bluuebunny/crossref_metadata_2025 huggingface dataset:
The Alteration of Giglio Island Granite: Relevance to the Conservation of Monumental Architecture
Authors: Fratini Fabio , Rescic Silvia , Cuzman Oana Adriana , Pierattini Paolo
Published: May 2022

The research examines the alteration phenomena of Giglio island granite, a rock quarried by Romans from the 3rd century, used for columns in the Italian peninsula and later reemployed in many Christian religious buildings. The study has shown that already in the bedrock there are small percentages of clay minerals. Starting from this condition, the alteration develops by an increase in porosity, which in turn favours the establishment of a slight hydrolysis of the silicates with a decrease in Na, Ca, and K, in accordance with the sericitisation process. The alteration proceeds with a further increase in porosity, apparently not related to a real loss of cohesion, which, however, occurs shortly after, highlighting the necessity of a continuous monitoring of the state of conservation of the material in the architectural heritage.
Research on an Evaluation Method for the Adaptability of TBM Tunnelling
Authors: Tan Zhongsheng , Li Zonglin , Zhou Zhenliang , Lai Haixiang , Jiao Yifeng , Li Fengyuan , Wang Liming
Published: May 2022

When a TBM carries out tunnelling in complex strata, there is often low tunnelling efficiency and an increase in tunnelling costs due to the improper selection of tunnelling parameters, the wrong estimation of geological conditions, or adverse geology, so it is necessary to evaluate the tunnelling adaptability of TBM construction. In this paper, based on hydraulic engineering in Xinjiang, 11 evaluation indexes of TBM tunnelling adaptability are determined by comprehensively considering the influence of tunnelling parameters, geological conditions, and adverse geological factors on TBM tunnelling adaptability. After that, the membership function of each evaluation index is determined by referring to the existing research results and fuzzy mathematics method, and the weight of each evaluation index is determined and adjusted by the analytic hierarchy process (AHP)–entropy weight (EW) method. Finally, the adaptability evaluation method and evaluation model of TBM tunnelling are put forward. The TBM tunnelling adaptability evaluation model proposed in this paper is verified by relying on the actual situation of three interval tunnels in the project, and good effects are obtained. This study can provide a reference for the evaluation of TBM tunnelling adaptability in similar strata.
Antimicrobial Efficacy of Edible Mushroom Extracts: Assessment of Fungal Resistance
Authors: Kim Jong H. , Tam Christina C. , Chan Kathleen L. , Mahoney Noreen , Cheng Luisa W. , Friedman Mendel , Land Kirkwood M.
Published: May 2022

Antimicrobial efficacy of the water or methanolic extracts of three medicinal mushrooms Taiwanofungus camphoratus, Agaricus blazei Murrill, and Ganoderma lucidum (Curtis) P. Karst were investigated against yeast and filamentous fungal pathogens as well as against commensal and pathogenic bacteria. The methanolic extract of T. camphoratus (TcM) exhibited both potent antifungal and antibacterial activity, while the water extract of T. camphoratus (TcW) showed limited antibacterial activity against Listeria monocytogenes. Neither the methanolic nor water extracts of A. blazei and G. lucidum exhibited antimicrobial activity. In the risk assessment testing monitoring the development of fungal tolerance to mushroom extracts in food matrices, two P. expansum mitogen-activated protein kinase (MAPK) mutants exhibited a tolerance to TcM. In a proof-of-concept bioassay using the natural benzoic salicylaldehyde (SA), P. expansum and A. fumigatus MAPK antioxidant mutants showed similar tolerance to SA, suggesting that natural ingredients in TcM such as benzoic derivatives could negatively affect the efficacy of TcM when antioxidant mutants are targeted. Conclusion: TcM could be developed as a food ingredient having antimicrobial potential. The antimicrobial activity of TcM operates via the intact MAPK antioxidant signaling system in microbes, however, mutants lacking genes in the MAPK system escape the toxicity triggered by TcM. Therefore, caution should be exercised in the use of TcM so as to not adversely affect food safety and quality by triggering the resistance of antioxidant mutants in contaminated food.
Effects of Grout Compactness on the Tensile Behavior of Grouted Splice Sleeve Connectors
Authors: Zhang Zhangrong , Jiang Shaofei , Cai Wanxia , Zhang Chunming
Published: May 2022

The quality of grouted sleeve has a significant influence on the performance of the sleeve splice. Incompactness of the infilled grout is inevitable in sleeve grouting. To investigate the tensile behavior of grouted splice sleeves due to different grout compactness, monotonic tensile tests on grouted splice sleeve connectors were performed at grout compactness of 100%, 90%, 70%, and 50%, respectively. The bond-slip analytical model of rebar-grout was deduced by fitting the tensile test data, and the formula for the tensile capacity of the grouted splice sleeve was proposed in the paper. The results show that the tensile strength of the splice sleeve reduces as the grout compactness decreases. It was found from the experiment that the calculated values of tensile capacity are in good agreement with the experimental values. The proposed formula can be adopted in determining whether reinforcing remedies or re-grouting should be taken in the case of incompact grout in grouted splice sleeve connectors.
Detailed Carbon Isotope Study of PM2.5 Aerosols at Urban Background, Suburban Background and Regional Background Sites in Hungary
Authors: Major István , Molnár Mihály , Futó István , Gergely Virág , Bán Sándor , Machon Attila , Salma Imre , Varga Tamás
Published: May 2022

