bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic correlations between gut microbiome genera, Alzheimer’s disease diagnosis, and APOE genotypes: a polygenic risk score study
Authors: Cammann Davis , Lu Yimei , Cummings Melika J. , Zhang Mark L. , Cue Joan Manual , Do Jenifer , Ebersole Jeffrey , Chen Xiangning , Oh Edwin C. , Cummings Jeffrey L. , Chen Jingchun 
Published: December 2022

Abstract
Background: A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer’s disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis (MGBA). The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual’s risk for the disease.
Methods: Using the largest genome-wide association study (GWAS) of gut microbiota genera from the MiBioGen consortium, we conducted the polygenic risk score (PRS) analysis with the “best-fit” model implemented in PRSice-2 and determine the genetic correlation between 119 genera and AD in a discovery sample (case/control: 1,278/1,293). We then replicated our findings in an independent sample (case/control: 799/778) and further confirmed the correlation with meta-analysis. Finally, we conducted a linear regression analysis to assess the correlation between the PRSs for the significant genera and the APOE genotypes.
Results: In the discovery sample, 20 gut microbiota genera were initially identified as genetically associated with AD case/control status. Three genera (Eubacterium fissicatena as a protective factor, Collinsella, and Veillonella as a risk factor) were replicated in the replication sample. The meta-analysis confirmed that ten genera have a significant correlation with AD, four of which were significantly associated with the APOErs429358 risk allele in a direction consistent with their protective/risk designation in AD association. Notably, the proinflammatory genus Collinsella, identified as a risk factor for AD, was positively correlated with the APOErs429358 risk allele in both samples.
Conclusion: Host genetic factors influencing the abundance of ten genera are significantly associated with AD, suggesting that these genera may serve as biomarkers and targets for AD treatment and intervention. Our results highlight that proinflammatory gut microbiota might promote AD development through interaction with APOE. Larger datasets and functional studies are required to understand their causal relationships.
Phosphorylation of TOPK at Y272 by FYN enhances proliferation and metastasis of gastric cancer
Authors: Peng SanFei , Yin YuHan , Zhang YiZheng , zhu feng , Yang Ge , Fu Yang 
Published: December 2022

Abstract
Background
FYN is a nonreceptor tyrosine kinase that regulates diverse pathological processes. The pro-cancer role of FYN in multiple malignancies has been elucidated. However, the mechanisms that FYN promotes gastric cancer(GC) progression remain largely unknown.
Methods
In vitro and in vivo assays were used to investigate the function of FYN. FYN, TOPK, p-TOPK expression in GC specimens were detected by immunohistochemistry. Phosphoproteomics assays identify TOPK downstream substrate molecules. The molecular mechanism was determined using COIP assays, pull-down assays, immunofluorescence co-localization assays, western blotting, 32p-labeled isotope radioautography assays, vitro kinase assays ,and TOPK knockout mice.
Results
FYN was found to be significantly upregulated in GC as well as in GC cells. Knockdown of FYN expression markedly attenuated the malignant phenotype of GC cells in vitro and in vivo. Mechanistically, we identified TOPK/PBK as a novel downstream substrate of FYN, FYN directly phosphorylates TOPK at Y272. One phosphospecific antibodies against Y272 was developed to validate the phosphorylation of TOPK by FYN. Moreover, the TOPK-272F mutation impaired the interaction between TOPK and FYN, leading to disappeared TOPK phosphorylation. Consistently, human GC tissues displayed increased p-TOPK(Y272), which correlated with poor survival. Phosphoproteomics results showed a significant downregulation of both HSPB1 and p-HSPB1(ser15) in TOPK-knockdown cells, which was confirmed by TOPK-konckout mice.
Conclusions
FYN directly binds to TOPK in GC cells and phosphorylates TOPK at the Y272, which leads to proliferation and metastasis of GC. FYN-TOPK axis facilitates GC progression by phosphorylating HSPB1 at S15. Collectively, our study elucidates the pivotal role of the FYN-TOPK-HSPB1 cascade in GC.
Sensitivity of extreme precipitation to climate change inferred using artificial intelligence shows high spatial variability
Authors: Bird Leroy , Bodeker Gregory , Clem Kyle 
Published: December 2022

