bluuebunny/crossref_metadata_2025 huggingface dataset:
Decrease in Secondhand Smoke Exposure in Work and Public Places among Adults in the Philippines: An Analysis of the Global Adult Tobacco Survey, 2009 and 2015
Authors: Kress Alissa C. , Mbulo Lazarous , Stadnik Carlen , Hemedez-Gonzalez Rizalina , Twentyman Evelyn , Dorotheo E. Ulysses , Pan Liping
Published: January 2023

The implementation of several tobacco control policies in the Philippines may have contributed to a decrease in secondhand smoke (SHS) exposure. We examined changes in SHS exposure at work and in public places between 2009 and 2015 among adults aged ≥15 years and interpreted these results within the tobacco policy landscape in the Philippines. We analyzed the Philippines Global Adult Tobacco Survey 2009 and 2015 data. We examined marginal effects in logistic regression to get the adjusted prevalence of SHS exposure at five work and public places, controlling for selected characteristics. We calculated adjusted prevalence ratios and adjusted prevalence differences between 2009 and 2015. Adjusted prevalence of SHS exposure decreased from 2009 to 2015 by 19% (5.7 percentage points) at work, 45% (11.2 percentage points) in government buildings, 48% (3.2 percentage points) in healthcare facilities, 29% (8.2 percentage points) in restaurants, and 33% (19.9 percentage points) on public transportation. Although the prevalence of SHS exposure at work and in public places decreased significantly between 2009 and 2015, a substantial proportion of adults remain exposed to SHS. This study highlights the importance of continued implementation, enforcement, monitoring, and evaluation of tobacco control and prevention measures in the Philippines.
Women’s Health and Working Life: A Scoping Review
Authors: Gjellestad Marianne , Haraldstad Kristin , Enehaug Heidi , Helmersen Migle
Published: January 2023

Women’s health matters for participation in working life. The objective of this study was to explore female physiology in a work–life context and to investigate possible associations between women’s health, sickness absence and work ability. A scoping review was conducted to develop a systematic overview of the current research and to identify knowledge gaps. The search strategy was developed through a population, concept and context (PCC) model, and three areas of women’s health were identified for investigation in the context of work. A total of 5798 articles were screened by title and abstract and 274 articles were screened by full text; 130 articles were included in the review. The material included research from 19 countries; the majority of the studies used quantitative methods. The results showed an impact on the occupational setting and an association between sickness absence, work ability and all three areas of women’s health, but a holistic and overall perspective on female biology in the work context is missing. This review calls for more knowledge on health and work and possible gender differences in this regard. Women’s health and working life involve a complex connection that has the potential to develop new knowledge.
Early Stage Combination Treatment with Methylprednisolone Pulse and Remdesivir for Severe COVID-19 Pneumonia
Authors: Mastruzzo Claudio , Commodari Elena , Grasso Umberto , La Rosa Valentina , Balsamo Daniela , Circo Cristina , Oliveri Rosario
Published: January 2023

Background: This study evaluated the clinical outcomes of patients with severe COVID-19 pneumonia treated with remdesivir plus standard corticosteroid treatment (SCT) or with remdesivir plus high-dose corticosteroid pulse therapy (HDCPT). Methods: One hundred and two patients with severe COVID-19 pneumonia and respiratory failure were included. The patients were divided into two cohorts. The first comprised patients who received remdesivir and SCT, consisting of 6 mg dexamethasone daily for up to 10 days or until hospital discharge. The second included patients who received remdesivir and HDCPT, composed of 250 mg iv of methylprednisolone for three days, followed by a slow reduction in the dose of steroids. The severity of hypoxemia was assessed using the SaO2/FiO2 peripheral oxygen saturation index. Results: 55 received remdesivir plus HDCPT, and 47 received remdesivir plus SCT. Mortality at 30 days was significantly lower among patients who received remdesivir plus HDCPT (4/55) than among those who did not (15/47). In patients who received remdesivir plus HDCPT, 7.3% required invasive mechanical ventilation and admission to the ICU and 36.4% non-invasive ventilation versus 29.8% and 61.7%, respectively, among those treated with remdesivir plus SCT. Remdesivir plus HDCPT induced a significantly faster improvement in the SaO2/FiO2 index. Conclusion: Early combination treatment with remdesivir plus HDCPT reduced in-hospital mortality and the need for admission to the ICU. Furthermore, it improved the SaO2/FiO2 index faster in patients with severe COVID-19 pneumonia.
Distribution, Risk Assessment and Source of Heavy Metals in Mangrove Wetland Sediments of Dongzhai Harbor, South China
Authors: Guo Yuan , Ke Xianzhong , Zhang Jingxian , He Xinhui , Li Qinghua , Zhang Yanpeng
Published: January 2023

