bluuebunny/crossref_metadata_2025_split huggingface dataset:
Don’t Jump to Faulty Conclusions: Using the Synthetic Control Method to Evaluate the Effect of a Counterfactual Lockdown in Sweden
Authors: Herby Jonas 
Published: September 2024

AbstractSeveral studies based on the Synthetic Control Method (SCM) link the many COVID-19 deaths in Sweden during the spring of 2020 to its decision not to lock down. These studies predominantly rely on a limited pre-intervention period and tend to focus on the very short run neglecting that Swedish health authorities emphasized that their public health strategy was designed for the long run. This paper handles these shortcomings expanding both the pre- and post-intervention period considerably using weekly mortality rates. I find no significant effect of the absence of lockdown on COVID-19 mortality neither in the short or long run. Using the timing of the winter holiday as a proxy for the extent/spread of COVID-19 in societies before lockdown – a variable which is unobservable due to limited testing – I suggest that the effect of lockdowns found in earlier studies using Sweden as a control are likely to be partially driven by unobserved variables rather than policies.
APOE4impact on soluble and insoluble tau pathology is mostly influenced by amyloid-beta
Authors: Cicognola Claudia , Salvadó Gemma , Smith Ruben , Palmqvist Sebastian , Stomrud Erik , Betthauser Tobey , Johnson Sterling , Janelidze Shorena , Mattsson-Carlgren Niklas , Hansson Oskar , Binette Alexa Pichet 
Published: September 2024

AbstractTheAPOE4allele is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). WhileAPOE4is strongly associated with amyloid-beta (Aβ) accumulation, its relationship with tau accumulation is less understood. Studies evaluating the role ofAPOE4on tau accumulation have shown conflicting results, particularly regarding the independence of these associations from Aβ load. To clarify the relations betweenAPOE4,Aβ and tau, we examined three independent longitudinal cohorts (the Swedish BioFINDER-1, BioFINDER-2 and WRAP cohorts) in which participants had cross-sectional and longitudinal measures of tau tangles (tau-PET; temporal meta-ROI and entorhinal) or soluble p-tau (p-tau217), Aβ-PET andAPOEgenotype. The study included a total of 1370 cognitively unimpaired (CU) and 449 mild cognitive impairment (MCI) subjects, followed longitudinally with tau-PET and p-tau217.APOE4carriers accounted for 40.2-50% of the cohorts. Different linear regressions (cross-sectional) and linear mixed-effect models (longitudinal) with tau measures as outcomes were fitted to test the effect ofAPOE4as independent predictor, as well as in combination with baseline Aβ load or the interaction term betweenAPOE4and Aβ load. All models included age, sex and cognitive status as covariates.We found no independent effects of theAPOE4carriership on insoluble tau aggregates in either cohort (BioFINDER-2 or WRAP), both on cross-sectional and longitudinal tau-PET levels in the temporal meta-ROI, when Aβ was present in the model (p=0.531-0.949). Aβ alone was the best predictor of insoluble tau accumulation, and there was no interaction betweenAPOE4and Aβ on tau-PET. Similarly, no independent effects of theAPOE4carriership on baseline (p=0.683-0.708) and longitudinal (p=0.188-0.570) soluble p-tau217 were observed when Aβ was included in the model in BioFINDER-1 and WRAP. No interaction betweenAPOE4and Aβ on soluble p-tau217 was observed. Furthermore, mediation analysis revealed that Aβ load fully mediated most associations betweenAPOE4and tau (46-112%, either cross-sectional or longitudinal tau-PET or soluble p-tau217). In the largest cohort (BioFINDER-2), looking atAPOE4groups based on the number of ε4 alleles, we found an interaction between APOE4 homozygotes only and Aβ on tau-PET levels at baseline and over time.In conclusion, althoughAPOE4is strongly associated with Aβ aggregation, it seems to be minimally associated with longitudinal changes in soluble or insoluble p-tau levels at a given level of Aβ pathology, confirming the primacy of Aβ in driving tau pathology.
Self-reported Health Literacy, Digital Literacy, and Barriers to accessing care at a Safety Net Breast Surgical Oncology Clinic
Authors: Burke Jamie , Higgins Madeline G , Vemuru Sudheer R , Adams Monica , Leonard Laura , Taft Nancy , Ahrendt Gretchen , Jaiswal Kshama , Rojas Kristin , Miles Randy , Tevis Sarah E. 
Published: September 2024

