bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paracoccus albicereus sp. nov., isolated from the shallow-sea hydrothermal system off Kueishantao Island
Authors: He Yajie , Lin Dan , Chen Beihan , Liu Xinzhu , Ye Jianing , Sun Jia , Tang Kai 
Published: August 2023

Strain designated TK19116T was isolated from the shallow-sea hydrothermal systems off Kueishantao Island in Taiwan, China. The bacterium was Gram-stain-negative, aerobic, oxidase-positive and catalase-positive. Cells of the strain TK19116T were short-rod-shaped and non-motile. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that strain TK19116T belonged to the genus

Paracoccus

, with the highest sequence similarity to

Paracoccus alkanivorans

4-2T (97.1 %). The average nucleotide identity values between the strain TK19116T with

Paracoccus alkanivorans

4-2T,

Paracoccus zhejiangensis

J6T,

Paracoccus siganidrum

M26T and

Paracoccus tegillarcae

BM15T were 75.3, 76.7, 76.7 and 75.8%, respectively. The digital DNA–DNA hybridization value between the strain TK19116T with

Paracoccus alkanivorans

4-2T,

Paracoccus zhejiangensis

J6T,

Paracoccus siganidrum

M26T and

Paracoccus tegillarcae

BM15T were 19.7, 20.3, 20.5 and 20.0%, respectively. The main respiratory quinone of strain TK19116T was ubiquinone 10. The polar lipids include aminolipid, phosphatidylcholine, diphosphatidylglycerol, glycolipid, phosphatidylglycerol and phospholipid. The principal fatty acid of strain TK19116T was summed feature 8 (C18 : 1
ω6c and/or C18 : 1
ω7c). The G+C content of the chromosomal DNA was 64.2 %. The combination of the results of the phylogenetic, phenotypic and chemotaxonomic analysis, strain TK19116T represents a novel species of the genus

Paracoccus

, for which the name Paracoccus albicereus sp. nov. is proposed. The type strain is TK19116T (= MCCC 1K08025T=JCM 35527T).
Normalization of Drug and Therapeutic Concepts with TheraPy
Authors: Cannon Matthew , Stevenson James , Kuzma Kori , Kiwala Susanna , Warner Jeremy L , Griffith Obi L , Griffith Malachi , Wagner Alex H 
Published: August 2023

AbstractWorking with therapeutic terminology in the field of medicine can be challenging due to both the number of ways terms can be addressed and the ambiguity associated with different naming strategies. A therapeutic concept can be identified across many facets from ontologies and vocabularies of varying focus, including natural product names, chemical structures, development codes, generic names, brand names, product formulations, or treatment regimens. This diversity of nomenclature makes therapeutic terminology difficult to manage and harmonize. As the number and complexity of available therapeutic ontologies continues to increase, the need for harmonized cross-resource mappings is becoming increasingly apparent. Harmonized concept mappings will enable the linking together of like-concepts despite source-dependent differences in data structure or semantic representation. To support these mappings, we introduce TheraPy, a Python package and web API that constructs stable, searchable merged concepts for drugs and therapeutic terminologies using publicly available resources and thesauri. By using a directed graph approach, TheraPy can capture commonly used aliases, trade names, annotations, and associations for any given therapeutic and combine them under a single merged concept record. Using this approach, we found that TheraPy tends to normalize therapeutic concepts to their underlying active ingredients (excluding non-drug therapeutics, e.g. radiation therapy, biologics), and unifies all available descriptors regardless of ontological origin. In this report, we highlight the creation of 16,069 unique merged therapeutic concepts from 9 distinct sources using TheraPy. Further, we analyze rates of normalization for therapeutic terms taken from publicly available vocabularies.
Graphical Learning and Causal Inference for Drug Repurposing
Authors: Xu Tao , Zhao Jinying , Xiong Momiao 
Published: August 2023

