bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function
Authors: Ashar Yunali , Teng Qiuxu , Wurpel John , Chen Zhe-Sheng , Reznik Sandra
Published: August 2022

Normal function of placental extravillous trophoblasts (EVTs), which are responsible for uteroplacental vascular remodeling, is critical for adequate delivery of oxygen and nutrients to the developing fetus and normal fetal programming. Proliferation and invasion of spiral arteries by EVTs depends upon adequate levels of folate. Multidrug resistance-associated protein 1 (MRP1), which is an efflux transporter, is known to remove folate from these cells. We hypothesized that palmitic acid increases MRP1-mediated folate removal from EVTs, thereby interfering with EVTs’ role in early placental vascular remodeling. HTR-8/SVneo and Swan-71 cells, first trimester human EVTs, were grown in the absence or presence of 0.5 mM and 0.7 mM palmitic acid, respectively, for 72 h. Palmitic acid increased ABCC1 gene expression and MRP1 protein expression in both cell lines. The rate of folate efflux from the cells into the media increased with a decrease in migration and invasion functions in the cultured cells. Treatment with N-acetylcysteine (NAC) prevented the palmitic acid-mediated upregulation of MRP1 and restored invasion and migration in the EVTs. Finally, in an ABCC1 knockout subline of Swan-71 cells, there was a significant increase in invasion and migration functions. The novel finding in this study that palmitic acid increases MRP1-mediated folate efflux provides a missing link that helps to explain how maternal consumption of saturated fatty acids compromises the in utero environment.
Biomarkers of Clot Activation and Degradation and Risk of Future Major Cardiovascular Events in Acute Exacerbation of COPD: A Cohort Sub-Study in a Randomized Trial Population
Authors: Kamstrup Peter , Sand Jannie Marie Bülow , Ulrik Charlotte Suppli , Janner Julie , Rønn Christian Philip , Rønnow Sarah Rank , Leeming Diana Julie , Jensen Sidse Graff , Wilcke Torgny , Mathioudakis Alexander G. , Miravitlles Marc , Lapperre Therese , Bendstrup Elisabeth , Frikke-Schmidt Ruth , Murray Daniel D. , Itenov Theis , Bossios Apostolos , Nielsen Susanne Dam , Vestbo Jørgen , Biering-Sørensen Tor , Karsdal Morten , Jensen Jens-Ulrik , Sivapalan Pradeesh
Published: August 2022

Cardiovascular diseases are common in patients with chronic obstructive pulmonary disease (COPD). Clot formation and resolution secondary to systemic inflammation may be a part of the explanation. The aim was to determine whether biomarkers of clot formation (products of von Willebrand Factor formation and activation) and clot resolution (product of fibrin degeneration) during COPD exacerbation predicted major cardiovascular events (MACE). The cohort was based on clinical data and biobank plasma samples from a trial including patients admitted with an acute exacerbation of COPD (CORTICO-COP). Neo-epitope biomarkers of formation and the activation of von Willebrand factor (VWF-N and V-WFA, respectively) and cross-linked fibrin degradation (X-FIB) were assessed using ELISAs in EDTA plasma at the time of acute admission, and analyzed for time-to-first MACE within 36 months, using multivariable Cox proportional hazards models. In total, 299/318 participants had samples available for analysis. The risk of MACE for patients in the upper quartile of each biomarker versus the lower quartile was: X-FIB: HR 0.98 (95% CI 0.65–1.48), VWF-N: HR 1.56 (95% CI 1.07–2.27), and VWF-A: HR 0.78 (95% CI 0.52–1.16). Thus, in COPD patients with an acute exacerbation, VWF-N was associated with future MACE and warrants further studies in a larger population.
Update on the Pharmacological Treatment of Primary Biliary Cholangitis
Authors: Floreani Annarosa , Gabbia Daniela , De Martin Sara
Published: August 2022

Ursodeoxycholic acid (UDCA) is the first-line therapy used for the treatment of PBC. In recent years, new pharmacological agents have been proposed for PBC therapy to cure UDCA-non-responders. Obeticholic acid (OCA) is registered in many countries for PBC, and fibrates also seem to be effective in ameliorating biochemistry alteration and symptoms typical of PBC. Moreover, a variety of new agents, acting with different mechanisms of action, are under clinical evaluation for PBC treatment, including PPAR agonists, anti-NOX agents, immunomodulators, and mesenchymal stem cell transplantation. Since an insufficient amount of data is currently available about the effect of these novel approaches on robust clinical endpoints, such as transplant-free survival, their clinical approval needs to be supported by the consistent improvement of these parameters. The intensive research in this field will hopefully lead to a novel treatment landscape for PBC in the near future, with innovative therapies based on the combination of multiple agents acting on different pathogenetic mechanisms.
Serum Osmolarity and Vasopressin Concentration in Acute Heart Failure—Influence on Clinical Course and Outcome
Authors: Guzik Mateusz , Sokolski Mateusz , Hurkacz Magdalena , Zdanowicz Agata , Iwanek Gracjan , Marciniak Dominik , Zymliński Robert , Ponikowski Piotr , Biegus Jan
Published: August 2022

