bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Sensory Reweighting on Postural Control and Cortical Activity in Parkinson’s Disease
Authors: Sadeghi Maryam , Bristow Thomas , Fakorede Sodiq , Liao Ke , Palmer Jacqueline A. , Lyons Kelly E. , Pahwa Rajesh , Huang Chun-Kai , Akinwuntan Abiodun , Devos Hannes 
Published: January 2024

AbstractAimsBalance requires the cortical control of visual, somatosensory, and vestibular inputs. The aim of this cross-sectional study was to compare the contributions of each of these systems on postural control and cortical activity using a sensory reweighting approach between participants with Parkinson’s disease (PD) and controls.MethodsTen participants with PD (age: 72 ± 9; 3 women; Hoehn & Yahr: 2 [1.5 – 2.50]) and 11 controls (age: 70 ± 3; 4 women) completed a sensory organization test in virtual reality (VR-SOT) while cortical activity was being recorded using electroencephalography (EEG). Conditions 1 to 3 were completed on a stable platform; conditions 4 to 6 on a foam. Conditions 1 and 4 were done with eyes open; conditions 2 and 5 in a darkened VR environment; and conditions 3 and 6 in a moving VR environment. Linear mixed models were used to evaluate changes in center of pressure (COP) displacement and EEG alpha and theta/beta ratio power between the two groups across the postural control conditions. Condition 1 was used as reference in all analyses.ResultsParticipants with PD showed greater COP displacement than controls in the anteroposterior (AP) direction when relying on vestibular input (condition 5; p<0.0001). The mediolateral (ML) COP sway was greater in PD than in controls when relying on the somatosensory (condition 2; p = 0.03), visual (condition 4; p = 0.002), and vestibular (condition 5; p < 0.0001) systems. Participants with PD exhibited greater alpha power compared to controls when relying on visual input (condition 2; p = 0.003) and greater theta/beta ratio power when relying on somatosensory input (condition 4; p = 0.001).ConclusionsPD affects reweighting of postural control, exemplified by greater COP displacement and increased cortical activity. Further research is needed to establish the temporal dynamics between cortical activity and COP displacement.
Cytotoxic CD4+T cells in the bone marrow compromise healthy ageing by enhancing granulopoiesis
Authors: Gabandé-Rodríguez Enrique , Soto-Heredero Gonzalo , Carrasco Elisa , Anerillas Carlos , Escrig-Larena José Ignacio , Delgado-Pulido Sandra , Francos-Quijorna Isaac , Gómez de las Heras Manuel M. , Fernández-Almeida Álvaro , Blanco Eva María , Winand-Osete Elia , Zorita Virginia , Martínez-Cano Jorge , Garrido Amanda , de Cabo Rafael , Mañes Santos , Gorospe Myriam , Mittelbrunn María 
Published: January 2024

AbstractNeutrophils are the most abundant leukocytes in the blood, with numbers further increasing with age. Despite their essential role as a primary line of defense, neutrophils can contribute to tissue damage and age-related diseases1and a high neutrophil-to-lymphocyte ratio predicts all causes of mortality in the elderly2–5. However, the precise mechanisms driving enhanced neutrophil generation during ageing remain poorly understood. Here, we show that a subset of CD4+T cells with a cytotoxic phenotype (CD4+CTLs) producing the chemokine CCL5 and harbouring dysfunctional mitochondria, infiltrate the bone marrow and induce granulopoiesis in aged mice. During ageing, hematopoietic stem cells upregulate CCR5, the primary receptor for CCL5, and its deficiency limits the T cell-mediated induction of granulopoiesis and neutrophil output. Treatment with the FDA-approved CCR5 inhibitor Maraviroc decreases granulopoiesis and lowers the levels of circulatory and tissue-infiltrating neutrophils, ameliorating multiple ageing biomarkers and improving functional outcomes in aged mice. These findings suggest that age-associated alterations in T cells reduce health outcomes by remodelling the bone marrow niche and enhancing neutrophil generation. Consequently, interventions to disrupt the interplay between T cells and hematopoietic stem cells hold substantial therapeutic potential to ameliorate age-associated diseases.
Persister cancer cells are characterized by H4K20me3 heterochromatin that defines a low inflammatory profile
Authors: Ramponi Valentina , Richart Laia , Kovatcheva Marta , Stephan-Otto Attolini Camille , Capellades Jordi , Lord Alice E. , Yanes Oscar , Ficz Gabriella , Serrano Manuel 
Published: January 2024

