Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting Purchase Behavior of Website Audiences

ABSTRACT This paper proposes a methodological framework that extends the advantages of behavioral targeting while preserving the privacy of the individual. Instead of profiling individual users according to their general interests, we profile website audiences according to their online purchase behavior. This presents a trade-off between looser, aggregate audience profiling and deeper understanding of actual purchase behavior, the holy grail of online advertising. Our framework is based on the analysis of raw clickstream data of Web users who explicitly agreed to participate in an online audience panel. We experiment with data collected by an online analytics company, SimilarWeb, which consists of 3,463,796 records of online purchases and 1.1 billion records of Website visits. We train a multilabeled classification model on the clickstream of panel members with distinctive online purchase profiles to predict the purchase potential of the entire panel. We aggregate the individual purchase behavior profiles (both ground-truth and predicted) into purchase behavior profiles of Web domain audiences and test the resulting methodology on 3,408 Web domains, with very promising results. If privacy-related regulation tightens up in the near future, the proposed panel-based, purchase-focused ad targeting mechanism might be the panacea for online advertisers.
Comparison of Glucose and Satiety Hormone Response to Oral Glucose vs. Two Mixed-Nutrient Meals in Rats

The obesity epidemic is driving interest in identifying strategies that enhance appetite control by altering the secretion of hormones that regulate satiety and food intake. An appropriate nutrient stimulus, such as a meal or oral nutrient solution, is needed to elicit the secretion of satiety hormones in order to evaluate the impact of dietary and other interventions. Our objective was to compare the effects of oral glucose vs. mixed nutrients on plasma concentrations of glucose and appetite-regulating hormones to determine the most appropriate oral nutrient challenge to trigger robust hormone secretion. A 120 min oral glucose tolerance test (OGTT) was compared with two meal tolerance tests (MTT) of differing formulation to evaluate glucose and satiety hormone responses. Following overnight feed deprivation, male Sprague-Dawley rats were given one of three oral gavages with equal carbohydrate content (2 g CHO/kg) in the form of: (1) Dextrose, (2) Ensure®, or (3) Mixed Meal. A fourth group was given saline as a control. Blood was collected via tail snip and analyzed for glucose, insulin, GLP-1, GIP, PYY, amylin, leptin, and ghrelin. Dextrose resulted in the highest blood glucose at T15 (P = 0.014), while the mixed meal was significantly higher than saline from T30-T120 (P < 0.05). Insulin was higher at T15 with dextrose compared to saline (P = 0.031) and Ensure® (P = 0.033). GLP-1 tAUC was significantly higher with dextrose compared to mixed meal (P = 0.04) while GIP tAUC was higher with dextrose and mixed meal compared to saline (P < 0.05). Changes in tAUC for insulin, amylin, leptin, ghrelin, and PYY did not reach significance. Based on these findings, dextrose appears to provide a robust acute glycemic and hormone response and is therefore likely an appropriate oral solution to reproducibly test the impact of various dietary, surgical, or pharmacological interventions on glucose and satiety hormone response.
Recovery of quality of life after laparoscopic myomectomy

It is commonly thought that laparoscopic surgery leads to faster postoperative recovery for its low invasiveness. We evaluated postoperative quality of life (QOL) after laparoscopic myomectomy (LM) by using the Euro‐QOL 5 dimension (EQ‐5D) score and analyzed its relationship to surgical factors.
Affective Communication through Air Jet Stimulation: Evidence from Event-Related Potentials

ABSTRACT In this article, effectiveness of air jet stimulation in mediated emotional communication was investigated by assessing cross-modal influences of visual emotional expressions on tactile perception. Brain responses to combined visual faces and air jet stimuli were measured using event-related potentials; whereas, emotional responses were assessed using self-reported pleasantness of the tactile stimulation. ERP results reveal significant differences between the different facial expressions for the same tactile air-jet intensity in the somatosensory area. Moreover, participants’ pleasantness ratings suggest an effect of the visual stimulus on the difference tactile conditions that correspond to air jet stimulation intensities: low, medium, and high. These promising results provide evidence in the potential efficiency of this stimulation technique in activating skin receptors that play an important role in social and affective behaviors.
Nucleolus vs Nucleus Count for Identifying Spiral Ganglion in Human Temporal Bone.

