bluuebunny/crossref_metadata_2025_split huggingface dataset:
EarlyDetect: Development of tool for early detection of stomach adenocarcinoma based on blood-lipid profile as clinicopathological feature
Authors: Prakash Om , Khan Feroz 
Published: February 2023

ABSTRACTBackgroundClinicopathological features are used for detection of diseases. Early detection of cancer can be significance for understanding the behavior of disease.ResultsWe developed a tool to observe stomach adenocarcinoma in reference of blood-lipid profile. Background of the tool is based on the study made on RNAseq expression analysis of stomach adenocarcinoma. Raw data for study was collected as gene-expression profile from population of cancer-vs-normal. A series of studies performed including: differential gene expression analysis, plasma proteome mapping, extraction of gene-signature enriched with LSTM system model, AI-guided simulation of systems model of gene network, and AI-guided mapping with blood lipid profile to develop R-Shiny web-application.Conclusion‘EarlyDetect’ is freely available athttps://csir-icmr.shinyapps.io/EarlyDetect/. The tool can be utilized for (i) virtual observation of impact of different combinations of lipid profile in cancer progression; (ii) early detection of cancer state for new comer patients.
Clinical feature, treatment pattern and survival of Esophageal cancer at Tikur Anbessa Specialized Hospital, Ethiopia: a prospective cohort study
Authors: Feyisa Jilcha Diribi , Adisse Adamu , Kantelhardt Eva Johanna , Zingeta Girum Tesema , Negash Eyoel , Wondimagegnewu Abigiya , Hirpha Selamawit , Gizaw Muluken , Aseffa Mathewos 
Published: February 2023

AbstractPurposeEthiopia is located within the esophageal belt of Africa. Esophageal cancer is the seventh leading cause of death in Ethiopia. There is a paucity of literature regarding the clinical features, treatment patterns, and survival of patients with esophageal cancer. We report the clinical profile, treatment pattern, and survival of patients with esophageal cancer at Tikur Anbessa Specialized Hospital, Ethiopia.MethodsAn unmatched prospective cohort study was conducted from February 27, 2018 to February 28, 2020. We used the Kaplan–Meier method to assess the overall survival time and survival time according to stage and treatment type. Multivariate Cox regression analysis with the backward LR selection method was used to fit the final model.ResultIn total, 230 patients with esophageal cancer were recruited for this study. The median survival time was six months (95%CI) (5, 7). A total of 170 (73.9%) patients died during the 1,244 person-month follow-up period, resulting in an overall event rate of 162 per 1,000 person– months. The overall survival rate was very low with 6 months, 1-, and 2-year survival rates of 54.6% (95%CI:47.5%-61.2%), 19.5% (13.8% -25.9%), and 2.0% (0.45%–5.9%), respectively. Chemotherapy, local recurrence, and brain metastases were variables that explained the model.Conclusionsurvival of patients with esophageal cancer at Tikur Anbessa Specialized Hospital was very short. We recommend multimodal treatment to improve treatment outcomes.
Wisely Frugal: Ensuring sustainable funding for novel cancer therapeutics using cost-effectiveness thresholds in resource limited settings
Authors: Joseph Nuradh , Peiris Vimukthini , Bamunuarachchi Vodathi , Abeysinghe Prasad , Jeyakumaran Nadarajah , Jayathilake Devinda , Perera Kanthi , Fernandopulle Rohini , Gunasekera Sanjeeva 
Published: February 2023

