bluuebunny/crossref_metadata_2025 huggingface dataset:
TFP5-Mediated CDK5 Activity Inhibition Improves Diabetic Nephropathy via NGF/Sirt1 Regulating Axis
Authors: Cao Shi-Lu , Luo Hong-Yan , Gao Yong-Cai , Lan Xiao-Mei , Liu Shun-Yao , Li Bo , Bao Li , E. Jing , Ma Danna , Zhang Guo-Qing , Yang Li-Rong , Bao Xi , Zheng Ya-Li
Published: July 2022

Diabetic nephropathy (DN) is one of the leading causes of chronic kidney disease (CKD), during which hyperglycemia is composed of the major force for the deterioration to end-stage renal disease (ESRD). However, the underlying mechanism triggering the effect of hyperglycemia on DN is not very clear and the clinically available drug for hyperglycemia-induced DN is in need of urgent development. Here, we found that high glucose (HG) increased the activity of cyclin-dependent kinase 5 (CDK5) dependent on P35/25 and which upregulated the oxidative stress and apoptosis of mouse podocytes (MPC-5). TFP5, a 25-amino acid peptide inhibiting CDK5 activity, decreased the secretion of inflammation cytokines in serum and kidney, and effectively protected the kidney function in db/db mouse from hyperglycemia-induced kidney injuries. In addition, TFP5 treatment decreased HG-induced oxidative stress and cell apoptosis in MPC-5 cells and kidney tissue of db/db mouse. The principal component analysis (PCA) of RNA-seq data showed that MPC-5 cell cultured under HG, was well discriminated from that under low glucose (LG) conditions, indicating the profound influence of HG on the properties of podocytes. Furthermore, we found that HG significantly decreased the level of NGF and Sirt1, both of which correlated with CDK5 activity. Furthermore, knockdown of NGF was correlated with the decreased expression of Sirt1 while NGF overexpression leads to upregulated Sirt1 and decreased oxidative stress and apoptosis in MPC-5 cells, indicating the positive regulation between NGF and Sirt1 in podocytes. Finally, we found that K252a, an inhibitor of NGF treatment could undermine the protective role of TFP5 on hyperglycemia-induced DN in db/db mouse model. In conclusion, the CDK5-NGF/Sirt1 regulating axis may be the novel pathway to prevent DN progression and TFP5 may be a promising compound to improved hyperglycemia induced DN.
Global Trends in Natural Biopolymers in the 21st Century: A Scientometric Review
Authors: Sun Yitao , Bai Yinping , Yang Wenlong , Bu Kangmin , Tanveer Sikander Khan , Hai Jiangbo
Published: July 2022

Since the 21st century, natural biopolymers have played an indispensable role in long-term global development strategies, and their research has shown a positive growth trend. However, these substantive scientific results are not conducive to our quick grasp of hotspots and insight into future directions and to understanding which local changes have occurred and which trend areas deserve more attention. Therefore, this study provides a new data-driven bibliometric analysis strategy and framework for mining the core content of massive bibliographic data, based on mathematical models VOS Viewer and CiteSpace software, aiming to understand the research prospects and opportunities of natural biopolymers. The United States is reported to be the most important contributor to research in this field, with numerous publications and active institutions; polymer science is the most popular subject category, but the further emphasis should be placed on interdisciplinary teamwork; mainstream research in this field is divided into five clusters of knowledge structures; since the explosion in the number of articles in 2018, researchers are mainly engaged in three fields: “medical field,” “biochemistry field,” and “food science fields.” Through an in-depth analysis of natural biopolymer research, this article provides a better understanding of trends emerging in the field over the past 22 years and can also serve as a reference for future research.
Selection and Surface Modifications of Current Collectors for Anode-Free Polymer-Based Solid-State Batteries
Authors: Garcia-Calvo Oihane , Gutiérrez-Pardo Antonio , Combarro Izaskun , Orue Ander , Lopez-Aranguren Pedro , Urdampilleta Idoia , Kvasha Andriy
Published: July 2022

Anode-free batteries (AFB) have attracted increasing interest in recent times because they allow the elimination of the conventional anode from the cell, exploiting lithium inventory from a lithiated cathode. This implies a much simpler, cost-effective, and sustainable approach. The AFB configuration with liquid electrolytes is being explored widely in research but rarely using solid electrolytes. One of the main issues of AFB is the poor reversibility of the lithium-plating/striping process at the anode side. Therefore, in this work, different metal foils have been tested as anode current collectors (CC), and copper foil has been selected as the most promising one. Surface modifications of the selected copper foil have been achieved by its coating using composite layers made of carbon and different metal nanoparticles—such as Ag, Sn, or Zn—in different proportions and with different amounts of a binder. The impact of such coatings and their thickness on the electrochemical performance of single-layer solid-state anode-free pouch cells, based on a PEO electrolyte and a LiFePO4 cathode has been systematically studied. Consequently, a post-mortem analysis of the investigated solid-state AFB is also presented, trying to identify and elucidate possible failure mechanisms to enhance the electrochemical performance of solid-state AFB in the future.
Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode
Authors: Song Xiangqing , Han Mi
Published: July 2022

Objective

The study aimed to evaluate and compare the pharmacokinetic/pharmacodynamic (PK/PD) exposure to vancomycin in the novel optimal two-step infusion (OTSI) vs. intermittent infusion (II) vs. continuous infusion (CI) mode, for MRSA bloodstream infections occurring in critical patients.

