bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Myocardial Infarction and Risk of Cognitive Impairment and Dementia: A Review
Authors: Thong Elizabeth Hui En , Quek Ethan J. W. , Loo Jing Hong , Yun Choi-Ying , Teo Yao Neng , Teo Yao Hao , Leow Aloysius S. T. , Li Tony Y. W. , Sharma Vijay K. , Tan Benjamin Y. Q. , Yeo Leonard L. L. , Chong Yao Feng , Chan Mark Y. , Sia Ching-Hui
Published: August 2023

Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI is associated with increased rates of CI, CI remains underreported and infrequently identified in patients with AMI. In this review, we discuss the evidence surrounding AMI and its links to dementia and CI, including pathophysiology, risk factors, management and interventions. Vascular dysregulation plays a major role in CI, with atherosclerosis, platelet activation, microinfarcts and perivascular inflammation resulting in neurovascular unit dysfunction, disordered homeostasis and a dysfunctional neurohormonal response. This subsequently affects perfusion pressure, resulting in enlarged periventricular spaces and hippocampal sclerosis. The increased platelet activation seen in coronary artery disease (CAD) can also result in inflammation and amyloid-β protein deposition which is associated with Alzheimer’s Dementia. Post-AMI, reduced blood pressure and reduced left ventricular ejection fraction can cause chronic cerebral hypoperfusion, cerebral infarction and failure of normal circulatory autoregulatory mechanisms. Patients who undergo coronary revascularization (percutaneous coronary intervention or bypass surgery) are at increased risk for post-procedure cognitive impairment, though whether this is related to the intervention itself or underlying cardiovascular risk factors is debated. Mortality rates are higher in dementia patients with AMI, and post-AMI CI is more prevalent in the elderly and in patients with post-AMI heart failure. Medical management (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) can reduce the risk of post-AMI CI; however, beta-blockers may be associated with functional decline in patients with existing CI. The early identification of those with dementia or CI who present with AMI is important, as subsequent tailoring of management strategies can potentially improve outcomes as well as guide prognosis.
Features of Protein Unfolding Transitions and Their Relation to Domain Topology Probed by Single-Molecule FRET
Authors: Bustorff Nuno , Fitter Jörg
Published: August 2023

A protein fold is defined as a structural arrangement of a secondary structure in a three-dimensional space. It would be interesting to know whether a particular fold can be assigned to certain features of the corresponding folding/unfolding transitions. To understand the underlying principles of the manifold folding transitions in more detail, single-molecule FRET is the method of choice. Taking the two-domain protein phosphoglycerate kinase (PGK) as an example, we investigated denaturant-induced unfolded states of PGK using the above method. For this purpose, different intramolecular distances within the two domains were measured. In addition to the known two-state transition, a transition with a compact folding intermediate was also identified in each of the two domains. Based on the structural homology of the domains (characterized by a Rossmann fold) and the striking similarity in the features of the measured distance changes during unfolding, clear evidence emerged that the underlying domain topology plays an important role in determining the observed structural changes.
Nab-Paclitaxel and Gemcitabine as First-Line Treatment of Metastatic Ampullary Adenocarcinoma with a Novel R-Spondin2 RNA Fusion and NTRK3 Mutation
Authors: Linscott Maryknoll P. , Markus Havell , Sennett Mackenzie , Abendroth Catherine , Yee Nelson S.
Published: August 2023

Ampullary adenocarcinoma is a rare malignancy that lacks standard systemic treatment. We describe a case of recurrent metastatic ampullary adenocarcinoma of the pancreaticobiliary subtype treated with nanoparticle albumin-bound (nab)-paclitaxel and gemcitabine as first-line treatment. This report also highlights the molecular profile of the ampullary adenocarcinoma and circulating tumor DNA (ctDNA). This is a case of pancreaticobiliary ampullary adenocarcinoma in a 67-year-old woman who initially presented with painless jaundice. Endoscopic and imaging evaluation revealed biliary ductal dilation secondary to an ampullary mass. Pathology confirmed the diagnosis of ampullary adenocarcinoma of the pancreaticobiliary subtype. She underwent surgical resection of the tumor, followed by adjuvant chemotherapy with gemcitabine and capecitabine. The tumor subsequently recurred in the liver. She received palliative chemotherapy with nab-paclitaxel and gemcitabine, resulting in an objective tumor response for 14 months. Molecular profiling of the tumor and ctDNA revealed a novel MATN2-RSPO RNA fusion and a novel NTRK3 mutation, respectively. Our report suggests that long-term durable response can be achieved in metastatic pancreaticobiliary ampullary adenocarcinoma using nab-paclitaxel and gemcitabine. Molecular profiling of the tumor identified a novel R-Spondin2 RNA fusion and NTRK3 mutation that can be potentially targeted for treatment.
Single-Cell RNA Sequencing and Microarray Analysis Reveal the Role of Lipid-Metabolism-Related Genes and Cellular Immune Infiltration in Pre-Eclampsia and Identify Novel Biomarkers for Pre-Eclampsia
Authors: Liu Yujie , Xu Borui , Fan Cuifang
Published: August 2023

