bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genistein effect on cognition in early Alzheimer’s disease patients. The GENIAL clinical trial
Authors: Viña José , Escudero Joaquín , Baquero Miquel , Carbonell-Asíns JA , Tarazona-Santabalbina Francisco J. , Cebrián Mónica , Muñoz José Enrique , Satorres Encarnación , Melendez Juan Carlos , Rebolleda José Ferrer , del Puig Cózar Santiago Ma. , Santabárbara Gomez Jose Manuel , Jové Mariona , Pamplona Reinald , Borrás Consuelo 
Published: June 2022

ABSTRACTBackgroundDelaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics.Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer’s dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model.MethodsIn this double-blind, placebo-controlled, bicentric clinical trial we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 early symptomatic Alzheimer’s patients. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T) Clock-drawing test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test.ResultsWe report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p=0.031; dichotomized delayed centil REY copy p=0.002 and a tendency to improve in all the rest of them.The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake which showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878) while placebo-treated did increase it (p=0.036) We did not observe significant changes in other brain areas studiedConclusionsThis study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer’s dementia in patients with mild cognitive impairment. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study.Trial registrationNCT01982578
Longitudinal profiles of plasma gelsolin, cytokines and antibody expression predict COVID-19 severity and hospitalization outcomes
Authors: Asare-Werehene Meshach , McGuinty Michaeline , Vranjkovic Agatha , Galipeau Yannick , Cowan Juthaporn , Cameron Bill , Cooper Curtis L. , Langlois Marc-André , Crawley Angela M. , Tsang Benjamin K. 
Published: June 2022

AbstractBackgroundPrognostic markers for COVID-19 disease outcome are currently lacking. Plasma gelsolin (pGSN) is an actin-binding protein and an innate immune marker involved in disease pathogenesis and viral infections. Here, we demonstrate the utility of pGSN as a prognostic marker for COVID-19 disease outcome; a test performance that is significantly improved when combined with cytokines and antibodies compared to other conventional markers such as CRP and ferritin.MethodsBlood samples were longitudinally collected from hospitalized COVID-19 patients as well as COVID-19 negative controls and the levels of pGSN in μg/mL, cytokines and anti-SARS-CoV-2 spike protein antibodies assayed. Mean±SEM values were correlated with clinical parameters to develop a prognostic platform.ResultspGSN levels were significantly reduced in COVID-19 patients compared to healthy individuals. Additionally, pGSN levels combined with plasma IL-6, IP-10 and M-CSF significantly distinguished COVID-19 patients from healthy individuals. While pGSN and anti-spike IgG titers together strongly predict COVID-19 severity and death, the combination of pGSN and IL-6 was a significant predictor of milder disease and favorable outcomes.ConclusionTaken together, these findings suggest that multi-parameter analysis of pGSN, cytokines and antibodies could predict COVID-19 hospitalization outcomes with greater certainty compared with conventional clinical laboratory markers such as CRP and ferritin. This research will inform and improve clinical management and health system interventions in response to SARS-CoV-2 infection.Trial RegistrationN/AFundingThe Ottawa Hospital Department of Medicine - Special Pandemic Agile Research Competition
Impact of the Pandemic: Screening for Social Risk Factors in the Intensive Care Unit
Authors: Ge Derek , Weber Alec M. , Vatson Jayanth , Andrews Tracy , Levytska Natalia , Shu Carol , Hussain Sabiha 
Published: June 2022

ABSTRACTDue to limitations in data collected through electronic health records, the social risk factors (SRF) that predate severe illness and restrict access to critical care services are poorly understood. This study explored the feasibility and utility of directly eliciting SRF in the ICU by implementing a screening program. 566 critically ill patients at the medical ICU of Robert Wood Johnson University Hospital from July 1, 2019, to September 31, 2021, were screened for seven SRF. We compared characteristics between those with and without each SRF through Chi-squared tests and Wilcoxon Rank Sum tests. Overall, 39.58% of critically ill patients reported at least one SRF. Age, socioeconomic status, insurance type, and severity score differed significantly depending on the SRF. Most notably, the prevalence of SRF, overall and individually, changed after March 2020 which represented the onset of the COVID-19 pandemic. Our findings indicate that SRF can induce low-risk severe illnesses and restrict access to critical care services.
Comparative ultrasonographic anatomy of “medial-oblique” probe position with classic “short axis” probe position for ultrasound guided axillary vein cannulation: A cross-over study
Authors: Maitra Souvik , Bhattacharjee Sulagna , Baidya Dalim K. , Ray Bikash R 
Published: June 2022

