bluuebunny/crossref_metadata_2025 huggingface dataset:
A Proximity Complementation Assay to Identify Small Molecules That Enhance the Traffic of ABCA4 Misfolding Variants
Authors: Piccolo Davide , Zarouchlioti Christina , Bellingham James , Guarascio Rosellina , Ziaka Kalliopi , Molday Robert S. , Cheetham Michael E.
Published: April 2024

ABCA4-related retinopathy is the most common inherited Mendelian eye disorder worldwide, caused by biallelic variants in the ATP-binding cassette transporter ABCA4. To date, over 2200 ABCA4 variants have been identified, including missense, nonsense, indels, splice site and deep intronic defects. Notably, more than 60% are missense variants that can lead to protein misfolding, mistrafficking and degradation. Currently no approved therapies target ABCA4. In this study, we demonstrate that ABCA4 misfolding variants are temperature-sensitive and reduced temperature growth (30 °C) improves their traffic to the plasma membrane, suggesting the folding of these variants could be rescuable. Consequently, an in vitro platform was developed for the rapid and robust detection of ABCA4 traffic to the plasma membrane in transiently transfected cells. The system was used to assess selected candidate small molecules that were reported to improve the folding or traffic of other ABC transporters. Two candidates, 4-PBA and AICAR, were identified and validated for their ability to enhance both wild-type ABCA4 and variant trafficking to the cell surface in cell culture. We envision that this platform could serve as a primary screen for more sophisticated in vitro testing, enabling the discovery of breakthrough agents to rescue ABCA4 protein defects and mitigate ABCA4-related retinopathy.
Aryl Hydrocarbon Receptor Signalling in the Control of Gut Inflammation
Authors: Marafini Irene , Monteleone Ivan , Laudisi Federica , Monteleone Giovanni
Published: April 2024

Aryl hydrocarbon receptor (AHR), a transcription factor activated by many natural and synthetic ligands, represents an important mediator of the interplay between the environment and the host’s immune responses. In a healthy gut, AHR activation promotes tolerogenic signals, which help maintain mucosal homeostasis. AHR expression is defective in the inflamed gut of patients with inflammatory bowel diseases (IBD), where decreased AHR signaling is supposed to contribute to amplifying the gut tissue’s destructive immune–inflammatory responses. We here review the evidence supporting the role of AHR in controlling the “physiological” intestinal inflammation and summarize the data about the therapeutic effects of AHR activators, both in preclinical mouse models of colitis and in patients with IBD.
Exploring the Anticancer Potential of Semisynthetic Derivatives of 7α-Acetoxy-6β-hydroxyroyleanone from Plectranthus sp.: An In Silico Approach
Authors: Merecz-Sadowska Anna , Isca Vera M. S. , Sitarek Przemysław , Kowalczyk Tomasz , Małecka Magdalena , Zajdel Karolina , Zielińska-Bliźniewska Hanna , Jęcek Mariusz , Rijo Patricia , Zajdel Radosław
Published: April 2024

The diterpene 7α-acetoxy-6β-hydroxyroyleanone isolated from Plectranthus grandidentatus demonstrates promising antibacterial, anti-inflammatory and anticancer properties. However, its bioactivity may be enhanced via strategic structural modifications of such natural products through semisynthesis. The anticancer potential of 7α-acetoxy-6β-hydroxyroyleanone and five derivatives was analyzed in silico via the prediction of chemicals absorption, distribution, metabolism, excretion, and toxicity (ADMET), quantum mechanical calculations, molecular docking and molecular dynamic simulation. The protein targets included regulators of apoptosis and cell proliferation. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Derivatives 7α-acetoxy-6β-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6β-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone achieved high predicted binding affinities towards their respective protein panels, with stable molecular dynamics trajectories. Both compounds demonstrated favorable ADMET parameters and toxicity profiles. Their stability and reactivity were confirmed via geometry optimization. Network analysis revealed their involvement in cancer-related pathways. Our findings justify the inclusion of 7α-acetoxy-6β-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6β-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone in in vitro analyses as prospective anticancer agents. Our binding mode analysis and stability simulations indicate their potential as selective inhibitors. The data will guide studies into their structure optimization, enhancing efficacy and drug-likeness.
The Pathophysiological, Genetic, and Hormonal Changes in Preeclampsia: A Systematic Review of the Molecular Mechanisms
Authors: Chiang Yi-Ting , Seow Kok-Min , Chen Kuo-Hu
Published: April 2024

Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal tissues and in circulation, acts as a mechanistic link between placental dysfunction and maternal complications in the two-stage model of preeclampsia. Hormones, complements, and cytokines play pivotal roles in the pathophysiology, influencing immune responses, arterial remodeling, and endothelial function. Also, soluble HLA-G, involved in maternal–fetal immune tolerance, is reduced in preeclampsia. Hypoxia-inducible factor 1-alpha (Hif-α) dysregulation leads to placental abnormalities and preeclampsia-like symptoms. Alterations in matrix metalloproteinases (MMPs), endothelins (ETs), chemokines, and cytokines contribute to defective trophoblast invasion, endothelial dysfunction, and inflammation. Preeclampsia’s genetic complexity includes circRNAs, miRNAs, and lncRNAs. CircRNA_06354 is linked to early-onset preeclampsia by influencing trophoblast invasion via the hsa-miR-92a-3p/VEGF-A pathway. The dysregulation of C19MC, especially miR-519d and miR-517-5p, affects trophoblast function. Additionally, lncRNAs like IGFBP1 and EGFR-AS1, along with protein-coding genes, impact trophoblast regulation and angiogenesis, influencing both preeclampsia and fetal growth. Besides aberrations in CD31+ cells, other potential biomarkers such as MMPs, soluble HLA-G, and hCG hold promise for predicting preeclampsia and its complications. Therapeutic interventions targeting factors such as peroxisome PPAR-γ and endothelin receptors show potential in mitigating preeclampsia-related complications. In conclusion, preeclampsia is a complex disorder with a multifactorial etiology and pathogenesis. Fetal microchimerism, hormones, complements, and cytokines contribute to placental and endothelial dysfunction with inflammation. Identifying novel biomarkers and therapeutic targets offers promise for early diagnosis and effective management, ultimately reducing maternal and fetal morbidity and mortality. However, further research is warranted to translate these findings into clinical practice and enhance outcomes for at-risk women.
Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer
Authors: Zafra Juan , Onieva Juan Luis , Oliver Javier , Garrido-Barros María , González-Hernández Andrea , Martínez-Gálvez Beatriz , Román Alicia , Ordóñez-Marmolejo Rafael , Pérez-Ruiz Elisabeth , Benítez José Carlos , Mesas Andrés , Vera Andrés , Chicas-Sett Rodolfo , Rueda-Domínguez Antonio , Barragán Isabel
Published: April 2024

Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)—complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease.
Ferroptosis, Inflammation, and Microbiome Alterations in the Intestine in the Göttingen Minipig Model of Hematopoietic-Acute Radiation Syndrome
Authors: Horseman Timothy , Rittase W. Bradley , Slaven John E. , Bradfield Dmitry T. , Frank Andrew M. , Anderson Joseph A. , Hays Evelyn C. , Ott Andrew C. , Thomas Anjali E. , Huppmann Alison R. , Lee Sang-Ho , Burmeister David M. , Day Regina M.
Published: April 2024

Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril’s effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42–0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI.
Profile of Lipoprotein Subclasses in Chinese Primary Open-Angle Glaucoma Patients
Authors: Fu Changzhen , Xu Jianming , Chen Shao-Lang , Chen Chong-Bo , Liang Jia-Jian , Liu Zibo , Huang Chukai , Wu Zhenggen , Ng Tsz Kin , Zhang Mingzhi , Liu Qingping
Published: April 2024

To investigate the plasma lipoprotein subclasses in patients with primary open-angle glaucoma (POAG), a total of 20 Chinese POAG patients on intraocular pressure (IOP)-lowering treatment and 20 age-matched control subjects were recruited. Based on the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), the study subjects were divided into elevated- and normal-level subgroups. The plasma lipoprotein, lipoprotein subclasses, and oxidized LDL (oxLDL) levels were quantitatively measured. The discrimination potential of the lipoproteins was evaluated using the area under the receiver operating characteristic curve (AUC), and their correlation with clinical parameters was also evaluated. Compared to the control subjects with elevated TC and/or LDL-C levels, the levels of TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL), LDL subclass LDL3 and small dense LDL (sdLDL), and oxLDL were significantly higher in POAG patients with elevated TC and/or LDL-C levels. No differences in any lipoproteins or the subclasses were found between the POAG patients and control subjects with normal TC and LDL-C levels. Moderate-to-good performance of TC, LDL-C, non-HDL, LDL3, sdLDL, and oxLDL was found in discriminating between the POAG patients and control subjects with elevated TC and/or LDL-C levels (AUC: 0.710–0.950). Significant negative correlations between LDL3 and sdLDL with retinal nerve fiber layer (RNFL) thickness in the superior quadrant and between LDL3 and average RNFL thickness were observed in POAG patients with elevated TC and/or LDL-C levels. This study revealed a significant elevation of plasma lipoproteins, especially the LDL subclasses, in POAG patients with elevated TC and/or LDL-C levels, providing insights on monitoring specific lipoproteins in POAG patients with elevated TC and/or LDL-C.
Developmental, Physiological and Phylogenetic Perspectives on the Expression and Regulation of Myosin Heavy Chains in Craniofacial Muscles
Authors: Hoh Joseph Foon Yoong
Published: April 2024

