bluuebunny/crossref_metadata_2025 huggingface dataset:
Command Filter-Based Adaptive Neural Control for Nonstrict-Feedback Nonlinear Systems with Prescribed Performance
Authors: Yang Xiaoli , Li Jing , Ge Shuzhi (Sam) , Liang Xiaoling , Han Tao
Published: June 2024

In this paper, a new command filter-based adaptive NN control strategy is developed to address the prescribed tracking performance issue for a class of nonstrict-feedback nonlinear systems. Compared with the existing performance functions, a new performance function, the fixed-time performance function, which does not depend on the accurate initial value of the error signal and has the ability of fixed-time convergence, is proposed for the first time. A radial basis function neural network is introduced to identify unknown nonlinear functions, and the characteristic of Gaussian basis functions is utilized to overcome the difficulties of the nonstrict-feedback structure. Moreover, in contrast to the traditional Backstepping technique, a command filter-based adaptive control algorithm is constructed, which solves the “explosion of complexity” problem and relaxes the assumption on the reference signal. Additionally, it is guaranteed that the tracking error falls within a prescribed small neighborhood by the designed performance functions in fixed time, and the closed-loop system is semi-globally uniformly ultimately bounded (SGUUB). The effectiveness of the proposed control scheme is verified by numerical simulation.
In Situ Gelling Behavior and Biopharmaceutical Characterization of Nano-Silver-Loaded Poloxamer Matrices Designed for Nasal Drug Delivery
Authors: Ivanova Nadezhda , Ermenlieva Neli , Simeonova Lora , Vilhelmova-Ilieva Neli , Bratoeva Kameliya , Stoyanov Georgi , Andonova Velichka
Published: June 2024

A combination of Poloxamer 407 (P407) and hydroxypropyl methylcellulose (HPMC) hydrosols is proposed as an in situ thermo-gelling vehicle for the nasal drug delivery of chlorhexidine–silver nanoparticles conjugates (SN-CX). Optimization of the formulation was carried out by applying varying ratios of P407 and HPMC in the presence and absence of SN-CX so that gelation would occur in the temperature range of the nasal cavity (30–34 °C). Mechanisms for the observed gelation phenomena were suggested based on viscosimetry, texture analysis, and dynamic light scattering. Tests were carried out for sprayability, washout time, in vitro drug release, ex vivo permeation, and antimicrobial activity. When applied separately, HPMC was found to lower the P407 gelation temperature (Tg), whereas SN-CX increased it. However, in the presence of HPMC, SN-CX interfered with the P407 micellar organization in a principally contrasting way while leading to an even further decrease in Tg. SN-CX-loaded nasal formulations composed of P407 16% and HPMC 0.1% demonstrated a desired gelation at 31.9 °C, good sprayability (52.95% coverage of the anterior nasal cavity), mucoadhesion for 70 min under simulated nasal clearance, expedient release and permeation, and preserved anti-infective activity against seasonal Influenza virus and beta-coronavirus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and other pathogens. Our findings suggest that the current development could be considered a potential formulation of a protective nasal spray against respiratory infections.
Geosites and Climate Change—A Review and Conceptual Framework
Authors: Migoń Piotr
Published: June 2024

Geosites are windows into the geological past, which may be recorded in rocks and their properties, the fossil content, and landform produced by processes no longer operating. Since the histories of sedimentation, life, and landscape evolution are to a certain extent controlled by climatic conditions, some geosites may be used as illustrations of various themes linked to the issue of climate change. In this paper, a coherent systematic framework is proposed for how to look at geosites through the lens of climate change. Four major aspects of relevance are recognized: (i) geosites providing evidence of changing climatic conditions in the past; (ii) geosites providing evidence of an environment different than that of today at the place; (iii) geosites providing evidence of extreme weather events; and (iv) dynamic geosites, subject to change as a response to ongoing climate change. The use of geosites to raise awareness and educate the public about climate change faces various interpretation challenges. In particular, linking with ongoing climate change requires caution and balanced presentation as most geosites record changes which occurred without any anthropogenic component. The preferred focus should be on environmental instability in general rather than on any specific reasons for change.
Access, Readiness and Willingness to Engage in Allied Health Telerehabilitation Services for Adults: Does Cultural and Linguistic Diversity Make a Difference?
Authors: Tang Clarice Y. , Bastani Andisheh , Sidhu Balwinder , Saberi Golsa , Baker Elise
Published: June 2024

Telerehabilitation is an appealing service delivery option for optimising recovery. Internationally, the equity of telerehabilitation services for people from culturally and linguistically diverse (CALD) backgrounds has been questioned. Using a 31-item survey, our study explored the access, readiness and willingness of 260 patients receiving allied health services from a large tertiary health service located in Sydney, Australia, to use telerehabilitation for adults. Overall, 72% patients reported having access to technology, 38% met our readiness criteria and 53% reported willingness to engage in telerehabilitation. There were no differences in access, readiness and willingness to engage in telerehabilitation between patients from CALD and non-CALD backgrounds. Age was the only factor that influenced access (OR = 0.94, 95% CI 0.90 to 0.97), readiness (OR = 0.95, 95% CI 0.92 to 0.98) and willingness (OR = 0.97, 95% CI 0.95 to 1.00) to engage in telerehabilitation. Past experience of telerehabilitation was related to willingness (OR = 2.73, 95% CI 1.55–4.79) but not access (OR = 1.79, 95% CI 0.87 to 3.68) or readiness (OR = 1.90, 95% CI 0.93 to 3.87). Our findings highlight the importance of ensuring positive patient experiences to promote ongoing willingness to use telerehabilitation. Efforts are needed to improve patients’ digital health literacy, especially patients from older age groups, to ensure equitable engagement in telerehabilitation services.
Radiologists’ Communicative Role in Breast Cancer Patient Management: Beyond Diagnosis
Authors: Mariano Luciano , Nicosia Luca , Sorce Adriana , Pesapane Filippo , Coppini Veronica , Grasso Roberto , Monzani Dario , Pravettoni Gabriella , Mauri Giovanni , Venturini Massimo , Pizzamiglio Maria , Cassano Enrico
Published: June 2024