AbstractGene expression profiles that connect drug perturbations, disease gene expression signatures, and clinical data are important for discovering potential drug repurposing indications. However, the current approach to gene expression reversal has several limitations. First, most methods focus on validating the reversal expression of individual genes. Second, there is a lack of causal approaches for identifying drug repurposing candidates. Third, few methods for passing and summarizing information on a graph have been used for drug repurposing analysis, with classical network propagation and gene set enrichment analysis being the most common. Fourth, there is a lack of graph-valued association analysis, with current approaches using real-valued association analysis one gene at a time to reverse abnormal gene expressions to normal gene expressions.To overcome these limitations, we propose a novel causal inference and graph neural network (GNN)-based framework for identifying drug repurposing candidates. We formulated a causal network as a continuous constrained optimization problem and developed a new algorithm for reconstructing large-scale causal networks of up to 1,000 nodes. We conducted large-scale simulations that demonstrated good false positive and false negative rates.To aggregate and summarize information on both nodes and structure from the spatial domain of the causal network, we used directed acyclic graph neural networks (DAGNN). We also developed a new method for graph regression in which both dependent and independent variables are graphs. We used graph regression to measure the degree to which drugs reverse altered gene expressions of disease to normal levels and to select potential drug repurposing candidates.To illustrate the application of our proposed methods for drug repurposing, we applied them to phase I and II L1000 connectivity map perturbational profiles from the Broad Institute LINCS, which consist of gene-expression profiles for thousands of perturbagens at a variety of time points, doses, and cell lines, as well as disease gene expression data under-expressed and over-expressed in response to SARS-CoV-2.
Dynamics of abdominal symptoms during the start of a new therapy with Elexacaftor/Tezacaftor/Ivacaftor using the novel CFAbd-day2day questionnaire
Authors: Mainz Jochen G. , Barucha Anton , Huang Pu , Bechinger Lilith , Duckstein Franziska , Polte Louise , Sadrieh Pauline , Nährlich Lutz , Eickmeier Olaf , van Dullemen Suzanne , Eschenhagen Patience , Schwarz Carsten , Lüth Stefan , Zagoya Carlos , Graepler-Mainka Ute 
Published: August 2023

AbstractBackgroundElexacaftor-tezacaftor-ivacaftor (ETI) is a novel highly effective CFTR modulator combination proven to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. Recently, we revealed significant reductions of abdominal symptoms (AS) in German, British and Irish pwCF after 24-26 weeks of ETI using the CFAbd-Score, the first PROM specifically developed and validated for pwCF following FDA guidelines. Notably, many pwCF reported marked changes in their AS during the first days of the new treatment. To capture these immediate effects, we developed the CFAbd-day2day, a CF-specific GI-diary, following FDA and COSMIN guidelines.AimsTo prospectively capture immediate dynamics of AS using the CFAbd-day2day 14 days before and 14-28 days after ETI initiation. In addition, we aim here to provide validation steps of the novel PROM concerning sensitivity to changes.MethodsTo develop the CFAbd-day2day, focus groups (community voice=pwCF and their proxies and CF specialists from different fields) were repeatedly consulted. Before and under the new ETI therapy pwCF prospectively scored AS on a daily basis with the CFAbd-day2day.ResultsAltogether, n=45 pwCF attended in 5 CF centers prospectively completed the CFAbd-day2day before (mean±sd: −14±7 days) and after (mean±sd: 28±23 days) ETI initiation. Whereas cumulative scores significantly decreased during the 3-4-week time frame after ETI initiation, compared to the two weeks prior to therapy, many patients who revealed a relatively stable level of AS before ETI reported changes during the first days of treatment with the highly effective CFTR modulators. Items like pain and flatulence increased in up to 21% of patients during the first 14 days of therapy but they improved during days 15-27.ConclusionThe CFAbd-day2day, specifically developed and in process of validation to prospectively capture GI symptoms in pwCF, provides new substantial insights into the dynamics of AS in pwCF receiving a new treatment with ETI. The novel tool is also helpful to prospectively monitor patients with specific GI problems. International implementation and further validation steps of the diary are ongoing.
Public awareness of and opinions on the use of mathematical transmission modelling to inform public health policy in the United Kingdom
Authors: McCabe Ruth , Donnelly Christl A. 
Published: August 2023

