Miracle-dz/UniFAR-FTUs huggingface dataset:
The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells

ABSTRACT ABTL0812 is a first-in-class small molecule with anti-cancer activity, which is currently in clinical evaluation in a phase 2 trial in patients with advanced endometrial and squamous non-small cell lung carcinoma (NCT03366480). Previously, we showed that ABTL0812 induces TRIB3 pseudokinase expression, resulting in the inhibition of the AKT-MTORC1 axis and macroautophagy/autophagy-mediated cancer cell death. However, the precise molecular determinants involved in the cytotoxic autophagy caused by ABTL0812 remained unclear. Using a wide range of biochemical and lipidomic analyses, we demonstrated that ABTL0812 increases cellular long-chain dihydroceramides by impairing DEGS1 (delta 4-desaturase, sphingolipid 1) activity, which resulted in sustained ER stress and activated unfolded protein response (UPR) via ATF4-DDIT3-TRIB3 that ultimately promotes cytotoxic autophagy in cancer cells. Accordingly, pharmacological manipulation to increase cellular dihydroceramides or incubation with exogenous dihydroceramides resulted in ER stress, UPR and autophagy-mediated cancer cell death. Importantly, we have optimized a method to quantify mRNAs in blood samples from patients enrolled in the ongoing clinical trial, who showed significant increased DDIT3 and TRIB3 mRNAs. This is the first time that UPR markers are reported to change in human blood in response to any drug treatment, supporting their use as pharmacodynamic biomarkers for compounds that activate ER stress in humans. Finally, we found that MTORC1 inhibition and dihydroceramide accumulation synergized to induce autophagy and cytotoxicity, phenocopying the effect of ABTL0812. Given the fact that ABTL0812 is under clinical development, our findings support the hypothesis that manipulation of dihydroceramide levels might represents a new therapeutic strategy to target cancer. Abbreviations: 4-PBA: 4-phenylbutyrate; AKT: AKT serine/threonine kinase; ATG: autophagy related; ATF4: activating transcription factor 4; Cer: ceramide; DDIT3: DNA damage inducible transcript 3; DEGS1: delta 4-desaturase, sphingolipid 1; dhCer: dihydroceramide; EIF2A: eukaryotic translation initiation factor 2 alpha; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; HSPA5: heat shock protein family A (Hsp70) member 5; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; MTORC1: mechanistic target of rapamycin kinase complex 1; NSCLC: non-small cell lung cancer; THC: Δ9-tetrahydrocannabinol; TRIB3: tribbles pseudokinase 3; XBP1: X-box binding protein 1; UPR: unfolded protein response.
Prevalence of anaemia in Brazilian children in different epidemiological scenarios: an updated meta-analysis

Abstract Objective: To update the estimation of the prevalence of anaemia in Brazilian children according to four different epidemiological scenarios. Design: A new systematic review was conducted with a meta-analysis of the results published between 2007 and May 2019. Literature search was carried out in the PubMed and LILACS databases using keywords anaemia, child and Brazil. A total of thirty-seven articles (17 741 children) were selected and categorised according to the origin of their respective samples: childcare centres (Childcare; n 13 studies/2697 individuals), health services (Services; n 4/755), populations with social inequities (Inequities, n 7/6798) and population-based studies (Populations; n 13/7491). Assuming a prevalence of 20·9 % as reference (Health National Survey; n 3455), the combined prevalence ratios (PR) were calculated. A random-effects model was used. Participants: Brazilian children 6–60 months of age. Results: The prevalence of anaemia, by scenario, was: Childcare 24·8 % (PR 1·06; 95 % CI 0·81, 1·40); Services 39·9 % (PR 1·76, 95 % CI 1·33, 2·35); Inequities 51·6 % (PR 2·02, 95 % CI 1·87, 2·18); and Populations 35·8 % (PR 1·42, 95 % CI 1·23, 1·64). Therefore, the values were all higher than the national prevalence; the Inequities had the highest prevalence, and only Childcare did not reach statistical significance. Concerning the previous meta-analysis, there was a reduction in anaemia prevalence in all scenarios: –52·3, –33·7, –22·4 and –10·7 %, respectively. Conclusions: Compared to the situation revealed in the previous meta-analysis, anaemia, although observed to a lesser extent, remains an important public health problem in the different scenarios analysed, especially for children living in Inequities. Access to Childcare mitigates the risk for this condition.
Retrospective analysis of harvest management performance for Bristol Bay and Fraser River sockeye salmon (Oncorhynchus nerka)