In the landscape of cancer treatment, particularly in the realm of breast cancer management, effective communication emerges as a pivotal factor influencing patient outcomes. This article delves into the nuanced intricacies of communication skills, specifically spotlighting the strategies embraced by breast radiologists. By examining the ramifications of communication on patient experience, interdisciplinary collaboration, and legal ramifications, this study underscores the paramount importance of empathetic and comprehensive communication approaches. A special emphasis is placed on the utilization of the SPIKES protocol, a structured method for conveying sensitive health information, and the deployment of strategies for navigating challenging conversations. Furthermore, the work encompasses the significance of communication with caregivers, the integration of artificial intelligence, and the acknowledgement of patients’ psychological needs. By adopting empathetic communication methodologies and fostering multidisciplinary collaboration, healthcare practitioners have the potential to enhance patient satisfaction, promote treatment adherence, and augment the overall outcomes within breast cancer diagnosis. This paper advocates for the implementation of guidelines pertaining to psychological support and the allocation of sufficient resources to ensure the provision of holistic and patient-centered cancer care. The article stresses the need for a holistic approach that addresses patients’ emotional and psychological well-being alongside medical treatment. Through thoughtful and empathetic communication practices, healthcare providers can profoundly impact patient experiences and breast cancer journeys in a positive manner.
Analysis of the Effectiveness of Coordinated Care in the Management of Pharmacotherapy of Patients with Hypertension and Comorbidities in Primary Care—Preliminary Reports
Authors: Galic Aleksandra , Tyranska-Fobke Anna , Kuich Aleksandra , Zapasnik Andrzej , Robakowska Marlena
Published: June 2024

Hypertension (HTN) is the dominant cause of cardiovascular disease and premature death worldwide. Also in Poland, the number of people with HTN is steadily increasing. In order to improve care for patients with HTN and other chronic diseases, a pilot of the POZ PLUS coordinated-care model was introduced. The pilot ran from 1 July 2018 to 30 September 2021 at 47 facilities nationwide. The purpose of this study was to conduct a preliminary analysis of the effectiveness of this model of care. The study focused on the management of pharmacotherapy in patients with hypertension and other comorbidities. The study included a group of 90 patients with HTN. Fifty-nine people were in the coordinated-care study group and 31 in the control group. Data were collected from electronic medical records. The analysis showed a trend toward greater blood-pressure reduction in patients under coordinated care (−4 mmHg difference in systolic blood pressure between the second and first visits and −2 mmHg difference in diastolic pressure between the second and first visits, p = 0.180 and p = 0.156). This suggests the preliminary conclusion that coordinated care in the PCP plus model might have positively affected the outcomes of patients with HTN. Further studies on the subject are planned.
Prognostic Factors and Clinical Outcomes of Surgical Treatment of Major Thoracic Trauma
Authors: Sibilia Maria Chiara , Danuzzo Federica , Spinelli Francesca , Cassina Enrico Mario , Libretti Lidia , Pirondini Emanuele , Raveglia Federico , Tuoro Antonio , Bertolaccini Luca , Isgro’ Stefano , Perrone Stefano , Rizzo Stefania , Petrella Francesco
Published: June 2024

Background: Major thoracic trauma represents a life-threatening condition, requiring a prompt multidisciplinary approach and appropriate pathways for effective recovery. While acute morbidity and mortality are well-known outcomes in thoracic-traumatized patients, long-term quality of life in patients surviving surgical treatment has not been widely investigated before. Methods: Between November 2016 and November 2023, thirty-two consecutive patients were operated on because of thoracic trauma. Age, sex, comorbidities, location and extent of thoracic trauma, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), Organ Injury Scale (OIS), intra and extrathoracic organ involvement, mechanism of injury, type of surgical procedure, postoperative complications, ICU and total length of stay, immediate clinical outcomes and long-term quality of life—by using the EQ-5D-3L scale and Numeric Rate Pain Score (NPRS)—were collected for each patient Results: Results indicated no significant difference in EQOL.5D3L among patients with thoracic trauma based on AIS (p = 0.55), but a significant difference was observed in relation to ISS (p = 0.000011). Conclusions: ISS is correlated with the EQOL.5D3L questionnaire on long-term quality of life, representing the best prognostic factor—in terms of long-term quality of life—in patients surviving major thoracic trauma surgical treatment.
Social and Economic Determinants of Life Expectancy at Birth in Eastern Europe
Authors: Țarcă Viorel , Țarcă Elena , Moscalu Mihaela
Published: June 2024

