bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for Dementia and Cognitive Decline in Adults With Down Syndrome
Authors: Prado Mattar Guilherme , Uchida Ricardo R. , Haddad Glenda G. , Shiozawa Pedro , Rebouças da Silva Maria de Fátima , Hoexter Marcelo Q. , Busatto Geraldo F. , de Campos Bottino Cassio M. , Fonseca Luciana M. , Forlenza Orestes V. 
Published: March 2022

Objective:
The aim was to examine the psychometric properties of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a diagnostic tool to screen for dementia in aging individuals with Down syndrome (DS).

Methods:
This was a cross-sectional study of 92 individuals with DS 30 y or above of age) evaluated with the IQCODE. Using the informant questionnaire of the Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities, we divided the subjects into 3 diagnostic groups: stable cognition; prodromal dementia; and dementia. The ability of the IQCODE to discriminate between diagnostic groups was analyzed by calculating the areas under the receiver operator characteristic curves (AUCs).

Results:
The optimal IQCODE cutoffs were 3.14 for dementia versus stable cognition (AUC=0.993; P<0.001) and 3.11 for prodromal dementia+dementia versus stable cognition (AUC=0.975; P<0.001), with sensitivity/specificity/accuracy of 100%/96.8%/97.3%, and 93.3%/91.9%/92.4%, respectively. The IQCODE showed a weak-to-moderate correlation with cognitive performance (P<0.05).

Conclusion:
The IQCODE is a useful tool to screen for cognitive decline in individuals with DS and is suitable for use in a primary care setting.
Analysis of Electrocorticography in Epileptic Patients With Responsive Neurostimulation Undergoing Scalp Electroencephalography Monitoring
Authors: Lemus Hernan Nicolas , Gururangan Kapil , Fields Madeline Cara , Jetté Nathalie , Bolden Dina , Yoo Ji Yeoun 
Published: March 2022

Purpose:To describe the relationship of electrocorticography events detected by a brain-responsive neurostimulation system (RNS) and their association with ictal and interictal activity detected on simultaneous scalp EEG.Methods:We retrospectively identified patients with drug-resistant epilepsy implanted with RNS who subsequently underwent long-term scalp EEG monitoring. RNS detections were correlated to simultaneous activity recorded on scalp EEG to determine the characteristics of electrocorticography-stored long episodes associated with seizures or other findings on scalp EEG.Results:Eleven patients were included with an average of 3.6 days of monitoring. Most RNS detections were of very brief duration (<10 seconds, 92.9%) and received one stimulation therapy (80.8%). A high proportion of long episodes (67.1%) were not identified as electrographic seizures on scalp EEG. Of those ictal-appearing (71.2%) long episodes, 68.2% had seizure correlates. Long episodes associated with seizures on scalp EEG had a longer median duration compared with those without (39.7 vs. 16.8 seconds,P< 0.002) and had broader spread pattern and were of higher amplitude on electrocorticography. Brief potentially ictal rhythmic discharges were the most common EEG findings associated with long episodes that did not have scalp EEG seizure correlates (100% for ictal- and 50% for non–ictal-appearing long episodes).Conclusions:Longer, broader spread and higher amplitude intracranial RNS detections are more likely to manifest as electrographic seizures on scalp EEG. Brief potentially ictal rhythmic discharges may serve as a scalp EEG biomarker of ictal intracranial episodes that are detected as long episodes by the RNS but not identified as electrographic seizures on scalp EEG.
Testing microbiome associations with censored survival outcomes at both the community and individual taxon levels
Authors: Hu Yingtian , Li Yunxiao , Satten Glen A. , Hu Yi-Juan 
Published: March 2022

