Miracle-dz/UniFAR-FTUs huggingface dataset:
Narrow-Margin Hepatectomy Resulted in Higher Recurrence and Lower Overall Survival for R0 Resection Hepatocellular Carcinoma

Purpose To evaluate the impact of resection margin on recurrence pattern and survival for hepatocellular carcinoma (HCC) with narrow margin resection, with the aim to guide postoperative treatment. Materials and Methods Two hundred forty HCC patients after curative hepatectomy between 2014 and 2016 were reviewed retrospectively. The cases were divided into narrow-margin (width of resection margin <1cm, n=106) and wide-margin (width of resection margin ≥1cm, n=134) groups based on the width of resection margin. Recurrence pattern, recurrence-free survival (RFS), and overall survival (OS) were compared between the above two groups. An additional cohort of nine cases with positive margin plus post-operative stereotactic body radiotherapy (SBRT) was also analyzed for the recurrence pattern. Results Postoperative recurrence was found in 128 (53.3%) patients. The recurrence rate was significantly higher in narrow-margin group than that in wide-margin group (P=0.001), especially for the pattern of marginal recurrence (20.8 vs. 4.5%, P=0.003). The 1-, 2-, 3-year RFS rates for the narrow-margin and wide-margin groups were 55.8, 43.9, 36.9, and 78.7, 67.9, 60.2%, respectively, with significant difference between the two groups (P<0.001). Patients with narrow margin showed a tendency of decreased OS than those with wide margin (P<0.001). As comparison, the nine cases with positive margin treated with postoperative SBRT showed low recurrence rate and no marginal recurrence was found. Conclusion Patients with narrow resection margin were associated with higher recurrence rate and worse survival than those with wide resection margin. These patients may benefit from adjuvant local treatment, such as radiotherapy.
Tourist Preferences for Seamount Conservation in the Galapagos Marine Reserve

Seamounts provide oases of hard substrate in the deep sea that are frequently associated with locally enhanced biological productivity and diversity. There is now increasing recognition of their ecological and socio-economic importance. However, management strategies for these habitats are constrained not only by limited ecological understanding but by the general public’s understanding of the pressures facing these ecosystems. This study adds to the growing literature on willingness to pay for conservation of deep-sea ecosystems and species by undertaking a stated preference survey to assess tourist’s awareness of seamounts and their preferences for protection within the Galapagos Marine Reserve. Visitors’ perceptions of seamount biodiversity must be studied because tourists are key drivers of the Galapagos economy and account for 41% of the Marine Reserve budget. Our survey captured the attitudes, perceptions and willingness to pay of tourists for an increase in the entrance fee to the Galapagos Marine Reserve. Results showed tourists were willing to pay on average US$48.93 in addition to existing entrance fees. The results of this study support the willingness to develop a multiuse management plan for the Galapagos Marine Reserve, balancing conservation, local communities livelihoods and sustainable tourism. Our results evidence a willingness to support and fund conservation, which is of critical importance to both the Galapagos National Park and local non-governmental organizations heavily reliant for their work on entrance fees and donations respectively. Overall, the conclusion from this study is that, despite limited knowledge, visitors of the Galapagos Islands attach positive and significant values to the conservation of seamount biodiversity.
The Traditional Chinese Medicine Fuyou Formula Alleviates Precocious Puberty by Inhibiting GPR54/GnRH in the Hypothalamus

The purpose of this study was to explore the effect of the traditional Chinese medicine Fuyou formula on precocious puberty (PP). The Fy formula may exert an effect in female rats with PP and GT-7 cells through the GPR54/GnRH signaling pathway. To confirm the effect of the Fy formula on PP through the GPR54/GnRH signaling pathway, we first treated GT1-7 cells with the Fy formula and observed changes in the expression of related genes and proteins and in GnRH secretion. Then, we randomly divided young female Sprague-Dawley rats into the control group, model group, leuprorelin group and the Fy formula group. A PP model was established by injection of danazol on postnatal day 5, and the Fy formula was administered on PND15. The time of vaginal opening, the wet weights of the ovary and uterus, serum hormone levels and the expression of hypothalamic-related genes were observed. We found that the Fy formula delayed vaginal opening, decreased the wet weights and coefficients of the ovary and uterus, decreased the levels of serum hormones (E2, follicle-stimulating hormone and luteinizing hormone) and the cellular GnRH level, and downregulated the gene expression of Kiss1, GPR54 and GnRH in the hypothalamus and the gene and protein expression of GPR54 and GnRH in GT1-7 cells. In conclusion, the Fy formula may alleviate PP via the GPR54/GnRH signaling pathway.
Microwave Drying of Black Olive Slices : Effects on Total Phenolic Contents and Colour

