Miracle-dz/UniFAR-FTUs huggingface dataset:
Accumulation of C-CTX1 in Muscle Tissue of Goldfish (Carassius auratus) by Dietary Experience

Simple Summary Some marine microalgae usually present in warm waters can produce ciguatoxins (CTXs); these toxins can accumulate in fish through the trophic chain, causing the food poisoning known as ciguatera in humans. It is important to understand how these compounds could be incorporated into fish muscle. For this purpose, this study was conducted using goldfish, an omnivorous freshwater species, daily fed raw fish flesh contaminated with a known toxicity concentration of CTX, seeking the accumulation profile in muscle and any signs of intoxication. Toxicity was detectable from day eight of the toxic diet and reached its maximum after two weeks. Signs of poisoning were observed after two weeks in all treated fish. However, two individuals developed strong symptoms, and one of them was separated and fed non-toxic food for 60 days; it showed recovery signs after the first week, and no toxicity was observed at the end of that non-toxic period. These results demonstrate that this toxin can accumulate in the muscle tissue of goldfish and produce associated symptomatology. Moreover, goldfish can recover and eliminate the CTX from its muscle if the toxin source is not available. Abstract Ciguatoxins (CTXs) are produced by dinoflagellates usually present in tropical and subtropical waters. These toxins are bioaccumulated and transformed in fish causing ciguatera fish poisoning (CFP) in humans. Few trials have been performed to understand how CTXs are incorporated into fish. This study developed an experimental model of goldfish (Carassius auratus) fed flesh contaminated with Caribbean ciguatoxin (C-CTX1). Fourteen goldfish were fed 0.014 ng CTX1B (Eq. g−1 of body weight) daily, and control goldfish received non-toxic flesh. CTX presence was determined by a cell-based assay on days 1, 8, 15, 29, 36, 43, and 84. Toxicity was detected in muscle from the second sampling and then seemed to stabilize at ~0.03 ng CTX1B Eq. g−1. After two weeks, all experimental goldfish developed lethargy and loss of brightness, but only two of them displayed erratic swimming and jerking movements near the sixth sampling. One of these fish had its toxic diet replaced by commercial food for 60 more days; the fish showed recovery signs within the first weeks and no CTX activity was detected. These results indicate that C-CTX1 could accumulate in goldfish muscle tissue and produce toxic symptoms, but also remarked on the detoxification and recovery capacity of this species.
Polyphenols and Human Health: The Role of Bioavailability

Polyphenols are a group of phytochemicals with potential health-promoting effects. They are classified as flavonoid (flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins) and non-flavonoid molecules (phenolic acids, hydroxycinnamic acids, lignans, stilbenes, and tannins). Although an increasing number of trials have shown a correlation among polyphenol consumption and a reduction in risk factors for chronic diseases, discrepancies in explaining their positive effects have been found in terms of the bioavailability. In fact, polyphenols show a low bioavailability due to several factors: interaction with the food matrix, the metabolic processes mediated by the liver (phase I and II metabolism), intestine and microbiota. On the other hand, the biological activities of phenol compounds may be mediated by their metabolites, which are produced in vivo, and recent studies have confirmed that these molecules may have antioxidant and anti-phlogistic properties. This review discusses the studies performed in vivo, which consider the polyphenol bioavailability and their different food sources. Factors influencing the biological effects of the main classes of polyphenols are also considered.
Beyond taxonomy: species complexes in New World phlebotomine sand flies

A species complex (= species group, species series) is an assemblage of species, which are related morphologically and phylogenetically. Recent research has revealed several arthropod vector species that were believed to be a single nominal species actually representing a group of closely related species, which are sometimes morphologically indistinguishable at one or more developmental stages. In some instances, differences in terms of vector competence, capacity, or both have been recorded. It highlights the importance of detecting and studying species complexes to improve our understanding of pathogen transmission patterns, which may be vectored more or less efficiently by different species within the complex. Considering more than 540 species, about one‐third of the phlebotomine sand flies in the New World present males and/or females morphologically indistinguishable to one or more species. Remarkably, several of these species may act in transmission of pathogenic agents. In this article, we review recent research on species complexes in phlebotomine sand flies from the Americas. Possible practical implications of recently acquired knowledge and future research needs are also discussed.
Investigating the use of a two-stage attention-aware convolutional neural network for the automated diagnosis of otitis media from tympanic membrane images: a prediction model development and validation study

