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Melanophryniscus fulvoguttatus is a small toad that inhabits the Cerrado, Atlantic Forest, and humid Chaco of South America. Due to its aposematic coloration and behavior, it is a species that may present chemical defenses such as alkaloids and a restricted diet similar to other species of the genus. Although it was described in the early 20th century, there is still little information on its natural history and ecology. Here, we described the diet, tested the sexual dimorphism, and calculated the fertility index of M. fulvoguttatus based on a sample of eight males and 21 females from a population within the Cerrado. Sexual dimorphism was assessed using 15 morphometric measures; diet was calculated as an index of relative importance by prey item and tested for sex differences; fertility was tested for relations between body size and the number of eggs; and we also estimated the reproductive investment. Our results demonstrate that this population’s diet consisted mostly of ant species, with Pheidole radoszkowskii being the most important, followed by Crematogaster sp. and Cyphomyrmex transversus. Regarding sexual dimorphism, we observed that females were significantly larger than males, with a positive relationship between female size and the number of eggs. We did not find significant differences in the diets of males and females. Although the diet and reproductive aspects of M. fulvoguttatus are similar to those of its congeneric species, further studies are needed in order to address the relationship between the species diet and its chemical defenses.

Background: This article evaluates the evolution of physical activity and health research in China through a bibliometric analysis focused on number of publications, study areas, and sex balance in authorship. Methods: A systematic review was conducted by the Global Observatory for Physical Activity for "physical activity and health" publications between 1950 and 2019. Here, we focus on the 610 Chinese publications identified, defined as those in which data collection took place in China. We assessed the number of publications, classified them into 5 areas (1) surveillance, (2) correlates and determinants, (3) health consequences, (4) interventions, and (5) policy, and analyzed female participation in authorship. Results: The first Chinese publication identified in the review was in 1990. Since, the average number of physical activity and health publications increased from one per year in the 1990s to 7.6 per year in the 2000s, and to 47 per year in the 2010s. Most publications focused on the correlates and determinants (38.7%) and the health consequences of physical activity (35.9%). Physical activity policy accounted for 2.3% of the publications. In the 1990s, 64% of the publications included at least one female author; this proportion increased to 90% in the 2010s. Conclusion: Despite a slow start, China's research on physical activity and health has grown rapidly since 2000. The distribution of publications by study areas and female participation in authorship is similar to that observed globally, with fewer publications focused on interventions and policy as compared with other topics. [ABSTRACT FROM AUTHOR]

Abstract Considering the profound transformation affecting pathology practice, we aimed to develop a scalable artificial intelligence (AI) system to diagnose colorectal cancer from whole-slide images (WSI). For this, we propose a deep learning (DL) system that learns from weak labels, a sampling strategy that reduces the number of training samples by a factor of six without compromising performance, an approach to leverage a small subset of fully annotated samples, and a prototype with explainable predictions, active learning features and parallelisation. Noting some problems in the literature, this study is conducted with one of the largest WSI colorectal samples dataset with approximately 10,500 WSIs. Of these samples, 900 are testing samples. Furthermore, the robustness of the proposed method is assessed with two additional external datasets (TCGA and PAIP) and a dataset of samples collected directly from the proposed prototype. Our proposed method predicts, for the patch-based tiles, a class based on the severity of the dysplasia and uses that information to classify the whole slide. It is trained with an interpretable mixed-supervision scheme to leverage the domain knowledge introduced by pathologists through spatial annotations. The mixed-supervision scheme allowed for an intelligent sampling strategy effectively evaluated in several different scenarios without compromising the performance. On the internal dataset, the method shows an accuracy of 93.44% and a sensitivity between positive (low-grade and high-grade dysplasia) and non-neoplastic samples of 0.996. On the external test samples varied with TCGA being the most challenging dataset with an overall accuracy of 84.91% and a sensitivity of 0.996.