AbstractIntroductionCancer care in Sri Lanka is predominantly provided through its public funded state health system which is free at the point of delivery. The health system faced unprecedented funding restrictions brought about by the post-pandemic recession. We performed a cost-effectiveness analysis of novel cancer drugs with a view to prioritising novel cancer therapeutics to its sustainability during these challenging times.MethodsThe direct cost of drug procurement was obtained, and the cost per life year gained was computed for each indication. Two thresholds - per capita GDP per life year gained (GDPx1) and three times per capita GDP per life year gained (GDPx3) were considered to determine cost effectiveness. The cumulative annual cost of these treatments were then determined by multiplying the cost per treatment course per patient by the estimated number of treated patients per year for each indication.ResultsData obtained on 42 novel cancer drugs spanning across 90 indications were included in the analysis. The cumulative annual treatment cost when the threshold was set at GDPx1 was US$ 6 million and it increased to US$ 16.3 million if the threshold was expanded GDPx3. Only 28 indications met the GDPx3 threshold while there were 18 drugs that did not meet the thresholds for any indication. Without a threshold, if every eligible patient were to receive the indicated currently used novel drugs, the total cost of treatment would reach almost US$ 300 million per year.ConclusionCost-effectiveness thresholds will lead to considerable savings and help prioritise procurement and supply of cost-effective novel agents in the state health system in Sri Lanka.Advances in KnowledgeIn this work, we show that significant savings can be achieved by performing simple cost-effectiveness analyses and defining thresholds. The absence of robust quality of life and costing data should not deter policy makers from such conducting analyses from available information.
Prognostic value of Coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with nonalcoholic fatty liver disease: Results from the Multi-Ethnic Study of Atherosclerosis
Authors: Ichikawa Keishi , Hansen Spencer , Manubolu Venkat S. , Pourafkari Leili , Fazlalizadeh Hooman , Aldana-Bitar Jairo , VanWagner Lisa B , Krishnan Srikanth , Budoff Matthew J. 
Published: February 2023

AbstractBackgroundNonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events, thus a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in NAFLD patients.MethodsA total of 718 NAFLD participants from Multi-Ethnic Study of Atherosclerosis (MESA) without previous cardiovascular events were followed for the occurrence of incident ASCVD. NAFLD was defined using non-enhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistic and net reclassification improvement were used to compare incremental contributions of CAC score when added to the clinical risk factors.ResultsIn multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR = 1.33, 95% CI = 1.22–1.44, p < 0.001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (p < 0.001) and the net reclassification index was 0.721 (95% CI = 0.494–0.977). In subgroup analyses, the incremental prognostic value of CAC score was more significant in NAFLD participants with low/borderline- (<7.5%) and intermediate- (7.5–20%) 10–year ASCVD risk score.ConclusionsThe inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with NAFLD, indicating a potential role for CAC screening in risk assessment.Clinical PerspectiveWith the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) individuals, there is an unmet need for a diagnostic approach to identify NAFLD individuals who are at higher risk for atherosclerotic cardiovascular disease (ASCVD) events. This study showed that higher coronary artery calcium (CAC) score was associated with ASCVD events during follow-up and improved the discriminative ability for future events in NAFLD individuals. Our study suggests routine CAC screening can be useful in assessing the risk of future ASCVD events. Future studies are needed to explore the therapeutic implications of CAC screening in this population.
Simulating Rumen Conditions using an Anaerobic Dynamic Membrane Bioreactor to Enhance Hydrolysis of Lignocellulosic Biomass
Authors: Fonoll Xavier , Zhu Kuang , Aley Lucy , Shrestha Shilva , Raskin Lutgarde 
Published: February 2023

ABSTRACTAn anaerobic dynamic membrane bioreactor (AnDMBR) was used to mimic rumen conditions to enhance the hydrolysis of lignocellulosic materials and the production of volatile fatty acids (VFA) when treating food waste. The AnDMBR was inoculated with cow rumen content and operated at a 0.5-day hydraulic retention time, 2 to 4-day solids retention time, a temperature of 39 °C, and a pH of 6.3, characteristics similar to those of a rumen. An operational strategy of repeating settle-permeate-mix cycles was utilized to simulate the regurgitation of ruminant animals. Removal rates of neutral detergent fiber (NDF) and acid detergent fiber (ADF) of 58.9 ± 8.4 % and 69.0 ± 8.6 %, respectively, and a VFA yield of 0.55 ± 0.12 g VFA/g CODfedwere observed when operating at an organic loading rate of 18 ± 2 kg VS/m3/day. Sequencing results of both 16S rRNA gene and 16S rRNA revealed that a microbial community resistant to both disruption and reinoculation developed six weeks after inoculation. Up to 66.7 ± 5.7 % of the active microbial populations (based on 16S rRNA sequence data) and 51.0 ± 7.0 % of the total microbial populations (based on 16S rRNA gene sequence data) present in the rumen-mimicking AnDMBR originated from the rumen inoculum. This study offers a reliable strategy to leverage the unique features of a rumen; the rumen-mimicking AnDMBR achieved high hydrolysis and acidogenesis rates even when treating substrates drastically different from those fed to ruminants.
A Metabolomics Study of Thrombosis after Cardiac Surgery in Children with Congenital Heart Disease
Authors: Li Shengxu , Watson Dave , Jorgenson Alissa , Adelekan Zainab , Tang Weihong , Garland Kathleen , Zupancich Leah , Dassenko David , Edens R. Erik , Overman David M. , Huntley Marnie T. 
Published: February 2023