Neurohormone activation plays an important role in Acute Heart Failure (AHF) pathophysiology. Serum osmolarity can affect this activation causing vasopressin excretion. The role of serum osmolarity and vasopressin concentration and its interaction remain still unexplored in AHF. The objective of our study was to evaluate the relationship of serum osmolarity with clinical parameters, vasopressin concentration, in-hospital course, and outcomes in AHF patients. The study group consisted of 338 AHF patients (male (76.3%), mean age of 68 ± 13 years) with serum osmolarity calculated by the equation: 1.86 × sodium [mmol/L] + (glucose [mg/dL]/18) + (urea [mg/dL]/2.8) + 9 and divided into osmolarity quartiles marked as: low: <287 mOsm/L, intermediate low: 287–294 mOsm/L, intermediate high: 295–304 mOsm/L, and high: >304 mOsm/L. There was an increasing age gradient in the groups and patients differed in the occurrence of comorbidities and baseline clinical and laboratory parameters. Importantly, analysis revealed that vasopressin presented a linear correlation with osmolarity (r = −0.221, p = 0.003) and its concentration decreased with quartiles (61.6 [44.0–81.0] vs. 57.8 [50.0–77.3] vs. 52.7 [43.1–69.2] vs. 45.0 [30.7–60.7] pg/mL, respectively, p = 0.034). This association across quartiles was observed among de novo AHF (63.6 [55.3–94.5] vs. 58.0 [50.7–78.6] vs. 52.0 [46.0–58.0] vs. 38.0 [27.0–57.0] pg/mL, respectively, p = 0.022) and was not statistically significant in patients with acute decompensated heart failure (ADHF) (59.5 [37.4–80.0] vs. 52.0 [38.0–74.5] vs. 57.0 [38.0–79.0] vs. 50.0 [33.0–84.0] pg/mL, respectively, p = 0.849). The worsening of renal function episodes were more frequent in quartiles with higher osmolarity (4 vs. 2 vs. 13 vs. 11%, respectively, p = 0.018) and patients that belonged to the quartiles with low and high osmolarity were characterized more often by incidence of worsening heart failure (20 vs. 9 vs. 10 vs. 22%, respectively, p = 0.032). There was also a U-shape distribution in relation to one-year mortality (31 vs. 19 vs. 23 vs. 37%, respectively, p = 0.022). In conclusion, there was an association of serum osmolarity with clinical status and both in-hospital and out-of-hospital outcomes. Moreover, the linear dependence between vasopressin concentration and serum osmolarity in the AHF population was identified and was driven mainly by patients with de novo AHF which suggests different pathophysiological paths in ADHF and AHF de novo.
Hidradenitis Suppurativa: A Perspective on Genetic Factors Involved in the Disease
Authors: Moltrasio Chiara , Tricarico Paola Maura , Romagnuolo Maurizio , Marzano Angelo Valerio , Crovella Sergio
Published: August 2022

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease of the pilosebaceous unit, clinically consisting of painful nodules, abscesses, and sinus tracts mostly in, but not limited to, intertriginous skin areas. HS can be defined as a complex skin disease with multifactorial etiologies, including—among others—genetic, immunologic, epigenetic, and environmental factors. Based on genetic heterogeneity and complexity, three different forms can be recognized and considered separately as sporadic, familial, and syndromic. To date, several genetic variants associated to disease susceptibility, disease-onset, and/or treatment response have been reported; some of these reside in genes encoding the gamma-secretase subunits whereas others involve autoinflammatory and/or keratinization genes. The aim of this perspective work is to provide an overview of the contribution of several genetic studies encompassing family linkage analyses, target candidate gene studies, and -omic studies in this field. In our viewpoint, we discuss the role of genetics in Hidradenitis suppurativa considering findings based on Sanger sequencing as well as the more recent Next Generation Sequencing (i.e., exome sequencing or RNA Sequencing) with the aim of better understanding the etio-pathogenesis of the disease as well as identifying novel therapeutic strategies.
Juvenile Idiopathic Arthritis, Uveitis and Multiple Sclerosis: Description of Two Patients and Literature Review
Authors: Chighizola Cecilia Beatrice , Ferrito Matteo , Marelli Luca , Pontikaki Irene , Nucci Paolo , Miserocchi Elisabetta , Caporali Roberto
Published: August 2022

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, while multiple sclerosis (MS) is a demyelinating disease of the central nervous system, characterized by remission and exacerbation phases. An association between MS and rheumatologic diseases, in particular rheumatoid arthritis, has been described and numerous studies acknowledge anti-TNF-α drugs as MS triggers. Conversely, the association between MS and JIA has been reported merely in five cases in the literature. We describe two cases of adult patients with longstanding JIA and JIA-associated uveitis, who developed MS. The first patient was on methotrexate and adalimumab when she developed dizziness and nausea. Characteristic MRI lesions and oligoclonal bands in cerebrospinal fluid led to MS diagnosis. Adalimumab was discontinued, and she was treated with three pulses of intravenous methylprednisolone. After a few months, rituximab was started. The second patient had been treated with anti-TNF-α and then switched to abatacept. She complained of unilateral arm and facial paraesthesias; brain MRI showed characteristic lesions, and MS was diagnosed. Three pulses of intravenous methylprednisolone were administered; neurological disease remained stable, and abatacept was reintroduced. Further studies are warranted to define if there is an association between JIA and MS, if MS represents JIA comorbidity or if anti-TNF-α underpins MS development.
Identification of Germinal Neurofibromin Hotspots
Authors: Lois Sergio , Báez-Flores Juan , Isidoro-García María , Lacal Jesus , Triviño Juan Carlos
Published: August 2022

