bluuebunny/crossref_metadata_2025_split huggingface dataset:
Encounters after Appointments Cancelled Due to COVID-19 in the Veterans Affairs Health Care System
Authors: Tran Linda Diem , Rose Liam , Urech Tracy , Vashi Anita 
Published: November 2021

AbstractThis statistical brief examines subsequent encounters after a cancellation due to COVID-19 in the Veterans Affairs System. We find that he vast majority of VA patients that had appointments cancelled in mid-March to mid-April of 2020 had another encounter within 180 days. The most common next encounter was a virtual visit with a VA provider on the same day of the original appointment. We also find that patients that saw a provider through VA community care had a lower median time to next encounter.
COVID-19 management in social care in England: a systematic review of changing policies and newspaper reported staff perspectives
Authors: Bertini Lavinia , Bogen-Johnston Leanne , Middleton Jo , Wood Wendy , Sadhwani Shanu , Forder Julien , Roland Daniel , Sharp Rebecca , Drury John , Cassell Jackie A 
Published: November 2021

AbstractAdult social care has been a major focus of public attention and infection control guidance during the COVID-19 pandemic, with a high mortality both for carers and those receiving care. To protect themselves and others from infection, staff in residential and domiciliary care settings had to quickly adapt to infection control measures that heavily impacted on their working and every-day life, whilst navigating new responsibilities, uncertainties and anxieties. We sought to explore the production and reception of guidance and look at ways these can be adapted to improve the working life of care staff in domiciliary and residential care whilst reducing the risk of SARS-CoV-2 transmission amid this pandemic and of future emerging infections.We conducted two complementary and integrated systematic reviews of published documents in the pre-vaccination era: (1) National guidance for social care (conducted between 29 July to 28 October 2020), and (2) Newspaper coverage of infection control issues in social care (conducted between 27th July to 10th September 2020).Three higher order common themes emerged in the integrated systematic review of guidance documents and newspaper articles: a) Testing, b) Personal Protective Equipment, c) Employment. The reviews revealed a sharp disjunction between the content of infection control guidance and its usability and applicability in social care settings. We suggest that infection control guidance needs to be better adapted to social care settings and informed by the sector. The practicalities of care work and care settings need to be at the core of the process for guidance to be relevant and effective. Modes and timings of communications also need to be optimised.
Durability of anti-Spike antibodies in the infant after maternal COVID-19 vaccination
Authors: Shook Lydia L. , Atyeo Caroline G. , Yonker Lael M. , Fasano Alessio , Gray Kathryn J. , Alter Galit , Edlow Andrea G. 
Published: November 2021

AbstractCOVID-19 vaccination in pregnancy generates functional anti-Spike IgG antibodies that are known to cross the placenta. However, the durability of vaccine-induced maternal anti-S IgG in infant circulation, and how it compares to durability of antibody from maternal natural infection, is unknown. We quantified anti-S IgG in 92 2-month and 6-month-old infants whose mothers were vaccinated in pregnancy, and in 12 6-month-old infants after maternal natural infection with SARS-CoV-2. In the vaccinated group, 94% (58/62) of infants had detectable anti-S IgG at 2 months, and 60% (18/30) had detectable antibody at 6 months. In contrast, 8% (1/12) of infants born to women infected with SARS-CoV-2 in pregnancy had detectable anti-S IgG at the 6-month timepoint. Vaccination resulted in significantly higher maternal and cord titers at delivery and significantly greater antibody persistence in infants at 6 months, compared to natural infection.
Economic evaluation of a cluster randomized, non-inferiority trial of differentiated service delivery models of HIV treatment in Zimbabwe
Authors: Benade Mariet , Nichols Brooke , Fatti Geoffrey , Kuchukhidze Salome , Takarinda Kudakwashe , Mabhena-Ngorima Nicoletta , Grimwood Ashraf , Rosen Sydney 
Published: November 2021

