bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Coating Effect on Charge Transfer Mechanisms in Composite Electrodes for Lithium-Ion Batteries
Authors: Fedorova Anna A. , Levin Oleg V. , Eliseeva Svetlana N. , Katrašnik Tomaž , Anishchenko Dmitrii V.
Published: May 2023

The performance of lithium-ion batteries (LIBs) relies on the characteristics of the cathode material, including both intentionally applied coatings and naturally formed surface layers or binder adhesion. This study investigated the influence of the ion-permeable surface fraction, distribution, and characteristics of the coating on the performance of a lithium iron phosphate (LFP) electrode material. We developed an extended Newman-type half-cell model and examined the impact of coating parameters on the galvanostatic discharge curves of the LFP electrode material. The study found that the ion-permeable surface fraction has a significant influence on the diffusion and charge transfer characteristics of the electrode material. A decrease in the ion-permeable surface fraction leads to a decrease in the measured diffusion coefficients and to an increase in the overall coating resistance of the electrode material. Interestingly, the distribution of the ion-permeable surface also plays a role in the diffusion characteristics, with a coarsely dispersed coating resulting in lower diffusion coefficients. Additionally, the coating characteristics significantly affect the polarization and capacity of the electrode material at different C-rates. The model was used to approximate the experimental discharge curves of the LFP-based composite electrodes with two different compositions, and the simulated data showed satisfactory agreement with the experiment. Thus, we believe that the developed model and its further extension will be useful in numerical simulations that aim to facilitate the search for optimal compositions.
The Lysyl Oxidase G473A Polymorphism Exacerbates Oral Cancer Development in Humans and Mice
Authors: Peymanfar Yaser , Mahjour Faranak , Shrestha Neha , de la Cueva Ana , Chen Ying , Huang Shengyuan , Kirsch Kathrin H. , Han Xiaozhe , Trackman Philip C.
Published: May 2023

Oral cancer is primarily squamous-cell carcinoma with a 5-year survival rate of approximately 50%. Lysyl oxidase (LOX) participates in collagen and elastin maturation. The propeptide of LOX is released as an 18 kDa protein (LOX-PP) in the extracellular environment by procollagen C-proteinases and has tumor-inhibitory properties. A polymorphism in the propeptide region of LOX (rs1800449, G473A) results in a single amino acid substitution of Gln for Arg. Here we investigated the frequency of rs1800449 in OSCC employing TCGA database resources and determined the kinetics and severity of precancerous oral lesion development in wildtype and corresponding knockin mice after exposure to 4-nitroquinoline oxide (4 NQO) in drinking water. Data show that the OSCC is more common in humans carrying the variant compared to the wildtype. Knockin mice are more susceptible to lesion development. The immunohistochemistry of LOX in mouse tissues and in vitro studies point to a negative feedback pathway of wildtype LOX-PP on LOX expression that is deficient in knockin mice. Data further demonstrate modulations of T cell phenotype in knockin mice toward a more tumor-permissive condition. Data provide initial evidence for rs1800449 as an oral cancer susceptibility biomarker and point to opportunities to better understand the functional mechanism of LOX-PP cancer inhibitory activity.
Time-Series Transcriptomic Analysis of Contrasting Rice Materials under Heat Stress Reveals a Faster Response in the Tolerant Cultivar
Authors: Cai Haiya , Wang Hongpan , Zhou Lei , Li Bo , Zhang Shuo , He Yonggang , Guo Ying , You Aiqing , Jiao Chunhai , Xu Yanhao
Published: May 2023

Short-term heat stress can affect the growth of rice (Oryza sativa L.) seedlings, subsequently decreasing yields. Determining the dynamic response of rice seedlings to short-term heat stress is highly important for accelerating research on rice heat tolerance. Here, we observed the seedling characteristics of two contrasting cultivars (T11: heat-tolerant and T15: heat-sensitive) after different durations of 42 °C heat stress. The dynamic transcriptomic changes of the two cultivars were monitored after 0 min, 10 min, 30 min, 1 h, 4 h, and 10 h of stress. The results indicate that several pathways were rapidly responding to heat stress, such as protein processing in the endoplasmic reticulum, glycerophospholipid metabolism, and plant hormone signal transduction. Functional annotation and cluster analysis of differentially expressed genes at different stress times indicate that the tolerant cultivar responded more rapidly and intensively to heat stress compared to the sensitive cultivar. The MAPK signaling pathway was found to be the specific early-response pathway of the tolerant cultivar. Moreover, by combining data from a GWAS and RNA-seq analysis, we identified 27 candidate genes. The reliability of the transcriptome data was verified using RT-qPCR on 10 candidate genes and 20 genes with different expression patterns. This study provides valuable information for short-term thermotolerance response mechanisms active at the rice seedling stage and lays a foundation for breeding thermotolerant varieties via molecular breeding.
Volatile Composition and Classification of Paeonia lactiflora Flower Aroma Types and Identification of the Fragrance-Related Genes
Authors: Zhao Qian , Gu Lina , Li Yuqing , Zhi Hui , Luo Jianrang , Zhang Yanlong
Published: May 2023