AbstractMathematical transmission modelling is a key component of scientific evidence used to inform public health policy and became particularly prominent during the COVID-19 pandemic. As key stakeholders, it is vital that the public perception of this set of tools is better understood. To complement a previously published article on the science-policy interface by the authors of this study, novel data were collected via responses to a survey via two methods: via an online panel (“representative” sample) and via social media (“non-probability” sample). Many identical questions were asked separately for the period “prior to” compared to “during” the COVID-19 pandemic.All respondents were increasingly aware of the use of modelling in informing policy during the pandemic, with significantly higher levels of awareness among social media respondents than online panel respondents. Awareness generally stemmed from the news media and social media during the pandemic. Transmission modelling informing public health policy was perceived as more reliable during the pandemic compared to the pre-pandemic period in both samples, with awareness being positively associated with reliability within both samples and time points, except for social media during the pandemic. Trust in government public health advice remained high across samples and time periods overall but was lower in the period of the pandemic compared to the pre-pandemic period. The decay in trust was notably greater among social media respondents. Many respondents from both samples explicitly made the distinction that their trust was reserved for “scientists” and not “politicians”. Almost all respondents, regardless of sample, believed governments have responsibility for the communication of modelling to the public.These results provide an important reminder of the potentially skewed conclusions that could be drawn from non-representative samples.
Electric field based dosing for TMS
Authors: Numssen Ole , Kuhnke Philipp , Weise Konstantin , Hartwigsen Gesa 
Published: August 2023

AbstractTranscranial magnetic stimulation (TMS) is an invaluable non-invasive brain stimulation (NIBS) technique to modulate cortical activity and behavior, but high within- and between-participant variability limits its efficacy and reliability. Here, we explore the potential of electric field (e-field) based TMS dosing to reduce its variability and discuss current challenges as well as future pathways. In contrast to previous dosing approaches, e-field dosing better matches the stimulation strength across cortical areas, both within and across individuals. Challenges include methodological uncertainties of the e-field simulation, target definitions, and comparability of different stimulation thresholds across cortical areas and NIBS protocols. Despite these challenges, e-field dosing promises to substantially improve NIBS applications in neuroscientific research and personalized medicine.Outstanding Questions BoxOutstanding QuestionsDoes the cortical threshold for effective stimulation differ between primary regions and higher-level association areas? How large is the impact of cytoarchitectonic differences between regions on a stimulation threshold?Do cortical stimulation thresholds differ across individuals? Are thresholds stable within an individual across the lifespan? What are the physiological factors influencing these thresholds?Can a cortical stimulation threshold measured with single-pulse TMS be transferred to repetitive TMS protocols for the study of cognition?How does the cortical stimulation threshold interact with the current brain state?Graphical abstract
Machine Learning Gene Signature to Metastatic ccRCC based on ceRNA Network
Authors: Farias Epitácio , Terrematte Patrick , Stransky Beatriz 
Published: August 2023

AbstractRenal carcinoma is a pathology of silent and multifactorial development characterized by a high rate of metastases in patients. After several studies have elucidated the activity of coding genes in the metastatic progression of renal carcinoma, new studies seek to evaluate the association of non-coding genes, such as competitive endogenous RNA (ceRNA). Thus, this study aims to build a gene signature for clear cell renal cell carcinoma (ccRCC) associated with metastatic development from a ceRNA network and to analyze the probable biological functions performed by the participants of the signature. Using ccRCC data from The Cancer Genome Atlas (TCGA), we constructed the ceRNA network with the differentially expressed genes, assembled nine gene signatures from eight feature selection techniques, and analyzed the evaluation metrics of the classification models in the benchmarking process. With the signature, we performed somatic and copy number alteration analysis, survival and metastatic progression risk analysis, and functional annotation analysis. In this study, we present an 11-gene signature (SNHG15, AF117829.1, hsa-miR-130a-3p, hsa-mir-381-3p, BTBD11, INSR, HECW2, RFLNB, PTTG1, HMMR, RASD1). Validation using the external dataset of the International Cancer Genome Consortium (ICGC-RECA) made it possible to assess the generalization of the signature, which showed an Area Under Curve of 81.5%. The genomic analysis identified the signature participants on chromosomes with highly mutated regions (G-index > 2). The hsa-miR-130a-3p, AF117829.1, hsa-miR-381-3p, and PTTG1 had a significant relationship between expression and patient survival, and the first two had a significant association with metastatic development. In addition, functional annotation resulted in relevant pathways for tumor development, such as PI3K/AKT, TNF, FoxO, RNA polymerase two transcription regulation, and cell control. Finally, by analyzing the connections of the signature genes within the ceRNA network in conjunction with studies in the literature, it was possible to obtain an overview of their activities within the ccRCC. Therefore, this gene signature identified new coding and non-coding genes and could act as potential biomarkers for a better understanding of renal carcinoma and in the development of future treatments in the clinical area.
Generating an organ-deficient animal model using a multi-targeted CRISPR-Cas9 system
Authors: Lim Jonathan Jun-Yong , Yuri Shunsuke , Kawai Taro , Isotani Ayako 
Published: August 2023