AbstractBackgroundAbout 85% of Zimbabwe’s >1.4 million people living with HIV are on antiretroviral treatment (ART). Further expansion of its treatment program will require more efficient use of existing resources. Two promising strategies for reducing resource utilization per patient are multi-month medication dispensing and community-based service delivery. We evaluated the costs to providers and patients of community-based, multi-month ART delivery models in Zimbabwe.MethodsWe used resource and outcome data from a cluster-randomized non-inferiority trial of three differentiated service delivery (DSD) models targeted to patients stable on ART: 3-month facility-based care (3MF), community ART refill groups (CAGs) with 3-month dispensing (3MC), and CAGs with 6-month dispensing (6MC). Using local unit costs, we estimated the annual cost in 2020 USD of providing HIV treatment per patient from the provider and patient perspectives.ResultsIn the trial, retention at 12 months was 93.0% in the 3MF, 94.8% in the 3MC, and 95.5% in the 6MC arms. The total average annual cost of HIV treatment per patient was $187 (standard deviation $39), $178 ($30), and $167 ($39) in each of the three arms, respectively. The annual cost/patient was dominated by ART medications (79% in 3MF, 87% in 3MC; 92% in 6MC), followed by facility visits (12%, 5%, 5%, respectively) and viral load (8%, 8%, 2%, respectively). When costs were stratified by district, DSD models cost slightly less, with 6MC the least expensive in all districts. Savings were driven by differences in the number of facility visits made/year, as expected, and low uptake of annual viral load tests in the 6-month arm. The total annual cost to patients to obtain HIV care was $10.03 ($2) in the 3MF arm, $5.12 ($0.41) in the 3MC arm, and $4.40 ($0.39) in the 6MF arm.ConclusionsFor stable ART patients in Zimbabwe, 3- and 6-month community-based multi-month dispensing models cost less for both providers and patients than 3-month facility-based care and had non-inferior outcomes.
Set1-mediated histone H3K4 methylation is required for azole induction of the ergosterol biosynthesis genes and antifungal drug resistance inCandida glabrata
Authors: Baker Kortany M. , Hoda Smriti , Saha Debasmita , Georgescu Livia , Serratore Nina D. , Zhang Yueping , Lanman Nadia A. , Briggs Scott D. 
Published: November 2021

ABSTRACTCandida glabratais an opportunistic pathogen that has developed the ability to adapt and thrive under azole treated conditions. The common mechanisms that can result inCandidadrug resistance are due to mutations or overexpression of the drug efflux pump or the target of azole drugs, Cdr1 and Erg11, respectively. However, the role of epigenetic histone modifications in azole-induced gene expression and drug resistance are poorly understood inC. glabrata. In this study, we show for the first time that Set1 mediates histone H3K4 mono-, di-, and trimethylation inC. glabrata. In addition, loss ofSET1and histone H3K4 methylation results in increased susceptibility to azole drugs in bothC. glabrataandS. cerevisiae. Intriguingly, this increase in susceptibility to azole drugs in strains lacking Set1-mediated histone H3K4 methylation is not due to altered transcript levels ofCDR1,PDR1or Cdr1’s ability to efflux drugs. Genome-wide transcript analysis revealed that Set1 is necessary for azole-induced expression of 12 genes involved in the late biosynthesis of ergosterol includingERG11andERG3. Importantly, chromatin immunoprecipitation analysis showed that histone H3K4 trimethylation was detected on chromatin of actively transcribedERGgenes. Furthermore, H3K4 trimethylation increased upon azole-induced gene expression which was also found to be dependent on the catalytic activity of Set1. Altogether, our findings show that Set1-mediated histone H3K4 methylation governs the intrinsic drug resistant status inC. glabratavia epigenetic control of azole-inducedERGgene expression.IMPORTANCEC. glabratais the second most commonly isolated species fromCandidainfections, coming in second toC. albicans. Treatment ofC. glabratainfections are difficult due to their natural resistance to antifungal azole drugs and their ability to adapt and become multidrug resistant. In this study, we investigated the contributing cellular factors for controlling drug resistance. We have determined that an epigenetic mechanism governs the expression of genes involved in the late ergosterol biosynthesis pathway, an essential pathway that antifungal drugs target. This epigenetic mechanism involves histone H3K4 methylation catalyzed by the Set1 methyltransferase complex (COMPASS). We also show that Set1-mediated histone H3K4 methylation is needed for expression of specific azole induced genes and azole drug resistance inC. glabrata. Identifying epigenetic mechanisms contributing to drug resistance and pathogenesis could provide alternative targets for treating patients with fungal infections.
Hidden temporal structure of the ongoing task impacts detection strategy and is reflected in pupillary dynamics
Authors: Lawlor Jennifer , Zagala Agnès , Jamali Sara , Boubenec Yves 
Published: November 2021

