bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and genetic analysis of Costa Rican patients with Parkinson’s disease
Authors: Torrealba-Acosta Gabriel , Yu Eric , Lobo-Prada Tanya , Ruiz-Martínez Javier , Gorostidi-Pagola Ana , Gan-Or Ziv , Carazo-Céspedes Kenneth , Fornaguera-Trías Jaime 
Published: October 2020

AbstractBackgroundParkinson’s disease (PD) involves environmental risk and protective factors as well as genetic variance. Most of the research in genomics has been done in subjects of European ancestry leading to sampling bias and leaving Latin American populations underrepresented.ObjectiveWe sought to phenotype and genotype Costa Rican PD cases and controls.MethodsWe enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes includingGBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, ATP13A2.ResultsMean age of PD probands was 62.12 ± 13.51 years, 57.6% were male. Prevalence of risk and protective factors reached 30%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants inLRRK2were nominally associated with PD, six were located between amino acids p.1620-1623 in the C-terminal-of-ROC (COR) domain of LRRK2. NonsynonymousGBAvariants (p.T369M, p.N370S, p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenicGCH1variant, p.K224R.ConclusionThis is the first study that reports on sociodemographic, risk factors, clinical presentation and genetics of Costa Rican patients with PD.
Spectrum of spinal cord involvement in COVID-19: A systematic review
Authors: Mondal Ritwick , Deb Shramana , Shome Gourav , Ganguly Upasana , Lahiri Durjoy , Leon Julian Benito 
Published: October 2020

AbstractBackground and aimsRecent reports reveal incidences of spinal cord involvement in form of para-infectious or post-infectious myelitis raising potential concerns about the possibilities of SARS-CoV-2 behind the pathogenesis of spinal cord demyelination. In this study, we intend to summarise so far available pieces of evidence documenting SARS-CoV-2 mediated spinal demyelination in terms of clinical, laboratory parameters and imaging characteristics.MethodologyThis review was carried out based on the existing PRISMA (Preferred Report for Systemic Review and Meta-analyses) consensus statement. Data was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase and Cochrane library and Preprint servers up till 10th September, 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes “SARS-COV-2”, “COVID-19”, “demyelination” etc.ResultsA total of 21 cases were included from 21 case reports after screening from various databases and preprint servers. Biochemical analysis reveals that the majority of cases showed elevated CSF protein as well as lymphocytic pleocytosis. Interestingly, a majority of cases were found to be associated with long extensive transverse myelitis (LETM), and remaining cases were found to be associated with isolated patchy involvement or isolated short segment involvement or combined LETM and patchy involvement. Few cases were also found with significant co-involvement of the brain and spine based on the imaging data.ConclusionIt can be interpreted that SARS-CoV-2 may play a potential role in spinal demyelinating disorders in both para-infectious and post-infectious forms.HighlightsImaging data reveals LETM, short and patchy involvementsPara infectious myelitis precedes post-infectious manifestationAltered CSF parameters and myelitis-like symptoms at the onset of COVID-19Similar spinal cord involvements in related HCoVs infections
The effect of maternal pre-/early-pregnancy BMI and pregnancy smoking and alcohol on congenital heart diseases: a parental negative control study
Authors: Taylor Kurt , Elhakeem Ahmed , Nader Johanna Lucia Thorbjørnsrud , Yang Tiffany , Isaevska Elena , Richiardi Lorenzo , Vrijkotte Tanja , de Moira Angela Pinot , Murray Deirdre M , Finn Daragh , Mason Dan , Wright John , Oddie Sam , Roeleveld Nel , Harris Jennifer R , Andersen Anne-Marie Nybo , Caputo Massimo , Lawlor Deborah A. 
Published: October 2020

AbstractBackgroundCongenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown, but intrauterine mechanisms appear to be important. Higher prenatal body mass index (BMI), smoking and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear.MethodsSeven European birth cohorts including 232,390 offspring were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression and combined estimates using a fixed-effects meta-analysis and compared maternal-specific confounder-adjusted associations to similarly adjusted associations of paternal exposures. If there is a causal intrauterine effect of a maternal pregnancy exposure, we would expect to see a maternal-specific association, with no (or weaker) association with the paternal exposure.ResultsThere were 2,469 CHD cases (1.1%). The association of mean BMI with CHD was null and similar in mothers (adjusted OR per 1kg/m2: 1.00 (95%CI: 0.99, 1.02)) and fathers (OR: 1.01 (0.99, 1.03)). The analyses of BMI categories resulted in similar increased odds of CHD in overweight (mothers OR: 1.15 (1.01, 1.31) and fathers 1.10 (0.96, 1.27)) and obesity (mothers OR: 1.12 (0.93, 1.36) and fathers 1.16 (0.90, 1.50)). Maternal smoking was associated with increased odds of CHD (OR: 1.11 (0.97, 1.25)) but paternal smoking was not (OR: 0.96 (0.85, 1.07)). The difference increased when removing offspring with genetic/chromosomal defects (mothers OR: 1.15 (1.01, 1.32) and fathers 0.93 (0.83, 1.05)). The positive association with maternal pregnancy smoking appeared to be driven by non-severe CHD cases (OR: 1.22 (1.04, 1.44)). Associations with maternal (OR: 1.16 (0.52, 2.58)) and paternal (OR: 1.23 (0.74, 2.06)) moderate/heavy pregnancy alcohol consumption were similar.ConclusionsWe have shown that maternal, but not paternal, pregnancy smoking is associated with an increase in odds of offspring CHDs, primarily non-severe CHDs, providing evidence of an intrauterine effect. We found no strong evidence of an intrauterine effect of higher maternal BMI or alcohol consumption on offspring CHDs. Our findings provide further evidence for why smoking cessation is important during pregnancy.
Identification of biological correlates associated with respiratory failure in COVID-19
Authors: Oh Jung Hun , Tannenbaum Allen , Deasy Joseph O 
Published: October 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) is a global public health concern. Recently, a genome-wide association study (GWAS) was performed with participants recruited from Italy and Spain by an international consortium group.MethodsSummary GWAS statistics for 1610 patients with COVID-19 respiratory failure and 2205 controls were downloaded. In the current study, we analyzed the summary statistics with the information of loci and p-values for 8,582,968 single-nucleotide polymorphisms (SNPs), using gene ontology analysis to determine the top biological processes implicated in respiratory failure in COVID-19 patients.ResultsWe considered the top 708 SNPs, using a p-value cutoff of 5×10−5, which were mapped to the nearest genes, leading to 144 unique genes. The list of genes was input into a curated database to conduct gene ontology and protein-protein interaction (PPI) analyses. The top ranked biological processes were wound healing, epithelial structure maintenance, muscle system processes, and cardiac-relevant biological processes with a false discovery rate < 0.05. In the PPI analysis, the largest connected network consisted of 8 genes. Through literature search, 7 out of the 8 genes were found to be implicated in both pulmonary and cardiac diseases.ConclusionGene ontology and protein-protein interaction analyses identified cardio-pulmonary processes that may partially explain the risk of respiratory failure in COVID-19 patients.
Congruence of Health-related Quality of Life Assessment between Patient-Physician and Patient-Caregiver Dyads
Authors: Tang Chia-Chun , Chen Hsi , Wu Wei-Wen , Tsai Jaw-Shiun 
Published: October 2020

