Search Results (1,234)

The fortified hilltop settlement of Monkodonja, located near Rovinj on the west coast of Istria, Croatia, provides insight into Bronze Age occupation and conflict in the Adriatic region. Established around 2000 BC, as evidenced by a series of C14 dates from human and animal bones, the settlement experienced significant construction phases, particularly in its defensive architecture. Its earliest fortifications, built with limestone blocks using dry-stone wall techniques, date to the 19th century BC, with major expansions in the 16th century BC, where the primary wall was doubled in width and reached over 3 m in thickness. Monkodonja’s architectural complexity, notably the West Gate and Acropolis fortifications, and certain types of artifacts reveal influences from southern regions such the eastern Aegean. However, the settlement appears to have met a violent end around the 15th century BC, suggested by destruction layers, widespread burning, and the presence of weapons such as a lance tip, bronze axe, and slingstones. Monkodonja’s destruction raises questions about broader military conflicts in the Adriatic region during this period. Possible causes could include localized warfare or connections to larger-scale disturbances. Research in Monkodonja is also significant in the context of the debate surrounding the emergence of the so-called Castellieri settlements in Istria at the beginning of the 2nd millennium BC. As early as the beginning of the 20th century, it was proposed that a migration of people to the Istrian peninsula brought this new settlement form and other influences, leading to a significant population increase. The appearance of the Castellieri settlement form coincides with a period marked by documented climatic changes and two major natural disasters in the form of volcanic eruptions. Full article

Thyroid cancer is the most common endocrine malignancy in the United States, with an overall favorable prognosis. However, some patients experience poor outcomes due to the development of resistance to conventional therapies. Genetic alterations, including mutations in BRAF, Met, and p53, play critical roles in thyroid cancer progression, with the BRAF V600E mutation detected in over 60% of cases. This study investigates the tumor-suppressive role of Annexin A7 (ANXA7) in thyroid cancer, focusing on its potential impact on tumor behavior and therapeutic response. Our analysis, which included RNA sequencing and protein profiling, revealed reduced ANXA7 expression in thyroid cancer cells, particularly in those harboring the BRAF V600E mutation. Upon treatment with inhibitors targeting BRAF and MEK, ANXA7 expression increased, leading to reduced phosphorylation of ERK and activation of apoptotic pathways. Additionally, we identified the cyclin-dependent kinase inhibitor p21 as a key player in modulating resistance to BRAF inhibitors. Combination therapies aimed at concurrently increasing p21 and ANXA7 levels resulted in a marked enhancement of apoptosis. These findings suggest a previously uncharacterized regulatory network involving the ANXA7/p21/BRAF/MAPK/p53 axis, which may contribute to drug resistance in thyroid cancer. This study provides new insights into overcoming resistance to BRAF and MAPK inhibitors, with implications for treating thyroid cancer and potentially other BRAF-mutant tumors. Future efforts will focus on high-throughput screening approaches to explore ANXA7-targeted therapeutic strategies for thyroid cancer. Full article

In summer, the urban heat island effect causes unbearable warmth in Shantou City, especially in the urban areas along the Inner Bay with densely populated neighborhoods. An investigation of the layout patterns of 100 residential neighborhoods along Shantou’s Inner Bay was conducted, leading to the establishment of four types and nine sub-types of idealized residential neighborhood models. Their wind speed, relative humidity, and air temperature were simulated in the ENVI-met software (version No.5.0.1). The simulation results show that high-rise buildings in the front areas play a decisive role in the overall microclimate environment. Accordingly, three principal drawbacks regarding neighborhood layout for thermal climate adaptation were extracted. Furthermore, by comparing the simulation results before and after modifying the layout of high-rise buildings, three spatial strategies to strengthen the humidification and cooling effect of sea–land breezes to optimize the outdoor microclimatic environment of neighborhoods were proposed, and these strategies were subsequently verified in the Golden-Harbor neighborhood. Full article