AbstractEstimating temporal regularities in incoming sensory inputs supports optimal decisions in noisy environments. In particular, inferred temporal structure can ease the detection of likely target events. Here we postulated that timely urgency signals can adapt subjects’ decision-making to the ongoing task temporal structure, possibly through neuromodulatory tone. To test this hypothesis, we used an auditory change detection task in which targets followed a block-based temporal contingency, unbeknownst to participants. False alarm occurrences were driven by the distribution of target timings, indicating that participants adapted their behavior to the ongoing temporal structure. Task-evoked pupillary responses were larger for blocks with earliest target timings, and correlated with individual subjects’ behavioral adaptation. Individual pupil responses matched an urgency signal extracted from a decision model fitted to behavior. This work demonstrates that internal temporal expectation can be tracked through pupillary dynamics, suggesting a role of neuromodulatory systems in context-dependent modulation of decision variable dynamics.
Anatomical connectivity along the anterior-posterior axis of the human hippocampus: new insights using quantitative fibre-tracking
Authors: Dalton Marshall A. , D’Souza Arkiev , Lv Jinglei , Calamante Fernando 
Published: November 2021

AbstractThe hippocampus supports multiple cognitive functions including episodic memory. Recent work has highlighted functional differences along the anterior-posterior axis of the human hippocampus but the neuroanatomical underpinnings of these differences remain unclear. We leveraged track-density imaging to systematically examine anatomical connectivity between the cortical mantle and the anterior-posterior axis of the in-vivo human hippocampus. We first identified the most highly connected cortical areas and detailed the degree to which they preferentially connect along the anterior-posterior axis of the hippocampus. Then, using a tractography pipeline specifically tailored to measure the location and density of streamline endpoints within the hippocampus, we characterised where, within the hippocampus, these cortical areas preferentially connect. Our results were striking in showing that different parts of the hippocampus preferentially connect with distinct cortical areas. Furthermore, we provide evidence that both gradients and circumscribed areas of dense extrinsic anatomical connectivity exist within the human hippocampus. These findings inform conceptual debates in the field by unveiling how specific regions along the anterior-posterior axis of the hippocampus are associated with different cortical inputs/outputs. Overall, our results represent a major advance in our ability to map the anatomical connectivity of the human hippocampus in-vivo and inform our understanding of the neural architecture of hippocampal dependent memory systems in the human brain. This detailed characterization of how specific portions of the hippocampus anatomically connect with cortical brain regions may promote a better understanding of its role in cognition and we emphasize the importance of considering the hippocampus as a heterogeneous structure.
A pilot randomised prospective comparison of two approaches for tibial nailing using clinical and novel imaging outcome measures – study protocol
Authors: Davies Benjamin M , Ali Erden , Chou Daud , Hull Peter , Rawal Jaikirty , McKay James , McCaskie Andrew , Carrothers Andrew 
Published: November 2021

