-beta deposition to influence response inhibition with aging
Authors: Palmer Jacqueline A. , Kaufman Carolyn S. , Vidoni Eric D. , Honea Robyn A. , Burns Jeffrey M. , Billinger Sandra A. 
Published: November 2021

AbstractThe etiology of cognitive dysfunction associated with Alzheimer’s disease (AD) and dementia is multifactorial. Yet, mechanistic interactions among key neurobiological factors linked to AD pathology are unclear. This study tested the effect of interactions between cerebrovascular function, individual genotype, and structural brain pathology on response inhibition performance, an early and sensitive indicator of cognitive executive dysfunction with aging.We quantified cerebrovascular response (CVR) to moderate-intensity aerobic exercise using transcranial doppler ultrasound and global amyloid-beta (Aβ) deposition using positron emission tomography in a group of cognitively normal older adults genotyped as APOE4 carriers and noncarriers. We quantified response inhibition during a cognitive Stroop test.Individuals with blunted CVR possessed greater Aβ deposition. There was CVR-by-carrier status-by-Aβ interaction on response inhibition. Blunted CVR was associated with impaired response inhibition specifically in carriers. Despite having greater Aβ deposition, carriers with higher CVR demonstrated better response inhibition.Cerebrovascular interactions with individual genotype and structural brain pathology may provide a physiologically-informed target for precision-medicine approaches for early treatment and prevention of cognitive dysfunction with aging.HighlightsNeurobiological interactions between CVR, APOE genotype, and Aβ are behaviorally significant.Blunted CVR to exercise is associated with impaired response inhibition specifically in APOE4 carriers.APOE4 carriers with more robust CVR have higher response inhibition performance, despite having greater Aβ deposition.Assessment of multifactorial neurobiological variables offers an early and sensitive biomarker of cognitive behavioral dysfunction with aging.
Genome sequencing in the Parkinson’s disease clinic
Authors: Hill Emily J. , Robak Laurie A. , Al-Ouran Rami , Deger Jennifer , Fong Jamie C. , Vandeventer Paul Jerrod , Schulman Emily , Rao Sindhu , Saade Hiba , von Coelln Rainer , Doddapaneni Harshavardhan , Salvi Sejal , Dugan-Perez Shannon , Muzny Donna M. , McGuire Amy , Liu Zhandong , Gibbs Richard , Shaw Chad , Jankovic Joseph , Shulman Lisa M. , Shulman Joshua M. 
Published: November 2021

AbstractBackground and ObjectivesGenetic variants impact both Parkinson’s disease (PD) risk and manifestations. While genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to perform genome sequencing and examine patient interest in comprehensive genetic testing for PD in 2 academic movement disorder clinics.MethodsIn 208 subjects with PD (age=63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well as a 90-variant PD genetic risk score. Separately, 231 patients (age=67 years, 63% male) were surveyed on interest in genetic testing at baseline and in response to vignettes covering (i) familial risk of PD (LRRK2); (ii) risk of PD dementia (GBA); (iii) PD genetic risk score; and (iv) secondary, medically-actionable variants (BRCA1).ResultsGenome sequencing revealed a LRRK2 variant in 3.4% and a GBA risk variant in 10.1% of our clinical sample. The genetic risk score was normally distributed, identifying 42 subjects with high risk of PD. Medically-actionable findings were discovered in 2 subjects (1%). In our survey, the majority (82%) responded they would share a LRRK2 variant with relatives. Most registered unchanged or increased interest in testing when confronted with potential risk for dementia or medically- actionable findings, and most (75%) expressed interest in learning their PD genetic risk score.DiscussionOur results highlight broad interest in comprehensive genetic testing among patients with PD and may facilitate integration of genome sequencing in clinical practice.
An interactive dashboard to track themes, development maturity, and global equity in clinical artificial intelligence research
Authors: Zhang J , Whebell S , Gallifant J , Budhdeo S , Mattie H , Lertvittayakumjorn P , Arias Lopez M P , Tiangco B J , Gichoya J W , Ashrafian H , Celi L A , Teo J T 
Published: November 2021

AbstractThe global clinical artificial intelligence (AI) research landscape is constantly evolving, with heterogeneity across specialties, disease areas, geographical representation, and development maturity. Continual assessment of this landscape is important for monitoring progress. Taking advantage of developments in natural language processing (NLP), we produce an end-to-end NLP pipeline to automate classification and characterization of all original clinical AI research on MEDLINE, outputting real-time results to a public, interactive dashboard (https://aiforhealth.app/).
SARS-CoV-2 variants of concern Alpha, Beta, Gamma and Delta have extended ACE2 receptor host-ranges
Authors: Thakur Nazia , Gallo Giulia , Newman Joseph , Peacock Thomas P. , Biasetti Luca , Hall Catherine N. , Wright Edward , Barclay Wendy , Bailey Dalan 
Published: November 2021