AbstractStudy objectiveSubclavian vein cannulation in the infraclavicular region may be a preferred approach as it is associated with less infection than internal jugular or femoral venous access in critically ill patients. ‘Short-axis view” has a problem that shaft of the puncture needle is not visualized and tip of the needle is only seen as ‘dot’; hence posterior wall of the vein puncture is always possible with ‘short-axis approach’. We have designed this study to know the ultrasonographic anatomy of subclavian vein in short axis and medial oblique view.DesignProspective randomized, cross-over.SettingOperating room.PatientsOne hundred consecutive patients aged between 18-50yrs of either sex, ASA PS I-III undergoing elective surgery under general anesthesia.InterventionThe ultrasonographic anatomy of axillary vein cannulation in infraclavicular region in one hundred patients was assessed as per randomization sequence in medial oblique probe position and short-axis probe position.MeasurementsAntero-posterior and transverse diameter of axillary vein, pleural line visibility.Main ResultsTransverse diameter of subclavian vein was higher in ‘medial-oblique’ view [mean difference (95% confidence interval) 0.12 cm (0.09-0.16) cm; p<0.0001]. However, mean (standard deviation) antero-posterior diameter was similar in two views [0.72(0.15) cm in short axis versus 0.68 (0.16) cm in medial oblique; p=0.07]. Visibility of pleural line was similar in both the view (p=0.84, Chi-square test).ConclusionMedial-oblique view may be useful in axillary approach of subclavian vein cannulation. Further clinical studies are required to know whether medial oblique view can reduce complications and increase success rate of ultrasound guided subclavian vein cannulation over short axis view.
Genomic Insights of Bruneian Malays
Authors: Azmi Mirza , Chen Lie , Idris Adi , Lu Zen H. 
Published: June 2022

AbstractThe Malays and their many sub-ethnic groups collectively make up one of the largest population groups in Southeast Asia. However, their genomes, especially those from Brunei, remain very much underrepresented and understudied. Here, we analysed the publicly available WGS and genotyping data of two and 39 Bruneian Malay individuals, respectively. NGS reads from the two individuals were first mapped against the GRCh38 human reference genome and their variants called. Of the total ∼5.28 million short nucleotide variants and indels identified, ∼217K of them were found to be novel; with some predicted to be deleterious and associated with risk factors of common non-communicable diseases in Brunei. Unmapped reads were next mapped against the recently reported novel Chinese and Japanese genomic contigs and de novo assembled. ∼227 Kbp genomic sequences missing in GRCh38 and a partial open reading frame encoding a potential novel small zinc finger protein were successfully discovered. Interestingly, although the Malays in Brunei, Singapore and Malaysia share >83% common variants, principal component and admixture analysis comparing the genetic structure of the local Malays against other Asian population groups suggested that they are genetically closer to some Filipino ethnic groups than the Malays in Malaysia and Singapore. Taken together, our work provides the first comprehensive insight into the genomes of the Bruneian Malay population.
A reference single-cell map of freshly dissociated human synovium in inflammatory arthritis with an optimized dissociation protocol for prospective synovial biopsy collection
Authors: Edalat Sam G. , Gerber Reto , Houtman Miranda , Kuret Tadeja , Ižanc Nadja , Micheroli Raphael , Burki Kristina , Burja Blaž , Pauli Chantal , Rotar Žiga , Tomšič Matija , Čučnik Saša , Distler Oliver , Ospelt Caroline , Sodin-Semrl Snežna , Robinson Mark D. , Bertoncelj Mojca Frank 
Published: June 2022