AbstractFractures of the tibia are frequently treated with an intra-medullary nail. This can be inserted through either a supra-patella or infra-patella surgical incision. Concerns over potential damage to the cartilage of the knee with supra-patella insertion has impacted upon its adoption despite benefits in terms of easier nail placement and potentially reduced blood loss and pain.This randomised pilot study will use patient reported outcome measures (PROMS) and novel MRI sequences designed to assess damage to the structure of cartilage to compare these two methods of tibial intra-medullary nailing.Twenty individuals with tibial shaft fractures will be randomised to either method of nail insertion (ten individuals in each arm). MRI scans and PROMS will be used to assess cartilage damage and general function up to 6 months post operatively.The results of the study will be used to inform a potential multi-centre study.
Proteolysis Targeting Chimeras With Reduced Off-targets
Authors: Nguyen Tuan M. , Sreekanth Vedagopuram , Deb Arghya , Kokkonda Praveen , Tiwari Praveen K. , Donovan Katherine A. , Shoba Veronika , Chaudhary Santosh K. , Mercer Jaron A. M. , Lai Sophia , Sadagopan Ananthan , Jan Max , Fischer Eric S. , Liu David R. , Ebert Benjamin L. , Choudhary Amit 
Published: November 2021

ABSTRACTProteolysis Targeting Chimeras (PROTACs), a class of heterobifunctional molecules that recruit target proteins to E3 ligases, have gained traction for targeted protein degradation. However, pomalidomide, a widely used E3 ligase recruiter in PROTACs, can independently degrade other targets, such as zinc-finger (ZF) proteins, that hold key functions in normal development and disease progression. This off-target degradation of pomalidomide-based PROTACs raises concerns about their therapeutic applicability and long-term side effects. Therefore, there is a crucial need to develop rules for PROTAC design that minimize off-target degradation. In this study, we developed a high-throughput platform that interrogates the off-target degradation of ZF domains and discovered, using this platform, that PROTACs with the current design paradigm induce degradation of several ZF proteins. To identify new rules for PROTAC design, we generated a library of pomalidomide analogs that allowed systematic exploration of the impact of positional isomerism (e.g., C4 and C5 positions of the phthalimide ring), hydrogen bonding, steric and hydrophobic effects on propensities for ZF protein degradation. We found that modifications of appropriate size on the C5 position reduced off-target ZF degradation. We validated these results using immunoblotting, target engagement, and global mass spectrometric studies. We applied our newfound design principles on a previously developed ALK oncoprotein-targeting PROTAC and generated PROTACs with enhanced potency and minimal off-target degradation. We envision the reported off-target profiling platform and pomalidomide analogs will find utility in design of specific PROTACs.
PURC v2.0: A Program for Improved Sequence Inference for Polyploid Phylogenetics and Other Manifestations of the Multiple-Copy Problem
Authors: Schafran Peter , Li Fay-Wei , Rothfels Carl J. 
Published: November 2021

AbstractInferring the true biological sequences from amplicon mixtures remains a difficult bioinformatic problem. The traditional approach is to cluster sequencing reads by similarity thresholds and treat the consensus sequence of each cluster as an “operational taxonomic unit” (OTU). Recently, this approach has been improved upon by model-based methods that correct PCR and sequencing errors in order to infer “amplicon sequence variants” (ASVs). To date, ASV approaches have been used primarily in metagenomics, but they are also useful for identifying allelic or paralogous variants and for determining homeologs in polyploid organisms. To facilitate the usage of ASV methods among polyploidy researchers, we incorporated ASV inference alongside OTU clustering inPURC v2.0, a major update to PURC (Pipeline for Untangling Reticulate Complexes). In addition to preserving original PURC functions,PURC v2.0allows users to process PacBio CCS/HiFi reads through DADA2 to generate and annotate ASVs for multiplexed data, with outputs including separate alignments for each locus ready for phylogenetic inference. In addition,PURC v2.0features faster demultiplexing than the original version and has been updated to be compatible with Python 3. In this chapter we present results indicating thatPURC v2.0(using the ASV approach) is more likely to infer the correct biological sequences in comparison to the earlier OTU-based PURC, and describe how to prepare sequencing data, runPURC v2.0under several different modes, and interpret the output. We expect thatPURC v2.0will provide biologists with a method for generating multi-locus “moderate data” datasets that are large enough to be phylogenetically informative and small enough for manual curation.
Sharing individualised template MRI data for MEG source reconstruction: a solution for open data while keeping subject confidentiality
Authors: Vinding Mikkel C. , Oostenveld Robert 
Published: November 2021