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of sarcomeric myosin heavy chains (MyHCs) that they express and changes in MyHC expression during phylogeny. Myogenic progenitors from the mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles (EOMs) express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB (nmMyH IIB). They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC and cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift toward expressing slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs that they express. Thyroid hormone shifts MyHC 2A toward 2B in jaw muscles, laryngeal muscles and possibly extraocular muscles. This review highlights the fact that the pattern of myosin expression in mammalian craniofacial muscles is principally influenced by the complex interplay of cell lineages, neural impulse patterns, thyroid and other hormones, functional demands and body mass. In these respects, craniofacial muscles are similar to limb muscles, but they differ radically in the types of cell lineage and the nature of their functional demands.
Lipid Peroxidation-Related Redox Signaling in Osteosarcoma
Authors: Borović Šunjić Suzana , Jaganjac Morana , Vlainić Josipa , Halasz Mirna , Žarković Neven
Published: April 2024

Oxidative stress and lipid peroxidation play important roles in numerous physiological and pathological processes, while the bioactive products of lipid peroxidation, lipid hydroperoxides and reactive aldehydes, act as important mediators of redox signaling in normal and malignant cells. Many types of cancer, including osteosarcoma, express altered redox signaling pathways. Such redox signaling pathways protect cancer cells from the cytotoxic effects of oxidative stress, thus supporting malignant transformation, and eventually from cytotoxic anticancer therapies associated with oxidative stress. In this review, we aim to explore the status of lipid peroxidation in osteosarcoma and highlight the involvement of lipid peroxidation products in redox signaling pathways, including the involvement of lipid peroxidation in osteosarcoma therapies.
Role of Dermal Factors Involved in Regulating the Melanin and Melanogenesis of Mammalian Melanocytes in Normal and Abnormal Skin
Authors: Hirobe Tomohisa
Published: April 2024

Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been fully investigated and the molecular analysis has been performed. Moreover, the role of paracrine factors derived from epidermis has also been studied. However, the role of dermis has not been fully studied. Thus, in this review, dermis-derived factors including soluble and insoluble components were overviewed and discussed in normal and abnormal circumstances. Dermal factors play an important role in the regulation of melanogenesis in the normal and abnormal mammalian skin.
Combined Analysis of Metabolomics and Biochemical Changes Reveals the Nutritional and Functional Characteristics of Red Palm Weevil Rhynchophus ferrugineus (Coleoptera: Curculionidae) Larvae at Different Developmental Stages
Authors: Chen Mengran , Kan Jintao , Zhang Yufeng , Zhao Jinhao , Lv Chaojun , Zhong Baozhu , Li Chaoxu , Qin Weiquan
Published: April 2024

In this study, the changes in the conventional nutrient and mineral compositions as well as the metabolomics characteristics of the red palm weevil (RPW) Rhynchophus ferrugineus Olivier (Curculionidae: Coleoptera) larvae at early (EL), middle (ML) and old (OL) developmental stages were investigated. Results showed that the EL and ML had the highest content of protein (53.87 g/100 g dw) and fat (67.95 g/100 g), respectively, and three kinds of RPW larvae were all found to be rich in unsaturated fatty acids (52.17–53.12%), potassium (5707.12–15,865.04 mg/kg) and phosphorus (2123.87–7728.31 mg/kg). In addition, their protein contained 17 amino acids with the largest proportion of glutamate. A total of 424 metabolites mainly including lipids and lipid-like molecules, organic acids and their derivatives, organic heterocycle compounds, alkaloids and their derivatives, etc. were identified in the RPW larvae. There was a significant enrichment in the ABC transport, citrate cycle (TCA cycle), aminoacyl-tRNA biosynthesis, and mTOR signaling pathways as the larvae grow according to the analysis results of the metabolic pathways of differential metabolites. The water extract of EL exhibited relatively higher hydroxyl, 2,2-diphenyl-1-pyrroline hydrochloride (DPPH) and 2,2’-azobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging ability with the EC50 values of 1.12 mg/mL, 11.23 mg/mL, and 2.52 mg/mL, respectively. These results contribute to a better understanding of the compositional changes of the RPW larvae during its life cycle and provide a theoretical grounding for its deep processing and high-value utilization.
Atherosclerosis Residual Lipid Risk-Overview of Existing and Future Pharmacotherapies
Authors: Omari Muntaser , Alkhalil Mohammad
Published: April 2024

