bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct Longitudinal Changes in Immunoglobulin G N-Glycosylation Associate with Therapy Response in Chronic Inflammatory Diseases
Authors: Štambuk Jerko , Vučković Frano , Habazin Siniša , Hanić Maja , Novokmet Mislav , Nikolaus Susanna , Tran Florian , Schreiber Stefan , Franke Andre , Rosenstiel Philip , Lauc Gordan , Aden Konrad , Pezer Marija
Published: August 2022

Immunosuppressants and biologicals are widely used therapeutics for various chronic inflammatory diseases (CID). To gain more detailed insight into their downstream effects, we examined their impact on serum immunoglobulin G (IgG) glycosylation. We analyzed IgG subclass-specific fragment crystallizable (Fc) N-glycosylation in patients suffering from various CID using the LC-MS approach. Firstly, we compared IgG Fc N-glycosylation between 128 CID patients and 204 healthy controls. Our results replicated previously observed CID-related decrease in IgG Fc galactosylation (adjusted p-value range 1.70 × 10−2–5.95 × 10−22) and sialylation (adjusted p-value range 1.85 × 10−2–1.71 × 10−18). Secondly, to assess changes in IgG Fc N-glycosylation associated with therapy and remission status, we compared 139 CID patients receiving either azathioprine, infliximab, or vedolizumab therapy. We observed an increase in IgG Fc galactosylation (adjusted p-value range 1.98 × 10−2–1.30 × 10−15) and sialylation (adjusted p-value range 3.28 × 10−6–4.34 × 10−18) during the treatment. Furthermore, patients who reached remission displayed increased Fc galactosylation levels (p-value range 2.25 × 10−2–5.44 × 10−3) in comparison to patients with active disease. In conclusion, the alterations in IgG Fc glycosylation and the fact these changes are even more pronounced in patients who achieved remission, suggest modulation of IgG inflammatory potential associated with CID therapy.
Argan (Argania spinosa L.) Seed Oil Cake as a Potential Source of Protein-Based Film Matrix for Pharmaco-Cosmetic Applications
Authors: Mirpoor Seyedeh , Giosafatto Concetta , Mariniello Loredana , D’Agostino Antonella , D’Agostino Maria , Cammarota Marcella , Schiraldi Chiara , Porta Raffaele
Published: August 2022

Various different agri-food biomasses might be turned into renewable sources for producing biodegradable and edible plastics, potentially attractive for food, agricultural and cosmeceutical sectors. In this regard, different seeds utilized for edible and non-edible oil extraction give rise to high amounts of organic by-products, known as seed oil cakes (SOCs), potentially able to become protein-rich resources useful for the manufacturing of biodegradable films. This study reports the potential of SOC derived from Argania spinosa (argan), a well-known plant containing valuable non-refined oil suitable for food or cosmetic use, to be a promising valuable source for production of a protein-based matrix of biomaterials to be used in the pharmaco-cosmetic sector. Thus, glycerol-plasticized films were prepared by casting and drying using different amounts of argan seed protein concentrate, in the presence of increasing glycerol concentrations, and characterized for their morphological, mechanical, barrier, and hydrophilicity properties. In addition, their antioxidant activity and effects on cell viability and wound healing were investigated. The hydrophobic nature of the argan protein-based films, and their satisfying physicochemical and biological properties, suggest a biorefinery approach for the recycling of argan SOC as valuable raw material for manufacturing new products to be used in the cosmeceutical and food industries.
Involvement of Auxin-Mediated CqEXPA50 Contributes to Salt Tolerance in Quinoa (Chenopodium quinoa) by Interaction with Auxin Pathway Genes
Authors: Sun Wenjun , Yao Min , Wang Zhen , Chen Ying , Zhan Junyi , Yan Jun , Jiang Shuangqing , Jian Shanshan , Chen Hui , Bu Tongliang , Tang Zizong , Li Qingfeng , Zhao Haixia , Wu Qi
Published: August 2022

Soil salinization is a global problem that limits crop yields and threatens agricultural development. Auxin-induced expansins contribute to plant salt tolerance through cell wall loosening. However, how auxins and expansins contribute to the adaptation of the halophyte quinoa (Chenopodium quinoa) to salt stress has not yet been reported. Here, auxin was found to contribute to the salt tolerance of quinoa by promoting the accumulation of photosynthetic pigments under salt stress, maintaining enzymatic and nonenzymatic antioxidant systems and scavenging excess reactive oxygen species (ROS). The Chenopodium quinoa expansin (Cqexpansin) family and the auxin pathway gene family (Chenopodium quinoa auxin response factor (CqARF), Chenopodium quinoa auxin/indoleacetic acid (CqAux/IAA), Chenopodium quinoa Gretchen Hagen 3 (CqGH3) and Chenopodium quinoa small auxin upregulated RNA (CqSAUR)) were identified from the quinoa genome. Combined expression profiling identified Chenopodium quinoa α-expansin 50 (CqEXPA50) as being involved in auxin-mediated salt tolerance. CqEXPA50 enhanced salt tolerance in quinoa seedlings was revealed by transient overexpression and physiological and biochemical analyses. Furthermore, the auxin pathway and salt stress-related genes regulated by CqEXPA50 were identified. The interaction of CqEXPA50 with these proteins was demonstrated by bimolecular fluorescence complementation (BIFC). The proteins that interact with CqEXPA50 were also found to improve salt tolerance. In conclusion, this study identified some genes potentially involved in the salt tolerance regulatory network of quinoa, providing new insights into salt tolerance.
The Newly Sequenced Genome of Pisum sativum Is Replete with Potential G-Quadruplex-Forming Sequences—Implications for Evolution and Biological Regulation
Authors: Dobrovolná Michaela , Bohálová Natália , Peška Vratislav , Wang Jiawei , Luo Yu , Bartas Martin , Volná Adriana , Mergny Jean-Louis , Brázda Václav
Published: August 2022

