bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood temperamental, emotional, and behavioral predictors of clinical mood and anxiety disorders in adolescence
Authors: Bakken Nora R. , Hannigan Laurie J. , Shadrin Alexey , Hindley Guy , Ask Helga , Reichborn-Kjennerud Ted , Tesli Martin , Andreassen Ole A. , Havdahl Alexandra 
Published: March 2022

ABSTRACTBackgroundMood and anxiety disorders, often emerging during adolescence, account for a large share of the global burden of disability. Prospectively assessed premorbid early signs and trajectories can provide useful insights for early detection and development of these disorders.MethodsUsing the health registry linked Norwegian Mother, Father and Child Cohort Study (MoBa) of 110,367 children, we here examine cross-sectional and longitudinal association between temperamental traits, emotional and behavioral problems in childhood (0.5-8 years) and diagnosis of mood or anxiety (emotional) disorders in adolescence (10-18 years). We included birth year and sex, retrieved from the Medical Birth Registry of Norway, as covariates in all analyses.ResultsLogistic regression analyses showed consistent and increasing associations between childhood negative emotionality, behavioral and emotional problems and adolescent diagnosis of emotional disorders, present from 6 months of age (negative emotionality) and with similar magnitude of association for the associated traits. Latent profile analysis incorporating latent growth models identified five developmental profiles of emotional and behavioral problems. A profile of early increasing behavioral and emotional problems with combined symptoms at 8 years (1.3% of sample) was the profile most strongly associated with emotional disorders in adolescence (OR vs. reference: 5.00, 95% CI: 3.73-6.30).ConclusionsWe found a consistent and increasing association between negative emotionality, behavioral and emotional problems in early to middle childhood and mood and anxiety disorders in adolescence. A developmental profile coherent with early and increasing disruptive mood dysregulation across childhood was most predictive of adolescent emotional disorders. Our results highlight the importance of early emotional dysregulation and childhood as a formative period in the development of adolescent mood and anxiety disorders, supporting a potential for prevention and early intervention initiatives.
Withdrawal of Assisted Ventilation at the Patient’s Request in MND/ALS: A Retrospective Exploration of the Ethical and Legal Issues Concerning Relatives, Nurses and Allied Health Care Professionals
Authors: Phelps K. , Regen E. , McDermott C.J. , Oliver D.J. , Faull C. 
Published: March 2022

ABSTRACTBackgroundThere is little literature focusing on the issues relatives and health professionals encounter when withdrawing assisted ventilation at the request of a patient with MND/ALS.AimTo explore with relatives, nurses and allied health professionals the ethical and legal issues that they had encountered in the withdrawal of ventilation at the request of a patient with MND/ALS.MethodA retrospective qualitative interview study with 16 family members and 26 professionals. Data was analysed thematically and compared with results from a previous study with doctors.ResultsThe events surrounding ventilation withdrawal were extraordinarily memorable for both HCPs and family members with clear recall of explicit details, even from years previously. The events had had a profound and lasting effect due to the emotional intensity of the experiences. Withdrawal of ventilation posed legal, ethical and moral challenges for relatives and health are professionals. Relatives looked to health care professionals for knowledge, guidance and reassurance on these issues, worried about how the withdrawal would be perceived by others, and found professional ignorance and disagreement distressing. Many health care professionals lacked theoretical knowledge and confidence on the legal and ethical considerations of withdrawal and struggled morally knowing the outcome of the withdrawal would be death. Health care professionals also worried about the perception of others of their involvement, which in turn influenced their practice. There was a lack of consistency in understanding across professions, and professionals often felt uncomfortable and anxiousConclusionsLegal, ethical and practical guidance is needed and open discussion of the ethical challenges as well as education and support for health care professionals and relatives would improve the experience of all involved.
Health behaviours and their determinants among immigrants residing in Italy
Authors: Minchio Giovanni , Rusciani Raffaella , Costa Giuseppe , Sciortino Giuseppe , Spadea Teresa 
Published: March 2022

