bluuebunny/crossref_metadata_2025_split huggingface dataset:
The External Exposome and Allergies: From the Perspective of the Epithelial Barrier Hypothesis
Authors: Celebi Sozener Zeynep , Özbey Yücel Ümüs , Altiner Seda , Ozdel Oztürk Betül , Cerci Pamir , Türk Murat , Gorgülü Akin Begüm , Akdis Mübeccel , Yilmaz Insu , Ozdemir Cevdet , Mungan Dilsad , Akdis Cezmi A. 
Published: July 2022

IntroductionIn the last decades, we have seen a rapid increase in the prevalence of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergies. The environmental changes caused by industrialization, urbanization and modernization, including dramatic increases in air pollutants such as particulate matter (PM), diesel exhaust, nitrogen dioxide (NO2), ozone (O3), alarming effects of global warming, change and loss of biodiversity, affect both human health and the entire ecosystem.ObjectiveIn this review, we aimed to discuss the effects of the external exposome on epithelial barriers and its relationship with the development of allergic diseases by considering the changes in all stakeholders of the outer exposome together, in the light of the recently proposed epithelial barrier hypothesis.MethodTo reach current, prominent, and comprehensive studies on the subject, PubMed databases were searched. We included the more resounding articles with reliable and strong results.ResultsExposure to altered environmental factors such as increased pollution, microplastics, nanoparticles, tobacco smoke, food emulsifiers, detergents, and household cleaners, and climate change, loss and change in microbial biodiversity, modifications in the consumption of dietary fatty acids, the use of emulsifiers, preservatives and the decrease in the antioxidant content of the widely consumed western diet may disrupt the epithelial barriers of the skin, respiratory and gastrointestinal tracts, making us more vulnerable to exogeneous allergens and microbes. Epithelial cell activation, microbial dysbiosis and bacterial translocation disrupt the immune balance and a chronic Th2 inflammation ensues.ConclusionDramatic increases in air pollution, worrisome effects of global warming, dysbiosis, changing dietary habits and the complex interactions of all these factors affect the epithelial barriers and local and systemic inflammation. We want to draw attention to the emerging health effects of environmental changes and to motivate the public to influence government policies for the well-being of humans and the nature of the earth and the well-being of future generations.
Printability of Double Network Alginate-Based Hydrogel for 3D Bio-Printed Complex Structures
Authors: Greco Immacolata , Miskovic Vanja , Varon Carolina , Marraffa Chiara , Iorio Carlo S. 
Published: July 2022

Three-dimensional (3D) bio-printing has recently emerged as a crucial technology in tissue engineering, yet there are still challenges in selecting materials to obtain good print quality. Therefore, it is essential to study the influence of the chosen material (i.e., bio-ink) and the printing parameters on the final result. The “printability” of a bio-ink indicates its suitability for bio-printing. Hydrogels are a great choice because of their biocompatibility, but their printability is crucial for exploiting their properties and ensuring high printing accuracy. However, the printing settings are seldom addressed when printing hydrogels. In this context, this study explored the printability of double network (DN) hydrogels, from printing lines (1D structures) to lattices (2D structures) and 3D tubular structures, with a focus on printing accuracy. The DN hydrogel has two entangled cross-linked networks and a balanced mechanical performance combining high strength, toughness, and biocompatibility. The combination of poly (ethylene glycol)-diacrylate (PEDGA) and sodium alginate (SA) enables the qualities mentioned earlier to be met, as well as the use of UV to prevent filament collapse under gravity. Critical correlations between the printability and settings, such as velocity and viscosity of the ink, were identified. PEGDA/alginate-based double network hydrogels were explored and prepared, and printing conditions were improved to achieve 3D complex architectures, such as tubular structures. The DN solution ink was found to be unsuitable for extrudability; hence, glycerol was added to enhance the process. Different glycerol concentrations and flow rates were investigated. The solution containing 25% glycerol and a flow rate of 2 mm/s yielded the best printing accuracy. Thanks to these parameters, a line width of 1 mm and an angle printing inaccuracy of less than 1° were achieved, indicating good shape accuracy. Once the optimal parameters were identified, a tubular structure was achieved with a high printing accuracy. This study demonstrated a 3D printing hydrogel structure using a commercial 3D bio-printer (REGEMAT 3D BIO V1) by synchronizing all parameters, serving as a reference for future more complex 3D structures.
Efficient Production of 2,5-Diketo-D-gluconic Acid by Reducing Browning Levels During Gluconobacter oxydans ATCC 9937 Fermentation
Authors: Li Guang , Shan Xiaoyu , Zeng Weizhu , Yu Shiqin , Zhang Guoqiang , Chen Jian , Zhou Jingwen 
Published: July 2022