AbstractObjectiveThrombosis is a major complication after cardiac surgery in children with congenital heart disease (CHD). The mechanisms underlying thrombosis development remain poorly understood. We aimed to identify novel circulating metabolites before cardiac surgery that are associated with the development of thrombosis after surgery in children with CHD.Approach and resultsAll blood samples were drawn right before surgical incision and after the induction of anesthesia, and plasma was separated immediately under 4 °C. Untargeted metabolomic data were measured by Metabolon in plasma from children (age range: 0 days-18 years) with CHD undergoing cardiac surgery. The primary outcome was thrombosis within 30 days of surgery or before discharge. Associations of individual metabolites with thrombosis were assessed with logistic regression with false discovery rate (FDR) correction for multiple comparison and adjustment for clinical characteristics; elastic net regression was used to select a prediction model. Out of 1,115 metabolites measured in samples from 203 children, 776 met the quality control criteria. In total, 26 children (12.8%) developed thrombosis. Among the 776 metabolites, 195 were significantly associated with thrombosis (FDR q-value < 0.05). The top three metabolites showing the strongest associations with thrombosis were eicosapentaenoate, steroid monosulfate C19H28O6S, and formiminoglutamate (FDR = 0.01 for all). Pathway analysis showed that the pathways of nicotinate and nicotinamide metabolism (P = 0.0007) and glycerophospholipid metabolism (P = 0.002) were enriched and had significant impacts on the development of thrombosis. In elastic net regression analysis, the area under the receiver operating-characteristic curve of a prediction model for thrombosis was 0.94 in the training sample (70% of the total sample) and 0.84 in the testing sample (the remaining 30%).ConclusionWe have identified promising novel metabolites and metabolic pathways associated with thrombosis. Future studies are warranted to confirm the findings and examine the mechanistic pathways to thrombosis.
Acute and Subacute Ischemia of Lower Limbs: Angiography and Peripheral Hemodynamics
Authors: Bulvas Miroslav , Sommerová Zuzana 
Published: February 2023

ABSTRACTObjectiveTo identify pretreatment characteristics related to ischemia severity and symptoms duration in patients with acute (ALI) and subacute lower limb ischemia (SLI).MethodsComparative study, a part of prospective, single-arm, single-center trial of 316 consecutive patients with threatened extremities (all-comers, mean age: 70.9±12.0 years, range: 23-96; 184 men) of whom 99. 4 % suffered from acute or subacute supratibial occlusions (target occlusions).ResultsMultisegmental (supratibial plus infrapopliteal) arterial occlusions were documented in 90.6 % of ALI patients and in 78.1 % of SLI patients with threatened lower extremity. The value of ABI related to the number of occluded tibial arteries. Occlusion locations associated with ALI (IIA+IIB) were the aortoiliac segment and/or profunda femoris. Furthermore, ALI subjects presented additional infrapopliteal occlusion (acute and/or subacute), smaller number of patent tibial arteries and lower ABI.ConclusionAnatomically, the most important factor related to the ischemia severity and symptoms duration was the status of infrapopliteal vascular bed. The number of acutely, subacutely or chronically occluded tibial vessels was related to clinical categories of ALI and SLI and to ABI. This suggests that tibial reperfusion can be essential for the salvage of threatened limb and should be always considered.
Associations between SARS-CoV-2 infection and incidence of new chronic condition diagnoses: a systematic review
Authors: Gaudet Lindsay A. , Pillay Jennifer , Saba Sabrina , Zakaria Dianne , Cheta Nicholas , Gardiner Hélène , Shaver Larry , Middleton Jacqueline , Tan Maria , Vandermeer Ben , Hartling Lisa 
Published: February 2023

