bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical factors associated with racial differences in the prevalence of occult hypoxemia: a retrospective case-control study
Authors: Mettler Sofia K. , Charoenngam Nipith , Jaroenlapnopparat Aunchalee , Tern Courtney , Xanthavanij Nutchapon , Economidou Sofia , Strand Matthew J. , Hobbs Brian D. , Moll Matthew , Cho Michael H. 
Published: March 2024

BackgroundRecent studies showed that Black patients more often have falsely normal oxygen saturation on pulse oximetry compared to White patients. However, whether the racial differences in occult hypoxemia are mediated by other clinical differences is unknown.MethodsWe conducted a retrospective case-control study utilizing two large ICU databases (eICU and MIMIC-IV). We defined occult hypoxemia as oxygen saturation on pulse oximetry within 92-98% despite oxygen saturation on arterial blood gas below 90%. We assessed associations of commonly measured clinical factors with occult hypoxemia using multivariable logistic regression and conducted mediation analysis of the racial effect.ResultsAmong 24,641 patients, there were 1,855 occult hypoxemia cases and 23,786 controls. In both datasets, Black patients were more likely to have occult hypoxemia (unadjusted odds ratio 1.66 [95%-CI: 1.41-1.95] in eICU and 2.00 [95%-CI: 1.22-3.14] in MIMIC-IV). In multivariable models, higher respiratory rate, PaCO2 and creatinine as well as lower hemoglobin were associated with increased odds of occult hypoxemia. Differences in the commonly measured clinical markers accounted for 9.2% and 44.4% of the racial effect on occult hypoxemia in eICU and MIMIC-IV, respectively.ConclusionClinical differences, in addition to skin tone, might mediate some of the racial differences in occult hypoxemia.
Unraveling interindividual differences and functional consequences of gut microbial metabolism of immunosuppressants
Authors: Baghai Arassi Maral , Karcher Nicolai , Mastrorilli Eleonora , Gross Matthias , Brauer-Nikonow Amber , Hackett Raymund , Czock David , Tönshoff Burkhard , Zeller Georg , Zimmermann Michael 
Published: March 2024

AbstractA major challenge in kidney transplantation (KT) is the large interpatient variability in the pharmacokinetics of immunosuppressive drugs. Here, we explored the role of the gut microbiome in interindividual variation in immunosuppressive drug metabolism. Analysis of 38 fecal communities, including 10 from KT recipients, and 45 bacterial species against 25 drugs, revealed significant interindividual and drug-specific differences in metabolism. Notably, 15 of 16 immunosuppressants tested were metabolized by at least one microbial community, and we found specific bacterial species, such asBacteroides uniformis, to be potent metabolizers. We identified 18 different metabolites for 16 drugs, including two previously undescribed metabolites for sirolimus and everolimus. Our study reveals the functional impact of microbial metabolism on key immunosuppressants, including inactivation of tacrolimus, activation and potential increase in toxicity of mycophenolate mofetil (MMF), and shows that the microbial metabolite of methylprednisolone exhibits a 2.6-fold increase in epithelial permeability compared to the parent drug. Through a gain-of-function genetic screen we identified theB. uniformisenzyme BACUNI_RS05305 to be responsible for MMF activation. Using machine learning to model microbial community drug metabolism, abundance features of prevalent species predicted the biotransformation of some drugs well, while for others, a priori experimental information on bacterial genes and enzyme protein structures led to improved predictions. Our research highlights the potential of gut microbiome features to explain interindividual variability in immunosuppressive therapies and sets the stage for clinical trials to identify microbiome-encoded signatures predictive of drug metabolism in KT patients.
Genetic interaction library screening with a next-generation dual guide CRISPR system
Authors: Burgold Thomas , Karakoc Emre , Gonçalves Emanuel , Dwane Lisa , Barrio-Hernandez Inigo , Silva Romina Oliveira , Souster Emily , Sharma Mamta , Beck Alexandra , Koh Gene , Zalmas Lykourgos-Panagiotis , Garnett Mathew , Bassett Andrew 
Published: March 2024

