bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the genetic relationship between depression symptoms and Alzheimer’s Disease in clinically diagnosed and proxy cases
Authors: Gilchrist Lachlan , Spargo Thomas P. , Green Rebecca E. , Coleman Jonathan R.I. , Howard David M. , Thorp Jackson G. , Adey Brett , Lord Jodie , Davies Helena L. , Mundy Jessica , ter Kuile Abigail , Davies Molly R. , Hübel Christopher , Bristow Shannon , Lee Sang Hyuck , Rogers Henry , Curtis Charles , Kalsi Gursharan , Arathimos Ryan , Corbett Anne , Ballard Clive , Brooker Helen , Creese Byron , Aarsland Dag , Hampshire Adam , Velayudhan Latha , Eley Thalia C. , Breen Gerome , Iacoangeli Alfredo , Koks Sulev , Lewis Cathryn M. , Proitsi Petroula 
Published: June 2023

AbstractDepression is a risk factor for Alzheimer’s disease (AD), but evidence for their genetic relationship is mixed. Assessing depression symptom specific genetic associations may better clarify this relationship.Using data from the UK Biobank, the GLAD Study and PROTECT, we performed the largest genome-wide meta-analyses (GWAS) of the nine depression symptom items, plus their sum score, on the Patient Health Questionnaire (PHQ-9) (GWAS equivalent N: 224,535—308,421). We assessed global/local genetic correlations and statistical colocalisation between depression phenotypes and AD across six AD GWAS with varying proportions of clinical and proxy (family history) case ascertainment. We assessed bi-directional causal associations using Mendelian randomisation (MR) and the predictiveness of depression phenotype polygenic risk scores (PRS) for AD case/control status in three clinical AD cohorts.Our GWAS meta-analyses identified 37 genomic risk loci across the ten depression symptom phenotypes. Of the 72 global genetic correlation tests conducted between depression/depression symptoms and AD, 20 were significant at pFDR≤ 0.05. Only one significant genetic correlation was identified with AD GWAS containing clinical-only cases. Colocalisation was not identified at loci contains local genetic correlation but was identified in the region of transmembrane protein 106B (TMEM106B) between multiple depression phenotypes and both clinical-only and clinical+proxy AD. MR and PRS analyses did not yield statistically significant results.Our findings do not demonstrate a causal role of depression/depression symptoms on AD and suggest that previous evidence of their genetic overlap may be driven by the inclusion of proxy cases/controls. However, the identification of colocalisation at TMEM106B warrants further investigation.
Pulmonary Radioaerosol Mucociliary Clearance Parameters as Potential Outcomes in Primary Ciliary Dyskinesia Trials
Authors: Marthin June K. , Holgersen Mathias G. , Nielsen Kim G. , Mortensen Jann 
Published: June 2023

ABSTRACTBackgroundPulmonary Radioaerosol Mucociliary Clearance (PRMC) is anin vivowhole lung ciliary function test reliable for assessing mucociliary clearance for diagnostic purposes in individuals suspected of primary ciliary dyskinesia (PCD). We aimed to evaluate expanded use of PRMC by providing advantages and limitations for its potential use in providing outcome parameters in future trials aiming to restore ciliary activity.Material and MethodsIn this retrospective study, PRMC tests performed over a period of 24 years (1999-2022) were meticulously re-analyzed. Patients with genetically verified PCD and non-PCD controls were included. Originally, nebulized99mTc-albumin colloid was inhaled, and static and dynamic imaging acquired for 60 and 120 minutes, and 24 hours.For the purpose of the present study 3 PRMC parameters were defined: 1 hour lung retention (LR1), tracheobronchial velocity (TBV), and cough clearance.ResultsSixty-nine patients were included from the Danish PCD cohort. PRMC was overall completely absent regardless of PCD genotypes. In one patient with CCDC103 mutation, residual ciliary function and normal nasal NO, we found normal PRMC LR1 and measurable, however low, TBV.Voluntary cough significantly increased clearance with a median (IQR) of 11 (4;24) %.ConclusionAbsolute absence of PRMC would be the expected baseline result in by far the majority of patients with PCD regardless of genotype before introducing ciliary protein correctors in a clinical trial.Measurable PRMC TBV and normal LR1 in one patient with residual ciliary function, indicated that PRMC parameters could potentially improve if ciliary function was to be restored during a clinical trial.Involuntary cough and peripheral radioaerosol deposition were the main challenges of the PRMC method.
Association of Long COVID with housing insecurity in the United States, 2022-2023
Authors: Packard Samuel E. , Susser Ezra 
Published: June 2023