Heavy metals are common environmental contaminants that are toxic, non-biodegradable, and bioaccumulative. They can bioaccumulate through the food chain and present a risk to both public health and ecology. Therefore, this study takes the mangrove wetland of Dongzhai Harbor as an example. The concentrations of heavy metals such as As, Cd, Cr, Cu, Ni, Pb, and Zn in the surface sediments of mangrove wetlands were measured to reveal their distribution, the contamination level was assessed, and the sources of contamination were analyzed. The distribution of Cr, Zn, Ni, Pb, Cu, and Cd concentrations are: Yanfeng East River > Sanjiang River > Yanzhou River > Yanfeng West River, while the As concentration in the Yanfeng West River is greater than that in the Yanfeng East River. According to the correlation analysis, the concentrations of Cr, Zn, Ni, Cu, and Cd are significantly and positively correlated with total organic carbon (TOC), total phosphorus (TP), total nitrogen (TN), and salinity (SAL) and shared a significantly negative correlation with pH. There is moderate contamination risk of As and slight contamination risk of Cd, Cr, Cu, Ni, Pb, and Zn in most regions within the study area. Cd, Cr, Cu, Ni, Pb, and Zn exhibit the same sources, which are mainly influenced by human sources such as aquaculture, agricultural cultivation, and livestock farming, while the source of As comes from aquaculture.
The Effects of Yoga Exercise on Blood Pressure and Hand Grip Strength in Chronic Stroke Patients: A Pilot Controlled Study
Authors: Lai Yen-Ting , Huang Hsiao-Ling , Hsieh City C. , Lin Chien-Hung , Yang Jung-Cheng , Tsou Han-Hsing , Lin Chih-Ching , Li Szu-Yuan , Chan Hsiang-Lin , Liu Wen-Sheng
Published: January 2023

Background: We investigated the beneficial effect of add-on yoga with rehabilitation on blood pressure (BP) and hand grip strength in patients with chronic stroke (more than 90 days). Methods: The study included patients 30–80 years of age who could stand independently for 1 min. Patients with psychiatric diseases or undergoing other therapies (like acupuncture) were excluded. The yoga group received training (1 h session twice weekly) with standard rehabilitation for 8 weeks. The control group received standard rehabilitation only. There were no differences in age, gender, hand grip strength, or BP between the two groups (16 subjects in each group) at baseline. Results: The systolic BP (p = 0.01) decreased significantly, and the diastolic BP also decreased but not significantly in the yoga group (p = 0.11). For hand grip strength, both the unaffected hand (p = 0.00025) and the affected hand (p = 0.027) improved significantly. The control group showed no significant change in systolic or diastolic BP, nor did the grip strength change in both hands. Gender and age also affected the results of overall rehabilitation in that women benefited more from a decrease in BP, while men and young people (lower than the mean age of 60) benefited from hand grip strength improvement. Conclusions: Combining yoga with rehabilitation in chronic stroke patients can improve hand grip strength and decrease systolic BP.
Public Knowledge, Practice, and Attitude Regarding Cancer Screening: A Community-Based Study in Saudi Arabia
Authors: Elmaghraby Dalia Ahmed , Alshalla Ahmed Ali , Alyahyan Anas , Altaweel Muntathir , Al ben Hamad Ahmad Mohammed , Alhunfoosh Khalid Mohammed , AlJuwaysim Mohammed F. , Aljumah Duaa Jawad , Albahrani Mohammed Abdullah
Published: January 2023

(1) Background: Cancer screening tests discover cancer at early stages, even before symptoms appear. When abnormal tissues or a malignant mass is found early, treatment and cure rates are improved. In late stages, the cancer may have grown and metastasized. This can negatively affect cancer treatment and reduce the overall survival rate. Screening tests are performed when a person is asymptomatic. Public awareness about cancer screening is crucial for the success of cancer screening programs and for consequently decreasing the morbidity and mortality rate due to cancer. (2) Aim: Assess the knowledge and perception of the community regarding cancer screening in Saudi Arabia. (3) Methodology: A descriptive cross-sectional study targeting the general population of Saudi Arabia was conducted from January to June 2022. The data were collected using a structured validated electronic questionnaire. The study questionnaire covered participants’ personal data, medical history, source of data, and participants’ knowledge, attitude, and practice items. The questionnaire was used as a digital survey and was distributed electronically to the target population. (4) Results: A total of 1313 participants completed the study questionnaire. The participants’ ages ranged from 18 to 67 years, with a mean age of 28.3 ± 11.4 years old. Overall, 60.4% of the study participants knew about cancer screening. Regarding the benefits of cancer screening, 91.8% of the participants reported knowing that the early detection of cancer helps treatment, and 81.1% knew that the early detection of cancer improves treatment outcomes. Moreover, 441 (33.6%) of the participants had good knowledge regarding cancer and cancer screening, while 872 (66.4%) had poor levels of knowledge. Furthermore, 106 (8.1%) of the participants underwent cancer screening. (5) Conclusions: The study results revealed that participants’ awareness regarding cancer and cancer screening was low, especially for approaches to reduce cancer risk. Additionally, the study participants’ practice regarding cancer screening was low. The health care authority should plan for population-based efficacious cancer screening programs. In addition, cancer screening information and the benefits of early detection can be disseminated through social media to target the desired populations.
Exploring the Association between Oxygen Concentration and Life Expectancy in China: A Quantitative Analysis
Authors: Zou Qing , Lai Yingsi , Lun Zhao-Rong
Published: January 2023