SUMMARYAnti-cancer therapies may induce proliferative arrest in cancer cells in the form of senescence or drug-tolerant persistency, the latter being a reversible arrest with similarities to embryonic diapause. Here, we use mTOR/PI3K inhibition to develop and characterize a model of persistency/diapause-like arrest in human cancer cells of various origins. We show that persister and senescent cancer cells share an expanded lysosomal compartment and hypersensitivity to BCL-XL inhibition. However, persister cells do not exhibit other features of senescence, such as the loss of Lamin B1, senescence-associated b-galactosidase activity, and an inflammatory phenotype. Compared to senescent cells, persister cells have a profoundly diminished senescence-associated secretory phenotype (SASP), low activation of interferon signaling pathways and lack upregulation of MHC-I presentation. Based on a genome-wide CRISPR/Cas9 screen performed in diapause mouse embryonic stem cells (mESC), we discover that persister human cancer cells are hypersensitive to the inhibition of one-carbon metabolism. This finding led us to uncover that the repressive heterochromatic mark H4K20me3 is enriched at promoters of SASP and interferon response genes in persister cells, but not in senescent cells. Collectively, we define novel features and vulnerabilities of persister cancer cells and we provide insight into the epigenetic mechanisms underlying their low inflammatory and immunogenic activity.
Self-incompatibility based functional genomics for rapid phenotypic characterization of seed metabolism genes
Authors: Azeez Abdul , Bates Philip D. 
Published: January 2024

SummaryReverse-genetic characterization of plant gene function through technologies such as CRISPR/Cas, RNAi, or gene overexpression requires the ability to efficiently transform the plant species of interest. However, efficient transformation systems are not available for most plant species.Physaria fendleriis an oilseed plant valued for its unusual hydroxylated fatty acids (HFA, e.g. lesquerolic acid) that accumulates up to 60% of seed oil and is a non-toxic alternative to castor (Ricinus communis) seeds as a source for HFA for the chemical industry. Domestication and improvement ofP. fendleriseed oil requires characterization of genes involved in developing seed metabolism. Tissue culture-based transformation ofP. fendleriis laborious, low-efficiency, and time-consuming (T1 ∼18 months). Additionally,P. fendleriis self-incompatible requiring laborious hand pollination for propagation and seed collection from transgenic lines. We developed a rapid virus-induced gene silencing (VIGS) method to characterize genes within developing seeds. Identification of the self-incompatibility mechanisms inP. fendleriallowed the use of self-compatibility as a novel visual selectable marker by co-targeting the gene of interest (GOI) with the self-incompatibility gene S-locus receptor kinase (SRK). Seeds develop without cross-pollination from silenced SRK and each of those seeds contain the GOI silenced, allowing rapid phenotypic characterization of the seeds in the first generation. Through this methodology we confirmed the in vivo function of two key genes (FAH12, FAE1) involved in lesquerolic acid production. Thus, this self-compatibility based functional genomics approach is a rapid methodology for in vivo reverse-genetic gene characterization in self-incompatible plants.
Integrated Plankton and Trace Metal Analysis as Indicators of Organic Pollution Threats from Carp-Cultured Ponds to Adjacent Ecosystems: Implications for Sustainability
Authors: Mukherjee Manasi , Jarzembowski Paweł , Polechoński Ryszard , Proćków Jarosław 
Published: January 2024

AbstractStawy Milickie (Milicz Ponds) is a natural reserve that has a great ecological importance as a Ramsar site and economic importance as one of the largest carp breeding centres in Europe. Continuous anthropogenic pressure on these large ecosystems can lead to a high disturbance on its natural ecology and sustainability. Phytoplankton, one of the most important indicators of any anthropogenic load, especially organic pollution have been studied in the present study. This is the first work ever from Milicz ponds, wherein the diversity, community structure and seasonal variability of phytoplankton with respect to changes in physicochemical parameters and trace metals have been studied. Periodic samples of water and phytoplankton were collected from four selected ponds of various sizes from October 2018 to September 2019. Of the four selected ponds one was unused for carp cultivation. The study reports the presence of 147 phytoplankton species in nine distinct taxonomic groups. The Genera based Algal pollution index indicated presence of organic pollution in both noncultured pond and carp-cultured pond. The heavy metals detected in the concentration order of Cd>Mn>Fe>Zn>Cu>Pb remained much higher than the safe limits of freshwater aquaculture ponds. The probable sources of these pollutants were identified as artificial feed used in the cultivation of carp and inundation from the river basin. This study emphasizes the urgent need for continuous qualitative and quantitative assessment and monitoring of water parameters, including plankton, in these ponds. This study highlights how the structure of microplankton communities, in conjunction with heavy metal analysis, serves as indicators of the spread of organic pollution in non-cultivated aquaculture environments. It strongly advocates for implementing sustainable measures to safeguard this vital ecosystem.
DeepGOMeta: Predicting functions for microbes
Authors: Tawfiq Rund , Niu Kexin , Hoehndorf Robert , Kulmanov Maxat 
Published: January 2024

