bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discerning asthma endotypes through comorbidity mapping
Authors: Jia Gengjie , Zhong Xue , Im Hae Kyung , Schoettler Nathan , Pividori Milton , Hogarth D. Kyle , Sperling Anne I. , White Steven R. , Naureckas Edward T. , Lyttle Christopher S. , Terao Chikashi , Kamatani Yoichiro , Akiyama Masato , Matsuda Koichi , Kubo Michiaki , Cox Nancy J. , Ober Carole , Rzhetsky Andrey , Solway Julian 
Published: November 2022

AbstractAsthma is a heterogeneous, complex syndrome, and identifying asthma endotypes has been challenging. We hypothesize that distinct endotypes of asthma arise in disparate genetic variation and life-time environmental exposure backgrounds, and that disease comorbidity patterns serve as a surrogate for such genetic and exposure variations. Here, we computationally discover 22 distinct comorbid disease patterns among individuals with asthma (asthma comorbidity subgroups) using diagnosis records for >151 M US residents, and re-identify 11 of the 22 subgroups in the much smaller UK Biobank. GWASs to discern asthma risk loci for individuals within each subgroup and in all subgroups combined reveal 109 independent risk loci, of which 52 are replicated in multi-ancestry meta-analysis across different ethnicity subsamples in UK Biobank, US BioVU, and BioBank Japan. Fourteen loci confer asthma risk in multiple subgroups and in all subgroups combined. Importantly, another six loci confer asthma risk in only one subgroup. The strength of association between asthma and each of 44 health-related phenotypes also varies dramatically across subgroups. This work reveals subpopulations of asthma patients distinguished by comorbidity patterns, asthma risk loci, gene expression, and health-related phenotypes, and so reveals different asthma endotypes.
Tunable critical Casimir forces counteract Casimir–Lifshitz attraction
Authors: Schmidt Falko , Callegari Agnese , Daddi-Moussa-Ider Abdallah , Munkhbat Battulga , Verre Ruggero , Shegai Timur , Käll Mikael , Löwen Hartmut , Gambassi Andrea , Volpe Giovanni 
Published: November 2022

AbstractIn developing micro- and nanodevices, stiction between their parts, that is, static friction preventing surfaces in contact from moving, is a well-known problem. It is caused by the finite-temperature analogue of the quantum electrodynamical Casimir–Lifshitz forces, which are normally attractive. Repulsive Casimir–Lifshitz forces have been realized experimentally, but their reliance on specialized materials severely limits their applicability and prevents their dynamic control. Here we demonstrate that repulsive critical Casimir forces, which emerge in a critical binary liquid mixture upon approaching the critical temperature, can be used to counteract stiction due to Casimir–Lifshitz forces and actively control microscopic and nanoscopic objects with nanometre precision. Our experiment is conducted on a microscopic gold flake suspended above a flat gold-coated substrate immersed in a critical binary liquid mixture. This may stimulate the development of micro- and nanodevices by preventing stiction as well as by providing active control and precise tunability of the forces acting between their constituent parts.
Computational simulation and target prediction studies of solubility optimization of decitabine through supercritical solvent
Authors: Alshahrani Saad M. , Almutairy Bjad K. , Alfadhel Munerah M. , Belal Amany , Abourehab Mohammed A. S. , Saqr Ahmed Al. , Alshetaili Abdullah S. , Venkatesan Kumar , Alsubaiyel Amal M. , Pishnamazi Mahboubeh 
Published: November 2022