Objectives This study investigated the usefulness and performance of a two-stage attention-aware convolutional neural network (CNN) for the automated diagnosis of otitis media from tympanic membrane (TM) images. Design A classification model development and validation study in ears with otitis media based on otoscopic TM images. Two commonly used CNNs were trained and evaluated on the dataset. On the basis of a Class Activation Map (CAM), a two-stage classification pipeline was developed to improve accuracy and reliability, and simulate an expert reading the TM images. Setting and participants This is a retrospective study using otoendoscopic images obtained from the Department of Otorhinolaryngology in China. A dataset was generated with 6066 otoscopic images from 2022 participants comprising four kinds of TM images, that is, normal eardrum, otitis media with effusion (OME) and two stages of chronic suppurative otitis media (CSOM). Results The proposed method achieved an overall accuracy of 93.4% using ResNet50 as the backbone network in a threefold cross-validation. The F1 Score of classification for normal images was 94.3%, and 96.8% for OME. There was a small difference between the active and inactive status of CSOM, achieving 91.7% and 82.4% F1 scores, respectively. The results demonstrate a classification performance equivalent to the diagnosis level of an associate professor in otolaryngology. Conclusions CNNs provide a useful and effective tool for the automated classification of TM images. In addition, having a weakly supervised method such as CAM can help the network focus on discriminative parts of the image and improve performance with a relatively small database. This two-stage method is beneficial to improve the accuracy of diagnosis of otitis media for junior otolaryngologists and physicians in other disciplines.
Fast and Sensitive Screening of Oxandrolone and Its Major Metabolite 17-Epi-Oxandrolone in Human Urine by UHPLC—MS/MS with On-Line SPE Sample Pretreatment

Oxandrolone, a synthetic testosterone analog, is used for the treatment of several diseases associated with weight loss. Unfortunately, oxandrolone is abused by many athletes and bodybuilders due to its strong anabolic effect. We have developed and validated a highly sensitive and rapid on-line SPE-UHPLC-MS/MS method for the determination of oxandrolone and simultaneous identification of its major metabolite 17-epi-oxandrolone in urine matrices. Enrichment of the analytes via an integrated solid-phase extraction was achieved using an Acquity UPLC BEH C18 Column. Subsequently, the chromatographic separation of the on-line preconcentrated sample fraction was achieved using an Acquity HSS T3 C18 Column. For the structural identification of these analytes, a high-resolution mass spectrometer Synapt-G2Si coupled to the Acquity M-class nano-LC system with ionKey source was used. A highly sensitive determination of oxandrolone was achieved using a tandem quadrupole mass spectrometer XEVO TQD. The method was successfully validated in the linear range of oxandrolone from 81.63 pg·mL−1 (limit of quantification, LOQ) to 5000 pg·mL−1 in the human urine matrix. It was applied to the analysis of real urine samples obtained from a healthy volunteer after the oral administration of one dose (10 mg) of oxandrolone. Concentration vs. time dependence was tested in the time interval of 4 h–12 days (after oral administration) to demonstrate the ability of the method to detect the renal elimination of oxandrolone from the human body. Favorable performance parameters along with successful application indicate the usefulness of the proposed method for its routine use in antidoping control labs.
Leprosy perceptions and knowledge in endemic districts in India and Indonesia: Differences and commonalities.