Pre-eclampsia (PE) is a gestational hypertensive disorder that is characterized by hypertension and proteinuria, typically occurring after 20 weeks of gestation. Despite its global impact on pregnant women, the precise pathogenic mechanisms of PE remain unclear. Dysregulated lipid metabolism and immune cell infiltration contribute to PE development. Our study aimed to identify lipid-metabolism-related genes (LMRG-PEs) and investigate their association with immune infiltration. We utilized the “Seurat” R package for data quality control, cell clustering, and marker gene identification. The “SingleR” package enabled the matching of marker genes to specific cell types. Pseudotemporal ordering analysis was conducted using the “Monocle” package. Weighted correlation network analysis (WGCNA), gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA) approaches were employed to explore lipid-metabolism-related genes, while potential targeted drugs were predicted using the drug–gene interaction database (DGIdb). Hub gene expression was validated through RT–qPCR. By analyzing single-cell RNA sequencing data, we identified and classified 20 cell clusters into 5 distinct types. Differential gene expression analysis revealed 186 DEGs. WGCNA identified 9 critical modules and 265 genes significantly associated with PE diagnosis, emphasizing the importance of the core genes PLA2G7 and PTGS2. RT–qPCR confirmed the significantly decreased expression of PLA2G7 and PTGS2 in PE patient tissues. These findings offer valuable insights into the molecular mechanisms of PE, particularly those involving lipid metabolism and immune infiltration. The identified hub genes have potential as therapeutic targets and biomarkers for future research and clinical applications.
Editorial of the Special Issue: Recent Advances in Understanding of the Role of Synuclein Family Members in Health and Disease
Authors: Ninkina Natalia , Kukharsky Michail S.
Published: August 2023

Extensive studies of α-synuclein function and dysfunction revealed its involvement in multiple normal and aberrant molecular processes and, consequently, numerous and diverse effects on the neuronal cell biology [...]
Metformin Protects Rat Skeletal Muscle from Physical Exercise-Induced Injury
Authors: Abbadessa Giuliana , Maniscalco Eleonora , Grasso Loredana , Popara Jasmin , Di Scipio Federica , Franco Francesco , Mancardi Daniele , Pigozzi Fabio , Borrione Paolo , Berta Giovanni Nicolao , Racca Silvia
Published: August 2023

Metformin (Met) is a drug commonly prescribed in type 2 diabetes mellitus. Its efficacy is due to the suppression of hepatic gluconeogenesis, enhancement of peripheral glucose uptake and lower glucose absorption by the intestine. Recent studies have reported Met efficacy in other clinical applications, such as age-related diseases. Despite the wide clinical use of Met, its mechanism of action on muscle and its effect on muscle performance are unclear. We investigated the effects of Met combined with training on physical performance (PP) in healthy rats receiving Met for 8 weeks while undergoing daily moderate exercise. We evaluated the following: PP through graded endurance exercise test performed before the beginning of the training protocol and 48 h before the end of the training period; blood ALT, AST, LDH and CK–MB levels in order to address muscle damage; and several blood and muscle myokines and the expression of factors believed to be involved in muscle adaptation to exercise. Our data demonstrate that Met does not improve the positive effects of exercise on performance, although it protects myocytes from exercise-induced damage. Moreover, given that Met positively affects exercise-induced muscle adaptation, our data support the idea of the therapeutic application of Met when muscle function and structure are compromised.
The Role of Extracellular Signal-Regulated Kinase Pathways in Different Models of Cardiac Hypertrophy in Rats
Authors: Moady Gassan , Ertracht Offir , Shuster-Biton Efrat , Daud Elias , Atar Shaul
Published: August 2023

Cardiac hypertrophy develops following different triggers of pressure or volume overload. In several previous studies, different hypertrophy types were demonstrated following alterations in extracellular signal-regulated kinase (ERK) pathway activation. In the current study, we studied two types of cardiac hypertrophy models in rats: eccentric and concentric hypertrophy. For the eccentric hypertrophy model, iron deficiency anemia caused by a low-iron diet was implemented, while surgical aortic constriction was used to induce aortic stenosis (AS) and concentric cardiac hypertrophy. The hearts were evaluated using echocardiography, histological sections, and scanning electron microscopy. The expression of ERK1/2 was analyzed using Western blot. During the study period, anemic rats developed eccentric hypertrophy characterized by an enlarged left ventricle (LV) cavity cross-sectional area (CSA) (59.9 ± 5.1 mm2 vs. 47 ± 8.1 mm2, p = 0.002), thinner septum (2.1 ± 0.3 mm vs. 2.5 ± 0.2 mm, p < 0.05), and reduced left ventricular ejection fraction (LVEF) (52.6% + 4.7 vs. 60.3% + 2.8, p < 0.05). Rats with AS developed concentric hypertrophy with a thicker septum (2.8 ± 0.6 vs. 2.4 ± 0.1 p < 0.05), increased LV muscle cross-sectional area (79.5 ± 9.33 mm2 vs. 57.9 ± 5.0 mm2, p < 0.001), and increased LVEF (70.3% + 2.8 vs. 60.0% + 2.1, p < 0.05). ERK1/2 expression decreased in the anemic rats and increased in the rats with AS. Nevertheless, the p-ERK and the p-MEK did not change significantly in all the examined models. We concluded that ERK1/2 expression was altered by the type of hypertrophy and the change in LVEF.
AOBLMOA: A Hybrid Biomimetic Optimization Algorithm for Numerical Optimization and Engineering Design Problems
Authors: Zhao Yanpu , Huang Changsheng , Zhang Mengjie , Cui Yang
Published: August 2023

