Miracle-dz/UniFAR-FTUs huggingface dataset:
Stomach contents of long-finned pilot whales, Globicephala melas mass-stranded in Tasmania

New data are reported from analyses of stomach contents from 114 long-finned pilot whales mass-stranded at four locations around Tasmania, Australia from 1992–2006. Identifiable prey remains were recovered from 84 (74%) individuals, with 30 (26%) individuals (17 females and 13 males) having empty stomachs. Prey remains comprised 966 identifiable lower beaks and 1244 upper beaks, belonging to 17 families (26 species) of cephalopods. Ommastrephidae spp. were the most important cephalopod prey accounting for 16.9% by number and 45.6% by reconstructed mass. Lycoteuthis lorigera was the next most important, followed by Ancistrocheirus lesueurii. Multivariate statistics identified significant differences in diet among the four stranding locations. Long-finned pilot whales foraging off Southern Australia appear to be targeting a diverse assemblage of prey (≥10 species dominated by cephalopods). This is compared to other similar studies from New Zealand and some locations in the Northern Hemisphere, where the diet has been reported to be primarily restricted to ≤3 species dominated by cephalopods. This study emphasises the importance of cephalopods as primary prey for Southern long-finned pilot whales and other marine vertebrates, and has increased our understanding of long-finned pilot whale diet in Southern Ocean waters.
HIF‐1α/VEGF signaling‐mediated epithelial–mesenchymal transition and angiogenesis is critically involved in anti‐metastasis effect of luteolin in melanoma cells

Tumor metastasis is still the leading cause of melanoma mortality. Luteolin, a natural flavonoid, is found in fruits, vegetables, and medicinal herbs. The pharmacological action and mechanism of luteolin on the metastasis of melanoma remain elusive. In this study, we investigated the effect of luteolin on A375 and B16‐F10 cell viability, migration, invasion, adhesion, and tube formation of human umbilical vein endothelial cells. Epithelial–mesenchymal transition (EMT) markers and pivotal molecules in HIF‐1α/VEGF signaling expression were analysed using western blot assays or quantitative real‐time polymerase chain reaction. Results showed that luteolin inhibits cellular proliferation in A375 and B16‐F10 melanoma cells in a time‐dependent and concentration‐dependent manner. Luteolin significantly inhibited the migratory, invasive, adhesive, and tube‐forming potential of highly metastatic A375 and B16‐F10 melanoma cells or human umbilical vein endothelial cells at sub‐IC50 concentrations, where no significant cytotoxicity was observed. Luteolin effectively suppressed EMT by increased E‐cadherin and decreased N‐cadherin and vimentin expression both in mRNA and protein levels. Further, luteolin exerted its anti‐metastasis activity through decreasing the p‐Akt, HIF‐1α, VEGF‐A, p‐VEGFR‐2, MMP‐2, and MMP‐9 proteins expression. Overall, our findings first time suggests that HIF‐1α/VEGF signaling‐mediated EMT and angiogenesis is critically involved in anti‐metastasis effect of luteolin as a potential therapeutic candidate for melanoma.
Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma

Significance Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis and limited treatment options. MPM remains a serious public health problem, and novel therapeutic strategies are urgently needed. The antitumor properties of growth hormone-releasing hormone (GHRH) antagonists have been demonstrated in different cancers; however, their influence in MPM remains unexplored. Our work shows that GHRH antagonists MIA-602 and MIA-690 reduce survival, proliferation, and migration of human MPM cell lines and primary MPM cells in vitro by modulating apoptotic and oncogenic pathways. In vivo, GHRH antagonists inhibited the growth of MPM xenografts and blunted the production of growth factors in tumors. Overall, the inhibitory activities described in this study suggest that GHRH antagonists may be considered for development of therapies for MPM. Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with exposure to asbestos, with poor prognosis and no effective therapies. The strong inhibitory activities of growth hormone-releasing hormone (GHRH) antagonists have been demonstrated in different experimental human cancers, including lung cancer; however, their role in MPM remains unknown. We assessed the effects of the GHRH antagonists MIA-602 and MIA-690 in vitro in MPM cell lines and in primary MPM cells, and in vivo in MPM xenografts. GHRH, GHRH receptor, and its main splice variant SV1 were found in all the MPM cell types examined. In vitro, MIA-602 and MIA-690 reduced survival and proliferation in both MPM cell lines and primary cells and showed synergistic inhibitory activity with the chemotherapy drug pemetrexed. In MPM cells, GHRH antagonists also regulated activity and expression of apoptotic molecules, inhibited cell migration, and reduced the expression of matrix metalloproteinases. These effects were accompanied by impairment of mitochondrial activity and increased production of reactive oxygen species. In vivo, s.c. administration of MIA-602 and MIA-690 at the dose of 5 μg/d for 4 wk strongly inhibited the growth of MPM xenografts in mice, along with reduction of tumor insulin-like growth factor-I and vascular endothelial growth factor. Overall, these results suggest that treatment with GHRH antagonists, alone or in association with chemotherapy, may offer an approach for the treatment of MPM.
Circulating Angiopoietin-like 8 protein (ANGPTL8/Betatrophin) in patients with polycystic ovary syndrome: a systematic review and multi effect size meta-analysis