AbstractBackgroundFinding microbiome associations with possibly censored survival times is an important problem, especially as specific taxa could serve as biomarkers for disease prognosis or as targets for therapeutic interventions. The two existing methods for survival outcomes, MiRKAT-S and OMiSA, are restricted to testing associations at the community level and do not provide results at the individual taxon level. An ad hoc approach testing each taxon with a survival outcome using the Cox proportional hazard model may not perform well in the microbiome setting with sparse count data and small sample sizes.MethodsWe have previously developed the linear decomposition model (LDM) that unifies community-level and taxon-level tests into one framework. Here we extend the LDM to test survival outcomes. We propose to use the Martingale residuals or the deviance residuals obtained from the Cox model as continuous covariates in the LDM. We further construct tests that combine the results of analyzing each set of residuals separately. Finally, we extend PERMANOVA, the most commonly used distance-based method for testing community-level hypotheses, to handle survival outcomes in a similar manner.ResultsUsing simulated data, we showed that the LDM-based tests preserved the false discovery rate for testing individual taxa and had good sensitivity. The LDM-based community-level tests and PERMANOVA-based tests had comparable or better power than MiRKAT-S and OMiSA. An analysis of data on the association of the gut microbiome and the time to acute graft-versus-host disease revealed several dozen associated taxa that would not have been achievable by any community-level test, as well as improved community-level tests by the LDM and PERMANOVA over those obtained using MiRKAT-S and OMiSA.Availability and ImplementationThe new methods described here have been added to our R packageLDM, which is available on GitHub athttps://github.com/yijuanhu/LDM.
FGF10 triggers de novo alveologenesis in a BPD model: impact on the resident mesenchymal niche cells
Authors: Taghizadeh Sara , Chao Cho-Ming , Guenther Stefan , Glaser Lea , Gersmann Luisa , Michel Gabriela , Kraut Simone , Goth Kerstin , Koepke Janine , Heiner Monika , Vazquez-Armendariz Ana Ivonne , Herold Susanne , Samakovolis Christos , Weissmann Norbert , Ricci Francesca , Aquila Giorgio , Boyer Laurent , Ehrhardt Harald , Minoo Parviz , Bellusci Saverio , Rivetti Stefano 
Published: March 2022

AbstractBronchopulmonary dysplasia (BPD) is a neonatal lung disease developing in premature babies characterized by arrested alveologenesis and associated with decreased Fibroblast growth factor 10 (FGF10) expression. One-week hyperoxia (HYX) exposure of newborn mice leads to a permanent arrest in alveologenesis. To test the role of Fgf10 signaling to promote de novo alveologenesis following hyperoxia, we used transgenic mice allowing inducible expression of Fgf10 and recombinant FGF10 (rFGF10) protein delivered intraperitoneally. We carried out morphometry analysis, and IF on day 45. Alveolospheres assays were performed co-culturing AT2s from normoxia (NOX) with FACS-isolated Sca1Pos resident mesenchymal cells (rMC) from animals exposed to NOX, HYX+PBS, or HYX+FGF10. scRNAseq between rMC-Sca1Pos isolated from NOX and HYX+PBS were also carried out. Transgenic overexpression of Fgf10 and rFGF10 administration rescued the alveologenesis defects following HYX. Alveolosphere assays indicate that the activity of rMC-Sca1Pos is negatively impacted by HYX and partially rescued by rFGF10 treatment. Analysis by IF demonstrates a significant impact of rFGF10 on the activity of resident mesenchymal cells. scRNAseq results identified clusters expressing Fgf10, Fgf7, Pdgfra, and Axin2, which could represent the rMC niche cells for the AT2 stem cells. In conclusion, we demonstrate that rFGF10 administration is able to induce de-novo alveologenesis in a BPD mouse model and identified subpopulations of rMC-Sca1Pos niche cells potentially representing its cellular target.
Cellular redox metabolism is modulated by the distinct localization of cyclic nucleotide phosphodiesterase 5A isoforms
Authors: Cardarelli Silvia , Miele Adriana Erica , Campolo Federica , Massimi Mara , Mancini Patrizia , Biagioni Stefano , Naro Fabio , Giorgi Mauro , Saliola Michele 
Published: March 2022