AbstractAnalyzing microbial samples remains computationally challenging due to their diversity and complexity. The lack of robustde novoprotein function prediction methods exacerbates the difficulty in deriving functional insights from these samples. Traditional prediction methods, dependent on homology and sequence similarity, often fail to predict functions for novel proteins and proteins without known homologs. Moreover, most of these methods have been trained on largely eukaryotic data, and have not been evaluated or applied to microbial datasets. This research introduces DeepGOMeta, a deep learning model designed for protein function prediction, as Gene Ontology (GO) terms, trained on a dataset relevant to microbes. The model is validated using novel evaluation strategies and applied to diverse microbial datasets. Data and code are available athttps://github.com/bio-ontology-research-group/deepgometa
Low-coverage whole genome sequencing for a highly selective cohort of severe COVID-19 patients
Authors: Santos Renato , Moreno-Torres Víctor , Pintos Ilduara , Corral Octavio , de Mendoza Carmen , Soriano Vicente , Corpas Manuel 
Published: January 2024

AbstractDespite advances in identifying genetic markers associated to severe COVID-19, the full genetic characterisation of the disease remains elusive. This study explores the use of imputation in low-coverage whole genome sequencing for a severe COVID-19 patient cohort. We generated a dataset of 79 imputed variant call format files using the GLIMPSE1 tool, each containing an average of 9.5 million single nucleotide variants. Validation revealed a high imputation accuracy (squared Pearson correlation ≈0.97) across sequencing platforms, showing GLIMPSE1’s ability to confidently impute variants with minor allele frequencies as low as 2% in Spanish ancestry individuals. We conducted a comprehensive analysis of the patient cohort, examining hospitalisation and intensive care utilisation, sex and age-based differences, and clinical phenotypes using a standardised set of medical terms developed to characterise severe COVID-19 symptoms. The methods and findings presented here may be leveraged in future genomic projects, providing vital insights for health challenges like COVID-19.
Extraction of naringin dihydrochalcone and its effect on reducing blood lipid levels in vitro
Authors: Tian Mu-yang , Li Si-qi , Qi Jing-wen , Zhang Lei , Yu Xiao-lei 
Published: January 2024

AbstractResponse surface methodology (RSM) was used to optimize the extraction process of naringin. The central component design included three parameters of extraction, namely, temperature (X1), solid-liquid ratio (X2), and extraction time (X3). The optimum extraction temperature was 67℃; the ratio of material to liquid was 54:1mL/g, and the extraction time was 2.8h. According to the best extraction conditions, naringin was processed to verify the accuracy of the model. Five parallel experiments were set up, and a yield of 32.48 mg/g naringin was obtained, that was equivalent to the predicted yield of 32.56 mg/g. Naringin was purified to obtain naringin-refined products using DM101 macroporous adsorption resin. Naringin dihydrochalcone was synthesized following catalytic hydrogenation of purified naringin. The structures of naringin and naringin dihydrochalcone were determined via Fourier infrared spectrometer and nuclear magnetic resonance spectrometry. Evaluate the ability of naringin dihydrochalcone to bind with glycine bile sodium and bovine bile sodium by simulating the gastrointestinal environment in vitro. Further focusing on HepG2 cells, a high cholesterol induced high-fat HepG2 cell model was established. We measured the effects of different concentrations of naringin dihydrochalcone on intracellular lipids in denatured HepG2 cells and further validated the lipid-lowering effect of naringin at the cellular level. The results showed that naringin dihydrochalcone has potential application in functional foods for lowering blood lipids.
Budgeting and advocacy to improve water, sanitation, and hygiene in healthcare facilities: a case study in Nepal
Authors: Chettry Laxman Kharal , Bohara Prakash , Bohara Ramesh C. , Jajal Ram Hari , Khadha Sarad , Subedi Hari , Giri Debesh , Sharma Sarbesh , Dhungana Upendra , van der Valen Matteus Thijs , Brogan John , Anderson Darcy M. 
Published: January 2024