D-Glucose directly generates 2-keto-L-gulonic acid (2-KLG, precursor of vitamin C) through the 2,5-diketo-D-gluconic acid (2,5-DKG) pathway. 2,5-DKG is the main rate-limiting factor of the reaction, and there are few relevant studies on it. In this study, a more accurate quantitative method of 2,5-DKG was developed and used to screen G. oxydans ATCC9937 as the chassis strain for the production of 2,5-DKG. Combining the metabolite profile analysis and knockout and overexpression of production strain, the non-enzymatic browning of 2,5-DKG was identified as the main factor leading to low yield of the target compound. By optimizing the fermentation process, the fermentation time was reduced to 48 h, and 2,5-DKG production peaked at 50.9 g/L, which was 139.02% higher than in the control group. Effectively eliminating browning and reducing the degradation of 2,5-DKG will help increase the conversion of 2,5-DKG to 2-KLG, and finally, establish a one-step D-glucose to 2-KLG fermentation pathway.
dDAVP Downregulates the AQP3-Mediated Glycerol Transport via V1aR in Human Colon HCT8 Cells
Authors: Centrone Mariangela , D’Agostino Mariagrazia , Ranieri Marianna , Mola Maria Grazia , Faviana Pinuccia , Lippolis Piero Vincenzo , Silvestris Domenico Alessandro , Venneri Maria , Di Mise Annarita , Valenti Giovanna , Tamma Grazia 
Published: July 2022

Vasopressin (AVP) plays a key function in controlling body water and salt balance through the activation of the vasopressin receptors V1aR and V2R. Abnormal secretion of AVP can cause the syndrome of inappropriate antidiuresis that leads to hyponatremia, which is an electrolyte disorder often observed in the elderly hospitalized and oncologic patients. Beyond kidneys, the colonic epithelium modulates water and salt homeostasis. The water channel AQP3, expressed in villus epithelial cells is implicated in water absorption across human colonic surface cells. Here, the action of dDAVP, a stable vasopressin analog, was evaluated on the AQP3 expression and function using human colon HCT8 cells as an experimental model. Confocal and Western Blotting analysis revealed that HCT8 cells express both V1aR and V2R. Long-term (72 h) treatment with dDAVP reduced glycerol uptake and cell viability. These effects were prevented by SR49059, a synthetic antagonist of V1aR, but not by tolvaptan, a specific V2R antagonist. Of note, the SR49059 action was impaired by DFP00173, a selective inhibitor of AQP3. Interestingly, compared to the normal colonic mucosa, in the colon of patients with adenocarcinoma, the expression of V1aR was significantly decreased. These findings were confirmed by gene expression analysis with RNA-Seq data. Overall, data suggest that dDAVP, through the V1aR dependent pathway, reduces AQP3 mediated glycerol uptake, a process that is reversed in adenocarcinoma, suggesting that the AVP-dependent AQP3 pathway may represent a novel target in colon diseases associated with abnormal cell growth.
Updating Urinary Microbiome Analyses to Enhance Biologic Interpretation
Authors: Siddiqui Nazema Y. , Ma Li , Brubaker Linda , Mao Jialiang , Hoffman Carter , Dahl Erin M. , Wang Zhuoqun , Karstens Lisa 
Published: July 2022

