Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular biology of pancreatic neuroendocrine tumors: From mechanism to translation

Pancreatic neuroendocrine tumors (pNETs) are a group of heterogeneous tumors originated from progenitor cells. As these tumors are predominantly non-functional, most of them display asymptomatic characteristics, making it difficult to be realized from early onset. Therefore, patients with pNETs are usually diagnosed with metastatic disease or at a late disease stage. The relatively low incidence also limits our understanding of the biological background of pNETs, which largely impair the development of new effective drugs. The fact that up to 10% of pNETs develop in patients with genetic syndromes have promoted researchers to focus on the gene mutations and driver mutations in MEN1, DAXX/ATRX and mTOR signaling pathway genes have been implicated in disease development and progression. Recent advances in sequencing technologies have further enriched our knowledge of the complex molecular landscape of pNETs, pointing out crucial roles of genes in DNA damage pathways, chromosomal and telomere alterations and epigenetic dysregulation. These novel findings may not only benefit early diagnosis of pNETs, but also help to uncover tumor heterogeneity and shape the future of translational medical treatment. In this review, we focus on the current molecular biology of pNETs and decipher how these findings may translate into future development of targeted therapy.
Porcine bile acids promote the utilization of fat and vitamin A under low-fat diets

Fat-soluble vitamin malabsorption may occur due to low dietary fat content, even in the presence of an adequate supply of fat-soluble vitamins. Bile acids (BAs) have been confirmed as emulsifiers to promote fat absorption in high-fat diets. However, there are no direct evidence of exogenous BAs promoting the utilization of fat-soluble vitamins associated with fat absorption in vitro and in vivo. Therefore, we chose laying hens as model animals, as their diet usually does not contain much fat, to expand the study of BAs. BAs were investigated in vitro for emulsification, simulated intestinal digestion, and release rate of fat-soluble vitamins. Subsequently, a total of 450 healthy 45-week-old Hy-Line Gray laying hens were chosen for an 84-day feeding trial. They were divided into five treatments, feeding diets supplemented with 0, 30, 60, 90, and 120 mg/kg BAs, respectively. No extra fat was added to the basic diet (crude fat was 3.23%). In vitro, BAs effectively emulsified the water-oil interface. Moreover, BAs promoted the hydrolysis of fat by lipase to release more fatty acids. Although BAs increased the release rates of vitamins A, D, and E from vegetable oils, BAs improved for the digestion of vitamin A more effectively. Dietary supplementation of 60 mg/kg BAs in laying hens markedly improved the laying performance. The total number of follicles in ovaries increased in 30 and 60 mg/kg BAs groups. Both the crude fat and total energy utilization rates of BAs groups were improved. Lipase and lipoprotein lipase activities were enhanced in the small intestine in 60, 90, and 120 mg/kg BAs groups. Furthermore, we observed an increase in vitamin A content in the liver and serum of laying hens in the 60, 90, and 120 mg/kg BAs groups. The serum IgA content in the 90 and 120 mg/kg BAs groups was significantly improved. A decrease in serum malondialdehyde levels and an increase in glutathione peroxidase activity were also observed in BAs groups. The present study concluded that BAs promoted the absorption of vitamin A by promoting the absorption of fat even under low-fat diets, thereupon improving the reproduction and health of model animals.
Differential modulation of lung aquaporins among other pathophysiological markers in acute (Cl2 gas) and chronic (carbon nanoparticles, cigarette smoke) respiratory toxicity mouse models