ABSTRACTObjectivesTo assess the association of Long COVID with housing insecurity in the United States.MethodsTo compare the prevalence of 3 binary indicators of housing insecurity between people with Long COVID (symptoms > 3 months) and COVID-19 survivors who don’t report long-term symptoms, we used survey-weighted regression models on 203,807 responses from the Household Pulse Survey, a representative cross-sectional survey of US households collected September 2022 – April 2023. Among people with Long COVID, we assessed whether functional impairment, current COVID-19 related symptoms, and symptom impact on day-to- day life were associated with a higher prevalence of housing insecurity.ResultsDuring the study period, 54,446 (27.2%) respondents with COVID-19 experienced symptoms lasting 3 months or longer, representing an estimated 27 million US adults. People with Long COVID were nearly twice as likely to experience significant difficulty with household expenses (Prevalence ratio [PR] 1.85, 95% CI 1.74-1.96), be behind on housing payments (PR 1.76, 95% CI 1.57-1.99), and face likely eviction or foreclosure (PR 2.12, 95% CI 1.58-2.86). Functional limitation and current symptoms which impact day-to-day life were associated with higher prevalence of housing insecurity.ConclusionsCompared with COVID-19 survivors who don’t experience long-term symptoms, people with Long COVID are more likely to report indicators housing insecurity, particularly those with functional limitations and long-term COVID-19 related symptoms impacting day-to- day life. Policies are needed to support people living with chronic illnesses following SARS- CoV-2 infection.
How could a pooled testing policy have performed in managing the early stages of the COVID-19 pandemic? Results from a simulation study
Authors: Heath Bethany , Villar Sofía S. , Robertson David S. 
Published: June 2023

AbstractA coordinated testing policy is an essential tool for responding to emerging epidemics, as was seen with COVID-19. However, it is very difficult to agree on the best policy when there are multiple conflicting objectives. A key objective is minimising cost, which is why pooled testing (a method that involves pooling samples taken from multiple individuals and analysing this with a single diagnostic test) has been suggested. In this paper, we present results from an extensive and realistic simulation study comparing testing policies based on individually testing subjects with symptoms (a policy resembling the UK strategy at the start of the COVID-19 pandemic), individually testing subjects at random or pools of subjects randomly combined and tested. To compare these testing methods, a dynamic model compromised of a relationship network and an extended SEIR model is used. In contrast to most existing literature, testing capacity is considered as fixed and limited rather than unbounded. This paper then explores the impact of the proportion of symptomatic infections on the expected performance of testing policies. Only for less than 50% of infections being symptomatic does pooled testing outperform symptomatic testing in terms of metrics such as total infections and length of epidemic. Additionally, we present the novel feature for testing of non-compliance and perform a sensitivity analysis for different compliance assumptions. Our results suggest for the pooled testing scheme to be superior to testing symptomatic people individually, only a small proportion of the population (>2%) needs to not comply with the testing procedure.
More spice, less salt: how capsaicin affects liking for and perceived saltiness of foods in people with smell loss
Authors: Hunter Stephanie R. , Beatty Candelaria , Dalton Pamela H. 
Published: June 2023