The aim of this study was to estimate and refine the potential sources of carbon in the atmospheric PM2.5 fraction aerosol at three sampling sites in Hungary. Quantification of total, organic and elemental carbon (TC, OC and EC, respectively), as well as radiocarbon (14C) and stable carbon isotope analyses were performed on exposed filters collected at an urban background site, a suburban background site of the capital of Hungary, Budapest from October 2017 to July 2018. Results were also collected from the rural regional background site of K-puszta. Compared to TC concentrations from other regions of Europe, the ratio of the lowest and highest values at all sites in Hungary are lower than these European locations, probably due to the specific meteorological conditions prevailing in the Carpathian Basin over the observation period. The concentration of OC was constantly higher than that of EC and a seasonal variation with higher values in the heating period (October–March) and lower values in the non-heating vegetation period (April–September) could be observed for both EC and OC fractions. Using 14C, the seasonal mean fraction of contemporary carbon (fC) within the TC varied between 0.50 and 0.78 at the sites, suggesting that modern sources were remarkable during the year, regardless of the heating or vegetation period. At the two urban sites, assuming constant industrial emission during the year, the fossil fuel combustion sources were responsible for the seasonal variation of EC, while modern carbon emissions from biomass-burning and biogenic sources influenced the OC concentration. The higher EC/TC ratios at these sites were associated with lower fC and δ13C values, which can be explained by soot emission from transportation. The notably high EC/TC ratios in the spring were likely caused by the reduced concentration of OC instead of increased EC concentrations. This could probably be caused by the ending of winter biomass burning, which emits a huge amount of OC into the atmosphere. On the contrary, the rural K-puszta site showed some differences relative to the sites in Budapest. No correlation could be revealed between the EC/TC ratio, fC and δ13C results, suggesting that the structure of sources was very stagnant and balanced in each season. In autumn, however, some less depleted values were observed, and agricultural corn-stalk burning after harvesting in the southern and eastern directions from Hungary can be suggested as the main source.
Investigation of the Upper Respiratory Tract of a Male Smoker with Laryngeal Cancer by Inhaling Air Associated with Various Physical Activity Levels
Authors: Mortazavy Beni Hamidreza , Mortazavi Hamed , Tashvighi Ebrahim , Islam Mohammad S.
Published: May 2022

Smokers are at a higher risk of laryngeal cancer, which is a type of head and neck cancer in which cancer cells proliferate and can metastasize to other tissues after a tumor has formed. Cigarette smoke greatly reduces the inhaled air quality and can also lead to laryngeal cancer. In this study, the upper airway of a 70-year-old smoker with laryngeal cancer was reconstructed by taking a CT scan using Mimics software. To solve the governing equations, computational fluid dynamics (CFD) with a pressure base approach was used with the help of Ansys 2021 R1 software. As a result, the maximum turbulence intensity occurred in the larynx. At 13 L/min, 55 L/min, and 100 L/min, the maximum turbulence intensity was 1.1, 3.5, and 6.1, respectively. The turbulence intensity in the respiratory system is crucial because it demonstrates the ability to transfer energy. The maximum wall shear stress (WSS) also occurred in the larynx. At 13 L/min, 55 L/min, and 100 L/min, the maximum WSS was 0.62 Pa, 5.4 Pa, and 12.4 Pa, respectively. The WSS index cannot be calculated in vivo and should be calculated in vitro. Excessive WSS in the epiglottis is inappropriate and can lead to an airway obstruction. Furthermore, real mathematical modeling outcomes provide an approach for future prevention, treatment, and management planning by forecasting the zones prone to an acceleration of disease progression. In this regard, accurate computational modeling leads to pre-visualization in surgical planning to define the best reformative techniques to determine the most probable patient condition consequences.
Changes in Precipitation Conditions in the Warm Half-Year in the Polish–Saxon Border Region in Relation to the Atmospheric Circulation
Authors: Miszuk Bartłomiej
Published: May 2022

Precipitations are one of the most important factors affecting water resources in the transboundary Polish–Saxon region. The main goal of the research was to examine the multiannual changes in precipitations in the April–September period in 1971–2018, depending on circulation conditions, based on Ojrzyńska’s classification. The analysis was carried out based on meteorological data from Polish and German meteorological stations. The results showed that most of precipitation totals and intensive precipitations were observed under SW-A and SW-C circulation, whereas the anticyclonic types of NE-A, NW-A and SW-A were mainly responsible for dry days occurrence. In terms of multiannual changes, most of the stations were characterized by insignificant trends for the considered indices. Some positive trends were observed for intensive precipitations in the lower hypsometric zones. In the mountains, a decreasing tendency dominated for both precipitation totals and intensive precipitations, especially for the northern types of circulation. Furthermore, a significant increase was reported throughout the region for most of the indices for the SW-A type, including precipitation totals, strong precipitations and dry days. Considering the observed trends, floods related to heavy rains can intensify in the lowlands, while a potential increase in the anticyclonic circulation can significantly limit water resources in the region.
Investigation of Policy Relevant Background (PRB) Ozone in East Asia
Authors: Lam Yun Fat , Cheung Hung Ming
Published: May 2022

