bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spotless: a reproducible pipeline for benchmarking cell type deconvolution in spatial transcriptomics
Authors: Sang-aram Chananchida , Browaeys Robin , Seurinck Ruth , Saeys Yvan 
Published: March 2023

AbstractSpatial transcriptomics (ST) is an emerging field that aims to profile the transcriptome of a cell while keeping its spatial context. Although the resolution of non-targeted ST technologies has been rapidly improving in recent years, most commercial methods do not yet operate at single-cell resolution. To tackle this issue, computational methods such as deconvolution can be used to infer cell type proportions in each spot by learning cell type-specific expression profiles from reference single-cell RNA-sequencing (scRNA-seq) data. Here, we benchmarked the performance of 11 deconvolution methods using 63 silver standards, three gold standards, and two case studies on liver and melanoma tissues. The silver standards were generated using our novel simulation enginesynthspot, where we used seven scRNA-seq datasets to create synthetic spots that followed one of nine different biological tissue patterns. The gold standards were generated using imaging-based ST technologies at single-cell resolution. We evaluated method performance based on the root-mean-squared error, area under the precision-recall curve, and Jensen-Shannon divergence. Our evaluation revealed that method performance significantly decreases in datasets with highly abundant or rare cell types. Moreover, we evaluated the stability of each method when using different reference datasets and found that having sufficient number of genes for each cell type is crucial for good performance. We conclude that while cell2location and RCTD are the top-performing methods, a simple off-the-shelf deconvolution method surprisingly outperforms almost half of the dedicated spatial deconvolution methods. Our freely available Nextflow pipeline allows users to generate synthetic data, run deconvolution methods and optionally benchmark them on their dataset (https://github.com/saeyslab/spotless-benchmark).
Convergence of resistance and evolutionary responses inEscherichia coliandSalmonella entericaco-inhabiting chicken farms in China
Authors: Baker Michelle , Zhang Xibin , Guerra Alexandre Maciel , Babaarslan Kubra , Dong Yinping , Wang Wei , Hu Yujie , Renney David , Liu Longhai , Li Hui , Tong Zhiqin , Pearcy Nicole , Zhang Meimei , Geng Yingzhi , Zhao Li , Hao Zhihui , Chen Junshi , Peng Zixin , Li Fengqin , Dottorini Tania 
Published: March 2023

AbstractSharing among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661E. coliandS. entericaisolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using novel data-mining methods. Most isolates within same hosts possessed same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Machine learning revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials and primarily associated with resistance inEscherichia coliand susceptibility inSalmonella enterica. Many of these genes were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs.
Contrasting the form and strength of pre- and postcopulatory sexual selection in a transparent worm with fluorescent sperm
Authors: Marie-Orleach Lucas , Hall Matthew D. , Schärer Lukas 
Published: March 2023

AbstractSexual traits may be selected during multiple consecutive episodes of selection, occurring before, during, or after copulation. The overall strength and shape of selection acting on sexually selected traits may thus be determined by how selection (co-)varies along different episodes. However, it is challenging to measure pre- and postcopulatory phenotypic traits alongside variation in fitness components at each different episode. Here, we used a transgenic line of the transparent flatwormMacrostomum lignanoexpressing green fluorescent protein (GFP) in all cell types, including sperm cells, enablingin vivosperm tracking. We exposed GFP(+) focal worms to three groups in which we assessed their mating success, sperm-transfer efficiency, and sperm fertilising efficiency. Moreover, we measured 13 morphological traits on the focal worms to study the fitness landscape in multivariate trait space. We found linear selection on sperm production rate arising from pre- and postcopulatory components, and on copulatory organ shape arising from sperm fertilising efficiency. We further found nonlinear (mostly concave) selection on combinations of copulatory organ and sperm morphology traits arising mostly from sperm-transfer efficiency and sperm fertilising efficiency. Our study shows that contrasting patterns of phenotypic selection are observed by measuring how sexual selection builds-up over consecutive episodes of selection.
“It’s no use saying it in English”: A qualitative study exploring community leaders’ perceptions of the challenges and opportunities with translating and interpreting COVID-19 related public health messaging to reach ethnic minorities in Australia
Authors: Seale Holly , Harris-Roxas Ben , Heywood Anita , Abdi Ikram , Mahimbo Abela , Woodland Lisa , Waller Emily 
Published: March 2023

