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Tatton–Brown–Rahman syndrome is a rare autosomal dominant hereditary disease caused by pathogenic variants in the DNMT3A gene, which is an important participant in epigenetic regulation, especially during embryonic development, and is highly expressed in all tissues. The main features of the syndrome are
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Tatton–Brown–Rahman syndrome is a rare autosomal dominant hereditary disease caused by pathogenic variants in the DNMT3A gene, which is an important participant in epigenetic regulation, especially during embryonic development, and is highly expressed in all tissues. The main features of the syndrome are high growth, macrocephaly, intellectual disability, and facial dysmorphic features. We present a clinical case of Tatton–Brown–Rahman syndrome in a ten-year-old boy with macrocephaly with learning difficulties, progressive eye impairment, and fatigue suspected by a deep learning-based diagnosis assistance system, Face2Gene. The proband underwent whole-exome sequencing, which revealed a recurrent nonsense variant in the 12th exon of the DNMT3A, leading to the formation of a premature stop codon—NM_022552.5:c.1443C>A (p.Tyr481Ter), in a heterozygous state. This variant was not found in parents, confirming its de novo status. The patient case described here contributes to the understanding of the clinical diversity of Tatton–Brown–Raman syndrome with a mild clinical presentation that expands the phenotypic spectrum of the syndrome. We report the first recurrent nonsense variant in the DNMT3A gene, suggesting a mutational hot-spot. Differential diagnoses of this syndrome with Sotos syndrome, Weaver syndrome, and Cowden syndrome, as well as molecular confirmation, are extremely important, since the presence of certain types of pathogenic variants in the DNMT3A gene significantly increases the risk of developing acute myeloid leukemia.
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In the past few decades, with the advent of climate change, population growth, agricultural irrigation, and industrial development, there have been increasing demands for water resources across the globe, especially in widely distributed arid areas or densely populated areas [...]
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Hydrogen peroxide (H2O2) is a signaling molecule that has the capacity to control a variety of biological processes in organisms. Cancer cells release more H2O2 during abnormal tumor growth. There has been a considerable amount of
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Hydrogen peroxide (H2O2) is a signaling molecule that has the capacity to control a variety of biological processes in organisms. Cancer cells release more H2O2 during abnormal tumor growth. There has been a considerable amount of interest in utilizing H2O2 as a biomarker for the diagnosis of cancer tissue. In this study, an electrochemical sensor for H2O2 was constructed based on 3D reduced graphene oxide (rGO), MXene (Ti3C2), and multi-walled carbon nanotubes (MWCNTs) composite. Three-dimensional (3D) rGO–Ti3C2–MWCNTs sensor showed good linearity for H2O2 in the ranges of 1–60 μM and 60 μM–9.77 mM at a working potential of −0.25 V, with sensitivities of 235.2 µA mM−1 cm−2 and 103.8 µA mM−1 cm−2, respectively, and a detection limit of 0.3 µM (S/N = 3). The sensor exhibited long-term stability, good repeatability, and outstanding immunity to interference. In addition, the modified electrode was employed to detect real-time H2O2 release from cancer cells and cancer tissue ex vivo.
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The testis-specific double sex and mab-3-related transcription factor 1 (DMRT1) has long been recognized as a crucial player in sex determination across vertebrates, and its essential role in gonadal development and the regulation of spermatogenesis is well established. Here, we report
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The testis-specific double sex and mab-3-related transcription factor 1 (DMRT1) has long been recognized as a crucial player in sex determination across vertebrates, and its essential role in gonadal development and the regulation of spermatogenesis is well established. Here, we report the cloning of the key spermatogenesis-related DMRT1 cDNA, named Tc-DMRT1, from the gonads of Tridacna crocea (T. crocea), with a molecular weight of 41.93 kDa and an isoelectric point of 7.83 (pI). Our hypothesis is that DMRT1 machinery governs spermatogenesis and regulates gonadogenesis. RNAi-mediated Tc-DMRT1 knockdown revealed its critical role in hindering spermatogenesis and reducing expression levels in boring giant clams. A histological analysis showed structural changes, with normal sperm cell counts in the control group (ds-EGFP) but significantly lower concentrations of sperm cells in the experimental group (ds-DMRT1). DMRT1 transcripts during embryogenesis exhibited a significantly high expression pattern (p < 0.05) during the early zygote stage, and whole-embryo in-situ hybridization confirmed its expression pattern throughout embryogenesis. A qRT-PCR analysis of various reproductive stages revealed an abundant expression of Tc-DMRT1 in the gonads during the male reproductive stage. In-situ hybridization showed tissue-specific expression of DMRT1, with a positive signal detected in male-stage gonadal tissues comprising sperm cells, while no signal was detected in other stages. Our study findings provide an initial understanding of the DMRT1 molecular machinery controlling spermatogenesis and its specificity in male-stage gonads of the key bivalve species, Tridacna crocea, and suggest that DMRT1 predominantly functions as a key regulator of spermatogenesis in giant clams.