In this study, the drying behaviour of black olive slices using microwave was investigated and the effects of microwave power on total phenolic content and colour were determined. Black olive slices were dried at different power levels (180, 360, and 540 W) using a microwave cabin. The results showed that the drying time of the olive slices decreased considerably as the microwave power increased. The total phenolic content of the product dried at 540 W was found to be significantly lower than those dried at 180 or 360 W. For the microwave power range studied, the use of an irreversible first-order model adequately described the decrease in the total phenolic content. The effects of microwave power level on changes of the surface temperatures and weight loss ratios of the olive slices were also determined. The temperature increase and the weight loss were the highest at 540 W during drying. Changes in the colour values (L*, a*, and b*) of the black olive slices during drying were statistically different ( P<0.05 ) for each microwave power level and the maximum colour change in brightness occurred drying at 360 W. It is thought that results obtained in this study will provide valuable data for the design of microwave drying systems used for drying of olive slices in pilot or industrial scales.
Hunting by the Stroke: How Foraging Drives Diving Behavior and Locomotion of East-Greenland Narwhals (Monodon monoceros)

Deep diving air-breathing species by necessity must balance submergence time and level of exercise during breath-holding: a low activity level preserves oxygen stores and allows longer duration submergence whereas high activity levels consume oxygen quickly and shorten submergence time. In this study, we combined high-resolution multi sensor animal-borne tag data to investigate diving behavior and locomotion styles of the narwhal (Monodon monoceros) (n = 13, mean record length 91 h)–a deep diving Arctic species. Narwhals in this study dove down to >800 m but despite the deep diving abilities, one-third of the dives (33%) were shallow (>100 m) and short in duration (<5 min). Narwhals utilized energy saving measures such as prolonged gliding during descent with increasing target depth but stroked actively throughout the ascent indicating excess oxygen storages. Foraging behavior, as detected by the presence of buzzes, was a key factor influencing dive depth and spinning behavior—the rolling movement of the animal along its longitudinal axes. Narwhals in East Greenland utilized two foraging strategies, while transiting and while stationary, with different target depths and buzzing rates. The first targeted deep-dwelling, possibly solitary prey items and the latter, more schooling prey closer to the surface. The buzzing rate during stationary foraging was on average twice as high as during transiting foraging. Spinning was an integrated part of narwhal swimming behavior but the amount of spinning was correlated with foraging behavior. The odds for spinning during all dive phases were 2–3 times higher during foraging than non-foraging. Due to the spinning behavior, stroking rate might be better suited for estimating energy consumption in narwhals than ODBA (overall dynamic body acceleration). The narwhal is considered as one of the most sensitive species to climate change–the results from this study can act as a baseline essential for evaluating changes in the behavior and energy usage of narwhals caused by stressors evolving in the Arctic.
Impacts of Acclimation in Warm-Low pH Conditions on the Physiology of the Sea Urchin Heliocidaris erythrogramma and Carryover Effects for Juvenile Offspring