OBJECTIVES Spiral ganglion (SG) counting is used in experimental studies conducted on age-, noise-, and drug-induced sensorineural hearing loss, as well as in the assessment of cochlear implant performances. Different methods of counting have been reported, but no definite standardization of such procedure has been published. The aim of our study is to identify the best method to count human spiral ganglions (SGs). MATERIALS AND METHODS By identification of nuclei or nucleoli as described by Schucknect, seven researchers with different experience levels counted SGs in 123 human temporal bones (TBs). Data on time of post-mortem bone removal post-mortem, methods of specimen's fixation, decalcification, and coloration were collected to test their possible influence on human tissue. Percentage, two-tailed t-test, Spearman's test, and one-way ANOVA were used to analyze the data. RESULTS Nucleoli were identified in 61% of cases, whereas nuclei were recognized in 100% of cases (p<0.005). Nucleoli presence in all four segments in the same temporal bone (TB) was observed in 69 cases (92%), whereas nuclei were identified in all four segments in 103 cases (83.7%) (p<0.001). The junior investigators requested a double check by the seniors in 25 (20.3%) cases for identifying and counting nucleoli, whereas the senior researchers showed no doubts in their identification and count. The only parameter positively affecting nucleoli identification in tissue preparation was bone removal for <12 h with respect to longer post-mortem time (p<0.001). CONCLUSION We suggest counting nuclei, rather than nucleoli, for spiral ganglion computation because of easier recognition of nuclei, especially in case of investigator's limited experience.
Structures of human cytochrome P450 1A1 with bergamottin and erlotinib reveal active-site modifications for binding of diverse ligands

Human cytochrome P450 1A1 (CYP1A1) is an extrahepatic enzyme involved in the monooxygenation of structurally diverse compounds ranging from natural products to drugs and protoxins. Because CYP1A1 has a role in human carcinogenesis, inhibiting its activity may potentially aid in cancer chemoprevention, whereas utilizing CYP1A1's oxidative activity could help selectively activate anticancer prodrugs. Such potential therapeutic purposes require detailed knowledge of CYP1A1's interactions with potential ligands. Known CYP1A1 ligands also vary substantially in size, and it has not been apparent from a single existing CYP1A1 structure how larger, structurally diverse ligands are accommodated within the enclosed active site. Here, two new X-ray structures with the natural product furanocoumarin bergamottin (at 2.85 Å resolution) and the lung cancer drug erlotinib (3.0 Å) revealed binding orientations consistent with the formation of innocuous metabolites and of toxic metabolites, respectively. They also disclosed local changes in the roof of the active site that enlarge the active site and ultimately form a channel to the protein exterior. Although further structural modifications would be required to accommodate the largest CYP1A1 ligands, knowing which components of the active site are malleable provides powerful information for those attempting to use computational approaches to predict compound binding and substrate metabolism by this clinically relevant monooxygenase.
The relationship between histone posttranslational modification and DNA damage signaling and repair

Abstract Purpose: The cellular response to DNA damage occurs in the context of an organized chromatin environment in order to maintain genome integrity. Immediately after DNA damage, an array of histone modifications are induced to relieve the physical constraints of the chromatin environment, mark the site as damaged, and function as a platform for the assembly of mediator and effector proteins of DNA damage response signaling pathway. Changes in chromatin structure in the vicinity of the DNA double-strand break (DSB) facilitates the efficient initiation of the DNA damage signaling cascade. Failure of induction of DNA damage responsive histone modifications may lead to genome instability and cancer. Here we will discuss our current understanding of the DNA damage responsive histone modifications and their role in DNA repair as well as their implications for genome stability. We further discuss recent studies which highlight not only how histone modification has involved in the signaling and remodeling at the DSB but also how it influences the DNA repair pathway choice. Conclusions: Histone modifications pattern alter during the induction of DNA DSBs induction as well as during the repair and recovery phase of DNA damage response. It will be interesting to understand more precisely, how DSBs within chromatin are repaired by HR and NHEJ. The emergence of proteomic and genomic technologies in combination with advanced microscopy and imaging methods will help in better understanding the role of chromatin environment in the regulation of genome stability.
Complexation of novel thiomers and insulin to protect against in vitro enzymatic degradation – towards oral insulin delivery