AbstractPeople who lose their sense of smell self-report consuming more salt to compensate for a lack of flavor and enhance eating enjoyment. However, this can contribute to excess sodium intake and a poor diet. Capsaicin may help increase salt taste intensity and eating enjoyment in this population, but this has not been studied. The purpose of this study was to determine 1) whether salt intake in those with smell loss differs from population averages, 2) whether capsaicin increases flavor and salt taste intensity, and 3) if adding spice to foods increases food liking in individuals with smell loss. Participants 18-65 years old with confirmed partial or total smell loss for at least 12 weeks completed two sets of replicate test sessions (four total). In two sessions participants rated overall flavor intensity, taste qualities’ intensities, spicy intensity, and liking for model tomato soups with low or regular sodium content and three levels of capsaicin (none, low, or moderate). In the other two sessions, participants rated the same sensory attributes for model food samples with three levels of added spice (none, low, or moderate). 24-hour urine samples were also collected to determine sodium intake. Results indicate that although sodium intake is higher than recommended in those with smell loss (2893 ± 258 mg/day), they do not consume more sodium than population averages. Adding low and moderate amounts of capsaicin to a model tomato soup increased the intensity of overall flavor and saltiness compared to a model tomato soup without capsaicin. However, the effect of capsaicin on liking differed by food type. In conclusion, the addition of capsaicin can improve flavor, salt taste intensity, and eating enjoyment in people with smell loss.
Efficacy of conventional rehabilitation, transcutaneous electrical nerve stimulation, or early mobilization to reverse acquired weakness in the intensive care unit. Randomized controlled pilot trial
Authors: Bueno-Ardariz César Alejandro , Cagide Sabrina Gimena , Gamarra Claudio Gabriel , Paz Darío Leonel , Rotela Eliana Verónica , Aranda-Castro Ricard , Bustos Fernando Daniel , Muller Sebastián , Settembrino Esteban Sebastián , Carrera Melina , Giongo Cecilia Elena , Nannini Gonzalo Martín , Nardelli Paula Gimena , Diaz-Ballve Ladislao Pablo 
Published: June 2023

AbstractObjectiveTo compare the efficacy of conventional rehabilitation, transcutaneous electrical nerve stimulation, and early mobilization in reducing the time needed to reverse intensive care unit-acquired weakness (ICUAW), as assessed by the Medical Research Council muscle strength scale (MRC-MSS) score, in patients clinically diagnosed with ICUAW.SettingMedical-surgical ICU of a general acute care hospital with 26 beds.DesignPilot trial with random assignment and a control group.InterventionsGroup 1: standard or routine rehabilitation, Group 2: transcutaneous electrical nerve stimulation, and Group 3: early mobilization protocol.SubjectsIndividuals over 18 years old admitted to the ICU with invasive mechanical ventilation for more than 24 hours and diagnosed with ICUAW defined as Score MRC-MSS<48 measured over two consecutive days.Results18 subjects were included. One-way ANOVA showed differences in the treatment days needed to achieve an MRC-MSS ≥48 (p = 0.01), as well as in the number of sessions required to reverse ICUAW (p = 0.01) when comparing the different interventions. Through post hoc analysis, the group treated with transcutaneous electrical nerve stimulation was identified as requiring significantly more days and sessions to reverse ICUAW. Differences were observed in the Barthel index at the end and in the variation of the Barthel index as a result of functional capacity among the different treatments.ConclusionThe group treated with transcutaneous electrical nerve stimulation required a significantly greater number of days and sessions to achieve an MRC-SS ≥48. No differences in functional limitation were observed. These findings should be corroborated in similar studies. (Clinicaltrial.govNCT04613908)
Genetic Diagnosis of Facioscapulohumeral Muscular Dystrophy Type 1 Using Rare Variant Linkage Analysis and Long Read Genome Sequencing
Authors: Li Kun , Quiat Daniel , She Fei , Liu Yuanwei , He Rong , Haghighi Alireza , Liu Fang , Zhang Rui , DePalma Steven Robert , Yang Ying , Wang Wen , Seidman Christine E. , Zhang Ping , Seidman Jonathan G. 
Published: June 2023

AbstractFacioscapulohumeral dystrophy type 1 (FSHD1) is a progressive, debilitating skeletal myopathy that requires a multimodal approach for complete molecular characterization of pathogenic genotypes. Here, we report genomic analyses of a family with suspected facioscapulohumeral dystrophy type 1 (FSHD1). We first performed short read genome sequencing, followed by parametric linkage analysis using rare variants to map the disease locus to a single 1.7 MB interval on chromosome 4q35.2 with a LOD score of 3.2. We then used ultra-long read genome sequencing as a single molecular test to genotype a pathogenic FSHD allele containing a 4qA permissive haplotype and 5 KpnI repeat units at the D4Z4 locus. These results demonstrate that genome-wide rare variant-based linkage analysis is a powerful tool for mapping disease loci in families and ultra-long read genome sequencing is capable of genotyping pathogenic FSHD1 alleles.
Single-molecule studies reveal the off-pathway elemental pause state as a target of streptolydigin inhibition of RNA polymerase and its dramatic enhancement by Gre factors
Authors: Arseniev Anatolii , Panfilov Mikhail , Pobegalov Georgii , Potyseva Alina , Pavlinova Polina , Yakunina Maria , Lee Jookyung , Borukhov Sergei , Severinov Konstantin , Khodorkovskii Mikhail 
Published: June 2023