Patients with atherosclerotic disease remain at increased risk of future events despite receiving optimal medical treatment. This residual risk is widely heterogeneous, but lipoprotein particles and their content play a major role in determining future cardiovascular events. Beyond low-density lipoprotein cholesterol (LDL-c), other lipoprotein particles have not demonstrated similar contribution to the progression of atherosclerosis. Statins, ezetimibe, and more recently, proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors and bempedoic acid have confirmed the causal role of LDL-c in the development of atherosclerosis. Data on high-density lipoprotein cholesterol (HDL-c) suggested a possible causal role for atherosclerosis; nonetheless, HDL-c-raising treatments, including cholesteryl-ester transfer protein (CETP) inhibitors and niacin, failed to confirm this relationship. On the other hand, mendelian randomisation revealed that triglycerides are more implicated in the development of atherosclerosis. Although the use of highly purified eicosapentaenoic acid (EPA) was associated with a reduction in the risk of adverse cardiovascular events, this beneficial effect did not correlate with the reduction in triglycerides level and has not been consistent across large phase 3 trials. Moreover, other triglyceride-lowering treatments, such as fibrates, were not associated with a reduction in future cardiovascular risk. Studies assessing agents targeting angiopoietin-like 3 (lipoprotein lipase inhibitor) and apolipoprotein C3 antisense will add further insights into the role of triglycerides in atherosclerosis. Emerging lipid markers such as lipoprotein (a) and cholesterol efflux capacity may have a direct role in the progression of atherosclerosis. Targeting these biomarkers may provide incremental benefits in reducing cardiovascular risk when added to optimal medical treatment. This Review aims to assess available therapies for current lipid biomarkers and provide mechanistic insight into their potential role in reducing future cardiovascular risk.
Photon-Counting Detector Computed Tomography (PCD-CT): A New Era for Cardiovascular Imaging? Current Status and Future Outlooks
Authors: Lacaita Pietro G. , Luger Anna , Troger Felix , Widmann Gerlig , Feuchtner Gudrun M.
Published: April 2024

Photon-counting detector computed tomography (PCD-CT) represents a revolutionary new generation of computed tomography (CT) for the imaging of patients with cardiovascular diseases. Since its commercial market introduction in 2021, numerous studies have identified advantages of this new technology in the field of cardiovascular imaging, including improved image quality due to an enhanced contrast-to-noise ratio, superior spatial resolution, reduced artifacts, and a reduced radiation dose. The aim of this narrative review was to discuss the current scientific literature, and to find answers to the question of whether PCD-CT has yet led to a true step-change and significant progress in cardiovascular imaging.
Fasting Triglycerides in the Upper Normal Range Are Independently Associated with an Increased Risk of Diabetes Mortality in a Large Representative US Population
Authors: Wang Yutang
Published: April 2024

The association between normal-range triglyceride levels and diabetes mortality remains unclear. This cohort study aimed to elucidate this relationship by examining 19,010 US adult participants with fasting serum triglycerides below 150 mg/dL. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). Participants were followed up for a mean of 15.3 years, during which 342 diabetes deaths were recorded. A 1 natural log unit increase in triglycerides was associated with a 57% higher risk of diabetes mortality (adjusted HR, 1.57; 95% CI, 1.04–2.38). Comparable results were obtained when triglycerides were analyzed in quartiles. Receiver operating characteristic curve analysis identified an optimal triglyceride cutoff of 94.5 mg/dL for diabetes mortality; individuals with triglyceride levels above this threshold faced a greater risk of diabetes mortality (adjusted HR, 1.43; 95% CI, 1.12–1.83). Further investigation revealed a positive association between normal triglyceride levels and all-cause mortality, though no association was observed between normal triglycerides and mortality from hypertension or cardiovascular disease. In conclusion, elevated triglyceride levels within the normal range were associated with an increased risk of diabetes mortality. Individuals with triglyceride levels of 95 mg/dL or higher may require vigilant monitoring for diabetes and its associated complications.
Prevalence and Clinical Significance of Intraventricular Conduction Disturbances in Hospitalized Children
Authors: Cirillo Chiara , Monda Emanuele , Esposito Raffaella , Colonna Diego , Falcone Cristina , Irrissuto Federica , Cirillo Annapaola , Fusco Adelaide , Verrillo Federica , Diana Gaetano , Rubino Marta , Caiazza Martina , Sarubbi Berardo , Limongelli Giuseppe , Russo Maria Giovanna
Published: April 2024