Flower scent is one of the main ornamental characteristics of herbaceous peony, and the improvement of flower fragrance is a vital objective of herbaceous peony breeding. In this study, 87 herbaceous peony cultivars were divided into three groups (no/light fragrance, medium fragrance, and strong fragrance) based on their sensory evaluation scores, and 16 strong fragrance cultivars and one no fragrance cultivar were selected for subsequent analysis. Sixty-eight volatile components were detected in these 17 cultivars based on solid-phase microextraction (SPME) and gas chromatography/mass spectrometry (GC/MS), and 26 types were identified as important scent components. They were composed of terpenoids, benzenoids/phenylpropanoids, and fatty acid derivatives. According to the content and odor threshold of these main aroma components, the characteristic aroma substances of herbaceous peony were identified, including linalool, geraniol, citronellol, and phenylethyl alcohol (2-PE). The cultivars of strong scented herbaceous peony were divided into three types: rose scent, lily scent, and mixed scent. We explored the possible key genes of characteristic aroma substances in herbaceous peony petals with different odors through the qRT-PCR. The key genes encoding monoterpene biosynthesis were found to be PlDXS2, PlDXR1, PlMDS1, PlHDR1, PlGPPS3, and PlGPPS4. In addition, the linalool synthase (LIS) gene and the geraniol synthase (GES) gene were also found. PlAADC1, PlPAR1, and PlMAO1, related to the biosynthesis of 2-PE were detected, and the synthetic pathway of 2-PE was speculated. In conclusion, these findings revealed that the difference in gene expression of monoterpene and 2-PE synthesis pathway was related to the difference in the fragrance of herbaceous peony. This study explored the releasing pathway of herbaceous peony characteristic aroma substances and provided key genetic resources for fragrance improvement.
Mitogenome Characterization of Four Conus Species and Comparative Analysis
Authors: Wang Hao , Zhu Xiaopeng , Liu Yuepeng , Luo Sulan , Zhangsun Dongting
Published: May 2023

Cone snails, as a type of marine organism, have rich species diversity. Traditionally, classifications of cone snails were based mostly on radula, shell, and anatomical characters. Because of these phenotypic features’ high population variability and propensity for local adaptation and convergence, identifying species can be difficult and occasionally inaccurate. In addition, mitochondrial genomes contain high phylogenetic information, so complete mitogenomes have been increasingly employed for inferring molecular phylogeny. To enrich the mitogenomic database of cone snails (Caenogastropoda: Conidae), mitogenomes of four Conus species, i.e., C. imperialis (15,505 bp), C. literatus (15,569 bp), C. virgo (15,594 bp), and C. marmoreus (15,579 bp), were characterized and compared. All 4 of these mitogenomes included 13 protein-coding genes, 2 ribosomal RNA genes, 22 tRNA genes, and non-coding regions. All the Protein Codon Genes (PCGs) of both newly sequenced mitogenomes used TAA or TAG as a terminal codon. Most PCGs used conventional start codon ATG, but an alternative initiation codon GTG was detected in a gene (NADH dehydrogenase subunit 4 (nad4)) of C. imperialis. In addition, the phylogenetic relationships were reconstructed among 20 Conus species on the basis of PCGs, COX1, and the complete mitogenome using both Bayesian Inference (BI) and Maximum Likelihood (ML). The phylogenetic results supported that C. litteratus, C. quercinus, and C. virgo were clustered together as a sister group (PP = 1, BS = 99), but they did not support the phylogenetic relation of C. imperialis and C. tribblei (PP = 0.79, BS = 50). In addition, our study established that PCGs and complete mitogenome are the two useful markers for phylogenetic inference of Conus species. These results enriched the data of the cone snail’s mitochondrion in the South China Sea and provided a reliable basis for the interpretation of the phylogenetic relationship of the cone snail based on the mitochondrial genome.
Identification of a New RNA and Protein Integrated Biomarker Panel Associated with Kidney Function Impairment in DKD: Translational Implications
Authors: Scamporrino Alessandra , Di Mauro Stefania , Filippello Agnese , Di Marco Grazia , Di Pino Antonino , Scicali Roberto , Di Marco Maurizio , Martorana Emanuele , Malaguarnera Roberta , Purrello Francesco , Piro Salvatore
Published: May 2023

Diabetic kidney disease (DKD) is a complication that strongly increases the risk of end-stage kidney disease and cardiovascular events. The identification of novel, highly sensitive, and specific early biomarkers to identify DKD patients and predict kidney function decline is a pivotal aim of translational medicine. In a previous study, after a high-throughput approach, we identified in 69 diabetic patients 5 serum mitochondrial RNAs (MT-ATP6, MT-ATP8, MT-COX3, MT-ND1, and MT-RNR1) progressively downregulated with increasing eGFR stages. Here, we analyzed the protein serum concentrations of three well-validated biomarkers: TNFRI, TNFRII, and KIM-1. The protein biomarkers were gradually upregulated from G1 to G2 and G3 patients. All protein biomarkers correlated with creatinine, eGFR, and BUN. Performing multilogistic analyses, we found that, with respect to single protein biomarkers, the combination between (I) TNFRI or KIM-1 with each RNA transcript and (II) TNFRII with MT-ATP8, MT-ATP6, MT-COX-3, and MT-ND1 determined an outstanding improvement of the diagnostic performance of G3 versus G2 patient identification, reaching values in most cases above 0.9 or even equal to 1. The improvement of AUC values was also evaluated in normoalbuminuric or microalbuminuric patients considered separately. This study proposes a novel, promising multikind marker panel associated with kidney impairment in DKD.
Advanced Biomarkers of Hepatotoxicity in Psychiatry: A Narrative Review and Recommendations for New Psychoactive Substances
Authors: Golub Aniela , Ordak Michal , Nasierowski Tadeusz , Bujalska-Zadrozny Magdalena
Published: May 2023