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Despite advances in science and technology, agricultural yield losses due to plant pathogens and pests currently account for 30% of global production [...]
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Vincenzo Di Stefano, Pietro Guaraldi, Francesca Giglia, Ilaria Cani, Antonia Pignolo, Luca Codeluppi, Paolo Alonge, Elena Canali, Giovanni De Lisi, Ada Maria Florena, Eugenia Borgione and Filippo Brighina
Hereditary transthyretin amyloidosis (hATTR) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensory-motor nerves, heart, autonomic function, and other organs. There are over 130 mutations known in the TTR gene. The His90Asn mutation has been previously reported in several reports,
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Hereditary transthyretin amyloidosis (hATTR) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensory-motor nerves, heart, autonomic function, and other organs. There are over 130 mutations known in the TTR gene. The His90Asn mutation has been previously reported in several reports, but its pathogenetic role is still debated. We report two sporadic cases of adult women with a heterozygous His90Asn mutation in TTR gene and neurological involvement extensively investigated. A typical Congo red-positive pathologic deposition of amyloid fibrils in the salivary glands was documented in one subject. Patients were successfully treated with patisiran with a good clinical outcome. These data support a pathogenetic role of His90Asn mutation in hATTR, and suggest early treatment in symptomatic carriers of His90Asn mutation.
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The International Regulations for Preventing Collisions at Sea 1972 (COLREGs) have been the cornerstone of maritime navigation since their introduction. Knowledge and implementation of these rules are paramount in collision avoidance at sea. However, terms found in these rules are sometimes imprecise or
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The International Regulations for Preventing Collisions at Sea 1972 (COLREGs) have been the cornerstone of maritime navigation since their introduction. Knowledge and implementation of these rules are paramount in collision avoidance at sea. However, terms found in these rules are sometimes imprecise or fuzzy, as they are written by humans for humans, giving them some freedom in interpretation. The term Very Large Ship used in Rule 7 of the COLREGs is, by its nature, fuzzy. While human navigators understand this term’s meaning, it could be challenging for machines or autonomous ships to understand such an unprecise expression. Fuzzy sets could easily describe unprecise terms used in maritime navigation. A fuzzy set consists of elements with degrees of membership in a set, making them perfect for interpreting some terms where boundaries are unclear. This research was conducted among 220 navigational experts to describe linguistic variables used in maritime regulations. This research consists of an internationally distributed questionnaire. Membership data were collected with the adapted horizontal method, and the results were statistically analyzed, followed by regression analyses to describe the range and shape of membership functions. A conceptual model of the implementation of linguistic variables is presented. The novelty of this study derives from the data collecting, modeling, and quantification of the important but neglected linguistic term Very Large Ship based on a large number of navigational experts. The same quantification method could be easily used for other COLREGs linguistic variables, which could easily lift barriers to advances in intelligent solutions based on fuzzy sets. The obtained quantified fuzzy sets can be used in decision support or control systems used by conventional or autonomous ships in the future.
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In 2015, the 2030 Agenda for Sustainable Development adopted 17 Sustainable Development Goals (SDGs), with the aim of “peace and prosperity for people and the planet” FAO [...]
