bluuebunny/crossref_metadata_2025 huggingface dataset:
Air Quality Monitoring for Preventive Conservation of the Built Heritage Deteriorated by Salt Crystallization
Authors: Benavente David , Pla Concepción , Gil-Oncina Sara , Ruiz Maria Candela , Blanco-Quintero Idael Francisco , Huesca-Tortosa Jose Antonio , Spairani-Berrio Yolanda , Sanchez-Moral Sergio
Published: August 2022

The Santo Domingo Diocesan School (Orihuela, SE Spain) is a singular case study that relates air quality monitoring and stone conservation. The monument suffers severe damage due to salt crystallization by rising damp, which is related to the indoor environment dynamics, high groundwater salt content, and microstructure, the building’s porous stone (biocalcarenite). Results revealed that 222Rn concentration in indoor air is low due to the building’s high ventilation rate, despite the medium-low geogenic radon potential in the area. Wavelets analysis showed that ventilation is caused by outdoor and indoor temperature variations and directly affects the 222Rn and CO2 dynamics inside the church. CO2, as well as relative humidity (RH), presented periodicities with intermediate frequencies (5–8 days) related to visits. These RH and temperature (T) variations intensified the salt damage by increasing the frequency of dissolution-crystallization cycles. The mineralogical characterization and geochemical calculations concluded that chlorides (halite and sylvite), sulfates (thenardite, epsomite, hexahydrite and aphthitalite) and nitrates (niter) present from dissolution forms to whiskers and hopper-type morphologies. This indicates high saturation values and, therefore, higher crystallization pressure values within the porous media of the biocalcarenite. On the contrary, the near-equilibrium crystal shape and incongruent precipitation reaction for humberstonite suggest a lower alteration for this salt on the building stone.
Mindfulness Practice and Job Performance in Social Workers: Mediation Effect of Work Engagement
Authors: Huang Chien-Chung , Tu Bin , Zhang Huiyu , Huang Jamie
Published: August 2022

Despite a rapid increase in the work force over the last decade, the social work labor force is still suffering through high amounts of stress and burnout that could negatively affect work engagement and job performance in China. A potential solution worth exploring, however, is the practice of mindfulness, a concept based on expanding one’s awareness to target focus without judgement. Using 537 social workers from street-level social work service stations in Guangzhou, China, this paper examines the relation between mindfulness practice and job performance, and whether work engagement mediated the relation through the application of the job demand and resources theory. The findings indicate that that mindfulness practice directly increases work engagement (Beta = 0.33) and has an indirect effect on job performance (Beta = 0.21) through its effect on work engagement that fully mediated the relation between mindfulness practice and job performance. In contrast to formal mindful practices (Beta = 0.13), informal mindful practices (Beta = 0.22) encompass a broader impact on employee performance. The findings suggest that mindfulness practice can effectively be used in workspaces to enhance engagement and performance of social workers in China.
Novel Chimeric Vaccine Candidate Development against Leptotrichia buccalis
Authors: Alshammari Abdulrahman , Alasmari Abdullah F. , Alharbi Metab , Ali Nemat , Muhseen Ziyad Tariq , Ashfaq Usman Ali , Ud-din Miraj , Ullah Asad , Arshad Muhammad , Ahmad Sajjad
Published: August 2022

The misuse of antibiotics in our daily lives has led to the emergence of antimicrobial resistance. As a result, many antibiotics are becoming ineffective. This phenomenon is linked with high rates of mortality and morbidity. Therefore, new approaches are required to address this major health issue. Leptotrichia buccalis is a Gram-negative, rod-shaped bacterium which normally resides in the oral and vaginal cavities. It is an emerging bacterial pathogen which is developing new antibiotic-resistance mechanisms. No approved vaccine is available against this pathogen, which is a cause for growing concern. In this study, an in silico-based, multi-epitopes vaccine against this pathogen was designed by applying reverse vaccinology and immunoinformatic approaches. Of a total of 2193 predicted proteins, 294 were found to be redundant while 1899 were non-redundant. Among the non-redundant proteins, 6 were predicted to be present in the extracellular region, 12 in the periplasmic region and 23 in the outer-membrane region. Three proteins (trypsin-like peptidase domain-containing protein, sel1 repeat family protein and TrbI/VirB10 family protein) were predicted to be virulent and potential subunit vaccine targets. In the epitopes prediction phase, the three proteins were subjected to B- and T-cell epitope mapping; 19 epitopes were used for vaccine design. The vaccine construct was docked with MHC-I, MHC-II and TLR-4 immune receptors and only the top-ranked complex (based on global energy value) was selected in each case. The selected docked complexes were examined in a molecular dynamic simulation and binding free energies analysis in order to assess their intermolecular stability. It was observed that the vaccine binding mode with receptors was stable and that the system presented stable dynamics. The net binding free energy of complexes was in the range of −300 to −500 kcal/mol, indicating the formation of stable complexes. In conclusion, the data reported herein might help vaccinologists to formulate a chimeric vaccine against the aforementioned target pathogen.
The Determinants of User Acceptance of Mobile Medical Platforms: An Investigation Integrating the TPB, TAM, and Patient-Centered Factors
Authors: Wang Hailiang , Zhang Jiaxin , Luximon Yan , Qin Mingfu , Geng Ping , Tao Da
Published: August 2022