AbstractBackgroundExploring the congruence of health-related quality of life (HRQOL) evaluation provides valuable information regarding whether proxies can accurately reflect patient perceptions and the quality of symptom communication. It is particular important in advanced cancer population who experience poor HRQOL and have deteriorated ability to express their feeling. The main purpose of this study was to investigate the congruence of HRQOL reports between patient-physician and patient-caregiver dyads and to determine the association of variables, if any, with the congruence between dyads.MethodsThis observational study with a cross-sectional design first approached physicians who provided care for patients with advanced cancer at the participating institution. Then, participated physicians’ patients and their caregivers were recruited. All participants were required to independently fill out an HRQOL questionnaire during their outpatient visits. Descriptive statistics, weighted kappa, Wilcoxon signed-rank test, and linear regression were employed for data analysis.ResultsA total of 52 patient-physician and 27 patient-caregiver dyads were examined. Patients suffered from considerable problems in all three HRQOL domains: symptom, functioning, and overall HRQOL. The patients’ level of agreement was moderate with the caregivers and fair with the physicians. A significant relationship was found between several patient-related variables and disagreement.ConclusionThe study’s patient group experienced a compromised HRQOL, warranting immediate attention. When there are barriers to obtaining a patient’s self-repot, clinicians may consider caregivers as reasonable source. Some patients with special characteristics may need additional attention because their problems may be at greater risk of being overlooked.
Chromoplast differentiation in bell pepper (Capsicum annuum) fruits
Authors: Rödiger Anja , Agne Birgit , Dobritzsch Dirk , Helm Stefan , Müller Fränze , Pötzsch Nina , Baginsky Sacha 
Published: October 2020

AbstractWe report here a detailed analysis of the proteome adjustments that accompany chromoplast differentiation from chloroplasts during bell-pepper fruit ripening. While the two photosystems are disassembled and their constituents degraded, the cytochrome b6f complex, the ATPase complex as well as Calvin cycle enzymes are maintained at high levels up to fully mature chromoplasts. This is also true for ferredoxin (Fd) and Fd-dependent NADP reductase, suggesting that ferredoxin retains a central role in the chromoplasts redox metabolism. There is a significant increase in the amount of enzymes of the typical metabolism of heterotrophic plastids such as the oxidative pentose phosphate pathway (OPPP), amino acid and fatty acid biosynthesis. Enzymes of chlorophyll catabolism and carotenoid biosynthesis increase in abundance, supporting the pigment reorganization that goes together with chromoplast differentiation. The majority of plastid encoded proteins declines but constituents of the plastid ribosome and AccD increase in abundance. Furthermore, the amount of plastid terminal oxidase (PTOX) remains unchanged despite a significant increase in phytoene desaturase (PDS) levels, suggesting that the electrons from phytoene desaturation may be consumed by another oxidase. This may be a particularity of non-climacteric fruits such as bell pepper, that lack a respiratory burst at the onset of fruit ripening.
Cryptic genetic variation in a heat shock protein shapes the expressivity of a mutation affecting stem cell behaviour inC. elegans
Authors: Koneru Sneha L. , Hintze Mark , Katsanos Dimitris , Barkoulas Michalis 
Published: October 2020

AbstractA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of key mutations. We address this question by focusing on the epidermal seam cells, which display stem cell properties inCaenorhabditis elegans. We demonstrate that a null mutation in the GATA transcription factoregl-18, which is involved in seam cell fate maintenance, is more tolerated and thus has lower expressivity in the divergent CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in mutation expressivity between the two isolates. These QTLs reveal cryptic genetic variation, which acts to reinforce seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 lowersegl-18mutation expressivity. Our work underscores that natural variation in conserved heat shock proteins can shape mutation expressivity.
Within-species floral odor variation is maintained by spatial and temporal heterogeneity in pollinator communities
Authors: Szenteczki Mark A. , Godschalx Adrienne L. , Galmán Andrea , Espíndola Anahí , Gibernau Marc , Alvarez Nadir , Rasmann Sergio 
Published: October 2020