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“Obesity”, is defined as a body mass index (BMI) ≥ 30. Yet the tool, BMI, has been shown to be flawed in its weight classing. BMI categories were made by relying nearly exclusively on data about middle-class white males, creating “the normal (white)
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“Obesity”, is defined as a body mass index (BMI) ≥ 30. Yet the tool, BMI, has been shown to be flawed in its weight classing. BMI categories were made by relying nearly exclusively on data about middle-class white males, creating “the normal (white) man”. Yet, BMI continues to be used as a diagnostic tool, and is increasingly deployed to stigmatize fat persons as “diseased”. This has critical implications for women—especially Black women and Latinas—who have some of the highest BMIs in the country. But, despite the consternation over the size of the bodies women of color have, there are nearly no studies to date examining the relationship between BMI and rates of chronic illness by race and gender. In this study, we examined the associations between BMI and type 2 diabetes (T2D) for women across race in comparison to white men. Relying on 20 years of NHANES data, we found that while Latinas and Black women were nearly 3 times and over 5 times as likely to have T2D than white men, respectively, the association between BMI and T2D was significantly weaker for Latinas than for white men. The association between BMI and T2D was markedly weaker for Black women. This study shows that racial and gendered health disparities cannot be explained by differences in rates of “obesity” as defined by a white male norm.
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There is a growing interest in sustainable urban transport solutions in cities around the world. These changes, known as “smart urban mobility”, aim to reduce the negative effects of transport on the natural environment and enhance the standard of living for urban dwellers.
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There is a growing interest in sustainable urban transport solutions in cities around the world. These changes, known as “smart urban mobility”, aim to reduce the negative effects of transport on the natural environment and enhance the standard of living for urban dwellers. It should be noted that in addition to this transformation’s technological aspects, modifying the city’s structure and architecture also has a social dimension. The transformation of urban mobility has a significant impact on social relations. Introducing new modes of transport, such as city bikes and electric scooters, creates new ways of moving around the city and can impact social interactions. This can increase social integration and a community’s sense of belonging. At the same time, it is necessary to consider the differences between social groups to ensure equal access to the benefits of these changes in addition to deeper social elements, such as changing the habits and expectations of residents and adapting solutions to the specific needs of each city. This paper aims to look at the social aspects of smart urban mobility, including the impact of these changes on the lives and relationships of city residents.
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The genus Henricia is known to have intraspecific morphological variations, making species identification difficult. Therefore, molecular phylogeny analysis based on genetic characteristics is valuable for species identification. We present complete mitochondrial genomic sequences of Henricia longispina aleutica, H. reniossa, and H. [...] Read more.
The genus Henricia is known to have intraspecific morphological variations, making species identification difficult. Therefore, molecular phylogeny analysis based on genetic characteristics is valuable for species identification. We present complete mitochondrial genomic sequences of Henricia longispina aleutica, H. reniossa, and H. sanguinolenta for the first time in this study. This study will make a significant contribution to our understanding of Henricia species and its relationships within the class Asteroidea. Lengths of mitochondrial genomes of the three species are 16,217, 16,223, and 16,194 bp, respectively, with a circular form. These genomes contained 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a D-loop. The gene order and direction aligned with other asteroid species. Phylogenetic relationship analysis showed that our Henricia species were in a monophyletic clade with other Henricia species and in a large clade with species (Echinaster brasiliensis) from the same family. These findings provide valuable insight into understanding the phylogenetic relationships of species in the genus Henricia.
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Simone Detassis, Francesca Precazzini, Margherita Grasso, Valerio Del Vescovo, Francesca Maines, Orazio Caffo, Paola Campomenosi and Michela A. Denti
Int. J. Mol. Sci.2024, 25(11), 5573; https://doi.org/10.3390/ijms25115573 (registering DOI) - 21 May 2024
Abiraterone acetate (AA) serves as a medication for managing persistent testosterone production in patients with metastatic castration-resistant prostate cancer (mCRPC). However, its efficacy varies among individuals; thus, the identification of biomarkers to predict and follow treatment response is required. In this pilot study,
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Abiraterone acetate (AA) serves as a medication for managing persistent testosterone production in patients with metastatic castration-resistant prostate cancer (mCRPC). However, its efficacy varies among individuals; thus, the identification of biomarkers to predict and follow treatment response is required. In this pilot study, we explored the potential of circulating microRNAs (c-miRNAs) to stratify patients based on their responsiveness to AA. We conducted an analysis of plasma samples obtained from a cohort of 33 mCRPC patients before and after three, six, and nine months of AA treatment. Using miRNA RT-qPCR panels for candidate discovery and TaqMan RT-qPCR for validation, we identified promising miRNA signatures. Our investigation indicated that a signature based on miR-103a-3p and miR-378a-5p effectively discriminates between non-responder and responder patients, while also following the drug’s efficacy over time. Additionally, through in silico analysis, we identified target genes and transcription factors of the two miRNAs, including PTEN and HOXB13, which are known to play roles in AA resistance in mCRPC. In summary, our study highlights two c-miRNAs as potential companion diagnostics of AA in mCRPC patients, offering novel insights for informed decision-making in the treatment of mCRPC.