The Mayfly Optimization Algorithm (MOA), as a new biomimetic metaheuristic algorithm with superior algorithm framework and optimization methods, plays a remarkable role in solving optimization problems. However, there are still shortcomings of convergence speed and local optimization in this algorithm. This paper proposes a metaheuristic algorithm for continuous and constrained global optimization problems, which combines the MOA, the Aquila Optimizer (AO), and the opposition-based learning (OBL) strategy, called AOBLMOA, to overcome the shortcomings of the MOA. The proposed algorithm first fuses the high soar with vertical stoop method and the low flight with slow descent attack method in the AO into the position movement process of the male mayfly population in the MOA. Then, it incorporates the contour flight with short glide attack and the walk and grab prey methods in the AO into the positional movement of female mayfly populations in the MOA. Finally, it replaces the gene mutation behavior of offspring mayfly populations in the MOA with the OBL strategy. To verify the optimization ability of the new algorithm, we conduct three sets of experiments. In the first experiment, we apply AOBLMOA to 19 benchmark functions to test whether it is the optimal strategy among multiple combined strategies. In the second experiment, we test AOBLMOA by using 30 CEC2017 numerical optimization problems and compare it with state-of-the-art metaheuristic algorithms. In the third experiment, 10 CEC2020 real-world constrained optimization problems are used to demonstrate the applicability of AOBLMOA to engineering design problems. The experimental results show that the proposed AOBLMOA is effective and superior and is feasible in numerical optimization problems and engineering design problems.
The Impact of Intradialytic Cognitive and Physical Training Program on the Physical and Cognitive Abilities in End-Stage Kidney Disease Patients: A Randomized Clinical Controlled Trial
Authors: Kren Aljaž , Bogataj Špela
Published: August 2023

Background: Hemodialysis (HD) patients have lower cognitive functioning and reduced physical fitness than age-matched healthy individuals. Clinicians typically do not recognize the declining cognitive performance in these patients; therefore, cognitive impairment is greatly underestimated and not appropriately treated. This study aimed to evaluate the impact on cognitive function of combining cognitive training with physical exercise and physical performance in HD patients. Methods: Using a randomized, single-blinded control design, forty-four HD patients were recruited and randomly assigned to either an intradialytic physical exercise and cognitive training program (EXP group; n = 22; 54% male; 65.7 ± 9.7 years; 77.1 ± 21.9 kg; body mass index 26.8 ± 6.0) or a standard care control group (CON group; n = 21; 77% male; 67.2 ± 12.5 years; 74.2 ± 14.3 kg; body mass index 25.9 ± 3.8). The EXP group performed intradialytic cycling and cognitive training three days per week for 12 weeks. Study outcomes were assessed by the Symbol Digit Modalities Test (SDMT), Montreal Cognitive Assessment (MoCA), 10-repetition sit-to-stand test (10-STS), handgrip strength test (HGS), and stork balance test. Results: The results showed a significant time*group interaction effect for SDMT (p < 0.001; η2 = 0.267) and MoCA (p < 0.001; η2 = 0.266). Moreover, no significant interaction was observed for 10-STS, HGS, and stork balance test (p > 0.05). Conclusions: Our findings suggest that incorporating intradialytic cognitive and physical exercise training could help to improve the functional status of HD patients. The innovative, nonpharmacological, bimodal intervention is cost-effective, safe, and easy to implement during the intradialytic period and offers a potential impact on patients’ quality of life and well-being.
Integrative Lighting in Classrooms: Preliminary Results from Simulations and Field Measurements
Authors: Lo Verso Valerio R. M. , Giovannini Luigi , Valetti Lodovica , Pellegrino Anna
Published: August 2023

The paper presents results from a study on integrative lighting in real middle school classrooms located in a school building in Turin, Italy. The contribution of both daylighting and electric lighting was considered. Besides the existing configuration of electric lighting systems (fluorescent luminaires), a set of six possible retrofitting solutions was considered, all using LED luminaires. The research addressed two main objectives: (i) To verify if the circadian values (melanopic equivalent daylight illuminance m-EDI) in the classrooms could meet the recommended values reported in recent literature, for instance, in the WELL protocol, (ii) to assess the influence on integrative lighting (photopic and melanopic illuminances) played by the electric lighting, as a function of the different lighting systems, and by daylighting, as a function of different room orientations and sky conditions. Results showed that the existing spaces benefit from high daylighting amount, whilst the existing lighting systems provide an insufficient m-EDI. Even when last-generation LED lighting systems were ideally used for retrofitting, no solution was able to meet the three-point WELL recommendation, while two solutions only allowed the one-point recommendation to be met. Some design implications concerned with the results were critically discussed.
Monitoring of Interfractional Proton Range Verification and Dosimetric Impact Based on Daily CBCT for Pediatric Patients with Pelvic Tumors
Authors: Ates Ozgur , Uh Jinsoo , Pirlepesov Fakhriddin , Hua Chia-Ho , Merchant Thomas E. , Krasin Matthew J.
Published: August 2023