G-quadruplexes (G4s) have been long considered rare and physiologically unimportant in vitro curiosities, but recent methodological advances have proved their presence and functions in vivo. Moreover, in addition to their functional relevance in bacteria and animals, including humans, their importance has been recently demonstrated in evolutionarily distinct plant species. In this study, we analyzed the genome of Pisum sativum (garden pea, or the so-called green pea), a unique member of the Fabaceae family. Our results showed that this genome contained putative G4 sequences (PQSs). Interestingly, these PQSs were located nonrandomly in the nuclear genome. We also found PQSs in mitochondrial (mt) and chloroplast (cp) DNA, and we experimentally confirmed G4 formation for sequences found in these two organelles. The frequency of PQSs for nuclear DNA was 0.42 PQSs per thousand base pairs (kbp), in the same range as for cpDNA (0.53/kbp), but significantly lower than what was found for mitochondrial DNA (1.58/kbp). In the nuclear genome, PQSs were mainly associated with regulatory regions, including 5′UTRs, and upstream of the rRNA region. In contrast to genomic DNA, PQSs were located around RNA genes in cpDNA and mtDNA. Interestingly, PQSs were also associated with specific transposable elements such as TIR and LTR and around them, pointing to their role in their spreading in nuclear DNA. The nonrandom localization of PQSs uncovered their evolutionary and functional significance in the Pisum sativum genome.
Pan-Cancer Analysis Identifies CHD5 as a Potential Biomarker for Glioma
Authors: Xu Lei , Shao Fengling , Luo Tengling , Li Qijun , Tan Dongmei , Tan Yi
Published: August 2022

The chromodomain helicase DNA binding domain 5 (CHD5) is required for neural development and plays an important role in the regulation of gene expression. Although CHD5 exerts a broad tumor suppressor effect in many tumor types, its specific functions regarding its expression levels, and impact on immune cell infiltration, proliferation and migration in glioma remain unclear. Here, we evaluated the role of CHD5 in tumor immunity in a pan-cancer multi-database using the R language. The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Cancer Cell Lines Encyclopedia (CCLE) datasets were utilized to determine the role of CHD5 in 33 types of cancers, including the expression level, prognosis, tumor progression, and immune microenvironment. Furthermore, we explored the effect of CHD5 on glioma proliferation and migration using the cell counting kit 8 (CCK-8) assay, transwell assays and western blot analysis. The findings from our pan-cancer analysis showed that CHD5 was differentially expressed in the tumor tissues as compared to the normal tissues. Survival analysis showed that CHD5 was generally associated with the prognosis of glioblastoma (GBM), low Grade Glioma (LGG) and neuroblastoma, where the low expression of CHD5 was associated with a worse prognosis in glioma patients. Then, we confirmed that the expression level of CHD5 was associated with tumor immune infiltration and tumor microenvironment, especially in glioma. Moreover, si-RNA mediated knockdown of CHD5 promoted the proliferation and migration of glioma cells in vitro. In conclusion, CHD5 was found to be differentially expressed in the pan-cancer analysis and might play an important role in antitumor immunity. CHD5 is expected to be a potential tumor prognostic marker, especially in glioma.
Identification and Functional Analysis of the Caffeic Acid O-Methyltransferase (COMT) Gene Family in Rice (Oryza sativa L.)
Authors: Liang Shaoming , Xu Shanbin , Qu Di , Yang Luomiao , Wang Jingguo , Liu Hualong , Xin Wei , Zou Detang , Zheng Hongliang
Published: August 2022

Caffeic acid O-methyltransferase (COMT) is one of the core enzymes involved in lignin synthesis. However, there is no systematic study on the rice COMT gene family. We identified 33 COMT genes containing the methyltransferase-2 domain in the rice genome using bioinformatic methods and divided them into Group I (a and b) and Group II. Motifs, conserved domains, gene structure and SNPs density are related to the classification of OsCOMTs. The tandem phenomenon plays a key role in the expansion of OsCOMTs. The expression levels of fourteen and thirteen OsCOMTs increased or decreased under salt stress and drought stress, respectively. OsCOMTs showed higher expression levels in the stem. The lignin content of rice was measured in five stages; combined with the expression analysis of OsCOMTs and multiple sequence alignment, we found that OsCOMT8, OsCOMT9 and OsCOMT15 play a key role in the synthesis of lignin. Targeted miRNAs and gene ontology annotation revealed that OsCOMTs were involved in abiotic stress responses. Our study contributes to the analysis of the biological function of OsCOMTs, which may provide information for future rice breeding and editing of the rice genome.
Anesthesia Resistant Memories in Drosophila, a Working Perspective
Authors: Bourouliti Anna , Skoulakis Efthimios M. C.
Published: August 2022

Memories are lasting representations over time of associations between stimuli or events. In general, the relatively slow consolidation of memories requires protein synthesis with a known exception being the so-called Anesthesia Resistant Memory (ARM) in Drosophila. This protein synthesis-independent memory type survives amnestic shocks after a short, sensitive window post training, and can also emerge after repeated cycles of training in a negatively reinforced olfactory conditioning task, without rest between cycles (massed conditioning—MC). We discussed operational and molecular mechanisms that mediate ARM and differentiate it from protein synthesis-dependent long-term memory (LTM) in Drosophila. Based on the notion that ARM is unlikely to specifically characterize Drosophila, we examined protein synthesis and MC-elicited memories in other species and based on intraspecies shared molecular components and proposed potential relationships of ARM with established memory types in Drosophila and vertebrates.
Predicting Distribution of the Asian Longhorned Beetle, Anoplophora glabripennis (Coleoptera: Cerambycidae) and Its Natural Enemies in China
Authors: Zhang Quan-Cheng , Wang Jun-Gang , Lei Yong-Hui
Published: August 2022