Abstract The association between circulating betatrophin levels and polycystic ovary syndrome (PCOS) is controversial and the studies in the literature are inconsistent. The aim of our study was to systematically review and meta-analyze all available literature comparing circulating betatrophin levels between human PCOS patients and controls. Relevant studies were retrieved by online database and manual searching. A total of 11 studies were included in this meta-analysis. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. Meta-analysis of correlations was performed for the associations of betatrophin with anthropometric, lipid and hormonal covariates in PCOS patients. The results indicated that the betatrophin levels were significantly elevated in PCOS patients as compared to non-PCOS controls (SMD = 0.73, 95% CI = 0.22–1.24, Z = 2.83, p = .005). A one-study leave-out sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the robustness of this meta-analysis. Our sub-group analysis indicated that this increase in betatrophin concentrations was regardless of normo-weight or obese body mass index (BMI) and insulin resistance might have an important role. There were significant positive correlations of betatrophin with age, free androgen index and free-testosterone in PCOS patients. In summary, regardless of BMI, the circulatory betatrophin levels are elevated in PCOS patients compared to controls. PCOS patients with higher insulin resistance had substantially higher circulating betatrophin concentrations.
Basic Study of Drug-Drug Interaction between Memantine and the Traditional Japanese Kampo Medicine Yokukansan

Several basic pharmacokinetic and pharmacological studies were conducted as part of a group of studies to clarify the drug-drug interaction (DDI) between memantine (MEM), a drug used to treat Alzheimer’s disease, and yokukansan (YKS), a traditional Japanese Kampo medicine used to treat behavioral and psychological symptoms of dementia. The pharmacokinetic studies showed that there were no statistically significant differences in MEM concentrations in the plasma, brain, and urine between mice treated with MEM alone and with MEM plus YKS. Regarding candidate active ingredients of YKS, there were also no statistically significant differences in concentrations of geissoschizine methyl ether in the plasma and brain, urine, glycyrrhetinic acid in the plasma, and isoliquiritigenin in the urine, in mice treated with YKS alone or with MEM plus YKS. The pharmacological studies showed that isoliquiritigenin, which has an N-methyl-d-aspartic acid (NMDA) receptor antagonistic effect, did not affect the inhibitory effect of MEM on NMDA-induced intracellular Ca2+ influx in primary cultured rat cortical neurons. Moreover, YKS did not affect either the ameliorative effects of MEM on NMDA-induced learning and memory impairment, or the MEM-induced decrease in locomotor activities in mice. These results suggest that there is probably no pharmacokinetic or pharmacological interaction between MEM and YKS in mice, but more detailed studies are needed in the future. Our findings provide important information for future studies, to clarify the DDI more regarding the efficacy and safety of combined use of these drugs in a clinical situation.
Evaluation of spectral domain optical coherence tomography parameters in discriminating preperimetric glaucoma from high myopia.

