bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigated ultrasound bronchoscopy with integrated positron emission tomography - A human feasibility study
Authors: Kildahl-Andersen Arne , Hofstad Erlend Fagertun , Solberg Ole-Vegard , Sorger Hanne , Amundsen Tore , Langø Thomas , Leira Håkon Olav 
Published: June 2024

AbstractBackground and objectivePatients suspected to have lung cancer, undergo endobronchial ultrasound bronchoscopy (EBUS) for the purpose of diagnosis and staging. For presumptive curable patients, the EBUS bronchoscopy is planned based on images and data from computed tomography (CT) images and positron emission tomography (PET). Our study aimed to evaluate the feasibility of a multimodal electromagnetic navigation platform for EBUS bronchoscopy, integrating ultrasound and segmented CT, and PET scan imaging data.MethodsThe proof-of-concept study included patients with suspected lung cancer and pathological mediastinal/hilar lymph nodes identified on both CT and PET scans. Images obtained from these two modalities were segmented to delineate target lymph nodes and then incorporated into the CustusX navigation platform. The EBUS bronchoscope was equipped with a sensor, calibrated, and affixed to a 3D printed click-on device positioned at the bronchoscope’s tip. Navigation accuracy was measured postoperatively using ultrasound recordings.ResultsThe study enrolled three patients, all presenting with suspected mediastinal lymph node metastasis (N1-3). All PET-positive lymph nodes were displayed in the navigation platform during the EBUS procedures. In total, five distinct lymph nodes were sampled, yielding malignant cells from three nodes and lymphocytes from the remaining two. The median accuracy of the navigation system was 7.7 mm.ConclusionOur study introduces a feasible multimodal electromagnetic navigation platform that combines intraoperative ultrasound with preoperative segmented CT and PET imaging data for EBUS lymph node staging examinations. This innovative approach holds promise for enhancing the accuracy and effectiveness of EBUS procedures.
Depressive, anxiety and stress symptoms among university students from Bogotá, Colombia and electronic nicotine delivery systems (ENDS) use: Findings from a prevalence survey 2021
Authors: García Durán María Camila , Botero Ruge María Catalina , Perdomo Patiño Gustavo , Pulido Álvarez Adriana , Lüchau Manuela , Borrero Elizabeth , Moreno Sergio 
Published: June 2024

AbstractThe use of electronic nicotine delivery systems (ENDS) has increased in recent years, particularly among young people. The association between mental health disorders and conventional cigarettes is well established. However, information on ENDS use and mental health is still emerging. This study i) determines the frequency of depression, anxiety and stress symptoms among university students in Bogotá, Colombia, ii) examines the association between sociodemographic variables and mental health symptoms, and iii) analyses whether there is an association between tobacco and/or ENDS use and depression, anxiety and/or stress. The study is cross-sectional, analytical, retrospective and based on a multistage random sample. 3850 students from 21 universities completed an online survey and were included as participants. We assessed demographic variables, tobacco use, ENDS use and symptoms of depression, anxiety and stress. 667 participants from our sample had a previous diagnosis of a mental disorder, and the most common diagnoses were any type of anxiety disorder (7.27%) or depressive disorder (6.70%). Ever use of conventional cigarettes was 63.71% and ever use of ENDS was 31%. More than 65% of the participants had mild symptoms of depression, anxiety and stress. However, between 16.4% and 19.5% of participants reported severe or very severe symptoms of these three diagnoses. Severe or very severe symptoms were more likely to be reported by women, public university students and those from higher socio-economic backgrounds. Those who reported having tried conventional cigarettes or ENDS had more severe or extremely severe symptoms than those who had never tried them. Multivariate analysis using ordinal logistic regression showed that depression, anxiety and stress levels were more severe in participants who had tried ENDS. In addition, having nuclear family members, family members or close friends with a history of nicotine use was positively associated with higher levels of depression, anxiety and stress.
Leptin augmented model to include the role of obesity in insulin-glucose regulatory system for T2DM subjects
Authors: Aravindakshan Manoja Rajalakshmi , Ghosh Devleena , Mandal Chittaranjan , Sarkar Jit , Maity Sujay K , Chakrabarti Partha 
Published: June 2024