AbstractPairwise perturbation of gene function using the CRISPR/Cas9 system has huge potential in screening for genetic interactions and synthetic lethal gene pairs to identify novel combination therapies for cancer. However, existing dual guide expression systems are cumbersome to clone, often result in a large proportion of undesired guide pairs and have imbalance of guide expression from the two positions. Here, we demonstrate a next-generation system for dual guide delivery based around a tRNA spacer that allows a single step cloning strategy, as little as 2% of undesired guide pairs, and highly balanced expression of the two guides. This system allows efficient library-scale screening for hundreds of thousands of genetic interactions using the well understoodStreptococcus pyogenesCas9 (SpCas9) system. We use this to screen a 100,136 guide pair library in colorectal cancer cells and successfully identify synthetic lethal genetic interactions between paralogs, establishing our method for performing efficient large scale genetic interaction screens. This system is versatile and can be used with most guide RNA vector systems, and for other uses of paired guide delivery such as improving single gene knockout efficiency or improving guide detection in single cell or optical CRISPR screens.
CRISPR-MIP replaces PCR and reveals GC and oversampling bias in pooled CRISPR screens
Authors: Selinger Martin , Yakovenko Iryna , Nazir Iqra , Henriksson Johan 
Published: March 2024

AbstractPooled CRISPR screening is a powerful tool for finding the most important genes related to a biological process of interest. The quality of the generated gene list is however influenced by a range of technical parameters, such as CRISPR (single guide) sgRNA target efficiency, and further innovations are still called for. One open problem is the precise estimation of sgRNA abundances, as required for the statistical analysis. We do so using molecular inversion probes (MIPs) combined with the use of unique molecular identifiers (UMIs), thus enabling deduplication and absolute counting of cells. We show that this is a viable approach that eliminates sequencing depth bias. Furthermore, we find that GC% bias affects PCR, calling for a reanalysis of published CRISPR screen data and sgRNA efficiency estimates. We propose our method as a new gold standard for sgRNA quantification, especially for genes that are not top ranked but still of broad interest.
Arp2/3-dependent actin assembly shapes endosomes and promotes intracellular trafficking in fission yeast
Authors: Melero Alejandro , Muriel-Lopez Olivia , Basante-Bedoya Miguel , Martin Sophie G 
Published: March 2024

AbstractEndosomes serve as crucial sorting centres that streamline the distribution of cell surface proteins. The early endosome receives traffic from both the plasma membrane (PM) and the Golgi, and orchestrates the redistribution of cargoes for recycling to the PM or through retrograde movement to the Golgi, and for degradation to late endosomes and lysosomes1. In animal cells and amoebae, Arp2/3-mediated F-actin assembly plays critical roles in many aspects of endosome function, from capturing cargo to generating the forces required for membrane deformation and creating cargo-enriched transport carriers, thus promoting both recycling and degradative trafficking routes2. Yeast models, which allowed dissection of the major membrane trafficking routes3, exhibit highly simplified endosomes, as shown inSaccharomyces cerevisiae, where the trans-Golgi network (TGN) functions as recycling endosome4. Furthermore, there is no reported role for Arp2/3 or F-actin in endomembrane remodelling; in fact, the Arp2/3 activators on animal endosomes – the WASH complex promoting recycling of transmembrane receptors towards the PM or TGN5,6, and Annexin A2 necessary for endosome maturation and the movement of cargoes towards the degradative pathway7– do not exist in yeast cells8,9. Here, we report that Arp2/3 and F-actin are present on fission yeast endosomes. Through live-imaging and correlative light-electron tomography, we demonstrate that Arp2/3 activity controls endosomal morphology and that this activity is essential for trafficking from the endosome to the degradative vacuole. Thus, Arp2/3-dependent actin assembly has a deeply conserved role in shaping and promoting the function of the endomembrane trafficking system.
Multi-compartment impact of micropollutants and particularly antibiotics on bacterial communities using environmental DNA at river basin-level
Authors: Inostroza Pedro A. , Jessen Gerdhard L. , Li Feilong , Zhang Xiaowei , Brack Werner , Backhaus Thomas 
Published: March 2024