AbstractBackgroundThe mechanisms that influence the uptake of risky behaviours among immigrants are influenced by the interrelation between characteristics operating in different phases of their migratory experience. Characterizing their behavioural risk profile is needed to prioritize actions for prevention and health services organization. We therefore analysed health behaviours and their determinants among immigrants in Italy, jointly accounting for sociodemographic factors, migration pathways and integration indicators.MethodsData come from a national survey conducted in 2011-2012 on a sample of about 12000 households with at least one foreigner residing in Italy. The independent impact of a variety of sociodemographic, migratory and integration characteristics on obesity, smoking and daily alcohol consumption was assessed using multivariable Poisson models.ResultsThe survey involved more than 15,000 first generation immigrants. Unhealthy lifestyles are more common among men than among women and vary widely by ethnic group. There is a significant impact of employment status and family composition, while the educational level loses importance. Longer duration of residence and younger age at arrival are associated with an increased behavioural risk. Among women we also observed an independent impact of the integration indicators, less important for men.ConclusionsThe profile of the main unhealthy lifestyles among migrants is shaped by cultural, socioeconomic and migratory characteristics, which differ by gender. Understanding these factors can help to design tailored preventive messages, necessary to interrupt the deterioration of migrants’ health capital. Low levels of integration have an additional negative impact on health, so inclusion and integration policies should complement health promotion strategies.
Integrated Bile Acid Profile Analysis for The Non-invasive Staging Diagnosis of Ulcerative Colitis
Authors: Cao Lijuan , Wang Yun , Zhang Lu , Che Yuan , Huang Hai , Shen Hong , Hao Haiping 
Published: March 2022

AbstractClinical staging diagnosis and progression tracking for ulcerative colitis (UC) is challenging as poor patient compliance of endoscopic biopsy, we aimed to explore a non-invasive integrative biochemical index to quantitative track and monitor pathological activity. Here we perform a study that integrates bile acid metabolomic profiling, metagenomic sequencing and clinical monitoring on serum and feacal samples from 24 active-state UC patients, 25 remission-state UC patients and 20 healthy volunteers from China. Besides known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with UC, we found several bile acid-transforming species, including 7α-dehydroxygenase and 7α/β-dehydrogenase expressing microbiota, were significant correlated with UC pathological activity. We identified 7 microbial gene markers that differentiated active and remission-stage UC and healthy control microbiomes. Relevantly, decreased serum deoxycholic acid /cholic acid ratio and increased fecal ursodeoxycholic acid/chenodeoxycholic acid ratio were associated with pathological activity of UC. Moreover, receiver operating characteristic analysis based on serum/fecal bile acids ratios was much accurate in prediction of active and remission stage outcome. This species-specific temporal change and bile acid dysregulation pattern linked to disease severity indicating that integrated microbiome-bile acid profile maybe implied for disease activity prediction, and that targeting microbiome-mediated restoring gut flora and bile acids homeostasis may be implicative of therapy efficacy. Collectively, these insights will help improve clinical diagnosis and optimize existing medical treatments.
Exogenous application of dsRNA for the control of viruses in cucurbits
Authors: Delgado-Martín Josemaría , Ruiz Leticia , Janssen Dirk , Velasco Leonardo 
Published: March 2022

AbstractThe recurrent emergence of virus diseases in intensive horticultural crops requires alternative control strategies. Topical application of dsRNA molecules homologous to pathogens has been proposed as a tool for plant virus control. These dsRNAs induce the silencing mechanism (RNAi) that degrades homologous dsRNAs. Cucumber green mottle mosaic virus (CGMMV) represents a serious threat to cucurbit crops. Since genetic resistance to the virus is not yet available in commercial varieties, we aimed to control this virus by RNAi. For this purpose, we obtained constructions both for expressing dsRNA in bacteria to treat cucumber plants by topical application and for agroinoculation in experiments done in the growth chamber. Besides, greenhouse tests were performed in spring and in summer when plants were challenged with the virus and differences in several parameters were investigated, including severity of symptoms, dry weight, total height, virus accumulation and virus-derived small interfering RNAs (vsiRNAs). Spraying of plants with dsRNA reduced significatively CGMMV symptoms in the plants in growth chamber tests. Agroinfiltration experiments done under identical conditions were also effective in limiting the progress of CGMMV disease. In the greenhouse assay performed in spring, symptoms were significatively reduced in dsRNA-sprayed plants and the development of the plants improved with respect to non-treated plants. Virus titters and vsiRNAs were clearly reduced in dsRNA-treated plants. The effect of protection of the dsRNA was less evident in the greenhouse assay carried out in summer. Besides, we investigated the mobility of long (ds)RNA derived from spraying or agroinfiltrated dsRNA and found that it could be detected in local, close distal and far distal points from the site of application. VsiRNAs were also detected in local and distal points and the differences in accumulation were compared. In parallel, we investigated the capacity of dsRNAs derived from genes of tomato leaf curl New Delhi virus (ToLCNDV), another economically important virus in cucurbits, to limit the disease in zucchini, both by agroinfiltration or direct spraying, but found no protection effect. In view of the results, topical application of dsRNAs is postulated as a promising strategy for CGMMV control in cucumber.
Human alveolar macrophage response toMycobacterium tuberculosis: immune characteristics underlying large inter-individual variability
Authors: Sadee Wolfgang , Cheeseman Ian H. , Papp Audrey , Pietrzak Maciej , Seweryn Michal , Zhou Xiaofei , Lin Shili , Williams Amanda M. , Arnett Eusondia , Azad Abul K. , Schlesinger Larry S. 
Published: March 2022