The Asian longhorned beetle, Anoplophora glabripennis, is a forestry pest found worldwide. A. glabripennis causes serious harm because of the lack of natural enemies in the invaded areas. Dastarcus helophoroides and Dendrocopos major are important natural enemies of A. glabripennis. MaxEnt was used to simulate the distribution of D. helophoroides and D. major in China, and their suitable areas were superimposed to pinpoint which regions are potentially appropriate to release or establish natural enemy populations under current and future conditions. The results showed that, with climate change, the suitable areas of D. helophoroides and D. major migrated northward; the centroid shift of A. glabripennis was greater than those of D. helophoroides and D. major. From current conditions to 2090, the suitable area of A. glabripennis, D. helophoroides, and D. major will increase by 1.44 × 104, 20.10 × 104, and 31.64 × 104 km2, respectively. Northern China (e.g., Xinjiang, Gansu, and Inner Mongolia), where A. glabripennis causes more serious damage, is also a potentially suitable area for D. helophoroides and D. major, and this provides a potential strategy for the management of A. glabripennis. Therefore, we suggest that natural enemies should be included in the model used for predicting suitable areas for invasive pests.
Observation of the Antimicrobial Activities of Two Actinomycetes in the Harvester Ant Messor orientalis
Authors: Wu Yiyang , Liu Yaxuan , Yu Jinyong , Xu Yijuan , Chen Siqi
Published: August 2022

Observations have shown that seeds collected by harvester ants are less likely to mold. Based on evolutionary analysis and other research, it was hypothesized that harvester ants could apply actinomycetes to protect seeds, similar to the protection of mutualistic fungi by leafcutter ants. Two actinomycetes were successfully isolated from the harvester ant Messor orientalis. The taxonomic status of the actinomycetes was determined by 16S rRNA sequence analysis and biochemical experimental observations. Their inhibitory effects on plant pathogens were measured. One of the bacteria was identified as Brachybacterium phenoliresistens and denoted as B. phenoliresistens MO. The other belonged to the genus Microbacterium. It was named Microbacterium sp. Growth rate determination and coculture experiments were performed to explore the inhibitory effect of actinomycetes on indicator plant pathogens. The inhibition rates of the actinomycetes toward Peronophythora litchii and Rhizoctonia solani were 100% in media containing 30% or more fermentation broth, and they also showed an inhibitory effect on Colletotrichum siamense. The coculture experiment supported this result by showing that the growth of P. litchii and R. solani was inhibited in the presence of actinomycetes. Therefore, the results of this study show the agricultural application potential of these bacteria and may provide a reference for research on the symbiosis of harvester ants with actinomycetes.
Development of a Mathematical Model for Solid Fuel Gasification and Its Sensitivity Analysis
Authors: Komarov Ivan , Rogalev Nikolay , Osipov Sergey , Zlyvko Olga , Kharlamova Daria
Published: August 2022

Within the framework of this study, a brief review of the gasification technology was carried out, the best types of blowing agents and gasification methods used in terms of efficiency and environmental safety were identified, and a mathematical model of a steam–oxygen gasifier was developed in the MS Excel software package. The authors paid special attention to the consideration of the effect of changing the input parameters of the syngas, such as the temperature and relative mass flow rate of steam and oxygen, on the heat of the combustion of the produced syngas. As a result of the research, methods for increasing the heat of the combustion of the syngas and the conditions for using the described methods were formulated. The work also revealed the optimal ratios of the blowing agents and solid fuel supplied for gasification and presented the output parameters of the produced generator gas, including the heat of combustion of the gas, the gas temperature, and the gasification efficiency. Computer simulation models of the gasifier and gasification process were the basis for the analysis of a combined cycle (CC) facility with an integrated solid fuel gasifier. The heat flow thermodynamic analysis shows that the gasification steam bleeding from the turbine is the best solution for the improvement of cycle efficiency.
Characteristics and Prognostic Relevance of Ventricular Arrhythmia in Patients with Myocarditis
Authors: Kahle Ann-Kathrin , Güde Rebekka , Schwarzl Jana M. , Münkler Paula , Akbulak Ruken Ö. , Jahnke Charlotte , Bohnen Sebastian , Würger Tilman , Schwarzl Michael , Willems Stephan , Radunski Ulf K. , Meyer Christian
Published: August 2022

Myocarditis is characterized by various clinical manifestations, with ventricular arrhythmia (VA) as a frequent symptom at initial presentation. Here, we investigated characteristics and prognostic relevance of VA in patients with myocarditis. The study population consisted of 76 patients with myocarditis, verified by biopsy and/or cardiac magnetic resonance (CMR) imaging, including 38 consecutive patients with VA (45 ± 3 years, 68% male) vs. 38 patients without VA (NVA) (38 ± 2 years, 84% male) serving as a control group. VA was monomorphic ventricular tachycardia in 55% of patients, premature ventricular complexes in 50% and ventricular fibrillation in 29%. The left ventricular ejection fraction at baseline was 47 ± 2% vs. 40 ± 3% in VA vs. NVA patients (p = 0.069). CMR showed late gadolinium enhancement more often in VA patients (94% vs. 69%; p = 0.016), incorporating 17.6 ± 1.8% vs. 8.2 ± 1.3% of myocardial mass (p < 0.001). Radiofrequency catheter ablation for VA was initially performed in nine (24%) patients, of whom five remained free from any recurrence over 24 ± 3 months. Taken together, in patients with myocarditis, reduced left ventricular ejection fraction does not predict VA occurrence but CMR shows late gadolinium enhancement more frequently and to a larger extent in VA than in NVA patients, potentially guiding catheter ablation as a reasonable treatment of VA in this population.
Risk Factors for Postoperative Acute Kidney Injury in Patients Undergoing Redo Cardiac Surgery Using Cardiopulmonary Bypass
Authors: Zhao Can , Li Yuntao , Pan Guangyu , Xu Jianping , Liu Shen , Xiao Yaqiong
Published: August 2022