Methods

With PK/PD modeling and Monte Carlo simulations, the PK/PD exposure of 15 OTSI, 13 II, and 6 CI regimens for vancomycin, at 1, 2, 3, 4, 5, and 6 g daily dose, was evaluated. Using the Monte Carlo simulations, the vancomycin population PK parameters derived from critical patients, the PD parameter for MRSA isolates [i.e., minimum inhibitory concentration (MIC)], and the dosing parameters of these regimens were integrated into a robust mdel of vancomycin PK/PD index, defined as a ratio of the daily area under the curve (AUC0–24) to MIC (i.e., AUC0–24/MIC), to estimate the probability of target attainment (PTA) of these regimens against MRSA isolates with an MIC of 0.5, 1, 2, 4, and 8 mg/L in patients with varying renal function. The PTA at an AUC0–24/MIC ratio of >400, 400–600, and >600 was estimated. A regimen with a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, which is supposed to maximize both efficacy and safety, was considered optimal.

Results

At the same daily dose, almost only the OTSI regimens showed a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, and this profile seems evident especially in patients with creatinine clearance (CLcr) of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L. However, for patients with CLcr of <60 ml/min and for isolates with an MIC of ≥4 mg/L, the II regimens often displayed a higher or even ≥90% PTA at an AUC0–24/MIC ratio of >400 and of >600. The CI regimens frequently afforded a reduced PTA at an AUC0–24/MIC ratio of >400 and of >600, regardless of CLcr and MIC.

Conclusions

The data indicated that the OTSI regimens allowed preferred PK/PD exposure in terms of both efficacy and safety, and thus should be focused more on, especially in patients with CLcr of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L.
The Role of the Na+/Ca2+ Exchanger in Aberrant Intracellular Ca2+ in Cardiomyocytes of Chagas-Infected Rodents
Authors: Lopez Jose R. , Linares Nancy , Adams Jose A. , Mijares Alfredo
Published: July 2022

Chagas disease is produced by the parasite Trypanosoma cruzi (T. cruzi), which is the leading cause of death and morbidity in Latin America. We have shown that in patients with Chagas cardiomyopathy, there is a chronic elevation of diastolic Ca2+ concentration ([Ca2+]d), associated with deterioration to further address this issue, we explored the role Na+/Ca2+ exchanger (NCX). Experiments were carried out in noninfected C57BL/6 mice and infected with blood-derived trypomastigotes of the T. cruzi Y strain. Anesthetized mice were sacrificed and the cardiomyocytes were enzymatically dissociated. Diastolic [Ca2+] ([Ca2+]d) was measured using Ca2+ selective microelectrodes in cardiomyocytes from control mice (CONT) and cardiomyocytes from T. cruzi infected mice in the early acute phase (EAP) at 20 dpi, in the acute phase (AP) at 40 dpi, and in the chronic phase (CP) at 120 dpi. [Ca2+]d was 1.5-times higher in EAP, 2.6-times in AP, and 3.4-times in CP compared to CONT. Exploring the reverse mode activity of NCX, we replaced extracellular Na+ in equivalent amounts with N-methyl-D-glucamine. Reduction of [Na+]e to 65 mM caused an increase in [Ca2+]d of 1.7 times in cardiomyocytes from CONT mice, 2 times in EAP infected mice, 2.4 times in AP infected mice and 2.8 in CP infected mice. The Na+ free solution caused a further elevation of [Ca2+]d of 2.5 times in cardiomyocytes from CONT, 2.8 times in EAP infected mice, 3.1 times in AP infected mice, and 3.3 times in CP infected mice. Extracellular Ca2+ withdrawal reduced [Ca2+]d in both CONT and cardiomyocytes from Chagas-infected mice and prevented the increase in [Ca2+]d induced by Na+ depletion. Preincubation with 10µM KB-R7943 or in 1µM YM-244769 reduced [Ca2+]d in cardiomyocytes from infected mice, but not control mice. Furthermore, both NCX blockers prevented the increase in [Ca2+]d associated with exposure to a solution without Na+. These results suggest that Ca2+ entry through the reverse NCX mode plays a significant role in the observed [Ca2+]d dyshomeostasis in Chagas infected cardiomyocytes. Additionally, NCX inhibitors may be a viable therapeutic approach for treating patients with Chagas cardiomyopathy.
MicroRNA let-7 Suppresses Influenza A Virus Infection by Targeting RPS16 and Enhancing Type I Interferon Response
Authors: Wu Wenjiao , Wang Chao , Xia Changliang , Liu Shuwen , Mei Qinghua
Published: July 2022