AbstractFollowing the emergence of SARS-CoV-2 in China in late 2019 a number of variants have emerged, with two of these – Alpha and Delta – subsequently growing to global prevalence. One characteristic of these variants are changes within the Spike protein, in particular the receptor binding domain (RBD). From a public health perspective these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host-range of the virus. Using viral pseudotyping we examined whether the variants of concern (VOCs) Alpha, Beta, Gamma and Delta have differing host ACE2 receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes which we subsequently attribute to N501Y and E484K substitutions within the Spike RBD.
TreadWill: Development and pragmatic randomized controlled trial of an unguided, computerized cognitive behavioral therapy intervention in a lower middle-income country
Authors: Ghosh Arka , Cherian Rithwik J. , Wagle Surbhit , Sharma Parth , Kannan Karthikeyan R. , Bajpai Alok , Gupta Nitin 
Published: November 2021

AbstractMost individuals vulnerable to depression do not receive adequate or timely treatment globally. Unguided computerized cognitive behavioral therapy (cCBT) has the potential to bridge this treatment gap. However, the real-world effectiveness of unguided cCBT interventions, particularly in low- and middle-income countries (LMICs), remains inconclusive. In this study, we report the design and development of a new unguided cCBT intervention, TreadWill, and its pragmatic evaluation. TreadWill was designed to be fully automated, engaging, easy to use, and accessible in LMICs. To evaluate its effectiveness and engagement level, we performed a double-blind, fully-remote, randomized controlled trial with 598 participants in India. The use of TreadWill significantly reduced depression-related and anxiety-related symptoms. Compared with a plain-text version with the same therapeutic content, the full-featured version of TreadWill showed significantly higher engagement. Overall, our study provides a new resource and evidence for the use of unguided cCBT as a scalable intervention in LMICs.
The effect of secretor status and the vaginal microbiome on birth outcome
Authors: Kundu S , Lee YS , Sykes L , Chan D , Lewis H , Brown RG , Kindinger L , Dell A , Feizi T , Haslam S , Liu Y , Marchesi JR , MacIntyre DA , Bennett PR 
Published: November 2021

SummaryMutations in the FUT2 gene that result in a lack of expression of histo-blood group antigens on secreted glycoproteins may shape the vaginal microbiota with consequences for birth outcome. To test this, we analysed the relationship between secretor status, vaginal microbiota and gestational length in an ethnically diverse cohort of 313 pregnant women, including 91 who delivered prematurely. Lactobacillus species were found to co-occur less often with other microbial taxa in non-secretors. Moreover, non-secretors with Lactobacillus spp. depleted vaginal microbiota in early pregnancy had significantly shorter gestational length than Lactobacillus spp. dominated non-secretors (mean of 245.5 (SD=44.5) versus 265.9 (23.6)); p=0.045), but not compared to Lactobacillus spp. dominated (261.8 (27.5)) and depleted (264.3 days (21.2)) secretors. In identifying a relationship between blood-group antigen expression and vaginal microbiota-host interactions, our results point towards stratification by secretor status as an important factor for considering preterm birth risk and prevention.
MYC regulates a pan-cancer network of co-expressed oncogenic splicing factors
Authors: Urbanski Laura , Brugiolo Mattia , Park SungHee , Angarola Brittany , Leclair Nathan K. , Palmer Phil , Sahu Sangram Keshari , Anczuków Olga 
Published: November 2021

ABSTRACTMYC is dysregulated in >50% of cancers, but direct targeting of MYC has been clinically unsuccessful. Targeting downstream MYC effector pathways represents an attractive alternative. MYC regulates alternative mRNA splicing, a hallmark of cancer, but the mechanistic links between MYC and the splicing machinery remain underexplored. Here, we identify a network of splicing factors (SFs) co-expressed as SF-modules in MYC-active breast tumors. Of these, one is a pan-cancer SF-module, correlating with MYC-activity across 33 tumor types. In mammary cell models, MYC activation leads to co-upregulation of pan-cancer module SFs and to changes in >4,000 splicing events. In breast cancer organoids, co-overexpression of the pan-cancer SF-module is sufficient to induce splicing events that are also MYC-regulated in patient tumors and to increase organoid size and invasiveness, while its knockdown decreases organoid size. Finally, we uncover a pan-cancer splicing signature of MYC activity which correlates with survival in multiple tumor types. Our findings provide insight into the mechanisms and function of MYC-regulated splicing and for the development of therapeutics for MYC-driven tumors.
A global map of the Zika virus phosphoproteome reveals host-driven regulation of viral budding
Authors: Manuelyan Inessa , Schmoker Anna M. , Yount Boyd L. , Eisenhauer Philip , Keller Judith I. , Gold Clarissa , Terino Dante , Ziegler Christopher M. , Alexander Jeff , Driscoll Heather , Hutchinson Edward , Bhella David , Syme Christopher D. , Widman Douglas G. , Heise Mark T. , Baric Ralph S. , Ballif Bryan A. , Botten Jason W. 
Published: November 2021