The aim of this study was to investigate and quantify the association between oxygen concentration and life expectancy. The data from 34 provinces and 39 municipalities were included in all analyses. Bayesian regression modeling with spatial-specific random effects was used to quantify the impact of oxygen concentration (measured as partial pressure of oxygen) on life expectancy, adjusting for other potential confounding factors. We used hierarchical cluster analysis to group the provinces according to disease burden and analyzed the oxygen levels and the characteristics of causes of death between the clusters. The Bayesian regression analysis showed that the life expectancy at the provincial level increased by 0.15 (95% CI: 0.10–0.19) years, while at the municipal level, it increased by 0.17 (95% CI: 0.12–0.22) years, with each additional unit (mmHg) of oxygen concentration, after controlling for potential confounding factors. Three clusters were identified in the hierarchical cluster analysis, which were characterized by different oxygen concentrations, and the years of life lost from causes potentially related to hypoxia were statistically significantly different between the clusters. A positive correlation was found between oxygen concentration and life expectancy in China. The differences in causes of death and oxygen levels in the provincial clusters suggested that oxygen concentration may be an important factor in life expectancy when mediated by diseases that are potentially related to hypoxia.
Spatial Distribution, Pollution, and Ecological Risk Assessment of Metal(loid)s in Multiple Spheres of the Shennongjia Alpine Critical Zone, Central China
Authors: Song Xiannong , Ning Yongqiang , Yang Shaochen , Ye Jiaxin , Liu Jinling
Published: January 2023

The development of Earth’s critical zone concept has strengthened the capacity of environmental science to better solve real-world problems, such as metal(loid) pollution in the remote alpine areas. The selected metal(loid) contents in soil, moss, and water were investigated to explore the geochemical distribution patterns, pollution levels, and potential ecological risks of metal(loid)s in the Shennongjia (SNJ) alpine critical zone of central China. The distribution of metal(loid)s in different spheres had horizontal and vertical differences. The maximum V, Ni, and Zn contents in water occurred at the sampling sites close to the Hohhot–Beihai Highway, while Dajiuhu Lake had the maximum Cu, Cr, and Mn contents. Most metal(loid) contents in the mosses showed an increasing trend from the northeast low-altitude area to the southwest high-altitude area, while As, Co, V, Ni, Cr, and Zn in soil decreased significantly with altitude and were enriched near the service areas and the highway. The contents of water Co and Ni, soil Cu and Mn, and moss As were evenly distributed and showed no significant differences with altitude. The enrichment factors, pollution index, Nemerow integrated pollution index, geo-accumulation index, heavy metal pollution index, contamination factor, and potential ecological risk index (PERI) were used to assess the pollution levels and ecological risks of SNJ soil, water, and atmosphere. The overall pollution levels of SNJ soil, moss, and water were low to moderate, low, and low, respectively. Soil V, Cu, Zn, moss As, Co, V, and Dajiuhu Lake water Mn were the main pollution factors. The ecological risks in the three spheres of the SNJ alpine critical zone were low to moderate, and As, Co, and V were the most critical potential ecological risk factors. The metal(loid)s pollution problem caused by the continuous development of tourism needs further attention.
Clients’ Facial Expressions of Self-Compassion, Self-Criticism, and Self-Protection in Emotion-Focused Therapy Videos
Authors: Bailey Ghazaleh , Halamová Júlia , Vráblová Viktória
Published: January 2023

Clients’ facial expressions allow psychotherapists to gather more information about clients’ emotional processing. This study aims to examine and investigate the facial Action Units (AUs) of self-compassion, self-criticism, and self-protection within real Emotion-Focused Therapy (EFT) sessions. For this purpose, we used the facial analysis software iMotions. Twelve video sessions were selected for the analysis based on specific criteria. For self-compassion, the following AUs were significant: AUs 4 (brow furrow), 15 (lip corner depressor), and the AU12_smile (lip corner puller). For self-criticism, iMotions identified the AUs 2 (outer brow raise), AU1 (inner brow raise), AU7 (lid tighten), AU12_smirk (unilateral lip corner puller), and AU43 (eye closure). Self-protection was combined using the occurrence of AUs 1 and 4 and AU12_smirk. Moreover, the findings support the significance of discerning self-compassion and self-protection as two different concepts.
Root Canal Configuration and Its Relationship with Endodontic Technical Errors and Periapical Status in Premolar Teeth of a Saudi Sub-Population: A Cross-Sectional Observational CBCT Study
Authors: Al Yahya Rayan Suliman , Al Attas Mustafa Hussein , Javed Muhammad Qasim , Khan Kiran Imtiaz , Atique Sundus , Abulhamael Ayman M. , Bahammam Hammam Ahmed
Published: January 2023