Abstract
Evaluating changes in extreme precipitation, and how those extremes will change with climate, is challenged by the paucity, brevity and inhomogeneity of observational time series. Using global precipitation measurements from 10,000 stations, we successfully demonstrate an artificial intelligence-based method for quantifying the sensitivity of extreme precipitation to climate change that is robust against the limitations of the observational record; a convolutional neural network (CNN) is trained to learn the spatial structure of Generalized Extreme Value (GEV) parameters describing the statistics of precipitation extremes. Given an annual mean, global mean surface temperature time series as a climate covariate, the CNN also learns the non-stationarity of the GEV fit parameters. The trained CNN is used to generate maps of the sensitivity of extreme precipitation to global temperature change on ∼1.5km×1.5km grids over North America, Europe, Australia and New Zealand. This observations based method avoids the short-comings of regional and global climate models in simulating expected changes in extreme precipitation.
Spontaneous rupture of the renal pelvis caused by advanced cervical cancer: A case report
Authors: Peng Cheng-Xia , Xu Li , Wu Guang-Hao , Feng Chao , Zhou Xie-lai , Wang Kang-Er , Ye Chun-Hua 
Published: December 2022

Abstract
Background: Spontaneous rupture of the renal pelvis (SRRP) is a rare clinical condition caused by stone obstruction, and characterized by lumbar and abdominal pain. However, SRRP caused by gynecological tumors has not been reported to date. Here, we describe a case of SRRP caused by cervical cancer and discuss its pathogenesis, diagnosis, and treatment.
Case presentation: A 38-year-old woman was hospitalized due to right low back pain with a history of irregular vaginal bleeding. Computed tomography urography (CTU) showed right renal pelvis dilatation and massive extravasation. Thinprepcytologic test (TCT) suggested cervical squamous cell carcinoma. Thus, a diagnosis of SRRP caused by advanced cervical cancer was made. After two months of intravenous chemotherapy and conservative therapy, computed tomography (CT) showed an intact renal pelvis.
Conclusion: Upon clinical diagnosis of SRRP, its cause should be identified and treatment should be administered to achieve a satisfying outcome.
How Quality of Work-life Influence Employee Job Satisfaction in a Gas Processing Plant in Ghana
Authors: Hammond Mavis , Owusu Nichodemous Osei , Nunoo Edward Kweku , Boampong Georgina , Osman Aminu , Panin Anthony , Nyametso Johnie K , Essen Bernice 
Published: December 2022

Abstract
The influence of quality of work-life on job satisfaction is critical for sustaining high level skilled workers and enhancing productivity in the oil and gas industry. This study examined the influence of quality of work-life on job satisfaction among workers in a gas processing plant. Descriptive-analytical design and a census approach were used to assess 180 staff (N = 200). The analysis established positive relationship between employee job satisfaction and the four constructs of quality of work life; safe working environments (r = 0.333 p < 0.000), Work-life balance (r = 0.738 p < 0.000), personal development (r = 0.335 p < 0.000) and emotional well-being (r = 0.943 p < 0.000) at significant levels.With the later construct registering the highest correlation with job satisfaction, the study recommend to management a functional early guidance support system for workers who may exhibit early symptoms of emotional well-being distress. It is imperative for management to consolidate and significantly improve on established measures for employees to maximise both work output and avoid work-family conflicts. Management should maintain robust safety protocols and an emergency response unit to ensure employees work in a relaxed environment that promotes workplace well-being. These are envisaged to sustain employee workplace assistance programs that can confidently discuss and address workers' stress, anxiety, and other related concerns at the workplace.
EDTA is yesterday’s soil chelatant; evaluating a more environmentally-sensitive alternative for metal removal by Pistia stratiotes L.
Authors: Lebrun Manhattan , Szakova Jirina , Drabek Ondrej , Tejnecky Vaclav , Hough Rupert Lloyd , Beesley Luke , Wang Hailong , Trakal Lukas 
Published: December 2022