The concept of Policy Relevant Background (PRB) ozone has emerged in recent years to address the air quality baseline on the theoretical limits of air pollution controls. In this study, the influence of Long-range Transport (LRT) of air pollutants from North America and the effect of Stratosphere-Troposphere Transport (STT) on PRB ozone was investigated using GEOS-Chem coupled WRF-CMAQ modelling system. Four distinct seasons in 2006 were simulated to understand better the seasonal and geographical impacts of these externalities on PRB ozone over East Asia (EA). Overall, the LRT impact from North America has been found to be ~0.54 ppbv, while the maximum impacts were found at the mountain stations with values of 2.3 ppbv, 3.3 ppbv, 2.3 ppbv, and 3.0 ppbv for January, April, July, and October, respectively. In terms of PRB ozone, the effect of STT has enhanced the surface background ozone by ~3.0 ppbv, with a maximum impact of 7.8 ppbv found in the northeastern part of East Asia (near Korea and Japan). Springtime (i.e., April) has the most vital STT signals caused by relatively cold weather and unstable atmospheric condition resulting from the transition of the monsoon season. The simulated PRB ozone based on the mean values of the maximum daily 8-h average (MDA8) is 53 ppbv for spring (April) and 22 ppbv for summer (July). Up to ~1.0 ppbv and ~2.2 ppbv of MDA8 ozone were attributed to LRT and STT, respectively. Among the selected cities, Beijing and Guangzhou have received the most substantial anthropogenic enhancement in MDA8 ozone in summer, ranging from 40.0 ppbv to 56.0 ppbv.
An Estimation of Precipitation Retention Time Using Depth Metres in the Northern Basin of Lake Biwa
Authors: Iwaki Maho , Hayakawa Kazuhide , Goto Naoshige
Published: May 2022

To facilitate climate change adaptations and water management, estimates of precipitation retention time (time required for precipitation to reach a lake) can help to accurately determine a water body’s terrestrial water storage capacity and water cycle. Although estimating the precipitation retention time on land is difficult, estimating the lag between precipitation on land and a rise in lake water levels is possible. In this study, the delay times (using a depth metre installed in the mooring system in the northern basin of Lake Biwa from August 2017 to October 2018) were calculated using response functions, and it evaluated the precipitation retention time in the catchment. However, as several delays between the river surface flow (<1 d) and shallow subsurface flow (≈45 d) remained unidentified, the delay times resulting from direct precipitation on the lake as well as from internal seiches were determined. The results suggest that delay times of approximately 20 d correspond to the paddy–waterway system between the river inflow and the subsurface flow, and that this effect corresponds to that of large rivers such as the Ane River. These findings can enhance water management strategies regarding the regulation of river flows, adapting to climate change-induced fluctuations in precipitation.
Quasi-Static and Dynamic Photon Bubbles in Cold Atom Clouds
Authors: Rodrigues João D. , Giampaoli Ruggero , Rodrigues José A. , Ferreira António V. , Terças Hugo , Mendonça José T.
Published: May 2022

Turbulent radiation flow is ubiquitous in many physical systems where light–matter interaction becomes relevant. Photon bubble instabilities, in particular, have been identified as a possible source of turbulent radiation transport in astrophysical objects such as massive stars and black hole accretion disks. Here, we report on the experimental observation of a photon bubble instability in cold atomic gases, in the presence of multiple scattering of light. Two different regimes are identified, namely, the growth and formation of quasi-static structures of depleted atom density and increased photon number, akin to photon bubbles in astrophysical objects, and the destabilisation of these structures in a second regime of photon bubble turbulence. A two-fluid theory is developed to model the coupled atom–photon gas and to describe both the saturation of the instability in the regime of quasi-static bubbles and the low-frequency turbulent phase associated with the growth and collapse of photon bubbles inside the atomic sample. We also employ statistical dimensionality reduction techniques to describe the low-dimensional nature of the turbulent regime. The experimental results reported here, along with the theoretical model we have developed, may shed light on analogue photon bubble instabilities in astrophysical scenarios. Our findings are consistent with recent analyses based on spatially resolved pump–probe measurements.
Finite Time Blowup in a Fourth-Order Dispersive Wave Equation with Nonlinear Damping and a Non-Local Source
Authors: Vernier-Piro Stella
Published: May 2022

In this work, we consider a class of initial boundary value problems for fourth-order dispersive wave equations with superlinear damping and non-local source terms as well as time-dependent coefficients in Ω×(t>0), where Ω is a bounded domain in RN and N≥2. We prove that there exists a safe time interval of existence in the solution [0,T], with T being a lower bound of the blowup time t*. Moreover, we find an explicit lower bound of t*, assuming the coefficients are positive constants.
Soil Mineral Composition and Salinity Are the Main Factors Regulating the Bacterial Community Associated with the Roots of Coastal Sand Dune Halophytes
Authors: Vu Minh Thiet , Geraldi Almando , Do Hoang Dang Khoa , Luqman Arif , Nguyen Hoang Danh , Fauzia Faiza Nur , Amalludin Fahmi Ikhlasul , Sadila Aliffa Yusti , Wijaya Nabilla Hapsari , Santoso Heri , Manuhara Yosephine Sri Wulan , Bui Le Minh , Hariyanto Sucipto , Wibowo Anjar Tri
Published: May 2022