AbstractBackgroundSociodemographic factors, including language, education, race, and insurance status, significantly influence patient outcomes following breast surgery, especially in safety-net hospitals (SNHs) that serve vulnerable populations.ObjectiveTo assess the sociodemographic composition of a breast surgical oncology clinic at an urban SNH and evaluate how these factors impact digital literacy, health literacy, and access to care.MethodsEnglish and Spanish-speaking adult female patients at an urban SNH breast surgical oncology clinic between August and October 2022 completed a survey assessing digital and health literacy, barriers to care, and sociodemographic information. Descriptive statistics and comparative analyses were performed using Chi-squared and Fisher’s exact tests.ResultsOf 127 invited patients, 95 (75%) completed the survey. The median age was 50 years. Fifty-six percent identified as Hispanic, 43% preferred Spanish, and 40% had less than a high school education. Health literacy was lower among Spanish-speaking, older, and less-educated patients. Digital literacy was also lower among these groups, with notable disparities in access to computers, the internet, and smartphones.ConclusionSignificant disparities in health and digital literacy exist among vulnerable breast cancer patients at SNHs, particularly among Spanish-speaking, older, and less-educated individuals. Targeted interventions to improve education, access to digital resources, and supportive services are essential to ensure equitable care and improve health outcomes for these populations.
CRISPR-Cas12a2-based rapid and sensitive detection system for target nucleic acid
Authors: Yu Helin , Feng Meng , Liu Chuncao , Wang Feifei , Sui Guodong , Jing Wenwen , Cheng Xunjia 
Published: September 2024

AbstractInfectious diseases are extremely important public health issues, where the design of effective, rapid, and convenient detection platforms is critical. In this study, we used conventional PCR coupled with SuCas12a2, a novel Cas12 family RNA-targeting nuclease, to develop a detection approach. SuCas12a2 possesses collateral cleavage activity and cuts the additional single-stranded RNA (ssRNA) added to the reaction system once the ternary complex RNA-SuCas12a2-CRISPR RNA (crRNA) is formed. SuCas12a2 is specifically activated, where the cleaved fluorescent-labeled probes release fluorescent signals, with the strength of the fluorescent signal being proportional to the concentration of nucleic acids specifically bound to crRNA. Simultaneous transcription and SuCas12a2 detection can be performed in a single tube by introducing the T7 promoter sequence into the forward primer.Entamoeba histolyticawas used to evaluate the performance of the platform. PCR-SuCas12a2 has excellent capabilities, including high specificity with no cross-reactivity from other species and ultra-sensitivity that achieves a detection of one copy per reaction. There were five samples from amoebiasis patients confirmed by indirect immunofluorescence assay that were used as proof specimens, where the PCR-SuCas12a2 assay demonstrated 100% specificity. Furthermore, we replaced conventional PCR with recombinase polymerase amplification (RPA) to simplify the procedure for producing amplicons harboring the T7 promoter sequence. The sensitivity of the RPA-SuCas12a2 assay was 102copies per reaction, which was inferior to PCR-SuCas12a2, and demonstrated 100% specificity. The technique shows robust performance and suggests great potential for point-of-care testing of other pathogens to facilitate effective management and control of the spread of diseases.Abstract FigureFigure abstract
A novel method for characterizing cell-cell interactions at single-cell resolution reveals unique signatures in blood T cell-monocyte complexes during infection
Authors: Kang Ningxin , Chawla Ashu , Hillman Hannah , Tippalagama Rashmi , Kim Cheryl , Mikulski Zbigniew , Seumois Grégory , Vijayanand Pandurangan , Scriba Thomas J , De Silva Aruna D , Balmaseda Angel , Harris Eva , Weiskopf Daniela , Sette Alessandro , Arlehamn Cecilia Lindestam , Peters Bjoern , Burel Julie G 
Published: September 2024