Abstract3’-5’ cyclic nucleotide phosphodiesterases (PDEs) are a family of evolutionary conserved cAMP and/or cGMP hydrolysing enzymes, components of transduction pathways regulating crucial aspects of cell life. Among them, cGMP-specific PDE5, being a regulator of vascular smooth muscle contraction, is the molecular target of several drugs used to treat erectile dysfunction and pulmonary hypertension.Production of full-length murine PDE5A isoforms in the milk-yeast Kluyveromyces lactis showed that the quaternary assembly of MmPDE5A1 is a mixture of dimers and tetramers, while MmPDE5A2 and MmPDE5A3 only assembled as dimers. We showed that the N-terminal peptide is responsible for the tetramer assembly of MmPDE5A1, while that of MmPDE5A2 for its mitochondrial localization.Overexpression of the three isoforms alters at different levels the cAMP/cGMP equilibrium as well as the NAD(P)+/NAD(P)H balance and induces a metabolic switch from oxidative to fermentative. In particular, the mitochondrial localization of MmPDE5A2 unveiled the existence of a cAMP-cGMP signaling cascade in this organelle, for which we propose a metabolic model that could explain the role of PDE5 in some cardiomyopathies and some of the side effects of its inhibitors.
Protein prediction models support widespread post-transcriptional regulation of protein abundance by interacting partners
Authors: Srivastava Himangi , Lippincott Michael J. , Currie Jordan , Canfield Robert , Lam Maggie P. Y. , Lau Edward 
Published: March 2022

AbstractProtein and mRNA levels correlate only moderately. The availability of proteogenomics data sets with protein and transcript measurements from matching samples is providing new opportunities to assess the degree to which protein levels in a system can be predicted from mRNA information. Here we examined the contributions of input features in protein abundance prediction models. Using large proteogenomics data from 8 cancer types within the Clinical Proteomic Tumor Analysis Consortium (CPTAC) data set, we trained models to predict the abundance of over 13,000 proteins using matching transcriptome data from up to 958 tumor or normal adjacent tissue samples each, and compared predictive performances across algorithms, data set sizes, and input features. Over one-third of proteins (4,648) showed relatively poor predictability (elastic net r ≤ 0.3) from their cognate transcripts. Moreover, we found widespread occurrences where the abundance of a protein is considerably less well explained by its own cognate transcript level than that of one or more trans locus transcripts. The incorporation of additional trans-locus transcript abundance data as input features increasingly improved the ability to predict sample protein abundance. Transcripts that contribute to non-cognate protein abundance primarily involve those encoding known or predicted interaction partners of the protein of interest, including not only large multi-protein complexes as previously shown, but also small stable complexes in the proteome with only one or few stable interacting partners. Network analysis further shows a complex proteome-wide interdependency of protein abundance on the transcript levels of multiple interacting partners. The predictive model analysis here therefore supports that protein-protein interaction including in small protein complexes exert post-transcriptional influence on proteome compositions more broadly than previously recognized. Moreover, the results suggest mRNA and protein co-expression analysis may have utility for finding gene interactions and predicting expression changes in biological systems.
Contribution of Mendelian disorders in a population-based pediatric neurodegeneration cohort
Authors: Guo Rose , Mentch Frank D. , Li Dong , Will Erin E. , Ahrens-Nicklas Rebecca C. , Bhoj Elizabeth J. 
Published: March 2022

AbstractObjectivesTo evaluate Mendelian causes of neurodegenerative disorders in a cohort of pediatric patients as pediatric neurodegenerative disorders are a rare, diverse group of diseases. As molecular testing has advanced, many children can be diagnosed, but the relative contribution of various disorders is unclear.Study DesignPatients enrolled in the Center for Applied Genomics (CAG) Biobank at the Children’s Hospital of Philadelphia with neurodegenerative symptoms were identified using an algorithm that consisted of including and excluding selected ICD9 and ICD10 codes. A manual chart review was then performed to abstract detailed clinical information.ResultsOut of approximately 100,000 patients enrolled in the CAG Biobank, 76 had a neurodegenerative phenotype. Following chart review, 7 patients were excluded. Of the remaining 69 patients, 42 had a genetic diagnosis (60.9%) and 27 were undiagnosed (39.1%). There were 32 unique disorders. Common diagnoses included Rett syndrome, mitochondrial disorders and neuronal ceroid lipofuscinoses.ConclusionsThe disorders encountered in our cohort demonstrate the diverse diseases and pathophysiology that contribute to pediatric neurodegeneration. Establishing a diagnosis often informed clinical management, although curative treatment options are lacking. Many patients who underwent genetic evaluation remained undiagnosed, highlighting the importance of continued research efforts in this field.
Defining the genes required for survival of Mycobacterium bovis in the bovine host offers novel insights into the genetic basis of survival of pathogenic mycobacteria
Authors: Gibson Amanda J , Stiens Jennifer , Passmore Ian J , Faulkner Valwynne , Miculob Josephous , Willcocks Sam , Coad Michael , Berg Stefan , Werling Dirk , Wren Brendan W , Nobeli Irene , Villarreal-Ramos Bernardo , Kendall Sharon L 
Published: March 2022