AbstractLeptin is a fat cell-derived hormone involved in satiety and body weight regulation. It also plays a critical regulatory role in the insulin-glucose regulatory system by modulating glucose metabolism and energy homeostasis. However, existing insulin-glucose models often fail to consider the impact of body weight indicators mainly body mass index (BMI) and plasma leptin. To address this limitation, we propose augmenting the ordinary differential equations (ODE) of the Oral Minimal Model (OMM) with an additional equation, incorporating leptin as well as supplementary terms and parameters. By estimating the model parameters, the model behaviour is aligned with the observed data of glucose, insulin and leptin for individuals with type 2 diabetes mellitus (T2DM). Based on model behaviour, revised indices formulated from Oral Glucose Tolerance Test (OGTT) data by including BMI and fasting leptin values are found to have a better correlation with existing indices. Additionally, parameter sensitivity analysis is performed to investigate the influence of the model parameters on the observed variables. Validation of the augmented model with clinical data (without leptin) demonstrates a superior fit to glucose and insulin data compared to the base model. This model emphasizes the intricate associations between leptin, glucose, and insulin concentrations with a potential for developing targeted interventions and therapies for T2DM. Notably, this manuscript introduces the first ODE-based model that incorporates leptin and BMI in the insulin-glucose pathway.
Performance and validation of a digital memory test across the Alzheimer’s Disease continuum
Authors: Toniolo Sofia , Attaallah Bahaaeddin , Maio Maria Raquel , Tabi Younes Adam , Slavkova Elitsa , Klar Verena Svenja , Saleh Youssuf , Idris Mohamad Imran , Turner Vicky , Preul Christoph , Srowig Annie , Butler Christopher , Thompson Sian , Manohar Sanjay G. , Finke Kathrin , Husain Masud 
Published: June 2024

AbstractDigital cognitive testing using online platforms has emerged as a potentially transformative tool in clinical neuroscience. In theory, it could provide a powerful means of screening for and tracking cognitive performance in people at risk of developing conditions such as Alzheimer’s Disease (AD). Here we investigate whether digital metrics derived from a tablet-based short-term memory task – “What was where?” Oxford Memory Task – were able to clinically stratify patients at different points within the AD continuum and to track disease progression over time. Performance of these metrics to traditional neuropsychological pen-and-paper screening tests of cognition was also analyzed. A total of 325 people participated in this study: 49 patients with subjective cognitive impairment (SCI), 57 with mild cognitive impairment (MCI), 63 with AD dementia and 156 elderly healthy controls (EHC). Most digital metrics were able to discriminate between healthy controls and patients with MCI and between MCI and AD patients. Some, including Absolute Localization Error, also differed significantly between patients with SCI and MCI. Identification accuracy was the best predictor of hippocampal atrophy, performing as well as standard screening neuropsychological tests. A linear support vector model combining digital metrics achieved high accuracy and performed at par with standard testing in discriminating between EHC and SCI (AUC 0.82) and between SCI and MCI (AUC 0.92). Memory imprecision was able to predict cognitive decline on standard cognitive tests over one year. Overall, these findings show how it might be possible to use a digital memory test in clinics and clinical trial contexts to stratify and track performance across the Alzheimer’s disease continuum.
Differences in neuromusculoskeletal injury and disability rates between US Navy aircraft carrier and amphibious assault ships
Authors: Fraser John J. , Halfpap Joshua , Rosenthal Michael 
Published: June 2024