Given current knowledge of mean stock–recruitment relationships and variation in past recruitment, yield of sockeye salmon (Oncorhynchus nerka) in Bristol Bay, Alaska, and Fraser River, British Columbia, might have been at least 100%–300% larger since 1950 than was actually achieved. Most of these gains would have been due to knowledge of optimum mean spawning stock size rather than specific recruitment anomalies; knowing all future recruitment anomalies at the time of each spawning stock choice would have likely only added 2%–5% to total catches. For some stocks, delayed density dependence (cyclic dominance) might have resulted in somewhat lower yields, but under optimal management would still have been higher than were achieved. Even given only estimates of optimum spawning stock size each year based on data available as of that year, but following fixed escapement harvest policy rules, managers could likely have achieved 30%–40% higher total yield. Key management experiments for the future will involve.
Influence of Cooking Conditions on Nutritional Properties and Sensory Characteristics Interpreted by E-Senses: Case-Study on Selected Vegetables

This study investigates the effects of three cooking methods (boiling, steaming and microwaving) on the nutritional and physical properties of cauliflowers, carrots and sweet potatoes; e-senses were applied to interpret the sensory characteristics according to physico-chemical aspects. The nutritional quality was evaluated by determining the concentrations of key components and the antioxidant activity; e-sense data, combined with texture parameters, were processed by a principal component analysis. The cooking method and time significantly influenced the quality of the three products. Boiling, which detrimentally affected ascorbic acid, total phenolic concentration and antioxidant activity, enhanced carotene accessibility. Steaming produced losses in ascorbic acid, increasing total phenolics and carotenoids. Microwaving resulted in minor changes in ascorbic acid concentrations, preserved carotenoids and increased total phenolics. The nutritional quality was better preserved or enhanced using shorter cooking times. The elaboration of the data collected by the e-senses showed a clear evolution according to the cooking method and time. The results helped to determine the cooking method that best preserves the nutritional properties of the vegetables, highlighting the applicability of rapid instrumental methods to interpret the evolution of sensory characteristics.
Distribution of Red Blood Cell Alloantibodies Among Transfusion-Dependent β-Thalassemia Patients in Different Population of Iran: Effect of Ethnicity

Abstract The best approach for prevention of alloimmunization in β-thalassemia (β-thal) patients is perfect matching of all red blood cell (RBC) antigens associated with clinically significant antibodies, but this is expensive and may limit the blood supply. Knowing the most common alloantibodies in transfusion-dependent β-thal patients make it possible to establish more cost-effective matching strategies for high-risk antigens. With this in mind, we intended to determine the most common alloantibodies in different parts of Iran. A total of 480 alloimmunized β-thal major (β-TM) patients who were referred to the Tehran Adult Thalassemia Clinic in Tehran, Iran from all provinces between 2015 and 2017, were included in this study. Antibody screening was performed on the fresh serum of all patients. Subsequently, the specification of antibodies was identified using a panel of recognized blood group antigens. Anti-K was the most common alloantibody detected in β-TM patients in all regions of Iran. The prevalence of this antibody reached to 37.7% in the western area, but in southeastern region, anti-E was predominant. Interestingly, the rare alloantibody anti-Kpa was detected with a high prevalence in the western region. The antibodies against E and D antigens were also encountered with high prevalence in most regions of the country. The present study demonstrated the distribution of alloantibodies in alloimmunized transfusion-dependent β-thal patients from diverse ethnic and racial backgrounds of the Iranian population. The results of this study can be used as a basis to establish cost-effective RBC phenotyping and matching strategies for high-risk antigens in donors and chronic transfusion recipients in different regions of Iran.
Uptake and excretion of dimethylsulphoniopropionate is driven by salinity changes in the marine benthic diatom Cylindrotheca closterium