Mobile medical platforms (MMPs) can make medical services more accessible and effective. However, the patient-centered factors that influence patients’ acceptance of MMPs are not well understood. Our study examined the factors affecting patients’ acceptance of MMPs by integrating the theory of planned behavior (TPB), the technology acceptance model (TAM), and three patient-centered factors (i.e., perceived convenience, perceived credibility, and perceived privacy risk). Three hundred and eighty-nine Chinese respondents were recruited in this study and completed a self-administered online questionnaire that included items adapted from validated measurement scales. The partial least squares structural equation modeling results revealed that perceived privacy risk, perceived credibility, and perceived ease of use directly determined the perceived usefulness of an MMP. Perceived convenience, perceived credibility, and perceived usefulness significantly affected the patients’ attitudes toward MMPs. Perceived usefulness, attitude, perceived privacy risk, and perceived behavioral control were important determinants of the patients’ behavioral intentions to use MMPs. Behavioral intention and perceived behavioral control significantly influenced perceived effective use. Perceived credibility and perceived ease of use significantly affected perceived convenience. However, social influence had no significant effect on attitude and behavioral intention. The study provides important theoretical and practical implications, which could help practitioners enhance the patients’ use of MMPs for their healthcare activities.
Frontiers in Occupational Health and Safety Management
Authors: Ramos Delfina , Cotrim Teresa , Arezes Pedro , Baptista João , Rodrigues Matilde , Leitão João
Published: August 2022

This Special Issue of the International Journal of Environmental Research and Public Health is devoted to the “Frontiers in Occupational Health and Safety Management” [...]
Oral-Health-Related Quality of Life and Anxiety in Orthodontic Patients with Conventional Brackets
Authors: Curto Adrián , Alvarado-Lorenzo Alejandro , Albaladejo Alberto , Alvarado-Lorenzo Alfonso
Published: August 2022

The aim of this study was to evaluate the oral-health-related quality of life (OHRQoL) and anxiety levels of adult patients undergoing orthodontic treatment with fixed multibracket appliances. Materials and Methods: The study was carried out at the Dental Clinic of the University of Salamanca in 2021. It included 120 adult patients between 19 and 45 years of age undergoing orthodontic treatment with conventional metal brackets. The data collection instruments chosen were the state–trait anxiety inventory (STAI) to assess anxiety levels and the OHIP-14 questionnaire to measure the OHRQoL. Anxiety levels and OHRQoL were analyzed one month after starting treatment. Results: The mean age was 31.7 years ± 6.5 years; 68 patients were women (56.7%) and 52 were men (43.3%). Psychological disability was the dimension of the OHIP-14 questionnaire that was found to have the greatest impact (3.20 ± 1.08) on patients, as compared to the dimension of disability, which had the lowest impact on the oral-health quality of life (0.37 ± 0.56). The mean total score of the OHIP-14 questionnaire was 11.93 (±2.19). There was no statistically significant influence from either sex or age on the anxiety and oral-health quality of life of the participants; however, there was a significant relationship between the dimensions of physical disability and anxiety traits. Conclusions: The physical disability dimension of the OHIP-14 questionnaire increased the anxiety level of adult patients treated with conventional brackets. The impact of orthodontic treatment on adult patients may negatively influence their levels of anxiety.
Outcomes of COVID-19 Patients Admitted to the Intermediate Respiratory Care Unit: Non-Invasive Respiratory Therapy in a Sequential Protocol
Authors: Gasa Mercè , Ruiz-Albert Yolanda , Cordoba-Izquierdo Ana , Sarasate Mikel , Cuevas Ester , Suarez-Cuartin Guillermo , Méndez Lidia , Alfaro-Álvarez Julio-César , Sabater-Riera Joan , Pérez-Fernández Xosé , Molina-Molina María , Santos Salud
Published: August 2022

The intermediate respiratory care units (IRCUs) have a pivotal role managing escalation and de-escalation between the general wards and the intensive care units (ICUs). Since the COVID-19 pandemic began, the early detection of patients that could improve on non-invasive respiratory therapies (NRTs) in IRCUs without invasive approaches is crucial to ensure proper medical management and optimize limiting ICU resources. The aim of this study was to assess factors associated with survival, ICU admission and intubation likelihood in COVID-19 patients admitted to IRCUs. Observational retrospective study in consecutive patients admitted to the IRCU of a tertiary hospital from March 2020 to April 2021. Inclusion criteria: hypoxemic respiratory failure (SpO2 ≤ 94% and/or respiratory rate ≥ 25 rpm with FiO2 > 50% supplementary oxygen) due to acute COVID-19 infection. Demographic, comorbidities, clinical and analytical data, and medical and NRT data were collected at IRCU admission. Multivariate logistic regression models assessed factors associated with survival, ICU admission, and intubation. From 679 patients, 79 patients (12%) had an order to not do intubation. From the remaining 600 (88%), 81% survived, 41% needed ICU admission and 37% required intubation. In the IRCU, 51% required non-invasive ventilation (NIV group) and 49% did not (non-NIV group). Older age and lack of corticosteroid treatment were associated with higher mortality and intubation risk in the scheme, which could be more beneficial in severe forms. Initial NIV does not always mean worse outcomes.
Effects of Running-Specific Strength Training, Endurance Training, and Concurrent Training on Recreational Endurance Athletes’ Performance and Selected Anthropometric Parameters
Authors: Prieto-González Pablo , Sedlacek Jaromir
Published: August 2022