ABSTRACTAntibiotic streptolydigin (Stl) inhibits bacterial transcription by blocking the trigger loop folding in the active center of RNA polymerase (RNAP), which is essential for catalysis. We use acoustic force spectroscopy to characterize the dynamics of transcription elongation in ternary elongation complexes of RNAP (ECs) in the presence of Stl at a single-molecule level. We found that Stl induces long-lived stochastic pauses while the instantaneous velocity of transcription between the pauses is unaffected. Stl enhances the short-lived pauses associated with an off-pathway elemental paused state of the RNAP nucleotide addition cycle. Unexpectedly, we found that transcript cleavage factors GreA and GreB, which were thought to be Stl competitors, do not alleviate the streptolydigin-induced pausing; instead, they synergistically increase transcription inhibition by Stl. This is the first known instance of a transcriptional factor enhancing antibiotic activity. We propose a structural model of the EC-Gre-Stl complex that explains the observed Stl activities and provides insight into possible cooperative action of secondary channel factors and other antibiotics binding at the Stl-pocket. These results offer a new strategy for high-throughput screening for prospective antibacterial agents.
Trading acyls and swapping sugars: metabolic innovations inSolanumtrichomes
Authors: Fiesel Paul D. , Kerwin Rachel E. , Jones A. Daniel , Last Robert L. 
Published: June 2023

AbstractSolanaceae (nightshade family) species synthesize a remarkable array of clade- and tissue-specific specialized metabolites. Protective acylsugars, one such class of structurally diverse metabolites, are produced by AcylSugar AcylTransferases from sugars and acyl-coenzyme A esters. Published research revealed trichome acylsugars composed of glucose and sucrose cores in species across the family. In addition, acylsugars were analyzed across a small fraction of the >1200 species in the phenotypically megadiverseSolanumgenus, with a handful containing inositol and glycosylated inositol cores. The current study sampled several dozen species across subclades of theSolanumto get a more detailed view of acylsugar chemodiversity. In depth characterization of acylsugars from the Clade II speciesSolanum melongena(brinjal eggplant) led to the identification of eight unusual structures with inositol or inositol glycoside cores, and hydroxyacyl chains. Liquid chromatography-mass spectrometry analysis of 31 additional species in theSolanumgenus revealed striking acylsugar diversity with some traits restricted to specific clades and species. Acylinositols and inositol-based acyldisaccharides were detected throughout much of the genus. In contrast, acylglucoses and acylsucroses were more restricted in distribution. Analysis of tissue-specific transcriptomes and interspecific acylsugar acetylation differences led to the identification of theS. melongenaAcylSugar AcylTransferase 3-Like 1 (SmASAT3-L1; SMEL4.1_12g015780) enzyme. This enzyme is distinct from previously characterized acylsugar acetyltransferases, which are in the ASAT4 clade, and appears to be a functionally divergent ASAT3. This study provides a foundation for investigating the evolution and function of diverseSolanumacylsugar structures and harnessing this diversity in breeding and synthetic biology.
Engineering the Maize Root Microbiome: A Rapid MoClo Toolkit and Identification of Potential Bacterial Chassis for studying Plant-Microbe Interactions
Authors: Schaik John van , Li Zidan , Cheadle John , Crook Nathan 
Published: June 2023

ABSTRACTSustainably enhancing crop production is a necessity given the increasing demands for staple crops and their associated carbon/nitrogen inputs. Plant-associated microbiomes offer one avenue for addressing this demand; however, studying these communities and engineering them has remained a challenge due to limited genetic tools and methods. In this work, we detail the development of the Maize Root ToolKit (MRTK); a rapid Modular Cloning (MoClo) toolkit that only takes 2.5 hours to generate desired constructs (5400 potential plasmids) that replicate and express heterologous genes inEnterobacter ludwigiistrain AA4 (Elu),Pseudomonas putidaAA7 (Ppu),Herbaspirillum robiniaestrain AA6 (Hro),Stenotrophomonas maltophiliastrain AA1 (Sma) andBrucella pituitosastrain AA2 (Bpi) which comprise a model maize root synthetic community (SynCom). In addition to these genetic tools, we describe a highly efficient transformation protocol (10^7-10^9 transformants/µg of DNA) for each of these strains. Utilizing this highly efficient transformation protocol, we identified endogenous expression sequences for each strain (ES; promoter and ribosomal binding sites) via genomic promoter trapping. Overall, the MRTK is a scalable platform that expands the genetic engineering toolbox while providing a standardized, high efficiency transformation method that can be implemented across a diverse group of root commensals. These results unlock the ability to elucidate and engineer plant-microbe interactions promoting plant growth for each of the 5 bacterial strains in this study.
Illuminating Dark Proteins using Reactome Pathways
Authors: Brunson Timothy , Sanati Nasim , Matthews Lisa , Haw Robin , Beavers Deidre , Shorser Solomon , Sevilla Cristoffer , Viteri Guilherme , Conley Patrick , Rothfels Karen , Hermjakob Henning , Stein Lincoln , D’Eustachio Peter , Wu Guanming 
Published: June 2023