Introduction: Data on the prevalence and clinical significance of interventricular conduction disturbances (IVCDs) in children are scarce. While incomplete right bundle branch blocks (IRBBBs) seem to be the most frequent and benign findings, complete bundle blocks and fascicular blocks are often seen in children with congenital/acquired cardiac conditions. This study aims to delineate the prevalence and the diagnostic accuracy of IVCD in children admitted to a paediatric cardiology unit. Methods: Children admitted to the paediatric cardiology unit between January 2010 and December 2020 who had an ECG were included in the study. IVCDs were diagnosed according to standard criteria adjusted for age. Results: Three thousand nine hundred and ninety-three patients were enrolled. The median age was 3.1 years (IQR: 0.0–9.2 years), and 52.7% were males. IVCDs were present in 22.5% of the population: 17.4% of the population presented with IRBBBs, 4.8% with a complete right bundle branch block (CRBBB), 0.1% with a complete left bundle branch block (CLBBB), 0.2% with a left anterior fascicular block (LAFB) and 0.2% with a combination of CRBBB and LAFB. Also, 26% of children with congenital heart disease had an IVCD, and 18% of children with an IVCD had previous cardiac surgery. The overall sensitivity of IVCD in detecting a cardiac abnormality was 22.2%, with a specificity of 75.5%, a PPV of 83.1% and an NPV of 15.1%, but the values were higher for CLBBB and LAFB. Conclusions: IVCDs were present in one-fifth of children admitted to the cardiology unit. IRBBB was the most frequent disturbance, while CRBBB, CLBBB and fascicular blocks were much rarer, though they had a higher predictive value for cardiac abnormalities.
Validation of Perioperative Troponin Levels for Predicting Postoperative Mortality and Long-Term Survival in Patients Undergoing Surgery for Hepatobiliary and Pancreatic Cancer
Authors: Magouliotis Dimitrios E. , Tatsios Evangelos , Giamouzis Grigorios , Samara Athina A. , Xanthopoulos Andrew , Briasoulis Alexandros , Skoularigis John , Athanasiou Thanos , Bareka Metaxia , Kourek Christos , Zacharoulis Dimitris
Published: April 2024

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020–2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.
The Role of Heparin in Postural Orthostatic Tachycardia Syndrome and Other Post-Acute Sequelae of COVID-19
Authors: Gómez-Moyano Elisabeth , Pavón-Morón Javier , Rodríguez-Capitán Jorge , Bardán-Rebollar Daniel , Ramos-Carrera Teresa , Villalobos-Sánchez Aurora , Pérez de Pedro Iván , Ruiz-García Francisco , Mora-Robles Javier , López-Sampalo Almudena , Pérez-Velasco Miguel , Bernal-López Maria-Rosa , Gómez-Huelgas Ricardo , Jiménez-Navarro Manuel , Romero-Cuevas Miguel , Costa Francesco , Trenas Alicia , Pérez-Belmonte Luis
Published: April 2024

The therapeutic management and short-term consequences of the coronavirus disease 2019 (COVID-19) are well known. However, COVID-19 post-acute sequelae are less known and represent a public health problem worldwide. Patients with COVID-19 who present post-acute sequelae may display immune dysregulation, a procoagulant state, and persistent microvascular endotheliopathy that could trigger microvascular thrombosis. These elements have also been implicated in the physiopathology of postural orthostatic tachycardia syndrome, a frequent sequela in post-COVID-19 patients. These mechanisms, directly associated with post-acute sequelae, might determine the thrombotic consequences of COVID-19 and the need for early anticoagulation therapy. In this context, heparin has several potential benefits, including immunomodulatory, anticoagulant, antiviral, pro-endothelial, and vascular effects, that could be helpful in the treatment of COVID-19 post-acute sequelae. In this article, we review the evidence surrounding the post-acute sequelae of COVID-19 and the potential benefits of the use of heparin, with a special focus on the treatment of postural orthostatic tachycardia syndrome.
Three-Dimensional Printed Patient-Specific Vestibular Augmentation: A Case Report
Authors: Johansson Linh , Latorre Jose Luis , Liversain Margaux , Thorel Emilie , Raymond Yago , Ginebra Maria-Pau
Published: April 2024