Inhaled toxic chemicals and particulates are known to disrupt lung homeostasis causing pulmonary toxicity and tissue injury. However, biomarkers of such exposures and their underlying mechanisms are poorly understood, especially for emerging toxicants such as engineered nanoparticles and chemical threat agents such as chlorine gas (Cl2). Aquaporins (AQPs), commonly referred to as water channels, are known to play roles in lung homeostasis and pathophysiology. However, little is known on their regulation in toxicant-induced lung injuries. Here, we compared four lung toxicity models namely, acute chemical exposure (Cl2)-, chronic particulate exposure (carbon nanotubes/CNT)-, chronic chemical exposure (cigarette smoke extract/CSE)-, and a chronic co-exposure (CNT + CSE)- model, for modulation of lung aquaporins (AQPs 1, 3, 4, and 5) in relation to other pathophysiological endpoints. These included markers of compromised state of lung mucosal lining [mucin 5b (MUC5B) and surfactant protein A (SP-A)] and lung-blood barrier [protein content in bronchoalveolar lavage (BAL) fluid and, cell tight junction proteins occludin and zona-occludens]. The results showed toxicity model-specific regulation of AQPs measured in terms of mRNA abundance. A differential upregulation was observed for AQP1 in acute Cl2 exposure model (14.71-fold; p = 0.002) and AQP3 in chronic CNT exposure model (3.83-fold; p = 0.044). In contrast, AQP4 was downregulated in chronic CSE model whereas AQP5 showed no significant change in any of the models. SP-A and MUC5B expression showed a decreasing pattern across all toxicity models except the acute Cl2 toxicity model, which showed a highly significant upregulation of MUC5B (25.95-fold; p = 0.003). This was consistent with other significant pathophysiological changes observed in this acute model, particularly a compromised lung epithelial-endothelial barrier indicated by significantly increased protein infiltration and expression of tight junction proteins, and more severe histopathological (structural and immunological) changes. To our knowledge, this is the first report on lung AQPs as molecular targets of the study toxicants. The differentially regulated AQPs, AQP1 in acute Cl2 exposure versus AQP3 in chronic CNT nanoparticle exposure, in conjunction with the corresponding differentially impacted pathophysiological endpoints (particularly MUC5B) could potentially serve as predictive markers of toxicant type-specific pulmonary injury and as candidates for future investigation for clinical intervention.
Long-term excessive application of K2SO4 fertilizer alters bacterial community and functional pathway of tobacco-planting soil

To improve tobacco leaf quality, excessive K2SO4 fertilizers were applied to soils in major tobacco-planting areas in China. However, the effects of K2SO4 application on soil microbial community and functions are still unclear. An eight-year field experiment with three kinds of K2SO4 amounts (low amount, K2O 82.57 kg hm-2, LK; moderate amount, K2O 165.07 kg hm-2, MK; high amount, K2O 247.58 kg hm-2, HK) was established to assess the effects of K2SO4 application on the chemical and bacterial characteristics of tobacco-planting soil using 16S rRNA gene and metagenomic sequencing approaches. Results showed that HK led to lower pH and higher nitrogen (N), potassium (K), sulfur(S) and organic matter contents of the soil than LK. The bacterial community composition of HK was significantly different from those of MK and LK, while these of MK and LK were similar. Compared to LK, HK increased the relative abundance of predicted copiotrophic groups (e.g. Burkholderiaceae, Rhodospirillaceae families and Ellin6067 genus) and potentially beneficial bacteria (e.g. Gemmatimonadetes phylum and Bacillus genus) associated with pathogens and heavy metal resistance, N fixation, dissolution of phosphorus and K. While some oligotrophic taxa (e.g. Acidobacteria phylum) related to carbon, N metabolism exhibited adverse responses to HK. Metagenomic analysis suggested that the improvement of pathways related to carbohydrate metabolism and genetic information processing by HK might be the self-protection mechanism of microorganisms against environmental stress. Besides, the redundancy analysis and variation partitioning analysis showed that soil pH, available K and S were the primary soil factors in shifting the bacterial community and KEGG pathways. This study provides a clear understanding of the responses of soil microbial communities and potential functions to excessive application of K2SO4 in tobacco-planting soil.
Melatonin enhanced low-temperature combined with low-light tolerance of pepper (Capsicum annuum L.) seedlings by regulating root growth, antioxidant defense system, and osmotic adjustment