Soil salinity and mineral deficiency are major problems in agriculture. Many studies have reported that plant-associated microbiota, particularly rhizosphere and root microbiota, play a crucial role in tolerance against salinity and mineral deficiency. Nevertheless, there are still many unknown parts of plant–microbe interaction, especially regarding their role in halophyte adaptation to coastal ecosystems. Here, we report the bacterial community associated with the roots of coastal sand dune halophytes Spinifex littoreus and Calotropis gigantea, and the soil properties that affect their composition. Strong correlations were observed between root bacterial diversity and soil mineral composition, especially with soil Calcium (Ca), Titanium (Ti), Cuprum (Cu), and Zinc (Zn) content. Soil Ti and Zn content showed a positive correlation with bacterial diversity, while soil Ca and Cu had a negative effect on bacterial diversity. A strong correlation was also found between the abundance of several bacterial species with soil salinity and mineral content, suggesting that some bacteria are responsive to changes in soil salinity and mineral content. Some of the identified bacteria, such as Bacillus idriensis and Kibdelosporangium aridum, are known to have growth-promoting effects on plants. Together, the findings of this work provided valuable information regarding bacterial communities associated with the roots of sand dune halophytes and their interactions with soil properties. Furthermore, we also identified several bacterial species that might be involved in tolerance against stresses. Further work will be focused on isolation and transplantation of these potential microbes, to validate their role in plant tolerance against stresses, not only in their native hosts but also in crops.
Silk Fibroin-Based Biomaterials for Hemostatic Applications
Authors: Sultan Md. Tipu , Hong Heesun , Lee Ok Joo , Ajiteru Olatunji , Lee Young Jin , Lee Ji Seung , Lee Hanna , Kim Soon Hee , Park Chan Hum
Published: May 2022

Hemostasis plays an essential role in all surgical procedures. Uncontrolled hemorrhage is the primary cause of death during surgeries, and effective blood loss control can significantly reduce mortality. For modern surgeons to select the right agent at the right time, they must understand the mechanisms of action, the effectiveness, and the possible adverse effects of each agent. Over the past decade, various hemostatic agents have grown intensely. These agents vary from absorbable topical hemostats, including collagen, gelatins, microfibrillar, and regenerated oxidized cellulose, to biologically active topical hemostats such as thrombin, biological adhesives, and other combined agents. Commercially available products have since expanded to include topical hemostats, surgical sealants, and adhesives. Silk is a natural protein consisting of fibroin and sericin. Silk fibroin (SF), derived from silkworm Bombyx mori, is a fibrous protein that has been used mostly in fashion textiles and surgical sutures. Additionally, SF has been widely applied as a potential biomaterial in several biomedical and biotechnological fields. Furthermore, SF has been employed as a hemostatic agent in several studies. In this review, we summarize the several morphologic forms of SF and the latest technological advances on the use of SF-based hemostatic agents.
Hyperbaric Oxygen Therapy Improves Parkinson’s Disease by Promoting Mitochondrial Biogenesis via the SIRT-1/PGC-1α Pathway
Authors: Hsu Hung-Te , Yang Ya-Lan , Chang Wan-Hsuan , Fang Wei-Yu , Huang Shu-Hung , Chou Shah-Hwa , Lo Yi-Ching
Published: May 2022

Hyperbaric oxygen therapy (HBOT) has been suggested as a potential adjunctive therapy for Parkinson’s disease (PD). PD is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The aim of this study was to investigate the protective mechanisms of HBOT on neurons and motor function in a 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and 1-methyl-4-phenylpyridinium (MPP+)-mediated neurotoxicity in SH-SY5Y cells on the potential protective capability. In vivo: male C57BL/6 mice were randomly divided into three groups: control, MPTP group and MPTP+HBOT group. The MPTP-treated mice were intraperitoneally received MPTP (20 mg/kg) four times at 2 h intervals within a day. The day after MPTP treatment, MPTP+HBOT mice were exposed to hyperbaric oxygen at 2.5 atmosphere absolute (ATA) with 100% oxygen for 1 h once daily for 7 consecutive days. In vitro: retinoic acid (RA)-differentiated SH-SY5Y cells were treated with MPP+ for 1 h followed by hyperbaric oxygen at 2.5 ATA with 100% oxygen for 1 h. The results showed that MPTP induced a significant loss in tyrosine hydroxylase (TH)-positive neurons in the SNpc of mice. HBOT treatment significantly increased the number of TH-positive neurons, with enhanced neurotrophic factor BDNF, decreased apoptotic signaling and attenuated inflammatory mediators in the midbrain of MPTP-treated mice. In addition, MPTP treatment decreased the locomotor activity and grip strength of mice, and these effects were shown to improve after HBOT treatment. Furthermore, MPTP decreased mitochondrial biogenesis signaling (SIRT-1, PGC-1α and TFAM), as well as mitochondrial marker VDAC expression, while HBOT treatment was shown to upregulate protein expression. In cell experiments, MPP+ reduced neurite length, while HBOT treatment attenuated neurite retraction. Conclusions: the effects of HBOT in MPTP-treated mice might come from promoting mitochondrial biogenesis, decreasing apoptotic signaling and attenuating inflammatory mediators in the midbrain, suggesting its potential benefits in PD treatment.
Paradoxical Behavior of Oncogenes Undermines the Somatic Mutation Theory
Authors: Monti Noemi , Verna Roberto , Piombarolo Aurora , Querqui Alessandro , Bizzarri Mariano , Fedeli Valeria
Published: May 2022