AIM To evaluate the diagnostic ability of macular ganglion cell-inner plexiform layer (GCIPL) thickness obtained by spectral-domain optical coherence tomography (SD-OCT) in discriminating non-highly myopic eyes with preperimetric glaucoma (PPG) from highly myopic healthy eyes. METHODS A total of 254 eyes, including 76 normal controls (NC), 116 eyes with high myopia (HM) and 62 non-highly myopic eyes with PPG were enrolled. The diagnostic ability of OCT parameters was accessed by the areas under the receiver operating characteristic (AUROC) curve in two distinguishing groups: PPG eyes with non-glaucomatous eyes including NC and HM (Group 1), and PPG eyes with HM eyes (Group 2). Differences in diagnostic performance between GCIPL and RNFL parameters were evaluated. RESULTS The minimum (AUROC curve of 0.782), inferotemporal (0.758) and inferior (0.705) GCIPL thickness were the top three GCIPL parameters in discriminating PPG from non-glaucomatous eyes, all of which had statistically significant lower diagnostic ability than average RNFL thickness (0.847). In discriminating PPG from HM, the best GCIPL parameter was minimum (0.689), statistically significant lower in diagnostic ability than average RNFL thickness (0.789) and three other RNFL thickness parameters of temporal and inferotemporal clock-hour sectors. CONCLUSION The minimum GCIPL thickness is the best GCIPL parameter to detect non-highly myopic PPG from highly myopic eyes, whose diagnostic ability is inferior to that of average RNFL thickness and RNFL thickness of several temporal and inferotemporal clock-hour sectors. The average RNFL thickness is recommended for discriminating PPG from highly myopic healthy eyes in current clinical practice in a Chinese population.
Acute Responses of Novel Cardiac Biomarkers to a 24-h Ultra-Marathon

The aim of the present study was to examine the acute effect of an ultra-endurance performance on N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac specific troponin T (cTnT), creatinine kinase-myocardial band (CK-MB), high sensitive C-reactive protein (hsCRP), ischemia modified albumin (IMA), heart-type fatty acid binding protein (H-FABP) and cardiovascular function. Cardiac biomarkers were evaluated in 14 male ultra-marathoners (age 40 ± 12 years) during a 24 h ultra-marathon at five points (i.e., Pre-race; Marathon, 12-h run, 24-h run, and 48-h post-race). All subjects underwent baseline echocardiography assessment at least 10 days prior to the ultra-marathon and 48 h post-race. The average distance covered during the race was 149.4 ± 33.0 km. Running the ultra-marathon led to a progressive increase in hsCRP and H-FABP concentrations (p < 0.001). CK-MB and cTnT levels were higher after a 24-h run compared to pre-race (p < 0.05). Diastolic function was altered post-race characterized by a reduction in peak early to late diastolic filling (p < 0.01). Running an ultra-marathon significantly stimulates specific cardiac biomarkers; however, the dynamic of secretion of biomarkers linked to myocardium ischemia were differentially regulated during the ultra-marathon race. It is suggested that both exercise duration and intensity play a crucial role in cardiovascular adaptive mechanisms and cause risk of cardiac stress in ultra-marathoners.
Implications of using two natural enemies of Tuta absoluta (Lepidoptera: Gelechiidae) toward tomato yield enhancement

Abstract Tomato leaf miner (TLM), Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) is one of the most destructive tomato pests worldwide. We tested quantity and quality of tomato fruits after simultaneous use of two biological control agents, the predatory mirid bug Nesidiocoris tenuis (Reuter) and the egg parasitoid Trichogramma brassicae Bezdenko against TLM. We varied the timing of predator releases (before or after pest establishment) and the number of parasitoids released (ten or 30 females per week per m2). The highest number of fruits per cage, percentage of undamaged fruits, total yield weight, and undamaged yield weight were all obtained with predator-in-first treatments, with or without parasitoid releases. Furthermore, measures of fruit quality were also highest in predator-in-first treatments, including, highest percentage of water, greatest proportional fresh weight of carbohydrates, most lycopene, most β-carotene, most flavonoids, and highest total chlorophyll. Thus, our findings support a predator-in-first augmentation approach for management of TLM.
Ten-Year Comparison Study of Type 1 and 2 Endometrial Cancers: Risk Factors and Outcomes