Background: Surrogate indexes of insulin resistance (IR) are less expensive than the euglycemic glucose clamp. The simultaneous impact of sex and gender, smoking, and combined oral contraceptives (COC) on IR surrogate indexes was studied in a cohort of healthy young men and women (stratified in COC-free women and COC users). Methods: Glycemia, insulin, C-peptide, TG, and HDL were measured in serum samples and used to calculate IGR, HOMA-IR-IR, QUICKI, FIRI, METS-IR, TG, and MCAi. Results: Men had higher BMI, glycemia, TG, METS-IR, TyG, and lower HDL than COC-free women and they had lower IGR and higher METS-IR and MCAi than COC users. TG, HDL, and TyG were lower and MCAi is higher in COC-free women than in COC users. In non-smokers, men had higher BMI and METS-IR and lower HDL than both cohorts of women. COC-free women showed a lower TyG index than men and COC women and lower TG, HDL, and IGR. MCAi was higher in COC-free women than in COC users. Smoking reduced sex and gender differences: HDL was lower in men than COC users and IGR was lower in men than COC-free women. Intra-sex differences were reported only in COC-free women: smokers had higher insulin, C-peptide, TG, and IGR and lower MCAi than non-smokers. Cluster analysis evidenced a significant separation between the sexes and smokers and non-smokers. Conclusions: Smoking leads to changes in the phenotype of both men and women, as well as COC in women; they should be considered independent variables in clinical studies given, representing a fundamental cornerstone in the personalization of prevention and care. Full article

Metabolic Syndrome (MetS) is a complex, multifactorial condition characterized by risk factors such as abdominal obesity, insulin resistance, dyslipidemia and hypertension, which significantly contribute to the development of cardiovascular disease (CVD), the leading cause of death worldwide. Early identification and effective monitoring of MetS is crucial for preventing serious cardiovascular complications. This article provides a comprehensive overview of various biomarkers associated with MetS, including lipid profile markers (triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio), inflammatory markers (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), leptin/adiponectin ratio, omentin and fetuin-A/adiponectin ratio), oxidative stress markers (lipid peroxides, protein and nucleic acid oxidation, gamma-glutamyl transferase (GGT), uric acid) and microRNAs (miRNAs) such as miR-15a-5p, miR5-17-5p and miR-24-3p. Additionally, this review highlights the importance of biomarkers in MetS and the need for advancements in their identification and use for improving prevention and treatment. Seaweed therapy is also discussed as a significant intervention for MetS due to its rich content of fiber, antioxidants, minerals and bioactive compounds, which help improve cardiovascular health, reduce inflammation, increase insulin sensitivity and promote weight loss, making it a promising nutritional strategy for managing metabolic and cardiovascular health. Full article

Temporomandibular disorders (TMDs) encompass various clinical conditions associated with the temporomandibular joint (TMJ) and the masticatory muscles. TMD symptoms include pain in the orofacial region, restricted or altered mandibular movement, and sounds associated with the temporomandibular joint (TMJ). This condition adversely affects quality of life, social functioning, and daily activities, and may also contribute to widespread pain syndromes and comorbidities, including irritable bowel syndrome (IBS). IBS is a common chronic functional disorder of the lower gastrointestinal tract, characterized by recurrent abdominal pain associated with impaired bowel symptoms. Previous studies indicate an association between TMD and IBS. This scoping review examined the correlation between TMD and IBS concerning their pathology, frequency, and severity, and the potential similarities in how the nervous and endocrine systems influence them. PubMed, SCOPUS, Web of Science, and Google Scholar search engines were utilized to identify suitable studies for this article. Following the application of selection criteria, a total of 58 clinical papers met the eligibility requirements for inclusion in the systematic review. Research showed that both conditions significantly enhance the development of one another and have mutual comorbidities. Both ailments were proven to modify central nervous system processing, leading to high comorbidity in patients. Combining dental and gastroenterological treatments, including a simultaneous therapeutic approach, can significantly enhance patients’ quality of life, but further research is needed for a holistic approach. Full article