Melatonin (MT) is an important biologically active hormone that plays a vital role in plant growth and development. In particular, it has been investigated for its roles in abiotic stress management. In this study, pepper seedlings were subjected to low-temperature combined with low-light stress (LL) (15/5°C, 100 μmol m-2s-1) prior to a foliar spray of 200mM MT for 168h to investigate the protective role of MT in pepper seedlings. Our results demonstrated that LL stress negatively affected root growth, and accelerated the accumulation of reactive oxygen species (ROS), including H2O2 and O 2 − , changed the osmolytes contents, and antioxidative system. However, these were reversed by exogenous MT application. MT effectively promoted the root growth as indicated by significant increase in root length, surface area, root volume, tips, forks, and crossings. In addition, MT reduced the burst of ROS and MDA contents induced by LL, enhanced the activities of SOD, CAT, POD, APX, DHAR, and MDHAR resulted by upregulated expressions of CaSOD, CaPOD, CaCAT, CaAPX, CaDHAR, and CaMDHAR, and elevated the contents of AsA and GSH, declined DHA and GSSH contents, which prevented membrane lipid peroxidation and protected plants from oxidative damages under LL stress. Furthermore, seedlings treated with MT released high contents of soluble sugar and soluble protein in leave, which might enhance LL tolerance by maintaining substance biosynthesis and maintaining cellular homeostasis resulted by high levels of osmolytes and carbohydrate in the cytosol. Our current findings confirmed the mitigating potential of MT application for LL stress by promoting pepper root growth, improving antioxidative defense system, ascorbate-glutathione cycle, and osmotic adjustment.
Uncertainties in ocean biogeochemical simulations: Application of ensemble data assimilation to a one-dimensional model

Marine biogeochemical (BGC) models are highly uncertain in their parameterization. The value of the BGC parameters are poorly known and lead to large uncertainties in the model outputs. This study focuses on the uncertainty quantification of model fields and parameters within a one-dimensional (1-D) ocean BGC model applying ensemble data assimilation. We applied an ensemble Kalman filter provided by the Parallel Data Assimilation Framework (PDAF) into a 1-D vertical configuration of the BGC model Regulated Ecosystem Model 2 (REcoM2) at two BGC time-series stations: the Bermuda Atlantic Time-series Study (BATS) and the Dynamique des Flux Atmosphériques en Méditerranée (DYFAMED). We assimilated 5-day satellite chlorophyll-a (chl-a) concentration and monthly in situ net primary production (NPP) data for 3 years to jointly estimate 10 preselected key BGC parameters and the model state. The estimated set of parameters resulted in improvements in the model prediction up to 66% for the surface chl-a and 56% for NPP. Results show that assimilating satellite chl-a concentration data alone degraded the prediction of NPP. Simultaneous assimilation of the satellite chl-a data and in situ NPP data improved both surface chl-a and NPP simulations. We found that correlations between parameters preclude estimating parameters independently. Co-dependencies between parameters also indicate that there is not a unique set of optimal parameters. Incorporation of proper uncertainty estimation in BGC predictions, therefore, requires ensemble simulations with varying parameter values.
Innate immune checkpoint inhibitor resistance is associated with melanoma sub-types exhibiting invasive and de-differentiated gene expression signatures

Melanoma is a highly aggressive skin cancer, which, although highly immunogenic, frequently escapes the body’s immune defences. Immune checkpoint inhibitors (ICI), such as anti-PD1, anti-PDL1, and anti-CTLA4 antibodies lead to reactivation of immune pathways, promoting rejection of melanoma. However, the benefits of ICI therapy remain limited to a relatively small proportion of patients who do not exhibit ICI resistance. Moreover, the precise mechanisms underlying innate and acquired ICI resistance remain unclear. Here, we have investigated differences in melanoma tissues in responder and non-responder patients to anti-PD1 therapy in terms of tumour and immune cell gene-associated signatures. We performed multi-omics investigations on melanoma tumour tissues, which were collected from patients before starting treatment with anti-PD1 immune checkpoint inhibitors. Patients were subsequently categorized into responders and non-responders to anti-PD1 therapy based on RECIST criteria. Multi-omics analyses included RNA-Seq and NanoString analysis. From RNA-Seq data we carried out HLA phenotyping as well as gene enrichment analysis, pathway enrichment analysis and immune cell deconvolution studies. Consistent with previous studies, our data showed that responders to anti-PD1 therapy had higher immune scores (median immune score for responders = 0.1335, median immune score for non-responders = 0.05426, p-value = 0.01, Mann-Whitney U two-tailed exact test) compared to the non-responders. Responder melanomas were more highly enriched with a combination of CD8+ T cells, dendritic cells (p-value = 0.03) and an M1 subtype of macrophages (p-value = 0.001). In addition, melanomas from responder patients exhibited a more differentiated gene expression pattern, with high proliferative- and low invasive-associated gene expression signatures, whereas tumours from non-responders exhibited high invasive- and frequently neural crest-like cell type gene expression signatures. Our findings suggest that non-responder melanomas to anti-PD1 therapy exhibit a de-differentiated gene expression signature, associated with poorer immune cell infiltration, which establishes a gene expression pattern characteristic of innate resistance to anti-PD1 therapy. Improved understanding of tumour-intrinsic gene expression patterns associated with response to anti-PD1 therapy will help to identify predictive biomarkers of ICI response and may help to identify new targets for anticancer treatment, especially with a capacity to function as adjuvants to improve ICI outcomes.
Association between bodyweight perception, nutritional status, and weight control practices: A cross-sectional analysis from the Chilean Health Survey 2016–2017