Neurofibromin is engaged in many cellular processes and when the proper protein functioning is impaired, it causes neurofibromatosis type 1 (NF1), one of the most common inherited neurological disorders. Recent advances in sequencing and screening of the NF1 gene have increased the number of detected variants. However, the correlation of these variants with the clinic remains poorly understood. In this study, we analyzed 4610 germinal NF1 variants annotated in ClinVar and determined on exon level the mutational spectrum and potential pathogenic regions. Then, a binomial and sliding windows test using 783 benign and 938 pathogenic NF1 variants were analyzed against functional and structural regions of neurofibromin. The distribution of synonymous, missense, and frameshift variants are statistically significant in certain regions of neurofibromin suggesting that the type of variant and its associated phenotype may depend on protein disorder. Indeed, there is a negative correlation between the pathogenic fraction prediction and the disorder data, suggesting that the higher an intrinsically disordered region is, the lower the pathogenic fraction is and vice versa. Most pathogenic variants are associated to NF1 and our analysis suggests that GRD, CSRD, TBD, and Armadillo1 domains are hotspots in neurofibromin. Knowledge about NF1 genotype–phenotype correlations can provide prognostic guidance and aid in organ-specific surveillance.
Identification of Key Endoplasmic Reticulum Stress-Related Genes in Non-Alcoholic Fatty Liver Disease
Authors: Li Zhuang , Yu Haozhen , Li Jun
Published: August 2022

Background: Endoplasmic reticulum stress (ERS) is involved in the etiology of non-alcoholic fatty liver disease (NAFLD). Thus, the current study was designed to identify key ERS-associated genes in NAFLD. Methods: RNA-Seq data of NAFLD and controls were sourced from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in NAFLD and controls were identified by limma. By overlapping DEGs and ERS-related genes, ERS-related DEGs were identified. The function of ERS-related DEGs was characterized by clusterProfiler. Next, the protein–protein interaction (PPI) network was created using the Cytoscape software and the STRING database to identify key ERS-related genes in NAFLD. Furthermore, the correlations among key ERS-related genes were calculated. Results: A total of 8965 DEGs were identified between NAFLD and controls in the GSE126848 dataset. After overlapping these DEGs and ERS-related genes, 20 genes were identified as ERS-related DEGs in NAFLD. Functional analysis revealed that the genes mainly participated in ER-related functions, such as the ER–nucleus signaling pathway, regulation of ERS response, and protein processing in ER. The PPI network revealed the interactions among 17 ERS-related DEGs, including ERN1, ATF6, and EIF2S1 as the key genes. The expressions of ERN1, ATF6, and EIF2S1 were significantly down-regulated in NAFLD and were strongly positively correlated with each other. Further, the expression of ERN1 and ATFA6 was also similar in the GSE89632 datasets. Conclusion: The present study identified ERN1, ATF6, and EIF2S1 as key ERS-related genes in NAFLD. These findings may provide a molecular basis for the role of ERS in NAFLD.
Multi-Factors Cooperatively Actuated Photonic Hydrogel Aptasensors for Facile, Label-Free and Colorimetric Detection of Lysozyme
Authors: Shen Peiyan , Shi Yuqing , Li Ran , Han Bo , Ma Haojie , Hou Xueyan , Zhang Yuqi , Jiang Lei
Published: August 2022

Responsive two-dimensional photonic crystal (2DPC) hydrogels have been widely used as smart sensing materials for constructing various optical sensors to accurately detect different target analytes. Herein, we report photonic hydrogel aptasensors based on aptamer-functionalized 2DPC poly(acrylamide-acrylic acid-N-tert-butyl acrylamide) hydrogels for facile, label-free and colorimetric detection of lysozyme in human serum. The constructed photonic hydrogel aptasensors undergo shrinkage upon exposure to lysozyme solution through multi-factors cooperative actuation. Here, the specific binding between the aptamer and lysozyme, and the simultaneous interactions between carboxyl anions and N-tert-butyl groups with lysozyme, increase the cross-linking density of the hydrogel, leading to its shrinkage. The aptasensors’ shrinkage decreases the particle spacing of the 2DPC embedded in the hydrogel network. It can be simply monitored by measuring the Debye diffraction ring of the photonic hydrogel aptasensors using a laser pointer and a ruler without needing sophisticated apparatus. The significant shrinkage of the aptasensors can be observed by the naked eye via the hydrogel size and color change. The aptasensors show good sensitivity with a limit of detection of 1.8 nM, high selectivity and anti-interference for the detection of lysozyme. The photonic hydrogel aptasensors have been successfully used to accurately determine the concentration of lysozyme in human serum. Therefore, novel photonic hydrogel aptasensors can be constructed by designing functional monomers and aptamers that can specifically bind target analytes.
In-Depth Characterization of Endo-Lysosomal Aβ in Intact Neurons
Authors: McKendell Alec K. , Houser Mei C. Q. , Mitchell Shane P. C. , Wolfe Michael S. , Berezovska Oksana , Maesako Masato
Published: August 2022