ABSTRACTFloral odor is a complex trait that mediates many biotic interactions, including pollination. While high intraspecific floral odor variation appears to be common, the ecological and evolutionary drivers of this variation are often unclear. Here, we investigated the influence of spatially and temporally heterogeneous pollinator communities on floral odor variation inArum maculatum(Araceae). Through Europe-wide field surveys, we identified high floral odor diversity and shifts in the dominant pollinator species within severalA. maculatumpopulations compared to pollinator data from the same sites ten years ago. Using common-garden experiments, we further confirmed that inflorescences from native and foreign pollinator backgrounds were equally efficient at attracting local pollinators. The substantial within-population floral odor variation we observed may therefore be advantageous when facing temporally heterogeneous pollinator communities. We propose spatio-temporal heterogeneity in pollinators as one potential mechanism maintaining diverse floral odor bouquets in angiosperms.
Hippocampal silent infarct leads to subtle cognitive decline that is associated with inflammation and gliosis at twenty-four hours after injury in a rat model
Authors: Finney Caitlin A. , Morris Margaret J. , Westbrook R. Frederick , Jones Nicole M. 
Published: October 2020

AbstractSilent infarcts (SI) are subcortical cerebral infarcts that occur in the absence of clinical symptoms commonly associated with ischemia and are linked to dementia development. Little is known about the pathophysiology underlying the cognitive dysfunction associated with SI, and few studies have examined the early cellular responses and neurobiological underpinnings. We induced SI in adult male Sprague-Dawley rats using an infusion of endothelin-1 in the CA1 dorsal hippocampus. Twenty-four hours later, we assessed cognition using the hippocampal-dependent object place recognition task. We also examined whether the resulting cognitive effects were associated with common markers of ischemia, specifically cell and synapse loss, gliosis, and inflammation, using histology and immunohistochemistry. Hippocampal SI led to subtle cognitive impairment on the object place recognition task 24-hours post-injury. This was characterized by a significant difference in exploration proportion relative to a pre-injury baseline and a positive association between time spent with both the moved and unmoved objects. SI did not result in any detectable cell or synaptophysin loss, but did increase apoptosis, gliosis and inflammation in the CA1. Principal component analysis indicated the main variables associated with hippocampal SI included increased time spent with the unmoved object, gliosis, apoptosis and inflammation as well as decreased exploration proportion and CA1 cells. Our data demonstrate that hippocampal SI can lead to cognitive dysfunction 24-hours after injury. Further, this appears to be driven by early degenerative processes including apoptosis, gliosis and inflammation, suggesting that these may be targets for early interventions treating hippocampal SI and its cognitive consequences.
Dynamics of brain function in chronic pain patients assessed by microstate analysis of resting-state electroencephalography
Authors: May Elisabeth S. , Gil Ávila Cristina , Dinh Son Ta , Heitmann Henrik , Hohn Vanessa D. , Nickel Moritz M. , Tiemann Laura , Tölle Thomas R. , Ploner Markus 
Published: October 2020

AbstractChronic pain is a highly prevalent and severely disabling disease, which is associated with substantial changes of brain function. Such changes have mostly been observed when analyzing static measures of brain activity during the resting-state. However, brain activity varies over time and it is increasingly recognized that the temporal dynamics of brain activity provide behaviorally relevant information in different neuropsychiatric disorders. Here, we therefore investigated whether the temporal dynamics of brain function are altered in chronic pain. To this end, we applied microstate analysis to eyes-open and eyes-closed resting-state electroencephalography (EEG) data of 101 patients suffering from chronic pain and 88 age- and gender-matched healthy controls. Microstate analysis describes EEG activity as a sequence of a limited number of topographies termed microstates, which remain stable for tens of milliseconds. Our results revealed that sequences of 5 microstates, labelled with the letters A to E, described resting-state brain activity in both groups and conditions. Bayesian analysis of the temporal characteristics of microstates revealed that microstate D has a less predominant role in patients than in healthy participants. This difference was consistently found in eyes-open and eyes-closed EEG recordings. No evidence for differences in other microstates was found. As microstate D has been previously related to attentional networks and functions, abnormalities of microstate D might relate to dysfunctional attentional processes in chronic pain. These findings add to the understanding of the pathophysiology of chronic pain and might eventually contribute to the development of an EEG-based biomarker of chronic pain.
Jasmonate biosynthesis arising from altered cell walls is prompted by turgor-driven mechanical compression and guides root hydrotropism
Authors: Mielke Stefan , Zimmer Marlene , Meena Mukesh Kumar , Dreos René , Stellmach Hagen , Hause Bettina , Voiniciuc Cătălin , Gasperini Debora 
Published: October 2020