AbstractMycobacterium tuberculosis(M.tb) establishes residence and growth in human alveolar macrophages (AMs). Large inter-individual variation inM.tb-AM interactions is a potential early indicator of TB risk and efficacy of therapies and vaccines. Herein, we systematically analyze interactions of a virulentM.tbstrain with freshly isolated human AMs from 28 healthy adult donors, measuring host RNA expression and secreted candidate proteins associated with TB pathogenesis over 72h. We observe large inter-individual differences in bacterial uptake and growth, with tenfold variation inM.tbload at 72h, reflected by large variation of gene expression programs. Systems analysis of differential and variable RNA and protein expression identifies TB-associated genes and networks (e.g., IL1BandIDO1). RNA time profiles document early stimulation of M1-type macrophage gene expression followed by emergence of an M2-type profile. The fine-scale resolution of this work enables the separation of genes and networks regulating earlyM.tbgrowth dynamics, and development of potential markers of individual susceptibility toM.tbinfection and response to therapies.
Claudin5 protects the peripheral endothelial barrier in an organ and vessel type-specific manner
Authors: Richards M , Nwadozi E , Pal S , Martinsson P , Kaakinen M , Gloger M , Sjöberg E , Koltowska K , Betsholtz C , Eklund L , Nordling S , Claesson-Welsh L 
Published: March 2022

AbstractThe pathogenesis of numerous diseases is characterised by disruption of the junctions that form the endothelial cell (EC) barrier, the composition of which may differ greatly between organs. However, the expression level variability and precise contribution of different junctional proteins is poorly understood. Here, we focus on organs with continuous endothelium to identify structural and functional in vivo characteristics of the EC barrier. Assembly of multiple single-cell RNAseq datasets into a single integrated database revealed the variability in EC barrier patterning. Across tissues Claudin5 exhibited diminishing expression along the arteriovenous axis, which correlates with EC barrier integrity. Functional analysis identified tissue-specific differences in leakage patterning and response to agonist-induced leakage. We uncover that Claudin5 loss enhances agonist-induced leakage in an organotypic, vessel type-specific and size-selective manner in an inducible, EC-specific, knock-out mouse. Mechanistically, Claudin5 loss induces no change in junction ultrastructure but alters composition, with concomitant loss of zonula occludens-1 (ZO-1) expression and upregulation of VE-Cadherin. These findings uncover the organ-specific organisation of the EC barrier and distinct importance of Claudin5 in different vascular beds and will aid our ability to modify EC barrier stability in a targeted, organ-specific manner.
Reciprocal feature encoding by cortical excitatory and inhibitory neurons
Authors: Duszkiewicz Adrian J. , Orhan Pierre , Skromne Carrasco Sofia , Brown Eleanor H. , Owczarek Eliott , Vite Gilberto R. , Wood Emma R. , Peyrache Adrien 
Published: March 2022