AbstractTuberculosis has severe impacts in both humans and animals. Understanding the genetic basis of survival of both Mycobacterium tuberculosis, the human adapted species, and Mycobacterium bovis, the animal adapted species is crucial to deciphering the biology of both pathogens. There are several studies that identify the genes required for survival of M. tuberculosis in vivo using mouse models, however, there are currently no studies probing the genetic basis of survival of M. bovis in vivo. In this study we utilise transposon insertion sequencing in M. bovis to determine the genes required for survival in cattle. We identify genes encoding established mycobacterial virulence functions such as the ESX-1 secretion system, PDIM synthesis, mycobactin synthesis and cholesterol catabolism that are required in vivo. We show that, as in M. tuberculosis, phoPR is required by M. bovis in vivo despite the known defect in signalling through this system. Comparison to studies performed in glycerol adapted species such as M. bovis BCG and M. tuberculosis suggests that there are differences in the requirement for genes involved in cholesterol import (mce4 operon), oxidation (hsd) and detoxification (cyp125). We report good correlation with existing mycobacterial virulence functions, but also find several novel virulence factors, including genes involved in protein mannosylation, aspartate metabolism and glycerol-phosphate metabolism. These findings further extend our knowledge of the genetic basis of survival in vivo in bacteria that cause tuberculosis and provide insight for the development of novel diagnostics and therapeutics.ImportanceThis is the first report of the genetic requirements of an animal adapted member of the MTBC in a natural host. M. bovis has devastating impacts in cattle and bovine tuberculosis is a considerable economic, animal welfare and public health concern. The data highlight the importance of mycobacterial cholesterol catabolism and identifies several new virulence factors. Additionally, the work informs the development of novel differential diagnostics and therapeutics for TB in both human and animal populations.
Halophilic bacteria Bacillus altitudinis MIM2 producing bioactive melanin isolated from Mundra port, Kutch, Gujarat, India
Authors: Gordhanbhai Pankhaniya Mira , Jigna Chavda , Kurian Noble K 
Published: March 2022

AbstractMelanins are ubiquitous black or brown color pigments exhibiting a wide variety of bioactivities. They are stable and insoluble in nature. Melanin are industrially important pigment currently used in cosmetics, medicine and pharmaceuticals, industries. Bacteria mainly produce three types of melanin namely, Eumelanin, pheomelanin and pyomelanin which is usually extracellularly secreted. This makes the downstream processing of bacterial melanin easier. Stress conditions like salt stress, radiation stress etc. triggers the bacteria to produce melanin and several bacterial species were found to produce melanin under different stress induced conditions. In this present study we had isolated melanin producing bacteria from saline sediment sample of Mundra port, Kutch region of Gujarat state of India. The melanin producing bacteria was characterized using staining, biochemical and molecular methods. The melanin produced was extracted and analyzed using physicochemical techniques. The extracted melanin had shown good anti-bacterial and radical scavenging activity. To our knowledge, this is the first report on Bacillus altitudinis producing melanin.
A Unique Cellular Organization of Human Distal Airways and Its Disarray in Chronic Obstructive Pulmonary Disease
Authors: Rustam Samir , Hu Yang , Mahjour Seyed Babak , Randell Scott H. , Rendeiro Andre F. , Ravichandran Hiranmayi , Urso Andreacarola , D’Ovidio Frank , Martinez Fernando J. , Richmond Bradley , Polosukhin Vasiliy , Kropski Jonathan A. , Blackwell Timothy S. , Elemento Olivier , Shaykhiev Renat 
Published: March 2022

