bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Clinical Validation of a Miniaturized Finger Probe for Bedside Hemodynamic Monitoring
Authors: Panula Tuukka , Sirkiä Jukka-Pekka , Koivisto Tero , Pänkäälä Mikko , Niiranen Teemu , Kantola Ilkka , Kaisti Matti 
Published: August 2022

AbstractBackgroundHypertension, or elevated blood pressure (BP), is a marker for many cardiovascular diseases and can lead to life-threatening conditions such as heart failure, coronary artery disease, and stroke. BP monitoring using a traditional arm cuff device is often inconvenient and possibly painful in long-term use, i.e. during sleep.MethodsWe present a miniature cuffless tonometric finger probe system, that uses the oscillometric method to measure blood pressure (BP). Our approach uses a motorized press that is used to apply pressure to the finger tip to measure BP.ResultsWe verified the functionality of the device in a clinical trial (n=43) resulting in systolic (SBP) and diastolic (DBP) pressures ((mean±SD) mmHg) of (−3.5 ± 8.4) mmHg and (−4.0 ± 4.4) mmHg, respectively. Comparison was made with manual auscultation (n=26) and automated cuff oscillometry (n=18). In addition to BP, we demonstrated the ability of the device to assess arterial stiffness (n=18) and detect atrial fibrillation (n=6).ConclusionsWe were able to introduce a sufficiently small device that could be used for convenient ambulatory measurements and worn during sleep with minimal discomfort. Lastly, we evaluate methods to further develop the concept and discuss future directions.Plain language summaryTraditional cuff-based automated BP instruments are mainly suitable for individual measurements and are often inconvenient to use. Patients in a hospital ward are typically monitored with many systems and devices. Our aim is to develop a blood pressure measurement technology that could be integrated into a finger-worn pulse oximeter. This way the need for a bulky and inconvenient arm cuff could be eliminated and the number of needed monitoring devices could be reduced. The proposed technology is especially suitable for pseudo-continuous BP measurement, that is, taking automated measurements periodically, enabling BP trend tracking and analysis. In this study, we clinically validate our technology for blood pressure monitoring and further demonstrate its potential to measure arterial stiffness and detect atrial fibrillation.
Cytokine and chemokine gene expression in patients with clinically suspect arthralgia; a longitudinal study during progression to inflammatory arthritis or non-progression
Authors: Heutz J.W. , Rogier C. , Niemantsverdriet E. , van den Eeden S.J.F. , de Jong P.H.P. , Lubberts E. , Geluk A. , van der Helm-van Mil A.H.M. 
Published: August 2022

AbstractBackgroundAutoantibody-responses rise years before onset of inflammatory arthritis (IA) and are stable during transitioning from clinically suspect arthralgia (CSA) to IA. Cytokine and chemokine levels can also rise years before IA-onset, but the course after CSA-onset is unknown. To better understand the processes in this symptomatic at-risk phase, we studied the course of cytokine, chemokine and related receptors gene expression in CSA-patients during progression to IA, and in CSA-patients who ultimately did not develop IA. Differential expressed genes between ACPA-positive and ACPA-negative CSA-patients who developed IA were also explored.MethodsWhole blood RNA expression of 37 inflammatory cytokines/chemokines/related receptors was determined by dual-color reverse-transcription multiplex ligation-dependent probe amplification, in paired samples of CSA-patients at CSA-onset and either at IA-development or after 24-months without IA-development. ACPA-positive and ACPA-negative CSA-patients developing IA were compared at CSA-onset and during progression to IA. GEE-models tested changes over time. A false discovery rate approach was applied to correct for multiple testing.ResultsNone of the cytokines/chemokine genes significantly changed in expression between CSA-onset and IA-development. In CSA-patients without IA development, G-CSF expression decreased (p=0.001), whereas CCR6 and TNIP expression increased (p<0.001 and p=0.002, respectively) over a 2-year period. Expression levels in ACPA-positive and ACPA-negative CSA-patients who developed IA were similar.ConclusionWhole blood gene expression of cytokines, chemokines and related receptors did not change significantly from CSA to IA-development. This suggests that changes in expression of these molecules occurred preceding CSA-onset and may not relate to the final hit of developing chronic arthritis. Observed changes in CSA-patients not developing IA can provide clues for processes related to resolution.
Potential health and economic impact of paediatric vaccination using next generation influenza vaccines in Kenya: a modelling study
Authors: Waterlow Naomi R , Radhakrishnan Sreejith , Dawa Jeanette , van Leeuwen Edwin , Lambach Philipp , Bresee Joseph , Mazur Marie , Eggo Rosalind M , Jit Mark 
Published: August 2022