Life expectancy at birth is considered a parameter of the social development, health system, or economic development of a country. We aimed to investigate the effects of GDP per capita (as the economic factor), health care expenditure, the number of medical doctors (as social factors), and CO2 emissions (as the environmental factor) on life expectancy. We used panel data analysis for 13 Eastern European countries over the 2000–2020 period. After performing the analysis, we used a cross-country fixed-effects panel (GLS with SUR weights). According to our model, a one percent increase in health expenditure (as % of GDP) increases life expectancy at birth by 0.376 years, whereas each additional medical doctor per 10,000 inhabitants increases life expectancy at birth by 0.088 years on average. At the same time, each additional 10,000 USD per capita each year would increase life expectancy at birth by 1.8 years on average. If CO2 emissions increase by 1 metric ton per capita, life expectancy at birth would decrease by 0.24 years, suggesting that higher carbon emissions are capable of reducing longevity. Every European country has to make special efforts to increase the life expectancy of its inhabitants by applying economic and health policies focused on the well-being of the population.
European Smalt in 17th-Century Japan: Porcelain Decoration and Sacred Art
Authors: Montanari Riccardo , Colomban Philippe , Alberghina Maria Francesca , Schiavone Salvatore , Pelosi Claudia
Published: June 2024

Japanese art tradition, contrary to the case of China, is characterized by an efficient and continued, although mostly undocumented, use of smalt from the late 16th century onward. Recent studies have successfully identified this pigment, the cobalt-colored glass that spread throughout the Old Continent during the Renaissance period, as the coloring agent employed for overglaze-blue enameling on Japanese porcelains produced at the kilns of Arita (the porcelain production center of Japan) from the early 1640s until the 20th century. Fragmentary evidence of the use of smalt in Japanese sacred art has also been reported, yet its earliest incorporation into such a type of traditional art form could not be identified. In order to resolve this crucial issue, portable EDXRF was employed for the non-destructive analyses of Japanese porcelains and sacred images bearing blue decoration. Scientific analysis allowed, for the first time ever, to establish a clear timeline of smalt use. Furthermore, this evidence and the literature data both agree, leading to the identification of the origin of the blue material used on both art productions.
Selective Retention of Cross-Fertilised Fruitlets during Premature Fruit Drop of Hass Avocado
Authors: Hapuarachchi Nimanie S. , Kämper Wiebke , Hosseini Bai Shahla , Ogbourne Steven M. , Nichols Joel , Wallace Helen M. , Trueman Stephen J.
Published: June 2024

The productivity of many tree crops is limited by low yield, partly due to high rates of fruitlet abscission during early fruit development. Early studies suggested that cross-pollinated fruitlets may be selectively retained during fruit development, although paternity testing of fruitlets to test this hypothesis was technically challenging. We used MassARRAY genotyping to determine the effects of pollen parentage on fruitlet retention and fruit quality of Hass avocado. We identified the paternity of abscised and retained fruitlets at 6 and 10 weeks, and mature fruit at 36 weeks, after peak anthesis. We measured the embryo mass, pericarp mass, total mass and nutrient concentrations of fruitlets, and the seed mass, flesh mass, total mass, diameter, length, nutrient concentrations and fatty-acid composition of mature fruit. The percentages of progeny on the tree that were cross-fertilised increased from 4.6% at 6 weeks after peak anthesis to 10.7% at fruit maturity. Only 1.0% of freshly abscised fruitlets on the ground at 10 weeks after peak anthesis were cross-pollinated even though 6.5% of retained fruitlets on the tree were cross-pollinated. At this stage, cross-pollinated fruitlets had similar nutrient concentrations to self-pollinated fruitlets, but they had higher total contents of P, K, Al, Ca, Fe, Mn and Zn due to having greater fruitlet mass. At maturity, cross-pollinated fruit were 6% heavier and had 2% greater diameter than self-pollinated fruit, without significant differences in flesh nutrient concentrations or fatty acid composition. The results demonstrate that Hass avocado trees selectively retain cross-pollinated fruitlets, which are larger than self-pollinated fruitlets and ultimately produce larger mature fruit. Avocado growers can increase fruit size and yield by improving the opportunities for cross-pollination, possibly by closely interplanting type A and type B cultivars and introducing more beehives into orchards.
Impact of Program Region and Prestige on Industry Supplemental Earnings for Pediatric Orthopedic Surgery Fellowships in the United States: A Retrospective Analysis
Authors: Balu Abhinav R. , Baumann Anthony N. , Talaski Grayson M. , Pottayil Faheem , Walley Kempland C. , Anastasio Albert T. , Baldwin Keith D.
Published: June 2024