Endodontic technical errors are the foremost cause of treatment failure. A thorough understanding of root canal configuration (RCC) is essential to prevent these iatrogenic errors. This study used CBCT images to determine the association between root canal configuration, endodontic technical errors, and periapical status. CBCT images of 101 patients, including total of 212 obturated premolars (256 canals) were assessed. RCCs were classified according to the Vertucci system. The presence of endodontic errors and periapical lesions associated with each RCC was noted. Presence or absence of coronal restoration and its association with periapical radiolucency was recorded. The most frequent RCC was Type I (199 cases; 77.73%), followed by Type II (26 cases; 10.15%), Type IV (22 cases; 8.59%), Type V (4 cases; 1.56%), Type III (4 cases; 1.56%), and Type VI (1 case; 0.39%). Under-filling and non-homogeneous filling were the most common technical errors. Prevalence of periapical radiolucency was 81% in the presence of technical errors. The absence of coronal restoration caused apical lesions in 93% of cases. The frequency of endodontic technical errors increased as the root canal configurations became more complex. Periapical lesions occurred more often in teeth with endodontic errors and/or absent coronal restoration.
Influence of Public Sports Services on Residents’ Mental Health at Communities Level: New Insights from China
Authors: Lu Liu , Wei Wei
Published: January 2023

It is generally believed that sports play an important role in healing and boosting mental health. The provision of public sports services is important for enhancing residents’ physical fitness and mental health, and for promoting their satisfaction with government public services. To build and strengthen a high-quality sports service-oriented society, it is important to explore whether community public sports services influence residents’ mental health. To explore this phenomenon, the study gathered data from China and employed multi-level regression models to meet the study objective. The results show that the residents’ age difference is 0.03, and the average daily exercise time is 0.02, which is significantly correlated with residents’ mental health. The results show that the lower the availability and greening of sports facilities, and the fewer rest facilities there are, the higher the mental distress of residents may be. Conversely, the improvement of the greening and availability of sports facilities can facilitate the promotion of residents’ mental health levels. Moreover, it was found that the mental health of residents is mainly and positively affected by the cleanliness of sports facilities. The street environment affects mental health and is attributed to the damage to sports facilities. Neighborhood communication also improves residents’ mental health, and trust between neighbors has the greatest impact on reducing mental distress. Finally, the study proposes that the government should propose strategies to optimize the provision of community public sports services in the study area to boost both social and mental health benefits.
A Critical Review on Artificial Intelligence—Based Microplastics Imaging Technology: Recent Advances, Hot-Spots and Challenges
Authors: Zhang Yan , Zhang Dan , Zhang Zhenchang
Published: January 2023

Due to the rapid artificial intelligence technology progress and innovation in various fields, this research aims to use science mapping tools to comprehensively and objectively analyze recent advances, hot-spots, and challenges in artificial intelligence-based microplastic-imaging field from the Web of Science (2019–2022). By text mining and visualization in the scientific literature we emphasized some opportunities to bring forward further explication and analysis by (i) exploring efficient and low-cost automatic quantification methods in the appearance properties of microplastics, such as shape, size, volume, and topology, (ii) investigating microplastics water-soluble synthetic polymers and interaction with other soil and water ecology environments via artificial intelligence technologies, (iii) advancing efficient artificial intelligence algorithms and models, even including intelligent robot technology, (iv) seeking to create and share robust data sets, such as spectral libraries and toxicity database and co-operation mechanism, (v) optimizing the existing deep learning models based on the readily available data set to balance the related algorithm performance and interpretability, (vi) facilitating Unmanned Aerial Vehicle technology coupled with artificial intelligence technologies and data sets in the mass quantities of microplastics. Our major findings were that the research of artificial intelligence methods to revolutionize environmental science was progressing toward multiple cross-cutting areas, dramatically increasing aspects of the ecology of plastisphere, microplastics toxicity, rapid identification, and volume assessment of microplastics. The above findings can not only determine the characteristics and track of scientific development, but also help to find suitable research opportunities to carry out more in-depth research with many problems remaining.
“How Do I Exist in This Body…That’s Outside of the Norm?” Trans and Nonbinary Experiences of Conformity, Coping, and Connection in Atypical Anorexia
Authors: Harrop Erin N. , Hecht Hillary K. , Harner Vern , Call Jarrod , Holloway Brendon T.
Published: January 2023