AbstractMicrobial communities, in particular bacterial assemblies, play pivotal roles in sustaining biogeochemical processes within ecosystems. They are also responsible for the degradation of toxic chemicals, while the development of resistance against antimicrobial drugs jeopardises human health. Bacterial communities respond to environmental conditions with diverse structural and functional changes depending on their compartment (water, biofilm or sediment), type of environmental stress, and type of pollution to which they are exposed. In this study, we combined amplicon sequencing of bacterial 16S rRNA genes from water, biofilm, and sediment samples collected in the anthropogenically impacted River Aconcagua basin (Central Chile, South America), in order to evaluate whether micropollutants alter bacterial community structure and functioning based on the type and degree of chemical pollution. Furthermore, we evaluated the potential of bacterial communities from differently polluted sites to degrade contaminants. Our results show a lower diversity at sites impacted by agriculture and urban areas, featuring high loads of micropollution with pesticides, pharmaceuticals and personal care products as well as industrial chemicals. Nutrients, antibiotic stress, and micropollutant loads explain most of the variability in the sediment and biofilm bacterial community, showing a significant increase of bacterial groups known for their capabilities to degrade various organic pollutants, such asNistrospiraand also selecting for taxa known for antibiotic resistance such asExiguobacteriumandPlanomicrobium. Moreover, potential ecological functions linked to the biodegradation of toxic chemicals at the basing level revealed significant reductions in ecosystem-related services in sites affected by agriculture and wastewater treatment plant (WWTP) discharges across all investigated environmental compartments. Finally, we suggest transitioning from simple concentration-based assessments of environmental pollution to more meaningful toxic pressure values in order to comprehensively evaluate the role of micropollutants at the ecological (biodiversity) level.Graphical abstractHighlightsMicropollutant mixtures altered bacterial community structure and functioningAntibiotic stress correlated significantly with changes in community structureReduction of ecological functions related to the degradation of contaminantsWater, biofilm, and sediments relevant for microbial ecotoxicology
Biologically Interpretable VAE with Supervision for Transcriptomics Data Under Ordinal Perturbations
Authors: Niyakan Seyednami , Yoon Byung-Jun , Qian Xiaoning , Luo Xihaier 
Published: March 2024

AbstractLatent variable models such as the Variational Auto-Encoders (VAEs) have shown impressive performance for inferring expression patterns for cell subtyping and biomarker identification from transcriptomics data. However, the limited interpretability of their latent variables obscures deriving meaningful biological understanding of cellular responses to different external and internal perturbations. We here propose a novel deep learning framework, EXPORT (EXPlainable VAE forORdinally perturbedTranscriptomics data), for analyzing ordinally perturbed transcriptomics data that can incorporate any biological pathway knowledge in the VAE latent space. With the corresponding pathway-informed decoder, the learned latent expression patterns can be explained as pathway-level responses to perturbations, offering direct interpretability with biological understanding. More importantly, we explicitly model the ordinal nature of many real-world perturbations into the EXPORT framework by training an auxiliary ordinal regressor neural network to capture corresponding expression changes in the VAE latent representations, for example under different dosage levels of radiation exposure. By incorporating ordinal constraints during the training of our proposed framework, we further enhance the model interpretability by guiding the VAE latent space to organize perturbation responses in a hierarchical manner. We demonstrate the utility of the inferred guided latent space for downstream tasks, such as identifying key regulatory pathways associated with specific perturbation changes by analyzing transcriptomics datasets on both bulk and single-cell data. Overall, we envision that our proposed approach can unravel unprecedented biological intricacies in cellular responses to various perturbations while bringing an additional layer of interpretability to biology-inspired deep learning models.
SMARCA2 and SMARCA4 participate in DNA damage repair
Authors: Yu Lily , Wu Duo 
Published: March 2024