Structured SummaryIntroductionMusculoskeletal injuries (MSKI) are the most common clinical condition in the military that affect medical readiness. Evaluation of MSKI burden and the effects of these injuries on readiness in large deck Navy ships is warranted.Materials and MethodsA retrospective cohort study assessing population-level MSKI rates, limited duty (LIMDU), and long-term disability episode counts of all Sailors assigned to US Navy Aircraft Carriers (CVNs) and Amphibious Assault Ships (LHA/LHD) from November 2016 to February 2023 were extracted from the Musculoskeletal Naval Epidemiological Surveillance Tool. A negative binomial regression and general additive (gaussian) models evaluated the association of ship platform, deployment status, days underway, and sex on MSKI rates and the proportion of cases that resulted in LIMDU, returned-to-duty following LIMDU, or progressed to long-term disability.ResultsSailors attached to CVNs contributed a mean 17893.8±23280.6 person-months, with those attached to LHA/LHDs contributing an average 5981.8±8432.7 person-months. Aboard CVNs, MSKI occurred at a rate of 0.30±0.16/1000 person-months while deployed and 0.64±0.31/1000 person-months in homeport. Aboard LHA/LHDs, Sailors incurred MSKI at a rate of 0.59±0.58/1000 person-months while on deployment and 1.24±0.68/1000 person-months in homeport. Among Sailors aboard CVNs, LIMDU occurred in 7.95±7.75% of MSKI cases while deployed and 5.13±5.26% while in homeport. Aboard LHA/LHDs, 8.57±13.42% of MSKI cases were placed on LIMDU while deployed and 4.95±5.27% while in homeport. In the multivariable assessment of LIMDU, being deployed underway was a significant factor (B=3.62 p=.03, variance explained=3.86%). Sailors that were female and served aboard LHA/LHDs returned to full duty at a significantly greater frequency compared to their male counterparts and Sailors serving aboard CVNs. None of the independent variables evaluated were associated with long-term disability.ConclusionThe findings in the current study demonstrate the substantial burden of MSKI aboard large deck ships, both in homeport and while deployed. Inclusion of a PT aboard LHA/LHDs, like the CVN, may help to prevent and mitigate the effects of MSKI through early access to specialized care and integral injury prevention and performance optimization methods.
Knock-down of genes essential for homoacetogenic growth using sugar inducible promoters in the thermophileThermoanaerobacter kivui
Authors: Zeldes Benjamin , Mittelstedt Sabina , Baum Christoph , Shakirova Adilia , Poehlein Anja , Daniel Rolf , Müller Volker , Basen Mirko 
Published: June 2024

AbstractGiven recent interest in hydrogen (H2) as a medium for storing and transporting renewable energy, the ability of acetogenic bacteria to use H2to directly fix carbon dioxide (CO2) shows great promise. Thermophilic bacteria have long been of interest as industrial strains due to their resistance to contamination.Thermoanaerobacter kivuiis among the most thermophilic acetogens. It can be genetically manipulated, but as yet only in an all-or-nothing manner, either complete gene knockouts or very strong constitutive promoters leading to protein overexpression. The sugar inducible promoters characterized here provide the finer control necessary to close remaining gaps in understanding ofT. kivui’s energy metabolism and for controlled expression of recombinant genes of industrial relevance.Acetogenic bacteria are capable of growing on mixtures of the gasses H2, CO2, and CO using the Wood-Ljungdahl pathway, the most energy efficient CO2fixation pathway.T. kivuiis a thermophilic (Topt= 66°C) acetogen also capable of growth on sugars including glucose, mannitol, and fructose. RNA-sequencing indicated an operon of phosphotransferase import genes up-regulated on mannitol, and growth on a mixture of glucose and mannitol was diauxic. Given this evidence for sugar responsive transcriptional regulation, the promoter region from the mannitol operon, and a similar operon involved in fructose uptake were used to control expression of a thermostable β-galactosidase reporter gene. Both promoters resulted in higher reporter gene activity when grown on their inducing sugar relative to glucose. The inducible promoters were used to create “knock-down” mutants of the proton-pumping Ech1 hydrogenase. Ech1 is believed to be essential because repeated attempts to knock-out the gene operon have failed. The resulting sugar-inducible Ech1 expression strains grew better on their inducing sugar than on glucose. The mannitol inducible promoter was also used to control expression of an essential gene of the Wood-Ljungdahl pathway, formyl-THF synthetase (fhs), involved in consuming the metabolic intermediate formate. Whenfhsrepressed by growth on glucose significantly more formate accumulated in the culture medium than during growth on mannitol, clear evidence of a metabolic bottleneck under the knock-down condition. The promoters characterized here provide finer control of recombinant or native gene expression inT. kivui, while the thermostable reporter gene allows for rapid characterization of new promoters.
TENT-5 regulates the expression of male-specific genes inCaenorhabditis elegans
Authors: Mackiewicz Zuzanna , Liudkovska Vladyslava , Dziembowski Andrzej 
Published: June 2024

