Miracle-dz/UniFAR-FTUs huggingface dataset:
Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study

This study evaluated the efficacy of cationic nanoparticle (leciplex) to deliver carvedilol to ocular surface for glaucoma treatment as recent studies pointed out the effect of topical carvedilol on intraocular pressure, therefore carvedilol loaded leciplex formulae were prepared using soy phosphatidyl choline (SPC) and cationic surfactant (CTAB/DDAB) and characterized for morphology, entrapment efficiency, particle size, zeta potential and ex-vivo corneal permeation. Then the selected formula was evaluated via in-vivo studies in comparison with carvedilol solution. Leciplex nanoparticles appeared spherical in shape with entrapment efficiency exceeded 95% in all formulae. Leciplex formula composed of SPC and DDAB in (1:1) molar ratio showed the smallest particle size (16.04 ± 1.2 nm), highest zeta potential value (53.9 ± 0.91 mv) and highest apparent corneal permeability coefficient (0.1157 cm/h). Carvedilol leciplex reduced intraocular pressure (IOP) to normal range in ocular hypertensive rabbits after 30 min and duration of action lasted for 24 h, while carvedilol solution reduced IOP to normal value after 60 min and duration of action lasted for 6 h. Furthermore, histological examination of eyeballs of rabbits treated with carvedilol leciplex showed improvement of retinal atrophy of glaucomatous eyes. This study concluded that leciplex improve transcorneal permeation and bioavailability of carvedilol.
Association of Caffeine Intake and Caffeinated Coffee Consumption With Risk of Incident Rosacea in Women

Importance Caffeine is known to decrease vasodilation and have immunosuppressant effects, which may potentially decrease the risk of rosacea. However, the heat from coffee may be a trigger for rosacea flares. The relationship between the risk of rosacea and caffeine intake, including coffee consumption, is poorly understood. Objective To determine the association between the risk of incident rosacea and caffeine intake, including coffee consumption. Design, Setting, and Participants This cohort study included 82 737 women in the Nurses’ Health Study II (NHS II), a prospective cohort established in 1989, with follow-up conducted biennially between 1991 and 2005. All analysis took place between June 2017 and June 2018. Exposures Data on coffee, tea, soda, and chocolate consumption were collected every 4 years during follow-up. Main Outcomes and Measures Information on history of clinician-diagnosed rosacea and year of diagnosis was collected in 2005. Results A total of 82 737 women responded to the question regarding a diagnosis of rosacea in 2005 in NHS II and were included in the final analysis (mean [SD] age at study entry, 50.5 [4.6] years). During 1 120 051 person-years of follow-up, we identified 4945 incident cases of rosacea. After adjustment for other risk factors, we found an inverse association between increased caffeine intake and risk of rosacea (hazard ratio for the highest quintile of caffeine intake vs the lowest, 0.76; 95% CI, 0.69-0.84; P < .001 for trend). A significant inverse association with risk of rosacea was also observed for caffeinated coffee consumption (HR, 0.77 for those who consumed ≥4 servings/d vs those who consumed <1/mo; 95% CI, 0.69-0.87; P < .001 for trend), but not for decaffeinated coffee (HR, 0.80; 95% CI, 0.56-1.14; P = .39 for trend). Further analyses found that increased caffeine intake from foods other than coffee (tea, soda, and chocolate) was not significantly associated with decreased risk of rosacea. Conclusions and Relevance Increased caffeine intake from coffee was inversely associated with the risk of incident rosacea. Our findings do not support limiting caffeine intake as a means to prevent rosacea. Further studies are required to explain the mechanisms of action of these associations, to replicate our findings in other populations, and to explore the relationship of caffeine with different rosacea subtypes.
Long-Term Effect on Bioactive Components and Antioxidant Activity of Thermal and High-Pressure Pasteurization of Orange Juice