The currently accepted theory on the influence of DNA mutations on carcinogenesis (the Somatic Mutation Theory, SMT) is facing an increasing number of controversial results that undermine the explanatory power of mutated genes considered as “causative” factors. Intriguing results have demonstrated that several critical genes may act differently, as oncogenes or tumor suppressors, while phenotypic reversion of cancerous cells/tissues can be achieved by modifying the microenvironment, the mutations they are carrying notwithstanding. Furthermore, a high burden of mutations has been identified in many non-cancerous tissues without any apparent pathological consequence. All things considered, a relevant body of unexplained inconsistencies calls for an in depth rewiring of our theoretical models. Ignoring these paradoxes is no longer sustainable. By avoiding these conundrums, the scientific community will deprive itself of the opportunity to achieve real progress in this important biomedical field. To remedy this situation, we need to embrace new theoretical perspectives, taking the cell–microenvironment interplay as the privileged pathogenetic level of observation, and by assuming new explanatory models based on truly different premises. New theoretical frameworks dawned in the last two decades principally focus on the complex interaction between cells and their microenvironment, which is thought to be the critical level from which carcinogenesis arises. Indeed, both molecular and biophysical components of the stroma can dramatically drive cell fate commitment and cell outcome in opposite directions, even in the presence of the same stimulus. Therefore, such a novel approach can help in solving apparently inextricable paradoxes that are increasingly observed in cancer biology.
The Influence of Different Footwear Insole Stiffness on Center of Pressure and Ankle Kinematics during Walking: A Case Report
Authors: Jin Li
Published: May 2022

During locomotion, the foot–ankle system plays an important role for forward progression of the body. The center of pressure (COP) is regarded as the point of the ground reaction force (GRF) vector acting on the foot surface during the stance phase. COP movement trajectory and velocity reflect the stance phase forward progression of the foot segment and the ankle joint motion characteristics. This study aimed to investigate different levels of footwear insole stiffness on COP forward velocity, GRF and ankle joint angles during walking stance phase. Two healthy subjects (one female, one male; age 26.5 ± 6.4 years, height 168.5 ± 2.1 cm, weight 64.9 ± 5.4 kg) participated in this study. Subjects were asked to walk along a 10 m walkway at two different speeds: self–selected normal (SSN) and self–selected fast (SSF). Within each walking speed, subjects were required to walk under two different insole stiffness conditions: (1) normal shoe insole (NSI) from the testing shoe (Nike Free RN Flyknit 2017) used in this study; (2) 1.6 mm thick carbon fiber insole (CFI) fitted within the testing shoe. Stiffer insole (CFI) significantly decreased peak ankle internal rotation angle (p = 0.001) and sagittal plane angle ROM (p = 0.022); additionally, CFI significantly increased peak ankle eversion angle compared to the NSI condition (p = 0.028). In conclusion, increasing footwear insole stiffness would alter stance phase ankle joint motion at SSF walking speed. Additionally, stiffer insoles may tend to decrease COP peak velocity at the initial heel strike and the terminal stance phase. Future research should investigate the combined effects of various insole properties on lower extremity system kinematic and kinetic patterns in various locomotion activities.
Ammonium Glycyrrhizinate and Bergamot Essential Oil Co-Loaded Ultradeformable Nanocarriers: An Effective Natural Nanomedicine for In Vivo Anti-Inflammatory Topical Therapies
Authors: Cristiano Maria Chiara , d’Avanzo Nicola , Mancuso Antonia , Tarsitano Martine , Barone Antonella , Torella Daniele , Paolino Donatella , Fresta Massimo
Published: May 2022

Bergamot essential oil (BEO) and Ammonium glycyrrhizinate (AG), naturally derived compounds, have remarkable anti-inflammatory properties, thus making them suitable candidates for the treatment of skin disorders. Despite this, their inadequate physicochemical properties strongly compromise their topical application. Ultradeformable nanocarriers containing both BEO and AG were used to allow their passage through the skin, thus maximizing their therapeutic activity. Physicochemical characterization studies were performed using Zetasizer Nano ZS and Turbiscan Lab®. The dialysis method was used to investigate the release profile of the active compounds. In vivo studies were performed on human healthy volunteers through the X-Rite spectrophotometer. The nanosystems showed suitable features for topical cutaneous administration in terms of mean size, surface charge, size distribution, and long-term stability/storability. The co-delivery of BEO and AG in the deformable systems improved both the release profile kinetic of ammonium glycyrrhizinate and deformability properties of the resulting nanosystems. The topical cutaneous administration on human volunteers confirmed the efficacy of the nanosystems. In detail, BEO and AG-co-loaded ultradeformable vesicles showed a superior activity compared to that recorded from the ones containing AG as a single agent. These results are promising and strongly encourage a potential topical application of AG/BEO co-loaded nanocarriers for anti-inflammatory therapies.
Genetic Alterations in Benign Adrenal Tumors
Authors: Pitsava Georgia , Stratakis Constantine A.
Published: May 2022