(1) Background: Synthetic CT images of the pelvis were generated from daily CBCT images to monitor changes in water equivalent path length (WEPL) and determine the dosimetric impact of anatomy changes along the proton beam’s path; (2) Methods: Ten pediatric patients with pelvic tumors treated using proton therapy with daily CBCT were included. The original planning CT was deformed to the same-day CBCT to generate synthetic CT images for WEPL comparison and dosimetric evaluation; (3) Results: WEPL changes of 20 proton fields at the distal edge of the CTV ranged from 0.1 to 12 mm with a median of 2.5 mm, and 75th percentile of 5.1 mm for (the original CT—rescanned CT) and ranged from 0.3 to 10.1 mm with a median of 2.45 mm and 75th percentile of 4.8 mm for (the original CT—synthetic CT). The dosimetric impact was due to proton range pullback or overshoot, which led to reduced coverage in CTV Dmin averaging 12.1% and 11.3% in the rescanned and synthetic CT verification plans, respectively; (4) Conclusions: The study demonstrated that synthetic CT generated by deforming the original planning CT to daily CBCT can be used to quantify proton range changes and predict adverse dosimetric scenarios without the need for excessive rescanned CT scans during large interfractional variations in adaptive proton therapy of pediatric pelvic tumors.
Studies in Cancer Epigenetics through a Sex and Gendered Lens: A Comprehensive Scoping Review
Authors: Huerne Katherine , Jackson Sarah S. , Lall Rina , Palmour Nicole , Berner Alison May , Dupras Charles , Joly Yann
Published: August 2023

Background: Sex and gender are vitally important in the study of epigenetic mechanisms for various types of cancer. However, little has been done to assess the state of sex and gender-based analyses (SGBA) in this field. The aim was to undertake a critical evaluation of sex and gender representation, discussion, and data analysis within the cancer epigenetics field since 2010. Methods: A PRISMA-ScR scoping review was conducted with 111 peer-reviewed studies comprising of colorectal, gastric, head and neck, hepatocellular carcinoma, and lung cancers. Data extraction and a quality appraisal were performed by a team of epidemiologists and bioethicists. Results: Of the 111 included studies, only 17 studies (15.3%) explicitly stated sex and gender analysis to be their primary aim. A total of 103 studies (92.8%) provided a detailed analysis of sex/gender as a biological or social variable, while the remaining 8 studies (7.2%) only stratified results by sex/gender. Although sex and gender were a key facet in all the eligible studies, only 7 studies (6.3%) provided an explicit definition of the terms “sex” or “gender”, while the remaining 104 studies (93.7%) used the words “sex” or “gender” without providing a definition. A total of 84 studies (75.7%) conflated the concepts of “sex” and “gender”, while 44 studies (39.6%) were inconsistent with their usage of the “sex” and “gender” terms. Conclusions: Very few studies offered a robust analysis of sex/gender data according to SAGER guidelines. We call for clear and directed guidelines regarding the use of sex/gender as a variable in epigenetics research.
Catalytic Transfer Hydrogenation Performance of Magnesium-Doped ZrO2 Solid Solutions
Authors: Iwanek (nee Wilczkowska) Ewa M. , Kirk Donald W. , Gliński Marek , Kaszkur Zbigniew
Published: August 2023

This is the first study to investigate the activity of a solid solution containing magnesium ions in a zirconia matrix in the catalytic transfer hydrogenation (CTH) of acetophenone with 2-pentanol. The results have shown that magnesium oxide is very highly active in CTH when physically mixed with zirconia. However, the same concentration of Mg2+ ions (Mg:Zr = 3:97) inserted into a zirconia lattice did not yield high activity in CTH. A higher concentration of Mg2+ ions (5%) was also tested in the two types of systems, i.e., a physical mixture of oxides and a solid solution. The increase in the concentration of Mg2+ ions in the physical mixture led to a pronounced increase in the activity of the system, whereas in the case of the solid solution it led to a slight decrease in activity. The impact of the zirconyl salt used in the synthesis was also examined, but showed little effect on the properties and activity of the systems. The study has also shown that the increase of the concentration of magnesium ions caused a decrease in the m-ZrO2 to t-ZrO2 ratio. Nevertheless, the rate of heating had an even bigger effect on this ratio.
Pathophysiology of Disseminated Intravascular Coagulation in Sepsis: A Clinically Focused Overview
Authors: Unar Ahsanullah , Bertolino Lorenzo , Patauner Fabian , Gallo Raffaella , Durante-Mangoni Emanuele
Published: August 2023

Sepsis is a major global health problem that results from a dysregulated and uncontrolled host response to infection, causing organ failure. Despite effective anti-infective therapy and supportive treatments, the mortality rate of sepsis remains high. Approximately 30–80% of patients with sepsis may develop disseminated intravascular coagulation (DIC), which can double the mortality rate. There is currently no definitive treatment approach for sepsis, with etiologic treatment being the cornerstone of therapy for sepsis-associated DIC. Early detection, diagnosis, and treatment are critical factors that impact the prognosis of sepsis-related DIC. Over the past several decades, researchers have made continuous efforts to better understand the mechanisms of DIC in sepsis, as well as improve its quantitative diagnosis and treatment. This article aims to provide a comprehensive overview of the current understanding of sepsis-related DIC, focusing on common causes and diagnoses, with the goal of guiding healthcare providers in the care of patients with sepsis.
Desmosomes in Cell Fate Determination: From Cardiogenesis to Cardiomyopathy
Authors: Moazzen Hoda , Bolaji Mistura Dolapo , Leube Rudolf E.
Published: August 2023

