bluuebunny/crossref_metadata_2025_split huggingface dataset:
The scope and needs related to training, research, and mentorship among early-career addiction medicine professionals: an online global survey followed by expert group discussions
Authors: Bhad Roshan , Achab Sophia , Rafei Parnian , Kathiresan Preethy , Ardabili Hossein Mohaddes , Butner Jenna L. , Orsolini Laura , Melby Katrine , Farokhnia Mehdi , Narasimha Venkata Lakshmi , Ridley Kelly , Tolomeo Serenella , Kanabar Mitika , Matanje Beatrice , Grandinetti Paolo ,   ISAM NExT Consortium, Potenza Marc N. , Ekhtiari Hamed , Baldacchino Alexander 
Published: March 2022

AbstractAddiction medicine is a developing field, with many young professionals opting for a career in this area. However, globally, early-career professionals often face challenges in this field, such as lack of competency-based training due to a shortage of trainers, low availability of institutions with appropriate infrastructure, and limited resources for adequate training, particularly in developing countries. On the other hand, in developed countries, early career professionals may struggle with mentorship, limited job opportunities, and challenges with establishing a suitable research area.The International Society of Addiction Medicine (ISAM) New Professionals Exploration, Training & Education (NExT) committee, a global platform for early-career addiction medicine professionals (ECAMPs), conducted an online survey using a modified Delphi-based approach among ECAMPs across 56 countries to assess and understand the need and scope for standardized training, research opportunities, and mentorship. The survey was conducted in 2 phases. A total of 110 respondents participated in Phase I (online key informant survey), and 28 respondents participated in Phase II (online expert group discussions on the three themes identified in Phase I). Most participants agreed with the lack of standardized training, structured mentorship programmes, research funding, and research opportunities in addiction medicine for ECAMPs. There is a need for standardized training programmes, improving research opportunities, and effective mentorship programmes to promote the next generation of addiction medicine professionals and further development to the entire field. The efforts of ISAM-NExT are well-received and give a template of how this gap can be addressed.
A screening tool enhances home-based identification of adolescents (aged 10-14) living with HIV in Zambia and South Africa: HPTN 071 (PopART) Study
Authors: Chaila Mwate Joseph , Macleod David , Vermund Sten H , Thornicroft Moomba Mbolongwe , Mbewe Madalitso , Mubekapi-Musadaidzwa Constance , Harper Abigail , Schaap Albertus , Floyd Sian , Hoddinott Graeme , Hayes Richard , Fidler Sarah , Ayles Helen , Shanaube Kwame 
Published: March 2022

ABSTRACTIntroductionThe HPTN071 (PopART) for Youth (P-ART-Y) study evaluated the acceptability and uptake of a community-level combination HIV prevention package including universal testing and treatment (UTT) among young people in Zambia and South Africa (SA). We determined whether a four-question primary care level screening tool, validated for use in clinical settings, could enhance community (door-to-door) identification of undiagnosed HIV-positive younger adolescents (aged 10-14) who are frequently left out of HIV interventions.MethodCommunity HIV-care Providers (CHiPs) contacted and consented adolescents in their homes and offered them participation in the PopART intervention. CHiPs used a four question-screening tool, which included: history of hospital admission; recurring skin problems; poor health in last 3 months; and death of at least one parent. A “yes” response to one or more questions was classified as being “at risk” of being HIV-positive. The data were captured through an electronic data capturing device from August 2016 to December 2017. Proportions of adolescents who were deemed “at risk” were calculated and the association of screening “at risk” with age, sex and community was tested using a chi-squared test. The adjusted odds ratio (OR) comparing the odds of testing HIV-positive if “at risk” with the odds of testing positive if “not at risk” was estimated using logistic regression.ResultsIn our 14 study sites, 33,283 adolescents aged 10-14 in Zambia and 8,610 in SA participated in the study. About 1.3% (427/33,710) and 1.2% (106/8,610) self-reported to be HIV positive. Excluding the self-reported HIV-positive, we classified 11.3% (3,746/33,283) of adolescents in Zambia and 17.5% (1,491/8,504) in SA as “at risk”. In Zambia and SA, the “at risk” adolescents were 4.6 and nearly 16.7 times more likely to test HIV-positive compared to the “not at risk”, respectively (both p<0.001). Using the screening tool, one-third of HIV-positive adolescents could be diagnosed using just a tenth of the number of HIV tests compared to universal testing.ConclusionThe screening tool may be of some value where UTT is not possible and limited resources must be prioritised toward adolescents who are more likely to be living with HIV. Further, the tool is of greater value in settings where there are more adolescents living with HIV who are undiagnosed. However, given our goal is to identify and treat all ALHIV, as well as link all HIV uninfected young people to prevention services, this screening tool should not be a substitute for UTT in community settings.Clinical Trial NumberNCT01900977
Vimentin intermediate filaments organize organellar architecture in response to ER stress
Authors: Cremer Tom , Voortman Lenard M. , Bos Erik , van Elsland Daphne M. , ter Haar Laurens R. , Koning Roman I. , Berlin Ilana , Neefjes Jacques 
Published: March 2022