Addressing eating disorders (EDs) within trans and nonbinary (TNB) populations is a growing concern, as TNB individuals are two to four times more likely to experience EDs than cisgender women. This study explored the lived experiences of TNB people with atypical anorexia by examining how gender identity impacted experiences of ED illness and (potential) recovery. Nine TNB adults with atypical anorexia were followed for one year and completed semi-structured, in-depth, longitudinal qualitative interviews at baseline, 6 months, and 12 months. Interviews were coded using Braun and Clark’s thematic analysis procedures. Four themes, along with subthemes, emerged regarding the intersection of gender identity and ED experiences: (1) Conforming, (2) Coping, (3) Connecting, and (4) Critiquing. In Conforming, participants highlighted how societal pressures around gender contributed to ED vulnerability. In Coping, participants explained that their EDs represented attempts to cope with the overlapping influences of body dissatisfaction, gender dysphoria, and body disconnection. In Connecting, participants described ED recovery as a process of connecting to self, others, and communities that welcomed and affirmed their diverse identities. In Critiquing, participants described how current ED treatment settings were often unwelcoming of or unprepared for non-cisgender patients. Overall, participants viewed their EDs as intricately linked to their gender identity and experiences of social pressure and discrimination. This study suggests the need for targeted ED prevention and intervention efforts within TNB communities, and the ethical imperative to meaningfully address the needs of TNB patients in ED treatment settings.
Diagnosis and Planning Strategies for Quality of Urban Street Space Based on Street View Images
Authors: Wang Jiwu , Hu Yali , Duolihong Wuxihong
Published: January 2023

Under the background of stock planning, improving the quality of urban public space has become an important work of urban planning, design, and construction management. An accurate diagnosis of the spatial quality of streets and the effective implementation of street renewal planning play important roles in the high-quality development of urban spatial environments. However, traditional planning design and study methods, typically based on questionnaires, interviews, and on-site research, are inefficient and make it difficult to objectively and comprehensively grasp the overall construction characteristics and problems of urban street space in a large area, thus making it challenging to meet the needs of practical planning. Therefore, based on street view images, this study combined machine learning with an artificial audit to put forward a methodological framework for diagnosing the quality issues of street space. The Gongshu District of Hangzhou, China, was selected as a case study, and the diagnosis of quality problems for streets at different grades was achieved. The diagnosis results showed the current situation and problems of the selected area. Simultaneously, a series of targeted strategies for street spatial update planning was proposed to solve these problems. This diagnostic method, based on a combination of subjective and objective approaches, can be conducive to the precise and comprehensive identification of urban public spatial problems, which is expected to become an effective tool to assist in urban renewal and other planning decisions.
Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase
Authors: Okamoto Michio , Mizuno Rei , Kawada Kenji , Itatani Yoshiro , Kiyasu Yoshiyuki , Hanada Keita , Hirata Wataru , Nishikawa Yasuyo , Masui Hideyuki , Sugimoto Naoko , Tamura Takuya , Inamoto Susumu , Sakai Yoshiharu , Obama Kazutaka
Published: January 2023

Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase–DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases.
Stereoselective Synthesis and Antiproliferative Activities of Tetrafunctional Diterpene Steviol Derivatives
Authors: Bai Dorottya , Schelz Zsuzsanna , Erdős Dóra , Kis Anna K. , Nagy Viktória , Zupkó István , Balogh György T. , Szakonyi Zsolt
Published: January 2023

A new family of diterpene-type aminotriol derivatives has been synthesised from stevioside in a stereoselective manner. The key intermediate spiro-epoxide was prepared through the methyl ester of the allilyc diol derived from steviol. The oxirane ring was opened with primary and secondary amines, providing a versatile library of aminotriols. The corresponding primary aminotriol was formed by palladium-catalysed hydrogenation, and an N,O-heterocyclic compound was synthesised in a regioselective reaction. All new compounds were characterised by 1D- and 2D-NMR techniques and HRMS measurements. In our in vitro investigations, we found that the aromatic N-substituted derivatives exhibited high inhibition of cell growth on human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231). The antiproliferative activities were assayed by the MTT method. Furthermore, the introduction of an additional hydroxy group slightly increased the biological activity. The drug-likeness of the compounds was assessed by in silico and experimental physicochemical characterisations, completed by kinetic aqueous solubility and in vitro intestinal-specific parallel artificial membrane permeability assay (PAMPA-GI) measurements.
The Impact of Molecular Biology in the Seeding, Treatment Choices and Follow-Up of Colorectal Cancer Liver Metastases—A Narrative Review
Authors: Pavel Mihai-Calin , Ramirez-Maldonado Elena , Pueyo-Périz Eva , Memba Robert , Merino Sandra , Geoghegan Justin , Jorba Rosa
Published: January 2023

There is a clear association between the molecular profile of colorectal cancer liver metastases (CRCLM) and the degree to which aggressive progression of the disease impacts patient survival. However, much of our knowledge of the molecular behaviour of colorectal cancer cells comes from experimental studies with, as yet, limited application in clinical practice. In this article, we review the current advances in the understanding of the molecular behaviour of CRCLM and present possible future therapeutic applications. This review focuses on three important steps in CRCLM development, progression and treatment: (1) the dissemination of malignant cells from primary tumours and the seeding to metastatic sites; (2) the response to modern regimens of chemotherapy; and (3) the possibility of predicting early progression and recurrence patterns by molecular analysis in liquid biopsy.
Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson’s Disease
Authors: Barrera-Vazquez Oscar , Santiago-de-la-Cruz Jose Alberto , Rivero-Segura Nadia Alejandra , Estrella-Parra Edgar Antonio , Morales-Paoli Genaro Salvador , Flores-Soto Edgar , Gomez-Verjan Juan Carlos
Published: January 2023