Ocean warming (OW) and acidification (OA) affects nearly all aspects of marine organism physiology and it is important to consider both stressors when predicting responses to climate change. We investigated the effects of long-term exposure to OW and OA on the physiology of adults of the sea urchin, Heliocidaris erythrogramma, a species resident in the southeast Australia warming hotspot. The urchins were slowly introduced to stressor conditions in the laboratory over a 7-week adjustment period to three temperature (ambient, +2°C, +3°C) and two pH (ambient: pHT 8.0; −0.4 units: pHT 7.6) treatments. They were then maintained in a natural pattern of seasonal temperature and photoperiod change, and fixed pH, for 22 weeks. Survival was monitored through week 22 and metabolic rate was measured at 4 and 12 weeks of acclimation, feeding rate and ammonia excretion rate at 12 weeks and assimilation efficiency at 13 weeks. Acclimation to +3°C was deleterious regardless of pH. Mortality from week 6 indicated that recent marine heatwaves are likely to have been deleterious to this species. Acclimation to +2°C did not affect survival. Increased temperature decreased feeding and increased excretion rates, with no effect of acidification. While metabolic rate increased additively with temperature and low pH at week 4, there was no difference between treatments at week 12, indicating physiological acclimation in surviving urchins to stressful conditions. Regardless of treatment, H. erythrogramma had a net positive energy budget indicating that the responses were not due to energy limitation. To test for the effect of parental acclimation on offspring responses, the offspring of acclimated urchins were reared to the juvenile stage in OW and OA conditions. Parental acclimation to warming, but not acidification altered juvenile physiology with an increase in metabolic rate. Our results show that incorporation of gradual seasonal environmental change in long-term acclimation can influence outcomes, an important consideration in predicting the consequences of changing climate for marine species.
Comparative mRNA and LncRNA Analysis of the Molecular Mechanisms Associated With Low Silk Production in Bombyx mori

Naked pupa sericin and Naked pupa are two mutant strains of Bombyx mori with extremely low or no fibroin production compared to the Qiufeng and Baiyu strains, both of which exhibit very high silk fibroin production. However, the molecular mechanisms by which long non-coding RNAs regulate fibroin synthesis need further study. In this study, we performed high-throughput RNA-seq to investigate lncRNA and mRNA expression profiles in the posterior silk gland of Qiufeng, Baiyu, Nd-sD, and Nd silkworms at the third day of the 5th instar. Our efforts yielded 26,767 novel lncRNAs and 6,009 novel mRNAs, the expression levels of silk protein genes and silk gland transcription factors were decreased in Qiufeng vs. Nd-sD and Qiufeng vs. Nd, while those of many genes related to autophagy, apoptosis, RNA degradation, ubiquitin-mediated proteolysis and heat shock proteins were increased. Moreover, the expression of a large number of genes responsible for protein synthesis and secretion was significantly decreased in Nd. GO and KEGG analysis results showed that nucleotide excision repair, mRNA surveillance pathways, amino acid degradation, protein digestion and absorption, ER-associated degradation and proteasome pathways were significantly enriched for the Qiufeng vs. Nd-sD and Qiufeng vs. Nd comparisons. In conclusion, our findings contribute to the lncRNA and mRNA database of Bombyx mori, and the identified differentially expressed mRNAs and lncRNAs help to reveal the molecular mechanisms of low silk production in Nd-sD and Nd, providing new insights for improvement of silk yield and elucidation of silk mechanical properties.
Transporter Gene Regulation in Sandwich Cultured Human Hepatocytes Through the Activation of Constitutive Androstane Receptor (CAR) or Aryl Hydrocarbon Receptor (AhR)

The induction potentials of ligand-activated nuclear receptors on metabolizing enzyme genes are routinely tested for new chemical entities. However, regulations of drug transporter genes by the nuclear receptor ligands are underappreciated, especially in differentiated human hepatocyte cultures. In this study, gene induction by the ligands of constitutive androstane receptor (CAR) and aryl hydrocarbon receptor (AhR) was characterized in sandwich-cultured human hepatocytes (SCHH) from multiple donors. The cells were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), omeprazole (OP), 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO) and phenobarbital (PB) for three days. RNA samples were analyzed by qRT-PCR method. As expected, CITCO, the direct activator, and PB, the indirect activator of CAR, induced CYP3A4 (31 and 40-fold), CYP2B6 (24 and 28-fold) and UGT1A1 (2.9 and 4.2-fold), respectively. Conversely, TCDD and OP, the activators of AhR, induced CYP1A1 (38 and 37-fold), and UGT1A1 (4.3 and 5.0-fold), respectively. In addition, OP but not TCDD induced CY3A4 by about 61-fold. Twenty-four hepatic drug transporter genes were characterized, and of those, SLC51B was induced the most by PB and OP by about 3.3 and 6.5 fold, respectively. Marginal inductions (about 2-fold) of SLC47A1 and SLCO4C1 genes by PB, and ABCG2 gene by TCDD were observed. In contrast, SLC10A1 gene was suppressed about 2-fold by TCDD and CITCO. While clinical relevance of SLC51B gene induction or SLC10A1 gene suppression warrants further investigation, the results verified that the assessment of transporter gene inductions are not required for new drug entities, when a drug does not remarkably induce metabolizing enzyme genes by CAR and AhR activation.
Development of an Immune-Related Gene Signature for Prognosis in Melanoma