ABSTRACTDespite the vital roles of jasmonoyl-isoleucine (JA-Ile) in governing plant growth and environmental acclimation, it remains unclear what intracellular processes lead to its induction. Here, we provide compelling genetic evidence that mechanical and osmotic regulation of turgor pressure represents a key factor in eliciting JA-Ile biosynthesis. After identifying cell wall mutant alleles inKORRIGAN1(KOR1) with elevated JA-Ile in seedling roots, we found that ectopic JA-Ile resulted from cell non-autonomous signals deriving from enlarged cortex cells compressing inner tissues and stimulating JA-Ile production. Restoring cortex cell size by cell-type-specific KOR1 complementation, by isolating a genetickor1suppressor, and by lowering turgor pressure with hyperosmotic treatments, abolished JA-Ile signalling. Strikingly, heightened JA-Ile levels guidedkor1roots towards greater water availability, uncovering a previously unrecognized JA-Ile function in root hydrotropism. Collectively, these findings enhance our understanding of JA-Ile biosynthesis initiation, and reveal a novel role of JA-Ile in orchestrating environmental resilience.
Transcriptome and interactome analyses identify theTP53interacting geneRCCD1as a candidate susceptibility gene at the 15p26.1 breast and ovarian cancer risk locus
Authors: Plummer Jasmine , Dezem Felipe Segato , Chen Stephanie S. , Dhungana Subash , Wali Deepika , Davis Brian , Kanska Justyna , Safi Niko , Seo Ji-Heui , Corona Rosario I , Schildkraut Joellen M , Pharoah Paul DP , Lawrenson Kate , Knott Simon RV , Freedman Matthew L , Kar Siddhartha P , Gayther Simon A 
Published: October 2020

ABSTRACTCommon genetic variation in a region on chromosome 15q26 confers susceptibility to breast and ovarian cancer. The P53 interacting gene RCCD1 in this region is a candidate susceptibility gene for both cancers. In this study, a colocalization analysis of breast and ovarian cancer case-control genetic association studies in over 145,000 and 146,000 controls fine mapped the shared association in this region to 17 pleiotropic credible causal risk variants (Pbreast< 1.16 × 10−14andPovary< 7.50 × 10−7). These variants were strongly associated with the expression of RCCD1 in normal breast and ovarian tissues. Circular chromosome conformation capture (4C) analysis ofRCCD1in breast and ovarian cancer cells identified similar patterns ofcis-interaction and significant binding site enrichment for theBRCA2interacting geneEMSY(Padjusted= 9.24 × 10−6). The 4C analysis pinpointed a single 2kB RCCD1 cis-interaction that contained two of the 17 shared risk variants. RCCD1trans-interacting regions mapped to previously identified genome wide significant (P < 5 × 10−8) breast cancer risk loci (1p34.2 and 3p14.1) and to the pleiotropic breast-ovarian cancer risk locus at chromosome 9q34.2. Stable overexpression of RCCD1 in breast and ovarian cancer precursor cells identified 13 and 11 differentially expressed genes (DEGs) respectively associated with breast and ovarian cancer risk at genome-wide significance (PMAGMA< 2.6 × 10−6after Bonferroni correction). Eighty-two DEGs shared between breast and ovarian cancer were strongly enriched in TP53 (P = 9.9 × 10−4), Hippo (P = 2.51 × 10−3) and TNF signaling (P = 4.7 × 10−3) pathways.