AbstractSingle-cell RNA-sequencing is advancing our understanding of synovial pathobiology in inflammatory arthritis. Here, we optimized the protocol for the dissociation of fresh synovial biopsies and created a reference single-cell map of fresh human synovium in inflammatory arthritis. We utilized the published method for dissociating cryopreserved synovium and optimized it for dissociating small fresh synovial biopsies. The optimized protocol enabled the isolation of a good yield of consistently highly viable cells, minimizing the dropout rate of prospectively collected biopsies. Our reference synovium map comprised over 100’000 unsorted single-cell profiles from 25 synovial tissues of patients with inflammatory arthritis. Synovial cells formed 11 lymphoid, 15 myeloid and 16 stromal cell clusters, including IFITM2+ synovial neutrophils. Using this reference map, we successfully annotated published synovial scRNA-seq datasets. Our dataset uncovered endothelial cell diversity and identified SOD2highSAA1+SAA2+ and SERPINE1+COL5A3+ fibroblast clusters, expressing genes linked to cartilage breakdown (SDC4) and extracellular matrix remodelling (LOXL2, TGFBI, TGFB1), respectively. We broadened the characterization of tissue resident FOLR2+COLEC12highand LYVE1+SLC40A1+ macrophages, inferring their extracellular matrix sensing and iron recycling activities. Our research brings an efficient synovium dissociation protocol and a reference annotation resource of fresh human synovium, while expanding the knowledge about synovial cell diversity in inflammatory arthritis.
scMuffin: an R package for disentangling solid tumor heterogeneity from single-cell expression data
Authors: Nale Valentina , Chiodi Alice , Di Nanni Noemi , Cifola Ingrid , Moscatelli Marco , Cocola Cinzia , Gnocchi Matteo , Piscitelli Eleonora , Sula Ada , Zucchi Ileana , Reinbold Rolland , Milanesi Luciano , Mezzelani Alessandra , Pelucchi Paride , Mosca Ettore 
Published: June 2022

AbstractINTRODUCTIONSingle-cell (SC) gene expression analysis is crucial to dissect the complex cellular heterogeneity of solid tumors, which is one of the main obstacles for the development of effective cancer treatments. Such tumors typically contain a mixture of cells with aberrant genomic and transcriptomic profiles affecting specific sub-populations that might have a pivotal role in cancer progression, whose identification eludes bulk RNA-sequencing approaches. We presentscMuffin, an R package that enables the characterization of cell identity in solid tumors on the basis of a various and complementary analyses on SC gene expression data.RESULTSscMuffin provides a series of functions to calculate qualitative and quantitative scores, such as: expression of marker sets for normal and tumor conditions, pathway activity, cell state trajectories, CNVs, transcriptional complexity and proliferation state. Thus, scMuffin facilitates the combination of various evidences that can be used to distinguish normal and tumoral cells, define cell identities, cluster cells in different ways, link genomic aberrations to phenotypes and identify subtle differences between cell subtypes or cell states. We analysed public SC expression datasets of human high-grade gliomas as a proof-of-concept to show the value of scMuffin and illustrate its user interface. Nevertheless, these analyses lead to interesting findings, which suggest that some chromosomal amplifications might underlie the invasive tumor phenotype and the presence of cells that possess tumor initiating cells characteristics.CONCLUSIONSThe analyses offered by scMuffin and the results achieved in the case study show that our tool helps addressing the main challenges in the bioinformatics analysis of SC expression data from solid tumors.
The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice
Authors: Moffat Jeffrey J. , Sakhai Samuel A. , Hoisington Zachary W. , Ehinger Yann , Ron Dorit 
Published: June 2022