ABSTRACTBackgroundThe Australian Government implemented a range of public health response strategies and communication approaches to reduce the spread of COVID-19; however, concerns have been raised around a failure to consider culturally and linguistically diverse (CaLD) communities sufficiently in these processes. This research aimed to understand the factors that have impacted COVID-19 communication and engagement efforts during the pandemic from the perspective of key CaLD community stakeholders and community members. A further aim was to understand the processes that could be adopted to support future communication strategies, including the promotion of pandemic-related vaccines.ApproachThis study included 29 key informant interviews with community and faith-based leaders in New South Wales, Australia.ResultsThe overwhelming message from community leaders was a sense of shared responsibility between their organisations and the government in communicating pertinent and accurate COVID-19 related information to CaLD communities. They expressed a sense of duty to keep their community members safe. While acknowledging this shared responsibility, community leaders and others shouldered significant costs related to resources and time that need to be acknowledged by governments in preparing for future disease outbreaks. They felt that governments should consider: 1) improving communication between governments and CaLD organisations; 2) responding to the specific CaLD needs with greater agility; 3) foregrounding social media in their communication strategy; 4) reinvesting in local public health units to know their population; 5) investing in a health ambassadors model program; 6) preparing a hybrid model of translators/interpreters to fill the gap; and, 7) reimagining vaccine information campaigns to better target CaLD communities.ConclusionGiven the technical details about the COVID-19 virus conveyed in government information campaigns and the media, ensuring the most vulnerable populations, including people from CaLD backgrounds, access clear, concise and timely public health messaging from both governments and community organisations requires further attention.
Plasma concentrations of curcumin in individuals using curcumin with adjuvants or lipid formulated curcumin supplements: a real world cohort
Authors: Kroon Maurice A.G.M. , Berbee Jacqueline K. , Majait Soumia , Swart Noortje E.L. , van Tellingen Olaf , van Laarhoven Hanneke W.M , Kemper E. Marleen 
Published: March 2023

AbstractThe spice curcumin and its metabolites have been linked to many beneficial health effects. These effects have, thus far, not been duplicated in independent research most likely due to low plasma concentrations of curcumin. Despite the many reports, the public’s interest in curcumin continues to grow and many people use curcumin in daily life. Moreover, companies seize the popularity of curcumin and claim that their formulations increase systemic expose of curcumin. In this independent study we determined the plasma concentration of curcumin after oral intake in daily life to determine if the systemic exposure is sufficient to achieve beneficial health effects.We used a validated HPLC-MS/MS assay to determine the plasma concentration of curcumin and its metabolites in 47 individuals (patient or healthy) using their own curcumin formulations. Through questionnaires, we assessed which other supplements and (self-)medication(s) were used. The concentrations of curcumin and its metabolites were analyzed in plasma samples collected just before and 1.5 h after curcumin intake. Each sample was pretreated with and without β-glucuronidase to determine the levels of conjugated and unconjugated curcumin.After oral intake of the curcumin supplement, plasma concentrations of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin ranged between 2 and 4 nM. Use of adjuvants like piperine did not result in higher curcumin plasma concentrations. Adding β-glucuronidase to the plasma sample increased curcumin plasma levels from below LLQ to 25.3 ng/mL, however still below any plasma concentration to which a beneficial health effect can be expected.The observed plasma concentration of unchanged curcumin remained several orders below the concentration of 2-100 μg/mL used inin vitrostudies. Therefore, our study confirms the low plasma levels of curcumin and indicates the need to be critical towards the claimed beneficial systemic health effects of current curcumin supplement use in daily life among patients and healthy individuals.
Spatial variation in the non-use of modern contraception and its predictors in Bangladesh
Authors: Khan Md Nuruzzaman , Harris Melissa L. 
Published: March 2023

AbstractObjectiveWe assessed spatial variations in the non-use of modern contraception in Bangladesh, and identified associated individual, household and community level factors.MethodsWe analysed data from 16,135 women extracted from the 2017/18 Bangladesh Demographic and Health Survey. The study outcome was non-use of modern contraception (yes, no), and the explanatory variables were factors at the individual (e.g., women’s education), household (e.g., husband education) and community level (e.g., community level poverty and illiteracy). Moran’s I statistics was applied to examine whether any geographical heterogeneity in non-use of modern contraception exists in Bangladesh. The Gettis-ord Gi*was calculated to measure how spatial autocorrelation differed across study locations. A geographically weighted regression model was used to assess the relationship of non-use of modern contraception at the cluster level.ResultsOverall, 42.8% (95% CI, 41.6-43.8) of respondents reported non-use of modern contraception in Bangladesh with a significant variation across geographical locations (p<0.001). Clusters of high non-use of modern contraception (hot spots) were found mostly located in the Sylhet, Barishal and part of the Chattogram divisions while clusters of low use of modern contraception(cold spots) were mostly located in the Rangpur, Mymensingh and part of the Rajshahi divisions. The likelihood of non-use of modern contraception was strongest among women and parteners with low levels of education. Other risk factors analysed including partner’s occupation, community-level illiteracy and poverty had varying effects on the non-use of modern contraception across the locations (clusters) of the country included in the survey.ConclusionPrevalence of, and risk factors for, modern contraception non-use in Bangladesh differed depending on geographical location. This suggests a need for targeted area-specific policies and programs to improve knowledge and uptake of modern contraception.
Statistical learning shapes pain perception and prediction independently of external cues
Authors: Onysk Jakub , Gregory Nicholas , Whitefield Mia , Jain Maeghal , Turner Georgia , Seymour Ben , Mancini Flavia 
Published: March 2023