AbstractBackgroundInfluenza is a major year-round cause of respiratory illness in Kenya, particularly in children under 5. Current influenza vaccines result in short-term, strain-specific immunity and were found in a previous study not to be cost-effective in Kenya. However, next generation vaccines are in development that may have a greater impact and cost-effectiveness profile.MethodsWe expanded a model previously used to evaluate cost-effectiveness of seasonal influenza vaccines in Kenya to include next generation vaccines by allowing for enhanced vaccine characteristics and multi-annual immunity. We specifically examined vaccinating children under 5 years of age with improved vaccines, evaluating vaccines with combinations of increased vaccine effectiveness, cross protection between strains (breadth) and duration of immunity. We evaluated cost-effectiveness using incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits (INMBs) for a range of values for the willingness-to-pay (WTP) per DALY averted. Finally, we estimated threshold per-dose vaccine prices at which vaccination becomes cost-effective.ResultsNext generation vaccines can be cost-effective, dependent on the vaccine characteristics and assumed WTP thresholds. Universal vaccines (assumed to provide long-term and broad immunity) are most cost-effective in Kenya across three of four WTP thresholds evaluated, with the lowest median value of ICER per DALY averted ($263, 95% Credible Interval (CrI): $-1698, $1061) and the highest median INMBs. At a WTP of $623, universal vaccines are cost-effective at or below a median price of $5.16 per dose (95% CrI: $0.94, $18.57). We also show that the assumed mechanism underlying infection-derived immunity strongly impacts vaccine outcomes.ConclusionThis evaluation provides evidence for country-level decision makers about future next generation vaccine introduction, as well as global research funders about the potential market for these vaccines. Next generation vaccines may offer a cost-effective intervention to reduce influenza burden in low-income countries with year-round seasonality like Kenya.
Longitudinal health survey of women from Venezuela in Colombia (ELSA-VENCOL): first report
Authors: Acosta-Reyes Jorge , Bonilla-Tinoco Laura Juliana , Aguirre Melissa , Rojas-Botero Maylen , Anillo Luis Ángel , Rodríguez David Alejandro , Cifuentes Lida Yoana , Jiménez Iván , León Luisa Fernanda , Bojorquez-Chapela Ietza , Fernández-Niño Julián Alfredo 
Published: August 2022

AbstractBackgroundColombia is currently the world’s main recipient country for Venezuelan migrants, and women represent a high proportion of them. This article presents the first report of a cohort of Venezuelan migrant women entering Colombia through Cúcuta and its metropolitan area (the main land entry point to this country). The study aimed to describe the health status and access to healthcare services among Venezuelan migrant women in Colombia with irregular migration status, and to analyze changes in those conditions at a one-month follow-up.MethodsA longitudinal cohort study of Venezuelan migrant women, 18 to 45 years, who entered Colombia with an irregular migration status, was carried out in 2021. Study participants were recruited in temporary shelters, transit points, and migrant settlements in Cúcuta and the metropolitan area. At baseline, we administered a structured questionnaire including sociodemographic characteristics, migration history, health history, access to health services, sexual and reproductive health, practice of early detection of cervical cancer and breast cancer, food insecurity, and depressive symptoms. The women were again contacted by phone one month later, between March and July 2021, and a second questionnaire was applied.ResultsA total of 2,298 women were included in the baseline measurement and 56.4% could be contacted again at the one-month follow-up. A significant increase was found in the percentage of women who had a health problem during the past month (from 23.1% to 31.4%; p<0.01); as well as in the share who reported moderate, severe, or extreme difficulty working or performing daily chores (from 5.5% to 11.0%; p= 0.03) and who rated their health as fair (from 13.0% to 31.2%; p<0.01). Meanwhile, the percentage of women with depressive symptoms decreased from 80.5% to 71.2% (p<0.01).ConclusionThis report is a starting point for the longitudinal follow-up of the cohort, which will allow us to better understand how the health status of Venezuelan women changes during the migration flow in Colombia.
A network of mixed actin polarity in the leading edge of spreading cells
Authors: Chung Wen-Lu , Eibauer Matthias , Li Wenhong , Boujemaa-Paterski Rajaa , Geiger Benjamin , Medalia Ohad 
Published: August 2022