The genetic basis of most types of adrenal adenomas has been elucidated over the past decade, leading to the association of adrenal gland pathologies with specific molecular defects. Various genetic studies have established links between variants affecting the protein kinase A (PKA) signaling pathway and benign cortisol-producing adrenal lesions. Specifically, genetic alterations in GNAS, PRKAR1A, PRKACA, PRKACB, PDE11A, and PDE8B have been identified. The PKA signaling pathway was initially implicated in the pathogenesis of Cushing syndrome in studies aiming to understand the underlying genetic defects of the rare tumor predisposition syndromes, Carney complex, and McCune-Albright syndrome, both affected by the same pathway. In addition, germline variants in ARMC5 have been identified as a cause of primary bilateral macronodular adrenal hyperplasia. On the other hand, primary aldosteronism can be subclassified into aldosterone-producing adenomas and bilateral idiopathic hyperaldosteronism. Various genes have been reported as causative for benign aldosterone-producing adrenal lesions, including KCNJ5, CACNA1D, CACNA1H, CLCN2, ATP1A1, and ATP2B3. The majority of them encode ion channels or pumps, and genetic alterations lead to ion transport impairment and cell membrane depolarization which further increase aldosterone synthase transcription and aldosterone overproduction though activation of voltage-gated calcium channels and intracellular calcium signaling. In this work, we provide an overview of the genetic causes of benign adrenal tumors.
Recent Advances on Familial Hypercholesterolemia in Children and Adolescents
Authors: Mainieri Francesca , Tagi Veronica Maria , Chiarelli Francesco
Published: May 2022

Familial hypercholesterolemia is a common autosomal hereditary disorder characterized by elevated concentrations of low-density lipoprotein cholesterol and the development of premature atherosclerosis and cardiovascular disease. Early diagnosis, as well as prompt and aggressive treatment, are fundamental steps to prevent cardiovascular complications and a high rate of premature mortality in children and adolescents. Clinics and genetics are the two main aspects on which diagnosis is based. Widespread screening programs are a respectable option for the early detection of familial hypercholesterolemia. Different types of screening have been proposed so far; however, the optimal screening program has not yet been found. The treatment approach for both heterozygous and homozygous familial hypercholesterolemia in the pediatric population is multidisciplinary, including lifestyle modifications, standard lipid-lowering medications, and novel pharmacological agents. The latter show promising results, especially for patients who experience intolerance to other treatment or present with more severe conditions. Our purpose is to focus on the importance of the early detection of familial hypercholesterolemia, and to highlight the best therapeutic strategies, including the recent approaches based on current clinical evidence, that need to be adopted from the earliest stages of life.
Blood Neutrophil Counts Define Specific Clusters of Bronchiectasis Patients: A Hint to Differential Clinical Phenotypes
Authors: Wang Xuejie , Olveira Casilda , Girón Rosa , García-Clemente Marta , Máiz Luis , Sibila Oriol , Golpe Rafael , Menéndez Rosario , Rodríguez-López Juan , Prados Concepción , Martinez-García Miguel Angel , Rodriguez Juan Luis , de la Rosa David , Qin Liyun , Duran Xavier , Garcia-Ojalvo Jordi , Barreiro Esther
Published: May 2022

We sought to investigate differential phenotypic characteristics according to neutrophil counts, using a biostatistics approach in a large-cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 1034 patients who met the inclusion criteria were clustered into two groups on the basis of their blood neutrophil levels. Using the Mann–Whitney U test to explore potential differences according to FACED and EFACED scores between the two groups, a neutrophil count of 4990 cells/µL yielded the most balanced cluster sizes: (1) above-threshold (n = 337) and (2) below-threshold (n = 697) groups. Patients above the threshold showed significantly worse lung function parameters and nutritional status, while systemic inflammation levels were higher than in the below-threshold patients. In the latter group, the proportions of patients with mild disease were greater, while a more severe disease was present in the above-threshold patients. According to the blood neutrophil counts using biostatistics analyses, two distinct clinical phenotypes of stable patients with non-CF bronchiectasis were defined. Patients falling into the above-threshold cluster were more severe. Severity was characterized by a significantly impaired lung function parameters and nutritional status, and greater systemic inflammation. Phenotypic profiles of bronchiectasis patients are well defined as a result of the cluster analysis of combined systemic and respiratory variables.
Cerebrospinal Fluid Neurofilament Light Predicts Risk of Dementia Onset in Cognitively Healthy Individuals and Rate of Cognitive Decline in Mild Cognitive Impairment: A Prospective Longitudinal Study
Authors: Dhiman Kunal , Villemagne Victor L. , Fowler Christopher , Bourgeat Pierrick , Li Qiao-Xin , Collins Steven , Bush Ashley I. , Rowe Christopher C. , Masters Colin L. , Ames David , Blennow Kaj , Zetterberg Henrik , Martins Ralph N. , Gupta Veer
Published: May 2022