ABSTRACTThe placebo and nocebo effects highlight the importance of expectations in modulating pain perception, but in everyday life we don’t need an external source of information to form expectations about pain. The brain can learn to predict pain in a more fundamental way, simply by experiencing fluctuating, non-random streams of noxious inputs, and extracting their temporal regularities. This process is called statistical learning. Here we address a key open question: does statistical learning modulate pain perception? We asked 27 participants to both rate and predict pain intensity levels in sequences of fluctuating heat pain. Using a computational approach, we show that probabilistic expectations and confidence were used to weight pain perception and prediction. As such, this study goes beyond well-established conditioning paradigms associating non-pain cues with pain outcomes, and shows that statistical learning itself shapes pain experience. This finding opens a new path of research into the brain mechanisms of pain regulation, with relevance to chronic pain where it may be dysfunctional.
Social Determinants of Health and Cardiologist Involvement in the Care of Adults Hospitalized for Heart Failure
Authors: Zhang David T. , Onyebeke Chukwuma , Nahid Musarrat , Balkan Lauren , Musse Mahad , Pinheiro Laura C. , Sterling Madeline R. , Durant Raegan W. , Brown Todd M. , Levitan Emily B. , Safford Monika M. , Goyal Parag 
Published: March 2023

AbstractIntroductionThe involvement of a cardiologist in the care of adults during a hospitalization for heart failure (HF) is associated with reduced rates of in-hospital mortality and hospital readmission. However, not all patients see a cardiologist when they are hospitalized for HF. Since reasons for this are not entirely clear, we sought to determine whether social determinants of health (SDOH) are associated with cardiologist involvement in the management of adults hospitalized for HF. We hypothesized that SDOH would be inversely associated with cardiologist involvement in the care of adults hospitalized for HF.MethodsWe included adult participants from the national REasons for Geographic And Racial Difference in Stroke (REGARDS) cohort, who experienced an adjudicated hospitalization for HF between 2009 and 2017. We excluded participants who were hospitalized at institutions that lacked cardiology services (n=246). We examined nine candidate SDOH, which align with the Healthy People 2030 conceptual model: Black race, social isolation (0–1 visits from a family or friend in the past month), social network/caregiver availability (having someone to care for them if ill), educational attainment < high school, annual household income < $35,000, living in rural areas, living in a zip code with high poverty, living in a Health Professional Shortage Area, and residing in a state with poor public health infrastructure. The primary outcome was cardiologist involvement, a binary variable which was defined as involvement of a cardiologist as the primary responsible clinician or as a consultant, collected via chart review. We examined associations between each SDOH and cardiologist involvement using Poisson regression with robust standard errors. Candidate SDOH with statistically significant associations (p<0.10) were retained for multivariable analysis. Potential confounders/covariates for the multivariable analysis included age, race, sex, HF characteristics, comorbidities, and hospital characteristics.ResultsWe examined 876 participants hospitalized at 549 unique US hospitals. The median age was 77.5 years (IQR 71.0-83.7), 45.9% were female, 41.4% were Black, and 56.2% had low income. Low household income (<$35,000/year) was the only SDOH that had a statistically significant association with cardiologist involvement in a bivariate analysis (RR: 0.88 [95% CI: 0.82-0.95]). After adjusting for potential confounders, low income remained inversely associated (RR: 0.89 [95% CI: 0.82-0.97]).ConclusionsAdults with low household income were 11% less likely to have a cardiologist involved in their care during a hospitalization for HF. This suggests that socioeconomic status may implicitly bias the care provided to patients hospitalized for HF.
Antiviral activities of two nucleos(t)ide analogs against vaccinia and mpox viruses in primary human fibroblasts
Authors: Dsouza Lara , Pant Anil , Offei Samuel , Priyamvada Lalita , Pope Blake , Satheshkumar Panayampalli S. , Wang Zhengqiang , Yang Zhilong 
Published: March 2023