Objective: The present study aimed to verify the effects of running-specific strength training alone, endurance training alone, and concurrent training on recreational endurance athletes’ performance and selected anthropometric parameters. Method: Thirty male recreational endurance runners were randomly assigned using a blocking technique to either a running-specific strength training group (RSSTG), an endurance training group (ETG), or a concurrent training group (CTG). RSSTG performed three strength-training sessions per week orientated to running, ETG underwent three endurance sessions per week, and CTG underwent a 3-day-per-week concurrent training program performed on non-consecutive days, alternating the strength and endurance training sessions applied to RSSTG and ETG. The training protocol lasted 12 weeks and was designed using the ATR (Accumulation, Transmutation, Realization) block periodization system. The following assessments were conducted before and after the training protocol: body mass (BM), body mass index (BMI), body fat percentage (BFP), lean mass (LM), countermovement jump (CMJ), 1RM (one-repetition maximum) squat, running economy at 12 and 14 km/h (RE12 and RE14), maximum oxygen consumption (VO2max), and anaerobic threshold (AnT). Results: RSSTG significantly improved the results in CMJ, 1RM squat, RE12, and RE14. ETG significantly improved in RE12, RE14, VO2max, and AnT. Finally, CTG, obtained significant improvements in BFP, LM, CMJ, 1RM squat, RE12, RE14, VO2max, and AnT. RSSTG obtained improvements significantly higher than ETG in CMJ, 1RM squat, and RE14. ETG results were significantly better than those attained by RSSTG in AnT. Moreover, CTG marks were significantly higher than those obtained by ETG in CMJ and RE14. Conclusion: Performing a 12-week concurrent training program integrated into the ATR periodization system effectively improves body composition and performance variables that can be obtained with exclusive running-specific strength and endurance training in recreational runners aged 30 to 40. Running-specific strength training enhances maximum and explosive strength and RE, whereas exclusive endurance training improves VO2max, AnT, and RE. Performing concurrent training on non-consecutive days effectively prevents the strength and endurance adaptations attained with single-mode exercise from being attenuated. The ATR periodization system is useful in improving recreational endurance athletes’ performance parameters, especially when performing concurrent training programs.
Metric, Topological, and Syntactic Accessibility in Three-Dimensional Urban Networked Spaces: Modeling Options and Visualization
Authors: Dao Thi Hong Diep , Thill Jean-Claude
Published: August 2022

In this paper, we take the position that cities gain to be represented as three-dimensional spaces populated by scores of micro-scale-built spaces (buildings, rooms, passageways, squares, etc.). Effective algorithms that evaluate place-based accessibility in built structures while considering the indoor spaces’ complexity at a fine granularity are essential for indoor–outdoor seamless urban planning, navigation, way findings, and supporting emergencies. We present a comprehensive set of spatial modeling options and visualizations of indoor accessibility for an entire built structure based on various notions of travel impedance. Notably, we consider the metric length of the paths and their cognitive complexities due to topologic, syntactic, or integrated intricacy within our approaches. Our work presents a comprehensive selection of indoor accessibility analysis with a detailed implemental discussion that can be applied as a solid foundation for smart city applications or seamless urban research and planning. The analysis and visualization techniques presented in this paper can be easily applied to analyze and visualize built interior geographic spaces to study accessibility differentials in cities with vast vertical expansion aimed at achieving (or at avoiding) specific accessibility outcomes.
Estrogen Regulates the Expression and Localization of YAP in the Uterus of Mice
Authors: Moon Sohyeon , Lee Ok-Hee , Kim Byeongseok , Park Jinju , Hwang Semi , Lee Siyoung , Lee Giwan , Kim Hyukjung , Song Hyuk , Hong Kwonho , Cho Jaejin , Choi Youngsok
Published: August 2022

The dynamics of uterine endometrium is important for successful establishment and maintenance of embryonic implantation and development, along with extensive cell differentiation and proliferation. The tissue event is precisely and complicatedly regulated as several signaling pathways are involved including two main hormones, estrogen and progesterone signaling. We previously showed a novel signaling molecule, Serine/threonine protein kinase 3/4 (STK3/4), which is responded to hormone in the mouse uterine epithelium. However, the role and regulation of its target, YES-associated protein (YAP) remains unknown. In this study, we investigated the expression and regulation of YAP in mouse endometrium. We found that YAP was periodically expressed in the endometrium during the estrous cycle. Furthermore, periodic expression of YAP was shown to be related to the pathway under hormone treatment. Interestingly, estrogen was shown to positively modulate YAP via endometrial epithelial receptors. In addition, the knockdown of YAP showed that YAP regulated various target genes in endometrial cells. The knockdown of YAP down-regulated numerous targets including ADAMTS1, AMOT, AMOTL1, ANKRD1, CTNNA1, MCL1. On the other hand, the expressions of AREG and AXL were increased by its knockdown. These findings imply that YAP responds via Hippo signaling under various intrauterine signals and is considered to play a role in the expression of factors important for uterine endometrium dynamic regulation.
The Role of Protein Arginine Methyltransferases in DNA Damage Response
Authors: Brobbey Charles , Liu Liu , Yin Shasha , Gan Wenjian
Published: August 2022