Given the frequent emergence of drug-resistant influenza virus strains and new highly pathogenic influenza virus strains, there is an urgent need to identify new antiviral drugs and targets. We found that influenza A virus (IAV) infection caused a significant decrease of microRNA let-7 expression in host cells; that overexpression of let-7 increased interferon expression and effectively inhibit IAV infection; and that let-7 targets the 3’-untranslated region (UTR) of the ribosomal protein 16 (RPS16) gene, decreasing its expression. Knocking down the expression of RPS16 increased the expression of type I interferon and inhibited viral replication. The present study uncovered the regulatory effect of let-7b and let-7f on influenza A infection, which is a potential biomarker of IAV infection. In addition, let-7 may be a promising therapeutic agent against influenza A.
Structural New Data for Mitochondrial Peroxiredoxin From Trypanosoma cruzi Show High Similarity With Human Peroxiredoxin 3: Repositioning Thiostrepton as Antichagasic Drug
Authors: Rivera-Santiago Lucio , Martínez Ignacio , Arroyo-Olarte Ruben , Díaz-Garrido Paulina , Cuevas-Hernandez Roberto I. , Espinoza Bertha
Published: July 2022

Trypanosoma cruzi, the causal agent of Chagas disease, has peroxiredoxins (PRXs) expressed in all stages of the parasite and whose function is to detoxify oxidizing agents, such as reactive oxygen species (ROS). These proteins are central for the survival and replication of the parasite and have been proposed as virulence factors. Because of their importance, they have also been considered as possible therapeutic targets, although there is no specific drug against them. One of them, the mitochondrial PRX (TcMPX), is important in the detoxification of ROS in this organelle and has a role in the infectivity of T. cruzi. However, their structural characteristics are unknown, and possible inhibitors have not been proposed. The aim was to describe in detail some structural characteristics of TcMPX and compare it with several PRXs to find possible similarities and repositioning the antibiotic Thiostrepton as a potential inhibitor molecule. It was found that, in addition to the characteristic active site of a 2-cys PRX, this protein has a possible transmembrane motif and motifs involved in resistance to hyper oxidation. The homology model suggests a high structural similarity with human PRX3. This similarity was corroborated by cross-recognition using an anti-human PRX antibody. In addition, molecular docking showed that Thiostrepton, a potent inhibitor of human PRX3, could bind to TcMPX and affect its function. Our results show that Thiostrepton reduces the proliferation of T. cruzi epimastigotes, cell-derived trypomastigotes, and blood trypomastigotes with low cytotoxicity on Vero cells. We also demonstrated a synergic effect of Thriostepton and Beznidazol. The convenience of seeking treatment alternatives against T. cruzi by repositioning compounds as Thiostrepton is discussed.
Comparative Genomic Analysis of the Human Pathogen Wohlfahrtiimonas Chitiniclastica Provides Insight Into the Identification of Antimicrobial Resistance Genotypes and Potential Virulence Traits
Authors: Kopf Anna , Bunk Boyke , Coldewey Sina M. , Gunzer Florian , Riedel Thomas , Schröttner Percy
Published: July 2022

Recent studies suggest that Wohlfahrtiimonas chitiniclastica may be the cause of several diseases in humans including sepsis and bacteremia making the bacterium as a previously underappreciated human pathogen. However, very little is known about the pathogenicity and genetic potential of W. chitiniclastica; therefore, it is necessary to conduct systematic studies to gain a deeper understanding of its virulence characteristics and treatment options. In this study, the entire genetic repertoire of all publicly available W. chitiniclastica genomes was examined including in silico characterization of bacteriophage content, antibiotic resistome, and putative virulence profile. The pan-genome of W. chitiniclastica comprises 3819 genes with 1622 core genes (43%) indicating a putative metabolic conserved species. Furthermore, in silico analysis indicated presumed resistome expansion as defined by the presence of genome-encoded transposons and bacteriophages. While macrolide resistance genes macA and macB are located within the core genome, additional antimicrobial resistance genotypes for tetracycline (tetH, tetB, and tetD), aminoglycosides (ant(2’’)-Ia, aac(6’)-Ia,aph(3’’)-Ib, aph(3’)-Ia, and aph(6)-Id)), sulfonamide (sul2), streptomycin (strA), chloramphenicol (cat3), and beta-lactamase (blaVEB) are distributed among the accessory genome. Notably, our data indicate that the type strain DSM 18708T does not encode any additional clinically relevant antibiotic resistance genes, whereas drug resistance is increasing within the W. chitiniclastica clade. This trend should be monitored with caution. To the best of our knowledge, this is the first comprehensive genome analysis of this species, providing new insights into the genome of this opportunistic human pathogen.
Role of Cardiovascular Magnetic Resonance in Native Valvular Regurgitation: A Comprehensive Review of Protocols, Grading of Severity, and Prediction of Valve Surgery
Authors: Vermes Emmanuelle , Iacuzio Laura , Levy Franck , Bohbot Yohann , Renard Cédric , Gerber Bernhard , Maréchaux Sylvestre , Tribouilloy Christophe
Published: July 2022

Valvular regurgitation is common in developed countries with an increasing prevalence due to the aging of the population and more accurate diagnostic imaging methods. Echocardiography is the gold standard method for the assessment of the severity of valvular heart regurgitation. Nonetheless, cardiovascular magnetic resonance (CMR) has emerged as an additional tool for assessing mainly the severity of aortic and mitral valve regurgitation in the setting of indeterminate findings by echocardiography. Moreover, CMR is a valuable imaging modality to assess ventricular volume and flow, which are useful in the calculation of regurgitant volume and regurgitant fraction of mitral valve regurgitation, aortic valve regurgitation, tricuspid valve regurgitation, and pulmonary valve regurgitation. Notwithstanding this, reference values and optimal thresholds to determine the severity and prognosis of valvular heart regurgitation have been studied lesser by CMR than by echocardiography. Hence, further larger studies are warranted to validate the potential prognostic relevance of the severity of valvular heart regurgitation determined by CMR. The present review describes, analyzes, and discusses the use of CMR to determine the severity of valvular heart regurgitation in clinical practice.
Effects of Methylprednisolone on Myocardial Function and Microcirculation in Post-resuscitation: A Rat Model
Authors: Wang Changsheng , Bischof Evelyne , Xu Jing , Guo Qinyue , Zheng Guanghui , Ge Weiwei , Hu Juntao , Georgescu Margarint Elena Laura , Bradley Jennifer L. , Peberdy Mary Ann , Ornato Joseph P. , Zhu Changqing , Tang Wanchun
Published: July 2022