BACKGROUND Understanding how knowledge, attitudes and practices regarding leprosy differ in endemic countries can help us develop targeted educational and behavioural change interventions. This study aimed to examine the differences and commonalities in and determinants of knowledge, attitudes, practices and fears regarding leprosy in endemic districts in India and Indonesia. PRINCIPLE FINDINGS A cross-sectional mixed-methods design was used. Persons affected by leprosy, their close contacts, community members and health workers were included. Through interview-administered questionnaires we assessed knowledge, attitudes, practices and fears with the KAP measure, EMIC-CSS and SDS. In addition, semi-structured interviews and focus group discussions were conducted. The quantitative data were analysed using stepwise multivariate regression. Determinants of knowledge and stigma that were examined included age, gender, participant type, education, occupation, knowing someone affected by leprosy and district. The qualitative data were analysed using open, inductive coding and content analysis. We administered questionnaires to 2344 participants (46% from India, 54% from Indonesia) as an interview. In addition, 110 participants were interviewed in-depth and 60 participants were included in focus group discussions. Knowledge levels were low in both countries: 88% of the participants in India and 90% of the participants in Indonesia had inadequate knowledge of leprosy. In both countries, cause, mode of transmission, early symptoms and contagiousness of leprosy was least known, and treatment and treatability of leprosy was best known. In both countries, health workers had the highest leprosy knowledge levels and community members the highest stigma levels (a mean score of up to 17.4 on the EMIC-CSS and 9.1 on the SDS). Data from the interviews indicated that people were afraid of being infected by leprosy. Local beliefs and misconceptions differed, for instance that leprosy is in the family for seven generations (Indonesia) or that leprosy is a result of karma (India). The determinants of leprosy knowledge and stigma explained 10-29% of the variability in level of knowledge and 3-10% of the variability in level of stigma. CONCLUSION Our findings show the importance of investigating the perceptions regarding leprosy prior to educational interventions in communities: even though knowledge levels were similar, local beliefs and misconceptions differed per setting. The potential determinants we included in our study explained very little of the variability in level of knowledge and stigma and should be explored further. Detailed knowledge of local knowledge gaps, beliefs and fears can help tailor health education to local circumstances.
Physical and Frictional Properties of Orange and Sweet Lemon

Availability of physical and frictional properties data of citrus fruits is limited. Physical properties (size, unit mass, density, color) and frictional properties [peak static, peak dynamic and average dynamic coefficients of friction (COF)] for orange (Citrus reticulate) and sweet lemon (Citrus sinensis) on five common test surfaces were measured. Average geometrical mean diameter (GMD) of orange and sweet lemon was 64.6±6.2 mm and 67.6±6.1 mm, respectively. The sphericity of orange and sweet lemon was 0.93 and 0.97, respectively. Peak static coefficient of friction (COF) of orange and sweet lemon ranged from 0.27 (for aluminum) to 0.37 (for mild steel) and 0.24 (for plywood) to 0.32 (for galvanized iron), respectively. The average dynamic COF of orange and sweet lemon ranged from 0.27 (for plywood) to 0.42 (for mild steel), and 0.25 (for plywood) to 0.36 (for mild steel and galvanized iron), respectively. Test surfaces had a significant effect on variation in peak static COF and average dynamic COF for both of the fruits. No significant difference existed between peak static COF and average dynamic COF for orange but significant difference existed between these two COF for sweet lemon.
Gut Microbiota Modulation and Fecal Transplantation: An Overview on Innovative Strategies for Hepatic Encephalopathy Treatment

Simple Summary Treatment of advanced liver disease and its complications continue to be a challenge due to the complexity of this illness. In recent years, the gut microbiome has been recognized to play a beneficial role in our health. Studies have shown that overgrowth of harmful organisms in the gut can contribute to worsened outcomes in liver disease. Fecal microbiota transplant (FMT) is an approved and effective treatment in other gastrointestinal conditions. FMT involves the administration of a solution of a fecal suspension from a healthy donor into the intestinal tract of a recipient. This has led researchers to attempt this treatment in liver disease. There have now been small clinical trials showing that FMT is safe and could be effective in improving outcomes in advanced liver disease. There remain several questions to be answered before FMT is implanted in clinical practice, including the best route to administer this treatment, how many doses are needed to achieve a therapeutic response, and how long we need to wait between treatments. In this review paper, we explore the role of the gut microbiome in the human body with emphasis on the gastrointestinal system, how it changes in liver disease, and how we can improve it with fecal microbiota transplant. Abstract Hepatic encephalopathy (HE) is a major complication of cirrhosis, which is associated with gut microbial composition and functional alterations. Current treatments largely focus on gut microbiota using lactulose, rifaximin and other agents. However, despite these treatments, patients with HE have a high rate of readmission, morbidity and cognitive impairment. Fecal microbiota transplant (FMT) involves introduction of a donor microbiota into a recipient and is currently mainly used for recurrent C. difficile infection (rCDI). The role of FMT in cirrhosis and HE is evolving. There have been two randomized clinical trials (RCT) and several case reports/series in cirrhosis. Both RCTs were safety-focused phase 1 trials. One involved pre-FMT antibiotics and FMT enema versus standard of care, while the other involved 15 FMT capsules versus placebo without pre-FMT antibiotics. There was evidence of safety in both trials and the FMT group demonstrated reduction in hospitalizations compared to the non-FMT group. Changes in microbial function centered around short-chain fatty acids, bile acids and brain function showed improvement in the FMT groups. Long-term follow-up demonstrated continued safety and reduction in the antibiotic-resistance gene carriage. However, larger trials of FMT in HE are needed that can refine the dose, duration and route of FMT administration.
Contribution of the CK2 Catalytic Isoforms α and α’ to the Glycolytic Phenotype of Tumor Cells