Melanoma remains a potentially deadly malignant tumor. The incidence of melanoma continues to rise. Immunotherapy has become a new treatment method and is widely used in a variety of tumors. Original melanoma data were downloaded from TCGA. ssGSEA was performed to classify them. GSVA software and the "hclust" package were used to analyze the data. The ESTIMATE algorithm screened DEGs. The edgeR package and Venn diagram identified valid immune-related genes. Univariate, LASSO and multivariate analyses were used to explore the hub genes. The "rms" package established the nomogram and calibrated the curve. Immune infiltration data were obtained from the TIMER database. Compared with that of samples in the high immune cell infiltration cluster, we found that the tumor purity of samples in the low immune cell infiltration cluster was higher. The immune score, ESTIMATE score and stromal score in the low immune cell infiltration cluster were lower. In the high immune cell infiltration cluster, the immune components were more abundant, while the tumor purity was lower. The expression levels of TIGIT, PDCD1, LAG3, HAVCR2, CTLA4 and the HLA family were also higher in the high immune cell infiltration cluster. Survival analysis showed that patients in the high immune cell infiltration cluster had shorter OS than patients in the low immune cell infiltration cluster. IGHV1-18, CXCL11, LTF, and HLA-DQB1 were identified as immune cell infiltration-related DEGs. The prognosis of melanoma was significantly negatively correlated with the infiltration of CD4+ T cells, CD8+ T cells, dendritic cells, neutrophils and macrophages. In this study, we identified immune-related melanoma core genes and relevant immune cell subtypes, which may be used in targeted therapy and immunotherapy of melanoma.
Determination of the Optimum Excitation Wavelength for the Parathyroid Gland Using a Near-Infrared Camera

When performing thyroid/parathyroid surgery, difficulty detecting the parathyroid gland is a common experience because it is frequently mistaken with surrounding structures, including the thyroid gland, lymph nodes, and fat. To obtain successful surgical results, the auto fluorescent property of the parathyroid gland occurring at 820–830 nm has been used. Intraoperative visualization and detection by fluorescence enable protection of the gland from damage and unintended removal. Use of a near-infrared (NIR) camera has been proposed to indicate the parathyroid gland, but the devices and success rates have varied. This study aimed to define optimum excitation wavelength (EWL) by measuring the EWL of the parathyroid gland for its autofluorescence. Glands were exposed to EWL at 10-nm intervals from 670–790 nm with a light-emitting diode monochromator; autofluorescence intensity was recorded with a conventional NIR video camera. Autofluorescence intensity curves of three normal parathyroid glands were depicted; the optimum EWL was measured as 760–770 nm. Also, the illumination of the surrounding structures were compared at the optimum EWL. The auto fluorescent intensity of the parathyroid gland was 2-fold greater than for surrounding structures. This difference in fluorescence intensity should enable distinction of the parathyroid gland from surrounding structures. The clarification of the optimum EWL can guide refinements of the NIR camera for better surgical outcomes by improving detection of the parathyroid glands. Also, an understanding of optimum EWL should lead to developments for microscopic devices to unravel the still unknown mechanisms of the intrinsic autofluorescence of the parathyroid gland.
A Dimerization Site at SCR-17/18 in Factor H Clarifies a New Mechanism for Complement Regulatory Control