Background

Previous studies have demonstrated that inflammation and impaired microcirculation are key factors in post-resuscitation syndromes. Here, we investigated whether methylprednisolone (MP) could improve myocardial function and microcirculation by suppressing the systemic inflammatory response following cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA).

Methods

Sprague-Dawley rats were randomly assigned to (1) sham, (2) control, and (3) drug groups. Ventricular fibrillation was induced and then followed by CPR. The rats were infused with either MP or vehicle at the start of CPR. Myocardial function and microcirculation were assessed at baseline and after the restoration of spontaneous circulation. Blood samples were drawn at baseline and 60-min post-resuscitation to assess serum cytokine (TNF-α, IL-1β, and IL-6) levels.

Results

Myocardial function [estimated by the ejection fraction (EF), myocardial performance index (MPI), and cardiac output (CO)] improved post-ROSC in the MP group compared with those in the control group (p < 0.05). MP decreased the levels of the aforementioned pro-inflammatory cytokines and alleviated cerebral, sublingual, and intestinal microcirculation compared with the control (p < 0.05). A negative correlation emerged between the cytokine profile and microcirculatory blood flow.

Conclusion

MP treatment reduced post-resuscitation myocardial dysfunction, inhibited pro-inflammatory cytokines, and improved microcirculation in the initial recovery phase in a CA and resuscitation animal model. Therefore, MP could be a potential clinical target for CA patients in the early phase after CPR to alleviate myocardial dysfunction and improve prognosis.
The Diagnostic Challenge of Eosinophilic Granulomatosis With Polyangiitis Presenting as Acute Eosinophilic Myocarditis: Case Report and Literature Review
Authors: Yamamoto Hiroyuki , Hashimoto Katsuya , Ikeda Yoshihiko , Isogai Jun , Hashimoto Toru
Published: July 2022

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis involving small-to-medium-sized vessels characterized by asthma, vasculitis, and peripheral eosinophilia. EGPA-associated eosinophilic myocarditis (EM) occurs rarely, yet can be fatal if left untreated. Moreover, the accurate diagnosis of EGPA-associated EM without vasculitis is exceptionally difficult because of the overlapping features with EM of other causes. We report a case of probable EGPA with subclinical neurological involvement that presented with acute EM. The constellation of peripheral eosinophilia, left ventricular dysfunction, and normal epicardial coronary arteries raised suspicion of acute EM, which was confirmed by cardiac magnetic resonance (CMR) investigation and endomyocardial biopsy (EMB). Prompt systemic administration of corticosteroids completely restored and normalized myocardial structure and function. Although the patient's history suggested the presumed hypersensitivity myocarditis, EMB revealed EM without vasculitis, not hypersensitivity, leading to a tentative diagnosis of idiopathic hypereosinophilic syndrome. Interestingly, the characteristic findings of vasculitis on CMR imaging strongly suggested EGPA-associated EM. Although the patient had no clinical neurological manifestations, a nerve conduction study confirmed mononeuritis multiplex, leading to the final diagnosis of probable EGPA. Therefore, this case highlights the diagnostic challenge associated with EGPA and the diagnostic synergy of CMR and EMB for an exploratory diagnosis of EGPA-associated EM.
Directly Measured vs. Calculated Low-Density Lipoprotein Cholesterol Does Not Identify Additional Individuals With Coronary Artery Disease and Diabetes at Higher Risk of Adverse Events: Insight From a Large Percutaneous Coronary Intervention Cohort in Asia
Authors: Shi Boqun , Wang Hao-Yu , Liu Jinpeng , Cai Zhongxing , Song Chenxi , Jia Lei , Yin Dong , Wang Hongjian , Dou Ke-Fei , Song Weihua
Published: July 2022

Background

The objective of our study was to assess whether calculated low-density lipoprotein cholesterol (LDL-C) is inferior to direct LDL-C (dLDL-C) in identifying patients at higher risk of all-cause mortality, recurrent acute myocardial infarction (AMI), and major adverse cardiovascular event (MACE).

Methods

A total of 9,751 patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) in the Fuwai PCI registry were included. DLDL-C was measured by the selective solubilization method (Kyowa Medex, Tokyo, Japan). Correct classification was defined as the proportion of estimated LDL-C in the same category as dLDL-C based on dLDL-C levels: less than 1.4, 1.4–1.8, 1.8–2.6, 2.6–3.0, and 3.0 mmol/L or greater.