AbstractLimited knowledge about a substantial portion of protein coding genes, known as “dark” proteins, hinders our understanding of their functions and potential therapeutic applications. To address this, we leveraged Reactome, the most comprehensive, open source, open-access pathway knowledgebase, to contextualize dark proteins within biological pathways. By integrating multiple resources and employing a random forest classifier trained on 106 protein/gene pairwise features, we predicted functional interactions between dark proteins and Reactome-annotated proteins. We then developed three scores to measure the interactions between dark proteins and Reactome pathways, utilizing enrichment analysis and fuzzy logic simulations. Correlation analysis of these scores with an independent single-cell RNA sequencing dataset provided supporting evidence for this approach. Furthermore, systematic natural language processing (NLP) analysis of over 22 million PubMed abstracts and manual checking of the literature associated with 20 randomly selected dark proteins reinforced the predicted interactions between proteins and pathways. To enhance the visualization and exploration of dark proteins within Reactome pathways, we developed the Reactome IDG portal, deployed athttps://idg.reactome.org, a web application featuring tissue-specific protein and gene expression overlay, as well as drug interactions. Our integrated computational approach, together with the user-friendly web platform, offers a valuable resource for uncovering potential biological functions and therapeutic implications of dark proteins.
Systematic annotation of a complete adult maleDrosophilanerve cord connectome reveals principles of functional organisation
Authors: Marin Elizabeth C. , Morris Billy J. , Stürner Tomke , Champion Andrew S. , Krzeminski Dominik , Badalamente Griffin , Gkantia Marina , Dunne Christopher R. , Eichler Katharina , Takemura Shin-ya , Tamimi Imaan F. M. , Fang Siqi , Moon Sung Soo , Cheong Han S. J. , Li Feng , Schlegel Philipp , Ahnert Sebastian E. , Berg Stuart ,   Janelia FlyEM Project Team, Card Gwyneth M. , Costa Marta , Shepherd David , Jefferis Gregory S.X.E. 
Published: June 2023

SummaryNervous systems function as ensembles of neurons communicating via synaptic connections, and a functional understanding of nervous systems requires extensive knowledge of their connectomes. In a companion paper (Takemura et al., 2023), we describe the acquisition of a complete fruit fly nerve cord connectome, the first for an animal that can walk or fly. Here, to efficiently navigate and to appreciate the biological significance of this connectome, we categorise and name nearly all neurons systematically and link them to the experimental literature. We employ a system of hierarchical coarse annotations and group similar neurons across the midline and across segments, then define systematic cell types for sensory neurons, intrinsic neurons, ascending neurons, and non-motor efferent neurons. Stereotyped arrays of neuroblasts generate related neuron populations called hemilineages that repeat across the segments of the nerve cord. We confirm that larval-born neurons from a given hemilineage generally express the same neurotransmitter but find that earlier born neurons often express a different one. We match over 35% of intrinsic, ascending, and non-motor efferent neurons across segments, defining serial sets which were crucial for systematic typing of motor neurons and sensory neurons. We assign a sensory modality to over 5000 sensory neurons, cluster them by connectivity, and identify serially homologous cell types and a layered organisation likely corresponding to peripheral topography. Finally, we present selected examples of sensory circuits predicated on programmatic analysis of a complete VNC connectome. Our annotations are critical for analysing the structure of descending input to the nerve cord and of motor output, both described in a third companion paper (Cheong et al., 2023). These annotations are being released as part of theneuprint.janelia.organdclio.janelia.orgweb applications and also serve as the basis for programmatic analysis of the connectome through dedicated tools that we describe in this paper.