Objective: This paper aimed to investigate the incidence and risk factors of postoperative acute kidney injury (AKI) in adult patients undergoing redo cardiac surgery with cardiopulmonary bypass (CPB), and explore the impact of AKI on early outcomes. Methods: A total of 116 patients undergoing redo cardiac surgery with CPB between November 2017 and May 2021 were included. Patients were divided into two groups, AKI group and non-AKI group, according to the Kidney Disease Improving Global Outcomes criteria. Perioperative variables were retrospectively collected and analyzed. Risk factors for the development of AKI were investigated by univariate and multiple logistic regression models. Clinical outcomes were also compared between the groups. Results: Postoperative AKI occurred in 63 patients (54.3%), among whom renal replacement therapy was required in 12 patients (19.0%). The mechanical ventilation time (AKI: 43.00 (19.00, 72.00) hours; non-AKI: 18.00 (15.00, 20.00) hours; p < 0.001), ICU length of stay (AKI: 4.00 (2.00, 6.00) days; non-AKI: 3.00 (2.00, 4.00) days; p = 0.010), hospital length of stay since operation (AKI: 12.00 (8.00, 18.00) days; non-AKI: 9.00 (7.00, 12.50) days; p = 0.024), dialysis (AKI: 12.00 (19.05%); non-AKI: 0 (0%); p = 0.001), reintubation (AKI: 7.00 (11.11%); non-AKI: 0 (0%); p = 0.035), and hospital mortality (AKI: 8.00 (12.70%); non-AKI: 0 (0%); p = 0.020) were all higher in the AKI group than in the non-AKI group. Multivariate analysis revealed that high aspartate aminotransferase (OR, 1.028, 95% CI, 1.003 to 1.053, p = 0.025), coronary angiogram within 2 weeks before surgery (OR, 3.209, 95% CI, 1.307 to 7.878, p = 0.011) and CPB time (OR, 1.012, 95% CI, 1.005 to 1.019, p = 0.001) were independent risk factors for postoperative AKI. Conclusions: High aspartate aminotransferase, coronary angiogram within 2 weeks before surgery and CPB time seem to be associated with an increased incidence of postoperative AKI in patients with redo cardiac surgery.
Does Bone Marrow Edema Influence the Clinical Results of Intra-Articular Platelet-Rich Plasma Injections for Knee Osteoarthritis?
Authors: Boffa Angelo , Poggi Alberto , Romandini Iacopo , Asunis Emanuela , Pizzuti Valeria , Di Martino Alessandro , Zaffagnini Stefano , Filardo Giuseppe
Published: August 2022

Platelet-rich plasma (PRP) is increasingly used for the intra-articular treatment of knee osteoarthritis (OA). However, clinical studies on PRP injections reported controversial results. Bone marrow edema (BME) can cause symptoms by affecting the subchondral bone and it is not targeted by intra-articular treatments. The aim of this study was to investigate if the presence of BME can influence the outcome of intra-articular PRP injections in knee OA patients. A total of 201 patients were included in the study, 80 with and 121 without BME at the baseline MRI. BME area and site were evaluated, and BME was graded using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Patients were assessed with International Knee Documentation Committee (IKDC) score Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, the EuroQol-Visual Analogue Scale (EQ-VAS), and the Tegner score at baseline, 2, 6, and 12 months. Overall, the presence of BME did not influence the clinical results of intra-articular PRP injections in these patients treated for knee OA. Patients with BME presented a similar failure rate and clinical improvement after PRP treatment compared to patients without BME. The area and site of BME did not affect clinical outcomes. However, patients with a higher BME grade had a higher failure rate.
IOL Power Calculations and Cataract Surgery in Eyes with Previous Small Incision Lenticule Extraction
Authors: Lischke Roman , Sekundo Walter , Wiltfang Rainer , Bechmann Martin , Kreutzer Thomas C. , Priglinger Siegfried G. , Dirisamer Martin , Luft Nikolaus
Published: August 2022

Small incision lenticule extraction (SMILE), with over 5 million procedures globally performed, will challenge ophthalmologists in the foreseeable future with accurate intraocular lens power calculations in an ageing population. After more than one decade since the introduction of SMILE, only one case report of cataract surgery with IOL implantation after SMILE is present in the peer-reviewed literature. Hence, the scope of the present multicenter study was to compare the IOL power calculation accuracy in post-SMILE eyes between ray tracing and a range of empirically optimized formulae available in the ASCRS post-keratorefractive surgery IOL power online calculator. In our study of 11 post-SMILE eyes undergoing cataract surgery, ray tracing showed the smallest mean absolute error (0.40 D) and yielded the largest percentage of eyes within ±0.50/±1.00 D (82/91%). The next best conventional formula was the Potvin–Hill formula with a mean absolute error of 0.66 D and an ±0.50/±1.00 D accuracy of 45 and 73%, respectively. Analyzing this first cohort of post-SMILE eyes undergoing cataract surgery and IOL implantation, ray tracing showed superior predictability in IOL power calculation over empirically optimized IOL power calculation formulae that were originally intended for use after Excimer-based keratorefractive procedures.
Multicentric Carpotarsal Osteolysis Syndrome Associated Nephropathy: Novel Variants of MAFB Gene and Literature Review
Authors: Drovandi Stefania , Lugani Francesca , Boyer Olivia , La Porta Edoardo , Giordano Paolo , Hummel Aurélie , Knebelmann Bertrand , Cornet Joséphine , Baujat Genevieve , Lipska-Ziętkiewicz Beata S. , Ghiggeri Gian Marco , Caridi Gianluca , Angeletti Andrea
Published: August 2022