ABSTRACTThe brain-derived neurotrophic factor (BDNF) Valine 66 to Methionine human polymorphism results in impaired activity-dependent BDNF release and has been linked to psychiatric disorders including depression and anxiety. We previously showed that male knock-in mice carrying the mouse Methionine homolog (Met68BDNF) exhibit excessive and compulsive alcohol drinking behaviors as compared to the wild-type Val68BDNF mice. Here, we set out to determine the potential mechanism for the heightened and compulsive alcohol drinking phenotypes detected in Met68BDNF mice. We found that male, but not female Met68BDNF mice exhibit social anxiety-like behaviors. We further show that male Met68BDNF mice exhibit a preference for alcohol over social interaction. In contrast, alcohol place preference without an alternative social reward, is similar in male Met68BDNF and Val68BDNF mice. Since the Met68BDNF mice show social anxiety phenotypes, we tested whether alcohol reliefs anxiety similarly in Met68BDNF and Val68BDNF mice and found that male, but not female Met68BDNF mice are insensitive to the acute anxiolytic action of alcohol. Finally, we show that this acute tolerance to alcohol-dependent anxiolysis can be restored by overexpressing wild-type Val68BDNF in the ventral hippocampus (vHC) of Met68BDNF mice. Together, our results suggest that excessive alcohol drinking in the Met68BDNF may be attributed, in part, to heighted social anxiety and a lack of alcohol-dependent anxiolysis, a phenotype that is associated with malfunction of BDNF signaling in thevHC of male Met68BDNF mice.
Inter-regional delays fluctuate in the human cerebral cortex
Authors: Moon Joon-Young , Müsch Kathrin , Schroeder Charles E. , Valiante Taufik A. , Honey Christopher J. 
Published: June 2022

AbstractThe flow of information between cortical regions depends on the excitability at each site, which is reflected in fluctuating field potentials. It remains uncertain how global changes in field potentials affect the latency and strength of cortico-cortical couplings. Therefore, we measured changes in oscillations and inter-regional couplings by recording intracranially from the human cerebral cortex. As participants listened to an auditory narrative, global increases in low-frequency (4-14 Hz) power were associated with stronger and more delayed inter-regional couplings. Conversely, increases in broadband high-frequency power were associated with weaker coupling and zero lag. In network oscillator models, these changes in cortico-cortical latency can be generated by varying the effective influence of inter-regional projections relative to intra-regional dynamics. Altogether, low-frequency oscillations appear to modulate information flow across the human cerebral cortex, as they covary with the timing of peak excitability between regions, and this process may be regulated by nonspecific ascending projections.
Hi-TrAC reveals fine-scale chromatin structures organized by transcription factors
Authors: Liu Shuai , Cao Yaqiang , Cui Kairong , Tang Qingsong , Zhao Keji 
Published: June 2022

AbstractThe three-dimensional genomic structure plays a critical role in gene expression, cellular differentiation, and pathological conditions. It is pivotal to elucidate fine-scale chromatin architectures, especially interactions of regulatory elements, to understand the temporospatial regulation of gene expression. In this study, we report Hi-TrAC as a proximity ligation free, robust, and sensitive technique to profile genome-wide chromatin interactions at high-resolution among accessible regulatory elements. Hi-TrAC detects chromatin looping among accessible chromatin regions at single nucleosome resolution. With almost half-million identified loops, we constructed a comprehensive interaction network of regulatory elements across the genome. After integrating chromatin binding profiles of transcription factors, we discovered that cohesin complex and CTCF are responsible for organizing long-range chromatin loops, related to domain formation; whereas ZNF143 and HCFC1 are involved in structuring short-range chromatin loops between regulatory elements, which directly regulate gene expression. Thus, we developed a new methodology to identify a delicate and comprehensive network of cis-regulatory elements, revealing the complexity and a division of labor of TFs in chromatin looping for genome organization and gene expression.
Genetic or transcranial magnetic stimulation of B-RAF–MEK signaling promotes CST axon sprouting and functional regeneration
Authors: Boato Francesco , Guan Xiaofei , Zhu Yanjie , Ryu Youngjae , Voutounou Mariel , Rynne Christopher , Freschlin Chase R. , Zumbo Paul , Betel Doron , Matho Katie , Makarov Sergey N. , Wu Zhuhao , Son Young-Jin , Nummenmaa Aapo , Huang Josh Z. , Edwards Dylan J. , Zhong Jian 
Published: June 2022