AbstractComputational analysis of drug solubility was carried out using machine learning approach. The solubility of Decitabine as model drug in supercritical CO2 was studied as function of pressure and temperature to assess the feasibility of that for production of nanomedicine to enhance the solubility. The data was collected for solubility optimization of Decitabine at the temperature 308–338 K, and pressure 120–400 bar used as the inputs to the machine learning models. A dataset of 32 data points and two inputs (P and T) have been applied to optimize the solubility. The only output is Y = solubility, which is Decitabine mole fraction solubility in the solvent. The developed models are three models including Kernel Ridge Regression (KRR), Decision tree Regression (DTR), and Gaussian process (GPR), which are used for the first time as a novel model. These models are optimized using their hyper-parameters tuning and then assessed using standard metrics, which shows R2-score, KRR, DTR, and GPR equal to 0.806, 0.891, and 0.998. Also, the MAE metric shows 1.08E−04, 7.40E−05, and 9.73E−06 error rates in the same order. The other metric is MAPE, in which the KRR error rate is 4.64E−01, DTR shows an error rate equal to 1.63E−01, and GPR as the best mode illustrates 5.06E−02. Finally, analysis using the best model (GPR) reveals that increasing both inputs results in an increase in the solubility of Decitabine. The optimal values are (P = 400, T = 3.38E + 02, Y = 1.07E−03).
Comparative and pangenomic analysis of the genus Streptomyces
Authors: Otani Hiroshi , Udwary Daniel W. , Mouncey Nigel J. 
Published: November 2022

AbstractStreptomycetes are highly metabolically gifted bacteria with the abilities to produce bioproducts that have profound economic and societal importance. These bioproducts are produced by metabolic pathways including those for the biosynthesis of secondary metabolites and catabolism of plant biomass constituents. Advancements in genome sequencing technologies have revealed a wealth of untapped metabolic potential from Streptomyces genomes. Here, we report the largest Streptomyces pangenome generated by using 205 complete genomes. Metabolic potentials of the pangenome and individual genomes were analyzed, revealing degrees of conservation of individual metabolic pathways and strains potentially suitable for metabolic engineering. Of them, Streptomyces bingchenggensis was identified as a potent degrader of plant biomass. Polyketide, non-ribosomal peptide, and gamma-butyrolactone biosynthetic enzymes are primarily strain specific while ectoine and some terpene biosynthetic pathways are highly conserved. A large number of transcription factors associated with secondary metabolism are strain-specific while those controlling basic biological processes are highly conserved. Although the majority of genes involved in morphological development are highly conserved, there are strain-specific varieties which may contribute to fine tuning the timing of cellular differentiation. Overall, these results provide insights into the metabolic potential, regulation and physiology of streptomycetes, which will facilitate further exploitation of these important bacteria.
Transplacental transfer of total immunoglobulin G and antibodies to Plasmodium falciparum antigens between the 24th week of gestation and term
Authors: Kayatani Alexander K. K. , Leke Rose G. F. , Leke Robert I. J. , Fogako Josephine , Taylor Diane Wallace 
Published: November 2022

AbstractFull-term newborns have antibody (Ab) repertoires and levels similar to their mothers to help protect them from environmental pathogens. Unfortunately, preterm babies, especially those born < 34 weeks, have reduced levels of protective antibodies. In Africa, antibodies to Plasmodium falciparum are important in protection from malaria. This study investigated the transfer of total IgG and antibodies to 9 P. falciparum antigens and tetanus toxoid between 24 weeks and term. Paired maternal and cord samples from 166 preterm (24–37 weeks) and 154 term deliveries were used. Transfer efficiency was expressed as the ratio of Ab levels in cord to maternal plasma (CMR). At 24–25 weeks, CMR ranged from 0.31 to 0.94 for the different antigens; the rate of transfer was similar for all antigens between 24 and 40 weeks; resulting in median CMR of 0.49–0.95 at term. Babies of mothers with hypergammaglobulinemia and normal IgG levels had similar amounts of IgG, supporting data that saturation of the neonatal Fc-receptor occurs at ~ 16 mg IgG/ml. Thus, babies born prior to 34–35 weeks in Africa are likely to have reduced Ab levels to some, but not all antigens. Since IgG transfer is Fc-mediated, why differences exist in CMR among the antigens warrants further investigation.
Medication non-adherence and therapeutic inertia independently contribute to poor disease control for cardiometabolic diseases
Authors: Yan Xiaowei , Mudiganti Satish , Husby Hannah , Hudnut Andrew , Gbotoe Madina , Jones J. B. 
Published: November 2022