Multicentric carpo-tarsal osteolysis (MCTO) is a rare osteolysis syndrome mainly involving carpal and tarsal bones usually presenting in early childhood. MCTO has autosomal dominant inheritance with heterozygous mutation in the MAFB gene. The skeletal disorder is often associated with chronic kidney disease. Data on clinical characterization and best treatment option of MCTO-associated nephropathy are scarce and mostly limited to case reports. With the aim to better define the phenotype and long-term outcomes of MCTO-associated nephropathy, we launched an online survey through the Workgroup for hereditary glomerulopathies of the European Rare Kidney Disease Network (ERKNet). Overall, we collected clinical and genetic data of 54 MCTO patients, of which 42 previously described and 12 new patients. We observed a high rate of kidney involvement (70%), early age of kidney disease onset, nephrotic-range proteinuria, and a kidney survival around of 40% at long-term follow-up. Our finding confirmed the heterogeneity of clinical manifestations and widen the spectrum of phenotypes resulting from MCTO-associated nephropathy. Furthermore, we report the first case of complete remission after treatment with cyclosporine A. We demonstrated that multidisciplinary care is essential for MCTO patients and early referral to nephrologists is therefore warranted to facilitate prompt treatment.
Exosomal MicroRNA Analyses in Esophageal Squamous Cell Carcinoma Cell Lines
Authors: Kim Sora , Kim Gwang Ha , Park Su Jin , Kwon Chae Hwa , I Hoseok , Lee Moon Won , Lee Bong Eun
Published: August 2022

Exosomal miRNAs have been studied in various cancers as minimally invasive biomarkers. This study aimed to investigate the potential of exosomal microRNAs (miRNAs) as biomarkers for esophageal squamous cell carcinoma (ESCC). Exosomes were isolated from cultures of esophageal epithelial cell and ESCC cell lines using ExoDisc, and exosomal miRNAs were detected via miRNA sequencing. Of the differentially expressed 14 miRNAs, the top 2 up-regulated miRNAs (miR-205-5p and miR-429) and top 2 down-regulated miRNAs (miR-375-3p and miR-483-3p) were selected as ESCC target miRNAs. Four selected exosomal miRNAs were validated in the plasma of 20 healthy controls (HCs) and 40 ESCC patients via quantitative reverse transcription-polymerase chain reaction. The expression of plasma exosomal miR-205-5p and miR-429 significantly increased, while that of plasma exosomal miR-375-3p was significantly reduced in ESCC patients compared to that in HCs. At cut-off values of 5.04, 2.564, and 0.136, the sensitivity and specificity for the diagnosis of ESCC were 72.5% and 70.0% for miR-205-5p, 60.0% and 60.0% for miR-429, and 65.0% and 65.0% for miR-375-3p, respectively. Based on the exosomal miRNAs identified in ESCC cell lines, our study demonstrated that plasma exosomal miR-205-5p, miR-429, and miR-375-3p could serve as potential biomarkers for ESCC diagnosis.
Treatment of Secondary Aortoenteric Fistulas Following AORTIC Aneurysm Repair in a Tertiary Reference Center
Authors: Oikonomou Kyriakos , Pfister Karin , Kasprzak Piotr , Schierling Wilma , Betz Thomas , Sachsamanis Georgios
Published: August 2022

Objectives: To present our experience with various therapeutic approaches for the treatment of secondary aortoenteric fistulas following open and endovascular aortic aneurysm repair. Methods and Materials: A retrospective data analysis of patients treated for secondary aortoenteric fistulas in a single vascular institution between January 2005 and December 2018 was performed. Analyzed parameters included patients’ demographics, clinical presentation, diagnostic work-up, perioperative data and repair durability during follow-up. Results: Twenty-three patients with aortoenteric fistulas were treated in the target period. The fistulous connection was located in 21 cases (91.3%) in the duodenum and in two cases (8.7%) in the small intestine. Average time between the initial procedure and detection of the aortoenteric fistula was 69.4 ± 72.5 months. The most common presenting symptom was gastrointestinal bleeding (n = 12, 52.2%), followed by symptoms suggestive of chronic infection (n = 11, 47.8%). Open surgical repair was performed in 19 patients (bridging in 3 patients), and endovascular repair was carried out in two cases and one patient underwent a hybrid operation. One patient underwent abscess drainage due to significant comorbidities. Mean follow-up was 35.1 ± 35.5 months. In-hospital mortality and overall mortality were 43.5% (10/23) and 65.2% (15/23), respectively. Patients presenting with bleeding had a significantly higher perioperative mortality rate in comparison to patients presenting with chronic infection (66.7% (8/12) and 18.2% (2/11), respectively, p = 0.019). Patients who underwent stent-graft implantation for control of acute life-threatening bleeding showed significantly better perioperative survival in comparison to patients that were acutely treated with an open procedure (66.6%, (4/6) and 0% (0/6), respectively, p = 0.014). Perioperative mortality was also higher for ASA IV patients (71.4%, 5/7), when compared to ASA III Patients (31.2%, 5/16), although this did not reach statistical significance (p = 0.074). Conclusion: Treatment of secondary aortoenteric fistulas is associated with a high perioperative mortality rate. Patients who survive the perioperative period following open surgical repair in the absence of hemorrhagic shock show acceptable midterm results during follow-up. Stent-graft implantation for bleeding control in patients presenting with life-threatening bleeding seems to be associated with lower perioperative mortality rates.
The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review
Authors: Tsiogka Aikaterini , Kyriazopoulou Maria , Kontochristopoulos George , Nicolaidou Electra , Stratigos Alexander , Rigopoulos Dimitris , Gregoriou Stamatios
Published: August 2022