Background: Biomarkers that are indicative of early biochemical aberrations are needed to predict the risk of dementia onset and progression in Alzheimer’s disease (AD). We assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) chain for screening preclinical AD, predicting dementia onset among cognitively healthy (CH) individuals, and the rate of cognitive decline amongst individuals with mild cognitive impairment (MCI). Methods: Neurofilament light levels were measured in CSF samples of participants (CH, n = 154 and MCI, n = 32) from the Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL). Cases of preclinical AD were identified using biomarker-guided classification (CH, amyloid-β [Aβ]+, phosphorylated-tau [P-tau]+ and total-tau [T-tau]±; A+T+/N±). The prediction of dementia onset (questionable dementia) among CH participants was assessed as the risk of conversion from Clinical Dementia Rating [CDR = 0] to CDR ≥ 0.5 over 6 years. Mixed linear models were used to assess the utility of baseline CSF NfL levels for predicting the rate of cognitive decline among participants with MCI over 4.5 years. Results: Neurofilament light levels were significantly higher in preclinical AD participants (CH, A+T+/N±) as compared to A-T-N- (p < 0.001). Baseline levels of CSF NfL were higher in CH participants who converted to CDR ≥ 0.5 over 6 years (p = 0.045) and the risk of conversion to CDR ≥ 0.5 was predicted (hazard ratio [HR] 1.60, CI 1.03–2.48, p = 0.038). CH participants with CSF NfL > cut-off were at a higher risk of developing dementia (HR 4.77, CI 1.31–17.29, p = 0.018). Participants with MCI and with higher baseline levels of CSF NfL (>median) had a higher rate of decline in cognition over 4.5 years. Conclusion: An assessment of CSF NfL levels can help to predict dementia onset among CH vulnerable individuals and cognitive decline among those with MCI.
Trifluoperazine and Its Analog Suppressed the Tumorigenicity of Non-Small Cell Lung Cancer Cell; Applicability of Antipsychotic Drugs to Lung Cancer Treatment
Authors: Jeong Joo Yeon , Park Haangik , Yoo Hong , Kim Eun-Jin , Jeon Borami , Lee Jong Deog , Kang Dawon , Lee Changjoon Justin , Paek Sun Ha , Roh Eun Joo , Yi Gwan-Su , Kang Sang Soo
Published: May 2022

Despite significant advances in diagnostic and therapeutic technologies, lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Recently, some antipsychotics have been shown to possess anticancer activity. However, the effects of antipsychotics on NSCLC need to be further explored. We examined the effects of trifluoperazine (TFP), a commonly used antipsychotic drug, and its synthetic analogs on A549 human lung cancer cells. In addition, cell proliferation analysis, colony formation assay, flow cytometry, western blot analysis, and in vivo xenograft experiments were performed. Key genes and mechanisms possibly affected by TFP are significantly related to better survival outcomes in lung cancer patients. Treatment with TFP and a selected TFP analog 3dc significantly inhibited the proliferation, anchorage-dependent/independent colony formation, and migration of A549 cells. Treatment with 3dc affected the expression of genes related to the apoptosis and survival of A549 cells. Treatment with 3dc promoted apoptosis and DNA fragmentation. In all experiments, including in vivo studies of metastatic lung cancer development, 3dc had more substantial anticancer effects than TFP. According to our analysis of publicly available clinical data and in vitro and in vivo experiments, we suggest that some kinds of antipsychotics prevent the progression of NSCLC. Furthermore, this study indicates a synthetic TFP analog that could be a potential therapeutic for lung cancer.
The Relevance of Calibration in Machine Learning-Based Hypertension Risk Assessment Combining Photoplethysmography and Electrocardiography
Authors: Cano Jesús , Fácila Lorenzo , Gracia-Baena Juan M. , Zangróniz Roberto , Alcaraz Raúl , Rieta José J.
Published: May 2022

The detection of hypertension (HT) is of great importance for the early diagnosis of cardiovascular diseases (CVDs), as subjects with high blood pressure (BP) are asymptomatic until advanced stages of the disease. The present study proposes a classification model to discriminate between normotensive (NTS) and hypertensive (HTS) subjects employing electrocardiographic (ECG) and photoplethysmographic (PPG) recordings as an alternative to traditional cuff-based methods. A total of 913 ECG, PPG and BP recordings from 69 subjects were analyzed. Then, signal preprocessing, fiducial points extraction and feature selection were performed, providing 17 discriminatory features, such as pulse arrival and transit times, that fed machine-learning-based classifiers. The main innovation proposed in this research uncovers the relevance of previous calibration to obtain accurate HT risk assessment. This aspect has been assessed using both close and distant time test measurements with respect to calibration. The k-nearest neighbors-classifier provided the best outcomes with an accuracy for new subjects before calibration of 51.48%. The inclusion of just one calibration measurement into the model improved classification accuracy by 30%, reaching gradually more than 96% with more than six calibration measurements. Accuracy decreased with distance to calibration, but remained outstanding even days after calibration. Thus, the use of PPG and ECG recordings combined with previous subject calibration can significantly improve discrimination between NTS and HTS individuals. This strategy could be implemented in wearable devices for HT risk assessment as well as to prevent CVDs.
Sex Differences in Plasma Lysophosphatidic Acid Species in Patients with Alcohol and Cocaine Use Disorders
Authors: Flores-López María , García-Marchena Nuria , Araos Pedro , Requena-Ocaña Nerea , Porras-Perales Oscar , Torres-Galván Sandra , Suarez Juan , Pizarro Nieves , de la Torre Rafael , Rubio Gabriel , Ruiz-Ruiz Juan Jesús , Rodríguez de Fonseca Fernando , Serrano Antonia , Pavón-Morón Francisco Javier
Published: May 2022