Abstract A significant barrier to oral insulin delivery is its enzymatic degradation in the gut. Nano-sized polymer-insulin polyelectrolyte complexes (PECS) have been developed to protect insulin against enzymatic degradation. Poly(allylamine) (Paa) was trimethylated to yield QPaa. Thiolation of Paa and QPaa was achieved by attaching either N-acetylcysteine (NAC) or thiobutylamidine (TBA) ligands (Paa-NAC/QPaa-NAC and Paa-TBA/QPaa-TBA thiomers). PEC formulations were prepared in Tris buffer (pH 7.4) at various polymer: insulin mass ratios (0.2:1–2:1). PECS were characterized by %transmittance of light and photon correlation spectroscopy. Insulin complexation efficiency and enzyme-protective effect of these complexes were determined by HPLC. Complexation with insulin was found to be optimal at mass ratios of 0.4–1:1 for all polymers. PECS in this mass range were positively-charged (20–40 mV), nanoparticles (50–200 nm), with high insulin complexation efficiency (>90%). Complexation with TBA polymers appeared to result in disulfide bridge formation between the polymers and insulin. In vitro enzymatic degradation assays of QPaa, Paa-NAC, and QPaa-NAC PECS showed that they all offered some protection against insulin degradation by trypsin and α-chymotrypsin, but not from pepsin. QPaa-NAC complexes with insulin are the most promising formulation for future work, given their ability to offer protection against intestinal enzymes. This work highlights the importance of optimizing polymer structure in the delivery of proteins.
Reduced Free Energy Perturbation/Hamiltonian Replica Exchange Molecular Dynamics Method with Unbiased Alchemical Thermodynamic Axis.

Replica-exchange molecular dynamics (REMD) has been proven to efficiently improve the convergence of free-energy perturbation (FEP) calculations involving considerable reorganization of their surrounding. We previously introduced the FEP/(λ,H)-REMD algorithm for ligand binding, in which replicas along the alchemical thermodynamic coupling axis λ were expanded as a series of Hamiltonian boosted replicas along a second axis to form a two-dimensional replica-exchange exchange map [Jiang, W. ; Roux, B. , J. Chem. Theory Comput. 2010, 6 (9), 2559-2565]. Aiming to achieve a similar performance at a lower computational cost, we propose here a modified version of this algorithm in which only the end-states along the alchemical axis are augmented by boosted replicas. The reduced FEP/(λ,H)-REMD method with one-dimensional unbiased alchemical thermodynamic coupling axis λ is implemented on the basis of generic multiple copy algorithm (MCA) module of the biomolecular simulation program NAMD. The flexible MCA framework of NAMD enables a user to design customized replica-exchange patterns through Tcl scripting in the context of a highly parallelized simulation program without touching the source code. Two Hamiltonian tempering boosting scheme were examined with the new algorithm: a first one based on potential energy rescaling of a preidentified "solute" and a second one via the introduction of flattening torsional free-energy barriers. As two illustrative examples with reliable experiment data, the absolute binding free energies of p-xylene and n-butylbenzene to the nonpolar cavity of the L99A mutant of T4 lysozyme were calculated. The tests demonstrate that the new protocol efficiently enhances the sampling of torsional motions for backbone and side chains around the binding pocket and accelerates the convergence of the free-energy computations.
Cytological Findings of Gastrointestinal Stromal Tumor-Derived Bone Metastasis