Desmosomes play a vital role in providing structural integrity to tissues that experience significant mechanical tension, including the heart. Deficiencies in desmosomal proteins lead to the development of arrhythmogenic cardiomyopathy (AC). The limited availability of preventative measures in clinical settings underscores the pressing need to gain a comprehensive understanding of desmosomal proteins not only in cardiomyocytes but also in non-myocyte residents of the heart, as they actively contribute to the progression of cardiomyopathy. This review focuses specifically on the impact of desmosome deficiency on epi- and endocardial cells. We highlight the intricate cross-talk between desmosomal proteins mutations and signaling pathways involved in the regulation of epicardial cell fate transition. We further emphasize that the consequences of desmosome deficiency differ between the embryonic and adult heart leading to enhanced erythropoiesis during heart development and enhanced fibrogenesis in the mature heart. We suggest that triggering epi-/endocardial cells and fibroblasts that are in different “states” involve the same pathways but lead to different pathological outcomes. Understanding the details of the different responses must be considered when developing interventions and therapeutic strategies.
AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis
Authors: García-Bañuelos Jesús , Oceguera-Contreras Edén , Sandoval-Rodríguez Ana , Bastidas-Ramírez Blanca Estela , Lucano-Landeros Silvia , Gordillo-Bastidas Daniela , Gómez-Meda Belinda C. , Santos Arturo , Cerda-Reyes Eira , Armendariz-Borunda Juan
Published: August 2023

The development of several vaccines against the SARS-CoV2 virus and their application in millions of people have shown efficacy and safety in the transfer of genes to muscle turning this tissue into a protein-producing factory. Established advanced liver fibrosis, is characterized by replacement of hepatic parenchyma by tissue scar, mostly collagen type I, with increased profibrogenic and proinflammatory molecules gene expression. Matrix metalloproteinase 8 (MMP-8) is an interstitial collagen-degrading proenzyme acting preferentially on collagen type I when activated. This study was carried out to elucidate the effect of an intramuscularly delivered adenoviral vector containing proMMP-8 gene cDNA (AdhMMP8) in male Wistar rats with experimental advanced liver fibrosis induced by thioacetamide. Therapeutic effects were monitored after 1, 2, or 3 weeks of a single dose (3 × 1011 vp/kg) of AdhMMP8. Circulating and liver concentration of MMP-8 protein remained constant; hepatic fibrosis decreased up to 48%; proinflammatory and profibrogenic genes expression diminished: TNF-α 2.28-fold, IL-1 1.95-fold, Col 1A1 4-fold, TGF-β1 3-fold and CTGF 2-fold; and antifibrogenic genes expression raised, MMP-9 2.8-fold and MMP-1 10-fold. Our data proposes that the administration of AdhMMP8 in muscle is safe and effective in achieving liver fibrosis regression at a comparable extent as when the adenoviral vector is delivered systemically to reach the liver, using a minimally invasive procedure.
Sensing of Digestive Enzymes—Diagnosis and Monitoring of Pancreatitis
Authors: Yin Jiaju , Cui Tianrui , Yang Yi , Ren Tian-Ling
Published: August 2023

This paper is a comprehensive review of the techniques for the detection of pancreatic enzymes, which are common biochemical indicators of pancreatitis, including amylase, trypsin, chymotrypsin, elastase, and lipase. Pancreatitis is a disease with self-digestion due to the abnormal activation of digestive enzymes in the pancreas. Hospitalization is often required due to the lack of convenient therapeutic agents. The main recent results are reported in this review, especially the techniques that enable portability and Point-of-Care testing (POCT). This is because timely diagnosis at the early stage and avoiding recurrence after recovery are the keys to treatment. It is also important to reduce the rate of misdiagnosis and to avoid overtreatment. Various detection methods are discussed, with particular attention given to the implementation of chemical sensing and probe design. The new sensing technology for digestive enzymes makes it possible to perform early screening for pancreatitis in remote areas or in one’s own home.
Exercise Capacity in Very Low Birth Weight Adults: A Systematic Review and Meta-Analysis
Authors: Poole Grace , Harris Christopher , Greenough Anne
Published: August 2023

There is an association between very low birth weight (VLBW) and cardiovascular morbidity and mortality in adulthood. Aerobic fitness, measured as the maximal oxygen consumption (VO2 max), is a good indicator of cardiopulmonary health and predictor of cardiovascular mortality. Our aim was to determine the effect of birth weight on aerobic exercise capacity and physical activity. We systematically identified studies reporting exercise capacity (VO2 max and VO2 peak) and physical activity levels in participants born at VLBW aged eighteen years or older compared to term-born controls from six databases (MEDLINE, OVID, EMBASE, CI NAHL, CENTRAL, and Google Scholar). Meta-analysis of eligible studies was conducted using a random effect model. We screened 6202 articles and identified 15 relevant studies, 10 of which were eligible for meta-analysis. VLBW participants had a lower VO2 max compared to their term counterparts (−3.35, 95% CI: −5.23 to −1.47, p = 0.0005), as did VLBW adults who had developed bronchopulmonary dysplasia (−6.08, 95% CI −11.26 to −0.90, p = 0.02). Five of nine studies reported significantly reduced self-reported physical activity levels. Our systematic review and meta-analysis demonstrated reduced maximal aerobic exercise capacity in adults born at VLBW compared to term-born controls.
Does the Dizziness Handicap Inventory—Children and Adolescents (DHI-CA) Demonstrate Properties to Support Clinical Application in the Post-Concussion Population: A Rasch Analysis
Authors: Tiwari Devashish , Gochyyev Perman
Published: August 2023