AbstractThe increasing requirements for adoption of FAIR data management and sharing original research data from neuroimaging studies can be at odds with protecting the anonymity of the research participants due to the person-identifiable anatomical features in the data. We propose a solution to this dilemma for anatomical MRIs used in MEG source analysis. In MEG analysis, the channel-level data is reconstructed to the source-level using models derived from anatomical MRIs. Sharing data, therefore, requires sharing the anatomical MRI to replicate the analysis. The suggested solution is to replace the individual anatomical MRIs with individualised warped templates that can be used to carry out the MEG source analysis and that provide sufficient geometrical similarity to the original participants’ MRIs.First, we demonstrate how the individualised template warping can be implemented with one of the leading open-source neuroimaging analysis toolboxes. Second, we compare results from four different MEG source reconstruction methods performed with an individualised warped template to those using the participant’s original MRI. While the source reconstruction results are not numerically identical, there is a high similarity between the results for single dipole fits, dynamic imaging of coherent sources beamforming, and atlas-based virtual channel beamforming. There is a moderate similarity between minimum-norm estimates, as anticipated due to this method being anatomically constrained and dependent on the exact morphological features of the cortical sheet.We also compared the morphological features of the warped template to those of the original MRI. These showed a high similarity in grey matter volume and surface area, but a low similarity in the average cortical thickness and the mean folding index within cortical parcels.Taken together, this demonstrates that the results obtained by MEG source reconstruction can be preserved with the warped templates, whereas the anatomical and morphological fingerprint is sufficiently altered to protect the anonymity of research participants. In cases where participants consent to sharing anatomical MRI data, it remains preferable to share the original defaced data with an appropriate data use agreement. In cases where participants did not consent to share their MRIs, the individualised warped MRI template offers a good compromise in sharing data for reuse while retaining anonymity for those research participants.
Adhesion strength between cells regulate non-monotonic growth by a biomechanical feedback mechanism
Authors: Malmi-Kakkada Abdul N , Sinha Sumit , Li Xin , Thirumalai D. 
Published: November 2021

AbstractWe probe the interplay between intercellular interactions and pressure fluctuations associated with single cells in regulating cell proliferation using simulations of a minimal model for three-dimensional multicellular spheroid (MCS) growth. The emergent spatial variations in the cell division rate, that depends on the location of the cells within the MCS, is regulated by intercellular adhesion strength (fad). This in turn results in non-monotonic proliferation of cells in the MCS with varying adhesion strength, which accords well with experimental results. A biomechanical feedback mechanism coupling the fad and cell-dependent pressure fluctuations relative to a threshold value (pc) determines the onset of a dormant phase, and explains the non-monotonic proliferation response. Increasing fad from low values enhances cell proliferation because pressure on individual cells is smaller compared to pc. In contrast, at high fad, cells readily become dormant and cannot rearrange effectively, leading to arrested cell proliferation. Our work, which shows that proliferation is regulated by pressure-adhesion feedback loop, may be a general feature of tumor growth.
Ecological changes have driven biotic exchanges across the Indian Ocean
Authors: Bernardes Samuel C. , von Rintelen Kristina , von Rintelen Thomas , Pepato Almir R. , Page Timothy J. , de Bruyn Mark 
Published: November 2021

AbstractThe Indian Ocean has a complex geological history that has drawn the attention of naturalists for almost a century now. Due to its tectonic history, many geological elements and processes have been evoked to explain the exchange of species between landmasses. Here, we revisited previous studies on twenty-three taxa to investigate trends across time since the Gondwana breakup. We investigated these datasets by applying a time-calibrated Bayesian framework to them and reconstructing their ancestral ranges. We conclude that ecological transformations have presented opportunities for the establishment of migrants. The role of donating and receiving migrants has shifted several times according to these transformations. Time-specific trends show weak evidence for the stepping-stones commonly suggested as physical routes between landmasses. However, before its collision with Asia, India may have served as an intermediary for such exchanges.