Preclinical evidence suggests a main role of lysophosphatidic acid (LPA) signaling in drug addiction. Recently, we reported alterations in the plasma concentrations of LPA species in patients with alcohol use disorder (AUD). As there are sex differences in drug addiction, the main aim of the present study was to investigate whether relevant LPA species (16:0-LPA, 18:0-LPA, 18:1-LPA, 18:2-LPA and 20:4-LPA) were associated with sex and/or substance use disorder (SUD). This exploratory study was conducted in 214 abstinent patients with lifetime SUD, and 91 healthy control subjects. The SUD group was divided according to the diagnosis of AUD and/or cocaine use disorder (CUD). Participants were clinically assessed, and plasma samples were collected to determine LPA species and total LPA. We found that LPA concentrations were significantly affected by sex, and women showed higher concentrations than men. In addition, there were significantly lower 16:0-LPA, 18:2-LPA and total LPA concentrations in patients with SUD than in controls. Namely, patients with CUD and AUD + CUD showed lower LPA concentrations than controls or patients with AUD. In conclusion, our data suggest that LPA species could be potential biomarkers for SUD in women and men, which could contribute to a better stratification of these patients in treatment programs.
Dose Optimization of Anxiolytic Compounds Group in Valeriana jatamansi Jones and Mechanism Exploration by Integrating Network Pharmacology and Metabolomics Analysis
Authors: Zhao Chengbowen , Wei Xiaojia , Guo Jianyou , Ding Yongsheng , Luo Jing , Yang Xue , Li Jiayuan , Wan Guohui , Yu Jiahe , Shi Jinli
Published: May 2022

Anxiety disorder impacts the quality of life of the patients. The 95% ethanol extract of rhizomes and roots of Valeriana jatamansi Jones (Zhi zhu xiang, ZZX) has previously been shown to be effective for the treatment of anxiety disorder. In this study, the dose ratio of each component of the anxiolytic compounds group (ACG) in a 95% ethanol extract of ZZX was optimized by a uniform design experiment and mathematical modeling. The anxiolytic effect of ACG was verified by behavioral experiments and biochemical index measurement. Network pharmacology was used to determine potential action targets, as well as predict biological processes and signaling pathways, which were then verified by molecular docking analysis. Metabolomics was then used to screen and analyze metabolites in the rat hippocampus before and after the administration of ZZX-ACG. Finally, the results of metabolomics and network pharmacology were integrated to clarify the anti-anxiety mechanism of the ACG. The optimal dose ratio of ACG in 95% ethanol extract of ZZX was obtained, and our results suggest that ACG may regulate ALB, AKT1, PTGS2, CYP3A4, ESR1, CASP3, CYP2B6, EGFR, SRC, MMP9, IGF1, and MAPK8, as well as the prolactin signaling pathway, estrogen signaling pathway, and arachidonic acid metabolism pathway, thus affecting the brain neurotransmitters and HPA axis hormone levels to play an anxiolytic role, directly or indirectly.
RETRACTED: A Review on Building Design as a Biomedical System for Preventing COVID-19 Pandemic
Authors: Amran Mugahed , Makul Natt , Fediuk Roman , Borovkov Aleksey , Ali Mujahid , Zeyad Abdullah
Published: May 2022

Sustainable design methods aim to obtain architectural solutions that assure the coexistence and welfare of human beings, inorganic structures, and living things that constitute ecosystems. The novel coronavirus emergence, inadequate vaccines against the present severe acute respiratory syndrome-coronavirus-(SARS-CoV-2), and increases in microbial resistance have made it essential to review the preventative approaches used during pre-antibiotic periods. Apart from low carbon emissions and energy, sustainable architecture for facilities, building designs, and digital modeling should incorporate design approaches to confront the impacts of communicable infections. This review aims to determine how architectural design can protect people and employees from harm; it models viewpoints to highlight the architects’ roles in combating coronavirus disease 2019 (COVID-19) and designing guidelines as a biomedical system for policymakers. The goals include exploring the hospital architecture evolution and the connection between architectural space and communicable infections and recommending design and digital modeling strategies to improve infection prevention and controls. Based on a wide-ranging literature review, it was found that design methods have often played important roles in the prevention and control of infectious diseases and could be a solution for combating the wide spread of the novel coronavirus or coronavirus variants or delta.
Promotion Strategy of Smart Construction Site Based on Stakeholder: An Evolutionary Game Analysis
Authors: Guo Feng , Peng Xiaojing , Gu Jianglin
Published: May 2022

Smart Construction Sites (SCS) are important drivers for the construction of high-quality development. In order to determine the evolution of SCS advancement systems, an evolutionary game model consisting of government, enterprises and projects was constructed. The experimental simulations were performed by using a system dynamics approach. The findings were as follows: (1) There are three stable equilibrium strategies in the evolution of the game system: government, enterprises and projects all adopt positive strategies; government intervention, enterprises’ advancement, and projects’ non-participation; and government intervention, enterprises and projects adopting negative strategies. (2) Government penalties and balance of interests between enterprises and projects are the main factors affecting the evolution. (3) In the state (1,1,1), the influence of a government regulatory system is more significant in encouraging enterprises to promote SCS and projects to participate in building an SCS platform. (4) Government rewards and penalties, costs and benefits of corporate support for SCS, benefits when projects do not participate in SCS, are the main factors influencing the adoption of proactive strategies by companies and projects, and there are significant differences in the strategic directions and marginal impacts of each factor on stakeholders’ choices. These findings provide a reference for further refining stakeholder theory and for promoting the sustainable development of SCS.