The purpose of this cross-sectional validation study was to evaluate the clinical utility of the DHI-CA by (1) examining its dimensionality using exploratory factor analysis (EFA) and (2) calibrating DHI-CA items (using the multidimensional Rasch model) to obtain item difficulty levels. A retrospective chart review was conducted for 132 patients between the ages of 8 and 18 years (mean age = 15.3 ± 2.1 years) from a multidisciplinary post-concussion management tertiary center. Data were extracted on age, sex, and DHI-CA. EFA revealed that 12 out of 25 items did not fit in the subscale that they were originally described under, indicating poor dimensionality. Calibration of items on the Wright Maps revealed that 50% of the items pooled in the lower difficulty level, indicating a potential ceiling effect. Corrected item–rest correlations for the physical, emotional, walking/mobility, and community participation ranged from 0.44–0.66, 0.27–0.61, 0.54–0.57, and 0.32–0.69 (p < 0.001), respectively. The clinical utility of the DHI-CA was found to be questionable due to the presence of double-barreled items and the ceiling effect. Clinicians must supplement data from the DHI-CA with other measures and patient interviews to make informed clinical decisions specific to the post-concussion population until new, robust, and valid measures are developed.
Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study
Authors: Junge Norman , Hentschel Hanna , Krebs-Schmitt Dorothee , Stalke Amelie , Pfister Eva-Doreen , Hartleben Björn , Claßen Martin , Querfurt Alexander , Münch Veronika , Bufler Philip , Oh Jun , Grabhorn Enke
Published: August 2023

Crigler–Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (UGT1A1) and no need for daily phototherapy is called mild Crigler–Najjar Syndrome. Most of these patients need medical treatment for enzyme induction (phenobarbital) to lower blood levels of unconjugated bilirubin (UCB). Apart from this, no long-term problems have been described so far. The phenotype of patients with the homozygous pathogenic variant c.115C>G p.(His39Asp) in UGT1A1 is described as variable. Clinical observations of our patients led to the assumption that patients with variant c.115C>G have a mild CNS phenotype while having a high risk of developing progressive liver disease. For mild CNS disease, progressive liver disease has not been described so far. Therefore, we conducted a retrospective multicenter analysis of 14 patients with this particular variant, aiming for better characterization of this variant. We could confirm that patients with variant c.115C>G have a high risk of progressive liver disease (seven of fourteen), which increases with age despite having a very mild CNS phenotype. Earlier predictors and causes for an unfavorable disease course are not detectable, but close follow-up could identify patients with progressive liver disease at the beginning. In conclusion, these patients need close and specialized follow-up. Our study questions whether fibrosis in the CNS is really driven by high amounts of UCB or phototherapy.
Microbiological Non-Culture-Based Methods for Diagnosing Invasive Pulmonary Aspergillosis in ICU Patients
Authors: Scharmann Ulrike , Verhasselt Hedda Luise , Kirchhoff Lisa , Furnica Dan-Tiberiu , Steinmann Joerg , Rath Peter-Michael
Published: August 2023

The diagnosis of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is crucial since most clinical signs are not specific to invasive fungal infections. To detect an IPA, different criteria should be considered. Next to host factors and radiological signs, microbiological criteria should be fulfilled. For microbiological diagnostics, different methods are available. Next to the conventional culture-based approaches like staining and culture, non-culture-based methods can increase sensitivity and improve time-to-result. Besides fungal biomarkers, like galactomannan and (1→3)-β-D-glucan as nonspecific tools, molecular-based methods can also offer detection of resistance determinants. The detection of novel biomarkers or targets is promising. In this review, we evaluate and discuss the value of non-culture-based microbiological methods (galactomannan, (1→3)-β-D-glucan, Aspergillus PCR, new biomarker/targets) for diagnosing IPA in ICU patients.
Performance of T-Track® SARS-CoV-2, an Innovative Dual Marker RT-qPCR-Based Whole-Blood Assay for the Detection of SARS-CoV-2-Reactive T Cells
Authors: Kanis Franziska M. , Meier Johannes P. , Guldan Harald , Niller Hans-Helmut , Dahm Michael , Dansard Alexander , Zander Thomas , Struck Friedhelm , Soutschek Erwin , Deml Ludwig , Möbus Selina , Barabas Sascha
Published: August 2023

T-cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a central role in the control of the virus. In this study, we evaluated the performance of T-Track® SARS-CoV-2, a novel CE-marked quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay, which relies on the combined evaluation of IFNG and CXCL10 mRNA levels in response to the S1 and NP SARS-CoV-2 antigens, in 335 participants with or without a history of SARS-CoV-2 infection and vaccination, respectively. Of the 62 convalescent donors, 100% responded to S1 and 88.7% to NP antigens. In comparison, of the 68 naïve donors, 4.4% were reactive to S1 and 19.1% to NP. Convalescent donors <50 and ≥50 years of age demonstrated a 100% S1 reactivity and an 89.1% and 87.5% NP reactivity, respectively. T-cell responses by T-Track® SARS-CoV-2 and IgG serology by recomLine SARS-CoV-2 IgG according to the time from the last immunisation (by vaccination or viral infection) were comparable. Both assays showed a persistent cellular and humoral response for at least 36 weeks post immunisation in vaccinated and convalescent donors. Our results demonstrate the very good performance of the T-Track® SARS-CoV-2 molecular assay and suggest that it might be suitable to monitor the SARS-CoV-2-specific T-cell response in COVID-19 vaccinations trials and cross-reactivity studies.
Artificial Intelligence-Enabled Electrocardiography Detects B-Type Natriuretic Peptide and N-Terminal Pro-Brain Natriuretic Peptide
Authors: Liu Pang-Yen , Lin Chin , Lin Chin-Sheng , Fang Wen-Hui , Lee Chia-Cheng , Wang Chih-Hung , Tsai Dung-Jang
Published: August 2023