This research aimed (1) to examine the agreement between body mass index (BMI)-based nutritional status and perceived nutritional status overall and by socio-demographic factors and (2) to state the association between the accuracy of weight perception and weight control practices in the Chilean adult population. A population-based cross-sectional study was carried out with 5,192 Chilean adult participants from the Chilean National Health Survey 2016–2017. Agreement between BMI-based weight status and body weight perception for the total sample and across subgroups was determined using the weighted kappa coefficient. The agreement between BMI-based and perceived nutritional status of the total sample was fair (kappa = 0.38). A higher rate of weight perception accuracy was identified in women, younger respondents, and participants with higher education, a higher income, and from urban areas than their counterparts. Respondents with overweight or obesity tended to underestimate their nutritional status. Actions to lose weight were higher in those who had the right perception of their overweight/obesity condition and those who overestimated their body weight, regardless of their nutritional status. In all groups, weight loss behaviors were more related to the perceived than the BMI-based nutritional status. The consequences of accurate perception of the nutritional status are discussed including its effects on body weight and mental health.
Design and realization of a novel haptic graspable interface for augmenting touch sensations

A novel haptic grasper that renders touch sensations to the user in 3-DoF (degrees of freedom), namely linear, rotary, and grasping motions, is presented. The touch sensations of the grasper include the combination of kinesthetic and tactile modalities such as stiffness, texture, and shape. The device is equipped with two swappable modular segments that provide stiffness and shape sensations. To increase the haptic fidelity, the textural surfaces that surround the outer surface of the segments are equipped with vibro-actuators underneath them. These vibro-actuators contribute to increasing the number of perceivable textures by varying amplitude, frequency, duration, and envelope of vibrations. The proposed device is characterized in terms of stiffness, shape and texture rendering capabilities. The experimental results validate the effectiveness of the developed haptic grasper in virtual/remote interactions. Also, the user studies and statistical analysis demonstrate that the users could perceive the high-fidelity haptic feedback with the unified sensations of kinesthetic and tactile cues.
A Pilot Study of Sidewalk Equity in Seattle Using Crowdsourced Sidewalk Assessment Data

We examine the potential of using large-scale open crowdsourced sidewalk data from Project Sidewalk to study the distribution and condition of sidewalks in Seattle, WA. While potentially noisier than professionally gathered sidewalk datasets, crowdsourced data enables large, cross-regional studies that would be otherwise expensive and difﬁcult to manage. As an initial case study, we examine spatial patterns of sidewalk quality in Seattle and their relationship to racial diversity, income level, built density, and transit modes. We close with a reﬂection on our approach, key limitations, and opportunities for future work.
Adenosine receptor agonists suppress macrophage inflammatory protein-1α production and collageninduced arthritis.