Abstract
Background and Aims The accuracy of environmental risk assessment depends upon the selection of appropriate matrices to extract the most risk-relevant portion of contaminant(s) from the soil. Here we applied the chelatants Na-EDTA and tartaric acid (along with a H2O control) to extract a metal-contaminated soil (Cd, Cu, Pb & Zn).
Methods Pistia stratiotes was applied as an indicator plant to measure accumulation from the metal-laden bulk solutions generated, in a hydroponic experiment lasting 15 days. Speciation modelling was used to elucidate key geo-chemical mechanisms impacting matrix and metal-specific uptake revealed by experimental work.
Results The highest concentrations of soil-borne metals were extracted from soil by Na-EDTA (7.4 % for Cd), but their uptake and translocation to the plant were restricted due to the formation of stable metal complexes predominantly with DOC. Tartaric acid solubilized metals to a lesser extent (4.6 % for Cd), but a higher proportion were plant available due to its presence mainly in form of bivalent metal cations. The water extraction showed the lowest metal extraction (e.g., 3.9 % for Cd) but the metal species behaved similarly as those extracted by tartaric acid.
Conclusions This study demonstrates that not all extractions are equal, and that metal-specific speciation will impact accurate risk assessment in soil (water)-plant systems. In the case of EDTA, a deleterious impact on DOC leaching is an obvious drawback. As such, further work should now determine soil, and not only metal, specific impacts of chelatants on the extraction of environmentally relevant portions of metal(loid)s.
Expression of HIF-1α and Markers of angiogenesis and metabolic adaptation in molecular subtypes of Breast Cancer
Authors: Farooq Muzamil , Bhat Gh. Rasool , Besina Syed , Thakur Natasha , Zahoor Sheikh , Rather Rafiq A , Mushtaq Ifra , Dar Sadaf , Rah Bilal , Bhat Aijaz Ahmad , Macha Muzafar Ahmad , Afroze Dil 
Published: December 2022

Abstract
Hypoxic zones exist in solid tumors, where oxygen levels are significantly lower than in normal tissues.Hypoxia makes chemo-radiation therapeuticsless effective and renders the metastatic potential more favorable. Emerging research has found that the transcriptional expression of hypoxia-inducible factor-1alpha (HIF-1𝛼) promotes the transcription of vascular endothelial growth factor A (VEGF-A) and Hexokinase-I (HK-I), whichare associated to cellular growth, angiogenesis, and metastatic invasion in many malignancies.However, it is still unclear whether VEGFA and HK-I expression has any influence on survival based on the intrinsic subtypes of breast cancer. Their prognostic significance remains a debatable topic. In the present study,quantitative Real-time polymerase chain reaction (qRT-PCR) was employed to check the relative expression of HIF-1𝛼, VEGF-A and HK-I. The hazard ratios (HR) of breast cancer-specific and overall mortality were calculated using Cox proportional hazards model, which were adjusted for demographic, clinicopathological, and associated molecular variables, as well as the diagnosis year. The relative mRNA expression levels of HIF-1α (p = 0.0010) and VEGFA (p = 0.0119) were significantly higher in tumor tissues. The expression of both HIF-1α (p = 0.0111) and VEGFA (p = 0.0078) was higher in the TNBC group of breast cancers, while HK-I (p = 0.0106) was higher in ER/PR-positive, HER2-negativegroup.HIF-1𝛼 and HK-I overexpression were associated with a higher likelihood of survival, while overexpression of VEGFA was associated with a low survival rate, although it was not statistically significant.
Concomitant synthesis and stabilization of selenium nanoparticles using extract of endophytic fungus, Nigrospora gullinensis
Authors: Anmol Anmol , Jaiswal Sumit Kumar , Prakash Ranjana , Mihara Hisaaki , Prakash Nagaraja Tejo 
Published: December 2022