SummaryGene-knockout animal models with organ-deficient phenotypes used for blastocyst complementation are generally not viable. Animals need to be maintained as heterozygous mutants, and homozygous mutant embryos yield only one-fourth of all embryos. In this study, we generated organ-deficient embryos using the CRISPR-Cas9-sgRNAmssystem that induces cell death with a single-guide RNA (sgRNAms) targeting multiple sites in the genome. The Cas9-sgRNAmssystem interrupted cell proliferation and induced cell ablationin vitro. The mouse model had Cas9 driven by theFoxn1promoter with a ubiquitous expression cassette of sgRNAmsat theRosa26locus (Foxn1Cas9;Rosa26_ms). It showed an athymic phenotype similar to that of nude mice but was not hairless. Eventually, a rat cell-derived thymus in an interspecific chimera was generated by blastocyst complementation ofFoxn1Cas9;Rosa26_msmouse embryos with rat embryonic stem cells. Theoretically, half of the total embryos have the Cas9-sgRNAmssystem because Rosa26_ms could be maintained as homozygous.
Health inequalities in SARS-CoV-2 infection during the second wave in England: REACT-1 study
Authors: Wang Haowei , Ainslie Kylie E. C. , Walters Caroline E. , Eales Oliver , Haw David , Atchison Christina , Fronterre Claudio , Diggle Peter J. , Ashby Deborah , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Donnelly Christl A. , Riley Steven , Elliott Paul 
Published: August 2023

AbstractBackgroundThe rapid spread of SARS-CoV-2 infection caused high levels of hospitalisation and deaths in late 2020 and early 2021 during the second wave in England. Severe disease during this period was associated with marked health inequalities across ethnic and sociodemographic subgroups.MethodsWe analysed risk factors for test-positivity for SARS-CoV-2, based on self-administered throat and nose swabs in the community during rounds 5 to 10 of the REal-time Assessment of Community Transmission-1 (REACT-1) study between 18 September 2020 and 30 March 2021.ResultsCompared to white ethnicity, people of Asian and black ethnicity had a higher risk of infection during rounds 5 to 10, with odds of 1.46 (1.27, 1.69) and 1.35 (1.11, 1.64) respectively. Among ethnic subgroups, the highest and the second-highest odds were found in Bangladeshi and Pakistan participants at 3.29 (2.23, 4.86) and 2.15 (1.73, 2.68) respectively when compared to British whites. People in larger (compared to smaller) households had higher odds of infection. Health care workers with direct patient contact and care home workers showed higher odds of infection compared to other essential/key workers. Additionally, the odds of infection among participants in public-facing activities or settings were greater than among those not working in those activities or settings.InterpretationPlanning for future severe waves of respiratory pathogens should include policies to reduce inequality in risk of infection by ethnicity, household size, and occupational activity.
Divergent enlarged perivascular spaces volumes in early versus late age-of-onset Alzheimer’s disease
Authors: Younes Kyan , Cobbigo Yann , Tsuie Tori , Wang Earnest , Wolf Amy , Joie Renaud La , Soleimani-Meigooni David N , Asken Breton , Tosun Duygu , Kramer Joel H , Ferguson Adam R , Miller Bruce L , Mormino Elizabeth C , Schwartz Daniel , Silbert Lisa C , Rabinovici Gil , Rosen Howard J , Elahi Fanny M 
Published: August 2023