AbstractBecause of the large number of infected individuals, an estimate of the future burdens of the long-term consequences of SARS-CoV-2 infection is needed. This systematic review examined associations between SARS-CoV-2 infection and incidence of categories of and selected chronic conditions, by age and severity of infection (inpatient vs. outpatient/mixed care). MEDLINE and EMBASE were searched (Jan 1, 2020 to Oct 4, 2022) and reference lists scanned. We included observational studies from high-income OECD countries with a control group adjusting for sex and comorbidities. Identified records underwent a two-stage screening process. Two reviewers screened 50% of titles/abstracts, after which DistillerAI acted as second reviewer. Two reviewers then screened the full texts of stage one selections. One reviewer extracted data and assessed risk of bias; results were verified by another. Random-effects meta-analysis estimated pooled hazard ratios (HR). GRADE assessed certainty of the evidence. Twenty-five studies were included. Among the outpatient/mixed SARS-CoV-2 care group, there is high certainty of a small-to-moderate increase (i.e., HR 1.26 to 1.99) among adults ≥65 years of any cardiovascular condition, and of little-to-no difference (i.e., HR 0.75 to 1.25) in anxiety disorders for individuals <18, 18-64, and ≥65 years old. Among 18-64 and ≥65 year-olds receiving outpatient/mixed care there are probably (moderate certainty) large increases (i.e., HR ≥2.0) in encephalopathy, interstitial lung disease, and respiratory failure. After SARS-CoV-2 infection, there is probably an increased risk of diagnoses for some chronic conditions; whether the magnitude of risk will remain stable into the future is uncertain.
FitMultiCell: Simulating and parameterizing computational models of multi-scale and multi-cellular processes
Authors: Alamoudi Emad , Schälte Yannik , Müller Robert , Starruß Jörn , Bundgaard Nils , Graw Frederik , Brusch Lutz , Hasenauer Jan 
Published: February 2023

AbstractMotivationBiological tissues are dynamic and highly organized. Multi-scale models are helpful tools to analyze and understand the processes determining tissue dynamics. These models usually depend on parameters that need to be inferred from experimental data to achieve a quantitative understanding, to predict the response to perturbations, and to evaluate competing hypotheses. However, even advanced inference approaches such as Approximate Bayesian Computation (ABC) are difficult to apply due to the computational complexity of the simulation of multi-scale models. Thus, there is a need for a scalable pipeline for modeling, simulating, and parameterizing multi-scale models of multi-cellular processes.ResultsHere, we present FitMultiCell, a computationally efficient and user-friendly open-source pipeline that can handle the full workflow of modeling, simulating, and parameterizing for multi-scale models of multi-cellular processes. The pipeline is modular and integrates the modeling and simulation tool Morpheus and the statistical inference tool pyABC. The easy integration of high-performance infrastructure allows to scale to computationally expensive problems. The introduction of a novel standard for the formulation of parameter inference problems for multi-scale models additionally ensures reproducibility and reusability. By applying the pipeline to multiple biological problems, we demonstrate its broad applicability, which will benefit in particular image-based systems biology.AvailabilityFitMultiCell is available open-source athttps://gitlab.com/fitmulticell/fit.Contactjan.hasenauer@uni-bonn.deSupplementary informationSupplementary data are available athttps://doi.org/10.5281/zenodo.7646287online.
Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs
Authors: Haga-Yamanaka Sachiko , Nuñez-Flores Rogelio , Scott Christi Ann , Perry Sarah , Chen Stephanie Turner , Pontrello Crystal , Nair Meera Goh , Ray Anandasankar 
Published: February 2023