Results

Underestimation of LDL-C was found in 9.7% of patients using the Martin/Hopkins equation, compared with 13.9% using the Sampson equation and 24.6% with the Friedewald equation. Cox regression analysis showed compared the correct estimation group, underestimation of LDL-C by the Martin/Hopkins equation did not reduce all-cause mortality (HR 1.26, 95% CI: 0.72–2.20, P = 0.4), recurrent AMI (HR 1.24, 95% CI: 0.69–2.21, P = 0.5), and MACE (HR 1.02, 95% CI: 0.83–1.26, P = 0.9). Similarly, the overestimated group did not exacerbate all-cause mortality (HR 0.9, 95% CI: 0.45–1.77, P = 0.8), recurrent AMI (HR 0.63, 95% CI: 0.28–1.44, P = 0.3), and MACE (HR 1.07, 95% CI: 0.86–1.32, P = 0.6). The results of the diabetes subgroup analysis were similar to those of the whole population.

Conclusion

Compared with dLDL-C measurement, misclassification by the Martin/Hopkins and Sampson equations was present in approximately 20% of patients. However, directly measured vs. calculated LDL-C did not identify any more individuals in the PCI population with increased risk of all-cause mortality, recurrent AMI, and MACE, even in high-risk patients such as those with diabetes.
Evaluating the COVID-19 Identification ResNet (CIdeR) on the INTERSPEECH COVID-19 From Audio Challenges
Authors: Akman Alican , Coppock Harry , Gaskell Alexander , Tzirakis Panagiotis , Jones Lyn , Schuller Björn W.
Published: July 2022

Several machine learning-based COVID-19 classifiers exploiting vocal biomarkers of COVID-19 has been proposed recently as digital mass testing methods. Although these classifiers have shown strong performances on the datasets on which they are trained, their methodological adaptation to new datasets with different modalities has not been explored. We report on cross-running the modified version of recent COVID-19 Identification ResNet (CIdeR) on the two Interspeech 2021 COVID-19 diagnosis from cough and speech audio challenges: ComParE and DiCOVA. CIdeR is an end-to-end deep learning neural network originally designed to classify whether an individual is COVID-19-positive or COVID-19-negative based on coughing and breathing audio recordings from a published crowdsourced dataset. In the current study, we demonstrate the potential of CIdeR at binary COVID-19 diagnosis from both the COVID-19 Cough and Speech Sub-Challenges of INTERSPEECH 2021, ComParE and DiCOVA. CIdeR achieves significant improvements over several baselines. We also present the results of the cross dataset experiments with CIdeR that show the limitations of using the current COVID-19 datasets jointly to build a collective COVID-19 classifier.
Assessment of Atrazine Migration in Soil and Groundwater Using Nitrate as an Indicator in an Intensively Cultivated Sugarcane Field, Suphan Buri Province, Thailand
Authors: Ratchawang Sorranat , Chotpantarat Srilert , Charoenrojying Pimchaya
Published: July 2022

Groundwater has been widely used in Thailand for many purposes, including agricultural activities; therefore, groundwater can be contaminated and affect the environment and human health. One of the most commonly applied and imported pesticides is atrazine, which is an herbicide used to control annual broadleaf and grass weeds in sugarcane. Monitoring and reducing the atrazine leaching potential into groundwater would play an important role in preventing this problem. The aim of this study is to evaluate the leaching potential of atrazine in Song Phi Nong District, Suphan Buri Province, via the attenuation/retardation factor model (AF/RF model) and the groundwater ubiquity score (GUS). It was found that most of the agricultural areas, especially the sugarcane fields, had high leaching potential due to the low adsorption and water holding capacity of the soil. The performance of the model was then evaluated by the result of nitrate (NO3−) detection in groundwater, which has been reported to be a pesticide and herbicide leaching indicator. Interestingly, the area with high leaching potential was partly contaminated by high NO3− concentration. However, some factors relating to leaching potential in the area were not considered in the model, causing low nitrate concentration detection. The isotopic ratio was also measured in this study to identify sources of NO3−; most of the nitrate in the groundwater samples, as a result, was polluted by human activities, especially from domestic wastewater. The AF/RF model can be a risk management and groundwater resource planning assistant, leading to human health and environmental protection related to pesticide-contaminated groundwater.
Investigating Biases Associated With Dietary Starch Incorporation and Retention With an Oral Biofilm Model
Authors: Bartholdy Bjørn Peare , Henry Amanda G.
Published: July 2022