Abstract Background The use of prebiotics and/or probiotic bacteria with the potential to modulate the oral ecosystem may play an important role in the prevention and management of dental caries. To assess the evidence of the potential of pre/probiotics both in the prevention and treatment of dental caries, we focused on the PICO question “In individuals with caries, after probiotic administration, is there an improvement in outcomes directly related to caries risk and development?“. Methods An extensive systematic search was conducted in electronic databases PubMed, Web of Science, Scopus and Cochrane, to identify articles with relevant data. This systematic review included trials performed in Humans; published in English; including the observation of patients with caries, with clear indication of the probiotic used and measuring the outcomes directly involved with the cariogenic process, including the quantification of bacteria with cariogenic potential. To evaluate the methodological quality of the studies, the critical assessment tool from the Joanna Briggs Institute was used. Results Eight hundred and fifty articles, potentially relevant, were identified. Following PRISMA guidelines 14 articles were included in this systematic review. Outcomes such as reduction of cariogenic microorganism counts, salivary pH, buffer capacity, and caries activity were assessed. The probiotic most often referred with beneficial results in dental caries outcomes is Lacticaseibacillus rhamnosus. Regarding the most used administration vehicle, in studies with positive effects on the caries management, probiotic supplemented milk could be considered the best administration vehicle. Conclusions Evidence suggests a beneficial effect of probiotic supplemented milk (Lacticaseibacillus rhamnosus) as an adjuvant for caries prevention and management. However, comparable evidence is scarce and better designed and comparable studies are needed.

BACKGROUND. Metastases are the hallmark of lethal cancer, though underlying mechanisms that drive metastatic spread to specific organs remain poorly understood. Renal cell carcinoma (RCC) is known to have distinct sites of metastases, with lung, bone, liver, and lymph nodes being more common than brain, gastrointestinal tract, and endocrine glands. Previous studies have shown varying clinical behavior and prognosis associated with the site of metastatic spread; however, little is known about the molecular underpinnings that contribute to the differential outcomes observed by the site of metastasis. METHODS. We analyzed primary renal tumors and tumors derived from metastatic sites to comprehensively characterize genomic and transcriptomic features of tumor cells as well as to evaluate the tumor microenvironment at both sites. RESULTS. We included a total of 657 tumor samples (340 from the primary site [kidney] and 317 from various sites of metastasis). We show distinct genomic alterations, transcriptomic signatures, and immune and stromal tumor microenvironments across metastatic sites in a large cohort of patients with RCC. CONCLUSION. We demonstrate significant heterogeneity among primary tumors and metastatic sites and elucidate the complex interplay between tumor cells and the extrinsic tumor microenvironment that is vital for developing effective anticancer therapies., Introduction Renal cell carcinoma (RCC) is one of the most common cancers in the United States, affecting close to 80,000 patients annually (1). While most patients present with localized disease, [...]

BackgroundPrevious research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers.ObjectiveIt is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans.MethodsSerotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts.ResultsPharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil transendothelial migration. In contrast, eosinophil transendothelial migration was not inhibited by siRNA knockdown of HTR1A or HTR1B in eosinophils. Surprisingly, these HTRs were intracellular in endothelial cells and an extracellular supplementation with serotonin did not inhibit eosinophil transendothelial migration. This is consistent with the inability of serotonin to cross membranes, the lack of selective serotonin reuptake receptors on endothelial cells, and the studies showing minimal impact of selective serotonin reuptake inhibitors on asthma. To extend our HTR studies to humans with asthma, we examined the CHIRAH and GALA cohorts for HTR SNPs that affect HTR function or are associated with behavior disorders. A polygenic index of SNPs in HTRs was associated with lower lung function in asthmatics.ConclusionsSerotonin receptors mediate 5HTP inhibition of transendothelial migration and HTR SNPs associate with lower lung function. These results may serve to aid in design of novel interventions for allergic inflammation.