In response to DNA damage, cells have developed a sophisticated signaling pathway, consisting of DNA damage sensors, transducers, and effectors, to ensure efficient and proper repair of damaged DNA. During this process, posttranslational modifications (PTMs) are central events that modulate the recruitment, dissociation, and activation of DNA repair proteins at damage sites. Emerging evidence reveals that protein arginine methylation is one of the common PTMs and plays critical roles in DNA damage response. Protein arginine methyltransferases (PRMTs) either directly methylate DNA repair proteins or deposit methylation marks on histones to regulate their transcription, RNA splicing, protein stability, interaction with partners, enzymatic activities, and localization. In this review, we summarize the substrates and roles of each PRMTs in DNA damage response and discuss the synergistic anticancer effects of PRMTs and DNA damage pathway inhibitors, providing insight into the significance of arginine methylation in the maintenance of genome integrity and cancer therapies.
Anti-Tumor Effect of Heat-Killed Bifidobacterium bifidum on Human Gastric Cancer through Akt-p53-Dependent Mitochondrial Apoptosis in Xenograft Models
Authors: Kim SukJin , Lee Hwan Hee , Choi Wonhyeok , Kang Chang-Ho , Kim Gun-Hee , Cho Hyosun
Published: August 2022

Paraprobiotics, inactivated microbial cells, regulate immune system and exhibit antioxidant and anti-inflammatory activities in patients with weakened immunity or the elderly. This study evaluated the anti-tumor effects of heat-killed Bifidobacterium and Lactobacillus on human gastric cancer MKN1 cells in vitro and in vivo in xenograft animal models. First, cytotoxicity and apoptosis in MKN1 cells of 11 different heat-killed Bifidobacterium or Lactobacillus strains were examined using the MTT assay or flow cytometry, respectively. Then, BALB/c nude mice xenograft animal models were implanted with human gastric cancer MKN1 cells and orally administered a selected single or a mixture of heat-killed bacterial strains to investigate their inhibitory effect on tumor growth. In addition, the expression of p-Akt, p53, Bax, Bak, cleaved caspase-9, -3, and PARP in the tumor tissues was analyzed using Western blotting assay or immunohistochemistry staining. The results show that heat-killed B. bifidum MG731 (MG731), L. reuteri MG5346 (MG5346), and L. rhamnosus MG5200 (MG5200) induced relatively greater apoptosis than other strains in MKN1 cells. Oral administration of a single dose or a mixture of MG731, MG5346, or MG5200 significantly delayed tumor growth, and MG731 had the most effective anti-tumor effect in the xenograft model. Protein expression of p-Akt, p53, Bax, cleaved caspase-3 and -9, and PARP in tumors derived from the xenograft model correlated with the results of the immunohistochemistry staining.
Insights into the Black Box of Intra-Amniotic Infection and Its Impact on the Premature Lung: From Clinical and Preclinical Perspectives
Authors: Dong Ying , Rivetti Stefano , Lingampally Arun , Tacke Sabine , Kojonazarov Baktybek , Bellusci Saverio , Ehrhardt Harald
Published: August 2022

Intra-amniotic infection (IAI) is one major driver for preterm birth and has been demonstrated by clinical studies to exert both beneficial and injurious effects on the premature lung, possibly due to heterogeneity in the microbial type, timing, and severity of IAI. Due to the inaccessibility of the intra-amniotic cavity during pregnancies, preclinical animal models investigating pulmonary consequences of IAI are indispensable to elucidate the pathogenesis of bronchopulmonary dysplasia (BPD). It is postulated that on one hand imbalanced inflammation, orchestrated by lung immune cells such as macrophages, may impact on airway epithelium, vascular endothelium, and interstitial mesenchyme, resulting in abnormal lung development. On the other hand, excessive suppression of inflammation may as well cause pulmonary injury and a certain degree of inflammation is beneficial. So far, effective strategies to prevent and treat BPD are scarce. Therapeutic options targeting single mediators in signaling cascades and mesenchymal stromal cells (MSCs)-based therapies with global regulatory capacities have demonstrated efficacy in preclinical animal models and warrant further validation in patient populations. Ante-, peri- and postnatal exposome analysis and therapeutic investigations using multiple omics will fundamentally dissect the black box of IAI and its effect on the premature lung, contributing to precisely tailored and individualized therapies.
Lipid-Based Molecules on Signaling Pathways in Autism Spectrum Disorder
Authors: Yui Kunio , Imataka George , Yoshihara Shigemi
Published: August 2022

The signaling pathways associated with lipid metabolism contribute to the pathophysiology of autism spectrum disorder (ASD) and provide insights for devising new therapeutic strategies. Prostaglandin E2 is a membrane-derived lipid molecule that contributes to developing ASD associated with canonical Wnt signaling. Cyclooxygenase-2 plays a key role in neuroinflammation and is implicated in the pathogenesis of neurodevelopmental diseases, such as ASD. The endocannabinoid system maintains a balance between inflammatory and redox status and synaptic plasticity and is a potential target for ASD pathophysiology. Redox signaling refers to specific and usually reversible oxidation–reduction reactions, some of which are also involved in pathways accounting for the abnormal behavior observed in ASD. Redox signaling and redox status-sensitive transcription factors contribute to the pathophysiology of ASD. Cannabinoids regulate the redox balance by altering the levels and activity of antioxidant molecules via ROS-producing NADPH oxidase (NOX) and ROS-scavenging superoxide dismutase enzymes. These signaling cascades integrate a broad range of neurodevelopmental processes that may be involved in the pathophysiology of ASD. Based on these pathways, we highlight putative targets that may be used for devising novel therapeutic interventions for ASD.
Overexpression of MsRCI2D and MsRCI2E Enhances Salt Tolerance in Alfalfa (Medicago sativa L.) by Stabilizing Antioxidant Activity and Regulating Ion Homeostasis
Authors: Zhang Depeng , Zhang Zhenyue , Li Chunxin , Xing Yimei , Luo Yaqin , Wang Xinsheng , Li Donghuan , Ma Zhiyun , Cai Hua
Published: August 2022