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This article explores transgenerational return migration to Galicia, Spain, focusing on participants of the Scholarships for Outstanding Youth Abroad (BEME) programme. It examines how descendants of Galician emigrants, primarily grandchildren and great-grandchildren of Galician emigrants to Latin America, engage with the Spanish and
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This article explores transgenerational return migration to Galicia, Spain, focusing on participants of the Scholarships for Outstanding Youth Abroad (BEME) programme. It examines how descendants of Galician emigrants, primarily grandchildren and great-grandchildren of Galician emigrants to Latin America, engage with the Spanish and Galician languages. Drawing on semi-structured interviews with 30 participants, the article explores participants’ language ideologies regarding Galician as a minoritised language and Spanish as a global language. This article highlights the role of language as a symbolic resource in transgenerational return migration, offering a sociolinguistic perspective to the understanding of this migration phenomenon.
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In the majority of Abhidharmic Buddhist schools, smṛti serves the crucial function of ensuring the recollection of past events and is thus conceptualized as memory in scholarly discourse nowadays. Nevertheless, upon closer examination of various doctrinal perspectives, the interpretation of smṛti diverges significantly
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In the majority of Abhidharmic Buddhist schools, smṛti serves the crucial function of ensuring the recollection of past events and is thus conceptualized as memory in scholarly discourse nowadays. Nevertheless, upon closer examination of various doctrinal perspectives, the interpretation of smṛti diverges significantly among different schools. Notably, it is deemed to be omnipresent in every moment of perception within the Sarvāstivādin tradition, while in Yogācāra, it is regarded as a specific response to an experienced object. This paper seeks to delve into the concept of smṛti within the latter tradition, with a specific focus on the Cheng Weishi Lun (成唯識論, henceforth: CWSL). Drawing upon the foundational principles of Yogācāra doctrine, which posit the ālayavijñāna as an underlying substratum responsible for retaining past information, I contend that smṛti embodies a cognitive faculty that intensifies the apprehension of learned objects when they are present. Furthermore, I argue that smṛti serves as the inception point for a series of cognitive processes acquiring knowledge that helps decision-making. Additionally, I will demonstrate that the function of smṛti in the CWSL diverges from both traditional Buddhist conceptions of memory and contemporary understandings thereof.
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High-rise timber residential towers (≥eight-stories) represent a burgeoning and auspicious sector, predominantly due to their capability to provide significant ecological and financial advantages throughout their lifecycle. Like numerous other building types, spatial optimization in high-rise timber residential structures stands as a pivotal design
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High-rise timber residential towers (≥eight-stories) represent a burgeoning and auspicious sector, predominantly due to their capability to provide significant ecological and financial advantages throughout their lifecycle. Like numerous other building types, spatial optimization in high-rise timber residential structures stands as a pivotal design factor essential for project viability. Presently, there exists no comprehensive investigation on space efficiency in such towers. This study analyzed data from 51 case studies to enhance understanding of the design considerations influencing space efficiency in high-rise timber residential towers. Key findings included (1) the average space efficiency within the examined cases was recorded at 83%, exhibiting variances ranging from 70% to 93% across different cases, (2) the average percentage of core area to gross floor area (GFA) was calculated at 10%, demonstrating fluctuations within the range of 4% to 21% across diverse scenarios, and (3) no notable distinction was observed in the effect of various core planning strategies on spatial efficiency when properly designed, and similar conclusions were drawn regarding building forms and structural materials. This research will aid in formulating design guidelines tailored for various stakeholders such as architectural designers involved in high-rise residential timber building developments.