Suicide stands as one of the leading causes of non-accidental death among adolescents and young adults. The Integrated Motivational–Volitional Model (IMV) of suicidal behavior identifies feelings of defeat and entrapment as pivotal factors in the complex dynamics underlying suicidal behaviors. Additionally, depressive symptomatology plays a crucial role in the development of these behaviors. The aim of this work was to provide a systematic review of the scientific literature on the association of three risk factors—entrapment, defeat, and depressive symptomatology—with suicidal ideation in the adolescent and young adult population and to test a tentative theoretical model. The databases used were PubMed, Web of Science, and ProQuest. Primary studies were selected that examined the role of entrapment, defeat, and depressive symptomatology in suicidal ideation among adolescents and young adults (ages 10–35). Additionally, a model based on structural equation modeling was analyzed to assess the relationships between entrapment, defeat, and depressive symptomatology and suicidal ideation. Eleven studies met the established inclusion criteria. The results showed defeat and entrapment to be associated with depressive symptomatology and suicidal ideation, regardless of the country studied. Additionally, the model indicates that entrapment and defeat lead to depressive symptomatology, which in turn contributes to the occurrence of suicidal ideation. These findings suggest that defeat and entrapment could be universal factors in explaining suicidal behavior in adolescents and young adults. Consequently, the results of this work may contribute to the development of strategies for preventing suicidal ideation in this population. Full article

In this work, the effects of different sintering temperatures and TiO₂ concentrations on the dielectric properties of ZrO₂ and Nb₂O₅ pre-doped CaCu₃Ti₄O₁₂ (CCTO) ceramics were investigated. These doped ceramics were sintered at temperatures of 1020, 1030, and 1040 °C, exhibiting the lowest dielectric loss of 0.01, which consistently remained below 0.03 across a wide frequency range from 10 to 10⁵ Hz. Simultaneously, they maintained a high dielectric constant of more than 3000 and remarkably met the requirements for an X8P capacitor (Δε′ ≤ ±10% at temperature range from −55 to 150 °C). It was clarified that TiO₂ doping increased grain boundary resistance, leading to the reduced dielectric loss, and elevated the grain boundary activation energy, thereby enhancing the temperature stability. The TiO₂-doped CCTO-based ceramics also demonstrated reduced sensitivity to variations in sintering temperature, highlighting their excellent manufacturability. This characteristic holds great promise for the fabrication of CCTO-based ceramics, which usually exhibit poor repetitiveness. Full article

Assessing regional water quality and evaluating the associated risks to human health posed by aquatic contaminants are paramount for conserving and managing surface water resources and formulating effective local policy decisions. This study utilizes 17 water quality parameters collected monthly from nine national monitoring stations in Nanning City, China, from January 2021 to March 2023, i.e., water temperature (WT), pH, dissolved oxygen (DO), permanganate index (COD_Mn), chemical oxygen demand (COD), five-day biochemical oxygen demand (BOD₅), ammonia nitrogen (NH₃-N), total phosphorus (TP), copper (Cu), zinc (Zn), fluoride (F^-), selenium (Se), arsenic (As), mercury (Hg), cadmium (Cd), chromium (Cr), and lead (Pb). Analyses were performed utilizing the Water Quality Index (WQI) and multiple stepwise regression to ascertain seasonal and spatial variations in water quality and to identify key water quality parameters. Human health risks were evaluated, focusing on eight heavy metals. The results indicated that the average WQI for the designated area was 94.1, with individual monitoring stations displaying WQIs ranging from 93.22 to 96.44, categorizing the water quality as “excellent”. The WQI exhibited seasonal fluctuations, peaking in spring and winter while decreasing in summer and autumn. All measured parameters met national standards for Class I and II surface waters. The stepwise regression analysis facilitated the construction of minimized WQI models (WQI_min) derived from three different training and testing datasets, with a WQI_min model incorporating six key parameters, i.e., DO, COD_Mn, NH₃-N, Hg, WT, and Se. The concentration of heavy metals in the water exhibited a sequence of Zn (3.35 µg/L) > Cr (2.00 µg/L) > Cu (1.36 µg/L) > As (1.29 µg/L) > Se (0.32 µg/L) > Pb (0.17 µg/L) > Cd (0.03 µg/L) > Hg (0.01 µg/L), with all metals adhering to the Class I standard. Children are more susceptible to the adverse effects of heavy metal contamination than adults, exhibiting a total environmental health risk of 1.28 times greater. Cr was identified as the predominant contributor to the aggregate health risk, accounting for over 80% of the risk in adults and children, followed by As (19.1%). Future protection efforts are recommended to prioritize the control of Cr and As concentrations in Nanning City. Full article