Amyloid-beta (Aβ) peptides are produced within neurons. Some peptides are released into the brain parenchyma, while others are retained inside the neurons. However, the detection of intracellular Aβ remains a challenge since antibodies against Aβ capture Aβ and its precursor proteins (i.e., APP and C99). To overcome this drawback, we recently developed 1) the C99 720-670 biosensor for recording γ-secretase activity and 2) a unique multiplexed immunostaining platform that enables the selective detection of intracellular Aβ with subcellular resolution. Using these new assays, we showed that C99 is predominantly processed by γ-secretase in late endosomes and lysosomes, and intracellular Aβ is enriched in the same subcellular loci in intact neurons. However, the detailed properties of Aβ in the acidic compartments remain unclear. Here, we report using fluorescent lifetime imaging microscopy (FLIM) that intracellular Aβ includes both long Aβ intermediates bound to γ-secretase and short peptides dissociated from the protease complex. Surprisingly, our results also suggest that the dissociated Aβ is bound to the glycoproteins on the inner membrane of lysosomes. Furthermore, we show striking cell-to-cell heterogeneity in intracellular Aβ levels in primary neurons and APP transgenic mouse brains. These findings provide a basis for the further investigation of the role(s) of intracellular Aβ and its relevance to Alzheimer’s disease (AD).
A High Accuracy & Ultra-Low Power ECG-Derived Respiration Estimation Processor for Wearable Respiration Monitoring Sensor
Authors: Fan Jiajing , Yang Siqi , Liu Jiahao , Zhu Zhen , Xiao Jianbiao , Chang Liang , Lin Shuisheng , Zhou Jun
Published: August 2022

The respiratory rate is widely used for evaluating a person’s health condition. Compared to other invasive and expensive methods, the ECG-derived respiration estimation is a more comfortable and affordable method to obtain the respiration rate. However, the existing ECG-derived respiration estimation methods suffer from low accuracy or high computational complexity. In this work, a high accuracy and ultra-low power ECG-derived respiration estimation processor has been proposed. Several techniques have been proposed to improve the accuracy and reduce the computational complexity (and thus power consumption), including QRS detection using refractory period refreshing and adaptive threshold EDR estimation. Implemented and fabricated using a 55 nm processing technology, the proposed processor achieves a low EDR estimation error of 0.73 on CEBS database and 1.2 on MIT-BIH Polysomnographic Database while demonstrating a record-low power consumption (354 nW) for the respiration monitoring, outperforming the existing designs. The proposed processor can be integrated in a wearable sensor for ultra-low power and high accuracy respiration monitoring.
Self-Enhancement and the Medial Prefrontal Cortex: The Convergence of Clinical and Experimental Findings
Authors: Yasin Saeed , Fierst Anjel , Keenan Harper , Knapp Amelia , Gallione Katrina , Westlund Tessa , Kirschner Sydney , Vaidya Sahana , Qiu Christina , Rougebec Audrey , Morss Elodie , Lebiedzinski Jack , Dejean Maya , Keenan Julian Paul
Published: August 2022

Self-enhancement (SE) is often overlooked as a fundamental cognitive ability mediated via the Prefrontal Cortex (PFC). Here, we present research that establishes the relationship between the PFC, SE, and the potential evolved beneficial mechanisms. Specifically, we believe there is now enough evidence to speculate that SE exists to provide significant benefits and should be considered a normal aspect of the self. Whatever the metabolic or social cost, the upside of SE is great enough that it is a core and fundamental psychological construct. Furthermore, though entirely theoretical, we suggest that a critical reason the PFC has evolved so significantly in Homo sapiens is to, in part, sustain SE. We, therefore, elaborate on its proximate and ultimate mechanisms.
Are You Happy? A Validation Study of a Tool Measuring Happiness
Authors: Rizzato Matteo , Di Dio Cinzia , Miraglia Laura , Sam Carlo , D’Anzi Sharon , Antonelli Michele , Donelli Davide
Published: August 2022

This study aims at evaluating the psychometric properties of a new scale to measure experienced happiness—the Measure of Happiness (MH)—in a nonclinical sample composed of Italian adults from the general population. The MH was developed not only to provide a global measure of happiness, but also and more importantly to identify the specific areas of the individual’s life that are related to the experienced happiness. A total of 787 adults filled the MH and other self-report questionnaires, in order to assess the factor structure, reliability and external validity of the measure. The factorial analysis identified the following five dimensions: Psychophysics Status, Financial Status, Relational Private Sphere, Socio-Relational Sphere, and Life Perspective. The scale so defined was administered to a second independent group of 421 participants for the (multigroup) confirmatory factor analysis (CFA). A multigroup factor analysis based on gender confirmed the MH structure. The convergent validity of the MH was assessed by comparing the MH scores with a previously validated test of happiness and quality of life, as well as with dispositional constructs with which happiness is known to be negatively correlated, namely, anxiety and depression. The MH showed satisfactory psychometric properties and a strong significant positive relationship between the two measures of happiness, and a substantial negative association with the measures of anxiety and depression, supporting the validity of the MH to assess the construct of experienced happiness. The implications and possible applications of the MH are then discussed.
Difficulties with Emotion Regulation during COVID-19 and Associations with Boredom in College Students
Authors: Weybright Elizabeth H. , Doering Erica L. , Perone Sammy
Published: August 2022