Rare cold-inducible 2 (RCI2) genes from alfalfa (Medicago sativa L.) are part of a multigene family whose members respond to a variety of abiotic stresses by regulating ion homeostasis and stabilizing membranes. In this study, salt, alkali, and ABA treatments were used to induce MsRCI2D and MsRCI2E expression in alfalfa, but the response time and the expression intensity of the MsRCI2D,-E genes were different under specific treatments. The expression intensity of the MsRCI2D gene was the highest in salt- and alkali-stressed leaves, while the MsRCI2E gene more rapidly responded to salt and ABA treatment. In addition to differences in gene expression, MsRCI2D and MsRCI2E differ in their subcellular localization. Akin to MtRCI2D from Medicago truncatula, MsRCI2D is also localized in the cell membrane, while MsRCI2E is different from MtRCI2E, localized in the cell membrane and the inner membrane. This difference might be related to an extra 20 amino acids in the C-terminal tail of MsRCI2E. We investigated the function of MsRCI2D and MsRCI2E proteins in alfalfa by generating transgenic alfalfa chimeras. Compared with the MsRCI2E-overexpressing chimera, under high-salinity stress (200 mmol·L−1 NaCl), the MsRCI2D-overexpressing chimera exhibited a better phenotype, manifested as a higher chlorophyll content and a lower MDA content. After salt treatment, the enzyme activities of SOD, POD, CAT, and GR in MsRCI2D- and -E-overexpressing roots were significantly higher than those in the control. In addition, after salt stress, the Na+ content in MsRCI2D- and -E-transformed roots was lower than that in the control; K+ was higher than that in the control; and the Na+/K+ ratio was lower than that in the control. Correspondingly, H+-ATPase, SOS1, and NHX1 genes were significantly up-regulated, and the HKT gene was significantly down-regulated after 6 h of salt treatment. MsRCI2D was also found to regulate the expression of the MsRCI2B and MsRCI2E genes, and the MsRCI2E gene could alter the expression of the MsRCI2A, MsRCI2B, and MsRCI2D genes. MsRCI2D- and -E-overexpressing alfalfa was found to have higher salt tolerance, manifested as improved activity of antioxidant enzymes, reduced content of reactive oxygen species, and sustained Na+ and K+ ion balance by regulating the expression of the H+-ATPase, SOS1, NHX1, HKT, and MsRCI2 genes.
Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance
Authors: Farsa Oldřich , Ballayová Veronika , Žáčková Radka , Kollar Peter , Kauerová Tereza , Zubáč Peter
Published: August 2022

Aminopeptidase N (APN), also known as CD13 antigen or membrane alanyl aminopeptidase, belongs to the M1 family of the MA clan of zinc metallopeptidases. In cancer cells, the inhibition of aminopeptidases including APN causes the phenomenon termed the amino acid deprivation response (AADR), a stress response characterized by the upregulation of amino acid transporters and synthetic enzymes and activation of stress-related pathways such as nuclear factor kB (NFkB) and other pro-apoptotic regulators, which leads to cancer cell death by apoptosis. Recently, APN inhibition has been shown to augment DR4-induced tumor cell death and thus overcome resistance to cancer treatment with DR4-ligand TRAIL, which is available as a recombinant soluble form dulanermin. This implies that APN inhibitors could serve as potential weapons for overcoming cancer treatment resistance. In this study, a series of basically substituted acetamidophenones and the semicarbazones and thiosemicarbazones derived from them were prepared, for which APN inhibitory activity was determined. In addition, a selective anti-proliferative activity against cancer cells expressing APN was demonstrated. Our semicarbazones and thiosemicarbazones are the first compounds of these structural types of Schiff bases that were reported to inhibit not only a zinc-dependent aminopeptidase of the M1 family but also a metalloenzyme.
Inflammatory Biomarkers in Exhaled Breath Condensate: A Systematic Review
Authors: Ghelli Federica , Panizzolo Marco , Garzaro Giacomo , Squillacioti Giulia , Bellisario Valeria , Colombi Nicoletta , Bergamaschi Enrico , Guseva Canu Irina , Bono Roberto
Published: August 2022

Inflammation is a comprehensive set of physiological processes that an organism undertakes in response to a wide variety of foreign stimuli, such as viruses, bacteria, and inorganic particles. A key role is played by cytokines, protein-based chemical mediators produced by a broad range of cells, including the immune cells recruited in the inflammation site. The aim of this systematic review is to compare baseline values of pro/anti-inflammatory biomarkers measured in Exhaled Breath Condensate (EBC) in healthy, non-smoking adults to provide a summary of the concentrations reported in the literature. We focused on: interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-α), and C reactive protein (CRP). Eligible articles were identified in PubMed, Embase, and Cochrane CENTRAL. Due to the wide differences in methodologies employed in the included articles concerning EBC sampling, storage, and analyses, research protocols were assessed specifically to test their adherence to the ATS/ERS Task Force guidelines on EBC. The development of reference intervals for these biomarkers can result in their introduction and use in both research and clinical settings, not only for monitoring purposes but also, in the perspective of future longitudinal studies, as predictive parameters for the onset and development of chronic diseases with inflammatory aetiology.
Characterization of Virus-Inducible Orchid Argonaute 5b Promoter and Its Functional Characterization in Nicotiana benthamiana during Virus Infection
Authors: Kasi Viswanath Kotapati , Kuo Song-Yi , Huang Ying-Wen , Tsao Nai-Wen , Hu Chung-Chi , Lin Na-Sheng , Wang Sheng-Yang , Hsu Yau-Heiu
Published: August 2022