One of the factors that increase the effectiveness of the pharmacotherapy used in patients abusing various types of new psychoactive substances (NPSs) is the proper functioning of the liver. However, the articles published to date on NPS hepatotoxicity only address non-specific hepatic parameters. The aim of this manuscript was to review three advanced markers of hepatotoxicity in psychiatry, namely, osteopontin (OPN), high-mobility group box 1 protein (HMGB1) and glutathione dehydrogenase (GDH, GLDH), and, on this basis, to identify recommendations that should be included in future studies in patients abusing NPSs. This will make it possible to determine whether NPSs do indeed have a hepatotoxic effect or whether other factors, such as additional substances taken or hepatitis C virus (HCV) infection, are responsible. NPS abusers are at particular risk of HCV infection, and for this reason, it is all the more important to determine what factors actually show a hepatotoxic effect in them.
Roles of Noncoding RNAs in Regulation of Mitochondrial Electron Transport Chain and Oxidative Phosphorylation
Authors: Kobayashi Ami , Takeiwa Toshihiko , Ikeda Kazuhiro , Inoue Satoshi
Published: May 2023

The mitochondrial electron transport chain (ETC) plays an essential role in energy production by inducing oxidative phosphorylation (OXPHOS) to drive numerous biochemical processes in eukaryotic cells. Disorders of ETC and OXPHOS systems are associated with mitochondria- and metabolism-related diseases, including cancers; thus, a comprehensive understanding of the regulatory mechanisms of ETC and OXPHOS systems is required. Recent studies have indicated that noncoding RNAs (ncRNAs) play key roles in mitochondrial functions; in particular, some ncRNAs have been shown to modulate ETC and OXPHOS systems. In this review, we introduce the emerging roles of ncRNAs, including microRNAs (miRNAs), transfer-RNA-derived fragments (tRFs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), in the mitochondrial ETC and OXPHOS regulation.
Network Analysis of Biomarkers Associated with Occupational Exposure to Benzene and Malathion
Authors: Santos Marcus Vinicius C. , Feltrin Arthur S. , Costa-Amaral Isabele C. , Teixeira Liliane R. , Perini Jamila A. , Martins David C. , Larentis Ariane L.
Published: May 2023

Complex diseases are associated with the effects of multiple genes, proteins, and biological pathways. In this context, the tools of Network Medicine are compatible as a platform to systematically explore not only the molecular complexity of a specific disease but may also lead to the identification of disease modules and pathways. Such an approach enables us to gain a better understanding of how environmental chemical exposures affect the function of human cells, providing better perceptions about the mechanisms involved and helping to monitor/prevent exposure and disease to chemicals such as benzene and malathion. We selected differentially expressed genes for exposure to benzene and malathion. The construction of interaction networks was carried out using GeneMANIA and STRING. Topological properties were calculated using MCODE, BiNGO, and CentiScaPe, and a Benzene network composed of 114 genes and 2415 interactions was obtained. After topological analysis, five networks were identified. In these subnets, the most interconnected nodes were identified as: IL-8, KLF6, KLF4, JUN, SERTAD1, and MT1H. In the Malathion network, composed of 67 proteins and 134 interactions, HRAS and STAT3 were the most interconnected nodes. Path analysis, combined with various types of high-throughput data, reflects biological processes more clearly and comprehensively than analyses involving the evaluation of individual genes. We emphasize the central roles played by several important hub genes obtained by exposure to benzene and malathion.
Vitamin D and Bone fragility in Individuals with Osteogenesis Imperfecta: A Scoping Review
Authors: Gnoli Maria , Brizola Evelise , Tremosini Morena , Di Cecco Alessia , Sangiorgi Luca
Published: May 2023

Vitamin D affects several body functions, and thus general health, due to its pleiotropic activity. It plays a key role in bone metabolism, and its deficiency impacts bone development, leading to bone fragility. In osteogenesis imperfecta (OI), a group of hereditary connective tissue disorders characterized by bone fragility, additional factors, such as vitamin D deficiency, can affect the expression of the phenotype and aggravate the disorder. The aim of this scoping review was to assess the incidence of vitamin D deficit in OI patients and the association between vitamin D status and supplementation in individuals affected by OI. We searched the PubMed Central and Embase databases and included studies published between January/2000 and October/2022 evaluating vitamin D measurement and status (normal, insufficiency, deficiency) and supplementation for OI. A total of 263 articles were identified, of which 45 were screened by title and abstract, and 10 were included after a full-text review. The review showed that low levels of vitamin D was a frequent finding in OI patients. Vitamin D supplementation was mainly indicated along with drug therapy and calcium intake. Even if widely used in clinical practice, vitamin D supplementation for OI individuals still needs a better characterization and harmonized frame for its use in the clinical setting, as well as further studies focusing on its effect on bone fragility.
Synthesis, Structural Properties, and Resistance to High-Temperature Degradation of Perovskite Ceramics Based on Lanthanum–Strontium Ferrite
Authors: Borgekov Daryn B. , Kozlovskiy Artem L. , Zdorovets Maxim V. , Shlimas Dmitriy I.
Published: May 2023