Parkinson’s disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015–2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis.
β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus
Authors: Milano Serena , Maqoud Fatima , Rutigliano Monica , Saponara Ilenia , Carmosino Monica , Gerbino Andrea , Lucarelli Giuseppe , Battaglia Michele , Svelto Maria , Procino Giuseppe
Published: January 2023

We previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of β3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the β3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease.
Zymosan Particle-Induced Hemodynamic, Cytokine and Blood Cell Changes in Pigs: An Innate Immune Stimulation Model with Relevance to Cytokine Storm Syndrome and Severe COVID-19
Authors: Kökény Gábor , Bakos Tamás , Barta Bálint András , Nagy Georgina Viktória , Mészáros Tamás , Kozma Gergely T. , Szabó András , Szebeni János , Merkely Béla , Radovits Tamás
Published: January 2023

Hemodynamic disturbance, a rise in neutrophil-to-lymphocyte ratio (NLR) and release of inflammatory cytokines into blood, is a bad prognostic indicator in severe COVID-19 and other diseases involving cytokine storm syndrome (CSS). The purpose of this study was to explore if zymosan, a known stimulator of the innate immune system, could reproduce these changes in pigs. Pigs were instrumented for hemodynamic analysis and, after i.v. administration of zymosan, serial blood samples were taken to measure blood cell changes, cytokine gene transcription in PBMC and blood levels of inflammatory cytokines, using qPCR and ELISA. Zymosan bolus (0.1 mg/kg) elicited transient hemodynamic disturbance within minutes without detectable cytokine or blood cell changes. In contrast, infusion of 1 mg/kg zymosan triggered maximal pulmonary hypertension with tachycardia, lasting for 30 min. This was followed by a transient granulopenia and then, up to 6 h, major granulocytosis, resulting in a 3–4-fold increase in NLR. These changes were paralleled by massive transcription and/or rise in IL-6, TNF-alpha, CCL-2, CXCL-10, and IL-1RA in blood. There was significant correlation between lymphopenia and IL-6 gene expression. We conclude that the presented model may enable mechanistic studies on late-stage COVID-19 and CSS, as well as streamlined drug testing against these conditions.
Prolonged B-Lymphocyte-Mediated Immune and Inflammatory Responses to Tuberculosis Infection in the Lungs of TB-Resistant Mice
Authors: Linge Irina , Kondratieva Elena , Apt Alexander
Published: January 2023

During tuberculosis (TB) infection, B-lymphocytes migrate to the lungs and form B-cell follicles (BCFs) in the vicinity of TB granulomata. B-cell-lacking mice display enhanced susceptibility to TB infection, and early B-cell depletion in infected non-human primates alters T-lymphocyte cytokine responses and increases bacterial burdens in the lungs. However, the role of B cells during late TB stages remained unaddressed. Here, we demonstrate that B cells and BCFs persist up to weeks 25–45 post-challenge in the lungs of TB-resistant C57BL/6 (B6) mice. In hyper-susceptible I/St mice, B-cell content markedly drops between weeks 12–16 post-infection, paralleled by diffuse lung tissue inflammation and elevated gene expression levels for pro-inflammatory cytokines IL-1, IL-11, IL-17a, and TNF-α. To check whether B-cells/BCFs control TB infection at advanced stages, we specifically depleted B-cells from B6 mice by administrating anti-CD20 mAbs at week 16 post-infection. This resulted in more rapid cachexia, a shortened lifespan of the infected animals, an increase in (i) lung-infiltrating CD8+ T cells, (ii) IL-6 production by F4/80+ macrophages, (iii) expression levels of genes for neutrophil-attracting factors CXCL1 and IL-17, and tissue-damaging factors MMP8, MMP9, and S100A8. Taken together, our results suggest that lung B cells and BCFs are moderately protective against chronic TB infection.
Functional Relationships between Long Non-Coding RNAs and Estrogen Receptor Alpha: A New Frontier in Hormone-Responsive Breast Cancer Management
Authors: Melone Viola , Salvati Annamaria , Brusco Noemi , Alexandrova Elena , D’Agostino Ylenia , Palumbo Domenico , Palo Luigi , Terenzi Ilaria , Nassa Giovanni , Rizzo Francesca , Giurato Giorgio , Weisz Alessandro , Tarallo Roberta
Published: January 2023