AbstractFlaviviruses are enveloped, positive-strand RNA viruses that cause millions of infections in the human population annually. Although Zika virus (ZIKV) had been detected in humans as early as the 1950s, its reemergence in South America in 2015 resulted in a global health crisis. While flaviviruses encode 10 proteins that can be post-translationally modified by host enzymes, little is known regarding post-translational modifications (PTMs) of the flavivirus proteome. We used mass spectrometry to comprehensively identify host-driven PTMs on the ZIKV proteome. This approach allowed us to identify 43 PTMs across 8 ZIKV proteins, including several that are highly conserved within theFlavivirusgenus. Notably, we found two phosphosites on the ZIKV envelope protein that are functionally important for viral propagation and appear to regulate viral budding. Additionally, we discovered 115 host kinases that interacted with ZIKV proteins and determined that Bosutinib, an FDA-approved tyrosine kinase inhibitor that targets ZIKV interacting host kinases, impairs ZIKV growth. Thus, we have defined a high-resolution map of host-driven PTMs on ZIKV proteins as well as cellular interacting kinases, uncovered a novel mechanism of host driven-regulation of ZIKV budding, and identified an FDA-approved inhibitor of ZIKV growth.
Single-domain antibodies efficiently neutralize SARS-CoV-2 variants of concern, including Omicron variant
Authors: Favorskaya Irina A. , Shcheblyakov Dmitry V. , Esmagambetov Ilias B. , Dolzhikova Inna V. , Alekseeva Irina A. , Korobkova Anastasia I. , Voronina Daria V. , Ryabova Ekaterina I. , Derkaev Artem A. , Kovyrshina Anna V. , Iliukhina Anna A. , Botikov Andrey G. , Voronina Olga L. , Egorova Daria A. , Zubkova Olga V. , Ryzhova Natalia N. , Aksenova Ekaterina I. , Kunda Marina S. , Logunov Denis Y. , Naroditsky Boris S. , Gintsburg Alexandr L. 
Published: November 2021

ABSTRACTVirus-neutralizing antibodies are one of the few treatment options for COVID-19. The evolution of SARS-CoV-2 virus has led to the emergence of virus variants with reduced sensitivity to some antibody-based therapies. The development of potent antibodies with a broad spectrum of neutralizing activity is urgently needed. Here we isolated a panel of single-domain antibodies that specifically bind to the receptor-binding domain of SARS-CoV-2 S glycoprotein. Three of the selected antibodies exhibiting most robust neutralization potency were used to generate dimeric molecules. We observed that these modifications resulted in up to a 200-fold increase in neutralizing activity. The most potent heterodimeric molecule efficiently neutralized each of SARS-CoV-2 variant of concern, including Alpha, Beta, Gamma, Delta and Omicron variants. This heterodimeric molecule could be a promising drug candidate for a treatment for COVID-19 caused by virus variants of concern.
Fibroblastic reticular cells provide a supportive niche for lymph node-resident macrophages
Authors: D’Rozario Joshua , Knoblich Konstantin , Lütge Mechthild , Pérez Shibayama Christian , Cheng Hung-Wei , Alexandre Yannick O. , Roberts David , Campos Joana , Astarita Jillian , Dutton Emma , Suliman Muath , Denton Alice E. , Turley Shannon J. , Boyd Richard L. , Mueller Scott , Ludewig Burkhard , Heng Tracy , Fletcher Anne L 
Published: November 2021

SummaryThe lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis. The T cell paracortical zone is a major site of macrophage efferocytosis of apoptotic cells, but key factors controlling this niche are undefined. Here we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Macrophages co-localised with FRCs in human LNs, and murine single-cell RNA-sequencing revealed that most reticular cells expressed master macrophage regulator CSF1. Functional assays showed that CSF1R signalling was sufficient to support macrophage development. In the presence of LPS, FRCs underwent a mechanistic switch and maintained support through CSF1R-independent mechanisms. These effects were conserved between mouse and human systems. Rapid loss of macrophages and monocytes from LNs was observed upon genetic ablation of FRCs. These data reveal a critically important role for FRCs in the creation of the parenchymal macrophage niche within LNs.
An exploratory study of EEG connectivity during the first year of life in preterm and full-term infants
Authors: Gonzalez-Moreira Eduardo , Paz-Linares Deirel , Cubero-Rego Lourdes , Areces-Gonzalez Ariosky , Valdés-Sosa Pedro A. , Harmony Thalia 
Published: November 2021