Plant ARGONAUTES (AGOs) play a significant role in the defense against viral infection. Previously, we have demonstrated that AGO5s encoded in Phalaenopsis aphrodite subsp. formosana (PaAGO5s) took an indispensable part in defense against major viruses. To understand the underlying defense mechanism, we cloned PaAGO5s promoters (pPaAGO5s) and analyzed their activity in transgenic Nicotiana benthamiana using β-glucuronidase (GUS) as a reporter gene. GUS activity analyses revealed that during Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) infections, pPaAGO5b activity was significantly increased compared to pPaAGO5a and pPaAGO5c. Analysis of pPaAGO5b 5′-deletion revealed that pPaAGO5b_941 has higher activity during virus infection. Further, yeast one-hybrid analysis showed that the transcription factor NbMYB30 physically interacted with pPaAGO5b_941 to enhance its activity. Overexpression and silencing of NbMYB30 resulted in up- and downregulation of GUS expression, respectively. Exogenous application and endogenous measurement of phytohormones have shown that methyl jasmonate and salicylic acid respond to viral infections. NbMYB30 overexpression and its closest related protein, PaMYB30, in P. aphrodite subsp. formosana reduced CymMV accumulation in P. aphrodite subsp. formosana. Based on these discoveries, this study uncovers the interaction between virus-responsive promoter and the corresponding transcription factor in plants.
Sex and APOE Genotype Alter the Basal and Induced Inflammatory States of Primary Microglia from APOE Targeted Replacement Mice
Authors: Mhatre-Winters Isha , Eid Aseel , Han Yoonhee , Tieu Kim , Richardson Jason R.
Published: August 2022

The sex and APOE4 genotype are significant risk factors for Alzheimer’s disease (AD); however, the mechanism(s) responsible for this interaction are still a matter of debate. Here, we assess the responses of mixed-sex and sex-specific APOE3 and APOE4 primary microglia (PMG) to lipopolysaccharide and interferon-gamma. In our investigation, inflammatory cytokine profiles were assessed by qPCR and multiplex ELISA assays. Mixed-sex APOE4 PMG exhibited higher basal mRNA expression and secreted levels of TNFa and IL1b. In sex-specific cultures, basal expression and secreted levels of IL1b, TNFa, IL6, and NOS2 were 2–3 fold higher in APOE4 female PMG compared to APOE4 males, with both higher than APOE3 cells. Following an inflammatory stimulus, the expression of pro-inflammatory cytokines and the secreted cytokine level were upregulated in the order E4 female > E4 male > E3 female > E3 male in sex-specific cultures. These data indicate that the APOE4 genotype and female sex together contribute to a greater inflammatory response in PMG isolated from targeted replacement humanized APOE mice. These data are consistent with clinical data and indicate that sex-specific PMG may provide a platform for exploring mechanisms of genotype and sex differences in AD related to neuroinflammation and neurodegeneration.
Canine B Cell Lymphoma- and Leukemia-Derived Extracellular Vesicles Moderate Differentiation and Cytokine Production of T and B Cells In Vitro
Authors: Zmigrodzka Magdalena , Witkowska-Pilaszewicz Olga , Pingwara Rafał , Pawlak Aleksandra , Winnicka Anna
Published: August 2022

Extracellular vesicles (EVs) are formed in physiological and pathological conditions by almost all mammalian cells. They are known as submicron “molecules” that transport and horizontally transfer their cargo from maternal cells to donor cells. Moreover, cancer cells produce tumor-derived EVs (TEVs), which are present in blood of patients with solid tumors and those with hematological malignancies. Their role in evading immune system surveillance and induction of immunosuppression in hematological cancer is limited. According to the authors’ best knowledge, there is no information about the impact of TEVs from canine lymphoma (CLBL-1) and leukemia (CLB70) on lymphocytes isolated from peripheral blood mononuclear cells (PBMCs). In conclusion, we demonstrate in in vitro experiments that CLBL-1 EVs and CLB70 EVs are effectively taken up by T and B lymphocytes. TEVs decrease the percentage of B lymphocytes and increase that of T lymphocytes, and change T cells’ phenotype into the effector memory (EM) or terminally differentiated effector memory (TEMRA) subtype after in vitro co-culturing. Moreover, CLBL70 EVs have pro-tumorogenic properties by inhibiting the production of CD8+IL-17+ cells.
Combination of Whole Genome Sequencing and Metagenomics for Microbiological Diagnostics
Authors: Purushothaman Srinithi , Meola Marco , Egli Adrian
Published: August 2022