In the complex and articulated machinery of the human genome, less than 2% of the transcriptome encodes for proteins, while at least 75% is actively transcribed into non-coding RNAs (ncRNAs). Among the non-coding transcripts, those ≥200 nucleotides long (lncRNAs) are receiving growing attention for their involvement in human diseases, particularly cancer. Genomic studies have revealed the multiplicity of processes, including neoplastic transformation and tumor progression, in which lncRNAs are involved by regulating gene expression at epigenetic, transcriptional, and post-transcriptional levels by mechanism(s) that still need to be clarified. In breast cancer, several lncRNAs were identified and demonstrated to have either oncogenic or tumor-suppressive roles. The functional understanding of the mechanisms of lncRNA action in this disease could represent a potential for translational applications, as these molecules may serve as novel biomarkers of clinical use and potential therapeutic targets. This review highlights the relationship between lncRNAs and the principal hallmark of the luminal breast cancer phenotype, estrogen receptor α (ERα), providing an overview of new potential ways to inhibit estrogenic signaling via this nuclear receptor toward escaping resistance to endocrine therapy.
In Vitro Studies Demonstrate Antitumor Activity of Vanadium Ions from a CaO-P2O5-CaF2:V2O5 Glass System in Human Cancer Cell Lines A375, A2780, and Caco-2
Authors: Lujerdean Cristian , Zăhan Marius , Dezmirean Daniel Severus , Ștefan Răzvan , Simedru Dorina , Damian Grigore , Vedeanu Nicoleta Simona
Published: January 2023

In this research, we investigated the structural and biological properties of phosphate glasses (PGs) after the addition of V2O5. A xV2O5∙(100 − x)[CaF2∙3P2O5∙CaO] glass system with 0 ≤ x ≤ 16 mol% was synthesized via a conventional melt-quenching technique. Several analysis techniques (dissolution tests, pH, SEM-EDS, FT-IR, and EPR) were used to obtain new experimental data regarding the structural behavior of the system. In vitro tests were conducted to assess the antitumor character of V2O5-doped glass (x = 16 mol%) compared to the matrix (x = 0 mol%) and control (CTRL-) using several tumoral cell lines (A375, A2780, and Caco-2). The characterization of PGs showed an overall dissolution rate of over 90% for all vitreous samples (M and V1–V7) and the high reactivity of this system. EPR revealed a well-resolved hyperfine structure (hfs) typical of vanadyl ions in a C4v symmetry. FT-IR spectra showed the presence of all structural units expected for P2O5, as well as very clear depolymerization of the vitreous network induced by V2O5. The MTT assay indicated that the viability of tumor cells treated with V7-glass extract was reduced to 50% when the highest concentration was used (10 µg/mL) compared to the matrix treatment (which showed no cytotoxic effect at any concentration). Moreover, the matrix treatment (without V2O5) provided an optimal environment for tumor cell attachment and proliferation. In conclusion, the two types of treatment investigated herein were proven to be very different from a statistical point of view (p < 0.01), and the in vitro studies clearly underline the cytotoxic potential of vanadium ions from phosphate glass (V7) as an antitumor agent.
Phytochemical Profiling of Sambucus nigra L. Flower and Leaf Extracts and Their Antimicrobial Potential against Almond Tree Pathogens
Authors: Sánchez-Hernández Eva , Balduque-Gil Joaquín , González-García Vicente , Barriuso-Vargas Juan J. , Casanova-Gascón José , Martín-Gil Jesús , Martín-Ramos Pablo
Published: January 2023

Despite extensive research on the chemical composition of elderberries and their numerous uses in pharmaceutical, beverage, and food production, there is still a lack of knowledge about Sambucus nigra leaves and flowers’ antimicrobial activity against plant pathogens. In this study, the phytoconstituents of their aqueous ammonia extracts were first characterized by infrared spectroscopy and gas chromatography–mass spectrometry. The major phytocompounds identified in the flower extract were octyl 2-methylpropanoate; 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one; propyl malonic acid; adenine; and 1-methyl-2-piperidinemethanol. Concerning the leaf extract, 1,6-anhydro-β-D-glucopyranose; oleic acid; 2,1,3-benzothiadiazole; 2,3-dihydro-benzofuran; and 4-((1E)-3-hydroxy-1-propenyl)-2-methoxyphenol and other phenol derivatives were the main constituents. The potential of the extracts to act as bioprotectants was then investigated against three almond tree pathogens: Diaporthe amygdali, Phytophthora megasperma, and Verticillium dahliae. In vitro tests showed higher activity of the flower extract, with EC90 values in the 241–984 μg·mL−1 range (depending on the pathogen) vs. 354–1322 μg·mL−1 for the leaf extract. In addition, the flower extract led to full protection against P. megasperma at a dose of 1875 μg·mL−1 in ex situ tests on artificially-infected excised almond stems. These inhibitory concentrations were lower than those of commercial fungicides. These findings suggest that S. nigra aerial organs may be susceptible to valorization as an alternative to synthetic fungicides for the protection of this important crop.
UPLC-Q-TOF/MS-Based Metabolomics Approach Reveals Osthole Intervention in Breast Cancer 4T1 Cells
Authors: Li Xiuyun , Zhang Chenglun , Wu Enhui , Han Liang , Deng Xiangliang , Shi Zhongfeng
Published: January 2023