Antibody-drug conjugates and bicycle toxin conjugates represent a tremendous advance in drug delivery technology and have shown great promise in the treatment of urothelial cancer. Previously approved systemic therapies, including chemotherapy and immunotherapy, are often impractical due to comorbidities, and outcomes for patients with advanced disease remain poor, even when receiving systemic therapy. In this setting, antibody-drug and bicycle toxin conjugates have emerged as novel treatments, dramatically altering the therapeutic landscape. These drugs harness unique designs consisting of antibody or bicycle peptide, linker, and cytotoxic payload with more targeted delivery than conventional chemotherapy, thus eliminating malignant cells while reducing systemic toxicities. Potential targets investigated in urothelial cancer include Nectin-4, TROP2, HER2, and EphA2. Initial clinical trials demonstrated efficacy in treatment of refractory advanced urothelial cancer, as well as improvement in quality of life. These initial studies led to FDA approval of two antibody-drug conjugates, enfortumab vedotin and sacituzumab govitecan. Moreover, antibody-drug and bicycle toxin conjugates are being studied in ongoing clinical trials in frontline treatment of advanced disease as well as for localized cancer. These studies highlight the potential for additional future therapies with novel targets, novel antibodies, cytotoxic and immunomodulatory payloads, and unique structural designs enhancing efficacy and safety. There is increasing evidence that combinations with other cancer therapies, especially immunotherapy, improve treatment outcomes. The combination of enfortumab vedotin and pembrolizumab was recently approved for first-line treatment of advanced urothelial carcinoma. Despite the great promise of these novel drugs, robust predictive biomarkers are needed to determine the patients who would maximally benefit. This review surveys the rationale and current state of the evidence for these new drugs and describes future directions actively being explored.

En este artículo se aborda la cuestión de la producción, comercialización y consumo de vino en el Noroeste peninsular, en particular en la región portuguesa de Trás-os-Montes, inscrita en el sur del conventus Asturum (antigua provincia de la Gallaecia). A pesar de la total ausencia de ánforas en el yacimiento romano de Castro de Avelãs (Bragança) y en su entorno inmediato, es posible que este producto, tan importante en época romana, se haya consumido y quizás hasta producido y distribuido en la zona usando contenedores diferentes. En par ticular se propone que un tipo de tinajas se hayan usado para el almacenamiento, transpor te y quizás hasta para la producción de vino. Esta hipótesis se refuerza con los análisis realizados mediante cromatografia de gases/espectometría de masas sobre tres de estos recipientes cerámicos recuperados en el yacimiento, registrando marcadores compatibles con el vino. Ante estos datos, se ha abierto la discusión sobre el consumo y la producción de vino (y de otros productos) en este territorio del sureste de la Gallaecia.

Abstract Background White spot lesions represent the first stage of caries and their prevalence has been increasing in recent years, particularly in patients undergoing orthodontic treatment. DIferential diagnosis and lesion activity are essential to decide on the clinical approaches to treatment. The aim of this study is to understand if the new diagnostic tools such as fluorescence, microradiography and computed microtomography have the potential to change the conventional treatment of white spots”. Methods A systematic search of available studies in the literature was carried out, using PRISMA guidelines, in Pubmed and Scopus electronic databases and manually to identify relevant articles to answer the PICO question: “Do the new diagnostic tools have the potential to change the conventional treatment of white spots?”. This systematic review included randomized controlled trials (RCT), cross-sectional and longitudinal studies complying with the following inclusion criteria: (i) studies in humans, (ii) studies about white spot lesions, (iii) studies published between 2012 and 2023, (iv) studies having both diagnosis and treatment and (v) studies with full text available. In this review we excluded other systematic reviews of clinical trials and in vitro studies. The RoB tool was used to assess the risk of bias. Results The systematic literature search identified 143 potentially relevant references, which after applying the exclusion criteria, resulted in 20 articles. Regarding diagnostic methods, most articles found were based on conventional methods of visual examination (n:10) or fluorescence (n:7). The least referenced diagnostic techniques were based on the use of clinical photographs (n:2), cross-sectional microradiography (n:1) and computed microtomography (n:1). The use of DIAGNOdent was reported by 3 in vitro studies. With regard to therapies, most studies reported the use of infiltrating resin (n:7) and fluoride-based products (n:5). Other studies have reported the use of self-assembling peptide P11-4 (n:1), home care (n:1), casein phosphopeptide-amorphous calcium phosphate (n:2) and hydrochloric acid (n:1). Combination therapies were also considered. Conclusion Diagnostic tool does not have the potential to change the form of treatment, whether it is a conventional method or a more differentiated one.