AbstractIn the human lung, terminal bronchioles (TBs), the most distal conducting airways, open to respiratory bronchioles (RBs) that lead to the alveolar region where gas exchange takes place. This transition occurs in pulmonary lobules, lung tissue units supplied by pre-TBs, which give rise to TBs. Accumulating evidence suggests that remodeling and loss of pre-TBs and TBs underlies progressive airflow limitation in chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. Understanding the nature of these changes at the single-cell level has so far been limited by poor accessibility of pre-TBs and TBs. Here, we introduce a novel method of region-precise airway dissection, which enables capture of the entire anatomical continuum of peripheral airways, from pre-TBs to RBs, and the associated alveolar region within the lobule. This approach allowed us to identify terminal airway-enriched secretory cells (TASCs), a unique epithelial cell population of distal airways expressing secretoglobin 3A2 (SCGB3A2) and/or surfactant protein B (SFTPB). TASCs were enriched in TBs, particularly, in areas of TB-RB transition and exhibited an intermediate, broncho-alveolar molecular pattern. TASC frequency was markedly decreased in pre-TBs and TBs of COPD patients compared to those in non-diseased lungs, accompanied by changes in cellular composition of vascular and immune microenvironments. In vitro regeneration assays identified basal cells (BCs) of pre-TBs and TBs as a cellular origin of TASCs in the human lung. Generation of TASCs by these region-specific progenitors was suppressed by IFN-γ signaling that was augmented in distal airways of COPD patients. Thus, altered maintenance of region-specific cellular organization of pre-TBs and TBs represents a key component of distal airway pathology in COPD.
‘Merging of ventral fibers at adhesions drives the remodeling of cellular contractile systems in fibroblasts.’
Authors: Narasimhan Shwetha , Holmes William R. , Kaverina Irina 
Published: March 2022

AbstractVentral stress fibers (VSFs) are contractile actin fibers present in the ventral plane of the cell and existing in a dynamic attachment with cell-matrix focal adhesions. VSFs are critical in cellular mechanobiological functions such as traction force production, cell polarization, and migration. VSF within their intracellular network vary from short, thinner fibers that are randomly oriented to long, thick fibers that span along the whole long axis of a cell.De novoVSF formation was shown to occur by condensation from the cortical actin mesh or by crosslinking of other stress fiber subtypes (dorsal stress fibers and transverse arcs) at the cell front. However, formation of long VSFs that extend across the whole cell axis is not well understood. Here, we report a novel phenomenon of VSF merging in migratory fibroblast cells, which is guided by mechanical force balance and contributes to VSF alignment along the long cell axis. The mechanism of VSF merging involves two steps: connection of two ventral fibers by an emerging myosin II bridge at an intervening adhesion and intervening adhesion dissolution to form a cohesive, contractile VSF. Our data indicate that these two steps are interdependent, since under conditions where adhesion disassembly is slowed, formation of the myosin bridge is slowed as well. Cellular data and computational modeling show that the angle of contact between merging fibers decides successful merging, with angles closer to 180 yielding merging events and shallower angles leading to merge failure. Our data and modeling further show that merging increases the share of uniformly aligned long VSFs, which would contribute to directional traction force production. Thus, we thoroughly characterize merging as process for dynamic reorganization of VSFs in steady state, investigating the steps and variants of the process as well as its functional significance in migratory cells.
Dose-efficient multimodal microscopy of human tissue at a hard X-ray nanoprobe beamline
Authors: Sala Simone , Zhang Yuhe , De La Rosa Nathaly , Dreier Till , Kahnt Maik , Langer Max , Dahlin Lars B. , Bech Martin , Villanueva-Perez Pablo , Kalbfleisch Sebastian 
Published: March 2022

X-ray fluorescence microscopy performed at nanofocusing synchrotron beamlines produces quantitative elemental distribution maps at unprecedented resolution (down to a few tens of nanometres), at the expense of relatively long measuring times and high absorbed doses. In this work, a method was implemented in which fast low-dose in-line holography was used to produce quantitative electron density maps at the mesoscale prior to nanoscale X-ray fluorescence acquisition. These maps ensure more efficient fluorescence scans and the reduction of the total absorbed dose, often relevant for radiation-sensitive (e.g. biological) samples. This multimodal microscopy approach was demonstrated on human sural nerve tissue. The two imaging modes provide complementary information at a comparable resolution, ultimately limited by the focal spot size. The experimental setup presented allows the user to swap between them in a flexible and reproducible fashion, as well as to easily adapt the scanning parameters during an experiment to fine-tune resolution and field of view.