AbstractPoorly controlled cardiometabolic biometric health gap measures [e.g.,uncontrolled blood pressure (BP), HbA1c, and low-density lipoprotein cholesterol (LDL-C)] are mediated by medication adherence and clinician-level therapeutic inertia (TI). The study of comparing relative contribution of these two factors to disease control is lacking. We conducted a retrospective cohort study using 7 years of longitudinal electronic health records (EHR) from primary care cardiometabolic patients who were 35 years or older. Cox-regression modeling was applied to estimate how baseline proportion of days covered (PDC) and TI were associated with cardiometabolic related health gap closure. 92,766 patients were included in the analysis, among which 89.9%, 85.8%, and 73.3% closed a BP, HbA1c, or LDL-C gap, respectively, with median days to gap closure ranging from 223 to 408 days. Patients who did not retrieve a medication were the least likely to achieve biometric control, particularly for LDL-C (HR = 0.58, 95% CI: 0.55–0.60). TI or uncertainty of TI was associated with a high risk of health gap persistence, particularly for LDL-C (HR ranges 0.46–0.48). Both poor medication adherence and TI are independently associated with persistent health gaps, and TI has a much higher impact on disease control compared to medication adherence, implying disease management strategies should prioritize reducing TI.
Modeling a semi-optimal deceleration of a rigid body rotational motion in a resisting medium
Authors: El-Sabaa F. M. , Amer T. S. , Sallam A. A. , Abady I. M. 
Published: November 2022

AbstractThis paper studies the shortest time of slowing rotation of a free dynamically asymmetric rigid body (RB), analogous to Euler’s case. This body is influenced by a rotatory moment of a tiny control torque with closer coefficients but not equal, a gyrostatic moment (GM) due to the presence of three rotors, and in the presence of a modest slowing viscous friction torque. Therefore, this problem can be regarded as a semi-optimal one. The controlling optimal decelerating law for the rotation of the body is constructed. The trajectories that are quasi-stationary are examined. The obtained new results are displayed to identify the positive impact of the GM. The dimensionless form of the regulating system of motion is obtained. The functions of kinetic energy and angular momentum besides the square module are drawn for various values of the GM’s projections on the body’s principal axes of inertia. The effect of control torques on the body's motion is investigated in a case of small perturbation, and the achieved results are compared with the unperturbed one. For the case of a lack of GM, the comparison between our results and those of the prior ones reveals a high degree of consistency, in which the deviations between them are examined. As a result, these outcomes generalized those that were acquired in previous studies. The significance of this research stems from its practical applications, particularly in the applications of gyroscopic theory to maintain the stability and determine the orientation of aircraft and undersea vehicles.
Biosynthesis of gamma-aminobutyric acid by Lactiplantibacillus plantarum K16 as an alternative to revalue agri-food by-products
Authors: Diez-Gutiérrez Lucía , Vicente Leire San , Sáenz Jessica , Esquivel Argitxu , Barron Luis Javier R. , Chávarri María 
Published: November 2022

AbstractProbiotic metabolites, known as postbiotics, have received attention due to their wide variety of promoting health effects. One of the most exciting postbiotic is gamma-aminobutyric acid (GABA), widely produced by lactic acid bacteria, due to its benefits in health. In addition, the performance of the biosynthesis of GABA by Lactiplantibacillus plantarum could be modulated through the modification of fermentation parameters. Due to their high nutritional value, agri-food by-products could be considered a useful fermentation source for microorganisms. Therefore, these by-products were proposed as fermentation substrates to produce GABA in this study. Previously, several experiments in Man Rogosa Sharpe (MRS) broth were performed to identify the most critical parameters to produce GABA using the strain Lactiplantibacillus plantarum K16. The percentage of inoculum, the initial pH, and the concentration of nutrients, such as monosodium glutamate or glucose, significantly affected the biosynthetic pathway of GABA. The highest GABA yield was obtained with 500 mM of monosodium glutamate and 25 g/L of glucose, and an initial pH of 5.5 and 1.2% inoculum. Furthermore, these investigated parameters were used to evaluate the possibility of using tomato, green pepper, apple, or orange by-products to get GABA-enriched fermented media, which is an excellent way to revalorise them.
A multi-marker integrative analysis reveals benefits and risks of bariatric surgery
Authors: Palleschi Simonetta , Guglielmi Valeria , Nisticò Lorenza , Ferreri Carla , Tabolacci Claudio , Facchiano Francesco , Iorio Egidio , Giuliani Alessandro , Brescianini Sonia , Medda Emanuela , Fagnani Corrado , Rossi Barbara , Minoprio Anna , Chirico Mattea , Pisanu Maria Elena , Di Nolfo Federica , Fortini Paola , Simonelli Valeria , Baccarini Sara , Laterza Serena , Morretti Tiziana , Dell’Orso Ambra , Manganello Federico , Gentileschi Paolo , Sbraccia Paolo , Dogliotti Eugenia 
Published: November 2022

AbstractBariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success.
Mortality among hospitalized COVID-19 patients during surges of SARS-CoV-2 alpha (B.1.1.7) and delta (B.1.617.2) variants
Authors: Zali Alireza , Khodadoost Mahmood , Gholamzadeh Saeid , Janbazi Shahriar , Piri Hassan , Taraghikhah Nazanin , Hannani Khatereh , Looha Mehdi Azizmohammad , Mohammadi Gohar 
Published: November 2022

AbstractThe aim of this study was to evaluate the death proportion and death risk of COVID-19 hospitalized patients over time and in different surges of COVID-19. This multi-center observational study was conducted from March 21, 2021 to October 3, 2021 which included the alpha and delta SARS-CoV-2 surges occurred in April and August in Tehran, respectively. The risk of COVID-19 death was compared in different months of admission. A total of 270,624 patients with COVID-19, of whom 6.9% died, were admitted to hospitals in Tehran province. Compared to patients admitted in March, a higher risk of COVID-19 death was observed among patients admitted to the hospital in July (HR 1.28; 95% CI 1.17, 1.40), August (HR 1.40; 95% CI 1.28, 1.52), September (HR 1.37; 95% CI 1.25, 1.50) and October (HR 4.63; 95% CI 2.77, 7.74). The ICU death proportion was 36.8% (95% CI: 35.5, 38.1) in alpha surge and increased significantly to 39.8 (95% CI 38.6, 41.1) in delta surge. The risk of COVID-19 death was significantly higher in delta surge compared to alpha surge (HR 1.22; 95% CI 1.17, 1.27). Delta surge was associated with a higher risk of death compared to alpha surge. High number of hospitalizations, a shortage of hospital beds, ICU spaces and medical supplies, poor nutritional status of hospitalized patients, and lack of the intensivist physicians or specialized nurses in the ICU were factors that contributed to the high mortality rate in the delta surge in Iran.
Microsatellite analysis and polymorphic marker development based on the full-length transcriptome of Camellia chekiangoleosa
Authors: Tian Qianqian , Huang Bin , Huang Jianjian , Wang Bo , Dong Le , Yin Xin , Gong Chun , Wen Qiang 
Published: November 2022

AbstractCamellia chekiangoleosa is a popular variety of Oil-camellia that has high oil production and ornamental value. Microsatellite (SSR) markers are the preferred tool for the molecular marker-assisted breeding of C. chekiangoleosa. By focusing on the problems of the low development efficiency of polymorphic SSR markers and the lack of available functional markers in Oil-camellia, we identified 97,510 SSR loci based on the full-length transcriptome sequence of C. chekiangoleosa. An analysis of SSR characteristics showed that mononucleotide (51.29%) and dinucleotide (34.36%) SSRs were the main repeat types. The main SSR distribution areas based on proportion covered were ordered as follows: 5'UTR > 3'UTR > CDS. By comparing our data with those in databases such as GO and KEGG, we obtained functional annotations of unigene sequences containing SSR sites. The data showed that the amplification efficiency of the SSR primers was 51.72%, and the development efficiency of polymorphic SSR primers was 26.72%. Experiments verified that dinucleotide and pentanucleotide SSRs located in UTR regions could produce more polymorphic markers. An investigation into the genetic diversity of several C. chekiangoleosa populations also suggested that the developed SSR markers had higher levels of polymorphism. This study will provide a reference and high-quality markers for the large-scale development of functional SSR markers and genetic research in Oil-camellia.
Improvement of the signal to noise ratio for fluorescent imaging in microfluidic chips
Authors: Liu Xiaocheng , Zhu Hanliang , Sabó Ján , Lánský Zdeněk , Neužil Pavel 
Published: November 2022