AbstractPhysical interactions of cells with the underlying extracellular matrix (ECM) play key roles in multiple cellular processes, such as tissue morphogenesis, cell motility, wound healing, cancer invasion and metastasis. The actin cytoskeletal network is a central driver and regulator of cellular dynamics, that produces membrane protrusions such as lamellipodia and filopodia. In this study, we examined actin organization in the expanding lamellipodia during the early stages of cell spreading. To gain insight into the 3D actin organization, at a molecular resolution, we plated cultured fibroblasts on galectin-8 coated EM grids, an ECM protein presents in disease states. We then combined cryo-electron tomography (cryo-ET) with advanced image processing tools for reconstructing the structure of F-actin in the lamellipodia. This approach enabled us to resolve the polarity and orientation of the filaments, and the structure of the Arp2/3 complexes associated with F-actin branches. We show here that F-actin in lamellipodial protrusions forms a dense network with three distinct sub-domains. One consists primarily of radial filaments, with their barbed ends pointing towards the membrane, the other is enriched with parallel filaments that run between the radial fibers, in addition to an intermediate sub-domain. Surprisingly, a minor, yet significant (∼10%) population of actin filaments, are oriented with their barbed ends towards the cell center. Our results provide novel structural insights into F-actin assembly and dynamic reorganization in the leading edge of spreading cells.
Effect of reduced genomic representation on using runs of homozygosity for inbreeding characterization
Authors: Lavanchy Eléonore , Goudet Jérôme 
Published: August 2022

ABSTRACTRuns of homozygosity (ROHs) are proxy for genomic Identical-by-Descent segments and are increasingly used to measure individual inbreeding. ROHs analyses are mostly carried out on SNPs-arrays and whole-genome-sequencing data. Softwares recurrently used for their detection usually assume that genomic positions which have not been genotyped are non-variant. This might be true for whole-genome-sequencing data, but not for reduced genomic representations and can lead to spurious ROHs detection. We simulated the outputs of whole-genome-sequencing, two SNP-arrays and RAD-sequencing for three populations with different sizes. We compare the results of ROHs calling with two softwares: PLINK and RZooRoH. We demonstrate that to obtain meaningful estimates of inbreeding coefficients, RZooRoH requires fraction of genome seven times smaller compared to PLINK. When the SNP density is above 20 SNPs/Mb for PLINK and 3 SNPs/Mb for RZooRoH, ranks of ROHs-based inbreeding coefficients are conserved among individuals. With reduced genomic representations, ROHs distributions are consistently biased towards an underestimation of the total numbers of small and an overestimation of the total numbers of large ROHs, except for RZooRoH and high-density SNPs-arrays. We conclude that both ROHs-based inbreeding coefficients and ROHs distributions exact quantification are highly dependent on the fraction of genome sequenced and should thus be treated with caution. However, relative inbreeding estimates, such as comparison between individuals or populations, are reliable with reduced genomic representations providing that the fraction of genome sequenced is large enough. Consequently, we advise researchers working with reduced genomic data to use SNPs-independent measures or model-based ROHs calling methods for inbreeding estimations.
Unraveling the Potential Role of Tecomella undulatain Experimental NASH
Authors: Srinivas Akshatha N. , Suresh Diwakar , Suvarna Deepak , Pathak Pankaj , Giri Suresh , Suman  , Satish Suchitha , Chidambaram Saravana Babu , Kumar Divya P. 
Published: August 2022