This work is dedicated to the study of the properties of perovskite ceramics based on lanthanum–strontium ferrite, and to the evaluation of their resistance to long-term thermal aging. As a method for obtaining perovskite ceramics, the method of solid-phase mechanochemical grinding and consequent thermal annealing of the resulting mixtures was chosen. The novelty of the study consists in the assessment of the phase transformation dynamics in lanthanum–strontium ferrite-based ceramics in relation to the annealing temperature, alongside the study of the effect of the phase composition of ceramics on the resistance to high-temperature aging, which is characteristic of the operating modes of these ceramics as materials for solid oxide fuel cells. To study the properties, the methods of scanning electron microscopy, energy dispersive analysis, and scanning electron microscopy were applied. Pursuant to the outcome of elemental analysis, it was established that no impurity inclusions appear in the ceramic structure during the synthesis, and a growth in the annealing temperature results into a decline in the grain size and a growth in their density. During the analysis of the acquired X-ray diffraction patterns, it was found that a growth in the annealing temperature above 500 °C results in phase transformations of the LaFeO3/SrFe2O4 → La0.3Sr0.7FeO3/LaSr2FeO8/La3FeO6 type, followed by structural ordering and a decline in deformation distortions with a growth in the annealing temperature. An analysis of the conductive properties of ceramics has established that the dominance of the La0.3Sr0.7FeO3 phase in the structure results in a growth in conductivity and a decline in resistance. Life tests for degradation resistance have shown that for three-phase ceramics, the rate of degradation and amorphization is significantly lower than for two-phase ceramics.
Precipitative Coating of Calcium Phosphate on Microporous Silica–Titania Hybrid Particles in Simulated Body Fluid
Authors: Kimura Reo , Shiba Kota , Fujiwara Kanata , Zhou Yanni , Yamada Iori , Tagaya Motohiro
Published: May 2023

Titania and silica have been recognized as potential drug delivery system (DDS) carriers. For this application, controllable biocompatibility and the suppression of the initial burst are required, which can be provided by a calcium phosphate (CP) coating. However, it is difficult to control the morphology of a CP coating on the surface of carrier particles owing to the homogeneous nucleation of CP. In this study, we report the development of a CP-coating method that homogeneously corresponds to the shapes of silica–titania (SiTi) porous nanoparticles. We also demonstrate that controlled surface roughness of CP coatings could be achieved in SBF using SiTi nanoparticles with a well-defined spherical shape, a uniform size, and a tunable nanoporous structure. The precipitation of CP was performed on mono-dispersed porous SiTi nanoparticles with different Si/Ti molar ratios and pore sizes. The pore size distribution was found to significantly affect the CP coating in SBF immersion; the surfaces of the nanoparticles with bimodal pore sizes of 0.7 and 1.1–1.2 nm became rough after CP precipitation, while those with a unimodal pore size of 0.7 nm remained smooth, indicating that these two pore sizes serve as different nucleation sites that lead to different surface morphologies.
Pt Nanoparticles Supported on Ultrathin Ni(OH)2 Nanosheets for Highly Efficient Reduction of 4-Nitrophenol
Authors: Cui Jia-Lin , Liu Zhong-Liang , Li Hui-Hui , Li Chun-Zhong
Published: May 2023

The synthesis of highly efficient heterogeneous catalysts with uniformly dispersed noble metal particles and a suitable size is crucial for various industrial applications. However, the high cost and rarity of noble metals limit their economic efficiency, making it essential to improve the catalytic performance with lower noble metal loading. Herein, a two-step method was developed for the synthesis of uniformly dispersed ~3 nm Pt nanoparticles (NPs), strongly anchored on Ni(OH)2 nanosheets (NSs), which was proven by adequate structural characterizations. XPS analysis demonstrated that Ni(OH)2 NSs with abundant oxygen vacancies provided sufficient anchor sites for Pt NPs and prevented their agglomeration. The catalytic performance of Ptn/Ni(OH)2 (n (represents the addition amount of Pt precursors during the synthesis, μmol) = 5, 10, 15, and 20) NSs with controllable Pt loading were evaluated via the reduction of 4-nitrophenol to 4-aminophenol as a model reaction. The Pt10/Ni(OH)2 NSs exhibited the best activity and stability, with a reaction rate constant of 0.02358 s−1 and negligible deterioration in ten reaction cycles. This novel synthetic method shows potentials for the synthesis of highly efficient noble-metal-supported catalysts for heterogeneous catalysis.
Effect of AST Atmosphere on Pt/C Electrocatalyst Degradation
Authors: Paperzh Kirill , Moguchikh Elizaveta , Pankov Ilya , Belenov Sergey , Alekseenko Anastasia
Published: May 2023