ObjectiveAn approach for assessing the urinary microbiome is 16S rRNA gene sequencing, where analysis methods are rapidly evolving. This re-analysis of an existing dataset aimed to determine whether updated bioinformatic and statistical techniques affect clinical inferences.MethodsA prior study compared the urinary microbiome in 123 women with mixed urinary incontinence (MUI) and 84 controls. We obtained unprocessed sequencing data from multiple variable regions, processed operational taxonomic unit (OTU) tables from the original analysis, and de-identified clinical data. We re-processed sequencing data with DADA2 to generate amplicon sequence variant (ASV) tables. Taxa from ASV tables were compared to the original OTU tables; taxa from different variable regions after updated processing were also compared. Bayesian graphical compositional regression (BGCR) was used to test for associations between microbial compositions and clinical phenotypes (e.g., MUI versus control) while adjusting for clinical covariates. Several techniques were used to cluster samples into microbial communities. Multivariable regression was used to test for associations between microbial communities and MUI, again while adjusting for potentially confounding variables.ResultsOf taxa identified through updated bioinformatic processing, only 40% were identified originally, though taxa identified through both methods represented &gt;99% of the sequencing data in terms of relative abundance. Different 16S rRNA gene regions resulted in different recovered taxa. With BGCR analysis, there was a low (33.7%) probability of an association between overall microbial compositions and clinical phenotype. However, when microbial data are clustered into bacterial communities, we confirmed that bacterial communities are associated with MUI. Contrary to the originally published analysis, we did not identify different associations by age group, which may be due to the incorporation of different covariates in statistical models.ConclusionsUpdated bioinformatic processing techniques recover different taxa compared to earlier techniques, though most of these differences exist in low abundance taxa that occupy a small proportion of the overall microbiome. While overall microbial compositions are not associated with MUI, we confirmed associations between certain communities of bacteria and MUI. Incorporation of several covariates that are associated with the urinary microbiome improved inferences when assessing for associations between bacterial communities and MUI in multivariable models.
Saccharomyces boulardii Allows Partial Patients to Avoid Reusing Bismuth Quadruple for Helicobacter pylori Rescue Therapy: A Single-Center Randomized Controlled Study
Authors: Qu Peng , Liu Xiaoming , Xia Xiujuan , Xie Xiaoran , Luo Ju , Cheng Sha , Chi Jingshu , Liu Peng , Li Huan , Zhao Wenfang , Yang Huihao , Xu Canxia 
Published: July 2022

BackgroundThe increasing rate of drug resistance often leads to Helicobacter pylori (H. pylori) eradication failure and needs the rescue therapy. Thus, the exploration of new rescue therapeutic regimens is important. The present study was designed to test the beneficial effects of Saccharomyces boulardii (S.boulardii) prior to H. pylori rescue therapy basing on bismuth quadruple.MethodsOne hundred H. pylori-infected patients were randomly divided into two groups: study group and control group. Patients in the study group (n=50) underwent two-stages therapy: patients started with S.boulardii monotherapy for 2 weeks, and then tested for H. pylori infection after resting for 4 weeks without any therapy, patients who were still positive for H. pylori continued with bismuth quadruple eradication therapy. For the control group (n=50), all patients were observed and were not treated with any gastric drugs or antibiotics for 6 weeks, then those who were still positive for H. pylori received the same eradication therapy as the study group. Eradication rate, adverse events and the cost-effectiveness of two regimens were analyzed in this study.ResultsThe H.pylori eradication rate of ITT (intent-to-treat) analysis and PP (per-protocol) analysis in the first phase of treatment were significantly higher in the study group than the control groups respectively (28.0% vs 2.0%, p&lt;0.001 and 30.4% vs 2.1% p&lt;0.001). For the total treatment effect, there were no significant differences in the eradication rate of ITT analysis (78.0% vs 80.0%) or PP analysis (90.7% vs 88.9%) between the study group and the control group. The cost‐effectiveness ratio of the study group was slightly higher than that of the control group (8.95 vs 8.55). There were two patients in the study group and four patients in the control group with the adverse events, respectively. There was no significant difference on the incidence of adverse events between the two groups (p=0.68).ConclusionS.boulardii may serve as a beneficial treatment option before H. pylori rescue therapy since it callowed partial patients to avoid reusing bismuth quadruple.
Performance of PRECISE-DAPT and Age–Bleeding–Organ Dysfunction Score for Predicting Bleeding Complication During Dual Antiplatelet Therapy in Chinese Elderly Patients
Authors: Dong Liang , Lu Cao , Wensen Chen , Fuzhong Chen , Khalid Muhammad , Xiaoyu Dong , Guangjuan Li , Yanxia Qian , Yufeng Zhang , Xinjian Liu , Leilei Chen , Junhong Wang 
Published: July 2022