AbstractPolyadenylation is an important post-transcriptional process that governs mRNA stability and expression. Advancements in direct RNA sequencing in recent years have clarified many aspects of this intricate regulation, revealing the influence of various factors. Here, we used Nanopore Direct RNA Sequencing to investigate the association between genome-wide mRNA poly(A) tail profiles and sexual dimorphism inCaenorhabditis elegans. Our results demonstrate sex-dependent differences in both gene expression and poly(A) tail metabolism. Notably, we discovered that cytoplasmic poly(A) polymerase TENT-5 regulates multiple male-specific transcripts, predominantly encoding putative seminal fluid components with predicted extracellular localization. TENT-5 expression in male-specific tissues, such as seminal vesicle and vas deference, corroborates its functional significance. Intriguingly, despite extensive TENT-5-mediated polyadenylation of male-specific transcripts, males devoid of TENT-5 show no abnormalities in mating behavior, sperm morphology, or fertility. Our findings suggest that TENT-5 plays a role in regulating sex-related processes in males, although the physiological consequences remain to be fully elucidated.
Increase of permissive secondary antiviral mutations in the evolution of A(H1N1)pdm09 influenza virus neuraminidases
Authors: Duwe Susanne , Milde Jeanette , Heider Alla , Wedde Marianne , Schweiger Brunhilde , Dürrwald Ralf 
Published: June 2024

AbstractBackgroundThe unexpected emergence of oseltamivir-resistant A(H1N1) viruses in 2008 was facilitated in part by the establishment of permissive secondary neuraminidase (NA) substitutions that compensated for the fitness loss due to the NA-H275Y resistance substitution. These viruses were replaced in 2009 by oseltamivir-susceptible A(H1N1)pdm09 influenza viruses.MethodsGenetic analysis and screening A(H1N1)pdm09 viruses circulating in Germany between 2009 and 2024 were conducted to identify any potentially permissive or resistance-associated NA substitutions. Selected viruses were then subjected to further characterization in vitro.ResultsIn the NA gene of circulating A(H1N1)pdm09 viruses, two secondary permissive substitutions, NA-V241I and NA-N369K, were identified. These substitutions demonstrated a stable lineage in phylogenetic analysis since the 2010-2011 influenza season. The data indicates a slight increase in viral NA bearing two additional potentially permissive substitutions, NA-I223V and NA-S247N, in the 2023-2024 season, that both result in a slight reduction in susceptibility to NA inhibitors.ConclusionsThe accumulation of secondary permissive substitutions in the NA of A(H1N1)pdm09 viruses increases the probability of the emergence of antiviral-resistant viruses. Therefore, it is crucial to closely monitor the evolution of circulating influenza viruses and to develop additional antiviral drugs against different target proteins.
Changes in urinary proteome in healthy individuals taking multi-vitamin/mineral supplements
Authors: Shen Ziyun , Yang Minhui , Wang Haitong , Liu Yuqing , Gao Youhe 
Published: June 2024

AbstractMultivitamin/mineral supplements are widely used in many populations. Urine proteome has not been used to investigate its overall effects on healthy individuals. In this study, the urine proteome changed after taking compound nutrient supplements for 2 weeks and 4 weeks, and the differential proteins and their enriched pathways may be associated with nutrient supplementation. We noted that after taking the supplements for 2 weeks, the amount of erythropoietin receptor in urine was average 449 times higher than before, with four out of nine people experiencing changes from 0 to 14635, 11851, 11181, and 5930. The results of this study revealed that the urine proteome can provide new clues about the relatively short-term health effects of the supplements. It may help optimize guidelines and recommendations for the use of supplements.
Telomeric lncRNA TERRA localizes to stress granules in human ALT cells
Authors: Larini Luca , Goretti Elena , Zulian Eleonora , Busarello Emma , Marino Stefano Maria , Hajikazemi Mona , Paeschke Katrin , Tebaldi Toma , Cusanelli Emilio , Jurikova Katarina 
Published: June 2024

AbstractTERRA, the lncRNA derived from the ends of chromosomes, has a number of well-described nuclear roles including telomere maintenance and homeostasis. A growing body of evidence now points at its role in human cells outside of nucleus—it has been found to be a component of extracellular vesicles, a player in inflammation signalling and its capacity for translation has been shown. In this work, using a combination of sensitive microscopy methods, cellular fractionation, proteomics and transcriptome analysis, we demonstrate directly for the first time that TERRA is present in the cytoplasm of human telomerase-negative cells, especially upon various stress stimuli, and that it associates with stress granules. Confirming the presence of TERRA in the cytoplasm, our work fills an important gap in the field, and contributes to the discussion about the role of TERRA as a transcript involved in nucleo-cytoplasmic stress communication.
Functional segregation of conversational production and comprehension when using word predictability
Authors: Arvidsson Caroline , Sundström Johanna , Uddén Julia 
Published: June 2024