Female fertility and reproductive system disorders are influenced by a complex interplay of biological, physiological, and environmental factors. Minerals have emerged as crucial yet often overlooked elements that impact fertility and the prevalence of reproductive system disorders. Background/Objectives: This review aims to provide a comprehensive overview of the multifaceted role of minerals in female fertility, focusing on key areas such as oocyte quality, ovulation, embryo development, oxidative stress, miscarriage, hormonal regulation, environmental exposure, and in-vitro fertilization (IVF) outcomes. Methods: A systematic review was conducted, focusing on randomized controlled trials (RCTs), prospective cohort studies, case-control studies, nested case-control, and observational studies examining mineral supplementation and nutrition in women planning pregnancy or utilizing assisted reproduction technologies (ARTs). Relevant literature was sourced from multiple electronic databases, including PubMed, Scopus, Google Scholar, Web of Science, and the Cochrane Library, using keywords related to minerals and female fertility. The quality of studies was assessed using the Newcastle–Ottawa Scale (NCO) for non-randomized studies and the Risk of Bias (RoB) tool for RCTs. This systematic review has been registered on PROSPERO (registration number is CDR 42024547656). Results: From an initial pool of 20,830 records, 39 articles met the inclusion criteria and were analyzed. The studies addressed various reproductive outcomes influenced by minerals: embryo development, oocyte quality, oxidative stress, miscarriage, hormonal regulation, IVF outcomes, environmental exposure, and minerals as biomarkers. The analysis revealed that minerals like selenium, zinc, and copper are essential for maintaining reproductive health, while exposure to toxic metals such as cadmium and lead is detrimental. Conclusions: This review highlights the crucial role of both mineral supplementation and serum mineral status in female fertility. The findings provide key insights for clinicians to improve reproductive health through targeted mineral intake and monitoring. Further research is needed to refine guidelines for supplementation and serum levels in women with fertility issues. Full article

Metabolic syndrome (MetS) is a cluster of interrelated risk factors, including insulin resistance, hypertension, dyslipidemia, and visceral adiposity, all of which contribute to kidney microvascular injury and the progression of chronic kidney disease (CKD). However, the specific impact of each component of MetS on kidney microcirculation remains unclear. Given the increasing prevalence of obesity, understanding how visceral fat—particularly fat surrounding the kidneys—affects kidney microcirculation is critical. This review examines the consequences of visceral obesity and other components of MetS on renal microcirculation. These kidney-related fat deposits can contribute to the mechanical compression of renal vasculature, promote inflammation and oxidative stress, and induce endothelial dysfunction, all of which accelerate kidney damage. Each factor of MetS initiates a series of hemodynamic and metabolic disturbances that impair kidney microcirculation, leading to vascular remodeling and microvascular rarefaction. The review concludes by discussing therapeutic strategies targeting the individual components of MetS, which have shown promise in alleviating inflammation and oxidative stress. Integrated approaches that address both of the components of MetS and kidney-related adiposity may improve renal outcomes and slow the progression of CKD. Full article

In this study, a novel solar-assisted heat pump (SAHP) system with hybrid thermal energy storage is proposed. The system can address the problems of large space requirements and the unstable heating of solar heating systems and tackle the energy-efficient degradation of air source heat pumps (ASHPs) in winter. This study utilized TRNSYS18 software to establish a dynamic simulation model of the system, including the system’s model construction and the control scheme’s design. This performance study focused on analyzing the effects of the collector area and thermal energy storage (TES). The results show that with the increase in the collector area, the collector and power generation efficiencies decrease, and the system performance coefficient improves; the rise in the volume of TES leads to the collector and power generation efficiencies first increasing, and then they tend to stabilize, and the performance coefficient shows a trend of firstly increasing, and then decreasing. In terms of parameter optimization, a target optimization scheme and an evaluation model are constructed. The results indicate that the heating demand for a 116-square-meter building in the Tianjin area is met. The equivalent annual cost (EAC) of the system cost is the lowest, which is CNY 3963, when the collector area of the system is 31 square meters, the heat storage tank (HST) volume is 0.4 cubic meters and the phase-change energy storage (PCES) volume is 0.2 cubic meters. The payback period of the system is 10.59 years, which was compared to that of the ASHP. The further comparison of the economic feasibility of the system in the Lhasa, Shenyang, and Tianjin regions shows that the Lhasa region has the lowest EAC and payback period of CNY 1579 and 8.53 years, respectively, while the payback periods of Tianjin and Shenyang are 10.59 and 10.3 years, with EACs of CNY 3963 and CNY 5096, respectively. Full article