COVID-19 related restrictions resulted in a significant lifestyle change for many young adults in the United States. Although boredom and emotional self-regulation are clearly connected in empirical research, the question remains of what this association looks like in unique circumstances, such as early in COVID-19 pandemic at the height of restrictions. The purpose of the current study is to identify the association between boredom proneness and emotion regulation in college students during the COVID-19 pandemic. College students who completed a Boredom Coping Survey between October and December 2019 (n = 481) were recruited for a follow-up COVID-19 Boredom Survey in April 2020. Data from this sub-sample (n = 58) were used in a hierarchical regression predicting the role of boredom proneness on COVID-19 pandemic emotion regulation difficulties while controlling for age, sex, and COVID-19 related lifestyle changes. Findings indicated higher levels of emotion regulation difficulties were associated with higher levels of boredom proneness above and beyond demographic variables and COVID-19 lifestyle changes. Results are in line with prior theory and research on the importance of the environment or situational factors to the experience of boredom.
Empirical Investigation of Work-Related Social Media Usage and Social-Related Social Media Usage on Employees’ Work Performance
Authors: Dantas Rui Miguel , Aftab Hira , Aslam Sumaira , Majeed Muhammad Ussama , Correia Anabela Batista , Qureshi Hamza Ahmad , Lucas João Luis
Published: August 2022

The trend of using social media in the workplace is now becoming ubiquitous. Along witbenefits, social media also has negative consequences. Employees use social media for both work and social purposes. Therefore, using a quantitative approach, this study explores the impact of work-related social media usage and social-related social media usage on employees’ work performance. This study also investigates the mediating effect of extra-role behaviors on social media usage (professional and personal purpose) and work performance relationships. We examined survey data of 241 employees working in different organizations with the help of the partial least square (PLS) 3.0 version. Convenience sampling has been used to reach respondents. The outcomes of this study demonstrate that both professional and personal-related social media usage have a positive and significant impact on employees’ work performance. This study also highlighted that extra-role behavior positively and significantly mediates the relationship between social media usage (work and personal) and employees’ work performance. This study provides practical insights to managers, such as that, instead of banning social media usage in companies, there must be some limits and regulations for using social media that would facilitate firms to increase employees’ engagement and productivity.
Boredom in a Time of Uncertainty: State and Trait Boredom’s Associations with Psychological Health during COVID-19
Authors: Weiss Emily R. , Todman McWelling , Maple Emily , Bunn Rebecca R.
Published: August 2022

Throughout the COVID-19 pandemic, studies have demonstrated increases in boredom and its negative impact on mental health. This cross-sectional study examines state and trait boredom at four different points of the pandemic using an online sample of participants from the United States (n = 783). The results showed significant increases in boredom proneness, state boredom, substance use, loneliness, and distress. Boredom was associated with increases in each of these variables and a greater likelihood of testing positive for COVID-19. Moreover, the increases in distress, loneliness, and substance use became non-significant when controlling for boredom. Boredom proneness remained associated with all adverse outcomes when accounting for state boredom. In contrast, the relationships between state boredom and most adverse outcomes lost significance when controlling for boredom proneness, and state boredom was positively associated with increased hope for the future. Overall, the results suggest that high boredom proneness is an important vulnerability factor for poor psychological health and risky behaviors during the pandemic. However, high levels of recent state boredom, independent of boredom proneness, do not predict similarly negative outcomes. State boredom may indicate the extent to which one remains hopeful that circumstances will improve without resorting to risky, potentially maladaptive coping strategies.
“In-Between Area” Design Method: An Optimization Design Method for Indoor Public Spaces for Elderly Facilities Evaluated by STAI, HRV and EEG
Authors: Wang Haining , Hou Keming , Kong Zhe , Guan Xi , Hu Songtao , Lu Mingli , Piao Xun , Qian Yuchong
Published: August 2022

The indoor public spaces of most elderly facilities in China have a monotonous space form, which, thus, causes low comprehensive performance and is less likely to satisfy participants’ various requirements. This study proposes an optimization design method of “In-Between Area” for a space form operation to improve the performance of indoor public spaces. First, two models were established: Model A to reflect current indoor public spaces and Model B to represent the indoor public spaces designed by using the “In-Between Area” method. Second, a walk-through video was created from each model, with a duration of 196 s. Subjective assessment (STAI) data and objective physiological data (HRV and EEG), were collected from 40 participants while they were watching walk-through videos. The comparison analysis showed statistically significant differences between Model A and Model B. The results of STAI, HRV and EEG proved that the “In-Between Area” method, as an optimization design method, created a more pleasant and comfortable environment for the elderly and improved the overall efficiency of the indoor space.
Assessment of Integrated Solutions for the Combined Energy Efficiency Improvement and Seismic Strengthening of Existing URM Buildings
Authors: Requena-Garcia-Cruz Maria-Victoria , Díaz-Borrego Julia , Romero-Sánchez Emilio , Morales-Esteban Antonio , Campano Miguel-Angel
Published: August 2022