Whole genome sequencing (WGS) provides the highest resolution for genome-based species identification and can provide insight into the antimicrobial resistance and virulence potential of a single microbiological isolate during the diagnostic process. In contrast, metagenomic sequencing allows the analysis of DNA segments from multiple microorganisms within a community, either using an amplicon- or shotgun-based approach. However, WGS and shotgun metagenomic data are rarely combined, although such an approach may generate additive or synergistic information, critical for, e.g., patient management, infection control, and pathogen surveillance. To produce a combined workflow with actionable outputs, we need to understand the pre-to-post analytical process of both technologies. This will require specific databases storing interlinked sequencing and metadata, and also involves customized bioinformatic analytical pipelines. This review article will provide an overview of the critical steps and potential clinical application of combining WGS and metagenomics together for microbiological diagnosis.
Remdesivir Treatment in Moderately Ill COVID-19 Patients: A Retrospective Single Center Study
Authors: Terkes Vedrana , Lisica Karla , Marusic Martina , Verunica Nikola , Tolic Anela , Morovic Miro
Published: August 2022

Almost two years after remdesivir was approved and extensively used in numerous clinical studies for the treatment of COVID-19 patients, there is still no clear recommendation for the time and phase of the disease of remdesivir administration. This retrospective observational study included adults (≥18 years) with severe COVID-19, radiologically confirmed pneumonia, a need for supplemental oxygen and an interval from symptom onset to enrolment of 10 days or less. All patients were treated with remdesivir for 5 to 10 days, or with clinical improvement within that period. The primary goal was the outcome in patients treated with remdesivir during the early stage of the disease considering the different disease severity. The median time from symptom onset to treatment was 8.4 days (3–10). Clinical improvements and good outcomes were observed in 104 of 137 patients (75.9%); 33 (24.1%) of 137 patients died. Subgroup analyses showed that the mortality rate was significantly lower in moderately ill patients (3 out of 51 patients; 5.9%) than in the group of severely/critically ill patients (30 out of 86 patients; 34.8%; p < 0.005). Older age, rise of CRP and CT score were shown to be significant predictors of disease outcome. Overall, remdesivir was well tolerated, and the treatment was discontinued in only four patients. The results of this observational study in 137 patients with different disease severity contribute to the attitude concerning remdesivir administration in the early stage of COVID-19, at least in moderately ill patients with a high risk of progression, before the transition to a more severe stage.
Diagnostic Performance of AFP, AFP-L3, or PIVKA-II for Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Multicenter Analysis
Authors: Liu Siyu , Sun Liyang , Yao Lanqing , Zhu Hong , Diao Yongkang , Wang Mingda , Xing Hao , Lau Wan Yee , Guan Mingcheng , Pawlik Timothy M. , Shen Feng , Xu Min , Tong Xiangmin , Yang Tian
Published: August 2022

Background and Aim: Alpha-fetoprotein (AFP), a lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), is a protein that is induced by vitamin K deficiency or antagonist-II (PIVKA-II) that has been clinically used as a serum biomarker for early detection and diagnosis of hepatocellular carcinoma (HCC). Diagnostic performance of each serum biomarker alone, or their combinations for the detection of hepatitis C virus (HCV)-associated HCC were compared. Methods: Serum AFP, AFP-L3, and PIVKA-II levels were evaluated in patients with HCV-associated HCC, and those with chronic HCV infection without HCC (HCV-controls). The areas under the curve (AUC), sensitivity, and specificity were compared to identify the diagnostic performance of each serum HCC biomarker alone or in combination. Results: Overall, 172 HCV controls and 105 patients with HCV-associated HCC were enrolled. The AFP, AFP-L3, and PIVKA-II levels were significantly increased among patients with HCV-associated HCC when compared with HCV patients without HCC (p < 0.001). When these biomarkers were analyzed individually, PIVKA-II revealed the best predictive performance (AUC: PIVKA-II 0.90 vs. AFP 0.80 vs. AFP-L3 0.69, p < 0.001). In evaluating the combinations of any two biomarkers, the best predictive performance was found in PIVKA-II + AFP (0.93 vs. AFP + AFP-L3 0.78, p = 0.001; and PIVKA-II + AFP-L3 0.89, p < 0.001), which had no difference compared to the predictive performance of the combination of all three serum biomarkers (AFP + AFP-L3 + PIVKA-II 0.93, p = 0.277). Similar results were identified in the subgroups of patients with HCV-induced cirrhosis, and among patients with early-stage HCC defined by BCLC and TNM staging. Conclusions: The addition of the PIVKA-II test to routine AFP test maybe provide a more suitable biomarker approach to detect HCV-induced HCC in patients with HCV infection undergoing HCC surveillance.
Evaluation of a New Monoclonal Chemiluminescent Immunoassay Stool Antigen Test for the Diagnosis of Helicobacter pylori Infection: A Spanish Multicentre Study
Authors: Resina Elena , Donday María G. , Martínez-Domínguez Samuel J. , Laserna-Mendieta Emilio José , Lanas Ángel , Lucendo Alfredo J. , Sánchez-Luengo Marta , Alcaide Noelia , Fernández-Salazar Luis , De La Peña-Negro Luisa , Bujanda Luis , Arbulo Marta Gómez-Ruiz de , Alcedo Javier , Pérez-Aísa Ángeles , Rodríguez Raúl , Hermida Sandra , Brenes Yanire , Nyssen Olga P. , Gisbert Javier P.
Published: August 2022