Objective: To describe the evolution of physical activity (PA) research in Africa, examine income and gender inequalities, and discuss future possibilities. Methods: A secondary analyses of the Global Observatory for Physical Activity data on PA research in Africa (1950–2019). Results: We identified 514 PA articles from 47 African countries in the past 70 years. Majority (83.1%) of the articles were published between 2012 and 2019. Fifteen countries had no publications. Six countries (South Africa [n = 156], Nigeria [n = 85], Ethiopia [n = 44], Ghana [n = 41], Kenya [n = 39], and Cameroon [n = 20]) accounted for about 75% of the publications. Most articles were observational (92.4%), single-country studies (78.4%), with male first (58.4%) and last authors (68%), and were classified as surveillance studies (45.1%). Few studies addressed interventions (5.8%) and policy (3.5%) or used device-based PA measurement (14.0%). The number of articles per country was positively related to human population level (r =.552, P =.000) and gross domestic product % spent on research and development (r =.301, P =.040). The publication rate per 100,000 people was positively related with the human development index (r =.349, P =.016) and negatively with the gender inequality index (r = −.360, P =.019). Conclusions: Our results provide an overview and status of PA research in Africa, highlighting country differences and gender inequalities in authorship. The findings may be used to benchmark the evolution of research in the region and to inform areas for improvement. There is an urgent need for more PA interventions and policy studies in Africa. [ABSTRACT FROM AUTHOR]

Background: National physical activity (PA) policy processes are only beginning to be studied in Latin America, and little attention has focused at the subnational level. This study examined national–subnational relations in the policy process (agenda setting, policy formulation, adoption, implementation, and evaluation) in selected Latin American countries. Methods: The Global Observatory for Physical Activity's (GoPA!) INTEGRATE-PA-Pol tool was applied in Colombia, Costa Rica, Ecuador, and Mexico. Data were collected in matched pairs of the capital plus one noncapital city among national and subnational policymakers (n = 27), previously identified by the GoPA! Country Contacts. PA policy development and implementation were assessed using descriptive statistics. Results: Twenty-three (response rate = 85.2%) informants provided data, mainly from the health sector (52.2%), followed by the sport (26.1%), transport (13.0%), and education (8.7%) sectors. Most informants reported that their countries had a current PA policy embedded within noncommunicable diseases prevention plans (46.2%), other plans (46.2%), or obesity prevention/management/control plans (7.7%). Respondents at the subnational level rated PA promotion as central (64.3%), while the national-level role was important but not central (75.0%). National and subnational policymakers indicated low-to-little involvement in the other level's PA policy processes across the 5 policy stages. Conclusions: This study demonstrated that collecting national and subnational PA policy data across countries with the active collaboration of the GoPA! network was feasible. We also successfully identified governmental interactions throughout the PA policy process, suggesting suboptimal engagement between national and subnational levels. [ABSTRACT FROM AUTHOR]

Biostimulants (Bio-effectors, BEs) comprise plant growth-promoting microorganisms and active natural substances that promote plant nutrient-acquisition, stress resilience, growth, crop quality and yield. Unfortunately, the effectiveness of BEs, particularly under field conditions, appears highly variable and poorly quantified. Using random model meta-analyses tools, we summarize the effects of 107 BE treatments on the performance of major crops, mainly conducted within the EU-funded project BIOFECTOR with a focus on phosphorus (P) nutrition, over five years. Our analyses comprised 94 controlled pot and 47 field experiments under different geoclimatic conditions, with variable stress levels across European countries and Israel. The results show an average growth/yield increase by 9.3% (n=945), with substantial differences between crops (tomato > maize > wheat) and growth conditions (controlled nursery + field (Seed germination and nursery under controlled conditions and young plants transplanted to the field) > controlled > field). Average crop growth responses were independent of BE type, P fertilizer type, soil pH and plant-available soil P (water-P, Olsen-P or Calcium acetate lactate-P). BE effectiveness profited from manure and other organic fertilizers, increasing soil pH and presence of abiotic stresses (cold, drought/heat or salinity). Systematic meta-studies based on published literature commonly face the inherent problem of publication bias where the most suspected form is the selective publication of statistically significant results. In this meta-analysis, however, the results obtained from all experiments within the project are included. Therefore, it is free of publication bias. In contrast to reviews of published literature, our unique study design is based on a common standardized protocol which applies to all experiments conducted within the project to reduce sources of variability. Based on data of crop growth, yield and P acquisition, we conclude that application of BEs can save fertilizer resources in the future, but the efficiency of BE application depends on cropping systems and environments.