AbstractSMARCA2 and SMARCA4 (SMARCA2/4) are paralogs and act as the key enzymatic subunits in the SWI/SNF complex for chromatin remodeling. However, the role of SMARCA2/4 in DNA damage response remains unclear. Here, we show that SMARCA2/4 relocate to DNA lesions in response to DNA damage, which requires their ATPase activities. Moreover, these ATPase activities are also required for the relocation of other subunits in the SWI/SNF complex to DNA lesions. Interestingly, the relocation of SMARCA2/4 is independent of γH2AX, ATM, ATR, p300/CBP, or PARP1/2, indicating that it may directly recognize DNA lesions as a DNA damage sensor. Lacking SMARCA2/4 prolongs the retention of γH2AX, RNF8 and BRCA1 at DNA lesions and impairs RAD51-dependent homologous recombination repair. Moreover, the treatment of SMARCA2/4 inhibitor sensitizes tumor cells to PARP inhibitor treatment. Collectively, this study reveals SMARCA2/4 as a DNA damage repair factor for double-strand break repair.
Comparative network pharmacology of artificial sweeteners to understand Its health consequences
Authors: Tankala Gohit , Kumar Arun HS 
Published: March 2024

AbstractBackgroundArtificial sweeteners (ASwt) are widely consumed sugar substitutes, but their long-term health effects remain a subject of debate. While regulatory bodies generally consider them safe at recommended doses, concerns persist regarding potential adverse effects. This study aimed to investigate the interactions between ASwt and biological targets using in silico analysis, focusing on target affinity, selectivity, and tissue expression.MethodsFive common ASwt – acesulfame K (Ac), aspartame (As), sucralose (Su), steviol (St), and saccharin (Sa) were evaluated. Their target interactions were predicted using a cheminformatics approach, analysing affinity towards functional groups and protein targets. Concentration/affinity (C/A) ratios were calculated to assess the likelihood of target activation at achievable doses. Expression of high-affinity targets with significant C/A ratios in various organs was assessed using the Human Protein Atlas database.Results: The ASwt displayed potential to modulate most of the functional groups at physiologically feasible affinities. Ac exhibited a broad range of targets, while St showed a preference for kinases and proteases. Notably, As and Su demonstrated interactions with membrane receptors and kinases. C/A ratio analysis revealed potential concerns for As and Su. Several of its targets, including ROCK2, ACE, ITGA2/5, PIM2, KDM5C, PIM1, SLC1A2, SETD2, CAPN1, LTA4H, MKNK2, HDAC1 and CDK, showed high C/A ratios, suggesting possible functional modulation at achievable intake levels. Organ specific expression analysis identified the endocrine, respiratory, renal, reproductive, central nervous, digestive, and musculoskeletal systems as a region particularly susceptible due to the high expression of high affinity targets linked to cell growth, extracellular matrix, epigenetic regulations, and inflammation. Interestingly, 30 tissues expressed high-affinity targets for both As and Su, while 14 tissues exclusively expressed targets for As.Conclusion: This study highlights the potential for ASwt to interact with various biological targets, particularly As and Su. The high C/A ratios of some As targets and the tissue-specific expression patterns suggest potential safety concerns that require in vivo validation.
How names and shapes correspond to the nature of products: an evaluation of auspicious foods
Authors: Kim Jong-Hyeong , Song Hanqun 
Published: March 2024