Long-term ( ⩽ 14 d) and short-term ( ⩽ 9 h) effects of salinity on the dimethylsulphoniopropionate (DMSP) content of the marine benthic diatom Cylindrotheca closterium were investigated. When grown in batch cultures at various salinities, intracellular DMSP increased from 13.8 to 823 μmol g − 1 protein at salinities of 11 and 44 psu, respectively, but increasing salinity further did not result in a higher content. Instead, the concentration of the amino acid proline increased from 17.5 to 149.6 μmol g − 1 protein when salinity increased from 33 to 55, indicating that this compound is more important than DMSP as an osmoprotectant at higher salinities. In addition, another, hitherto unidentified, compound increased strongly in response to salinity. During salinity up- and down-shock experiments, changes in the DMSP content of C. closterium corresponded with the changes in salinity. DMSP was excreted into the medium after salinity down-shock, while salinity up-shock induced a slow synthesis of DMSP. However, C. closterium was also able to take up DMSP from the medium; the amount depended on the salinity difference applied. This is the first report of uptake of DMSP by an alga. The results demonstrate that synthesis of DMSP is too slow to be important for short-term acclimation and that its contribution to the intracellular osmotic potential of C. closterium is probably small. However, the observation that uptake of DMSP was faster after salinity up-shock from 11 to 33 than from 11 to 22, indicates that DMSP does have an osmoprotective function in C. closterium. Uptake of DMSP and other organic osmolytes from the environment may serve as a mechanism of osmoacclimation for diatoms living under highly fluctuating salinities in intertidal sediments.
HPLC-MS/MS Method for the Detection of Selected Toxic Metabolites Produced by Penicillium spp. in Nuts

Penicillium spp. are emerging as producers of mycotoxins and other toxic metabolites in nuts. A HPLC-MS/MS method was developed to detect 19 metabolites produced by Penicillium spp. on chestnuts, hazelnuts, walnuts and almonds. Two extraction methods were developed, one for chestnuts and one for the other three nuts. The recovery, LOD, LOQ and matrix effect were determined for each analyte and matrix. Correlation coefficients were always >99.99%. In walnuts, a strong signal suppression was observed for most analytes and patulin could not be detected. Six strains: Penicillium bialowiezense, P. brevicompactum, P. crustosum, P. expansum, P. glabrum and P. solitum, isolated from chestnuts, were inoculated on four nuts. Chestnuts favored the production of the largest number of Penicillium toxic metabolites. The method was used for the analysis of 41 commercial samples: 71% showed to be contaminated by Penicillium-toxins. Cyclopenin and cyclopenol were the most frequently detected metabolites, with an incidence of 32% and 68%, respectively. Due to the risk of contamination of nuts with Penicillium-toxins, future studies and legislation should consider a larger number of mycotoxins.
NLRC4, ASC and Caspase-1 Are Inflammasome Components That Are Mediated by P2Y2R Activation in Breast Cancer Cells

The inflammasomes are reported to be associated with tumor progression. In our previous study, we determined that extracellular ATP enhances invasion and tumor growth by inducing inflammasome activation in a P2Y purinergic receptor 2 (P2Y2R)-dependent manner. However, it is not clear which inflammasome among the diverse complexes is associated with P2Y2R activation in breast cancer. Thus, in this study, we determined which inflammasome components are regulated by P2Y2R activation and are involved in tumor progression in breast cancer cells and radiotherapy-resistant (RT-R)-breast cancer cells. First, we found that NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3); NLR family caspase activation and recruitment domain (CARD) containing 4 (NLRC4); apoptosis-associated speck-like protein containing a CARD complex (ASC); and caspase-1 mRNA levels were upregulated in RT-R-MDA-MB-231 cells compared to MDA-MB-231 cells, whereas tumor necrosis factor-α (TNF-α) or ATP treatment induced NLRC4, ASC, and caspase-1 but not NLRP3 protein levels. Moreover, TNF-α or ATP increased protein levels of NLRC4, ASC, and caspase-1 in a P2Y2R-dependent manner in MDA-MB-231 and RT-R-MDA-MB-231 cells. In addition, P2Y2R activation by ATP induced the secretion of IL-1β and VEGF-A, as well as invasion, in MDA-MB-231 and RT-R-MDA-MB-231 cells, which was inhibited by NLRC4, ASC, and caspase-1 small interfering RNA (siRNA). Taken together, this report suggests that P2Y2R activation by ATP induces tumor invasion and angiogenesis through inflammasome activation, specifically by regulating the inflammasome components NLRC4, ASC, and caspase-1.
Pollen Germination and Tube Growth in Selfing and Outcrossing Populations of Clarkia tembloriensis (Onagraceae)