Background: The anterior maxilla is challenging regarding aesthetic rehabilitation. Current bone augmentation techniques are complex and 3D-printed bioceramic bone grafts can simplify the intervention. Aim: A four-teeth defect in the anterior maxilla was reconstructed with a 3D-printed synthetic patient-specific bone graft in a staged approach for dental implant delivery. Methods: The bone graft was designed using Cone-Beam Computed Tomography (CBCT) images. The bone graft was immobilized with fixation screws. Bone augmentation was measured on CBCT images at 11 days and 8 and 13 months post-surgery. A biopsy sample was retrieved at reentry (10 months post-augmentation) and evaluated by histological and micro-computed tomography assessments. The definitive prosthesis was delivered 5 months post-reentry and the patient attended a visit 1-year post-loading. Results: A total bone width of 8 mm was achieved (3.7 mm horizontal bone gain). The reconstructed bone remained stable during the healing period and was sufficient for placing two dental implants (with an insertion torque > 35 N·cm). The fractions of new bone, bone graft, and soft tissue in the biopsy were 40.77%, 41.51%, and 17.72%, respectively. The histological assessment showed no signs of encapsulation, and mature bone was found in close contact with the graft, indicating adequate biocompatibility and suggesting osteoconductive properties of the graft. At 1-year post-loading, the soft tissues were healthy, and the dental implants were stable. Conclusions: The anterior maxilla’s horizontal ridge can be reconstructed using a synthetic patient-specific 3D-printed bone graft in a staged approach for implant placement. The dental implants were stable and successful 1-year post-loading.
A Novel Surgical Treatment Management Algorithm for Elbow Posterolateral Rotatory Instability (PLRI) Based on the Common Extensor Origin Integrity
Authors: Koukos Christos , Kotsapas Michail , Sidiropoulos Konstantinos , Traverso Aurélien , Bilsel Kerem , Montoya Fredy , Arrigoni Paolo
Published: April 2024

Background: Here, we introduce a comprehensive treatment algorithm for posterolateral rotatory instability (PLRI) of the elbow, a condition affecting elbow mobility. We outline a diagnostic approach and a novel surgical management plan through the arthroscopic surgeon’s point of view. Methods: The central focus of this management approach is the integrity of common extensor origin (CEO). High clinical suspicion must be evident to diagnose PLRI. Special clinical and imaging tests can confirm PLRI but sometimes the final confirmation is established during the arthroscopic treatment. The most appropriate treatment is determined by the degree of CEO integrity. Results: The treatment strategy varies with the CEO’s condition: intact or minor tears require arthroscopic lateral collateral ligament imbrication, while extensive tears may need plication reinforced with imbrication or, in cases of retraction, a triceps tendon autograft reconstruction of the lateral ulnar collateral ligament alongside CEO repair. These approaches aim to manage residual instability and are complemented using a tailored rehabilitation protocol to optimize functional outcomes. Conclusion: PLRI is a unique clinical condition and should be treated likewise. This algorithm offers valuable insights for diagnosing and treating PLRI, enhancing therapeutic decision-making.
Vascular Access Perception and Quality of Life of Haemodialysis Patients
Authors: Sikora Kamil , Zwolak Agnieszka , Łuczyk Robert Jan , Wawryniuk Agnieszka , Łuczyk Marta
Published: April 2024

Background: Patient quality of life is widely used as a non-clinical determinant of care. For patients undergoing hemodialysis, vascular access is vital to the delivery of hemodialysis and its function may affect not only the clinical outcome of treatment but also the overall quality of life of the patient, highlighting the need for increased efforts to improve the quality of hemodialysis vascular access care. The objective of this study was to evaluate the correlation between vascular access perception and quality of life in patients undergoing hemodialysis. Methods: A total of 202 patients with active hemodialysis vascular access were included in the study. Quality of life was assessed using the Kidney Disease Quality of Life Instrument (KDQOL™) questionnaire, while vascular access perception was evaluated using the Vascular Access Questionnaire (VAQ). Results: The study presented evidence on the influence of vascular access for hemodialysis patients on their quality of life. This impact is related to factors directly associated with vascular access, such as the type of access and the patient’s subjective evaluation of the access. Conclusions: The perception of vascular access is one of the factors that determines the quality of life of hemodialysis patients. The quality of life of hemodialysis patients decreases as the number of vascular access-related problems increases.
Influence of a Concomitant Medial Meniscus Injury on Knee Joint Function and Osteoarthritis Presence after Anterior Cruciate Ligament Reconstruction
Authors: Bayerl Darian , Moser Lukas B. , Neubauer Markus , Neugebauer Johannes , Dammerer Dietmar , Winnisch Markus , Schabus Rudolf
Published: April 2024

(1) Background: The aim of this study was to investigate how a medial meniscus injury accompanying an anterior cruciate ligament rupture affects the clinical outcome 10 years after ACL reconstruction. (2) Methods: A total of 37 patients who received anterior cruciate ligament reconstruction (ACLR) were included in this retrospective study. Two groups were analyzed at a single follow-up of 10 years: (i) “isolated (ACLR)” (n = 20) and (ii) “ACLR with medial meniscal injury” (n = 17). The following clinical scores were recorded: International Knee Documentation Committee (IKDC), the Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm Score and Tegner Activity Score. To determine the degree of osteoarthritis the Kellgren–Lawrence score was used. (3) Results: The “isolated ACLR” study group scored significantly higher (p < 0.05) on the IKDC subjective questionnaire (mean: 88.4) than the “ACLR with medial meniscus injury” group (mean: 81). The KOOS category “activities of daily living” showed significantly better results in the isolated ACLR group (p < 0.05). The “ACLR with medial meniscus injury” group had significantly higher degree of osteoarthritis (p < 0.05). No significant differences were found in all the other clinical scores. (4) Conclusions: The results of this study further indicate that patients with a concomitant medial meniscus injury have slightly more discomfort in everyday life and increased risk of developing osteoarthritis 10 years after surgery.
Robotic-Assisted Minimally Invasive Direct Coronary Artery Bypass Grafting: A Surgical Technique
Authors: Giroletti Laura , Graniero Ascanio , Agnino Alfonso
Published: April 2024