AbstractCommunication between immune cells through direct contact is a critical feature of immune responses. Here, we developed a novel high-throughput method to study the transcriptome and adaptive immune receptor repertoire of single cells forming complexes without needing bioinformatic deconvolution. We found that T cells and monocytes forming complexes in blood during active tuberculosis (TB) and dengue hold unique transcriptomic signatures indicative of TCR/MCH-II immune synapses. Additionally, T cells in complexes showed enrichment for effector phenotypes, imaging and transcriptomic features of active TCR signaling, and increased immune activity at diagnosis compared to after anti-TB therapy. We also found evidence for bidirectional RNA exchange between T cells and monocytes, since complexes were markedly enriched for “dual-expressing” cells (i.e., co-expressing T cell and monocyte genes). Thus, studying immune cell complexes at a single-cell resolution offers novel perspectives on immune synaptic interactions occurring in blood during infection.Graphical Abstract
Properties of DNA in concentrated aqueous solutions of LiCl suggest transition to C-DNA
Authors: Mazur Alexey K. , Maaloum Mounir , Gladyshev Eugene 
Published: September 2024

ABSTRACTC-DNA represents a canonical DNA form related to B-DNA. While C-DNA is known to exist in air-dried fibers, its occurrence in aqueous solutions remains subject to debate. In fibers, the transition from B- to C-DNA is promoted by reduced hydration in the presence of certain monovalent cations (most notably Li+), and this process is generally associated with an increase in the helical twist. To understand if the B-to-C transition can occur in liquid media in principle, we analyzed properties of several circular DNA substrates in aqueous solutions with varying concentrations of LiCl (0.1-8 M). To this end, we estimated changes in the helical twist directly from circular dichroism (CD) spectra of a large supercoiled plasmid and, in parallel, assayed conformational changes in DNA minicircles by atomic force microscopy (AFM). We found that the helical twist increased continuously over the entire range of tested LiCl concentrations, without being subject to saturation even at 8 M LiCl. The overall increase in the helical twist was compatible with the B-to-C transition occurring in solution at a concentration of LiCl of about 8 M, suggesting that C-DNA should be stable above this level.
Expanding Automated Multiconformer Ligand Modeling to Macrocycles and Fragments
Authors: Flowers Jessica , Echols Nathaniel , Correy Galen , Jaishankar Priya , Togo Takaya , Renslo Adam R. , van den Bedem Henry , Fraser James S. , Wankowicz Stephanie A. 
Published: September 2024

ABSTRACTSmall molecule ligands exhibit a diverse range of conformations in solution. Upon binding to a target protein, this conformational diversity is generally reduced. However, ligands can retain some degree of conformational flexibility even when bound to a receptor. In the Protein Data Bank (PDB), a small number of ligands have been modeled with distinct alternative conformations that are supported by X-ray crystallography density maps. However, the vast majority of structural models are fit to a single ligand conformation, potentially ignoring the underlying conformational heterogeneity present in the sample. We previously developed qFit-ligand to sample diverse ligand conformations and to select a parsimonious ensemble consistent with the density. While this approach indicated that many ligands populate alternative conformations, limitations in our sampling procedures often resulted in non-physical conformations and could not model complex ligands like macrocycles. Here, we introduce several improvements to qFit-ligand, including the use of routines within RDKit for stochastic conformational sampling. This new sampling method greatly enriches low energy conformations of small molecules and macrocycles. We further extended qFit-ligand to identify alternative conformations in PanDDA-modified density maps from high throughput X-ray fragment screening experiments. The new version of qFit-ligand improves fit to electron density and reduces torsional strain relative to deposited single conformer models and our previous version of qFit-ligand. These advances enhance the analysis of residual conformational heterogeneity present in ligand-bound structures, which can provide important insights for the rational design of therapeutic agents.
GuaCAMOLE: GC-bias aware estimation improves the accuracy of metagenomic species abundances
Authors: Holcik Laurenz , von Haseseler Arndt , Pflug Florian G. 
Published: September 2024