Abstract
Selenium has many beneficial bioactive properties yet has a narrow therapeutic window. This problem can be addressed by selenium in nanoform or selenium nanoparticles (SeNPs). There are several chemical and physical approaches that can be employed for the synthesis of SeNPs. However, the biological route for SeNP synthesis is known to be more eco-friendly, economical, and biocompatible when assessing bioactivities. The present study demonstrates a biological approach that effectively facilitates the synthesis and stabilization of SeNPs with the help of secondary metabolites derived from endophytic fungi. These capped SeNPs show prominent bioactivity in terms of in vitro anti-oxidant properties and anti-microbial activity on Escherichia coli, Enterobacter faecalis, and Staphylococcus aureus. The results indicated NL(C)-SeNPs portray potential anti-oxidant and anti-microbial activity. However, additional studies related to the toxicity and synergistic effects of SeNPs, are required before their therapeutic applications.
Non-figurative coloured arrangements, towards a new tool to visually facilitate odour imagery?
Authors: Hossu Gabriela , Fantin Luca , Charroud Céline , Felblinger Jacques , Jacquot Muriel , Ceyte Hadrien 
Published: December 2022

Abstract
Odour imagery, the ability to experience smell when an appropriate stimulus is absent, has widely been documented as being particularly difficult. However, previous studies have shown the beneficial effect of visual cues (e.g. pictures or words) to facilitate performance in numerous tasks of olfactory nature. Therefore, the use of visual cues to evoke odours seems relevant. In this study, our interest is directed towards non-figurative coloured arrangements, which result from a patented technology and aim at chromatically representing any smell from its chemical composition. We recorded and compared hemodynamic responses during odour imagery facilitated by non-figurative coloured arrangements and pictures using functional magnetic resonance imaging. Our findings reveal that the use of non-figurative coloured arrangements during odour imagery solicits olfactory and non-olfactory brain regions which have roles mainly in olfactory processing, multimodal integration. Moreover, very similar cortical activity was found between the use of non-figurative coloured arrangements and pictures during odour imagery. Overall, non-figurative coloured arrangements could become a robust tool to visually evoke odours without requiring prior familiarity with the depicted odour. Future studies are needed to determine the relationships between brain activation and vividness of the generated odour images as well as the necessary mental workload.
Characterizing diffusion-controlled release of small-molecules using quantitative MRI: Application to orthopedic infection
Authors: Hong Greg , Khazaee Tina , Cobos Santiago F. , Christiansen Spencer D. , Liu Junmin , Drangova Maria , Holdsworth David W. 
Published: December 2022

Abstract
Calcium sulphate is an established carrier for localized drug delivery, but a means to non-invasively measure drug release, which would improve our understanding of localized delivery, remains an unmet need. We aim to quantitatively estimate the diffusion-controlled release of small-molecules loaded into a calcium sulphate carrier through gadobutrol-based contrast agent, which acts as a surrogate small-molecule.
A central cylindrical core made of calcium sulphate, either alone or within a metal scaffold, is loaded with contrast agent that releases into agar. Multi-echo scans are acquired at multiple time-points over 4 weeks and processed into R2* and QSM maps. Mean R2*values are fit to a known drug delivery model, which are then compared to the decrease in core QSM.
Fitting R2* measurements of calcium sulphate core while constraining constants to a drug release model results in a R2-value of 0.991, yielding a diffusion constant of 4.59x10-11 m2/s. Incorporating the carrier within a metal scaffold results in a slower release. QSM shows the resulting loss of susceptibility in the non-metal core but is unreliable around metal.
R2* characterizes gadobutrol release and QSM detects the resulting decrease in susceptibility. The addition of a porous metal scaffold slows the release of gadobutrol, as expected.
Experimental flooding shifts carbon, nitrogen, and phosphorus pool distribution and microbial activity
Authors: Lieberman Hannah P , Rothman Maia , von Sperber Christian , Kallenbach Cynthia M 
Published: December 2022