CK2 is a Ser/Thr protein kinase overexpressed in many cancers. It is usually present in cells as a tetrameric enzyme, composed of two catalytic (α or α’) and two regulatory (β) subunits, but it is active also in its monomeric form, and the specific role of the different isoforms is largely unknown. CK2 phosphorylates several substrates related to the uncontrolled proliferation, motility, and survival of cancer cells. As a consequence, tumor cells are addicted to CK2, relying on its activity more than healthy cells for their life, and exploiting it for developing multiple oncological hallmarks. However, little is known about CK2 contribution to the metabolic rewiring of cancer cells. With this study we aimed at shedding some light on it, especially focusing on the CK2 role in the glycolytic onco-phenotype. By analyzing neuroblastoma and osteosarcoma cell lines depleted of either one (α) or the other (α’) CK2 catalytic subunit, we also aimed at disclosing possible pro-tumor functions which are specific of a CK2 isoform. Our results suggest that both CK2 α and α’ contribute to cell proliferation, survival and tumorigenicity. The analyzed metabolic features disclosed a role of CK2 in tumor metabolism, and suggest prominent functions for CK2 α isoform. Results were also confirmed by CK2 pharmacological inhibition. Overall, our study provides new information on the mechanism of cancer cells addiction to CK2 and on its isoform-specific functions, with fundamental implications for improving future therapeutic strategies based on CK2 targeting.
The Infratentorial Localization of Brain Metastases May Correlate with Specific Clinical Characteristics and Portend Worse Outcomes Based on Voxel-Wise Mapping

Simple Summary Brain metastases (BMs) are cancerous lesions that originated from cancers outside the brain. Specific types of BMs are found distributing in specific brain areas. The infratentorial regions are frequently affected, causing severe neurological symptoms. Thus, it is necessary to investigate what types of tumors tend to form infratentorial BMs and whether these lesions are more fatal. By analyzing substantial brain imaging data of BMs, we found the vulnerability of infratentorial regions to most types of BMs, and found the infratentorial localization of BMs was significantly associated with young age, male sex, lung neuroendocrine and squamous cell carcinomas, more active cell division of the tumors, and patients with poorer outcomes. Additionally, infratentorial involvement might predict worse outcomes for patients who received surgery. Our findings underlined the distinctive role of infratentorial localization of BMs and its potential relationship with specific clinical characteristics, which may assist diagnosis, treatment choice, and prognostic prediction of BMs. Abstract The infratentorial regions are vulnerable to develop brain metastases (BMs). However, the associations between the infratentorial localization of BMs and clinical characteristics remained unclear. We retrospectively studied 1102 patients with 4365 BM lesions. Voxel-wise mapping of MRI was applied to construct the tumor frequency heatmaps after normalization and segmentation. The analysis of differential involvement (ADIFFI) was further used to obtain statistically significant clusters. Kaplan-Meier method and Cox regression were used to analyze the prognosis. The parietal, insular and left occipital lobes, and cerebellum were vulnerable to BMs with high relative metastatic risks. Infratentorial areas were site-specifically affected by the lung, breast, and colorectal cancer BMs, but inversely avoided by melanoma BMs. Significant infratentorial clusters were associated with young age, male sex, lung neuroendocrine and squamous cell carcinomas, high expression of Ki-67 of primaries and BMs, and patients with poorer prognosis. Inferior OS was observed in patients with ≥3 BMs and those who received whole-brain radiotherapy alone. Infratentorial involvement of BMs was an independent risk factor of poor prognosis for patients who received surgery (p = 0.023, hazard ratio = 1.473, 95% confidence interval = 1.055–2.058). The current study may add valuable clinical recognition of BMs and provide references for BMs diagnosis, treatment evaluation, and prognostic prediction.
From hydroxychloroquine to ivermectin: what are the anti-viral properties of anti-parasitic drugs to combat SARS-CoV-2?