AbstractCompartmentalization of organelles in space and time affects their functional state and enables higher order regulation of essential cellular processes. How organellar residence is maintained in a defined area of the cell remains poorly understood. In this study, we uncover a new role for intermediate filaments in the maintenance of organellar architecture and dynamics, which is executed through a functional connection between Vimentin and the ER-embedded ubiquitin ligase ring finger protein 26 (RNF26). While the ubiquitin ligase function of RNF26 promotes perinuclear positioning of endolysosomes, its catalytically inactive mutant I382R preferentially binds Vimentin through the RNF26 C-terminal tail. Loss of either RNF26 or Vimentin redistributes endolysosomes throughout the cytosol and mobilizes ER membranes from the perinuclear ER towards the periphery. Furthermore, RNF26 and Vimentin control changes in ER morphology and organelle compartmentalization during ER stress. Collectively, we define a new function for Vimentin-containing intermediate filaments as anchors of a dynamic interplay between the ER and endosomes, critical to the integrity of the perinuclear ER and corresponding perinuclear endosomal cloud during homeostatic and stress conditions.SynopsisThe perinuclear area hosts a wide variety of cellular organelles, and their interaction with the ER governs essential cellular processes. To spatiotemporally organize endosomes and ER in the perinuclear region, the ER-embedded E3 ubiquitin ligase RNF26 interacts with Vimentin to physically link the perinuclear ER membrane with the intermediate filament cytoskeleton. As a result, Vimentin ensures perinuclear RNF26 retention, which in turn controls the perinuclear location of ER membranes and endosomes, which can be affected during stressed conditions.Vimentin interacts with inactive RNF26 in the ER membraneRNF26 by virtue of the Vimentin interaction controls perinuclear organization of ER membranes and the endosomal systemVimentin immobilizes ER membranes in the perinuclear areaVimentin and RNF26 compartmentalize organelles in the perinuclear region during ER stressWe define a new function of Vimentin intermediate filaments in the control of the perinuclear endosomal and ER organization
Patient-derived parathyroid organoids as tracer and drug-screening application model
Authors: Noltes Milou E. , Sondorp Luc H.J. , Kracht Laura , Antunes Inês F. , Wardenaar René , Kelder Wendy , Kemper Annelies , Szymanski Wiktor , Zandee Wouter T. , Jansen Liesbeth , Brouwers Adrienne H. , Coppes Robert P. , Kruijff Schelto 
Published: March 2022

AbstractParathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The understanding of parathyroid hyperplastic growth and the development of parathyroid-targeted treatment and imaging tracers could benefit from in vitro models. Therefore, we aim to establish stem cell-derived, three-dimensional organoids representing human parathyroid tissue in vitro. Patient-derived hyperplastic parathyroid tissue was dispersed and parathyroid organoids (PTO) were cultured and characterized. PTO-derived cells were shown to exhibit in vitro self-renewal over several passages, indicative of the presence of putative stem cells. Immunofluorescence and RNA-sequencing confirm that PTO phenocopy hyperplastic parathyroid tissue. Exposure of PTO to increasing calcium concentrations and to PTH-lowering drugs resulted in a significantly reduced PTH excretion. Next to this, the PTO showed specific binding of 11C-methionine to the targeted receptor. Additionally, when organoids were incubated with 99mTc-sestamibi, we observed a higher uptake in PTOs from patients with a 99mTc-sestamibi positive scan compared to patients with a negative scan. These data show functionality of PTOs resembling the parathyroid. In conclusion, we present a patient-derived PTO culture, that recapitulates the originating tissue on gene and protein expression and functionality. This PTO model paves the way for future physiology studies and therapeutic target and tracer discovery.
FKS1 is required for Cryptococcus neoformans fitness in vivo: application of copper-regulated gene expression to mouse models of cryptococcosis
Authors: Beattie Sarah R. , Jezewski Andrew J. , Ristow Laura C. , Wellington Melanie , Krysan Damian J. 
Published: March 2022