In recent years, there has been a growing interest in robotic-assisted coronary artery revascularization in Europe. Two different types of surgery can be performed using a robotic platform: RA-MIDCAB, in which the mammary artery is harvested endoscopically with robotic assistance and off-pump bypass graft is achieved under direct vision through mini thoracotomy, and TE-CAB, completely robotically performed. We started the robotic cardiac surgery program for mitral valve disease in our hospital, Humanitas Gavazzeni (Bergamo, Italy), in 2019; and in 2021, we addressed our experience with RA-MIDCAB. After a learning curve period, we have developed our technique to optimize the benefits offered by the robotic platform, tailoring strategy to individual patients, based on preoperative radiological images.
Vein of Marshall Ethanol Infusion for AF Ablation; A Review
Authors: O’Neill Louisa , De Becker Benjamin , De Smet Maarten , Francois Clara , Tavernier Rene , Duytschaever Mattias , Le Polain De Waroux Jean-Benoit , Knecht Sebastien
Published: April 2024

The outcomes of persistent atrial fibrillation (AF) ablation are modest with various adjunctive strategies beyond pulmonary vein isolation (PVI) yielding largely disappointing results in randomised controlled trials. Linear ablation is a commonly employed adjunct strategy but is limited by difficulty in achieving durable bidirectional block, particularly at the mitral isthmus. Epicardial connections play a role in AF initiation and perpetuation. The ligament of Marshall has been implicated as a source of AF triggers and is known to harbour sympathetic and parasympathetic nerve fibres that contribute to AF perpetuation. Ethanol infusion into the Vein of Marshall, a remnant of the superior vena cava and key component of the ligament of Marshall, may eliminate these AF triggers and can facilitate the ease of obtaining durable mitral isthmus block. While early trials have demonstrated the potential of Vein of Marshall ‘ethanolisation’ to reduce arrhythmia recurrence after persistent AF ablation, further randomised trials are needed to fully determine the potential long-term outcome benefits afforded by this technique.
Multidisciplinary Management of Descending Necrotizing Mediastinitis: Is Thoracoscopic Treatment Feasible?
Authors: Leonardi Beatrice , Natale Giovanni , Sagnelli Caterina , Marella Antonio , Leone Francesco , Capasso Francesca , Giorgiano Noemi Maria , Pica Davide Gerardo , Mirra Rosa , Di Filippo Vincenzo , Messina Gaetana , Vicidomini Giovanni , Motta Giovanni , Massimilla Eva Aurora , Motta Gaetano , Rendina Erino Angelo , Peritone Valentina , Andreetti Claudio , Fiorelli Alfonso , Sica Antonello
Published: April 2024

Background: Descending necrotizing mediastinitis (DNM) is a life-threatening condition, generally caused by downward dissemination of oropharyngeal infections through cervical fascial planes. Mediastinal drainage is conventionally achieved by thoracotomy, but a Video-Assisted Thoracoscopic Surgery (VATS) approach is gaining interest due to the reduced invasiveness of procedure. We aimed to evaluate the effectiveness of VATS treatment in patients with DNM. Methods: We conducted a retrospective multicenter study including patients with descending mediastinitis that underwent mediastinal drainage through VATS (VATS group) or thoracotomy (thoracotomy group), both in association with cervical drainage. Patients with mediastinitis secondary to cardiac, pulmonary, or esophageal surgery were excluded. The intergroup differences regarding surgical outcome and postoperative morbidity and mortality were compared. Results: A total of 21 patients were treated for descending mediastinitis during the study period. Cervicotomy and thoracotomy were performed in 15 patients (71%), while cervicotomy and VATS were performed in 6 patients (29%). There were no significant differences in surgical outcome, postoperative morbidity, and mortality between groups. VATS treatment was not associated with a higher complication rate. Patients in the VATS group had a shorter operative time (p = 0.016) and shorter ICU stay (p = 0.026). Conclusions: VATS treatment of DNM is safe and effective. The comparison with thoracotomy showed no significant differences in postoperative morbidity and mortality. The VATS approach is associated with a shorter operative time and ICU stay than thoracotomy.
Can Biomarkers and PET Imaging Predict Abdominal Aortic Aneurysm Growth Rate?
Authors: Bruls Samuel , Musumeci Lucia , Courtois Audrey , Hustinx Roland , Sakalihasan Sarah , Namur Gauthier , Defraigne Jean-Olivier , Sakalihasan Natzi
Published: April 2024