AbstractIn the cortex, the interplay between excitation and inhibition determines the fidelity of neuronal representations. However, while the receptive fields of excitatory neurons are often fine-tuned to the encoded features, the principles governing the tuning of inhibitory neurons are still elusive. We addressed this problem by recording populations of neurons in the postsubiculum (PoSub), a cortical area where the receptive fields of most excitatory neurons correspond to a specific head-direction (HD). In contrast to PoSub-HD cells, the tuning of fast-spiking (FS) cells, the largest class of cortical inhibitory neurons, was broad and heterogeneous. However, we found that PoSub-FS cell tuning curves were often fine-tuned in the spatial frequency domain, which resulted in various radial symmetries in their HD tuning. In addition, recordings and specific optogenetic manipulations of the upstream thalamic populations as well as computational models suggest that this population co-tuning in the frequency domain has a local origin. Together, these findings provide evidence that the resolution of neuronal tuning is an intrinsic property of local cortical networks, shared by both excitatory and inhibitory cell populations.
Neutralizing responses in fully vaccinated with BNT162b2, CoronaVac, ChAdOx1, and Ad26.COV2.S against SARS-CoV-2 lineages in Colombia, 2020-2021
Authors: Álvarez-Díaz Diego A. , Muñoz Ana Luisa , Herrera-Sepúlveda María T. , Tavera-Rodríguez Pilar , Laiton-Donato Katherine , Franco-Muñoz Carlos , Ruiz-Moreno Héctor Alejandro , Pelaez-Carvajal Dioselina , Muñoz-Suarez Alejandra M. , Galindo Marisol , Reales-Gonzalez Jhonnatan , Catama Jenssy D. , De Arco Beatriz Helena , Cobos Tatiana , Arias-Ramirez Edgar J. , Mercado-Reyes Marcela 
Published: March 2022

AbstractBackgroundBy March 2022, around 34 million people in Colombia had received a complete scheme of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) including, mRNA-based vaccines, viral vectored coronavirus vaccines, or the inactivated whole virus vaccine. However, as several SARS-CoV-2 variants of concern (VOC) and interest (VOI) co-circulate in the country, determining the resistance level to vaccine-elicited neutralizing antibodies (nAbs) is useful to improve the efficacy of COVID-19 vaccination programs.MethodsMicroneutralization assays with the most prevalent SARS-CoV-2 lineages in Colombia during 2020-2021 were performed using serum samples from immunologically naïve individuals between 9 and 13 weeks after receiving complete regimens of CoronaVac, BNT162b2, ChAdOx1, or Ad26.COV2.S. The mean neutralization titer (MN50) was calculated by the Reed–Muench method and used to determine differences in vaccine-elicited nAbs against the SARS-CoV-2 lineages B.1.111, P.1 (Gamma), B.1.621 (Mu), and AY.25.1 (Delta).ResultsThe most administered vaccines in the country, BNT162b2 and CoronaVac, elicited significantly different nAb responses against Mu, as the GMTs were 75.7 and 5.9-fold lower relative to the control lineage (B.1.111), while for Delta were 15.8 and 1.1-fold lower, respectively. In contrast, nAb responses against Mu and Delta were comparable between ChAd0×1-s and Ad26.COV2.S as the GMTs remained around 5 to 7-fold lower relative to B.1.111.ConclusionsThe emergence of SARS-CoV-2 variants in Colombia with a significant capacity to escape from vaccine-elicited nAbs indicates that a booster dose is highly recommended. Furthermore, other non-pharmacological measures should be retained in the vaccinated population.
Deep kinetoplast genome analyses result in a novel molecular assay for detecting Trypanosoma brucei gambiense-specific minicircles
Authors: Geerts Manon , Chen Zihao , Bebronne Nicolas , Savill Nicholas J. , Schnaufer Achim , Büscher Philippe , Van Reet Nick , Van den Broeck Frederik 
Published: March 2022

ABSTRACTThe World Health Organization targeted Trypanosoma brucei gambiense (Tbg) human African trypanosomiasis for elimination of transmission by 2030. Sensitive molecular markers that specifically detect Tbg type 1 (Tbg1) parasites will be important tools to assist in reaching this goal. Here, we aim at improving molecular diagnosis of Tbg1 infections by targeting the abundant mitochondrial minicircles within the kinetoplast of Trypanosoma brucei parasites. Using Next-Generation Sequencing of total cellular DNA extracts, we assembled and annotated the kinetoplast genome and investigated minicircle sequence diversity in 38 animal- and human-infective trypanosome strains. Computational analyses recognized a total of 241 Minicircle Sequence Classes as Tbg1-specific, of which three were shared by the 18 studied Tbg1 strains. We then developed a novel multiplex quantitative PCR assay (g-qPCR3) targeting one Tbg1-specific minicircle and three Tbg1-specific or Trypanozoon-specific markers. Molecular analyses revealed that the minicircle-based assay is applicable on animals and is as specific as the TgsGP-based assay, the current golden standard for molecular detection of Tbg1. The median copy number of the targeted minicircle was equal to eight, suggesting that our minicircle-based assay may be used for the sensitive detection of Tbg1 parasites. Finally, annotation of the targeted minicircle sequence indicated that it encodes genes essential for the survival of the parasite, and will thus likely be preserved in natural Tbg1 populations. These results demonstrated that our minicircle-based assay is a promising new tool for reliable and sensitive detection of Tbg1 infections in humans and animals.
SARS-CoV-2 infection during the Omicron surge among patients receiving dialysis: the role of circulating receptor-binding domain antibodies and vaccine doses
Authors: Montez-Rath Maria E. , Garcia Pablo , Han Jialin , Cadden LinaCel , Hunsader Patti , Morgan Curt , Kerschmann Russell , Beyer Paul , Dittrich Mary , Block Geoffrey A , Anand Shuchi , Parsonnet Julie , Chertow Glenn M 
Published: March 2022