PurposeRestaurant operators often use auspicious connotations embedded in the names and shapes of dishes to increase consumers’ purchase intentions. However, the interaction effect of multiple auspicious cues (i.e. food name and shape) on purchase intentions has rarely been examined in the restaurant context. Thus, grounded in processing fluency theory, this study investigates the direct influence of the two-way interaction effect of food name (auspicious vs nonauspicious) and shape (auspicious vs. nonauspicious) on purchase intentions and its indirect influence via perceived auspiciousness and positive emotions.Design/methodology/approachUtilizing a 2 (food name: auspicious name vs. nonauspicious name) × 2 (food shape: auspicious shape vs. nonauspicious shape) between-subjects design, the authors conducted two experimental studies with 356 Chinese customers. In Study 1, which focused on a main dish, we investigated the two-way interaction effect food name × food shape on purchase intentions. In Study 2, we replicated this experimental study by focusing on a different food type (i.e. dessert) to test the direct and indirect influences of the two-way interaction of food name × food shape on purchase intentions through perceived auspiciousness and positive emotions.FindingsThe results reveal that the congruity condition of auspicious names and shapes significantly influences consumers’ purchase intentions. Congruity with auspicious food cues also indirectly affects purchase intentions through consumers’ perceived auspiciousness and positive emotions. These effects were consistently observed in two experimental studies analyzing different dish types (main dish and dessert).Practical implicationsRestaurateurs should consider utilizing auspicious food cues to attract customers. Specifically, they should combine both food name and shape to increase their perceived auspiciousness and sales.Originality/valueThis study tested processing fluency theory using auspicious food cues. This study contributes to the hospitality literature by improving our understanding of the congruence effect by exemplifying the conceptual alignment between food name and food shape.
Beyond the bottom line: exploring the role of governance mechanisms in promoting corporate tax responsibility
Authors: Anwar Waqas , Hasan Arshad , Nakpodia Franklin 
Published: March 2024

Purpose
Because of growing corporate tax scandals, there is an enhanced focus on corporate taxation by governments, institutions and the general public. Transparency in tax matters has been identified as critical for effectively managing and promoting socially responsible tax behaviour. This study aims to explore the impact of ownership structure, board and audit committee characteristics on corporate tax responsibility (CTR) disclosure.

Design/methodology/approach
This research collected data from the annual reports of Pakistani-listed firms over 12 years, from 2009 to 2020. Consequently, the data set encompasses a total of 1,800 firm-year observations. This study uses regression analysis to test the relationship between corporate governance and CTR disclosure.

Findings
The results show that board gender diversity, managerial ownership and audit committee independence promote tax responsibility disclosure. In contrast, family board membership, CEO duality, foreign ownership and family ownership negatively impact tax responsibility disclosure. Additional analyses reveal the specific information categories that produce the overall effects on tax responsibility disclosure and assess the moderating impact of family firms on the governance and CTR disclosure nexus.

Practical implications
Corporations can use the results to encourage practices that enhance transparency and improve the quality of disclosures. Regulatory authorities can use the findings to stipulate better protocols. Doing so will be vital for developing countries such as Pakistan to improve tax revenue and cultivate economic growth.

Originality/value
While this research represents, to the best of the authors’ knowledge, one of the first empirical investigations of the association between corporate governance and CTR, the results contribute to the corporate governance literature and offer fresh insights into CTR, an emerging dimension of corporate social responsibility.
“We’re changing the system with this one”: Black students using critical race algorithmic literacies to subvert and survive AI-mediated racism in school
Authors: Tanksley Tiera Chante 
Published: March 2024

Purpose
This paper aims to center the experiences of three cohorts (n = 40) of Black high school students who participated in a critical race technology course that exposed anti-blackness as the organizing logic and default setting of digital and artificially intelligent technology. This paper centers the voices, experiences and technological innovations of the students, and in doing so, introduces a new type of digital literacy: critical race algorithmic literacy.

Design/methodology/approach
Data for this study include student interviews (called “talk backs”), journal reflections and final technology presentations.

Findings
Broadly, the data suggests that critical race algorithmic literacies prepare Black students to critically read the algorithmic word (e.g. data, code, machine learning models, etc.) so that they can not only resist and survive, but also rebuild and reimagine the algorithmic world.

Originality/value
While critical race media literacy draws upon critical race theory in education – a theorization of race, and a critique of white supremacy and multiculturalism in schools – critical race algorithmic literacy is rooted in critical race technology theory, which is a theorization of blackness as a technology and a critique of algorithmic anti-blackness as the organizing logic of schools and AI systems.