Dental calculus has proven to contain a wealth of information on the dietary habits of past populations. These insights have, to a large extent, been obtained by the extraction and identification of starch granules contained within the mineralised dental plaque from a wide range of regions and time periods. The scope of previous studies have been limited to microfossil extraction and identification to reconstruct dietary preferences from the archaeological record, and few studies have attempted to address the biases of starch retention in dental calculus. Those that have considered this problem have been limited to in vivo studies on modern humans and non-human primates. Here, we present a multispecies oral biofilm model, which allows experimental research on starch incorporation and retention to be conducted on in vitro dental calculus in a controlled laboratory setting. The biofilms were exposed to treatment solutions with known quantities of dietary starches (wheat and potato) during the 25 days growth period. After this, the starch granules were extracted from the mature biofilm (by dissolution in EDTA), and counted. We show that the granule counts extracted from the model dental calculus represented a low proportion (ranging from 0.06% to 0.16%) of the total number of granules exposed to the biofilms throughout the experiment. Additionally, we found that the ratios of granule sizes from the extracted starch granules differed from the original treatment solutions, with large granules (>20 μm) consistently being under-represented. We also found a positive correlation between the absolute granule counts and dry-weight of the biofilm (r = 0.659, 90%CI[0.463, 0.794]), meaning the absolute quantity of starch granules will increase as the size of the calculus deposit increases. A similar, but weaker correlation was found between the concentration (count per mg) of granules and dry-weight (r = 0.3, 90%CI[0.0618, 0.506]). Our results complement and reinforce previous in vivo studies suggesting that dental calculus presents a very small, and partly biased picture of the original dietary intake of starches, with an over-representation of plants producing granules smaller than 20 μm in size. The experimental model presented here is well-suited to address the need for further validation of methods and biases associated with dietary research on dental calculus.
Shallow Overpressure Formation in the Deep Water Area of the Qiongdongnan Basin, China
Authors: Ren Jinfeng , Xu Litao , Shi Wanzhong , Yang Wei , Wang Ren , He Yulin , Du Hao
Published: July 2022

The scarcity of drilling in the deep water area of Qiongdongnan Basin restricts the cognition and prediction of overpressure. In this paper, a shallow zone of overpressure at the depth of 900–1,200 m below the sea floor in the deep water area was found by analyzing electronic logs, mud pressure (Mud pressure is a product of the height of the column of mud, density and gravity acceleration) and test pressure from drill stem testing (DST) and modular dynamic testing (MDT), and the interpretation of anomalous seismic interval velocities. The shallow overpressure is a newly observed geological phenomenon in the South China Sea for which the generation mechanisms are not well understood, despite similar observations and analyses elsewhere in the world. Two representative wells, one each located in the shallow water and the deep water areas, respectively were selected to investigate the vertical distribution of the shallow overpressure. The top of the overpressure in Well A in the shallow water area is about 2,111 m below sea floor, while the top of the overpressure in Well B in the deep water area is about 1,077 m below sea floor. A pressure coefficient (i.e., ratio of pore pressure to the normal hydrostatic pressure measured from the sea surface) profile was constructed from the shallow water area to the deep water area using the calibrated relationship between seismic interval velocities and pressure data from 30 wells. The distance between the top of the overpressure and the seabed is predicted to be between 900 and 1,200 m in the deep water area Basin. Disequilibrium compaction is the interpreted primary cause of the shallow overpressure and the results of basin modeling indicate that the shallow overpressure was generated since 5.5 Ma.
Eruptions and Social Media: Communication and Public Outreach About Volcanoes and Volcanic Activity in Italy
Authors: Todesco Micol , De Lucia Maddalena , Bagnato Emanuela , Behncke Boris , Bonforte Alessandro , De Astis Gianfilippo , Giammanco Salvatore , Grassa Fausto , Neri Marco , Scarlato Piergiorgio , Neri Augusto
Published: July 2022

Italy is the land of iconic volcanoes, whose activity has been witnessed, described and portrayed for centuries. This legacy has greatly contributed to shaping the public perception of volcanoes and their impact, well beyond the national borders. Stories about famous eruptions overlap and nowadays easily mix up with the impressive footage that is readily available from ongoing eruptions worldwide. As a result, the public discourse may flatten the wide spectrum of possible phenomena into an oversimplified sketch of volcanic eruptions and their impact, where all events seem equally probable and look alike. Actual volcanoes differ in size, eruption magnitude, state of activity, eruptive style, geographical position, and each is located within a specific social and cultural context. All these elements combine in defining the consequences of volcanic activity as well as in determining the severity of the damage and the size of the impacted area. How can we convey such a complexity to the general public? Can social media contribute to raise awareness and build a more resilient society? An effective hazard communication should propose a comprehensible yet realistic description of volcanic settings and provide adequate tools to recognize and understand the specific features of each phenomenon and volcanic area. As we write, two Italian volcanoes display persistent eruptive activity, while other two are going through unrest phases that started in 2012, at Campi Flegrei, and in late summer of 2021, at Vulcano Island. Other active volcanoes (Vesuvius, Ischia, Colli Albani, Lipari, and Pantelleria) have been dormant for tens, hundreds, or thousands of years. Communication in these different contexts also require different approaches that take into account the specific needs of local communities. Social media may provide a unique opportunity to quickly share relevant news and information. Yet, this type of communication has its challenges and volcano observatories can rarely rely on expert social media managers. Sharing experiences and lessons learned is a key to ensure the growth of the volcanological community and improve its ability to connect and engage local residents. Here we discuss the online communication strategies implemented by the Istituto Nazionale di Geofisica e Vulcanologia (INGV) since 2018 to inform Internet and social media users about volcanoes, volcanology, and ongoing volcanic activity, both in Italy and abroad. We describe the internal procedures that we developed and practiced and the experience gathered so far, during both quiet periods and a few volcanic crises. Our experience confirms previous indications about the importance of a steady online presence and suggests that public interest is not always easily predictable.
Comparisons of the Relationships Between Multiple Lipid Indices and Diabetic Kidney Disease in Patients With Type 2 Diabetes: A Cross-Sectional Study
Authors: Lu Chun-feng , Liu Wang-shu , Chen Zhen-hua , Hua Ling-yan , Wang Xue-qin , Huang Hai-yan
Published: July 2022

Background

Dyslipidemia is a well-recognized risk factor for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Growing evidences have shown that compared with the traditional lipid parameters, some lipid ratios may provide additional information of lipid metabolism. Thus, the present study aimed to investigate which lipid index was most related to DKD.