Abstract
Flooding transforms the soil environment, impacting small-scale controls on mineral associated carbon (C), nitrogen (N) and phosphorus (P) stabilization and mobilization. Yet during flood events, mineral associated C, N, and P may not respond in the same way, such that soluble C, N, and P concentrations and stoichiometry may change with unknown consequences for microbial activity. Using a laboratory incubation approach, we investigated how flooding impacts C, N, and P pool distribution and microbial activity across a 1-week flood event and after drying. We found that all three mineral associated pools responded dynamically to flooding, increasing and decreasing throughout the flood with a net increase of 5.9% in mineral associated C and 32.5% decrease in residual P. However, mineral associated C, N, and P each shifted at different temporal points, indicating that they are likely responding to separate destabilization mechanisms working at different temporal scales. The soluble C and N responses to flooding contrasted the mineral associated pool’s response, increasing by 57% and decreasing by 72% respectively at the beginning of the flood which remained post-flood. However, soluble P behaved more similarly to the mineral associated pool. The microbial community maintained and even increased their exo-cellular activity throughout the flood period, responding most strongly to changes in available P. Our research demonstrates that the mineral associated pool is sensitive to short-term flooding altering the composition and quantity of water extracted compounds and microbial activity.
Serine/threonine kinase of human Monkeypox virus: computational modeling and structural analysis
Authors: Abduljalil Jameel M. , Al-Madhagi Haitham A. , Elfiky Abdo A. , AlKhazindar Maha M. 
Published: December 2022

Abstract
Kinases catalyze phosphoryl transfer from a nucleoside triphosphate (usually ATP) to an amino acid residue on a protein (for activation purposes). These enzymes are well-appreciated drug targets against different viruses and cancers. However, some poxviruses are human and animal pathogens that lack effective therapeutic agents. In poxvirus, the production of infectious particles in the infected cells depends on F10 protein kinase that activates numerous proteins involved in the assembly of new virions. The ongoing outbreak of the human monkeypox virus (hMPXV) sparked the need for efficient antiviral drugs to control such outbreaks and lower their burden. In this work, we employed state-of-the-art computational resources to elucidate the structure of the major kinase in hMPXV using AlphaFold2. The predicted structure shows the atypical nature of this kinase; nonetheless, the overall structural fold is roughly conserved. Calculations of binding free energy determined the hotspot residues contributing to phosphate source (ATP) via Molecular Mechanics with Generalized Born and Surface Area solvation (MM/GBSA). The structural analysis in this work provides the basis for setting up a thorough experimental investigation to understand the enzymatic mechanism and development of small-molecule inhibitors against such a critical target.
Ultrafast Bioanalytical Assay for Vilazodone Quantification in Human Plasma Using Vilazodone D8 Internal Standard by Uplc- Ms/ms
Authors: Agrawal Nikhil , Mittal Amit 
Published: December 2022

Abstract
A selective and highly sensitive quantitative method has been established for assessment of pharmacokinetic parameters in human plasma using vilazodone D8 as a labelled internal standard. Liquid- Liquid extraction technique (LLE) was applied for plasma sample extraction. Mass detection was performed in positive electro spray ionization method. Quantitation was achieved by monitoring sum multiple transitions of m/z 442.022 → 155.000 + 197.000 for vilazodone and 450.093 → 157.000 + 205.000 for vilazodone D8. Chromatographic separation was performed on reverse phase Betabasic C8, 100*4.6mm, 5µ column with 0.700mL/min flow rate. Mobile phase consists of acetonitrile and 0.1% formic acid in water (60:40%v/v) was pumped through isocratic mode. The linearity of the method was validated from range 0.300ng/mL to 300.000ng/mL. Precision and accuracy batches were found to be consistent, reproducible and acceptable within the defined limits across the validation. No matrix effect was observed within the validated range and extraction efficiency or recovery was found to be consistent and reproducible at all concentration levels (low, middle and high). The stock solutions, working solutions, plasma samples and processed samples were found to be stable under all defined conditions. In this validated method, selective linearity range were used to cover quantitative analysis for various strength formulations. This work was typically aimed to develop a method with shorter analysis time and simple extraction procedure for reliable measurement of clinical samples. The validated method can be useful in determining plasma concentration of vilazodone for therapeutic drug monitoring and in high throughput clinical bio-studies.