Introduction: With the passage of the Physician Payment Sunshine Act, there has been increased transparency regarding the industrial financial relations that physicians have. Orthopedic surgeons have been highly studied in this domain with approximately 50% of all orthopedic surgeons engaging in industrial financial relationships. Furthermore, an increasing number of orthopedic surgeons are seeking fellowship training with pediatric fellowship programs gaining popularity in recent years. The purpose of this study is to evaluate the impact various pediatric orthopedic fellowship programs have on industry earnings and academic productivity. Methods: Pediatric orthopedic fellowship programs were identified via the Orthopedic Society of North America (POSNA) website. Information on individual fellowship programs was obtained from their respective websites. Academic productivity was measured via an aggregate of all employed physicians’ H-index at a specific fellowship as found on the Scopus website. The Open Payments Database (OPD) website was used to assess lifetime industry earnings. Other variables such as Newsweek or Doximity ranking were taken directly from relevant websites. Statistical analysis was performed using a Kruskal–Wallis test with Bonferroni correction and Mann–Whitney U-test. Results: A total of 43 pediatric orthopedic surgery fellowships in the United States were identified with a total of 392 physicians as fellowship faculty. Complete OPD and H-index information were available for 336 of those physicians (85.7%). On average, there were 7.81 ± 5.18 physicians and 1.56 ± 0.93 fellows per program. The mean combined physician H-index was 117.23 ± 122.51, and the mean combined physician lifetime supplemental earnings in dollars was $646,684.37 ± $1,159,507.17. There was no significant relationship between region of pediatric orthopedic fellowship, Newsweek ranking of affiliated hospital, Doximity ranking of affiliated hospital, presence of MBA program, type of program (public, private, mixed), and the lifetime industry earnings or academic productivity of program graduates. Conclusions: Despite the observed lack of statistical significance, there were clear trends observed with fellowship programs in the northeast and west coast regions being the highest earning and fellowship programs with top 10 Newsweek ranking of affiliated hospital having by far the greatest industry earnings. Sample size limitations likely prevented the detection of statistical significance. Future studies should examine if any relation exists when accounting for type of industry payment received and case volume per fellowship program.
Association between Physical Activity and Dengue and Its Repercussions for Public Health: New Insights
Authors: Pitanga Francisco José Gondim , Matsudo Victor Keihan Rodrigues
Published: June 2024

Dengue is an endemic disease in tropical countries, mainly in South America, Southwest Asia, and Africa, which, despite having a low lethality rate, can overwhelm health systems. Strengthening the immune system through regular physical activity can be an important tool to prevent contagion, worsening, hospitalizations, and deaths caused by the disease, as seen in the COVID-19 pandemic. Therefore, this point of view aims to analyze the possible association between physical activity and dengue and its repercussions on public health. Comments were made on the main characteristics of dengue as well as on the main vaccines available to date. It was also discussed the impacts of dengue on health systems, in addition to the main repercussions for public health when a very large number of people are infected. It was also commented on the main factors that contribute to the worsening of the clinical stage of dengue, in addition to discussions and reflections on physical activity, strengthening the immune system, and dengue. There are assumptions that regular physical activity can be an important public health strategy to prevent contagion, severity, and hospitalizations caused by dengue and that it needs to be promoted by governments around the world as a tool for preventing and treating not only chronic communicable diseases but also infectious diseases.
Use of Dietary Supplements and Influencing Factors in Children
Authors: Koç Orkut , Tosyalı Merve , Gökçe Şule , Koç Feyza
Published: June 2024

Introduction: In recent years, the use of dietary supplements has increased in all age groups. Parents may also use these supplements for their children for different reasons. This study aims to determine the use of dietary supplements by children, the factors affecting this use, and the attitudes of parents about these products. Methods: A total of 1038 children aged 2–18 years without any chronic disease who presented to the pediatric outpatient clinics of Ege University Children’s Hospital were included in this study. Parents (n = 1000) who agreed to participate in the study were interviewed face-to-face, and a comprehensive questionnaire including questions about children’s use of dietary supplements, sociodemographic characteristics, and parents’ attitudes towards dietary supplements was administered. Analyses were performed with SPSS 25.0. Results: The mean age of the children included in our study was 8.6 ± 4.8 years, and 51% (n = 510) were male. It was found that 32.5% of the children used nutritional supplements, and vitamin–mineral preparations (23.2%) were the most frequently used. Omega-3 (19.3%) and immune support products (9.4%) were the second and third most frequently used supplements, respectively. A significant relationship was found between the use of dietary supplements and the child’s age, body weight, body mass index, parents’ educational level, being health worker, and economic status (p < 0.05). It was found that most of the families thought that vitamin–mineral and omega-3 products were beneficial for growth and development and that they received information from doctors most frequently before taking these products. However, it was found that families followed the media as the second most frequent source of information for these products. Conclusions: Approximately one-third of the children in our study use dietary supplements. It is very important to raise awareness among families about the use of these products when necessary and with the recommendation of a physician. To prevent families from using dietary supplements that are not necessary for their children, especially due to misinformation in the media, pediatricians should provide correct information to parents about these products at every clinic visit. A concerted effort is needed from policy makers, media organizations, and health care providers to guide the safe use of DS. The results obtained from this study will shed light on future randomized controlled prospective studies
Oral Health Literacy and Determinants among an Elderly Community in Portugal
Authors: Costa Helder , Lopes Pedro , Correia Maria José , Couto Patrícia , Silva Ana Margarida , López-Marcos Joaquin Francisco , Veiga Nélio
Published: June 2024