Aims: To compare baseline risk factors for type 1 vs. 2 endometrial cancers and analyze these risk factors for association with overall survival and time to recurrence. Methods: Retrospective review of 816 consecutive endometrial cancer cases was conducted with diagnosis from January 2005 to December 2010 and clinical course until 2016. Risk factors, treatment, recurrence, and death were compared using 2 sample t tests, χ2 test and Cox Regression models. Results: There were 550 cases of type 1 and 266 cases of type 2 cancer. Patients with type 2 disease were older (p < 0.001), less obese (p = 0.03), non-white (p < 0.001), and menopausal (p = 0.02). There was no difference in use of oral contraceptives, hormone replacement therapy (HRT), smoking, or major cardiovascular disease. Cox Regression models showed that type 2 disease (p < 0.001) and advanced stage (p = 0.001) were associated with recurrence. Conclusions: Consistent with previous literature, our analysis found that type 2 cancer is more common in non-white, older, and less obese patients and associated with higher mortality and recurrence. However, inconsistent with previous literature, we found no association between type 2 cancer and diabetes mellitus or use of HRT. These factors should be considered when approaching patients with endometrial cancer.
Current Pharmacotherapy Does Not Improve Severity of Hypoactive Delirium in Patients with Advanced Cancer: Pharmacological Audit Study of Safety and Efficacy in Real World (Phase-R).

BACKGROUND Pharmacotherapy is generally recommended to treat patients with delirium. We sought to describe the current practice, effectiveness, and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer, and to explore predictors of the deterioration of delirium symptoms after starting pharmacotherapy. SUBJECTS, MATERIALS, AND METHODS We included data of patients with advanced cancer who were diagnosed with hypoactive delirium and received pharmacotherapy for treatment of delirium. This was a pharmacovigilance study characterized by prospective registries and systematic data-recording using internet technology, conducted among 38 palliative care teams and/or units. The severity of delirium and other outcomes were assessed using established measures at days 0 (T0), 3 (T1), and 7 (T2). RESULTS Available data were obtained from 218 patients. The most frequently used agent was haloperidol (37%). A total of 67 and 42 patients (31% and 19%) had died or discontinued pharmacotherapy by T1 and T2, respectively. Delirium symptoms deteriorated between T0 and T1, but this trend did not reach statistical significance. The most prevalent adverse event was sedation (9%). Delirium severity worsened after starting pharmacotherapy in 121 patients (56%) at T1. In patients whose death was expected within a few days and those with delirium caused by organ failure, symptoms of delirium were significantly more likely to deteriorate after starting pharmacotherapy. CONCLUSION Current pharmacotherapy for hypoactive delirium in patients with advanced cancer is not recommended, especially in those whose death is expected within a few days and in those with delirium caused by organ failure. IMPLICATIONS FOR PRACTICE Delirium is common among patients with advanced cancer, and hypoactive delirium is the dominant motor subtype in the palliative care setting. Pharmacotherapy is recommended and regularly used to treat delirium. This article describes the effectiveness and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer. The findings of this study do not support the use of pharmacotherapy for treatment of hypoactive delirium in the palliative care setting. Pharmacotherapy should especially be avoided in patients whose death is expected within a few days and in those with delirium caused by organ failure.
Synaptotagmin oligomers are necessary and can be sufficient to form a Ca2+‐sensitive fusion clamp

The buttressed‐ring hypothesis, supported by recent cryo‐electron tomography analysis of docked synaptic‐like vesicles in neuroendocrine cells, postulates that prefusion SNAREpins are stabilized and organized by Synaptotagmin (Syt) ring‐like oligomers. Here, we use a reconstituted single‐vesicle fusion analysis to test the prediction that destabilizing the Syt1 oligomers destabilizes the clamp and results in spontaneous fusion in the absence of Ca2+. Vesicles in which Syt oligomerization is compromised by a ring‐destabilizing mutation dock and diffuse freely on the bilayer until they fuse spontaneously, similar to vesicles containing only v‐SNAREs. In contrast, vesicles containing wild‐type Syt are immobile as soon as they attach to the bilayer and remain frozen in place, up to at least 1 h until fusion is triggered by Ca2+.
Effect of Size and Location of Nevi on Postoperative Pain and Emergence Agitation in Children Undergoing Nevi Excision