ABSTRACTBackground and AimThe pathophysiology of NASH is complex owing to its diverse pathological drivers, and until recently, there were no approved drugs for this disease.Tecomella undulatais a popular herbal medicine used to treat hepatosplenomegaly, hepatitis, and obesity. However, the potential role ofTecomella undulatain NASH has not yet been scientifically investigated.Experimental ProcedureMice fed with chow diet and normal water (CDNW) or western diet and sugar water (WDSW) for 12 weeks were randomized to receive vehicle control, Saroglitazar, orTecomella undulatafor an additional 12 weeks. Insulin resistance, lipid profiles, histological analysis, and liver enzymes were assessed. The oxidative stress, ER and inflammatory markers were determined by quantitative RT-PCR (qRT-PCR) and western blot analysis.Results and ConclusionThe administration ofTecomella undulatavia oral gavage lowered body weight, insulin resistance, alanine transaminase (ALT), aspartate transaminase (AST), triglycerides, and total cholesterol in WDSW mice but had no effect on CDNW mice.Tecomella undulataimproved steatosis, lobular inflammation, and hepatocyte ballooning and resolved NASH in WDSW mice. Furthermore,Tecomella undulataalso alleviated the WDSW-induced ER stress and oxidative stress, enhanced antioxidant status, and thus reduced inflammation in the treated mice. Of note, these effects were on par with Saroglitazar, the approved drug used to treat human NASH and positive control used in the study.Thus, our findings indicate the potential ofTecomella undulatato ameliorate WDSW-induced steatohepatitis, and these preclinical data provide a strong rationale for assessingTecomella undulatafor the treatment of NASH in humans.
The direct and indirect pathways of the basal ganglia antagonistically influence cortical activity and perceptual decisions
Authors: van Beest Enny H. , Abdelwahab Mohammed A.O. , Cazemier J. Leonie , Baltira Chrysiida , Maes M. Cassandra , Peri Brandon D. , Self Matthew W. , Willuhn Ingo , Roelfsema Pieter R. 
Published: August 2022

AbstractThe striatum, input nucleus of the basal ganglia, receives topographically organized input from the cortex and gives rise to the direct and indirect pathways with antagonistic effects on the output of the basal ganglia. We optogenetically stimulated the direct and indirect pathways in mice and measured their influence on perceptual decisions and neuronal activity in the cortex. In a task in which mice had to detect a visual stimulus, unilateral direct-pathway stimulation increased the probability of lick responses to the non-stimulated side and increased cortical activity globally. In contrast, indirect-pathway stimulation increased the probability of licks to the stimulated side and decreased activity in visual cortical areas. To probe the possible role of the two pathways in working memory, we trained the mice to report the location of a stimulus with licking one of two spouts, after a memory delay. Direct-pathway stimulation prior to and during the memory delay enhanced both the neural representation of a contralateral visual stimulus and the number of contraversive choices, whereas indirect-pathway stimulation had the opposite effects, in accordance with an antagonistic influence of the direct and indirect pathways on licking direction. Our results demonstrate how these two pathways influence perceptual decisions and working memories, and modify activity in the cerebral cortex.One sentence summaryVisuomotor transformations are influenced antagonistically by the direct and indirect pathways of the basal ganglia during visual detection and working memory tasks
Introgression between highly divergent fungal sister species
Authors: Kinneberg Vilde Bruhn , Lü Dabao Sun , Peris David , Ravinet Mark , Skrede Inger 
Published: August 2022