BackgroundRecently, the Age–Bleeding–Organ Dysfunction (ABO) algorithm was recommended by the Asian Pacific Society of Cardiology Consensus as a binary approach to evaluate bleeding risk. This analysis made comparison of the predictive performances between the PRECISE-DAPT and ABO bleeding score in identifying the risk of 12-months major bleeding in Chinese elderly patients over 65 years old patients who underwent percutaneous coronary intervention (PCI) during dual-antiplatelet therapy period.MethodsA total of 2,037 elderly coronary artery disease (CAD) patients (≥65 years) receiving dual antiplatelet therapy (DAPT) after PCI were enrolled in the study. The predictive accuracy of the two bleeding risk scores (PRECISE-DAPT and ABO) was compared for identifying the risk of bleeding during the dual-antiplatelet therapy in patients who underwent PCI. Major clinically relevant bleeding events were defined according to the Bleeding Academic Research Consortium (BARC) criteria.ResultsThe PRECISE-DAPT score in the no bleeding, BARC = 1 bleeding, BARC ≥ 2 bleeding patients was 23.55 ± 10.46, 23.23 ± 10.03, and 33.54 ± 14.33 (p &lt; 0.001), respectively. Meanwhile, the ABO score in the three groups was 0.72 ± 0.80, 0.69 ± 0.81, and 1.49 ± 0.99 (p &lt; 0.001), respectively. The C-statistic of the PRECISE-DAPT model for prediction of BARC ≥ 2 bleeding in overall patients was 0.717 (95% CI, 0.656–0.777) and 0.720 (95% CI, 0.656–0.784) in acute coronary syndrome (ACS) patients. Similar discriminatory capacity was demonstrated in the ABO risk score [overall, patients, AUC: 0.712 (95% CI, 0.650–0.774); ACS patients, AUC: 0.703 (95% CI, 0.634–0.772)]. No differences were observed when the ABO model was in comparison with the PRECISE-DAPT model, regardless in overall patients (z = −0.199, p = 0.842) or ACS patients (z = −0.605, p = 0.545). The calibration for BARC ≥ 2 bleeding of the PRECISE-DAPT and ABO score were acceptable, regardless in overall patients [goodness-of-fit (GOF) Chi-square = 0.432 and 0.001, respectively; p-value = 0.806 and 0.999, respectively] or ACS patients (GOF Chi-square = 0.008 and 0.580, respectively; p-value = 0.996 and 0.748, respectively).ConclusionNo matter of clinical presentation in Asian 65-years older patients with DAPT, the PRECISE-DAPT, and ABO scores had the similar discriminative ability for 12-months BARC ≥ 2 bleeding. Considering the simplicity and reliability, the PRECISE-DAPT score might be more clinically applicable in the overall population and ACS patients in bleeding prediction.
Association Between the Expression of MicroRNA-125b and Survival in Patients With Acute Coronary Syndrome and Coronary Multivessel Disease
Authors: Gager Gloria M. , Eyileten Ceren , Postula Marek , Gasecka Aleksandra , Jarosz-Popek Joanna , Gelbenegger Georg , Jilma Bernd , Lang Irene , Siller-Matula Jolanta 
Published: July 2022

BackgroundMicroRNAs (miRNA, miR) have an undeniable physiological and pathophysiological significance and act as promising novel biomarkers. The aim of the study was to investigate blood-derived miRNAs and their association with long-term all-cause mortality in patients with multivessel disease (MVD) suffering from acute coronary syndrome (ACS).Materials and MethodsThis study was an observational prospective study, which included 90 patients with MVD and ACS. Expression of miR-125a, miR-125b, and miR-223 was analysed by polymerase chain reaction (PCR). Patients were followed-up for a median of 7.5 years. All-cause mortality was considered as the primary endpoint. Adjusted Cox-regression analysis was performed for prediction of events.ResultsElevated expression of miR-125b (&gt;4.6) at the time-point of ACS was associated with increased long-term all-cause mortality (adjusted [adj.] hazard ratio [HR] = 11.26, 95% confidence interval [95% CI]: 1.15–110.38; p = 0.038). The receiver operating characteristic (ROC) analysis showed a satisfactory c-statistics for miR-125b for the prediction of long-term all-cause mortality (area under the curve [AUC] = 0.76, 95% CI: 0.61–0.91; p = 0.034; the negative predictive value of 98%). Kaplan–Meier time to event analysis confirmed an early separation of the survival curves between patients with high vs low expression of miR-125b (p = 0.003). An increased expression of miR-125a and miR-223 was found in patients with non-ST-segment elevation ACS (NSTE-ACS) as compared to those with ST-segment elevation myocardial infarction (STEMI) (p = 0.043 and p = 0.049, respectively) with no difference in the expression of miR-125b between the type of ACS.ConclusionIn this hypothesis generating study, lower values of miR-125b were related to improved long-term survival in patients with ACS and MVD. Larger studies are needed to investigate whether miR-125b can be used as a suitable predictor for long-term all-cause mortality.
Human Diet Patterns During the Qijia Cultural Period: Integrated Evidence of Stable Isotopes and Plant Micro-remains From the Lajia Site, Northwest China
Authors: Ma Zhikun , Liu Shu , Li Zhao , Ye Maolin , Huan Xiujia 
Published: July 2022