High average life expectancy has caused an increase in the elderly population and with it arises the need to characterize this population regarding their health and, in particular, their oral health. The purpose of this study was to assess and characterize oral health, oral rehabilitation, oral health literacy, oral health perception and quality of life in a sample of elderly participants of a physical activity program in Portugal. An observational cross-sectional study was designed with a group of 206 individuals. All the individuals were clinically assessed, DMFT, PSR and the plaque index were registered, and a questionnaire was applied in the form of a “face-to-face” interview with questions related to the quality of life related to oral health (GOHAI index and the REALD-30 scale). Of the 206 study participants, 90.3% admit brushing their teeth daily, 6.3% practice daily flossing, and 5.8% had a dental appointment in the last 12 months. Applying the REALD-30 scale, 22.7% have a low level (score 0–14), 43.7% a moderate level (score 15–22) and 33.6% a high level (score 23–29) of oral health literacy. The GOHAI scale reveals that 37.4% have a high self-perception of their oral health. A considerable proportion of the sample studied present a moderate level of oral health literacy. Therefore, educating each person about their oral health when participating in a specific health program and developing proposals for oral health promotion activities should be widely considered as a strategy towards primary prevention. Future oral health literacy sessions should be held in order to improve oral health and quality of life among the community.
Evolving Strategies for Use of Phytochemicals in Prevention and Long-Term Management of Cardiovascular Diseases (CVD)
Authors: Haines Donald David , Cowan Fred M. , Tosaki Arpad
Published: June 2024

This report describes major pathomechanisms of disease in which the dysregulation of host inflammatory processes is a major factor, with cardiovascular disease (CVD) as a primary model, and reviews strategies for countermeasures based on synergistic interaction between various agents, including drugs and generally regarded as safe (GRAS) natural medical material (NMM), such as Ginkgo biloba, spice phytochemicals, and fruit seed flavonoids. The 15 well-defined CVD classes are explored with particular emphasis on the extent to which oxidative stressors and associated ischemia-reperfusion tissue injury contribute to major symptoms. The four major categories of pharmaceutical agents used for the prevention of and therapy for CVD: statins, beta blockers (β-blockers), blood thinners (anticoagulants), and aspirin, are presented along with their adverse effects. Analyses of major cellular and molecular features of drug- and NMM-mediated cardioprotective processes are provided in the context of their development for human clinical application. Future directions of the evolving research described here will be particularly focused on the characterization and manipulation of calcium- and calcineurin-mediated cascades of signaling from cell surface receptors on cardiovascular and immune cells to the nucleus, with the emergence of both protective and pathological epigenetic features that may be modulated by synergistically-acting combinations of drugs and phytochemicals in which phytochemicals interact with cells to promote signaling that reduces the effective dosage and thus (often) toxicity of drugs.
Contribution of Extracellular Particles Isolated from Morus sp. (Mulberry) Fruit to Their Reported Protective Health Benefits: An In Vitro Study
Authors: Garrett Neve R. , Pink Ryan C. , Lawson Charlotte
Published: June 2024

Morus sp. (mulberry) has a long tradition of use as a medicinal treatment, including for cardiovascular disease and type 2 diabetes, being shown to have antioxidant properties and to promote wound healing. Extracellular vesicles (EVs) are sub-micron, membrane-enclosed particles that were first identified in mammalian bodily fluids. EV-like particles have been described in plants (PDVs) and shown to have similar characteristics to mammalian EVs. We hypothesised that some of the health benefits previously attributed to the fruit of Morus sp. could be due to the release of PDVs. We isolated PDVs from Morus nigra and Morus alba via ultracentrifugation and incubated THP-1 monocytes, differentiated THP-1 macrophages, or HMEC-1 endothelial cells with pro-oxidant compounds DMNQ (THP-1) and glucose oxidase (HMEC-1) or lipopolysaccharide (LPS) in the presence of different fractions of mulberry EVs. Mulberry EVs augmented ROS production with DMNQ in THP-1 and caused the downregulation of ROS in HMEC-1. Mulberry EVs increased LPS-induced IL-1β secretion but reduced CCL2 and TGF-β secretion in THP-1 macrophages. In scratch wound assays, mulberry EVs inhibited HMEC-1 migration but increased proliferation in both low and high serum conditions, suggesting that they have opposing effects in these two important aspects of wound healing. One of the limitations of plant-derived therapeutics has been overcoming the low bioavailability of isolated compounds. We propose that PDVs could provide the link between physiological dose and therapeutic benefit by protecting plant active compounds in the GIT as well as potentially delivering genetic material or proteins that contribute to previously observed health benefits.
The Immune Response of Cancer Cells in Breast and Gynecologic Neoplasms
Authors: Rakoczy Katarzyna , Kaczor Justyna , Sołtyk Adam , Szymańska Natalia , Stecko Jakub , Drąg-Zalesińska Małgorzata , Kulbacka Julita
Published: June 2024

Cancer diseases constitute a major health problem which leads to the death of millions of people annually. They are unique among other diseases because cancer cells can perfectly adapt to the environment that they create themselves. This environment is usually highly hostile and for normal cells it would be hugely difficult to survive, however neoplastic cells not only can survive but also manage to proliferate. One of the reasons is that they can alter immunological pathways which allow them to be flexible and change their phenotype to the one needed in specific conditions. The aim of this paper is to describe some of these immunological pathways that play significant roles in gynecologic neoplasms as well as review recent research in this field. It is of high importance to possess extensive knowledge about these processes, as greater understanding leads to creating more specialized therapies which may prove highly effective in the future.
Arrhythmogenic Ventricular Remodeling by Next-Generation Bruton’s Tyrosine Kinase Inhibitor Acalabrutinib
Authors: Zhao Yanan , Chakraborty Praloy , Tomassetti Julianna , Subha Tasnia , Massé Stéphane , Thavendiranathan Paaladinesh , Billia Filio , Lai Patrick F. H. , Abdel-Qadir Husam , Nanthakumar Kumaraswamy
Published: June 2024