The targeted development of novel stress testing protocols as well as the production of highly active and stable catalysts require abandoning a trial-and-error approach and transitioning to identifying the principal degradation mechanisms of electrocatalysts for PEMFCs under various conditions. Methodological aspects of research related to both qualitative and quantitative assessment of the materials’ robustness against degradation and its mechanisms become the key issues. In this study, accelerated stress testing has been conducted in Ar and O2 to identify the influence of the atmosphere on the degradation and durability mechanisms of the Pt/C catalysts. Initial and final parameters after the AST have been studied in detail by transmission electron microscopy and voltammetry using the rotating disk electrode technique. The Ostwald ripening (redeposition) of platinum particles has been established to be the predominant degradation mechanism during the testing in an O2 atmosphere, this being the agglomeration of nanoparticles during the testing in Ar. An ultra-small size and a narrow size distribution of platinum nanoparticles, as well as their uniform spatial distribution over the surface of the carbon support, have been shown to allow both ORR activity to be increased and durability to be enhanced.
Effects of Finerenone on Cardiovascular and Chronic Kidney Diseases: A New Weapon against Cardiorenal Morbidity and Mortality—A Comprehensive Review
Authors: Piccirillo Francesco , Liporace Paola , Nusca Annunziata , Nafisio Vincenzo , Corlianò Andrea , Magarò Francesca , Antonelli Incalzi Raffaele , Ussia Gian Paolo , Grigioni Francesco
Published: May 2023

Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) show high rates of cardiorenal outcomes. In addition, the progression towards renal failure and cardiovascular events rises as CKD worsens. Several studies suggest that the activation of the mineralocorticoid receptor (MR) induces cardiac and renal injury, including inflammation and fibrosis. Finerenone is a novel, nonsteroidal, selective MR antagonist (MRA) which has demonstrated anti-inflammatory and anti-fibrotic effects in pre-clinical studies. Moreover, two large trials (FIDELIO-DKD and FIGARO-DKD) investigated the renal and cardiovascular outcomes in patients with mild to severe CKD in type 2 diabetes which received finerenone. On these bases, this comprehensive review aims to summarize the current knowledge regarding finerenone and its effects on CKD and the cardiovascular system, emphasizing its role in modifying cardiorenal outcomes.
Importance of Tissue Doppler Evaluation in Dilated Cardiomyopathy: The Value of Diastolic Filling Pattern as a Prognostic Predictor
Authors: Iliuță Luminita , Andronesi Andreea Gabriella , Rac-Albu Marius , Rac-Albu Mădălina-Elena , Scafa-Udriște Alexandru , Moldovan Horațiu , Furtunescu Florentina Ligia , Rădulescu Bogdan Constantin , Panaitescu Eugenia
Published: May 2023

(1) Background: The presence of restrictive left ventricular diastolic filling pattern (LVDFP) is associated with an unfavorable prognosis in many cardiac diseases, but few data are available on the prognostic implications of this pattern in patients with dilated cardiomyopathy (DCM). We aimed to establish the main prognostic predictors at the 1- and 5-year follow-ups in DCM patients and the value of restrictive LVDFP in increasing morbidity and mortality. (2) Methods: A prospective study of 143 patients with DCM divided in non-restrictive LVDFP group (95 patients) and restrictive group (47 patients). The patients were evaluated at a 5-year follow-up through an in-patient visit during the pre-pandemic period and hybrid methods (face-to-face, teleconsultation and home monitoring with a telemedicine application) during the pandemic period. Statistical analysis compared the two groups in terms of NYHA class, quality of life, hospitalizations/emergency department (ED) visits due to HF exacerbation and total mortality. (3) Results: The mortality rate in the restrictive group was markedly higher than that in the non-restrictive group at 1 year (17.02% vs. 10.59%, respectively, p < 0.05) and at 5 years (68.08% vs. 50.53%, p < 0.05). In the restrictive group, hospitalizations/ED visits due to HF decompensations at 1 year were significantly higher (85.11% vs. 57.89%, p < 0.05), with hospitalizations for ventricular arrhythmia being almost three times higher (21.28% vs. 7.37%, respectively, p < 0.05). The percentage of patients with a favorable evolution (in terms of NYHA class and quality of life) at the 1- and 5-year follow-ups were higher in the non-restrictive LVDFP group. The main prognostic predictors in patients with DCM at the 1-year follow-up were: restrictive LVDFP, age > 75 years, markedly dilated LV, comorbidities (DM, COPD), 2nd-degree mitral regurgitation and severe pulmonary hypertension (p < 0.05). (4) Conclusions: At the 1- and 5-year follow-ups, the presence of the restrictive LVDFP in DCM patients was independently associated with a poor prognosis, being the best clinical predictor for unfavorable evolution, after adjustment for other well-established predictive parameters in DCM patients.
The Prevalence of and Predisposing Factors for Late Atrial Arrhythmias after Transcatheter Closure of Secundum Atrial Septal Defects in Children
Authors: Abu-Tair Tariq , Martin Claudia , Wiethoff Christiane M. , Kampmann Christoph
Published: May 2023