AbstractTo understand how species evolve and adapt to changing environments, it is important to study gene flow and introgression due to their influence on speciation and radiation events. Here, we apply a novel experimental system for investigating these mechanisms using natural populations. The system is based on two fungal sister species with morphological and ecological similarities occurring in overlapping habitats. We examined introgression between these species by conducting whole genome sequencing of individuals from populations in North America and Europe. We assessed genome wide nucleotide divergence and performed crossing experiments to study reproductive barriers. We further used ABBA-BABA statistics together with a network analysis to investigate introgression, and conducted demographic modelling to gain insight into divergence times and introgression events. The results revealed that the species are highly divergent and incompatible in vitro. Despite this, small regions of introgression were scattered throughout the genomes and one introgression event likely involves a ghost population (extant or extinct). This study demonstrates that introgression can be found among divergent species and that population histories can be studied without collections of all the populations involved. Moreover, the experimental system is shown to be a useful tool for research on reproductive isolation in natural populations.
Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation
Authors: Luda Katarzyna M. , Kitchen-Goosen Susan M. , Ma Eric H. , Watson McLane J. , Duimstra Lauren R. , Oswald Brandon M. , Longo Joseph , Fu Zhen , Madaj Zachary , Kupai Ariana , Dickson Bradley M. , Kaymak Irem , Lau Kin H. , Compton Shelby , DeCamp Lisa M. , Kelly Daniel P. , Puchalska Patrycja , Williams Kelsey S. , Krawczyk Connie M. , Lévesque Dominique , Boisvert François-Michel , Sheldon Ryan D. , Rothbart Scott B. , Crawford Peter A. , Jones Russell G. 
Published: August 2022

AbstractEnvironmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. However, the metabolic pathways critical for optimal T cell responses remain poorly understood. Here, we identify ketone bodies (KBs) – including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc) – as essential fuels supporting CD8+ T cell metabolism and effector function. Ketolysis is an intrinsic feature of highly functional CD8+ T effector (Teff) cells and βOHB directly increases CD8+ Teff cell IFN-γ production and cytolytic activity. Using metabolic tracers, we establish that CD8+ Teff cells preferentially use KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boost the respiratory capacity of CD8+ T cells and TCA cycle-dependent metabolic pathways that fuel T cell growth. Mechanistically, we find that βOHB is a major substrate for acetyl-CoA production in CD8+ T cells and regulates effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8+ T cell effector responses.One Sentence summaryKetone bodies promote CD8+ T cell metabolism and effector function through regulation of epigenetic programming
Mutation in the TRKB cholesterol recognition site that blocks antidepressant binding does not influence the basal or BDNF-stimulated activation of TRKB
Authors: Biojone Caroline , Cannarozzo Cecilia , Seiffert Nina , Diniz Cassiano RAF , Brunello Cecilia A , Castrén Eero , Casarotto Plinio 
Published: August 2022

AbstractBrain-derived neurotrophic factor (BDNF) acting upon its receptor Neurotrophic tyrosine kinase receptor 2 (NTRK2, TRKB) plays a central role in the development and maintenance of synaptic function and activity- or drug-induced plasticity. TRKB possesses an inverted cholesterol-recognition and alignment consensus sequence (CARC), suggesting this receptor can act as a cholesterol sensor. We have recently shown that antidepressants drugs directly bind to the CARC domain of TRKB dimers, and that this binding as well as biochemical and behavioral responses to antidepressants are lost with a mutation in the TRKB CARC motif (Y433F). However, it is not clear if this mutation can also compromise the receptor function and lead to behavioral alterations. Here, we observed that Y433F mutation does not alter BDNF binding to TRKB, or BDNF-induced dimerization of TRKB. In this line, primary cultures from embryos of heterozygous Y433F mutant mice (hTRKB.Y433F) are responsive to BDNF-induced activation of TRKB, and samples from adult mice do not show any difference on TRKB activation compared to wild-type littermates (TRKB.wt). The behavioral phenotype of hTRKB.Y433F mice is indistinguishable from the wild-type mice in cued fear conditioning, contextual discrimination task or the elevated plus maze, whereas mice heterozygous to BDNF null allele show a phenotype in context discrimination task. Taken together, our results indicate that Y433F mutation in the TRKB CARC motif does not show signs of loss-of-function of BDNF responses, while antidepressant binding to TRKB and responses to antidepressants are lost in Y433F mutants, making them an interesting mouse model for antidepressant research.