Cardiac arrhythmias remain a significant concern with Ibrutinib (IBR), a first-generation Bruton’s tyrosine kinase inhibitor (BTKi). Acalabrutinib (ABR), a next-generation BTKi, is associated with reduced atrial arrhythmia events. However, the role of ABR in ventricular arrhythmia (VA) has not been adequately evaluated. Our study aimed to investigate VA vulnerability and ventricular electrophysiology following chronic ABR therapy in male Sprague–Dawley rats utilizing epicardial optical mapping for ventricular voltage and Ca2+ dynamics and VA induction by electrical stimulation in ex-vivo perfused hearts. Ventricular tissues were snap-frozen for protein analysis for sarcoplasmic Ca2+ and metabolic regulatory proteins. The results show that both ABR and IBR treatments increased VA vulnerability, with ABR showing higher VA regularity index (RI). IBR, but not ABR, is associated with the abbreviation of action potential duration (APD) and APD alternans. Both IBR and ABR increased diastolic Ca2+ leak and Ca2+ alternans, reduced conduction velocity (CV), and increased CV dispersion. Decreased SERCA2a expression and AMPK phosphorylation were observed with both treatments. Our results suggest that ABR treatment also increases the risk of VA by inducing proarrhythmic changes in Ca2+ signaling and membrane electrophysiology, as seen with IBR. However, the different impacts of these two BTKi on ventricular electrophysiology may contribute to differences in VA vulnerability and distinct VA characteristics.
Navigating the Maze of Kinases: CaMK-like Family Protein Kinases and Their Role in Atherosclerosis
Authors: Teuwen Jules T. J. , van der Vorst Emiel P. C. , Maas Sanne L.
Published: June 2024

Circulating low-density lipoprotein (LDL) levels are a major risk factor for cardiovascular diseases (CVD), and even though current treatment strategies focusing on lowering lipid levels are effective, CVD remains the primary cause of death worldwide. Atherosclerosis is the major cause of CVD and is a chronic inflammatory condition in which various cell types and protein kinases play a crucial role. However, the underlying mechanisms of atherosclerosis are not entirely understood yet. Notably, protein kinases are highly druggable targets and represent, therefore, a novel way to target atherosclerosis. In this review, the potential role of the calcium/calmodulin-dependent protein kinase-like (CaMKL) family and its role in atherosclerosis will be discussed. This family consists of 12 subfamilies, among which are the well-described and conserved liver kinase B1 (LKB1) and 5′ adenosine monophosphate-activated protein kinase (AMPK) subfamilies. Interestingly, LKB1 plays a key role and is considered a master kinase within the CaMKL family. It has been shown that LKB1 signaling leads to atheroprotective effects, while, for example, members of the microtubule affinity-regulating kinase (MARK) subfamily have been described to aggravate atherosclerosis development. These observations highlight the importance of studying kinases and their signaling pathways in atherosclerosis, bringing us a step closer to unraveling the underlying mechanisms of atherosclerosis.
Potential Effects of Low-Level Toluene Exposure on the Nervous System of Mothers and Infants
Authors: Yu So Yeon , Kim Seung Hwan , Choo Jeong Hyeop , Jang Sehun , Kim Jihyun , Ahn Kangmo , Hwang Seung Yong
Published: June 2024

In day-to-day living, individuals are exposed to various environmentally hazardous substances that have been associated with diverse diseases. Exposure to air pollutants can occur during breathing, posing a considerable risk to those with environmental health vulnerabilities. Among vulnerable individuals, maternal exposure can negatively impact the mother and child in utero. The developing fetus is particularly vulnerable to environmentally hazardous substances, with potentially greater implications. Among air pollutants, toluene is neurotoxic, and its effects have been widely explored. However, the impact of low-level toluene exposure in daily life remains unclear. Herein, we evaluated 194 mothers and infants from the Growing children’s health and Evaluation of Environment (GREEN) cohort to determine the possible effects of early-life toluene exposure on the nervous system. Using Omics experiments, the effects of toluene were confirmed based on epigenetic changes and altered mRNA expression. Various epigenetic changes were identified, with upregulated expression potentially contributing to diseases such as glioblastoma and Alzheimer’s, and downregulated expression being associated with structural neuronal abnormalities. These findings were detected in both maternal and infant groups, suggesting that maternal exposure to environmental hazardous substances can negatively impact the fetus. Our findings will facilitate the establishment of environmental health policies, including the management of environmentally hazardous substances for vulnerable groups.
Extrusion of Neutrophil Extracellular Traps (NETs) Negatively Impacts Canine Sperm Functions: Implications in Reproductive Failure
Authors: León Marion , Moya Claudia , Rivera-Concha Rodrigo , Pezo Felipe , Uribe Pamela , Schulz Mabel , Sánchez Raúl , Taubert Anja , Hermosilla Carlos , Zambrano Fabiola
Published: June 2024