AbstractAimto evaluate EEG connectivity during the first year of age in healthy full-term infants and preterm infants with prenatal and perinatal risk factors for perinatal brain damage.MethodsThree groups of infants were studied: healthy at full-term infants (n = 71), moderate and late preterm infants (n = 54), and very preterm infants (n = 56). All preterm infants had perinatal or/and perinatal risk factors for brain damage. EEG was obtained during phase II of natural NREM sleep. EEG analysis was performed in 24 segments of 2.56 s free of artifacts. For the calculation of EEG sources, the spectral Structured Sparse Bayesian Learning (sSSBL) was used. Connectivity was computed by the phase-lag index.ResultsIn healthy full-term infants, EEG interhemispheric connectivity in the different frequency bands followed similar trends with age to those reported in each frequency band: delta connectivity decreases, theta increases at the end of the year, in the alpha band, different trends were observed according to the region studied, and beta interhemispheric connectivity decreases with age. EEG connectivity in preterm infants showed differences from the results of the term group.DiscussionImportant structural findings may explain the differences observed in EEG connectivity between the term and preterm groups.ConclusionThe study of EEG connectivity during the first year of age gives essential information on normal and abnormal brain development.
A Novel Approach Towards Less Invasive Multi ‘Omics Gut Analyses: A Pilot Study
Authors: Berlinberg Adam J. , Brar Ana , Stahly Andrew , Gerich Mark E. , Fennimore Blair P. , Scott Frank I. , Kuhn Kristine A. 
Published: November 2021

AbstractNewer ‘omics approaches such as metatranscriptomics and metabolomics allow functional assessments of the interaction(s) between the gut microbiome and the human host. In order to generate meaningful data with these approaches, though, the method of sample collection is critical. Prior studies have relied upon expensive and invasive means towards sample acquisition such as intestinal biopsy, while other studies have relied upon easier methods of collection such as fecal samples that do not necessarily represent those microbes in contact with the host. In this pilot study, we attempt to characterize a novel, minimally invasive method towards sampling the human microbiome using mucosal cytology brush sampling compared to intestinal gut biopsy on 5 healthy participants undergoing routine screening colonoscopy. We compared metatranscriptomic analyses between the two collection methods, identifying increased taxonomic evenness and beta diversity in the cytology brush samples, and similar community transcriptional profiles between the two methods. Metabolomics assessment demonstrated striking differences between the two methods, implying a difference in bacterial-derived versus human absorbed metabolites. Put together, this study supports the use of a less invasive method of microbiome sampling with cytology brushes, but caution must be exercised when performing metabolomics assessment as this represents differential metabolite production but not absorption by the host.ImportanceIn order to generate meaningful metabolomic and microbiome data, the method of sample collection is critical. This study utilizes and compares two methods to intestinal tissue collection for evaluation of metabolites and microbiome, finding that using a brush to sample the microbiome is superior to tissue biopsy. However, for metabolomics assessment, biopsy may still be required.
Day length-dependent thermal COP1 dynamics integrate conflicting seasonal cues in the control ofArabidopsiselongation
Authors: Nieto Cristina , Catalán Pablo , Luengo Luis Miguel , Legris Martina , López-Salmerón Vadir , Davière Jean Michel , Casal Jorge , Ares Saúl , Prat Salomé 
Published: November 2021

ABSTRACTAs the summer approaches, plants experience enhanced light inputs and elevated temperatures, two environmental cues with an opposite morphogenic impact. How plants integrate this conflicting information throughout seasons remains unclear. Key components of the plant response to light and temperature include phytochrome B (phyB), PHYTOCROME INTERACTING FACTOR 4 (PIF4), EARLY FLOWERING 3 (ELF3) and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). Here, we used hypocotyl lengths of single and double mutant/over-expression lines to fit a mathematical model incorporating known interactions of these genes. The fitted model recapitulates day length-dependent thermoelongation of all lines studied, and correctly predicts temperature responsiveness of new genotypes. Whilst previous works pointed to a lightindependent thermal function of COP1, simulations of our model suggested that COP1 has a role in temperature-signaling only during daytime. Based on by this prediction, we show that COP1 overexpression increases thermal response in continuous white light, while it has little effect in darkness. Defective thermal response ofcop1-4mutants is epistatic tophyB-9andelf3-8, indicating that COP1 activity is essential to the transduction of phyB and ELF3 thermosensory function. Our model accurately captures phyB, ELF3 and PIF4 dynamics, providing an excellent toolbox for identification of best allelic combinations towards optimized crops resilience to climate change at different geographical latitudes.