AbstractThere is an urgent need for new antifungals to treat cryptococcal meningoencephalitis, a leading cause of mortality in people living with HIV/AIDS. An important aspect of antifungal drug development is the validation of targets to determine whether they are required for the survival of the organism in animal models of disease. In Cryptococcus neoformans, a copper-regulated promoter (pCTR4-2) has been used to modulate gene expression in vivo previously. The premise for these experiments is that copper concentrations vary depending on the host niche. Here, we directly test this premise and confirm that the expression of CTR4, the promoter used to regulate gene expression, is much lower in the mouse lung compared to the brain. To further explore this approach, we applied to the gene encoding 1,3-β-glucan synthase, FKS1. In vitro, reduced expression of FKS1 has little effect on growth but does activate the cell wall integrity stress response and increase susceptibility to caspofungin, a direct inhibitor of Fks1. These data suggest that compensatory pathways that reduce C. neoformans resistance do so through post-transcriptional effects. In vivo, however, a less pronounced reduction in FKS1 expression leads to a much more significant reduction in lung fungal burden (~1 log10 CFU), indicating that the compensatory responses to a reduction in FKS1 expression are not as effective in vivo as they are in vitro. In summary, use of copper-regulated expression of putative drug targets in vitro and in vivo can provide insights into the biological consequences of reduced activity of the target during infection.ImportanceConditional expression systems are widely used to genetically validate antifungal drug targets in mouse models of infection. Copper-regulated expression using the promoter of the CTR4 gene has been sporadically used for this purpose in C. neoformans. Here, we show that CTR4 expression is low in the lung and high in the brain, establishing the basic premise behind this approach. We applied it to the study of FKS1, the gene encoding for the target of the echinocandin class of 1,3-β-glucan synthase inhibitors. Our in vitro and in vivo studies indicate that C. neoformans tolerates extremely low levels of FKS1 expression. This observation provides a potential explanation for the poor activity of 1,3-β-glucan synthase inhibitors toward C. neoformans.
Effects of mucin and DNA concentrations in airway mucus on Pseudomonas aeruginosa biofilm recalcitrance
Authors: Rouillard Kaitlyn R. , Kissner William J. , Markovetz Matthew R. , Hill David B. 
Published: March 2022

AbstractThe pathological properties of airway mucus in cystic fibrosis (CF) are dictated by mucus concentration and composition, with mucins and DNA being responsible for mucus viscoelastic properties. As CF pulmonary disease progresses, the concentrations of mucins and DNA increase and are associated with increased mucus viscoelasticity and decreased transport. Similarly, the biophysical properties of bacterial biofilms are heavily influenced by the composition of their extracellular polymeric substances (EPS). While the roles of polymer concentration and composition in mucus and biofilm mechanical properties have been evaluated independently, the relationship between mucus concentration and composition and the biophysical properties of biofilms grown therein remains unknown. Pseudomonas aeruginosa biofilms were grown in airway mucus as a function of overall concentration and DNA concentration to mimic healthy and CF physiology and biophysical properties were evaluated with macro- and microrheology. Biofilms were also characterized after exposure to DNase or DTT to examine the effects of DNA and mucin degradation, respectively. Identifying critical targets in biofilms for disrupting mechanical stability in highly concentrated mucus may lead to the development of efficacious biofilm therapies and ultimately improve CF patient outcomes. Overall mucus concentration was the predominant contributor to biofilm viscoelasticity and both DNA degradation and mucin reduction resulted in compromised biofilm mechanical strength.
Stairway visual contrast enhancement to reduce fall-related events
Authors: Harper Sara A. , Long Christopher , Corbridge Samantha , Barrett Tyson S. , Braeger Alex , Zollinger Brevin J. , Hale Amy E. , Brown Chayston B. , Harrison Kenneth , Poulsen Shandon L. , Boman Travis , Dakin Christopher J. 
Published: March 2022