Objective: Procedures for diagnosing bone tumors should be rapid and minimally invasive. Thus, cytological examinations are more useful for such purposes than histological examinations. In order to identify cytomorphological findings that could be used to diagnose bone metastasis from gastrointestinal stromal tumors (GIST), previous cases were reviewed. Study Design: Cytological samples of 7 lesions from 4 patients with GIST-derived bone metastasis, which were obtained from 2001 to 2017 at the JFCR Cancer Institute Hospital, were reviewed. Results: The metastasis of GIST to the bone was clinically suspected before the cytological and histological examinations in all cases since they all involved other metastatic lesion(s), and characteristic osteolytic lesions were detected on radiological images. Although various cell shapes were encountered, spindle cell proliferation was seen in all cytological samples. No pleomorphism was apparent. Characteristic nuclear findings were observed. All of the cases could be diagnosed as GIST-derived bone metastasis. Conclusion: GIST-derived bone metastasis can be diagnosed by examining cytological samples.
The Ins and Outs of Autophagy and Metabolism in Hematopoietic and Leukemic Stem Cells: Food for Thought

Discovered over fifty years ago, autophagy is a double-edged blade. On one hand, it regulates cellular energy sources by “cannibalization” of its own cellular components, feeding on proteins and other unused cytoplasmic factors. On the other, it is a recycling process that removes dangerous waste from the cytoplasm keeping the cell clean and healthy. Failure of the autophagic machinery is translated in dysfunction of the immune response, in aging, and in the progression of pathologies such as Parkinson disease, diabetes, and cancer. Further investigation identified autophagy with a protective role in specific types of cancer, whereas in other cases it can promote tumorigenesis. Evidence shows that treatment with chemotherapeutics can upregulate autophagy in order to maintain a stable intracellular environment promoting drug resistance and cell survival. Leukemia, a blood derived cancer, represents one of the malignancies in which autophagy is responsible for drug treatment failure. Inhibition of autophagy is becoming a strategic target for leukemic stem cell (LSC) eradication. Interestingly, the latest findings demonstrate that LSCs show higher levels of mitochondrial metabolism compared to normal stem cells. With this review, we aim to explore the links between autophagy and metabolism in the hematopoietic system, with special focus on primitive LSCs.
A nonalcoholic fatty liver disease model in human induced pluripotent stem cell-derived hepatocytes, created by endoplasmic reticulum stress-induced steatosis

ABSTRACT Hepatic steatosis, a reversible state of metabolic dysregulation, can promote the onset of nonalcoholic steatohepatitis (NASH), and its transition is thought to be critical in disease evolution. The association between endoplasmic reticulum (ER) stress response and hepatocyte metabolism disorders prompted us to characterize ER stress-induced hepatic metabolic dysfunction in human induced pluripotent stem cell-derived hepatocytes (hiPSC-Hep), to explore regulatory pathways and validate a phenotypic in vitro model for progression of liver steatosis. We treated hiPSC-Hep with a ratio of unsaturated and saturated fatty acids in the presence of an inducer of ER stress to synergistically promote triglyceride accumulation and dysregulate lipid metabolism. We monitored lipid accumulation by high-content imaging and measured gene regulation by RNA sequencing and reverse transcription quantitative PCR analyses. Our results show that ER stress potentiated intracellular lipid accumulation by 5-fold in hiPSC-Hep in the absence of apoptosis. Transcriptome pathway analysis identified ER stress pathways as the most significantly dysregulated of all pathways affected. Obeticholic acid dose dependently inhibited lipid accumulation and modulated gene expression downstream of the farnesoid X receptor. We were able to identify modulation of hepatic markers and gene pathways known to be involved in steatosis and nonalcoholic fatty liver disease (NAFLD), in support of a hiPSC-Hep disease model that is relevant to clinical data for human NASH. Our results show that the model can serve as a translational discovery platform for the understanding of molecular pathways involved in NAFLD, and can facilitate the identification of novel therapeutic molecules based on high-throughput screening strategies. Summary: Our study demonstrates expanded use of human induced pluripotent stem cell-derived hepatocytes for molecular studies and drug screening, to evaluate new therapeutics with an antisteatotic mechanism of action for nonalcoholic fatty liver disease.
Insight Into the Pico- and Nano-Phytoplankton Communities in the Deepest Biosphere, the Mariana Trench