BACKGROUND: The B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (pBNP) are predictors of cardiovascular morbidity and mortality. Since the artificial intelligence (AI)-enabled electrocardiogram (ECG) system is widely used in the management of many cardiovascular diseases (CVDs), patients requiring intensive monitoring may benefit from an AI-ECG with BNP/pBNP predictions. This study aimed to develop an AI-ECG to predict BNP/pBNP and compare their values for future mortality. METHODS: The development, tuning, internal validation, and external validation sets included 47,709, 16,249, 4001, and 6042 ECGs, respectively. Deep learning models (DLMs) were trained using a development set for estimating ECG-based BNP/pBNP (ECG-BNP/ECG-pBNP), and the tuning set was used to guide the training process. The ECGs in internal and external validation sets belonging to nonrepeating patients were used to validate the DLMs. We also followed-up all-cause mortality to explore the prognostic value. RESULTS: The DLMs accurately distinguished mild (≥500 pg/mL) and severe (≥1000 pg/mL) an abnormal BNP/pBNP with AUCs of ≥0.85 in the internal and external validation sets, which provided sensitivities of 68.0–85.0% and specificities of 77.9–86.2%. In continuous predictions, the Pearson correlation coefficient between ECG-BNP and ECG-pBNP was 0.93, and they were both associated with similar ECG features, such as the T wave axis and correct QT interval. ECG-pBNP provided a higher all-cause mortality predictive value than ECG-BNP. CONCLUSIONS: The AI-ECG can accurately estimate BNP/pBNP and may be useful for monitoring the risk of CVDs. Moreover, ECG-pBNP may be a better indicator to manage the risk of future mortality.
Opportunities and Advances in Radiomics and Radiogenomics for Pediatric Medulloblastoma Tumors
Authors: Ismail Marwa , Craig Stephen , Ahmed Raheel , de Blank Peter , Tiwari Pallavi
Published: August 2023

Recent advances in artificial intelligence have greatly impacted the field of medical imaging and vastly improved the development of computational algorithms for data analysis. In the field of pediatric neuro-oncology, radiomics, the process of obtaining high-dimensional data from radiographic images, has been recently utilized in applications including survival prognostication, molecular classification, and tumor type classification. Similarly, radiogenomics, or the integration of radiomic and genomic data, has allowed for building comprehensive computational models to better understand disease etiology. While there exist excellent review articles on radiomics and radiogenomic pipelines and their applications in adult solid tumors, in this review article, we specifically review these computational approaches in the context of pediatric medulloblastoma tumors. Based on our systematic literature research via PubMed and Google Scholar, we provide a detailed summary of a total of 15 articles that have utilized radiomic and radiogenomic analysis for survival prognostication, tumor segmentation, and molecular subgroup classification in the context of pediatric medulloblastoma. Lastly, we shed light on the current challenges with the existing approaches as well as future directions and opportunities with using these computational radiomic and radiogenomic approaches for pediatric medulloblastoma tumors.
A Complex Case of Pulmonary Silico-Tuberculosis and Review of Literature
Authors: D’Sa Lauren , Pezzuto Federica , Lunardi Francesca , Scalvenzi Francesca , Tinè Mariaenrica , Comacchio Giovanni , Giraudo Chiara , Calabrese Fiorella
Published: August 2023

Silicosis caused by the inhalation/deposition of free silica particles is characterized by pulmonary inflammation/fibrosis. Among the clinical disorders associated with silicosis, tuberculosis is by far the most prominent. A 66-year-old male non-smoker, originally from North Africa, reported a dry cough and significant weight loss. He was a foundry worker. He had a medical history of bladder carcinoma associated with schistosomiasis. Computed tomography (CT) and positron emission tomography (PET)/CT showed bilateral multiple hypermetabolic lung nodules, some with cavitation. The patient underwent surgical resection of the largest nodule, which was highly suspicious of lung metastasis. The histological examination revealed multiple nodular formations. Several lesions showed the characteristic features of silicotic nodules. There were also adjacent well-formed granulomas, some with central caseous necrosis. A real-time polymerase chain reaction, performed for the identification and quantification of the DNA of the Mycobacterium tuberculosis complex, was positive. Pulmonary silico-tuberculosis is often encountered in patients with a history of silica exposure in tuberculosis-endemic areas. This case serves as a reminder to never underestimate patient occupational exposure and geographic origin. A careful histological diagnosis and molecular investigation are mandatory when approaching difficult cases, especially patients with a prior cancer history and clinical/radiological features suggestive of tumour recurrence/metastasis.
Is There a New Road to Spinal Cord Injury Rehabilitation? A Case Report about the Effects of Driving a Go-Kart on Muscle Spasticity
Authors: Farì Giacomo , Ranieri Maurizio , Marvulli Riccardo , Dell’Anna Laura , Fai Annatonia , Tognolo Lucrezia , Bernetti Andrea , Caforio Laura , Megna Marisa , Losavio Ernesto
Published: August 2023