In recent years, the broadening understanding of the pathogenesis of atopic dermatitis (AD) has led to the development of novel therapeutic molecules, that target core inflammatory components of the disease. The Janus kinase (JAK)/signal transducer and activation of transcription (STAT) pathway constitutes the principal signaling cascade for a large number of cytokines and growth factors and is involved in intracellular signal transduction and subsequent regulation of gene transcription. Current knowledge suggests that the robust activation of the T-helper (Th)-2 [interleukin (IL)-4, IL-5, IL-13, IL-31] and Th22 (IL-22) immune responses in both skin and serum plays a pivotal role in the immunopathogenesis of AD especially at the acute stage, followed by a variable degree of Th1 (interferon-γ, tumor necrosis factor alpha) and Th17 (IL-17) activation in chronic disease. Of note, most of the aforementioned inflammatory cytokines utilize the JAK/STAT pathway for downstream signal transduction, explaining the emerging role of JAK inhibitors in the therapeutic armamentarium of AD. The present systematic review aims to discuss the involvement of JAK/STAT pathway in the pathogenesis of AD and summarize the clinical data available on the efficacy and safety of JAK inhibitors which have been used in the treatment of AD thus far.
Corneal Disease & Transplantation
Authors: Coco Giulia , Romano Vito
Published: August 2022

Corneal diseases represent the third leading cause of blindness worldwide, and corneal transplantation, which aims at restoring corneal clarity and vision, is the most frequently performed transplant worldwide [...]
Parasomnias and Disruptive Sleep-Related Disorders: Insights from Local Sleep Findings
Authors: Scarpelli Serena , Alfonsi Valentina , Gorgoni Maurizio
Published: August 2022

Parasomnias are sleep disorders that involve abnormal behaviors, emotional experiences, perceptions, and dream activity, occurring during specific sleep stages or sleep–wake transitions [...]
An Artificial Neural Network Model for the Prediction of Perioperative Blood Transfusion in Adult Spinal Deformity Surgery
Authors: De la Garza Ramos Rafael , Hamad Mousa K. , Ryvlin Jessica , Krol Oscar , Passias Peter G. , Fourman Mitchell S. , Shin John H. , Yanamadala Vijay , Gelfand Yaroslav , Murthy Saikiran , Yassari Reza
Published: August 2022

Prediction of blood transfusion after adult spinal deformity (ASD) surgery can identify at-risk patients and potentially reduce its utilization and the complications associated with it. The use of artificial neural networks (ANNs) offers the potential for high predictive capability. A total of 1173 patients who underwent surgery for ASD were identified in the 2017–2019 NSQIP databases. The data were split into 70% training and 30% testing cohorts. Eighteen patient and operative variables were used. The outcome variable was receiving RBC transfusion intraoperatively or within 72 h after surgery. The model was assessed by its sensitivity, positive predictive value, F1-score, accuracy (ACC), and area under the curve (AUROC). Average patient age was 56 years and 63% were female. Pelvic fixation was performed in 21.3% of patients and three-column osteotomies in 19.5% of cases. The transfusion rate was 50.0% (586/1173 patients). The best model showed an overall ACC of 81% and 77% on the training and testing data, respectively. On the testing data, the sensitivity was 80%, the positive predictive value 76%, and the F1-score was 78%. The AUROC was 0.84. ANNs may allow the identification of at-risk patients, potentially decrease the risk of transfusion via strategic planning, and improve resource allocation.
Defining the Impact of Social Drivers on Health Outcomes for People with Inherited Bleeding Disorders
Authors: Lopez Karina , Norris Keri , Hardy Marci , Valentino Leonard A.
Published: August 2022

The ways in which the social drivers of health, also known as the social determinants of health (SDOH), affect health outcomes for people with inherited bleeding disorders (PwIBDs) is unclear. This systematic review of the published literature examines the impact of SDOH on health outcomes in PwIBDs. Articles that included the following parameters in PubMed informed this study: published in English between 2011–2021; available in free full text; study population diagnosed with an inherited bleeding disorder; and study measured at least one of the clinical/non-clinical outcome measures: bleeding frequency, chronic pain, mortality, quality of life (QOL), and/or cost. The main findings from the 13 included articles emphasized the unmet need for reducing the economic burden with sustainable population health strategies and treatment options for PwIBDs. Rural location was also a significant contributor to both delayed diagnosis and decreased access to care. Furthermore, the need for a multidisciplinary comprehensive care team to address physical, psychosocial, and emotional needs of PwIBDs was raised as a priority target in the desire for equitable and optimal health. This systematic literature review suggests that the SDOH are associated with inferior health outcomes and may influence the clinical progression of inherited bleeding disorders.
Back to the Future with Osteotomies around the Hip
Authors: Ahmad Sufian S. , Windhagen Henning , Khanduja Vikas
Published: August 2022

If we were to look back at the history of orthopedics only two generations ago, the intertrochanteric osteotomy was a well-established procedure for the treatment of osteoarthritis of the hip [...]
Relationship between Serum Ferritin and Outcomes in β-Thalassemia: A Systematic Literature Review
Authors: Shah Farrukh , Huey Krystal , Deshpande Sohan , Turner Monica , Chitnis Madhura , Schiller Emma , Yucel Aylin , Moro Bueno Luciana , Oliva Esther Natalie
Published: August 2022