The European building stock is an aging infrastructure, mainly built prior to building codes. Furthermore, 65% of these buildings are located in seismic regions, which need to be both energetic and seismically retrofitted to comply with performance targets. Given this, this manuscript presents integrated constructive solutions that combine both energy efficiency improvement and seismic strengthening. The goal and novelty is to design and to evaluate one-shot, compatible, noninvasive, and complementary solutions applied to the façades of buildings with a minimum cost. To do so, different constraints have been borne in mind: the urban environment, achievable seismic and energy performance targets, and reduced construction costs. The method was applied to an old Spanish neighbourhood constructed in the 1960s. Different retrofitting packages were proposed for an unreinforced masonry case study building. A sensitivity analysis was performed to assess the effects of each configuration. A benefit/cost ratio was proposed to comparatively assess and to rank the solutions. The results of the seismoenergetic performance assessment showed that improving the behaviour of walls leads to higher benefit ratios than improving the openings. However, this latter strategy generates much lower construction costs. Integrating seismic into energetic retrofitting solutions supposes negligible additional costs but can improve the seismic behaviour of buildings by up to 240%. The optimal solution was the addition of higher ratios of steel grids and intermediate profiles in openings while adding thermal insulation in walls and renovating the window frames with PVC and standard 4/6/4 double glazing.
Physical, Mechanical, and Durability Properties of Concrete Containing Wood Chips and Sawdust: An Experimental Approach
Authors: Dias Sara , Tadeu António , Almeida João , Humbert Pedro , António Julieta , de Brito Jorge , Pinhão Pedro
Published: August 2022

With a circular economy in the spotlight, wood waste has emerged as an important secondary raw material. Bearing this in mind, a comprehensive experimental study was carried out to evaluate the feasibility of using concrete compositions containing wood chips and sawdust for structural and non-structural building applications. First, the mineral and wood aggregates used in the composite design were fully characterized. Twelve compositions containing varying types of wood particles in different amounts were then produced and characterized in terms of physical and mechanical performance (e.g., mass density, compressive strength, modulus of elasticity, and flexural strength). Subsequently, two compositions with optimized features (mass density below 2125 kg/m3, compressive strength above 25 MPa, and maximum volume content of wood) were selected to undergo additional experimental tests. These included microstructural characterization, as well as the evaluation of relevant durability (e.g., wetting–drying, freeze–thaw, and thermal shock cycles) and hygrothermal (e.g., thermal conductivity, water absorption, and shrinkage and expansion) properties. All compositions showed compressive strength above 30 MPa. The durability assessment of selected compositions further showed that compressive strength after relevant artificial aging was still higher than the predefined criteria. Promising hygrothermal properties (minimal water absorption and low thermal conductivity) were also recorded.
Exploring Guardians’ Perceptions towards Edutainment Environments: The Case of Kidzania, Cairo, Egypt
Authors: Salama Mennatalla Mostafa A. , Abou El-Ela Manal S. , Khalil Marwa H.
Published: August 2022

Over the last few decades, the concept of combining education and entertainment has become increasingly popular. Edutainment (education and entertainment) environments started appearing in 1970 and have expanded, ever since, across the globe. This study seeks to explore the perception of guardians towards the edutainment experience and its impact on their children, with special reference to Kidzania’s branch in Cairo, Egypt. The study adopted an interpretive qualitative approach that combines different data gathering methods, including informal discussions, in-depth semi-structured interviews, on-site sketches, observation, field notes, photographs, and archival sources. The number of guardians involved in the study was 12, accompanying 23 children. A thematic analysis of the data revealed two important overarching themes: qualities of the edutainment environment, and the factors affecting the interaction between guardians and children. The first theme, qualities of the edutainment environment, includes three categories: safe environment, exploratory environment, and well-maintained environment. The second theme, factors affecting the interaction between guardians and children, encompasses three categories: physical proximity, visual connectivity, and provision of basic amenities. The findings of the study were discussed in light of relevant previous accounts and studies. In its conclusion, the study confirms that such edutainment environments can be considered as significant informal educational play settings in which children learn valuable life skills, complementing those learned in formal learning environments. Such findings are expected to provide useful insights that could inform different initiatives aiming to create thriving edutainment centers and engaging informal learning environments.
Prediction of Rubble-Stone Masonry Walls Response under Axial Compression Using 2D Particle Modelling
Authors: Azevedo Nuno Monteiro , Pinho Fernando F. S. , Cismaşiu Ildi , Souza Murilo
Published: August 2022

To predict the structural behaviour of ancient stone masonry walls is still a challenging task due to their strong heterogeneity. A rubble-stone masonry modeling methodology using a 2D particle model (2D-PM), based on the discrete element method is proposed given its ability to predict crack propagation by taking directly into account the material structure at the grain scale. Rubble-stone (ancient) masonry walls tested experimentally under uniaxial compression loading conditions are numerically evaluated. The stone masonry numerical models are generated from a close mapping process of the stone units and of the mortar surfaces. A calibration procedure for the stone-stone and mortar-mortar contacts based on experimental data is presented. The numerical studies show that the 2D-PM wall models can predict the formation and propagation of cracks, the initial stiffness and the maximum load obtained experimentally in traditional stone masonry walls. To reduce the simulation times, it is shown that the wall lateral numerical model adopting a coarser mortar discretization is a viable option for these walls. The mortar behaviour under compression with lateral confinement is identified as an important micro-parameter, that influences the peak strength and the ductility of rubble-masonry walls under uniaxial loading.
The Role of Carbon Nanoparticles in Lymph Node Dissection and Parathyroid Gland Preservation during Surgery for Thyroid Cancer: A Systematic Review and Meta-Analysis
Authors: Koimtzis Georgios , Stefanopoulos Leandros , Alexandrou Vyron , Tteralli Nikos , Brooker Verity , Alawad Awad Ali , Carrington-Windo Eliot , Karakasis Nikolaos , Geropoulos Georgios , Papavramidis Theodosios
Published: August 2022