Background: A 24 h Holter study in children after transcatheter secundum ASD (ASD II) closure was conducted to detect the prevalence of defects and/or device-related late atrial arrhythmias (LAAs). ASD II closure with an Amplatzer septal occluder (ASO) is an established procedure. Little is known about LAAs after device implantation. Methods: The eligible participants were children who had undergone ASO implantation, with a follow-up of ≥5 years, as well as one pre- and at least one post-procedural Holter ECG. Results: In total, 161 patients (mean age: 6.2 ± 4.3 years), with a mean follow-up of 12.9 ± 3.1 years (range 5–19), were included. A median of four Holter ECGs per patient were available. LAAs occurred before intervention in four patients (2.5%), and it was peri-interventional in four patients (2.5%), sustained in three patients (1.9%), and developed in three patients (1.9%). In patients with pre- and peri-interventional LAAs, the Qp/Qs ratio was higher (6.4 ± 3.9 vs. non-AA: 2.0 ± 1.1 (p = 0.002)) and the IAS/ASO ratio was lower (1.18 ± 0.27 vs. non-AA: 1.7 ± 0.4 (p < 0.001)). The patients with LAAs differed from those without LAAs in their Qp/Qs (6.8 ± 3.5 vs. 2.0 ± 1.3; p < 0.0001) and IAS/ASO ratios (1.14 ± 0.19 vs. 1.73 ± 0.45; p < 0.001). The patients with LAAs had a Qp/Qs ratio ≥2.94:1, and those who developed LAAs had an IAS/ASO ratio <1.15. Conclusions: LAAs occurred in 1.9% of patients and were sustained in another 1.9% of patients but persisted in those with large shunt defects and large occluders in relation to the atrial septal length. The predisposing factors for LAAs after ASD closure were a high Qp/Qs ratio, pre-existing atrial arrhythmias, and a low IAS/ASO ratio.
Normothermic Ex Vivo Machine Perfusion for Liver Transplantation: A Systematic Review of Progress in Humans
Authors: Risbey Charles W. G. , Pulitano Carlo
Published: May 2023

Background: Liver transplantation is a lifesaving procedure for patients with end-stage liver disease (ESLD). However, many patients never receive a transplant due to insufficient donor supply. Historically, organs have been preserved using static cold storage (SCS). However, recently, ex vivo normothermic machine perfusion (NMP) has emerged as an alternative technique. This paper aims to investigate the clinical progress of NMP in humans. Methods: Papers evaluating the clinical outcomes of NMP for liver transplantation in humans were included. Lab-based studies, case reports, and papers utilizing animal models were excluded. Literature searches of MEDLINE and SCOPUS were conducted. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) and the risk of bias in nonrandomised studies for interventions (ROBINS-I) tools were used. Due to the heterogeneity of the included papers, a meta-analysis was unable to be completed. Results: In total, 606 records were identified, with 25 meeting the inclusion criteria; 16 papers evaluated early allograft dysfunction (EAD) with some evidence for lower rates using NMP compared to SCS; 19 papers evaluated patient or graft survival, with no evidence to suggest superior outcomes with either NMP or SCS; 10 papers evaluated utilization of marginal and donor after circulatory death (DCD) grafts, with good evidence to suggest NMP is superior to SCS. Conclusions: There is good evidence to suggest that NMP is safe and that it likely affords clinical advantages to SCS. The weight of evidence supporting NMP is growing, and this review found the strongest evidence in support of NMP to be its capacity to increase the utilization rates of marginal and DCD allografts.
A Systematic Review on Combined [18F]FDG and 68Ga-SSA PET/CT in Pulmonary Carcinoid
Authors: Prosperi Daniela , Carideo Luciano , Russo Vincenzo , Meucci Rosaria , Campagna Giuseppe , Lastoria Secondo , Signore Alberto
Published: May 2023

Pulmonary carcinoids (PCs) are part of a spectrum of well-differentiated neuroendocrine neoplasms (NENs) and are classified as typical carcinoid (TC) and atypical carcinoid (AC). TC differ from AC not only for its histopathological features but also for its “functional imaging pattern” and prognosis. ACs are more undifferentiated and characterized by higher aggressiveness. Positron emission tomography/computed tomography (PET/CT) with somatostatin analogs (SSA) labeled with Gallium-68 (68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE) has widely replaced conventional imaging with gamma camera using 111In- or 99mTc-labelled compounds and represents now the gold standard for diagnosis and management of NENs. In this setting, as already described for gastro-entero-pancreatic NENs, 18F-Fluorodeoxiglucose ([18F]FDG) in addition to 68Ga-SSA can play an important role in clinical practice, particularly for ACs that show a more aggressive behavior compared to TCs. The aim of this systematic review is to analyze all original studies collected from the PubMed and Scopus databases regarding PCs in which both 68Ga-SSA PET/CT and [18F]FDG PET/CT were performed in order to evaluate the clinical impact of each imaging modality. The following keywords were used for the research: “18F, 68Ga and (bronchial carcinoid or carcinoid lung)”. A total of 57 papers were found, of which 17 were duplicates, 8 were reviews, 10 were case reports, and 1 was an editorial. Of the remaining 21 papers, 12 were ineligible because they did not focus on PC or did not compare 68Ga-SSA and [18F]FDG. We finally retrieved and analyzed nine papers (245 patients with TCs and 110 patients with ACs), and the results highlight the importance of the combined use of 68Ga-SSA and [18F]FDG PET/CT for the correct management of these neoplasms.
Outcomes of Laparoscopic Cesarean Scar Defect Repair: Retrospective and Observational Study
Authors: Nezhat Camran , Zaghi Benjamin , Baek Kelly , Nezhat Azadeh , Nezhat Farr , Lindheim Steven , Nezhat Ceana
Published: May 2023