AbstractBarriers to achieving and sustaining access to water, sanitation, hygiene, waste management (collectively, “WASH”) in healthcare facilities include a supportive policy environment and adequate funding. While guidelines exist for assessing needs and making initial infrastructure improvements, there is little guidance on how to develop budgets and policies to sustain WASH services in the long-term. We conducted costing and advocacy activities in Thakurbaba municipality, Nepal, with the aim of developing a budget and operations and maintenance policy for WASH in healthcare facilities in partnership with the municipal government. Our objectives for this study are to (1) describe the process and methods used for costing and advocacy, (2) report the costs to achieve and maintain basic WASH services in the eight healthcare facilities of Thakurbaba municipality, and (3) report the outcomes of advocacy activities and policy development. We applied bottom-up costing to enumerate the resources necessary to achieve and maintain basic WASH services and their costs. The annual costs of WASH services ranged from USD 4,881 to 9,527 (including operations and maintenance and annualized capital investments). Cost findings were used to prepare annual budgets recommended to achieve and maintain basic access, which were presented to municipal government and incorporated into an operations and maintenance policy. To-date, the municipality has adopted the policy and established a recovery fund of USD 3,831 for repair and maintenance of infrastructure, and an additional USD 192 per facility for discretionary WASH spending. Advocacy at the national level for WASH in healthcare facilities is currently being championed by the municipality, and findings from this project are being used to inform development of a nationally costed plan for universal access. This study is intended to provide a roadmap for how cost data can be collected and applied to inform policy.
Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost
Authors: Zhong Allison Y. , Lui Asona J. , Kuznetsova Svetlana , Kallis Karoline , Conlin Christopher , Do Deondre D. , Domingo Mariluz Rojo , Manger Ryan , Hua Patricia , Karunamuni Roshan , Kuperman Joshua , Dale Anders M. , Rakow-Penner Rebecca , Hahn Michael E. , van der Heide Uulke A. , Ray Xenia , Seibert Tyler M. 
Published: January 2024

AbstractPurposeThe focal radiotherapy (RT) boost technique was shown in the FLAME trial to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. The ReIGNITE RT Boost study evaluated radiation oncologists’ accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists’ contour inaccuracies would yield meaningfully worse clinical outcomes.Materials & Methods44 radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the FLAME trial protocol. Probability of biochemical failure (BF) was determined using a model from the FLAME trial. The primary metric evaluated was delta BF (ΔBF=Participant BF – Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful.Results8 patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. 37% of participant plans were noted to have an absolute increase in BF of 5% or more.ConclusionRadiation oncologists’ attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients.
Benefits of Aeroallergen Testing on Oral Corticosteroid Bursts in Adults with Asthma
Authors: Gleeson Patrick K. , Morales Knashawn H. , Buckey Timothy M. , Fadugba Olajumoke O. , Apter Andrea J. , Christie Jason D. , Himes Blanca E. 
Published: January 2024

ABSTRACTBACKGROUNDAeroallergen testing can improve precision care for persistent asthma and is recommended by the U.S. clinical guidelines. How testing benefits diverse populations of adults with asthma, and the importance of the testing modality used, are not fully understood.OBJECTIVEWe sought to evaluate whether receipt of aeroallergen testing was associated with a reduction in oral corticosteroid (OCS) bursts.METHODSWe used electronic health record data to conduct a retrospective, observational cohort study of adults with asthma who were prescribed an inhaled corticosteroid and had an Allergy/Immunology visit in a large health system between 1/1/2017-6/30/2022. Negative binomial regression models were used to evaluate whether OCS bursts in the 12-month period after an initial visit were reduced for patients who received aeroallergen testing. We also measured differences in benefit after excluding patients with chronic obstructive pulmonary disease (COPD) and smoking histories, and whether testing receipt was via skin prick or serum.RESULTS668/1,383 (48.3%) patients received testing. Receipt of testing was not associated with fewer bursts in all patients (incidence rate ratio (IRR)=0.83 versus no testing, p=0.059), but it was among never smokers without COPD (417/844 tested, IRR=0.68, p=0.004). The receipt ofskintesting was associated with fewer bursts in all patients (418/1,383 tested, IRR=0.77, p=0.02) and among never smokers without COPD (283/844 tested, IRR=0.59 versus no testing, p=0.001).CONCLUSIONGuideline-concordant aeroallergen testing in the context of Allergy/Immunology care was associated with clinical benefit in a real-life, diverse cohort of adults with asthma. This benefit varied according to patient comorbidities and the testing modality.
Spike transmission failures in axons from mouse cortical pyramidal neurons in vivo
Authors: Ofer Netanel , Cornejo Victor Hugo , Yuste Rafael 
Published: January 2024

AbstractThe propagation of action potentials along axons is traditionally considered to be reliable, as a consequence of the high safety factor of action potential propagation. However, numerical simulations have suggested that, at high frequencies, spikes could fail to invade distal axonal branches. Given the complex morphologies of axonal trees, with extensive branching and long-distance projections, spike propagation failures could be functionally important. To explore this experimentallyin vivo, we used an axonal-targeted calcium indicator to image action potentials at axonal terminal branches in superficial layers from mouse somatosensory cortical pyramidal neurons. We activated axons with an extracellular electrode, varying stimulation frequencies, and computationally extracted axonal morphologies and associated calcium responses. We find that axonal boutons have higher calcium accumulations than their parent axons, as was reportedin vitro. But, contrary to previousin vitroresults, our data reveal spike failures in a significant subset of branches, as a function of branching geometry and spike frequency. The filtering is correlated with the geometric ratio of the branch diameters, as expected by cable theory. These findings suggest that axonal morphologies contribute to signal processing in the cortex.