Thyroid cancer is the most common endocrine malignancy with an increasing incidence over the past few years. Surgery is considered the primary therapeutic option, which often involves lymph node dissection. The aim of this study was to assess the role of carbon nanoparticles, a novel agent, in thyroid cancer surgery. For that purpose, we conducted a systematic review of the literature on MEDLINE, EMBASE, Scopus, Cochrane and Google Scholar databases from 1 January 2002 to 31 January 2022. Ultimately, 20 articles with a total number of 2920 patients were included in the analysis. The outcome of the analysis showed that the use of carbon nanoparticles is associated with a higher number of harvested lymph nodes (WMD, 1.47, 95% CI, 1.13 to 1.82, p < 0.001) and a lower rate of accidental parathyroid gland removal (OR 0.34, CI 95% 0.24 to 0.50, p < 0.001). Based on these results, we suggest that carbon nanoparticles are applied in thyroid cancer surgery on a wider scale, so that these findings can be confirmed by future research on the subject.
Early-Onset Cancers in Adults: A Review of Epidemiology, Supportive Care Needs and Future Research Priorities
Authors: Hamilton Ashleigh C. , Donnelly David W. , Fitzpatrick Deirdre , Coleman Helen G.
Published: August 2022

Rising incidence of specific types of early-age onset cancers in adults aged 18–49 years has been reported in high-income countries. In this review, we summarise the epidemiology of early-onset cancers using exemplar data from a high-income UK region, discuss supportive care needs for young patients and outline future research directions. The incidence rate of early-onset cancers increased by 20.5% from 1993 to 2019 in Northern Ireland. Differences in types of cancer were observed between sexes and across age groups of 18–29, 30–39 and 40–49 years. One and five-year net survival was mostly better in 18–29-year-olds for all cancers combined compared to older age groups for both sexes, but there were variations in specific cancer types. Poorer survival was observed for patients with brain/central nervous system, connective and soft tissue or lung cancers. Patients with early-onset cancers face unique supportive care needs and require holistic care. The impact of cancer treatment on fertility and fertility preservation treatments is an important consideration. Social media can be used for patient support, information, fundraising, advocacy work and recruitment to research studies. We also outline suggested future research priorities for early-onset cancers, spanning prevention, diagnosis, treatment and supportive care needs.
Prognostic Impact of Post-Diagnosis Smoking Cessation among Bladder Cancer Patients: A Systematic Literature Review and Meta-Analysis
Authors: Caini Saverio , Del Riccio Marco , Vettori Virginia , Francolini Giulio , D’Ecclesiis Oriana , Cai Tommaso , Gaeta Aurora , Bonaccorsi Guglielmo , Zanna Ines , Palli Domenico , Gandini Sara
Published: August 2022

We reviewed the studies examining whether quitting smoking at or around diagnosis favourably affects the prognosis of bladder cancer (BC) patients, who are often active smokers at diagnosis. We found only nine eligible articles published until 31 January 2022, which encompassed around 5500 BC in total, the majority of which were nonmuscle invasive BC (only one paper included muscle-invasive BC). We used random effects meta-analysis to obtain a summary hazard ratio (SHR) and 95% confidence intervals (CI). The median proportion of smokers who quit at or around diagnosis was 29.8% (range 8.4–43.1%). For the overall, BC-specific, and progression-free survival, the studies were limited in number (n = 3) and provided conflicting results. At the same time, quitters did not appear to have a lower risk of recurrence than continued smokers (SHR 0.99, 95% CI 0.61–1.61). In conclusion, while the evidence is currently not sufficient to draw firm conclusions (especially for patients with muscle-invasive BC), physicians should not refrain from educating smoking BC patients about the benefits of smoking cessation and provide the necessary support.
Quantitative Analysis of Colonic Perfusion Using ICG Fluorescence Angiography and Its Consequences for Anastomotic Healing in a Rat Model
Authors: Wada Toshiaki , Kawada Kenji , Hanada Keita , Obama Kazutaka
Published: August 2022

Forty-three rats were randomly assigned to the following four groups: non-ischemic group (Control Group), 1 cm-long ischemic group (Group 1), 2 cm-long ischemic group (Group 2), and 3 cm-long ischemic group (Group 3). The rates of AL were 0% (0/10) in the Control Group, 22.2% (2/9) in Group 1, 25% (2/8) in Group 2, and 50% (4/8) in Group 3. The bursting pressure of the Control Group was significantly higher than that of the other groups (p < 0.01). Regarding the pathological findings, the granulation thickness and the number of blood vessels at the anastomosed site were significantly higher in the Control Group than in Group 3 (p < 0.05). Receiver operating characteristics analysis revealed that Slope was the most significant predictor of AL, with an area under the curve of 0.861. When the cutoff value of Slope was 0.4, the sensitivity and specificity for the prediction of AL were 75% and 81.4%, respectively. Quantitative analysis of ICG fluorescence angiography could predict AL in a rat model.
Connected-SegNets: A Deep Learning Model for Breast Tumor Segmentation from X-ray Images
Authors: Alkhaleefah Mohammad , Tan Tan-Hsu , Chang Chuan-Hsun , Wang Tzu-Chuan , Ma Shang-Chih , Chang Lena , Chang Yang-Lang
Published: August 2022