Cesarean scar defect, also known as niche, isthmocele, uteroperitoneal fistula and uterine diverticulum, is a known complication after cesarean delivery. Due to the rising cesarean delivery rates, niche has become more common and can present as irregular bleeding, pelvic pain, infertility, cesarean scar pregnancy and uterine rupture. Treatments for symptomatic cesarean scar defect vary and include hormonal therapy, hysteroscopic resection, vaginal or laparoscopic repair, and hysterectomy. We report on the safety and efficacy of our method of repairing cesarean scar defects in 27 patients without adverse outcomes: two-layer repair where the suture does not enter the uterine cavity. Our method of laparoscopic niche repair improves symptoms in nearly 77% of patients, restores fertility in 73% of patients, and decreases the time to conception.
Severe Acute Pancreatitis Treated with Negative Pressure Wound Therapy System: Influence of Laboratory Markers
Authors: Ciuntu Bogdan Mihnea , Vintilă Dan , Tanevski Adelina , Chiriac Ștefan , Stefănescu Gabriela , Abdulan Irina Mihaela , Balan Gheorghe G. , Veliceasa Bogdan , Bădulescu Oana Viola , Ghiga Gabriela , Fătu Ana Maria , Georgescu Andrei , Vascu Mihai Bogdan , Vasilescu Alin Mihai
Published: May 2023

(1) Background: An open abdomen is a serious medical condition that requires prompt and effective treatment to prevent complications and improve patient outcomes. Negative pressure therapy (NPT) has emerged as a viable therapeutic option for temporary closure of the abdomen, offering several benefits over traditional methods. (2) Methods: We included 15 patients with pancreatitis who were hospitalized in the I–II Surgery Clinic of the Emergency County Hospital “St. Spiridon” from Iasi, Romania, between 2011–2018 and received NPT. (3) Results: Preoperatively, the mean IAP level was 28.62 mmHg, decreasing significantly postoperatively to 21.31 mmHg. The mean level of the highest IAP value recorded in pancreatitis patients treated with VAC did not differ significantly by lethality (30.31 vs. 28.50; p = 0.810). In vacuum-treated pancreatitis patients with a IAP level > 12, the probability of survival dropped below 50% during the first 7 days of stay in the ICU, so that after 20 days the probability of survival was approximately 20%. IAP enters the determinism of surgery with a sensitivity of 92.3% and a specificity of 99%, the cut-off value of IAP being 15 mmHg. (4) Conclusions: The timing of surgical decompression in abdominal compartment syndrome is very important. Consequently, it is vital to identify a parameter, easy to measure, within the reach of any clinician, so that the indication for surgical intervention can be made judiciously and without delay.
Physical Function of RA patients Tapering Treatment—A Post Hoc Analysis of the Randomized Controlled RETRO Trial
Authors: Stephan Marlene , Tascilar Koray , Yalcin-Mutlu Melek , Hagen Melanie , Haschka Judith , Reiser Michaela , Hartmann Fabian , Kleyer Arnd , Hueber Axel J. , Manger Bernhard , Figueiredo Camille , Cobra Jayme Fogagnolo , Tony Hans-Peter , Finzel Stephanie , Kleinert Stefan , Wendler Jörg , Schuch Florian , Ronneberger Monika , Feuchtenberger Martin , Fleck Martin , Manger Karin , Ochs Wolfgang , Schmitt-Haendle Matthias , Lorenz Hannes Martin , Nüsslein Hubert , Alten Rieke , Henes Joerg , Krüger Klaus , Schett Georg , Rech Jürgen
Published: May 2023

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline.
Multimodal Prehabilitation in Heart Transplant Recipients Improves Short-Term Post-Transplant Outcomes without Increasing Costs
Authors: López-Baamonde Manuel , Arguis María José , Navarro-Ripoll Ricard , Gimeno-Santos Elena , Romano-Andrioni Bárbara , Sisó Marina , Terès-Bellès Silvia , López-Hernández Antonio , Burniol-García Adrià , Farrero Marta , Sebio-García Raquel , Sandoval Elena , Sanz-de la Garza María , Librero Julián , García-Álvarez Ana , Castel María Ángeles , Martínez-Pallí Graciela
Published: May 2023

(1) Background and aim: This study aimed to investigate the impact of prehabilitation on the postoperative outcomes of heart transplantation and its cost-effectiveness. (2) Methods: This single-center, ambispective cohort study included forty-six candidates for elective heart transplantation from 2017 to 2021 attending a multimodal prehabilitation program consisting of supervised exercise training, physical activity promotion, nutritional optimization, and psychological support. The postoperative course was compared to a control cohort consisting of patients transplanted from 2014 to 2017 and those contemporaneously not involved in prehabilitation. (3) Results: A significant improvement was observed in preoperative functional capacity (endurance time 281 vs. 728 s, p < 0.001) and quality-of-life (Minnesota score 58 vs. 47, p = 0.046) after the program. No exercise-related events were registered. The prehabilitation cohort showed a lower rate and severity of postoperative complications (comprehensive complication index 37 vs. 31, p = 0.033), lower mechanical ventilation time (37 vs. 20 h, p = 0.032), ICU stay (7 vs. 5 days, p = 0.01), total hospitalization stay (23 vs. 18 days, p = 0.008) and less need for transfer to nursing/rehabilitation facilities after hospital discharge (31% vs. 3%, p = 0.009). A cost-consequence analysis showed that prehabilitation did not increase the total surgical process costs. (4) Conclusions: Multimodal prehabilitation before heart transplantation has benefits on short-term postoperative outcomes potentially attributable to enhancement of physical status, without cost-increasing.
Predictive Value of Total Metabolic Tumor Burden Prior to Treatment in NSCLC Patients Treated with Immune Checkpoint Inhibition
Authors: Kudura Ken , Ritz Nando , Templeton Arnoud J. , Kutzker Tim , Foerster Robert , Antwi Kwadwo , Kreissl Michael C. , Hoffmann Martin H. K.
Published: May 2023