Reproductive failure in dogs is often due to unknown causes, and correct diagnosis and treatment are not always achieved. This condition is associated with various congenital and acquired etiologies that develop inflammatory processes, causing an increase in the number of leukocytes within the female reproductive tract (FRT). An encounter between polymorphonuclear neutrophils (PMNs) and infectious agents or inflammation in the FRT could trigger neutrophil extracellular traps (NETs), which are associated with significantly decreased motility and damage to sperm functional parameters in other species, including humans. This study describes the interaction between canine PMNs and spermatozoa and characterizes the release of NETs, in addition to evaluating the consequences of these structures on canine sperm function. To identify and visualize NETs, May–Grünwald Giemsa staining and immunofluorescence for neutrophil elastase (NE) were performed on canine semen samples and sperm/PMN co-cultures. Sperm viability was assessed using SYBR/PI and acrosome integrity was assessed using PNA-FITC/PI by flow cytometry. The results demonstrate NETs release in native semen samples and PMN/sperm co-cultures. In addition, NETs negatively affect canine sperm function parameters. This is the first report on the ability of NETs to efficiently entrap canine spermatozoa, and to provide additional data on the adverse effects of NETs on male gametes. Therefore, NETs formation should be considered in future studies of canine reproductive failure, as these extracellular fibers and NET-derived pro-inflammatory capacities will impede proper oocyte fertilization and embryo implantation. These data will serve as a basis to explain certain reproductive failures of dogs and provide new information about triggers and molecules involved in adverse effects of NETosis for domestic pet animals.
New Molecules in Type 2 Diabetes: Advancements, Challenges and Future Directions
Authors: Chatzianagnostou Kyriazoula , Gaggini Melania , Suman Florentin Adrian , Simonini Ludovica , Vassalle Cristina
Published: June 2024

Although good glycemic control in patients with type 2 diabetes (T2D) can prevent cardiovascular complications, many diabetic patients still have poor optimal control. A new class of antidiabetic drugs (e.g., glucagon-like peptide-1-GLP-1 receptor agonists, sodium-glucose co-transporters-SGLT2 inhibitors), in addition to the low hypoglycemic effect, exert multiple beneficial effects at a metabolic and cardiovascular level, through mechanisms other than antihyperglycemic agents. This review aims to discuss the effects of these new antidiabetic drugs, highlighting cardiovascular and metabolic benefits, through the description of their action mechanisms as well as available data by preclinical and clinical studies. Moreover, new innovative tools in the T2D field will be described which may help to advance towards a better targeted T2D personalized care in future.
Tumor-Homing Peptides as Crucial Component of Magnetic-Based Delivery Systems: Recent Developments and Pharmacoeconomical Perspective
Authors: Milewska Sylwia , Sadowska Anna , Stefaniuk Natalia , Misztalewska-Turkowicz Iwona , Wilczewska Agnieszka Z. , Car Halina , Niemirowicz-Laskowska Katarzyna
Published: June 2024

According to data from the World Health Organization (WHO), cancer is considered to be one of the leading causes of death worldwide, and new therapeutic approaches, especially improved novel cancer treatment regimens, are in high demand. Considering that many chemotherapeutic drugs tend to have poor pharmacokinetic profiles, including rapid clearance and limited on-site accumulation, a combined approach with tumor-homing peptide (THP)-functionalized magnetic nanoparticles could lead to remarkable improvements. This is confirmed by an increasing number of papers in this field, showing that the on-target peptide functionalization of magnetic nanoparticles improves their penetration properties and ensures tumor-specific binding, which results in an increased clinical response. This review aims to highlight the potential applications of THPs in combination with magnetic carriers across various fields, including a pharmacoeconomic perspective.
Guardians and Mediators of Metastasis: Exploring T Lymphocytes, Myeloid-Derived Suppressor Cells, and Tumor-Associated Macrophages in the Breast Cancer Microenvironment
Authors: Ruocco Maria Rosaria , Gisonna Armando , Acampora Vittoria , D’Agostino Anna , Carrese Barbara , Santoro Jessie , Venuta Alessandro , Nasso Rosarita , Rocco Nicola , Russo Daniela , Cavaliere Annachiara , Altobelli Giovanna Giuseppina , Masone Stefania , Avagliano Angelica , Arcucci Alessandro , Fiume Giuseppe
Published: June 2024

Breast cancers (BCs) are solid tumors composed of heterogeneous tissues consisting of cancer cells and an ever-changing tumor microenvironment (TME). The TME includes, among other non-cancer cell types, immune cells influencing the immune context of cancer tissues. In particular, the cross talk of immune cells and their interactions with cancer cells dramatically influence BC dissemination, immunoediting, and the outcomes of cancer therapies. Tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) represent prominent immune cell populations of breast TMEs, and they have important roles in cancer immunoescape and dissemination. Therefore, in this article we review the features of TILs, TAMs, and MDSCs in BCs. Moreover, we highlight the mechanisms by which these immune cells remodel the immune TME and lead to breast cancer metastasis.
Revealing Spermatogenesis in Smooth-Hound Sharks Mustelus mustelus: Insights into the Morphological and Macromolecular Composition of Spermatogenic Cells
Authors: Chemello Giulia , De Santis Lorenzo Jacopo , Trotta Erica , Zarantoniello Matteo , Santoni Chiara , Maradonna Francesca , Olivotto Ike , Giorgini Elisabetta , Gioacchini Giorgia
Published: June 2024