---------------------------------------------------------------------------------------------------------------------------------------ABSTRACT: The production of pro- and anti-inflammatory cytokines is modulated by ligands of various adenosine receptor subtypes. In this study, we looked at how adenosine and different ligands for the adenosine collageninduced arthritis. IB-MECA decreased neutrophil infiltration and inhibited the production of MIP-1a, IL-12, and nitrotyrosine (a marker of reactive nitrogen species) in the paws.We conclude that adenosine receptor agonists, particularly the A3 agonist IB-MECA, inhibit MIP-a synthesis and have anti-inflammatory properties. As a result, stimulating adenosine receptor subtypes A3 and A2 may be a promising technique for the treatment of acute and chronic inflammatory diseases. with a 32P-radiolabeled oligonucleotide probe for 18S ribosomal RNA after probing for MIP-1a.In RAN 264.3 cells, the effect of IB-MECA on cytokine and NO production
High temperature Raman analysis of hydrogen phase IV from molecular dynamics

We extend our previous studies on phase IV of solid hydrogen by employing larger cells and k-sampling. We show that uncorrelated hexagonal rotations in the weakly bounded G"-layers are needed to account for the experimentally measured Raman spectrum. In large simulations we find no evidence of proton diffusion or layer fluctuations, which we believe are the result of finite size effects. In calculations at higher pressures (above 400 GPa) we identify a new possible candidate for phase IV. We, finally, proposed a revised phase diagram based on our previous and present results.
That is a good looking car !: Visual Aspect based Sentiment Controlled Personalized Response Generation

In a conversational system, generating utter-001 ances that communicate consistent and rele-002 vant preferences is vital for more personal-003 ized conversations. In this paper, we pro-004 pose a task of generating utterances grounded 005 on some assigned aspect-preferences-profile. 006 These aspect-preference profiles consist of a list 007 of aspect-sentiment tuples, denoting the pref-008 erence of the speaker for some aspect in the 009 form of sentiment (“positive” or “negative”). 010 Since no prior dataset containing such profiles 011 is available, we enhance Image-Chat data by 012 assigning these profiles to each user in a con-013 versation. The conversations in this dataset are 014 based on an image, therefore the aspects are 015 present in images as well as dialogue history. 016 We build a BERT and ResNet-based encoder-017 decoder model with a memory network to store 018 preference-profile. Through our experiments, 019 we show that our model can generate responses 020 that convey the sentiment of relevant aspects 021 in accordance with the assigned profile. Both 022 automatic and manual evaluations show the ef-023 fectiveness of our model and dataset 1 . Our 024 proposed system when using these profiles 025 achieves a BLEU-1 score of 15.93 on this new 026 task, which is an improvement of 2.92 points 027 from the baseline experiment that does not use 028 aspect-preference profiles. 029
Psych-E: Conﬁgurable Response Generation using Personality Traits and Pragmatics

Personality traits inﬂuence human actions and 001 thoughts, which is manifested in day to day 002 conversations. Although glimpses of person-003 ality traits are observable in existing open do-004 main conversation corpora, leveraging generic 005 language modelling for response generation 006 overlooks the interlocutor idiosyncrasies, re-007 sulting in non-customizable personality agnos-008 tic responses. With the motivation of enabling 009 conﬁgurable response generators, in this paper 010 we experiment with ways to ground neural re-011 sponse generators based on both (i) interlocu-012 tor Big-5 personality traits, and (ii) discourse 013 intent as control codes, training an end-to-end 014 dialogue agent that can not only leverage the 015 control codes as policy for nuanced response 016 generation, but also predict and decide the gen-017 eration policy to be utilized by the generator. 018 Since most of the existing large scale open do-019 main chat corpora do not include Big-5 person-020 ality traits and discourse intent, we employ au-021 tomatic annotation schemes to enrich the cor-022 pora with policy consisting of noisy estimates 023 of these features as control codes, and lever-024 age automatic evaluation metrics along with 025 ablation studies, to assess the impact of us-026 ing control codes for response generation. Ad-027 ditionally, we leverage human judgement to 028 demonstrate the effectiveness of using such 029 personality and pragmatics based policy for re-030 sponse generation. Our experiments illustrate 031 the effectiveness of this strategy resulting in 032 improvements to existing benchmarks. 033