Among the difficulties of living with β-thalassemia, patients frequently require blood transfusions and experience iron overload. As serum ferritin (SF) provides an indication of potential iron overload, we conducted a systematic literature review (SLR) to assess whether SF levels are associated with clinical and economic burden and patient-reported outcomes (PROs). The SLR was conducted on 23 April 2020 and followed by analysis of the literature. Dual-screening was performed at the title, abstract, and full-text levels using predefined inclusion and exclusion criteria. Ten studies identified by the SLR were eligible for inclusion in the analysis. Seven studies were conducted in Europe, and most were prospective or retrospective in design. The patient populations had a median age of 20.7–42.6 years, with a percentage of men of 38–80%. Sparse data were found on the correlation between SF levels and mortality, and hepatic, skeletal, and cardiac complications; however, in general, higher SF levels were associated with worsened outcomes. The bulk of the evidence reported on the significant association between higher SF levels and endocrine dysfunction in its many presentations, including a 14-fold increase in the risk of diabetes for patients with persistently elevated SF levels. No studies reporting data on PROs or economic burden were identified by the SLR. SF levels provide another option for prognostic assessment to predict a range of clinical outcomes in patients with β-thalassemia.
Salvage Radiotherapy Plus Androgen Deprivation Therapy for High-Risk Prostate Cancer with Biochemical Failure after High-Intensity Focused Ultrasound as Primary Treatment
Authors: Huang Ying-Che , Kang Chih-Hsiung , Lee Wei-Chia , Cheng Yuan-Tso , Chuang Yao-Chi , Wang Hung-Jen , Fang Fu-Min , Chiang Po-Hui
Published: August 2022

We conduct a retrospective analysis of salvage radiotherapy plus androgen deprivation therapy (SRT+ADT) for high-risk prostate cancer patients with biochemical failure after high-intensity focused ultrasound (HIFU) as the primary treatment. A total of 38 patients, who met the criteria of biochemical failure and were consecutively treated with SRT+ADT, were enrolled. All patients received intensity modulated radiotherapy with a median dose of 70 Gy to the clinical target volume. ADT was given before, during or after the course of SRT with the duration of ≦6 months (n = 14), 6–12 months (n = 12) or >12 months (n = 12). The median follow-up was 45.9 months. A total of 10 (26.3%) patients had biochemical failure after SRT+ADT. The cumulative 5-year biochemical progression free survival (b-PFS) and overall survival (OS) rate was 73.0% and 80.3%, respectively. A nadir prostate-specific antigen (nPSA) value 0.02 ng/mL was observed to predict the b-PFS in multivariate analysis. The 5-year b-PFS was 81.6% for those with nPSA < 0.02 compared with 25.0% with nPSA ≧ 0.02. The adverse effects related to SRT+ADT were mild in most cases and only three (8%) patients experienced grade 3 urinary toxicities. For high-risk prostate cancer after HIFU as primary treatment with biochemical failure, our study confirms the feasibility of SRT+ADT with high b-PFS, OS and low toxicity.
Monoclonal Antibodies in Treating Chronic Spontaneous Urticaria: New Drugs for an Old Disease
Authors: Manti Sara , Giallongo Alessandro , Papale Maria , Parisi Giuseppe Fabio , Leonardi Salvatore
Published: August 2022

Background: H1-antihistamines (H1AH) represent the current mainstay of treatment for chronic spontaneous urticaria (CSU). However, the response to H1AH is often unsatisfactory, even with increased doses. Therefore, guidelines recommend the use of omalizumab as an add-on treatment in refractory CSU. This paved the way for the investigation of targeted therapies, such as monoclonal antibodies (mAbs), in CSU. Methods: A literature review was conducted including papers published between 2009 and 2022 and ongoing trials about the efficacy and safety of mAbs as treatment for CSU. Results: Twenty-nine articles, a trial with preliminary results, and seventeen ongoing or completed clinical trials on the use of mAbs in CSU were included. Randomized controlled trials (RCTs), meta-analysis, and real-life studies have proven the effectiveness and safety of omalizumab as a third-line treatment in refractory CSU. However, a percentage of patients remain unresponsive to omalizumab. Therefore, other mAbs, targeting different pathways, have been used off-label in case series and others are under investigation in RCTs. Most of them have showed promising results. Conclusions: Omalizumab remains the best choice to treat refractory CSU. Although results from other mAbs seem to be encouraging to achieve symptom control in refractory CSU, thus improving patients’ QoL, RCTs are needed to confirm their effectiveness and safety.
Continuous Positive Airway Pressure in Elderly Patients with Severe COVID-19 Related Respiratory Failure
Authors: Ceriani Elisa , Pitino Annalisa , Radovanovic Dejan , Salvi Emanuele , Matone Maddalena , Teatini Thomas , Gidaro Antonio , Tripepi Giovanni , Santus Pierachille , Gori Mercedes , Cogliati Chiara
Published: August 2022