Elasmobranchs have an ancestral reproductive system, which offers insights into vertebrate reproductive evolution. Despite their unchanged design over 400 million years, they evolved complex mechanisms ensuring reproductive success. However, human activities induced a significant decline in elasmobranch populations worldwide. In the Mediterranean basin, the smooth-hound shark (Mustelus mustelus) is one of the species that are considered vulnerable to human activities. Conservation efforts necessitate a thorough understanding of its reproductive strategy. This study focused on mature male specimens of smooth-hound sharks that were captured in the Adriatic area and successively analyzed to provide, for the first time, a histologically detailed description of testicular development in the species. Seven phases of the spermatogenesis process were identified, along with the macromolecular characterization of cells obtained using Fourier-transform infrared imaging. Histological analysis showed structural and cellular features similar to those documented in the spermatocysts of other elasmobranchs. The examination of the evolution and migration of both germinative and Sertoli cells at each phase revealed their close connection. Furthermore, different expression levels of lipids, proteins, and phosphates (DNA) at each spermatogenesis stage were observed. This research provided new information on spermatogenesis in the common smooth-hound shark, which is crucial for conservation efforts against population decline and anthropogenic pressures.
From the Microbiome to the Electrome: Implications for the Microbiota–Gut–Brain Axis
Authors: Bourqqia-Ramzi Marwane , Mansilla-Guardiola Jesús , Muñoz-Rodriguez David , Quarta Elisa , Lombardo-Hernandez Juan , Murciano-Cespedosa Antonio , Conejero-Meca Francisco José , Mateos González Álvaro , Geuna Stefano , Garcia-Esteban María Teresa , Herrera-Rincon Celia
Published: June 2024

The gut microbiome plays a fundamental role in metabolism, as well as the immune and nervous systems. Microbial imbalance (dysbiosis) can contribute to subsequent physical and mental pathologies. As such, interest has been growing in the microbiota–gut–brain brain axis and the bioelectrical communication that could exist between bacterial and nervous cells. The aim of this study was to investigate the bioelectrical profile (electrome) of two bacterial species characteristic of the gut microbiome: a Proteobacteria Gram-negative bacillus Escherichia coli (E. coli), and a Firmicutes Gram-positive coccus Enterococcus faecalis (E. faecalis). We analyzed both bacterial strains to (i) validate the fluorescent probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, DiBAC4(3), as a reliable reporter of the changes in membrane potential (Vmem) for both bacteria; (ii) assess the evolution of the bioelectric profile throughout the growth of both strains; (iii) investigate the effects of two neural-type stimuli on Vmem changes: the excitatory neurotransmitter glutamate (Glu) and the inhibitory neurotransmitter γ-aminobutyric acid (GABA); (iv) examine the impact of the bioelectrical changes induced by neurotransmitters on bacterial growth, viability, and cultivability using absorbance, live/dead fluorescent probes, and viable counts, respectively. Our findings reveal distinct bioelectrical profiles characteristic of each bacterial species and growth phase. Importantly, neural-type stimuli induce Vmem changes without affecting bacterial growth, viability, or cultivability, suggesting a specific bioelectrical response in bacterial cells to neurotransmitter cues. These results contribute to understanding the bacterial response to external stimuli, with potential implications for modulating bacterial bioelectricity as a novel therapeutic target.
Exploring the Interplay between the Hologenome and Complex Traits in Bovine and Porcine Animals Using Genome-Wide Association Analysis
Authors: Qadri Qamar Raza , Lai Xueshuang , Zhao Wei , Zhang Zhenyang , Zhao Qingbo , Ma Peipei , Pan Yuchun , Wang Qishan
Published: June 2024

Genome-wide association studies (GWAS) significantly enhance our ability to identify trait-associated genomic variants by considering the host genome. Moreover, the hologenome refers to the host organism’s collective genetic material and its associated microbiome. In this study, we utilized the hologenome framework, called Hologenome-wide association studies (HWAS), to dissect the architecture of complex traits, including milk yield, methane emissions, rumen physiology in cattle, and gut microbial composition in pigs. We employed four statistical models: (1) GWAS, (2) Microbial GWAS (M-GWAS), (3) HWAS-CG (hologenome interaction estimated using COvariance between Random Effects Genome-based restricted maximum likelihood (CORE-GREML)), and (4) HWAS-H (hologenome interaction estimated using the Hadamard product method). We applied Bonferroni correction to interpret the significant associations in the complex traits. The GWAS and M-GWAS detected one and sixteen significant SNPs for milk yield traits, respectively, whereas the HWAS-CG and HWAS-H each identified eight SNPs. Moreover, HWAS-CG revealed four, and the remaining models identified three SNPs each for methane emissions traits. The GWAS and HWAS-CG detected one and three SNPs for rumen physiology traits, respectively. For the pigs’ gut microbial composition traits, the GWAS, M-GWAS, HWAS-CG, and HWAS-H identified 14, 16, 13, and 12 SNPs, respectively. We further explored these associations through SNP annotation and by analyzing biological processes and functional pathways. Additionally, we integrated our GWA results with expression quantitative trait locus (eQTL) data using transcriptome-wide association studies (TWAS) and summary-based Mendelian randomization (SMR) methods for a more comprehensive understanding of SNP-trait associations. Our study revealed hologenomic variability in agriculturally important traits, enhancing our understanding of host-microbiome interactions.