Objectives: We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Methods: Pre-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by totalMTV and totalTLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment. Results: A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean totalMTV ± standard deviation (SD) 72.2 ± 78.7; mean totalTLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean totalMTV ± SD 58.1 ± 233.8; mean totalTLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, p < 0.01), PFS (HR 30.89, p < 0.01) and CB (parameter estimation PE 3.46, p < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS (p = 0.04) and PFS (p = 0.01) after treatment given the hazard ratios of 1.00, but also on CB (p = 0.01) given the PE < 0.01. Overall, biomarkers on pre-treatment PET/CT scans showed greater predictive power in patients receiving ICIs, compared to patients without ICI treatment. Conclusions: Morphological and metabolic properties of the primary tumors prior to treatment in advanced NSCLC patients treated with ICI showed great outcome prediction performances, as opposed to the pre-treatment total metabolic tumor burdens, captured by totalMTV and totalTLG, both with negligible impact on OS, PFS and CB. However, the outcome prediction performance of the total metabolic tumor burden might be influenced by the value itself (e.g., poorer prediction performance at very high or very low values of total metabolic tumor burden). Further studies including subgroup analysis with regards to different values of total metabolic tumor burden and their respective outcome prediction performances might be needed.
Abdominal Aortic Aneurysm Detection in Bioelectrical Impedance Cardiovascular Screenings—A Pilot Study
Authors: Hofmann Amun , Shoumariyeh Tarik , Domenig Christoph , Skrabal Falko , Kovarik Johannes
Published: May 2023

Screening and diagnosing abdominal aortic aneurysms (AAA) are currently dependent on imaging studies such as ultrasound or computed tomography angiography. All imaging studies offer distinct advantages but also suffer from inherent limitations such as examiner dependency or ionizing radiation. Bioelectrical impedance analysis has previously been investigated with respect to its use in the detection of several cardiovascular and renal pathologies. The present pilot study assessed the feasibility of AAA detection based on bioimpedance analysis. In this single-center exploratory pilot study, measurements were conducted among three different cohorts: patients with AAA, end-stage renal disease patients without AAA, and healthy controls. The device used in the study, CombynECG, is an open-market accessible device for segmental bioelectrical impedance analysis. The data was preprocessed and used to train four different machine learning models on a randomized training sample (80% of the full dataset). Each model was then evaluated on a test set (20% of the full dataset). The total sample included 22 patients with AAA, 16 chronic kidney disease patients, and 23 healthy controls. All four models showed strong predictive performance in the test partitions. Specificity ranged from 71.4 to 100%, while sensitivity ranged from 66.7 to 100%. The best-performing model had 100% accuracy for classification when applied to the test sample. Additionally, an exploratory analysis to approximate the maximum AAA diameter was conducted. An association analysis revealed several impedance parameters that might possess predictive ability with respect to aneurysm size. AAA detection via bioelectrical impedance analysis is technically feasible and appears to be a promising technology for large-scale clinical studies and routine clinical screening assessments.
Nailfold Videocapillaroscopic Alterations as Markers of Microangiopathy in COVID-19 Patients
Authors: Gualtierotti Roberta , Fox Sharon , Da Silva Lameira Fernanda , Giachi Andrea , Valenti Luca , Borghi Maria , Meroni Pier , Cugno Massimo , Peyvandi Flora ,   on behalf of the CAPCOVID Study Group
Published: May 2023

Nailfold videocapillaroscopic alterations have been described in COVID-19, but their correlations with biomarkers of inflammation, coagulation and endothelial perturbation are still unclear, and no information is available on nailfold histopathology. Nailfold videocapillaroscopy was performed on fifteen patients with COVID-19 in Milan, Italy and the signs of microangiopathy were correlated with plasma biomarkers of inflammation (C reactive protein [CRP], ferritin), coagulation (D-dimer, fibrinogen), endothelial perturbation (Von Willebrand factor [VWF]) and angiogenesis (vascular endothelial growth factor [VEGF]) along with genetic drivers of COVID-19 susceptibility. Histopathological analysis of autoptic nailfold excisions was performed on fifteen patients who died for COVID-19 in New Orleans, United States. All COVID-19 patients studied with videocapillaroscopy showed alterations rarely seen in healthy individuals consistent with microangiopathy, such as hemosiderin deposits (sign of microthrombosis and microhemorrhages) and enlarged loops (sign of endotheliopathy). The number of hemosiderin deposits correlated both with ferritin and CRP levels (r = 0.67, p = 0.008 for both) and the number of enlarged loops significantly correlated with the levels of VWF (r = 0.67, p = 0.006). Ferritin levels were higher in non-O groups, determined by the rs657152 C > A cluster, (median 619, min–max 551–3266 mg/dL) than in the O group (373, 44–581 mg/dL, p = 0.006). Nailfold histology revealed microvascular damage, i.e., mild perivascular lymphocyte and macrophage infiltration and microvascular ectasia in the dermal vessels of all cases, and microthrombi within vessels in five cases. Alterations in nailfold videocapillaroscopy and elevated biomarkers of endothelial perturbation that match histopathologic findings open new perspectives in the possibility of non-invasively demonstrating microangiopathy in COVID-19.