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In the context of climate change mitigation and adaptation, climate risks stemming from climate transition innovations have garnered significant attention due to concerns about the inadequate climate finance. To shed light on the climate transition risk posed by innovations, this study constructed low-carbon
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In the context of climate change mitigation and adaptation, climate risks stemming from climate transition innovations have garnered significant attention due to concerns about the inadequate climate finance. To shed light on the climate transition risk posed by innovations, this study constructed low-carbon innovation indicators of listed firms in China spanning 2015 to 2021. This study investigated the impact of climate transition innovations on the default risk, considering the mediation effect of investor attention, total factor productivity, and technology spillovers. The findings suggest that low-carbon innovations can mitigate the default risk of listed firms, as evidenced by three low-carbon innovation indicators. Additionally, the research reveals that the climate innovation effect on default risks was moderated when considering climate policy through heterogenous analysis. Furthermore, instrumental variable regressions using the time costs of innovation support the findings. Lastly, default risk was mitigated through lower levels of investor attention, greater total factor productivity, and technology spillovers.
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The late Roman discourse on divinatory dreams and their interpretation reflects a context of cultural fragmentation. The political turbulence of the 350s to 360s was due partly to the ongoing external war with the (Persian) Sasanians, but also to the internal struggle between
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The late Roman discourse on divinatory dreams and their interpretation reflects a context of cultural fragmentation. The political turbulence of the 350s to 360s was due partly to the ongoing external war with the (Persian) Sasanians, but also to the internal struggle between the heirs of Constantine for rule over the Roman empire, still undergoing a process of Christianization when Julian was acclaimed Augustus in 360. A third arena of fragmentation was religious beliefs and practices during the 350s and 360s. The contested transformation of Rome in the religious sphere was the context of Julian’s dynastic vision of the two trees, received in late 358 or 359.
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Under the new wave of scientific and technological revolution, the construction industry finds itself with a critical need to alter the traditional and outdated production mode through technological innovation in order to realize industry transformation and move towards a new era characterized by
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Under the new wave of scientific and technological revolution, the construction industry finds itself with a critical need to alter the traditional and outdated production mode through technological innovation in order to realize industry transformation and move towards a new era characterized by digitalization, informatization, and intelligence. As intelligent construction is the indispensable pathway for the transformation and upgrading of the construction industry, it is of great significance to conduct in-depth research on its evaluation indicators and causality. This paper adopts the system dynamics method, based on the overall structure of intelligent construction, extracts the causality chain and causal feedback loop of intelligent construction, and presents a causality diagram and system dynamics diagram to build a robust system dynamics model for intelligent construction. On this basis, an evaluation index system for intelligent construction is constructed from the five dimensions—investment, design, construction, operation, and environment—for a holistic assessment of the current state of intelligent construction. The research aims to provide a valuable reference for professionals focusing on intelligent construction and the broader development of the industry.
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For decades, linguists have been working to formulate an objective means of distinguishing dialects from languages, but dialect recognition has largely remained a subjective enterprise. Only recently have some studies proposed a processing-based psycholinguistic approach toward dialect recognition. These studies argued that dialect
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For decades, linguists have been working to formulate an objective means of distinguishing dialects from languages, but dialect recognition has largely remained a subjective enterprise. Only recently have some studies proposed a processing-based psycholinguistic approach toward dialect recognition. These studies argued that dialect words are stored as a co-dependent representation, not as an independent representation of the words of bilingual speakers. Based on these studies, we investigated the lexical selection and processing mechanisms of bilingual and bidialectal speakers of two understudied languages, Oromo and Amharic, using the picture–word interference paradigm. We found independent lexical representations for both the bilingual and the bidialectal groups, which implies the involvement of the same cognitive mechanisms in both language and dialect processing. Thus, we argue that bidialectal speakers have flexible lexical representation and selection mechanisms that are dependent on the speakers’ previous language experience. Here, we propose a dynamic lexical selection model that accommodates diverse dialect ecologies.