As photoautotrophs, phytoplankton are generally present in the euphotic zone of the ocean, however, recently healthy phytoplankton cells were found to be also ubiquitous in the dark deep sea, i.e., at water depths between 2000 and 4000 m. The distributions of phytoplankton communities in much deeper waters, such as the hadal zone, are unclear. In this study, the vertical distribution of the pico- and nano-phytoplankton (PN) communities from the surface to 8320 m, including the epipelagic, mesopelagic, bathypelagic, and hadal zones, were investigated via both 18S and p23S rRNA gene analysis in the Challenger Deep of the Mariana Trench. The results showed that Dinoflagellata, Chrysophyceae, Haptophyta, Chlorophyta, Prochloraceae, Pseudanabaenaceae, Synechococcaceae, and Eustigmatophyceae, etc., were the predominant PN in the Mariana Trench. Redundancy analyses revealed that depth, followed by temperature, was the most important environmental factors correlated with vertical distribution of PN community. In the hadal zone, the PN community structure was considerably different from those in the shallower zones. Some PN communities, e.g., Eustigmatophyceae and Chrysophyceae, which have the heterotrophic characteristics, were sparse in shallower waters, while they were identified with high relative abundance (94.1% and 20.1%, respectively) at the depth of 8320 m. However, the dinoflagellates and Prochloraceae Prochlorococcus were detected throughout the entire water column. We proposed that vertical sinking, heterotrophic metabolism, and/or the transition to resting stage of phytoplankton might contribute to the presence of phytoplankton in the hadal zone. This study provided insight into the PN community in the Mariana Trench, implied the significance of phytoplankton in exporting organic matters from the euphotic to the hadal zone, and also hinted the possible existence of some undetermined energy metabolism (e.g., heterotrophy) of phytoplankton making themselves adapt and survive in the hadal environment.
Vascular biomarker measurement using wrist-worn tonometer technology.

M any vascular biomarkers have been proposed as an aid for clinicians to refine cardiovascular risk stratification and decision-making [1]. One such biomarker is augmentation index (AIx), a variable calculated from the first and second peaks of arterial pressure waveforms, usually recorded at peripheral sites such as the radial, brachial or carotid arteries. An estimation of central aortic AIx can also be synthesized from radial or brachial waveforms using mathematical transfer functions, and this derived AIx signal is indicative of the magnitude of late systolic left ventricular loading, mostly attributed to arterial compliance and wave reflection [2]. Although there is incomplete evidence to currently recommend AIx for general clinical use [1], several factors underlie an interest in AIx as a potentially useful cardiovascular risk variable. Firstly, observational studies among different patient groups and the general community are fairly consistent in reporting an association between increased AIx and adverse cardiovascular events independent from blood pressure [3]. Secondly, there is no theoretical necessity to synthesize a central AIx using a transfer function because virtually identical AIx pressure waveform information is contained within the nontransformed peripheral (radial) artery waveform [4]. The difference in morphology being that the augmented component is generally responsible for the peak (systolic) pressure in the central aorta, whereas it modulates the shoulder in the peripheral artery waveform and does not contribute significantly to the magnitude of the systolic peak. Thirdly, therapeutic targeted lowering of AIx is possible with antihypertensive medications [5–7]. Lastly, even though AIx tends to be higher in people with high blood pressure, the index itself is calculated independent of blood pressure, thus, an indication of vascular risk can be identified even when cuff blood pressure measurement may be inaccurate
Malicious URL detection with feature extraction based on machine learning

Many web applications suffer from various web attacks due to the lack of awareness concerning security. Therefore, it is necessary to improve the reliability of web applications by accurately detecting malicious URLs. In previous studies, keyword matching has always been used to detect malicious URLs, but this method is not adaptive. In this paper, statistical analyses based on gradient learning and feature extraction using a sigmoidal threshold level are combined to propose a new detection approach based on machine learning techniques. Moreover, the naive Bayes, decision tree and SVM classifiers are used to validate the accuracy and efficiency of this method. Finally, the experimental results demonstrate that this method has a good detection performance, with an accuracy rate above 98.7%. In practical use, this system has been deployed online and is being used in large-scale detection, analysing approximately 2 TB of data every day.