ABSTRACTEukaryotes are often exposed to microbes and respond to their secreted metabolites, such as the microbiome in animals or commensal bacteria in roots. Little is known about the effects of long-term exposure to volatile chemicals emitted by microbes, or other volatiles that we are exposed to over a long duration. Using the model systemDrosophila melanogaster,we evaluate a yeast emitted volatile, diacetyl, found in high levels around fermenting fruits where they spend long periods of time. We find that exposure to just the headspace containing the volatile molecules can alter gene expression in the antenna. Experiments showed that diacetyl and structurally related volatile compounds inhibited human histone-deacetylases (HDACs), increased histone-H3K9 acetylation in human cells, and caused wide changes in gene expression in bothDrosophilaand mice. Diacetyl crosses the blood-brain barrier and exposure causes modulation of gene expression in the brain, therefore has potential as a therapeutic. Using two separate disease models known to be responsive to HDAC-inhibitors, we evaluated physiological effects of volatile exposure. First, we find that the HDAC inhibitor also halts proliferation of a neuroblastoma cell line in culture as predicted. Next, exposure to vapors slows progression of neurodegeneration in aDrosophilamodel for Huntington’s disease. These changes strongly suggest that unbeknown to us, certain volatiles in the surroundings can have profound effects on histone acetylation, gene expression and physiology in animals.
Active site mutations of F420-dependent alkene reductases reverse stereoselectivity
Authors: Kang Suk Woo , Antoney James , Lupton David W. , Speight Robert , Scott Colin , Jackson Colin J. 
Published: February 2023

AbstractEne-reductases from the Flavin/Deazaflavin Oxidoreductase (FDOR) family have potential value in biocatalysis as they typically exhibit complementary stereoselectivity to the widely utilized Old Yellow Enzyme (OYE) family, yet they are comparatively poorly understood at a mechanistic level. Here, we use a rational design approach to generate a library of 46 active site mutants of two FDORs fromMycobacterium smegmatisand examine the effects on conversion and stereoselectivity against a panel of substrates. Analysis of the effects of these mutations on stereoselectivity across all substrates revealed that the catalytic mechanism is highly sensitive to the polarity of the immediate active site. A conserved active site tyrosine in these enzymes, which does not serve as the proton donor, strongly affects stereochemical outcomes with Cα- (but not Cβ-) substituted substrates. Notably, a Tyr-Met mutation at this position reversed the diastereomeric excess (de) with (R)-carvone from 85.3% to −17.3% (cis/trans). Additionally, this mutation significantly increases activity with (1S)- verbenone. Finally, we show that the altered stereoselectivity is not due to a “flipped” substrate binding mode in these mutants, but rather that the hydrogenation mode is altered to favorsynrelative toantiaddition. These results show that the FDORs are highly engineerable and that, despite their superficial similarity, the OYE and FDOR families differ in crucial mechanistic aspects.
Gut microbiota promotes pain chronicity in Myosin1A deficient male mice
Authors: Reynders Ana , Jhumka Z. Anissa , Gaillard Stéphane , Hoeffel Guillaume , Mantilleri Annabelle , Malapert Pascale , Salio Chiara , Ugolini Sophie , Castets Francis , Saurin Andrew J. , Serino Matteo , Moqrich Aziz 
Published: February 2023

SummaryOver the past decade, the gut microbiota has emerged as an important regulator of nervous system’s health and disease states1. Yet, its contribution to the pathogenesis of chronic somatic pain remains poorly documented. Chronic pain is a heavily debilitating disease affecting more than 1.5 billion people worldwide that can manifest through a long-lasting hypersensitivity to mechanical and/or thermal stimulations2,3. Maladaptive responses of dorsal root ganglia (DRG) neurons and spinal cord (SC) interneurons to tissue injuries and also of non-neuronal cells including DRG macrophages and SC microglia are acknowledged as important drivers of sensory symptoms underlying chronic pain4,3,5–7. Recent evidence shows that signals from gut microbiota are required for the initiation of injury-induced sensory hypersensitivity, via the ability to interact with the immune system8–11. However, whether and how gut microbiota promotes pain chronicity remains unknown. Here, we report that male mice lackingMyosin1a(KO)12raised under single genotype housing conditions (KO-SGH) are predisposed to develop chronic injury-induced mechanical pain. We demonstrate that this predisposition is caused by their dysbiotic gut microbiota, which sustains the immune response in the DRG following neuropathic injury. Parental antibiotic treatment modifies gut microbiota composition and completely rescues the injury-induced chronic pain and associated DRG inflammatory response in male KO-SGH offspring. Together, our data establish a causal relationship between a dysbiotic gut microbiota and the predisposition to injury-induced chronic pain.