Methods

This study was a cross-sectional study that enrolled patients with T2D from January 2021 to October 2021. Each participant was screened for DKD, and the diagnostic criterion for DKD is estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g for 3 months. Fasting blood was collected to determine lipid profiles by an automatic biochemical analyzer, and lipid ratios were calculated based on corresponding lipid parameters. Spearman’s correlation analyses were conducted to assess the correlations between lipid indices and kidney injury indices, and binary logistic regression analyses were conducted to explore the relationship between lipid indices and the risk of DKD.

Results

A total of 936 patients with T2D were enrolled in the study, 144 (15.38%) of whom had DKD. The LDL-C/Apo B ratios were positively correlated with eGFR (r = 0.146, p < 0.05) and inversely correlated to cystatin C and UACR (r = -0.237 and -0.120, both p < 0.001). Multiple logistic regression demonstrated that even after adjusting for other clinical covariates, the LDL-C/Apo B ratios were negatively related to DKD, and the odds ratio (95% confidence interval) was 0.481 (0.275–0.843). Furthermore, subgroup analyses revealed that compared with patients with normal lipid profiles and a high LDL-C/Apo B ratio, the odds ratio of DKD in patients with normal lipid metabolism and a low LDL-C/Apo B ratio was 2.205 (1.136-4.280) after adjusting for other clinical covariates.

Conclusion

In patients with T2D, the LDL-c/Apo B ratio was most closely associated with DKD among various lipid indices, and a lower LDL-C/Apo B ratio was associated with increased risks of DKD among patients with T2D.
Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?
Authors: Faucher Quentin , Jardou Manon , Brossier Clarisse , Picard Nicolas , Marquet Pierre , Lawson Roland
Published: July 2022

Post-transplant diabetes mellitus (PTDM) is one of the most common and deleterious comorbidities after solid organ transplantation (SOT). Its incidence varies depending on the organs transplanted and can affect up to 40% of patients. Current research indicates that PTDM shares several common features with type 2 diabetes mellitus (T2DM) in non-transplant populations. However, the pathophysiology of PTDM is still poorly characterized. Therefore, ways should be sought to improve its diagnosis and therapeutic management. A clear correlation has been made between PTDM and the use of immunosuppressants. Moreover, immunosuppressants are known to induce gut microbiota alterations, also called intestinal dysbiosis. Whereas the role of intestinal dysbiosis in the development of T2DM has been well documented, little is known about its impacts on PTDM. Functional alterations associated with intestinal dysbiosis, especially defects in pathways generating physiologically active bacterial metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide, indole and kynurenine) are known to favour several metabolic disorders. This publication aims at discussing the potential role of intestinal dysbiosis and dysregulation of bacterial metabolites associated with immunosuppressive therapy in the occurrence of PTDM.
Costs and Its Determinants in Pituitary Tumour Surgery
Authors: Dekkers Alies J. , de Vries Friso , Zamanipoor Najafabadi Amir H. , van der Hoeven Emmy M. , Verstegen Marco J. T. , Pereira Alberto M. , van Furth Wouter R. , Biermasz Nienke R.
Published: July 2022

Purpose

Value-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice we evaluated healthcare costs and cost drivers in perioperative care for pituitary tumour patients.

Methods

We retrospectively assessed financial and clinical data for surgical treatment up to the first year after surgery of pituitary tumour patients treated between 2015 and 2018 in a Dutch tertiary referral centre. Multivariable regression analyses were performed to identify determinants of higher costs.

Results

271 patients who underwent surgery were included. Mean total costs (SD) were €16339 (13573) per patient, with the following cost determinants: surgery time (€62 per minute; 95% CI: 50, 74), length of stay (€1331 per day; 95% CI 1139, 1523), admission to higher care unit (€12154 in total; 95% CI 6413, 17895), emergency surgery (€10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (€14232; 95% CI 9667, 18797). Intradural (€7128; 95% CI 10421, 23836) and combined transsphenoidal/transcranial surgery (B: 38494; 95% CI 29191, 47797) were associated with higher costs than standard. Further, higher costs were found in these baseline conditions: Rathke’s cleft cyst (€9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (€19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (€14613; 95% CI 7613, 21613) and dependent functional status (€12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were €8879 (3210) and with complications €17551 (14250).