AbstractMany poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox. Identification of inhibitors of poxvirus replication is critical for drug development to manage poxvirus threats. Here we tested two compounds, nucleoside trifluridine and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV) and mpox virus (MPXV) in physiologically relevant primary human fibroblasts. Both trifluridine and adefovir dipivoxil potently inhibited replication of VACV and MPXV (MA001 2022 isolate) in a plaque assay. Upon further characterization, they both conferred high potency in inhibiting VACV replication with half maximal effective concentrations (EC50) at low nanomolar levels in our recently developed assay based on a recombinant VACV secreted Gaussia luciferase. Our results further validated that the recombinant VACV with Gaussia luciferase secretion is a highly reliable, rapid, non-disruptive, and simple reporter tool for identification and chracterization of poxvirus inhibitors. Both compounds inhibited VACV DNA replication and downstream viral gene expression. Given that both compounds are FDA-approved drugs, and trifluridine is used to treat ocular vaccinia in medical practice due to its antiviral activity, our results suggest that it holds great promise to further test trifluridine and adefovir dipivoxil for countering poxvirus infection, including mpox.
An extended Tudor domain within Vreteno interconnects Gtsf1L and Ago3 for piRNA biogenesis inBombyx mori
Authors: Bronkhorst Alfred W. , Lee Chop Y. , Möckel Martin M. , Ruegenberg Sabine , de Jesus Domingues Antonio M. , Sadouki Shéraz , Sumiyoshi Tetsutaro , Siomi Mikiko C. , Stelzl Lukas , Luck Katja , Ketting René F. 
Published: March 2023

AbstractPiwi-interacting RNAs (piRNAs) direct PIWI proteins to transposons to silence them, thereby preserving genome integrity and fertility. The piRNA population can be expanded in the ping-pong amplification loop. Within this process, piRNA-associated PIWI proteins (piRISC) enter the nuage to cleave target RNA, which is stimulated by Gtsf proteins. The resulting cleavage product gets loaded into an empty PIWI protein to form a new piRISC complex. However, for piRNA amplification to occur, it is required that new RNA substrates, Gtsf-piRISC and empty PIWI proteins are all in physical proximity. In this study we show that BmGtsf1L binds to piRNA-loaded BmAgo3 and co-localizes to BmAgo3-BmVreteno positive granules. Biochemical assays further revealed that conserved residues within the unstructured tail of BmGtsf1L directly interact with BmVreteno. Using a combination of AlphaFold modeling, atomistic molecular dynamics simulations and in vitro assays we identified a novel binding interface on a BmVreteno-eTudor domain, which is required for BmGtsf1L binding. Our study reveals that a single eTudor domain within BmVreteno provides two binding interfaces and thereby interconnects piRNA-loaded BmAgo3 and BmGtsf1L.
Hearing what is being said: The distributed neural substrate for early speech interpretation
Authors: Clarke Alex , Tyler Lorraine K. , Randall Billi , Marslen-Wilson William 
Published: March 2023

AbstractHuman speech comprehension is remarkable for the immediacy with which the listener hears what is being said. Here, we focus on the neural underpinnings of this process in isolated spoken words, to define the intrinsic properties of these core mechanisms independent of contextual constraints or predictions. We analysed source-localised MEG data for a set of 218 spoken nouns heard in isolation, using Representational Similarity Analysis to probe the spatiotemporal coordinates of processes sensitive to speech phonology, lexical form, and the semantics of emerging word candidates. Phonological model fit was detectable within 40-50 ms from onset, rapidly engaging a bilateral network including superior and middle temporal cortex and extending into anterior temporal and inferior parietal regions. Model fit to lexical form emerged within 60-70 ms, and model fit to cohort semantics from 100-110 ms, both overlapping strongly with the spatial pattern of phonological model fit in bilateral temporo-parietal cortices. Strikingly, the majority of vertices in a central core of brain regions showed significant model fit to all three dimensions tested, consistent with a fully distributed neural substrate for early speech analysis. The early interpretation of speech seems to be conducted in a unified integrative representational space, in conflict with the conventional view that speech analysis is underpinned by a linguistically stratified representational hierarchy.
Metabolomic, proteomic and single cell proteomic analysis of cancer cells treated with the KRASG12Dinhibitor MRTX1133
Authors: Orsburn Benjamin C. 
Published: March 2023

AbstractMutations in KRAS are common drivers of human cancers and are often those with the poorest overall prognosis for patients. A recently developed compound, MRTX1133, has shown promise in inhibiting the activity of KRASG12Dmutant proteins, one of the main drivers in pancreatic cancer. To better understand the mechanism of action of this compound I performed both proteomics and metabolomics on four KRASG12Dmutant pancreatic cancer cell lines. To obtain increased granularity in the proteomic observations, single cell proteomics was successfully performed on two of these lines. Following quality filtering, a total of 1,498 single cells were analyzed. From these cells 3,140 total proteins were identified with approximately 953 proteins quantified per cell. At 48 hours of treatment, two distinct populations of cells can be observed based on the level of effectiveness of the drug in decreasing total abundance of the KRAS protein in each respective cell, results that are effectively masked in the bulk cell analysis. All mass spectrometry data and processed results are publicly available at thewww.massive.ucsd.eduat accessions PXD039597, PXD039601 and PXD039600.Abstract Graphic