Complement Factor H (CFH), with 20 short complement regulator (SCR) domains, regulates the alternative pathway of complement in part through the interaction of its C-terminal SCR-19 and SCR-20 domains with host cell-bound C3b and anionic oligosaccharides. In solution, CFH forms small amounts of oligomers, with one of its self-association sites being in the SCR-16/20 domains. In order to correlate CFH function with dimer formation and the occurrence of rare disease-associated variants in SCR-16/20, we identified the dimerization site in SCR-16/20. For this, we expressed, in Pichia pastoris, the five domains in SCR-16/20 and six fragments of this with one-three domains (SCR-19/20, SCR-18/20, SCR-17/18, SCR-16/18, SCR-17 and SCR-18). Size-exclusion chromatography suggested that SCR dimer formation occurred in several fragments. Dimer formation was clarified using analytical ultracentrifugation, where quantitative c(s) size distribution analyses showed that SCR-19/20 was monomeric, SCR-18/20 was slightly dimeric, SCR-16/20, SCR-16/18 and SCR-18 showed more dimer formation, and SCR-17 and SCR-17/18 were primarily dimeric with dissociation constants of ~5 µM. The combination of these results located the SCR-16/20 dimerization site at SCR-17 and SCR-18. X-ray solution scattering experiments and molecular modelling fits confirmed the dimer site to be at SCR-17/18, this dimer being a side-by-side association of the two domains. We propose that the self-association of CFH at SCR-17/18 enables higher concentrations of CFH to be achieved when SCR-19/20 are bound to host cell surfaces in order to protect these better during inflammation. Dimer formation at SCR-17/18 clarified the association of genetic variants throughout SCR-16/20 with renal disease.
Modeling the Ruminant Placenta-Pathogen Interactions in Apicomplexan Parasites: Current and Future Perspectives

Neospora caninum and Toxoplasma gondii are one of the main concerns of the livestock sector as they cause important economic losses in ruminants due to the reproductive failure. It is well-known that the interaction of these parasites with the placenta determines the course of infection, leading to fetal death or parasite transmission to the offspring. However, to advance the development of effective vaccines and treatments, there are still important gaps on knowledge on the placental host-parasite interactions that need to be addressed. Ruminant animal models are still an indispensable tool for providing a global view of the pathogenesis, lesions, and immune responses, but their utilization embraces important economic and ethics restrictions. Alternative in vitro systems based on caruncular and trophoblast cells, the key cellular components of placentomes, have emerged in the last years, but their use can only offer a partial view of the processes triggered after infection as they cannot mimic the complex placental architecture and neglect the activity of resident immune cells. These drawbacks could be solved using placental explants, broadly employed in human medicine, and able to preserve its cellular architecture and function. Despite the availability of such materials is constrained by their short shelf-life, the development of adequate cryopreservation protocols could expand their use for research purposes. Herein, we review and discuss existing (and potential) in vivo, in vitro, and ex vivo ruminant placental models that have proven useful to unravel the pathogenic mechanisms and the host immune responses responsible for fetal death (or protection) caused by neosporosis and toxoplasmosis.
Changes in the Ice-Front Position and Surface Elevation of Glaciar Pío XI, an Advancing Calving Glacier in the Southern Patagonia Icefield, From 2000–2018

Glaciar Pío XI has advanced and thickened over the past several decades in contrast to the generally retreating and thinning trends seen in other glaciers in the Southern Patagonia Icefield (SPI). To quantify recent changes in ice-front positions and glacier surface elevation over the ablation area of Glaciar Pío XI, we analyzed satellite data acquired from 2000 to 2018. Two major glacier termini, and most of the small outlet glaciers, showed advancing trends, including the largest advance (1,400 m), observed at the southern terminus during the study period. Surface elevation increased by 37.3 ± 0.4 m as a mean over the study area, and the rate of the increase accelerated by 135 ± 10% from Period 1 (2000–2007) to Period 2 (2007–2017/18). Elevation change during Period 1 was only slightly positive except for extraordinary thickening (∼20 m a−1) observed near the southern terminus and one of the outlet glacier fronts, whereas significant thickening (∼2.7 m a−1) occurred over the entire ablation area during Period 2. Satellite imagery showed an emergence of sedimentary mounds in front of the southern terminus, suggesting that reduction in frontal ablation and increasingly compressive flow regime are the main drivers of the recent rapid thickening and advance. Most likely, the influence of the sediment deposition on the southern terminus subsequently propagated to the northern terminus and upper reaches of the glacier. The rate of ice mass increase during the study period was 0.48 ± 0.03 Gt a−1, which corresponds to 4% of the total mass loss from the SPI from 2000 to 2015/16.