ABSTRACTFacilitating axon regeneration in the injured central nervous system remains a challenging task. RAF–MEK signaling plays an important role in axon elongation during nervous system development. Here we show that activation of B-RAF in mature corticospinal neurons elicited the expression of a discrete set of transcription factors previously implicated in the regeneration of zebrafish optic nerve axons. Genetic activation of B-RAF–MEK signaling promoted robust regeneration and sprouting of corticospinal tract axons after injury. Newly sprouting axon collaterals formed synaptic connections with spinal interneurons, correlating with the recovery of skilled motor function. Seeking a non-invasive way to stimulate axon regeneration, we found that suprathreshold high-frequency repetitive transcranial magnetic stimulation activates the B-RAF canonical effectors MEK1/2 and requires MEK1/2 activity to promote corticospinal axon regeneration and sprouting after injury. These data demonstrate a central role of neuron-intrinsic RAF–MEK signaling in enhancing the growth capacity of mature corticospinal neurons and propose HF-rTMS as a potential therapy for spinal cord injury.One Sentence SummaryGenetic or HF-rTMS-mediated activation of B-RAF– MEK signaling promotes CST axon sprouting and functional regeneration after a spinal cord injury.
Comparative phyloproteomics identifies conserved plasmodesmal proteins
Authors: Johnston Matthew G. , Breakspear Andrew , Samwald Sebastian , Zhang Dan , Papp Diana , Faulkner Christine , de Keijzer Jeroen 
Published: June 2022

AbstractPlasmodesmata connect neighbouring plant cells across the cell wall. They are cytosolic bridges, lined by the plasma membrane and traversed by endoplasmic reticulum to connect these cell components between cells and tissues. While plasmodesmata are notoriously difficult to extract, tissue fractionation and proteomic analyses have yielded valuable knowledge of their composition. Most proteomic profiles originate from cell suspension cultures in which simple plasmodesmata dominate and have been exclusively generated from dicotyledonous plant species. Here we have generated two novel proteomes to expand tissue and taxonomic representation of plasmodesmata: one from mature Arabidopsis leaves and one from the moss Physcomitrium patens. We have leveraged these and existing data to perform a comparative analysis that, owing to comparing proteomes from an expanded taxonomic tree, allowed us to identify conserved protein families that are associated with plasmodesmata that likely serve as core structural or functional components. Thus, we identified β-1,3-glucanases, C2 lipid-binding proteins and tetraspanins as core plasmodesmal components, with proteins from P. patens and Arabidopsis maintaining plasmodesmal association across diverse species. Our approach has not only identified elements of a conserved, core plasmodesmal proteome, but also demonstrated the added power offered by comparative analysis. Conserved plasmodesmal proteins establish a basis upon which ancient plasmodesmal function can be further investigated to determine the essential roles these structures play in multicellular organism physiology in the green lineages.
Genomic analysis of the recent monkeypox outbreak
Authors: Giorgi Federico M. , Pozzobon Daniele , Di Meglio Antonio , Mercatelli Daniele 
Published: June 2022

AbstractThe Monkeypox virus is the etiological cause of a recent multi-country outbreak, with nearly one hundred distinct cases detected outside the endemic areas of Africa in May 2022. In this article, we analyze the sequences of two full genomes of Monkeypox virus from Portugal and Belgium, and compare them with all available Monkeypox sequences, annotated by year and geographic origin, as well as related Cowpox and Variola (smallpox) virus sequences. Our results show that the recent outbreak is most likely originating from the West African clade of Monkeypox, with >99% sequence identity with sequences derived from historical and recent cases, dating from 1971 to 2017. We analyze specific mutations occurring in viral proteins A42R (for which a crystal structure is available) and H3L (an important epitope in host immune recognition), highlighting specific amino acids varying between the current outbreak, previous Monkeypox and Cowpox sequences and the historical Variola virus. Genome-wide sequence analysis of the recent outbreak and other monkeypox/cowpox/variola viruses shows a very high conservation, with 97.9% (protein-based) and 97.8% (nucleotide-based) sequence identity.