ABSTRACTFalls on stairs occur frequently and pose a significant health and financial risk. Laboratory research has found that fall frequency can be reduced through contrast enhancement of the stairs by applying vinyl striping to the first and last steps’ faces, and all the steps’ top edges. Here we sought to determine if such step contrast enhancement can reduce the probability of fall-related events such as loss of balance, slips, trips, and falls in public university staircases. Cameras were used to capture stair users’ ascent and descent on contrast enhanced (‘striped’) and control stairways. Observed age group, observed gender, traverse direction (ascent, descent), fall-related events, and walking speed (m/s) were recorded. Fall-related events were reduced for the striped stairway compared to the control stairway (odds ratio = 2.87, average marginal effect = 0.002, p = .023) when controlling for observed gender, age category, and traverse direction. These results suggest contrast enhancement of first and last steps’ face and all steps’ edges may reduce fall- related events in public settings. Adding contrast enhancement to public stairways is a simple and cost-effective way to reduce the loss of balance, slips, and trips that could lead to catastrophic falls on stairs as well as the health and financial burden associated with such falls.PRECISContrast enhancement of stairway features may be a simple and cost-effective way to reduce falls on stairs. We show that monochrome striping on the first and last steps’ faces and black stripes on steps’ top edges reduce the probability of fall-related events in public stairways.
The effect of galvanic vestibular stimulation on postural balance in Parkinson’s Disease: A systematic review and meta-analysis
Authors: Mahmud Mohammad , Hadi Zaeem , Prendergast Mabel , Ciocca Matteo , Saad Abdel Rahman , Pondeca Yuscah , Tai Yen , Scott Gregory , Seemungal Barry M 
Published: March 2022

AbstractPeople with Parkinson’s disease (PD) experience postural imbalance, leading to considerably increased risk of falls. Galvanic Vestibular Stimulation (GVS) is postulated to modulate postural balance in humans and improve it in PD. This systematic review and meta-analysis investigate the effects of GVS on postural balance in PD.Six separate databases and research registers were searched for cross-over design trials that evaluated the effects of GVS on postural balance in PD. We used standardized mean difference (Hedges’ g) as a measure of effect size in all studies.We screened 223 studies, evaluated 14, of which five qualified for the meta-analysis. Among n = 40 patients in five studies (range n= 5 to 13), using a fixed effects model we found an effect size estimate of g = 0.43 (p < 0.001, 95% CI [0.29,0.57]). However, the test for residual heterogeneity was significant (p < 0.001), thus we used a random effects model and found a pooled effect size estimate of 0.62 (p > 0.05, 95% CI [– 0.17, 1.41], I2 = 96.21%). Egger’s test was not significant and thus trim and funnel plot indicated no bias. To reduce heterogeneity, we performed sensitivity analysis and by removing one outlier study (n = 7 patients), we found an effect size estimate of 0.16 (p < 0.05, 95% CI [0.01, 0.31], I2 = 0%).Our meta-analysis found GVS has a favourable effect on postural balance in PD patients, but due to limited literature and inconsistent methodologies, this favourable effect must be interpreted with caution.
THE IMPACT OF ROUTINES ON EMOTIONAL AND BEHAVIOURAL DIFFICULTIES IN CHILDREN AND ON PARENTAL ANXIETY DURING COVID-19
Authors: Lees Vera , Hay Rosie , Bould Helen , Kwong Alex S. F. , Major-Smith Daniel , Kounali Daphne , Pearson Rebecca M 
Published: March 2022