Congenital melanocytic nevi need surgical excisions. However, the effect of the size and location of the nevi on pain and emergence agitation have yet to be studied. The objective of this study was to evaluate (1) the ideal parameter of the nevus size and (2) the effects of the size and location of the nevus on pain and emergence agitation. This observational study enrolled 100 children scheduled for an excision of a nevus under sevoflurane anesthesia. The parameters of the nevus size included the long diameter, the area before resection, the area of resection, and the proportion (the area of resection/total body surface). The nevus locations included the trunk, face, scalp, and extremities. The proportion of the nevi was the most ideal parameter in evaluating the pain and emergence agitation. A large size showed a higher emergence agitation than a small size (median (range); 6 (0–20) in small groups vs. 12.5 (0–20) in large groups, p = 0.021). However, the pain was comparable. The nevus location did not influence pain or emergence agitation. In a multivariate regression analysis, a younger age and an extensive excision were associated with higher pain and emergence agitation. In conclusion, large nevi induced more severe emergence agitation. However, the nevus location did not affect the outcome. In addition, a younger age was associated with pain and emergence agitation. Clinicians need to consider the proportion of nevi when managing children undergoing a nevus excision.
Expression pattern of genes associated with tumor microenvironment in prostate cancer.

AIM To assess relative expression (RE) levels of CAF-, TAM-specific, immune defense-associated genes in prostate tumors and to show correlation of RE with clinical, pathological and molecular characteristics, with the aim to define clinically significant specific alterations in a gene expression pattern. METHODS RE of 23 genes was analyzed by a quantitative polymerase chain reaction in 37 freshly frozen samples of prostate cancer tissues of a different Gleason score (GS) and at various tumor stages, compared with RE in 37 paired conventionally normal prostate tissue (CNT) samples and 20 samples of prostate adenomas. RESULTS Differences in RE were shown for 11 genes out of 23 studied, when tumor samples were compared with corresponding CNTs. 7 genes, namely ACTA2, CXCL14, CTGF, THY1, FAP, CD163, CCL17 were upregulated in tumors. 4 genes, namely CCR4, NOS2A, MSMB, IL1R1 were downregulated in tumors. 14 genes demonstrated different RE in TNA at different stages: CXCL12, CXCL14, CTGF, FAP, HIF1A, THY1, CCL17, CCL22, CCR4, CD68, CD163, NOS2A, CTLA4, IL1R1. RE changes of 9 genes - CXCL12, CXCL14, HIF1A, CCR4, CCL17, NOS2A, CTLA4, IL1R1, IL2RA - were found in tumors with different GS. Moreover, 9 genes showed differences in RE in TNA, dependently on the presence or absence of the TMPRSS2/ERG fusion and 7 genes showed differences in RE of groups with differential PTEN expression. Significant correlations were calculated between RE of 9 genes in adenocarcinomas and the stage, and GS; also, between RE of 2 genes and the fusion presence; and between RE of 4 genes and PTEN expression. CONCLUSIONS Several gene expression patterns were identified that correlated with the GS, stage and molecular characteristics of tumors, i.e. presence of the TMPRSS2/ERG fusion and alterations in PTEN expression. These expression patterns can be used for molecular profiling of prostate tumors, with the aim to develop personalized medicine approaches. However, the proposed profiling requires a more detailed analysis and a larger cohort of patients with prostate tumor.
Antifungal activity of lichen compounds against dermatophytes: a review

The growth rate inhibition of dermatophytes by compounds extracted by acetone, ethanol, methanol and water derived from representatives of several lichen genera (e.g. Caloplaca, Everniastrum, Heterodermia, Hypotrachyna, Platismatia and Ramalina) were compared on the basis of a worldwide review of published research. The examined dermatophytes included Epidermophyton floccosum, Microsporum audouinii, M. canis, M. gypseum, M. nanum, Trichophyton longifusus, T. mentagrophytes, T. rubrum, T. tonsurans and T. violaceum. The influence of selected secondary lichen compounds, for example, usnic acid, on the growth rates of these dermatophytes was also reviewed. The measurement of inhibition by lichen compounds was performed by several methods, but mostly those employing disc diffusion, broth dilution and agar dilution. The fungicidal activity of water‐extracted compounds from Heterodermia leucomela and Hypotrachyna cirrhata and of methanol‐extracted compounds from Evernia divaricata and Ramalina pollinaria, as well as protolichesterinic and 2‐hydroxy‐4‐methoxy‐3,6‐dimethylbenzoic acids, are distinguished.