Background: Guillain–Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy that represents a leading cause of motor impairment. Robot-assisted therapy (RAT) has been widely applied in various neurological conditions. However, the use of RAT in GBS remains underexplored. This systematic review (SR) aims to evaluate the preliminary evidence regarding the efficacy of RAT in terms of motor recovery in people with GBS (pwGBSs). Secondly, the study protocol for a randomized RCT is reported. Methods: A comprehensive SR was conducted on PubMed, Scopus, EMBASE, Cochrane Library, and Epistemikos. Risk of bias was assessed using the National Institute of Health (NIH) study quality assessment. The SR’s protocol was recorded in the PROSPERO database. Results: Out of 116 articles found, four studies published in the past four years met the inclusion criteria. These studies investigated the effects of RAT on lower limbs (three studies) and upper limbs (one study) in four pwGBSs. The results showed improvements in motor function and patient engagement, but it is impossible to generalize the findings. Conclusions: Our SRs supports the rationale for an RCT to assess the efficacy of RAT in pwGBSs. We present the protocol for a double-blind RCT to evaluate the effects of RAT on upper limb motor function in pwGBSs. Full article

In modern manufacturing, there is an increasing demand for reliable in-process measurement methods directly on large CNC machine tools, eliminating the need to transport workpieces to metrological laboratories. This study assesses the capability and applicability of an articulated arm coordinate measuring machine and a machine tool touch-trigger probe when measuring to a specified tolerance of 0.05 mm in a production environment. Experiments were conducted using the KOBA calibration standard and included measurements with and without applying the articulated arm coordinate measuring machine leapfrog method. The results were evaluated according to ISO 22514-7:2021 and ISO 14253-1:2017, which establish criteria for measurement system capability. The findings revealed that neither measurement system met the capability requirements of ISO 22514-7:2021, particularly due to unsatisfactory Q_MS and C_MS values. However, under ISO 14253-1:2017, both systems were deemed conditionally suitable for verifying conformity to the specifications, with the articulated arm coordinate measuring machine showing lower applicability when using the leapfrog method. This research supports the idea that unreasonable demands for compliance with current standards may lead to questioning of the systems that previously met older standards. The study contributes to the ongoing discussion on integrating advanced metrological tools into the manufacturing process and underscores the need for careful evaluation to ensure the capability and reliability of measurement systems in industrial practice. Full article

This paper analyzes the impact of AI systems in the judicial domain, adopting an actor–network theory (ANT) framework and focusing on accountability issues emerging when such technologies are introduced. Considering three different types of AI applications used by judges, this paper explores how introducing non-accountable artifacts into justice systems influences the actor–network configuration and the distribution of accountability between humans and technology. The analysis discusses the actor–network reconfiguration emerging when speech-to-text, legal analytics, and predictive justice technologies are introduced in pre-existing settings and maps out the changes in agency and accountability between judges and AI applications. The EU legal framework and the EU AI Act provide the juridical framework against which the findings are assessed to check the fit of new technological systems with justice system requirements. The findings show the paradox that non-accountable AI can be used without endangering fundamental judicial values when judges can control the system’s outputs, evaluating its correspondence with the inputs. When this requirement is not met, the remedies provided by the EU AI Act fall short in costs or in organizational and technical complexity. The judge becomes the unique subject accountable for the use and outcome of a non-accountable system. This paper suggests that this occurs regardless of whether the technology is AI-based or not. The concrete risks emerging from these findings are that these technological innovations can lead to undue influence on judicial decision making and endanger the fair trial principle. Full article