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In 2019, the International Consortium for Personalised Medicine (ICPerMed) developed a vision on how the use of personalized medicine (PM) approaches will promote “next-generation” medicine in 2030 more firmly centered on the individual’s personal characteristics, leading to improved health outcomes within sustainable healthcare
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In 2019, the International Consortium for Personalised Medicine (ICPerMed) developed a vision on how the use of personalized medicine (PM) approaches will promote “next-generation” medicine in 2030 more firmly centered on the individual’s personal characteristics, leading to improved health outcomes within sustainable healthcare systems through research, development, innovation, and implementation for the benefit of patients, citizens, and society. Nevertheless, there are significant hurdles that healthcare professionals, researchers, policy makers, and patients must overcome to implement PM. The ICPerMed aims to provide recommendations to increase stakeholders’ awareness on actionable measures to be implemented for the realization of PM. Starting with best practice examples of PM together with consultation of experts and stakeholders, a careful analysis that underlined hurdles, opportunities, recommendations, and information, aiming at developing knowledge on the requirements for PM implementation in healthcare practices, has been provided. A pragmatic roadmap has been defined for PM integration into healthcare systems, suggesting actions to overcome existing barriers and harness the potential of PM for improved health outcomes. In fact, to facilitate the adoption of PM by diverse stakeholders, it is mandatory to have a comprehensive set of resources tailored to stakeholder needs in critical areas of PM. These include engagement strategies, collaboration frameworks, infrastructure development, education and training programs, ethical considerations, resource allocation guidelines, regulatory compliance, and data management and privacy.
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Chemical reactions, mineral diffusion, and deposition are pivotal in understanding the mechanisms of mineral deposition and the formation of seafloor sulfides in the hydrothermal circulation process. To understand the formation process of anhydrite in submarine hydrothermal systems, a computational model that combined component
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Chemical reactions, mineral diffusion, and deposition are pivotal in understanding the mechanisms of mineral deposition and the formation of seafloor sulfides in the hydrothermal circulation process. To understand the formation process of anhydrite in submarine hydrothermal systems, a computational model that combined component transport and chemical reactions was established and simulated using the mass transport model. The deposition rate of calcium sulfate was defined, and the effects of factors such as porosity, ion concentration, and inflow velocity on the temperature field in the reaction zone were thoroughly investigated. The distribution of temperature, porosity, and velocity during the reaction process was obtained, allowing for the identification of the chemical reaction patterns of certain ions in the early stages of hydrothermal activity. The simulation revealed the occurrence of biochemical reactions between two types of ions, leading to their deposition on the solid framework of a porous medium. With the increase in inflow velocity and solute concentration, the average porosities of the porous medium decreased by 0.495% and 0.468%, respectively, which consequently altered the structure of the rock. Such findings contribute to the inference of formation and extinction mechanisms of seafloor crusts and hydrothermal chimneys.
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Interest in psychosocial predictors of doping has been increasing as a way of finding new approaches to reduce the use of performance-enhancing drugs. This investigation aimed to test the psychometric properties of an instrument to assess doping attitudes in Brazilian athletes. The PEAS
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Interest in psychosocial predictors of doping has been increasing as a way of finding new approaches to reduce the use of performance-enhancing drugs. This investigation aimed to test the psychometric properties of an instrument to assess doping attitudes in Brazilian athletes. The PEAS was validated in Brazilian sports through a process of translation, back-translation and content validity assessment, presenting satisfactory evidence based on its content (CVC > 0.80). Then, 994 athletes from different sexes, types of sports and competitive levels answered the Brazilian version of the PEAS. The results showed satisfactory evidence of validity based on its response process, internal structure (X2/df = 2.04; RMSEA = 0.032 (0.026–0.038); CFI = 0.96; TLI = 0.95) and reliability (Cronbach’s α, McDonald’s ω and CR > 0.70). Network analysis was also used to further explore the PEAS’s internal structure. Overall, the results provide support for the adoption of the PEAS for Brazilian athletes and possibly other Portuguese-speaking countries.
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Abdullah Esmail, Mohamed Badheeb, Batool Alnahar, Bushray Almiqlash, Yara Sakr, Bayan Khasawneh, Ebtesam Al-Najjar, Hadeel Al-Rawi, Ala Abudayyeh, Yaser Rayyan and Maen Abdelrahim
Cancers2024, 16(11), 1946; https://doi.org/10.3390/cancers16111946 (registering DOI) - 21 May 2024
Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor
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Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53–79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.
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