Osthole (OST) is a simple coumarin derivative with pharmacological effects in many types of cancer cells. However, its role and its mechanism of action in breast cancer 4T1 cells remain unclear. In this study, we explored the effects and potential mechanisms of action of OST in 4T1 cells. The MTT, PI, and Annexin V-FITC/PI methods were used to evaluate the effects of OST-treated and untreated 4T1 cells on viability, cell cycle, and apoptosis, respectively. UPLC-Q-TOF/MS combined with multivariate data analysis was used to screen potential biomarkers relevant to the therapeutic mechanisms of OST. Additionally, mTOR, SREBP1, and FASN protein levels were detected using western blotting in OST-treated and untreated 4T1 cells. OST inhibited 4T1 cell proliferation, blocked the cells from remaining in S-phase, and induced apoptosis. In 4T1 cells, OST mainly affected the phospholipid biosynthesis, methyl histidine metabolism, pyrimidine metabolism, and β-oxidation of very long chain fatty acid pathways, suggesting that metabolic changes related to lipid metabolism-mediated signaling systems were the most influential pathways, possibly via inhibition of mTOR/SREBP1/FASN signaling. Our findings reveal biomarkers with potential therapeutic effects in breast cancer and provide insight into the therapeutic and metabolic mechanisms of OST in 4T1 cells.
The Beneficial Effects of Pine Nuts and Its Major Fatty Acid, Pinolenic Acid, on Inflammation and Metabolic Perturbations in Inflammatory Disorders
Authors: Takala Rabaa , Ramji Dipak P. , Choy Ernest
Published: January 2023

Inflammatory disorders such as atherosclerosis, diabetes and rheumatoid arthritis are regulated by cytokines and other inflammatory mediators. Current treatments for these conditions are associated with significant side effects and do not completely suppress inflammation. The benefits of diet, especially the role of specific components, are poorly understood. Polyunsaturated fatty acids (PUFAs) have several beneficial health effects. The majority of studies on PUFAs have been on omega-3 fatty acids. This review will focus on a less studied fatty acid, pinolenic acid (PNLA) from pine nuts, which typically constitutes up to 20% of its total fatty acids. PNLA is emerging as a dietary PUFA and a promising supplement in the prevention of inflammatory disorders or as an alternative therapy. Some studies have shown the health implications of pine nuts oil (PNO) and PNLA in weight reduction, lipid-lowering and anti-diabetic actions as well as in suppression of cell invasiveness and motility in cancer. However, few reviews have specifically focused on the biological and anti-inflammatory effects of PNLA. Furthermore, in recent bioinformatic studies on human samples, the expression of many mRNAs and microRNAs was regulated by PNLA indicating potential transcriptional and post-transcriptional regulation of inflammatory and metabolic processes. The aim of this review is to summarize, highlight, and evaluate research findings on PNO and PNLA in relation to potential anti-inflammatory benefits and beneficial metabolic changes. In this context, the focus of the review is on the potential actions of PNLA on inflammation along with modulation of lipid metabolism and oxidative stress based on data from both in vitro and in vivo experiments, and human findings, including gene expression analysis.
The Predictive Role of Extracellular NAPRT for the Detection of Advanced Fibrosis in Biopsy-Proven Non-Alcoholic Fatty Liver Disease
Authors: Armandi Angelo , Colombo Giorgia , Rosso Chiara , Caviglia Gian Paolo , Olivero Antonella , Abate Maria Lorena , Guariglia Marta , Perez Diaz del Campo Nuria , Castelnuovo Gabriele , Ribaldone Davide Giuseppe , Saracco Giorgio Maria , Genazzani Armando A. , Bugianesi Elisabetta
Published: January 2023

Intrahepatic oxidative stress is a key driver of inflammation and fibrogenesis in non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the role of extracellular Nicotinamide phosphoribosyltransferase (eNAMPT) and extracellular nicotinic acid phosphoribosyltransferase (eNAPRT) for the detection of advanced fibrosis. eNAMPT and eNAPRT were tested in 180 consecutive biopsy-proven NAFLD patients and compared with liver stiffness (LS) and the FIB-4 score. eNAMPT was similarly distributed across fibrosis stages, whereas eNAPRT was increased in patients with advanced fibrosis (p = 0.036) and was associated with advanced fibrosis (OR 1.08, p = 0.016). A multiple stepwise logistic regression model containing significant variables for advanced fibrosis (eNAPRT, type 2 diabetes, age, male sex, ALT) had an area under the curve (AUC) of 0.82 (Se 89.6%, Sp 67.3%, PPV 46.7%, NPV 93.8%) when compared to that of LS (0.79; Se 63.5%, Sp 86.2%, PPV 66.0%, NPV 84.8%) and to that of the FIB-4 score (0.73; Se 80.0%, Sp 56.8%, PPV 44.9%, NPV 86.6%). The use of eNAPRT in clinical practice might allow for the better characterization of NAFLD patients at higher risk of disease progression.