Background: Abdominal aortic aneurysm (AAA) is a life-threatening condition due to the risk of aneurysm growth and rupture. Biomarkers linked to AAA pathogenesis are attractive candidates for AAA diagnosis and prognosis. The aim of this study was to assess circulating biomarkers levels relationship with PET imaging positivity and their predictive value in AAA growth rate. Methods: A total of 164 patients with AAA had whole body [18F]FDG PET/CT examination and blood drawn for biomarkers analysis at inclusion. Of these, 121 patients had at least one follow-up imaging assessment for AAA progression. Median (quartiles) imaging follow-up period was 32.8 months (15.2–69.6 months). Results: At baseline, PET was visually positive in 28 (17%) patients. Among PET+ patients, female proportion was higher compared to PET−patients (respectively, n = 6, 21.4% vs. n = 11, 8.1%, p = 0.046). Biomarkers of inflammation (CRP, CCL18), of proteolytic activity (MMP9), of extracellular matrix, and calcification regulation (OPN, OPG) were all significantly increased in PET+ patients (p < 0.05). During follow-up, rapid AAA growth (increase in size ≥ 1 cm per year) was observed in 36 (29.8%) patients and several biomarkers (CRP, MMP9, OPN, and OPG) were increased in those patients compared to patients without rapid growth (p < 0.05). Conclusions: Although PET positivity at baseline was not associated with rapid growth, CRP levels showed a significant association.
Facilitating the Integrative Use of Security Knowledge Bases within a Modelling Environment
Authors: Shaked Avi
Published: April 2024

Security threat and risk assessment of systems requires the integrated use of information from multiple knowledge bases. Such use is typically carried out ad-hoc by security experts in an unstructured manner. Also, this ad-hoc use of information often lacks foundations that allow for rigorous, disciplined applications of policy enforcement and the establishment of a well-integrated body of knowledge. This hinders organisational learning as well as the maturation of the threat modelling discipline. In this article, we uncover a newly developed extension of a state-of-the-art modelling tool that allows users to integrate and curate security-related information from multiple knowledge bases. Specifically, we provide catalogues of threats and security controls based on information from CAPEC, ATT&CK, and NIST SP800-53. We demonstrate the ability to curate security information using the designed solution. We highlight the contribution to improving the communication of security information, including the systematic mapping between user-defined security guidance and information derived from knowledge bases. The solution is open source and relies on model-to-model transformations and extendable threat and security control catalogues. Accordingly, the solution allows prospective users to adapt the modelling environment to their needs as well as keep it current with respect to evolving knowledge bases.
Enhancing Sustainability in Construction: Investigating the Thermal Advantages of Fly Ash-Coated Expanded Polystyrene Lightweight Concrete
Authors: Wibowo Andi Prasetiyo , Saidani Messaoud , Khorami Morteza
Published: April 2024

This study investigates a sustainable coating method for modified expanded polystyrene (MEPS) beads to improve the thermal insulation of lightweight concrete intended for wall application. The method employed in this study is based on a novel coating technique that represents a significant advancement in modifying Expanded Polystyrene (EPS) beads for enhanced lightweight concrete. This study experimentally assessed the energy-saving capabilities of MEPS concrete in comparison to control groups of uncoated EPS beads and normal concrete by analysing early-stage temperature, thermal conductivity, specific heat capacity, heat flux, and thermal diffusivity. The thermal conductivity of MEPS concrete is approximately 40% lower than that of normal concrete, demonstrating its usefulness in enhancing insulation. The heat flux calculated for MEPS concrete is significantly reduced (approximately 35%), and it has a 20% lower specific heat capacity than ordinary concrete, indicating a reduction in energy transfer through the material and, thus, potential energy-efficiency benefits. Furthermore, the study discovered that all test objects have very low thermal diffusivity values (less than 0.5 × 10−6 m2/s), indicating a slower heat transport through the material. The sustainable coating method utilized fly ash-enhanced thermal efficiency and employed recycled materials, hence decreasing the environmental impact. MEPS concrete provides a practical option for creating sustainable and comfortable buildings through the promotion of energy-efficient wall construction. Concrete incorporating coated EPS can be a viable option for constructing walls where there is a need to balance structural integrity and adequate insulation.