Aims and hypothesisWe hypothesised that there would be an association between maintaining a routine during lockdown and both lower emotional and behavioural difficulties in children and lower parental anxiety. We also hypothesised that children of ‘keyworker’ parents would have fewer emotional and behavioural symptoms due to having maintained more normal routines.BackgroundThe Covid-19 pandemic and related public health measures have impacted on mental health of children.MethodsWe used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to explore associations between maintaining a routine, and emotional and behavioural difficulties in children, using linear regression models. We included measures of parental anxiety. We separately explored associations with having a keyworker parent. We used the Carey Infant Temperament Questionnaire and the Revised Rutter Parent Scale for Preschool Children to establish levels of emotional and behavioural difficulties.Results289 parents completed questionnaires about their 411 children. Keeping a routine was associated with emotional and behavioural difficulty scores 5.0 points lower (95% CI -10.0 to - 0.1), p=0.045 than not keeping a routine. Parents who reported keeping a routine had anxiety scores 4.3 points lower (95% CI -7.5 to -1.1), p=0.009 than those who did not. Children of keyworkers tended to have lower emotional and behavioural difficulty scores (−3.1 (95%CI -6.26 to 0.08), p=0.056) than children of non-keyworkers. All models were adjusted for relevant potential confounders.ConclusionMaintaining a routine may be beneficial for both child emotional wellbeing and parental anxiety, although it is also possible that lower parental anxiety levels made maintaining a routine easier. Being the child of a keyworker parent during lockdown may have been protective for child emotional wellbeing.
Large-bodied ornithomimosaurs inhabited Appalachia during the Late Cretaceous of North America
Authors: Chinzorig Tsogtbaatar , Cullen Thomas , Phillips George , Rolke Richard , Zanno Lindsay E. 
Published: March 2022

AbstractReconstructing the evolution, diversity, and paleobiogeography of North America’s Late Cretaceous dinosaur assemblages requires spatiotemporally contiguous data; however, there remains a spatial and temporal disparity in dinosaur data on the continent. The rarity of vertebrate-bearing sedimentary deposits representing Turonian–Santonian ecosystems, and the relatively sparse record of dinosaurs from the eastern portion of the continent, present persistent challenges for studies of North American dinosaur evolution. Here we describe an assemblage of ornithomimosaurian materials from the Santonian Eutaw Formation of Mississippi. Morphological data coupled with osteohistological growth markers suggest the presence of two taxa of different body sizes, including one of the largest ornithomimosaurians known worldwide. The regression predicts a femoral circumference and a body mass of the Eutaw individuals similar to or greater than that of large-bodied ornithomimosaurs,Beishanlong grandisandGallimimus bullatus. The paleohistology of MMNS VP-6332 demonstrates that the individual was at least 11 years of age (similar toB. grandis[∼375 kg, 13–14 years old at death]). Additional pedal elements share some intriguing features with ornithomimosaurs yet suggest a larger-body size closer toDeinocheirus mirificus. The presence of a large-bodied ornithomimosaur in this region during this time is consistent with the relatively recent discoveries of early-diverging, large-bodied ornithomimosaurs from mid-Cretaceous strata of Laurasia (Arkansaurus fridayiandB. grandis). The smaller Eutaw taxon is represented by a tibia preserving seven growth cycles, with osteohistological indicators of decreasing growth, yet belongs to an individual with near reaching somatic maturity of the larger taxon, suggesting the co-existence of medium- and large-bodied ornithomimosaur taxa during the Late Cretaceous Santonian of North America. The Eutaw ornithomimosaur materials provide key information on the diversity and distribution of North American ornithomimosaurs and Appalachian dinosaurs and fit with broader evidence of multiple cohabiting species of ornithomimosaurian dinosaurs in Late Cretaceous ecosystems of Laurasia.
Elucidating the role of c-di-AMP in Mycobacterium smegmatis: phenotypic characterization and functional analysis
Authors: Chaudhary Vikas , Pal Aditya , Singla Mamta , Ghosh Anirban 
Published: March 2022

AbstractCyclic-di-AMP (c-di-AMP) is a newly discovered secondary messenger molecule that plays a critical role in monitoring several important cellular processes, especially in several Gram-positive bacteria signal transduction pathways. In this study, we seek to unravel the physiological significance of the molecule c-di-AMP in Mycobacterium smegmatis under different conditions, using strains with altered c-di-AMP levels: c-di-AMP null mutant (ΔdisA) and a c-di-AMP over-expression mutant (Δpde). Our thorough analysis of the mutants revealed that the intracellular concentration of c-di-AMP could determine many basic phenotypes such as colony architecture, cell shape, cell size, membrane permeability etc. Additionally, it was shown to play a significant role in multiple stress adaptation pathways in the case of different DNA and membrane stresses. Our study also revealed how the biofilm phenotype of M. smegmatis cells are dependent on intracellular c-di-AMP concentration. Next, we checked how c-di-AMP contributes to antibiotic tolerance characteristics of M. smegmatis, which was followed by a detailed transcriptome profile analysis to reveal key genes and pathways regulated by c-di-AMP in mycobacteria.