Background: Traumatic spinal cord injury (SCI) is a neurological disorder that causes a traumatic anatomical discontinuity of the spinal cord. SCI can lead to paraplegia, spastic, or motor impairments. Go-karting for people with SCI is an adapted sport that is becoming increasingly popular. The purpose of this case report is to shed light on the effects of driving a go-kart on a patient with SCI-related spasticity and to deepen understanding of the possible related role of whole-body vibration (WBV) and neuroendocrine reaction. Methods: The patient was a 50-year-old male with a spastic paraplegia due to traumatic SCI. He regularly practiced go-kart racing, reporting a transient reduction in spasticity. He was evaluated before (T0), immediately after (T1), 2 weeks after (T2), and 4 weeks after (T3) a go-kart driving session. On both sides, long adductor, femoral bicep, and medial and lateral gastrocnemius spasticity was assessed using the Modified Ashworth Scale (MAS), and tone and stiffness were assessed using MyotonPro. Results: It was observed that a go-kart driving session could reduce muscle spasticity, tone, and stiffness. Conclusions: Go-kart driving can be a valid tool to obtain results similar to those of WBV and hormone production in the reduction of spasticity.
Tax Compliance Challenge through Taxpayers’ Typology
Authors: Paleka Hana , Vitezić Vanja
Published: August 2023

Tax compliance has become a very popular academic research topic. Understandably so, as all modern societies face the challenge of limiting tax evasion and the losses this phenomenon causes to government revenues. Given the increase in duties in the aftermath of the economic downturn affected by COVID-19, increasing taxpayer compliance is one of the main tasks for governments worldwide. This study aimed to identify critical gaps in understanding taxpayer heterogeneity. For this purpose, an exploratory factor analysis of taxpayer perceptual and attitudinal elements was carried out. Our analysis revealed six factors influencing taxpayer compliance with the tax system. Furthermore, the cluster analysis identified four groups of taxpayers, and significant differences between the clusters and the descriptive profile of each cluster were also found. The specificities of these clusters point to a conclusion that the time has come for policy makers to employ strategies that stimulate voluntary tax compliance with minimum cost to the tax system.
Explainable B2B Recommender System for Potential Customer Prediction Using KGAT
Authors: Cho Gyungah , Shim Pyoung-seop , Kim Jaekwang
Published: August 2023

The adoption of recommender systems in business-to-business (B2B) can make the management of companies more efficient. Although the importance of recommendation is increasing with the expansion of B2B e-commerce, not enough studies on B2B recommendations have been conducted. Due to several differences between B2B and business-to-consumer (B2C), the B2B recommender system should be defined differently. This paper presents a new perspective on the explainable B2B recommender system using the knowledge graph attention network for recommendation (KGAT). Unlike traditional recommendation systems that suggest products to consumers, this study focuses on recommending potential buyers to sellers. Additionally, the utilization of the KGAT attention mechanisms enables the provision of explanations for each company’s recommendations. The Korea Electronic Taxation System Association provides the Market Transaction Dataset in South Korea, and this research shows how the dataset is utilized in the knowledge graph (KG). The main tasks can be summarized in three points: (i) suggesting the application of an explainable recommender system in B2B for recommending potential customers, (ii) extracting the performance-enhancing features of a knowledge graph, and (iii) enhancing keyword extraction for trading items to improve recommendation performance. We can anticipate providing good insight into the development of the industry via the utilization of the B2B recommendation of potential customer prediction.
CyberHero: An Adaptive Serious Game to Promote Cybersecurity Awareness
Authors: Hodhod Rania , Hardage Harlie , Abbas Safia , Aldakheel Eman Abdullah
Published: August 2023

The lack of cybersecurity awareness among everyday users is a significant issue that can have detrimental effects on individuals and organizations alike. Traditional training methods such as slideshows and presentations have proven to be ineffective and can cause trainees to feel overwhelmed, overloaded, confused, or bored. To address this issue, the development of an adaptive serious game that teaches cybersecurity in an effective, engaging, and personalized manner is proposed. Serious games provide an immersive and simulated experience that can help users determine how they might act in real-life scenarios. However, existing cybersecurity serious games often measure effectiveness outside of the game using surveys, tests, and interviews, which can lessen immersion and the simulated experience. Therefore, measuring improvement within the game itself can provide more meaningful data and derive truer conclusions about the usefulness of serious games in teaching cybersecurity. The goal of this research study is to develop such a game and measure its effectiveness in a way that can inform future cybersecurity training programs. By providing an engaging and personalized experience, serious games can improve cybersecurity awareness and reduce the risk of cyber threats. The results show that 79% of the participants admitted that they learned new things by playing the game, 84% said that they were engaged by the background story, 68% agreed that they had fun while playing the game, and 84% would recommend the game to others.
Routes for Hydrogen Introduction in the Industrial Hard-to-Abate Sectors for Promoting Energy Transition
Authors: Franco Alessandro , Giovannini Caterina
Published: August 2023

This paper offers a set of comprehensive guidelines aimed at facilitating the widespread adoption of hydrogen in the industrial hard-to-abate sectors. The authors begin by conducting a detailed analysis of these sectors, providing an overview of their unique characteristics and challenges. This paper delves into specific elements related to hydrogen technologies, shedding light on their potential applications, and discussing feasible implementation strategies. By exploring the strengths and limitations of each technology, this paper offers valuable insights into its suitability for specific applications. Finally, through a specific analysis focused on the steel sector, the authors provide in-depth information on the potential benefits and challenges associated with hydrogen adoption in this context. By emphasizing the steel sector as a focal point, the authors contribute to a more nuanced understanding of hydrogen’s role in decarbonizing industrial processes and inspire further exploration of its applications in other challenging sectors.