The stool antigen test (SAT) represents an attractive alternative for detection of Helicobacter pylori. The aim of this study was to assess the accuracy of a new SAT, the automated LIAISON® Meridian H. pylori SA based on monoclonal antibodies, compared to the defined gold standard 13C-urea breath test (UBT). This prospective multicentre study (nine Spanish centres) enrolled patients ≥18 years of age with clinical indication to perform UBT for the initial diagnosis and for confirmation of bacterial eradication. Two UBT methods were used: mass spectrometry (MS) including citric acid (CA) or infrared spectrophotometry (IRS) without CA. Overall, 307 patients (145 naïve, 162 with confirmation of eradication) were analysed. Using recommended cut-off values (negative SAT < 0.90, positive ≥ 1.10) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 67%, 97%, 86%, 92% and 91%, respectively, obtaining an area under the receiver operating characteristic (ROC) curve (AUC) of 0.85. Twenty-eight patients, including seven false positives and 21 false negatives, presented a discordant result between SAT and UBT. Among the 21 false negatives, four of six tested with MS and 11 of 15 tested with IRS presented a borderline UBT delta value. In 25 discordant samples, PCR targeting H. pylori DNA was performed to re-assess positivity and SAT accuracy was re-analysed: sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC were 94%, 97%, 86%, 99%, 97% and 0.96, respectively. The new LIAISON® Meridian H. pylori SA SAT showed a good accuracy for diagnosis of H. pylori infection.
The Oscillometric Pulse Wave Analysis Is Useful in Evaluating the Arterial Stiffness of Obese Children with Relevant Cardiometabolic Risks
Authors: Mihuta Monica Simina , Paul Corina , Borlea Andreea , Cepeha Cristina Mihaela , Velea Iulian Puiu , Mozos Ioana , Stoian Dana
Published: August 2022

Early detection of all complications of childhood obesity is imperative in order to minimize effects. Obesity causes vascular disruptions, including early increased arterial stiffness and high blood pressure. This study’s aim is to assess the reliability of pulse wave analysis (PWA) in obese children and how additional risk factors influence the evaluated parameters. We analyzed 55 children aged 6–18 years old by measuring their pulse wave velocity (PWV), augmentation index (AIx), peripheral blood pressure (SBP, DBP), heart rate, central blood pressure (cSBP, cDBP) and central pulse pressure (cPP). We used the oscillometric IEM Mobil-O-Graph and performed a single-point brachial measurement. The subjects were divided into two groups: obese (n = 30) and normal-weight (n = 25) and were clinically and anamnestically assessed. BMI and waist circumference are significantly correlated to higher values for PWV, SBP, DBP, cSBP, and cDBP. Weight significantly predicts PWV, SBP, DBP and cPP. The risk factors that significantly influence the PWA and BP values are: a cardiometabolically risky pregnancy (higher PWV, AIx, SBP), active and passive smoking (higher PWV, SBP, cSBP, cDBP), sleep deprivation (higher PWV, SBP, cSBP) and sedentariness (higher PWV, AIx, peripheral and central BP). We conclude that obese children with specific additional cardiometabolic risk factors present increased arterial stiffness and higher blood pressure values.
Pharmacogenetics of Cardiovascular Prevention in Diabetes: From Precision Medicine to Identification of Novel Targets
Authors: Morieri Mario Luca , Pipino Caterina , Doria Alessandro
Published: August 2022

Pharmacogenetics—a branch of precision medicine—holds the promise of becoming a novel tool to reduce the social and healthcare burdens of cardiovascular disease (CVD) and coronary artery disease (CAD) in diabetes. The improvement in cardiovascular risk stratification resulting from adding genetic characteristics to clinical data has moved from the modest results obtained with genetic risk scores based on few genetic variants, to the progressively better performances of polygenic risk scores based on hundreds to millions of variants (CAD-PGRS). Similarly, over the past few years, the number of studies investigating the use of CAD-PGRS to identify different responses to cardio-preventive treatment has progressively increased, yielding striking results for lipid-lowering drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and statins. The use of CAD-PGRS to stratify patients based on their likely response to diabetes-specific interventions has been less successful, but promising results have been obtained with regard to specific genetic variants modulating the effects of interventions such as intensive glycemic control and fenofibrate. The finding of diabetes-specific CAD-loci, such as GLUL, has also led to the identification of promising new targets that might hopefully result in the development of specific therapies to reduce CVD burden in patients with diabetes. As reported in consensus statements from international diabetes societies, some of these pharmacogenetic approaches are expected to be introduced in clinical practice over the next decade. For this to happen, in addition to continuing to improve and validate these tools, it will be necessary to educate physicians and patients about the opportunities and limits of pharmacogenetics, as summarized in this review.
Personalized Diagnosis and Treatment for Neuroimaging in Depressive Disorders
Authors: Lee Jongha , Chi Suhyuk , Lee Moon-Soo
Published: August 2022

Depressive disorders are highly heterogeneous in nature. Previous studies have not been useful for the clinical diagnosis and prediction of outcomes of major depressive disorder (MDD) at the individual level, although they provide many meaningful insights. To make inferences beyond group-level analyses, machine learning (ML) techniques can be used for the diagnosis of subtypes of MDD and the prediction of treatment responses. We searched PubMed for relevant studies published until December 2021 that included depressive disorders and applied ML algorithms in neuroimaging fields for depressive disorders. We divided these studies into two sections, namely diagnosis and treatment outcomes, for the application of prediction using ML. Structural and functional magnetic resonance imaging studies using ML algorithms were included. Thirty studies were summarized for the prediction of an MDD diagnosis. In addition, 19 studies on the prediction of treatment outcomes for MDD were reviewed. We summarized and discussed the results of previous studies. For future research results to be useful in clinical practice, ML enabling individual inferences is important. At the same time, there are important challenges to be addressed in the future.