ABSTRACTThe extent to which the language production and comprehension systems overlap remains debated. We address this debate using a dataset where participants engaged in unscripted conversations, while scanned with fMRI. Word predictability was hypothesized to rely on different processes, depending on whether the word was uttered or heard. We employed the information-theoretic measure of surprisal (the negative log probability of a word occurring, given the preceding context) as a parametric modulator, controlling for the word’s overall frequency. The results for production surprisal revealed activation in the left superior and inferior frontal gyri and motor areas. A large bilateral cluster in the posterior part of the medial prefrontal cortex extended from the supplementary motor area to the anterior cingulate cortex. The results for comprehension surprisal replicated findings from non-conversational contexts, showing involvement of the bilateral superior temporal gyrus/sulcus, presumably supporting bottom-up processes for prediction error detection. Importantly, no overlap in the neural infrastructure of production and comprehension was observed, suggesting that word predictability processes in production and comprehension differ. We suggest that while the comprehension system handles prediction errors, the production system minimizes these errors through adaptation, all to achieve successful communication.
The HUSH epigenetic repressor complex silences PML nuclear bodies-associated HSV-1 quiescent genomes
Authors: Roubille Simon , Escure Tristan , Juillard Franceline , Corpet Armelle , Néplaz Rémi , Binda Olivier , Seurre Coline , Gonin Mathilde , Bloor Stuart , Cohen Camille , Texier Pascale , Haigh Oscar , Pascual Olivier , Ganor Yonatan , Magdinier Frédérique , Labetoulle Marc , Lehner Paul J. , Lomonte Patrick 
Published: June 2024

AbstractHerpes simplex virus 1 (HSV-1) latently infected neurons show multiple patterns in the distribution of the viral genomes within the nucleus, at least in mouse models. One of the major patterns is characterized by the presence of quiescent HSV-1 genomes trapped in promyelocytic leukemia nuclear bodies (PML NBs) to form viral DNA-containing PML-NBs (vDCP NBs). Using a cellular model reproducing the formation of vDCP NBs we previously showed that viral genomes are chromatinized with the H3.3 histone variant modified on its lysine 9 by tri-methylation (H3.3K9me3) a chromatin mark associated with transcriptional repression. Here we identify an essential role for the HUSH complex and its SETDB1 and MORC2 effectors in the acquisition of the H3K9me3 mark on the PML NBs-associated HSV-1 and in the maintenance of HSV-1 transcriptional repression. ChiP-seq analyses highlight the association of the H3K9me3 mark with the entire viral genome. Inactivating the HUSH-SETDB1-MORC2 repressor complex prior to viral infection results in a significant reduction of H3K9me3 on the viral genome, while the overall impact on the cellular genome is minimal, except for expected changes in families of LINE1 retroelements. Depletion of HUSH, SETDB1, or MORC2, relieves the repressive state of HSV-1 in infected primary human fibroblasts as well as human induced pluripotent stem cell-derived sensory neurons (hiPSDN). We discovered that the viral protein ICP0 induces MORC2 degradation via the proteasome machinery. This process is concurrent with ICP0 and MORC2 depletion capability to reactivate silenced HSV-1 in hiPSDN. Overall, our findings underscore the robust antiviral function of the HUSH-SETDB1-MORC2 repressor complex against a herpesvirus by modulating chromatin marks linked to repression, thus presenting promising avenues for novel anti-herpesvirus therapeutic strategies.Significance statementHerpes simplex virus 1 (HSV-1) is a major human pathogen, which remains latent in the trigeminal ganglia (TG) neurons of the infected individuals. Its reactivation is characterized by a variety of clinical symptoms the most severe ones being keratitis and herpesvirus encephalitis. The colonization of the CNS by the virus during the individual life is a well-known fact but the pathophysiological effects on neurons homeostasis are still underestimated. It is thus paramount to understand the molecular mechanisms that control HSV-1 latency and maintain the virus in a pseudo silent state.