The elderly population represents a high percentage of patients hospitalized for COVID-19 pneumonia and severe respiratory failure, for whom CPAP may be a treatment option. The aim of this study was to describe the CPAP support modalities and to explore factors associated with CPAP failure. In this retrospective study, 110 consecutive patients aged ≥ 75 years were enrolled. Median frailty score, baseline partial arterial pressure of oxygen to fraction of inspired oxygen ratio (P/F), and respiratory rate (RR) were 5, 108, and 30 cycles/min, respectively. Of the 110 patients that began CPAP treatment, 17 patients died within 72 h from baseline, while in 2 patients, CPAP was withdrawn for clinical improvement. Thus, of the 91 patients still on CPAP at day 3, 67% of them needed continuous CPAP delivery. Patients with RR ≥ 30 and with frailty score ≥ 5 had an odds ratio of continuous CPAP needing of 3 and 4, respectively. Patients unable to tolerate CPAP-free periods demonstrated higher mortality risk as compared to those able to tolerate intermittent CPAP (OR: 6.04, 95% CI 2.38–16.46, p < 0.001). The overall in-hospital mortality was 63.6%. Delirium occurred in 59.1%, with a mortality rate in this subgroup of 83.1%. In a time-varying Cox model, the hazard ratio of death was 2.9 in patients with baseline RR ≥ 30 cycle/min, 2.4 in those with baseline P/F < 100. In the same model, the hazard ratio of death was 20 in patients with delirium and a frailty score < 5 and 8.8 in those without delirium and with frailty ≥ 5, indicating a competitive effect between these two variables on the death risk. Conclusions: Respiratory impairment, frailty, and delirium predict treatment failure, with the latter two factors demonstrating a competitive effect on mortality risk. CPAP support may represent a feasible therapeutic option in elderly patients, although chances of a therapeutic benefit are markedly reduced in case of severe respiratory impairment, very frail baseline condition or delirium occurrence.
Role of Iron and Iron Overload in the Pathogenesis of Invasive Fungal Infections in Patients with Hematological Malignancies
Authors: Valković Toni , Damić Marija Stanić
Published: August 2022

Iron is an essential trace metal necessary for the reproduction and survival of fungal pathogens. The latter have developed various mechanisms to acquire iron from their mammalian hosts, with whom they participate in a continuous struggle for dominance over iron. Invasive fungal infections are an important problem in the treatment of patients with hematological malignancies, and they are associated with significant morbidity and mortality. The diagnosis of invasive clinical infections in these patients is complex, and the treatment, which must occur as early as possible, is difficult. There are several studies that have shown a possible link between iron overload and an increased susceptibility to infections. This link is also relevant for patients with hematological malignancies and for those treated with allogeneic hematopoietic stem cell transplantation. The role of iron and its metabolism in the virulence and pathogenesis of various invasive fungal infections is intriguing, and so far, there is some evidence linking invasive fungal infections to iron or iron overload. Clarifying the possible association of iron and iron overload with susceptibility to invasive fungal infections could be important for a better prevention and treatment of these infections in patients with hematological malignancies.
Efficacy and Safety of JAK Inhibitors for Rheumatoid Arthritis: A Meta-Analysis
Authors: Wang Faping , Tang Xiaoju , Zhu Min , Mao Hui , Wan Huajing , Luo Fengming
Published: August 2022

Background: More and more trials have been conducted. We aimed to assess the efficacy and safety of different JAKinibs in RA. Methods: A systematic search of randomized controlled trials (RCTs) with JAKinib treatment in RA published in the Medline, Embase, and Cochrane databases up to May 2021 was performed. Results: 37 trials involving 15,174 patients were identified. Pooled analysis revealed that JAKinibs were associated with significant therapeutic improvement in RA patients as determined by ACR20 (RR = 2.03, 95% CI: 1.85 to 2.28) and HAQ-DI (MD = −0.31, 95% CI: −0.33 to −0.28) over placebo. Compared to placebo, JAKinib treatment was also associated with more adverse events (RR = 1.10, p < 0.001; RR = 1.29, p < 0.001; RR = 1.59, p = 0.02). Baricitinib and upadacitinib were related to more frequent adverse events (RR = 1.10; 95% CI: 1.01, 1.21; RR = 1.19; 95% CI: 1.11, 1.28) and infection (RR = 1.22; 95% CI: 1.09, 1.37; RR = 1.38; 95% CI: 1.22, 1.56), whereas only baricitinib was associated with more herpes zoster (RR = 3.15; 95% CI: 1.19, 8.33). Conclusions: JAKinibs were superior to placebo for improving signs, symptoms, and health-related quality of life in RA patients at short term, whereas the overall risk of adverse events and infections were greater with baricitinib and upadacitinib, and a higher risk of herpes zoster was only associated with baricitinib. More trials are needed to investigate the long-term safety.
The Optimal Strategy of Dual Antiplatelet Therapy after Percutaneous Coronary Intervention with Drug-Eluting Stent
Authors: Hu Mengjin , Gao Xiaojin , Yang Jingang , Yang Yuejin
Published: August 2022

Objective: To test the optimal strategy of dual antiplatelet therapy (DAPT) after implantation of drug-eluting stents (DESs) according to specific DAPT time and subsequent monotherapy. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, and Web of Science to identify randomized controlled trials (RCTs). Six DAPT strategies were compared: 1-month DAPT followed by P2Y12 inhibitor monotherapy, 3-month DAPT followed by P2Y12 inhibitor monotherapy, 3-month DAPT followed by aspirin monotherapy, 6-month DAPT followed by aspirin monotherapy, 12-month DAPT, and >12-month DAPT. Pooled odd ratios (ORs) with 95% credible intervals (CrIs) were calculated to summarize the effect of each strategy tested. Results: We identified 24 RCTs containing 81,405 patients. In comparison with 12-month DAPT, 3-month DAPT followed by P2Y12 inhibitor monotherapy reduced net clinical events (OR: 0.72; CrI: 0.55–0.94). Major bleeding (OR: 0.57; CrI: 0.34–1.00) was marginally decreased without impact on ischemic events (OR: 0.93; CrI: 0.68–1.29). Moreover, the benefits of 3-month DAPT (P2Y12 inhibitor) were consistent for male patients with acute coronary disease, young age, complex lesion, single-vessel disease, low body mass index, and without diabetes. Although >12-month DAPT was associated with a lower risk of myocardial infarction (OR: 0.67; CrI: 0.51–0.93), the risk of major bleeding (OR: 1.70; CrI: 1.10–2.70) was increased. Conclusion: Among patients treated with DESs, 3-month DAPT followed by P2Y12 inhibitor monotherapy may be the optimal antiplatelet strategy, while DAPT beyond 1 year reduces myocardial infarction at the expense of increased major bleeding.