AbstractGuaCAMOLE is a novel computational method which detects and removes GC bias from metagenomic sequencing data. Metagenomic sequencing measures the species composition of microbial communities, and has revealed the crucial role of microbiomes in the etiology of a range of diseases such as colorectal cancer. Quantitative comparisons of microbial communities are, however, affected by GC-content dependent biases. GuaCAMOLE works regardless of the specific amount or direction of GC-bias present in the data and requires only a single sample. The algorithm reports unbiased abundances and quantifies the amount of bias present in terms of GC-depdendent sequencing efficiencies. Experimental mock community data confirms both estimates to be accurate across a wide range of experimental protocols. In gut microbiomes of colorectal cancer patients we observe a clear bias against GC-poor species in the abundances reported by existing methods. GuaCAMOLE successfully removes this bias and corrects the abundance of clinically relevant GC-poor species such asF. nucleatum(28% GC) by up to a factor of two. GuaCAMOLE thus contributes to a better quantitative understanding of microbial communities by improving the accuracy and comparability of species abundances across experimental setups.
Medicago truncatula CORYNEregulates inflorescence meristem branching, nutrient signaling, and arbuscular mycorrhizal symbiosis
Authors: Orosz Johnathan , Lin Erica Xinlei , Lindsay Penelope , Kappes Mikayla , Bashyal Sagar , Everett Hasani , Gautam Chandan Kumar , Jackson David , Müller Lena Maria 
Published: September 2024

AbstractThe CLAVATA signaling pathway regulates plant development and plant-environment interactions. CLAVATA signaling consists of mobile, cell-type or environment-specific CLAVATA3/ESR-related (CLE) peptides, which are perceived by a receptor complex consisting of leucine-rich repeat receptor-like kinases such as CLAVATA1 and receptor-like proteins such as CLAVATA2, which often functions with the pseudokinase CORYNE (CRN). CLAVATA signaling has been extensively studied in various plant species for its role in meristem maintenance and in legumes for modulating root interactions with nitrogen-fixing rhizobia. Some signaling proteins involved in development and nodulation, including CLAVATA1, also regulate plant interactions with mutualistic arbuscular mycorrhizal (AM) fungi. However, our knowledge on AM symbiosis regulation by CLAVATA signaling remains limited and only a handful of genetic regulators have been identified. Here we report thatMedicago truncatula CRNcontrols inflorescence meristem branching and negatively regulates root interactions with AM fungi.MtCRNfunctions partially independently of the AM autoregulation signalMtCLE53. Transcriptomic data revealed thatcrnroots display signs of perturbed signaling related to a range of responses to biotic and abiotic factors, suggesting thatMtCRNplays various roles in plant development and interactions with the environment.
Rational inattention in neural coding for economic choice
Authors: Fine Justin M. , Moreno-Bote Rubén , Hayden Benjamin Y. 
Published: September 2024

ABSTRACTMental operations like computing the value of an option are computationally expensive. Even before we evaluate options, we must decide how much attentional effort to invest in the evaluation process. More precise evaluation will improve choice accuracy, and thus reward yield, but the gain may not justify the cost.Rational Inattention theoriesprovide an accounting of the internal economics of attentionally effortful economic decisions. To understand this process, we examined choices and neural activity in several brain regions in six macaques making risky choices. We extended the rational inattention framework to incorporate the foraging theoretic understanding of local environmental richness or reward rate, which we predict will promote attentional effort. Consistent with this idea, we found local reward rate positively predicted choice accuracy. Supporting the hypothesis that this effect reflects variations in attentional effort, richer contexts were associated with increased baseline and evoked pupil size. Neural populations likewise showed systematic baseline coding of reward rate context. During increased reward rate contexts, ventral striatum and orbitofrontal cortex showed both an increase in value decodability and a rotation in the population geometries for value. This confluence of these results suggests a mechanism of attentional effort that operates by controlling gain through using partially distinct population codes for value. Additionally, increased reward rate accelerated value code dynamics, which have been linked to improved signal-to-noise. These results extend the theory of rational inattention to static and stationary contexts and align theories of rational inattention with specific costly, neural processes.
Derivation and validation of indices incorporating vasopressor dose and blood pressure values over time
Authors: Gervais Alain , Lamontagne François , Michaud Jean-Baptiste , Adhikari Neill KJ , Pagé Jean-Michel , Masse Marie-Hélène , Harhay Michael O , Chassé Michaël , Lamontagne Félix , Laforge Katia , Fortin Alexandra , Leclair Marc-André , Lévesque Simon , Domingue Marie-Pier , Momenzadeh Neda , Vallières Martin , Pinto Ruxandra , Morin-Lavoie Maxime , Carter Francis , Lemyre Félix Camirand 
Published: September 2024