Pollen germination, pollen tube growth, and seed set were compared in growth chamber-grown plants derived from a typically outcrossing (Idria-2) and a typically selfing (Cantua Creek-2) population of Clarkia tembloriensis. Pollen of Idria-2 plants germinated uniformly and rapidly, usually within 1 h after pollination. Pollen of Cantua Creek-2 plants germinated more slowly, over a period of 1-7 h after pollination. The styles of Idria-2 plants were nearly twice as long as those of Cantua Creek-2 plants, but the time elapsed between the moment of pollination and when the pollen tubes reached the ovary was the same for both populations. However, even though the pollen tubes reached the ovaries at approximately the same time after pollination for all plants, fertilization of ovules, as measured by seed set, occurred immediately in the Cantua Creek-2 plants, while fertilization was delayed by 2-3 h in the Idria-2 plants. These differences in pollen germination and tube growth were significant and may have evolved in response to different levels of pollen competition in the two populations.
Foraging by Swainson's Hawks in a Vineyard-Dominated Landscape

ABSTRACT We studied habitat use for foraging by Swainson's Hawks (Buteo swainsoni) within a complex agricultural crop matrix in California's Central Valley to ascertain if vineyards were used for foraging. Central Valley vineyard agriculture has increased recently, especially in areas supporting the highest regional numbers of Swainson's Hawks. There is concern that increased vineyard coverage may reduce the amount of foraging habitat available for Swainson's Hawks, because vineyards have been considered poor foraging habitat for this species, due to the height and density of the vines. In 2002 and 2003, we conducted road surveys to record observations of foraging Swainson's Hawks in relation to agricultural habitats. Using chi-square tests and 95% CIs, we assessed habitat selection for foraging Swainson's Hawks and determined whether habitat use varied throughout the breeding season. Swainson's Hawks used 10 unique habitat types for foraging during the breeding season. Swainson's Hawks used vineyards less than expected and irrigated hay and dryland grain habitats more than expected, with some variation in habitat use as the season progressed. The variety of habitats that Swainson's Hawks used for foraging in our study area suggests that maintenance of large heterogeneous areas of agricultural habitats that include crops such as alfalfa, as well as large tracts of grazed grasslands, should be one of the priorities for conservation of this species in this region.
Autochthonous Starter Cultures Are Able to Reduce Biogenic Amines in a Traditional Portuguese Smoked Fermented Sausage

Traditional smoked fermented sausages are highly appreciated in Portugal and are mostly manufactured according to traditional procedures. The aim of the present work was to evaluate the effect of autochthonous starter cultures on the safety and quality of a smoked fermented sausage, Painho da Beira Baixa (PBB), preserving its sensory quality. Physicochemical parameters, namely pH and water activity (aW), microbiological parameters, biogenic amines, colour, texture profile and sensory attributes were assessed. Different starters were selected based on our previous work. Staphylococcus equorum S2M7, Staphylococcus xylosus CECT7057, Lactobacillus sakei CV3C2, Lactobacillus sakei CECT7056 and a yeast strain (2RB4) were co-inoculated in meat batters at defined concentrations. Starters had a significant effect on the reduction of pH. Enterobacteria and Listeria monocytogenes were not detected in inoculated end-product sausages. Moreover, sausages inoculated with S. equorum S2M7/L. sakei CV3C2/yeast 2RB4 showed a significant reduction in the total content of biogenic amines. No significant differences between treatments were observed for colour and texture parameters, except for adhesiveness. The studied starters did not compromise the sensory characteristics of PBB. To our knowledge, this is the first comprehensive study on the quality and safety of this type of smoked fermented sausage from the central region of Portugal.
Carotid artery stenting before surgery for carotid artery occlusion associated with acute type A aortic dissection: Two case reports