Inspired by Connected-UNets, this study proposes a deep learning model, called Connected-SegNets, for breast tumor segmentation from X-ray images. In the proposed model, two SegNet architectures are connected with skip connections between their layers. Moreover, the cross-entropy loss function of the original SegNet has been replaced by the intersection over union (IoU) loss function in order to make the proposed model more robust against noise during the training process. As part of data preprocessing, a histogram equalization technique, called contrast limit adapt histogram equalization (CLAHE), is applied to all datasets to enhance the compressed regions and smooth the distribution of the pixels. Additionally, two image augmentation methods, namely rotation and flipping, are used to increase the amount of training data and to prevent overfitting. The proposed model has been evaluated on two publicly available datasets, specifically INbreast and the curated breast imaging subset of digital database for screening mammography (CBIS-DDSM). The proposed model has also been evaluated using a private dataset obtained from Cheng Hsin General Hospital in Taiwan. The experimental results show that the proposed Connected-SegNets model outperforms the state-of-the-art methods in terms of Dice score and IoU score. The proposed Connected-SegNets produces a maximum Dice score of 96.34% on the INbreast dataset, 92.86% on the CBIS-DDSM dataset, and 92.25% on the private dataset. Furthermore, the experimental results show that the proposed model achieves the highest IoU score of 91.21%, 87.34%, and 83.71% on INbreast, CBIS-DDSM, and the private dataset, respectively.
Adenosine Targeting as a New Strategy to Decrease Glioblastoma Aggressiveness
Authors: Bova Valentina , Filippone Alessia , Casili Giovanna , Lanza Marika , Campolo Michela , Capra Anna Paola , Repici Alberto , Crupi Lelio , Motta Gianmarco , Colarossi Cristina , Chisari Giulia , Cuzzocrea Salvatore , Esposito Emanuela , Paterniti Irene
Published: August 2022

Glioblastoma is the most commonly malignant and aggressive brain tumor, with a high mortality rate. The role of the purine nucleotide adenosine and its interaction with its four subtypes receptors coupled to the different G proteins, A1, A2A, A2B, and A3, and its different physiological functions in different systems and organs, depending on the active receptor subtype, has been studied for years. Recently, several works have defined extracellular adenosine as a tumoral protector because of its accumulation in the tumor microenvironment. Its presence is due to both the interaction with the A2A receptor subtype and the increase in CD39 and CD73 gene expression induced by the hypoxic state. This fact has fueled preclinical and clinical research into the development of efficacious molecules acting on the adenosine pathway and blocking its accumulation. Given the success of anti-cancer immunotherapy, the new strategy is to develop selective A2A receptor antagonists that could competitively inhibit binding to its endogenous ligand, making them reliable candidates for the therapeutic management of brain tumors. Here, we focused on the efficacy of adenosine receptor antagonists and their enhancement in anti-cancer immunotherapy.
Role of Exosomes in Immunotherapy of Hepatocellular Carcinoma
Authors: Tian Bao-Wen , Han Cheng-Long , Dong Zhao-Ru , Tan Si-Yu , Wang Dong-Xu , Li Tao
Published: August 2022

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, having a significantly poor prognosis and no sufficiently efficient treatments. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has provided new therapeutic approaches for HCC patients. Nevertheless, most patients with HCC do not benefit from immunotherapy. Exosomes are biologically active lipid bilayer nano-sized vesicles ranging in size from 30 to 150 nm and can be secreted by almost any cell. In the HCC tumor microenvironment (TME), numerous cells are involved in tumor progression, and exosomes—derived from tumor cells and immune cells—exhibit unique composition profiles and act as intercellular communicators by transporting various substances. Showing the dual characteristics of tumor promotion and suppression, exosomes exert multiple functions in shaping tumor immune responses in the crosstalk between tumor cells and surrounding immune cells, mediating immunotherapy resistance by affecting the PD-1/PD-L1 axis or the anti-tumor function of immune cells in the TME. Targeting exosomes or the application of exosomes as therapies is involved in many aspects of HCC immunotherapies (e.g., ICIs, tumor vaccines, and adoptive cell therapy) and may substantially enhance their efficacy. In this review, we discuss the impact of exosomes on the HCC TME and comprehensively summarize the role of exosomes in immunotherapy resistance and therapeutic application. We also discuss the potential of exosomes as biomarkers for predicting the efficacy of immunotherapy to help clinicians in identifying HCC patients who are amenable to immunotherapies.
Dendritic Cell Vaccines: A Promising Approach in the Fight against Ovarian Cancer
Authors: Caro Aarushi Audhut , Deschoemaeker Sofie , Allonsius Lize , Coosemans An , Laoui Damya
Published: August 2022

Ovarian cancer (OC) is the deadliest gynecological malignancy in developed countries and is the seventh-highest cause of death in women diagnosed with cancer worldwide. Currently, several therapies are in use against OC, including debulking surgery, chemotherapy, as well as targeted therapies. Even though the current standard-of-care therapies improve survival, a vast majority of OC patients relapse. Additionally, immunotherapies have only resulted in meager patient outcomes, potentially owing to the intricate immunosuppressive nexus within the tumor microenvironment. In this scenario, dendritic cell (DC) vaccination could serve as a potential addition to the therapeutic options available against OC. In this review, we provide an overview of current therapies in OC, focusing on immunotherapies. Next, we highlight the potential of using DC vaccines in OC by underscoring the different DC subsets and their functions in OC. Finally, we provide an overview of the advances and pitfalls of current DC vaccine strategies in OC while providing future perspectives that could improve patient outcomes.