Abstract Background Nearly a year into the COVID-19 pandemic, we still lack effective anti-SARS-CoV-2 drugs with substantial impact on mortality rates except for dexamethasone. As the search for effective antiviral agents continues, we aimed to review data on the potential of repurposing antiparasitic drugs against viruses in general, with an emphasis on coronaviruses. Methods We performed a review by screening in vitro and in vivo studies that assessed the antiviral activity of several antiparasitic agents: chloroquine, hydroxychloroquine (HCQ), mefloquine, artemisinins, ivermectin, nitazoxanide (NTZ), niclosamide, atovaquone and albendazole. Results For HCQ and chloroquine we found ample in vitro evidence of antiviral activity. Cohort studies that assessed the use of HCQ for COVID-19 reported conflicting results, but randomized controlled trials (RCTs) demonstrated no effect on mortality rates and no substantial clinical benefits of HCQ used either for prevention or treatment of COVID-19. We found two clinical studies of artemisinins and two studies of NTZ for treatment of viruses other than COVID-19, all of which showed mixed results. Ivermectin was evaluated in one RCT and few observational studies, demonstrating conflicting results. As the level of evidence of these data is low, the efficacy of ivermectin against COVID-19 remains to be proven. For chloroquine, HCQ, mefloquine, artemisinins, ivermectin, NTZ and niclosamide, we found in vitro studies showing some effects against a wide array of viruses. We found no relevant studies for atovaquone and albendazole. Conclusions As the search for an effective drug active against SARS-CoV-2 continues, we argue that pre-clinical research of possible antiviral effects of compounds that could have antiviral activity should be conducted. Clinical studies should be conducted when sufficient in vitro evidence exists, and drugs should be introduced into widespread clinical use only after being rigorously tested in RCTs. Such a search may prove beneficial in this pandemic or in outbreaks yet to come.
Antifungal Activity of Melaleuca alternifolia Essential Oil (TTO) and Its Synergy with Itraconazole or Ketoconazole against Trichophyton rubrum

Over the past 20–30 years, Trichophyton rubrum represented the most widespread dermatophyte with a prevalence accounting for 70% of dermatophytosis. The treatment for cutaneous infections caused by Trichophyton spp. are imidazoles (ketoconazole (KTZ)) and triazoles (itraconazole (ITZ)). T. rubrum can develop resistance to azoles after prolonged exposure to subinhibitory concentrations resulting in therapeutic failures and chronic infections. These problems have stimulated the search for therapeutic alternatives, including essential oils, and their potential use in combination with conventional antifungals. The purpose of this study was to evaluate the antifungal activity of tea tree oil (TTO) (Melaleuca alternifolia essential oil) and the main components against T. rubrum and to assess whether TTO in association with KTZ/ITZ as reference drugs improves the antifungal activity of these drugs. We used a terpinen-4-ol chemotype (35.88%) TTO, and its antifungal properties were evaluated by minimum inhibitory and minimum fungicidal concentrations in accordance with the CLSI guidelines. The interaction between TTO and azoles was evaluated through the checkerboard and isobologram methods. The results demonstrated both the fungicide activity of TTO on T. rubrum and the synergism when it was used in combination with azoles. Therefore, this mixture may reduce the minimum effective dose of azole required and minimize the side effects of the therapy. Synergy activity offered a promise for combination topical treatment for superficial mycoses.