The diet of prehistoric humans in the Qijia period (4,400–3,500 BP) was significantly changed by the advent of dry agriculture and food globalization. However, it is yet to be proven whether wild plants were exploited despite the cultivation of millet, and whether wheat crops, cattle, and sheep originating from southwestern Asia were adopted into the regional human diet. This study presents stable isotope, starch grain, and phytolith analyses of 24 human teeth from the Lajia site in Qinghai, which is a representative Qijia culture settlement site. The carbon and nitrogen isotope results show that the subjects primarily ate C4 plants and had a high protein diet. Starch grain and phytolith results showed that the inhabitants consumed broomcorn millet (Panicum miliaceum), foxtail millet (Setaria italica), Triticeae, tubers and roots, along with other Pooideae and Poaceae plants. This data proves that although broomcorn and foxtail millet formed the mainstay of the Qijia diet, it also included a wide range of plants, such as the tribe Triticeae, tubers and roots, which would have been foraged rather than grown. Compared with the other three contemporaneous sites in Northern China, the proportion of millet starches was highest at the Lajia site, while the type and proportion of foraged plants were the lowest. This was probably because of the arid environment in the region, which could not have supported sufficient plant resources for foraging, which in turn might have led to enhanced millet cultivation and/or a greater reliance on hunting. No wheat or barley traces were found in human teeth in Lajia, and the high proportion of nitrogen was possibly related to the consumption of sheep because sheep bones were found in a zooarchaeological study. This study enhances our understanding of the subsistence strategies present in Qijia culture and of prehistoric food globalization, which is of pivotal significance for a deeper understanding of interactions between east and west Asia during the Neolithic and Bronze ages.
Can Eu Anomaly Indicate a Hydrothermal Fluid Si Source? A Case Study of Chert Nodules From the Permian Maokou and Wujiaping Formations, South China
Authors: Li Chenqing , Cui Yixin , Ning Meng , Li Chao , Xing Chaochao , Xia Pan , Dong Lin 
Published: July 2022

The Middle–Late Permian witnessed an unusual chert accumulation event along the margin of the Pangea and Paleo-Tethys realms, known as the “Permian Chert Event (PCE).” The PCE is well recognized in the Permian limestone from South China, in the forms of nodular and bedded cherts. Previous studies suggested that PCE was caused by hydrothermal fluids related to the Emeishan large igneous province (ELIP). Meanwhile, another hypothesis supported the biogenic origin of PCE, i.e., the Permian chert derived from biosilicification of abundant sponges and radiolarian. Thus, sources of silica from the Permian chert remain uncertain. To understand linkages among PCE, biosilicification mechanism, and the ELIP event, this study focused on chert nodules collected from the Permian Maokou and Wujiaping formations in the Lianziya and Maoertang sections, South China. We measured germanium/silicon ratios (Ge/Si) and rare earth element (REE) compositions of chert nodules on the basis of petrographic analysis. Ge/Si ratios range from 0.14 to 0.63 μmol/mol with an average of 0.33 μmol/mol (n=18) in the Lianziya section and from 0.02 to 0.75 μmol/mol with an average of 0.18 μmol/mol (n=45) in the Maoertang section, both of which are close to the seawater value. The REE pattern is characterized by LREE depleted with a positive Eu anomaly ranging from 0.66 to 2.16 in the Lianziya section and from 1.05 to 9.57 in the Maoertang section. Our results indicate that the silica of the Permian chert predominantly originated from seawater with limited contributions from hydrothermal fluids. To further quantify the contributions of hydrothermal fluids, we applied a binary (seawater and hydrothermal fluid) mixing model based on two geochemical proxies, i.e., the Ge/Si ratio and Eu anomaly. The modeling results suggest a mixing of 0.5 vol% to 1 vol% hydrothermal fluids with contemporaneous seawater, verifying the dominant seawater source of silica in the PCE. Although it has been widely accepted that positive Eu anomaly points to the hydrothermal fluid origin of silica, our study demonstrates that positive Eu anomaly could also be present in cherts that was predominantly derived from normal seawater. Therefore, the analysis of the Ge/Si ratio or REE compositions is highly recommended when determining the Si source of cherts.