ABSTRACTBackgroundIt is unclear whether a third dose of mRNA platform vaccines, or antibody response to prior infection or vaccination confer protection from the Omicron variant among patients receiving dialysis.MethodsMonthly since February 2021, we tested plasma from 4,697 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. We assessed semiquantitative median IgG index values over time among patients vaccinated with at least one dose of the two mRNA vaccines. We ascertained documented COVID-19 diagnoses after December 25, 2021 and up to January 31, 2022. We estimated the relative risk for documented SARS-CoV-2 infection by vaccination status using a log-binomial model accounting for age, sex, and prior clinical COVID-19. Among patients with RBD IgG index value available during December 1-December 24, 2021, we also evaluated the association between the circulating RBD IgG titer and risk for Omicron variant SARS-CoV-2 infection.ResultsOf the 4,697 patients we followed with monthly RBD assays, 3576 are included in the main analysis cohort; among these, 852 (24%) were unvaccinated. Antibody response to third doses was robust (median peak index IgG value at assay limit of 150, equivalent to 3270 binding antibody units/mL). Between December 25-January 31, 2022, SARS-CoV-2 infection was documented 340 patients (7%), 115 (36%) of whom were hospitalized. The final doses of vaccines were given a median of 272 (25th, 75thpercentile, 245-303) days and 58 (25th, 75thpercentile, 51-95) days prior to infection for the 1-2 dose and 3 dose vaccine groups respectively. Relative risks for infection were higher among patients without vaccination (RR 2.1 [95%CI 1.6, 2.8]), and patients with 1-2 doses (RR 1.3 [95%CI 1.0, 1.8]), compared with patients with three doses of the mRNA vaccines. Relative risks for infection were higher among patients with RBD index values < 23 (506 BAU/mL), compared with RBD index value ≥ 23 (RR 2.4 [95%CI 1.9, 3.0]). The higher risk for infection among patients with RBD index values < 23 was present among patients who received three doses (RR 2.1 [95%CI 1.3, 3.4]).ConclusionsAmong patients receiving hemodialysis, patients unvaccinated, without a third mRNA vaccine dose, or those lacking robust circulating antibody response are at higher risk for Omicron variant infection. Low circulating antibodies could identify the subgroup needing intensified surveillance, prophylaxis or treatment in this patient population.
Molecular Crowding Facilitates Bundling of IMPDH Polymers and Cytoophidium Formation
Authors: Chang Chia-Chun , Peng Min , Zhong Jiale , Zhang Ziheng , Keppeke Gerson Dierley , Sung Li-Ying , Liu Ji-Long 
Published: March 2022

AbstractThe cytoophidium is a unique type of membraneless compartment comprising of filamentous protein polymers. Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step of de novo GTP biosynthesis and plays critical roles in active cell metabolism. However, the molecular regulation of cytoophidium formation is poorly understood. Here we show that human IMPDH2 polymers bundle up to form cytoophidium-like aggregates in vitro when macromolecular crowders are present. The self-association of IMPDH polymers is suggested to rely on electrostatic interactions. In cells, the increase of molecular crowding with hyperosmotic medium induces cytoophidia, while the decrease of that by the inhibition of RNA synthesis perturbs cytoophidium assembly. In addition to IMPDH, CTPS and PRPS cytoophidium could be also induced by hyperosmolality, suggesting a universal phenomenon of cytoophidium-forming proteins. Finally, our results indicate that the cytoophidium can prolong the half-life of IMPDH, which is proposed to be one of conserved functions of this subcellular compartment.