Background We experienced two cases of ischemic stroke resulting from carotid artery occlusion associated with acute type A aortic dissection (ATAAD), in which carotid artery stenting before the surgery for ATAAD resulted in good clinical outcomes. Case 1 description: A 63-year-old woman was hospitalized for conscious disturbance, right hemiparesis, and total aphasia. Computed tomography of the head showed no abnormal findings. Computed tomography angiography showed ATAAD and bilateral common carotid artery occlusion. Surgery was not indicated for ATAAD because of a poor prognosis of ischemic stroke. However, carotid artery stenting of the left common carotid artery occlusion was successfully performed, and her neurological findings improved. The patient underwent hemiarch replacement for ATAAD on the day after carotid artery stenting. Her final modified Rankin Scale was 1. Case 2 Description: A 57-year-old woman was hospitalized for mild left hemiparesis. Magnetic resonance imaging showed right watershed infarction and right common carotid artery occlusion. Computed tomography angiography showed ATAAD. After hospitalization, conscious disturbance appeared and left hemiparesis worsened. Ischemic stroke indicated a poor prognosis for revascularization by surgery for ATAAD. Thus, carotid artery stenting of the right common carotid artery occlusion was performed. The patient’s neurological findings improved and she underwent hemiarch replacement for ATAAD at 19 days after carotid artery stenting. Her final modified Rankin Scale was 1. Conclusions In the present cases, although ischemic stroke was serious and precluded surgical indication for ATAAD, carotid artery stenting before surgery for ATAAD resulted in good clinical outcomes. Performing carotid artery stenting before surgery for ATAAD is challenging but achievable, and is a valid treatment option depending on the individual cases.
Valorisation of Grape Stems as a Source of Phenolic Antioxidants by Using a Sustainable Extraction Methodology

Pressurized liquid extraction with ethanol:water mixtures was proposed for obtaining phenolic antioxidants from grape stems. The optimal extraction conditions were elucidated by using a central composite rotatable design (solvent (X1, 0–100% ethanol:water v/v), temperature (X2, 40–120 °C) and time (X3, 1–11 min)). Response surface methodology determined 30% ethanol:water, 120 °C and 10 min as the optimal extraction conditions regarding total phenolic content (TPC) (185.3 ± 2.9 mg gallic acid/g of extract) and antioxidant activity (3.55 ± 0.21 mmol Trolox/g, 1.22 ± 0.06 mmol Trolox/g and 1.48 ± 0.17 mmol Trolox/g of extract in ABTS, DPPH and ORAC methodologies, respectively). The antioxidant activity was attributed to total polymer procyanidins and flavan-3-ol monomers and oligomers, although other phenolic compound contributions should not be ruled out. Forty-two phenolic compounds were identified in the optimal extract, mainly polymer procyanidins and, to a lesser extent, monomers and oligomers of flavan-3-ols, quercetin-3-O-glucuronide, ε-viniferin, gallic and caftaric acid. Ethyl gallate, ellagic acid, protocatechuic aldehyde, delphinidin-7-O-glucoside and cyanidin-3-O-glucoside were reported for the first time in grape stem extracts. In conclusion, this study highlights the use of this winery side stream as a source of antioxidants within a sustainable food system.
Associations of chronotype, Big Five, and emotional competences with perceived stress in university students

ABSTRACT This study aimed to investigate the associations between individual difference factors (chronotype, Big Five, emotional competences) and perceived stress in French university students. In total, 362 students agreed to take part (M age = 20.19 ± 1.75 years). Participants completed the Caen Chronotype Questionnaire, Big Five Inventory, the Profile of Emotional Competences, and the Perceived Stress Scale. Results showed that chronotype amplitude (+), eveningness chronotype (+), neuroticism (+), conscientiousness (-), and intrapersonal emotional competences (-) were important for perceived stress. These findings have theoretical and practical implications in terms of identifying students who might benefit most from stress management interventions.
Scleral Inflammation around Collector Channels in Eyes with Primary Open-Angle Glaucoma

ABSTRACT Purpose: Investigating the existence of inflammation in the distal outflow system posterior of the Schlemm's canal in primary open-angle glaucoma (POAG). Methods: Scleral biopsies (n = 62) from POAG-patients were taken during deep sclerectomy and fixed either in formalin or RNAlater®. Histologic (hematoxylin & eosin) and immunohistological staining for CD 3 and CD 45RO were performed. Results: Cellular infiltration of immunocompetent cells (CD 3 and CD 45RO positive cells) exists around collector channels (CC). This inflammation is limited to the area around the CCs. Ninety-two percent of the biopsies are positive for inflammation. Untreated, dysgenetic glaucoma eyes and 8% of POAG eyes were negative for inflammation. Neither the use of benzalkonium chloride nor the number and type of preoperative antiglaucomatous medication correlated to the immunohistological result. Conclusion: In POAG a diverse cellular infiltration exists around the CCs in the vast majority of biopsies. This could have major diagnostic and therapeutic consequences for the treatment of POAG. Abbreviations: POAG: primary open-angle glaucoma; CC: collector channel; AH: aqueous humor; TM: trabecular meshwork; SC: Schlemm's canal; HE: hematoxylin & eosin; APC: antigen-presenting cell