AbstractRationaleThe blood pressure value below which the benefits of vasopressors clearly outweigh their disadvantages is uncertain.ObjectivesThe main objective of this analysis was to investigate the statistical properties and potential utility of indices estimating the vasopressor dose-rates as a function of blood pressure values over time.MethodsIn this single-center observational study, we collected blood pressure values from intensive care unit (ICU) monitors and norepinephrine dose-rates from infusion pumps corresponding to a derivation and a validation cohort. Patients included in each cohort were 18 years or older and received norepinephrine in the ICU. We defined and derived indices corresponding to vasopressor therapy above (>65 mmHg) and below (<60 mmHg) targets. We report the distribution of both indices over time from both cohorts as well as their associations with hospital mortality using logistic regression models adjusted for baseline variables.ResultsBetween July 30 2020 and March 28 2022, 283 patients were included in the derivation cohort. The median ICU stay was 5 days (interquartile range [IQR] 2-10.5) and the median duration of norepinephrine therapy was 27.3 hours (IQR 13.9-54.2). The median cumulative time with a MAP below 60 mmHg was 0.9 hours (IQR 0.2-3.1), whereas the cumulative time with a MAP above 65 mmHg was 22.5 hours (IQR 10.9-40.4). Adjusting for prespecified baseline variables, the above target index was associated with hospital mortality (OR 1.6, 95% CI 1.2 –2.3) but not the below target index (OR 1.1 95% CI 0.8 – 1.5). Between May 5 2022 and December 16 2022, 83 patients were included in the validation cohort. The duration of ICU stay and the proportion of norepinephrine exposure above MAP target were consistent with the derivation cohort. The point estimates of the associations between each index and mortality were also consistent with the derivation cohort, but not statistically significant.ConclusionIndices of vasopressor administration as a function of blood pressure suggest that during most of vasopressor therapy episodes, patients are treated above target. The association of these indices with patient outcomes remains uncertain but could be explored in larger datasets, and future clinical trials of target MAPs may consider measurement of these indices to adjust results for treatment adherence.
Evaluation of a Mental Health Support Service for Performing Artists
Authors: Ryan Finola M , Cordeaux Claire , Davison Dermott 
Published: September 2024

AbstractBackgroundPerforming artists frequently face mental health challenges, with risk factors including performance pressure, industry competitiveness, and irregular work patterns. Barriers to seeking help encompass confidentiality concerns, fear of misunderstanding by clinicians, and scheduling conflicts due to peripatetic work.AimsThis study aims to evaluate the accessibility, utilisation, and effectiveness of a Mental Health Support Service (MHSS) for performing artists.MethodsA 12-month evaluation of a UK-wide MHSS for performing artists was conducted. 555 self-referred performers received 6-8 sessions of talking therapy from experienced professionals. Pre- and post-intervention mental health was assessed using PHQ-9 and GAD-7 scales. Quantitative data were analysed using paired t-tests, and qualitative feedback underwent thematic analysis.Results240 performers completed pre- and post-intervention scores. Significant reductions in PHQ-9 (mean decrease 6.242, p<0.0001) and GAD-7 (mean decrease 6.225, p<0.0001) scores were observed post-intervention. Qualitative feedback (n=215) revealed high satisfaction, with 88% willing to recommend the service. Key themes included appreciation for tailored support and therapist-performer compatibility. Limited data on outcomes for global majority participants and gender differences necessitate further research.ConclusionsThis evaluation of a mental health support service for performing artists reveals high satisfaction rates and willingness to recommend the service, highlighting the value of tailored interventions that address industry-specific challenges. The findings underscore the importance of developing sector-specific mental health standards and support systems, particularly for industries with high proportions of freelance workers, which could have broader implications for improving mental health support across diverse professional fields.