AbstractMicrofluidics systems can be fabricated in various ways using original silicon glass systems, with easy Si processing and surface modifications for subsequent applications such as cell seeding and their study. Fluorescent imaging of cells became a standard technique for the investigation of cell behavior. Unfortunately, high sensitivity fluorescent imaging, e.g., using total internal reflection fluorescence (TIRF) microscopy, is problematic in these microfluidic systems because the uneven surfaces of the silicon channels’ bottoms affect light penetration through the optical filters. In this work, we study the nature of the phenomenon, finding that the problem can be rectified by using a silicon-on-insulator (SOI) substrate, defining the channel depth by the thickness of the top Si layer, and halting the etching at the buried SiO2 layer. Then the fluorescent background signal drops by = 5 times, corresponding to the limit of detection drop from = 0.05 mM to = 50 nM of fluorescein. We demonstrate the importance of a flat surface using TIRF-based single-molecule detection, improving the signal to a noise ratio more than 18 times compared to a conventional Si wafer. Overall, using very high-quality SOI substrates pays off, as it improves the fluorescence image quality due to the increase in signal-to-noise ratio. Concerning the cost of microfluidic device fabrication—design, mask fabrication, wafer processing, and device testing—the initial SOI wafer cost is marginal, and using it improves the system performance.
Optimization of 3D-aggregated spheroid model (3D-ASM) for selecting high efficacy drugs
Authors: Lee Sang-Yun , Hwang Hyun Ju , Lee Dong Woo 
Published: November 2022

AbstractVarious three-dimensional (3D) cell culture methods have been developed to implement tumor models similar to in vivo. However, the conventional 3D cell culture method has limitations such as difficulty in using an extracellular matrix (ECM), low experimental reproducibility, complex 3D cell culture protocol, and difficulty in applying to high array plates such as 96- or 384-plates. Therefore, detailed protocols related to robust 3D-aggregated spheroid model (3D-ASM) production were optimized and proposed. A specially designed wet chamber was used to implement 3D-ASM using the hepatocellular carcinoma (HCC) cell lines, and the conditions were established for the icing step to aggregate the cells in one place and optimized ECM gelation step. Immunofluorescence (IF) staining is mainly used to simultaneously analyze drug efficacy and changes in drug-target biomarkers. By applying the IF staining method to the 3D-ASM model, confocal microscopy imaging and 3D deconvolution image analysis were also successfully performed. Through a comparative study of drug response with conventional 2D-high throughput screening (HTS), the 3D-HTS showed a more comprehensive range of drug efficacy analyses for HCC cell lines and enabled selective drug efficacy analysis for the FDA-approved drug sorafenib. This suggests that increased drug resistance under 3D-HTS conditions does not reduce the analytical discrimination of drug efficacy, also drug efficacy can be analyzed more selectively compared to the conventional 2D-HTS assay. Therefore, the 3D-HTS-based drug efficacy analysis method using an automated 3D-cell spotter/scanner, 384-pillar plate/wet chamber, and the proposed 3D-ASM fabrication protocol is a very suitable platform for analyzing target drug efficacy in HCC cells.
The spread of Carpophilus truncatus is on the razor's edge between an outbreak and a pest invasion
Authors: de Benedetta Flavia , Gargiulo Simona , Miele Fortuna , Figlioli Laura , Innangi Michele , Audisio Paolo , Nugnes Francesco , Bernardo Umberto 
Published: November 2022

AbstractIn 2019, in southern Italy (Campania) there was an outbreak of a sap beetle infesting stored walnut fruits. A monitoring activity started to assess the spread and impact of the pest in walnut orchards and in warehouses, and an integrative characterization led to identify the beetle asCarpophilus truncatus. This species has been in Europe for a long time, rare and harmless until recently. We show also that this species is the same recently recorded in other two continents, Latin America and Australia, where it is causing massive damage on walnut and almond fruits. The sharing of a mitochondrial haplotype among populations recorded on three continents suggests that a worldwide invasion might be ongoing. A Geographic Profiling approach has determined that the more virulent population was first introduced in Italy, and the climate conditions of areas whereC. truncatusis currently widespread and harmful indicate that the entire walnuts world production is in jeopardy as this species could adapt to any of the main walnut and almond production areas.