STRUCTURED ABSTRACTINTRODUCTIONEnlarged perivascular spaces (EPVS) are considered a conduit for the brain’s waste clearance system. With aging, the brain’s ability to clear molecules is thought to decline, contributing to the retention of Alzheimer’s disease (AD) neuropathology. However, the role of EPVS in late-onset AD (LOAD) is complicated by co-morbidities. Early-onset AD (EOAD) offers a unique opportunity to understand the role of EPVS in AD.METHODSAutomatically-segmented EPVS volumes in biomarker-confirmed EOAD (n=58), LOAD (n=43), and age-matched controls (n=60) were correlated with amyloid and tau PET and cognition. Linear regression models were used.RESULTSIn LOAD, higher EPVS volumes were associated with better memory and functional performance. However, this association was not observed in EOAD. Additionally, higher tau was linked to increased EPVS in LOAD, but not in EOAD.DISCUSSIONEOAD and LOAD demonstrate distinct associations between EPVS, AD hallmarks, and cognition, suggesting differences in EPVS’s role in these AD subtypes, necessitating further investigation.
How do plant RNA viruses overcome the negative effect of Muller’s ratchet despite strong transmission bottlenecks?
Authors: Lafforgue Guillaume , Lefebvre Marie , Michon Thierry , Elena Santiago F. 
Published: August 2023

ABSTRACTMuller’s ratchet refers to the irreversible accumulation of deleterious mutations in small populations, resulting in a decline in overall fitness. This phenomenon has been extensively observed in experiments involving microorganisms, including bacteriophages and yeast. While the impact of Muller’s ratchet on viruses has been largely studied in bacteriophages and animal RNA viruses, its effects on plant RNA viruses remain poorly documented. Plant RNA viruses give rise to large and diverse populations that undergo significant bottlenecks during the colonization of distant tissues or through vector-mediated horizontal transmission. In this study, we aim to investigate the role of bottleneck size, the maximum population size between consecutive bottlenecks, and the generation of genetic diversity in countering the effects of Muller’s ratchet. We observed three distinct evolutionary outcomes for tobacco etch virus under three different demographic conditions: (i) a decline in fitness following periodic severe bottlenecks inChenopodium quinoa, (ii) a consistent fitness level with moderate bottlenecks inC. quinoa, and (iii) a net increase in fitness when severe bottlenecks inC. quinoawere alternated with large population expansions inNicotiana tabacum. By fitting empirical data to anin silicosimulation model, we found that initiating a lesion inC. quinoarequired only 1-5 virions, and approximately 40 new virions were produced per lesion. These findings demonstrate that Muller’s ratchet can be halted not only by increasing the number of founder viruses but also by incorporating phases of exponential growth to large populations between bottlenecks. Such population expansions generate genetic diversity, serving as a buffer against, and potentially even leveraging, the effects of genetic drift.
The Human Microglia Atlas (HuMicA) Unravels Changes in Homeostatic and Disease-Associated Microglia Subsets across Neurodegenerative Conditions
Authors: Martins-Ferreira Ricardo , Calafell-Segura Josep , Leal Bárbara , Rodríguez-Ubreva Javier , Mereu Elisabetta , Pinho e Costa Paulo , Ballestar Esteban 
Published: August 2023

ABSTRACTDysregulated microglia activation, leading to neuroinflammation, is crucial in neurodegenerative disease development and progression. The initial M1/M2 dual activation classification for microglia is outdated. Even the ‘disease-associated microglia’ (DAM) phenotype, firstly described in mice, falls short in representing the diverse microglia phenotypes in pathology. In this study, we have constructed a transcriptomic atlas of human brain immune cells by integrating single-nucleus (sn)RNA-seq datasets from multiple neurodegenerative conditions. Sixteen datasets were included, comprising 295 samples from patients with Alzheimer’s disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integratedHuman Microglia Atlas(HuMicA) dataset included 60,557 nuclei and revealed 11 microglial subpopulations distributed across all pathological and healthy conditions. Among these, we identified four different homeostatic clusters as well as pathological phenotypes. These included two stages of early and late activation of the DAM phenotype and the disease-inflammatory macrophage (DIM) phenotype, which was recently described in mice, and is also present in human microglia, as indicated by our analysis. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution in shaping pathological phenotypes. Our analysis showed overall depletion of four substates of homeostatic microglia, and expansion of niche subpopulations within the DAM and DIM spectrum across distinct neurodegenerative pathologies. TheHuMicAis invaluable in advancing the study of microglia biology in both healthy and disease settings.