Conclusions

Length of hospital stay, and complications are the main drivers of costs in perioperative pituitary tumour healthcare as were some baseline features, e.g. larger tumors, cysts and dependent functional status. Costs analysis may correspond with healthcare resource utilization and guide further individualized care path development and capacity planning.
The Extraglycemic Effect of SGLT-2is on Mineral and Bone Metabolism and Bone Fracture
Authors: Dong Bingzi , Lv Ruolin , Wang Jun , Che Lin , Wang Zhongchao , Huai Zhouyang , Wang Yangang , Xu Lili
Published: July 2022

Type 2 diabetes mellitus (T2DM) is a risk factor for osteoporosis. The effects of T2DM and anti-diabetic agents on bone and mineral metabolism have been observed. Sodium–glucose co-transporter 2 inhibitors (SGLT-2is) promote urinary glucose excretion, reduce blood glucose level, and improve the cardiovascular and diabetic nephropathy outcomes. In this review, we focused on the extraglycemic effect and physiological regulation of SGLT-2is on bone and mineral metabolism. SGLT-2is affect the bone turnover, microarchitecture, and bone strength indirectly. Clinical evidence of a meta-analysis showed that SGLT-2is might not increase the risk of bone fracture. The effect of SGLT-2is on bone fracture is controversial, and further investigation from a real-world study is needed. Based on its significant benefit on cardiovascular and chronic kidney disease (CKD) outcomes, SGLT-2is are an outstanding choice. Bone mineral density (BMD) and fracture risk evaluation should be considered for patients with a high risk of bone fracture.
Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence
Authors: Li Xuewen , Chen Hongyan , Yang Hongyan , Liu Jian , Li Yang , Dang Yue , Wang Jiajing , Wang Lei , Li Jun , Nie Guangning
Published: July 2022

Background

Management of menopausal dyslipidemia is the main measure to reduce the incidence of cardiovascular disease in postmenopausal women. Tonifying Kidney and Removing Dampness Formula (TKRDF) is a traditional Chinese medicine (TCM) formula that ameliorates dyslipidemia in postmenopausal women. This study applied network pharmacology, molecular docking, and in vitro and in vitro experiments to investigate the underlying mechanism of TKRDF against postmenopausal dyslipidemia.

Methods

Network pharmacology research was first conducted, and the active compounds and targets of TKRDF, as well as the targets of postmenopausal dyslipidemia, were extracted from public databases. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to identify the potential targets and signaling pathways of TKRDF in postmenopausal dyslipidemia. Molecular docking was then performed to evaluate the combination of active compounds with principal targets. Finally, an ovariectomized rat model was used for the in vivo experiment and alpha mouse liver 12 (AML12) cells treated with palmitic acid were used for the in vitro experiments to provide further evidence for the research.

Results

Based on network pharmacology analysis, we obtained 78 active compounds from TKRDF that acted on 222 targets of postmenopausal dyslipidemia. The analysis results indicated that IL6, TNF, VEGFA, AKT1, MAPK3, MAPK1, PPARG and PIK3CA, etc., were the potentially key targets, and the PI3K/AKT signaling pathway was the possibly crucial pathway for TKRDF to treat postmenopausal dyslipidemia. Molecular docking suggested that the active compounds have good binding activity with the core targets. The in vivo and in vitro experiments demonstrated that TKRDF ameliorates postmenopausal dyslipidemia by regulating hormone levels, inhibiting inflammation, promoting angiogenesis and inhibiting lipid synthesis, which appear to be related to TKRDF’s regulation of the ERK1/2 and PI3K/AKT signaling pathways.

Conclusion

This study clarified the active ingredients, potential targets, and molecular mechanisms of TKRDF for treating postmenopausal dyslipidemia. It also provided a feasible method to uncover the scientific basis and therapeutic mechanism for prescribing TCM in the treatment of diseases.
Bone Response to Weight Loss Following Bariatric Surgery
Authors: Mele Chiara , Caputo Marina , Ferrero Alice , Daffara Tommaso , Cavigiolo Beatrice , Spadaccini Daniele , Nardone Antonio , Prodam Flavia , Aimaretti Gianluca , Marzullo Paolo
Published: July 2022

Obesity is a global health challenge that warrants effective treatments to avoid its multiple comorbidities. Bariatric surgery, a cornerstone treatment to control bodyweight excess and relieve the health-related burdens of obesity, can promote accelerated bone loss and affect skeletal strength, particularly after malabsorptive and mixed surgical procedures, and probably after restrictive surgeries. The increase in bone resorption markers occurs early and persist for up to 12 months or longer after bariatric surgery, while bone formation markers increase but to a lesser extent, suggesting a potential uncoupling process between resorption and formation. The skeletal response to bariatric surgery, as investigated by dual-energy X-ray absorptiometry (DXA), has shown significant loss in bone mineral density (BMD) at the hip with less consistent results for the lumbar spine. Supporting DXA studies, analyses by high-resolution peripheral quantitative computed tomography (HR-pQCT) showed lower cortical density and thickness, higher cortical porosity, and lower trabecular density and number for up to 5 years after bariatric surgery. These alterations translate into an increased risk of fall injury, which contributes to increase the fracture risk in patients who have been subjected to bariatric surgery procedures. As bone deterioration continues for years following bariatric surgery, the fracture risk does not seem to be dependent on acute weight loss but, rather, is a chronic condition with an increasing impact over time. Among the post-bariatric surgery mechanisms that have been claimed to act globally on bone health, there is evidence that micro- and macro-nutrient malabsorptive factors, mechanical unloading and changes in molecules partaking in the crosstalk between adipose tissue, bone and muscle may play a determining role. Given these circumstances, it is conceivable that bone health should be adequately investigated in candidates to bariatric surgery through bone-specific work-up and dedicated postsurgical follow-up. Specific protocols of nutrients supplementation, motor activity, structured rehabilitative programs and, when needed, targeted therapeutic strategies should be deemed as an integral part of post-bariatric surgery clinical support.