The long-term effect of thermal pasteurization (TP) and high-pressure processing (HPP) of orange juices stored under refrigeration, on the bioactive components and antioxidant activity, was compared. Total phenolic content (TPC), flavonoid, anthocyanin, and carotenoid contents, the individual content of major phenolic components, and the antioxidant activity, were evaluated in TP- and HPP-treated juices over a 36-day period. At day 0, no significant differences in TPC, and a decrease in carotenoid content after both treatments, were observed. TP caused a decrease of flavonoid and anthocyanin contents, while HPP increased flavonoid content. Three major phenolic components were identified: apigenin-6,8-di-C-glucoside, naringenin-7-O-rutinoside, and hesperetin-7-O-rutinoside, the latter increasing ca. 45% immediately after HPP. During storage, a decrease in TPC, and in the anthocyanin and carotenoid contents of both treated juices was observed, with higher anthocyanin and phenolic contents in HPP juices. A significant increase of hesperetin-7-O-rutinoside content was observed in HPP juice. Both treatments caused a decrease (26% and 13%, respectively) of antioxidant activity. Most of the kinetic profiles followed zero-order patterns, with HPP juices showing a considerably higher half-life than TP ones. These results clearly demonstrate the advantages of HPP for orange juice preservation allowing, also, their nutritional benefits to be enhanced by increasing the content of some bioactive components.
Measuring User Satisfaction on Smart Speaker Intelligent Assistants Using Intent Sensitive Query Embeddings

Intelligent assistants are increasingly being used on smart speaker devices, such as Amazon Echo, Google Home, Apple Homepod, and Harmon Kardon Invoke with Cortana. Typically, user satisfaction measurement relies on user interaction signals, such as clicks and scroll movements, in order to determine if a user was satisfied. However, these signals do not exist for smart speakers, which creates a challenge for user satisfaction evaluation on these devices. In this paper, we propose a new signal, user intent, as a means to measure user satisfaction. We propose to use this signal to model user satisfaction in two ways: 1) by developing intent sensitive word embeddings and then using sequences of these intent sensitive query representations to measure user satisfaction; 2) by representing a user's interactions with a smart speaker as a sequence of user intents and thus using this sequence to identify user satisfaction. Our experimental results indicate that our proposed user satisfaction models based on the intent-sensitive query representations have statistically significant improvements over several baselines in terms of common classification evaluation metrics. In particular, our proposed task satisfaction prediction model based on intent-sensitive word embeddings has a 11.81% improvement over a generative model baseline and 6.63% improvement over a user satisfaction prediction model based on Skip-gram word embeddings in terms of the F1 metric. Our findings have implications for the evaluation of Intelligent Assistant systems.
Blood collection, platelet isolation and measurement of platelet count and size in mice—a practical guide

Abstract Inherited or acquired disorders of platelet production and function can result in thrombocytopenia and bleeding. Mouse models have proven useful for investigating the mechanisms that underlie these defects in humans. Precise methods for blood withdrawal, platelet isolation and measurement of platelet parameters are key for the generation of reproducible and conclusive data. Here, we provide three different protocols for mouse platelet isolation to encourage research knowledge transfer between experienced laboratories, while at the same time enabling less experienced researchers to implement a protocol that best suits their local expertise and equipment. We also address the issue that reported mouse platelet count and size vary considerably in the literature by investigating different factors that influence these important platelet parameters, namely: 1) genetic background and gender, 2) choice of analysis method (hematological analyzer or flow cytometry), 3) dilution of the blood sample and 4) choice of anticoagulant. The herein presented results and considerations may serve as a practical guide for both experienced and new researchers in the platelet field.
Preliminary Report: Multiple Clusters of Proliferating Cells in Non-dysplastic Corrupted Colonic Crypts Underneath Conventional Adenomas

Background: The finding was recently reported of clusters of colonic crypts lined with indigenous normal epithelium displaying irregular shapes underneath the adenomatous glands of conventional (tubular or villous) adenomas. These abnormal crypts were named non-dysplastic corrupted colonic crypts (NDCs). This study explored the characteristics of cell proliferation in NDCs present in a cohort of conventional adenomas. Materials and Methods: Sections from six conventional adenomas were challenged with the proliferation marker Ki-67 (MIB1). MIB+ proliferating clusters were regarded as those exhibiting two or more adjoining MIB+ cells. Results: A total of 46 (range=1-18) NDCs were found underneath the six conventional adenomas. Out of the 46 NDCs, two exhibited only one proliferative cluster/crypt, 14 NDCs two clusters/crypt, 14 three clusters/crypt and the remaining 16 NDCs more than four distinct clusters/crypt. Conclusion: This preliminary study showed, evidently for the first time, that multiple, apparently haphazardly distributed clusters of proliferating cells are present in NDCs. Since the Ki-67 proliferation marker only labels progenitor daughter cells generated by stem cells, each MIB+ cluster in each NDC must have been produced by a single stem cell. Consequently, individual NDCs may harbor several stem cells, a deduction that is in concert with recent studies showing that in the normal human colon, the number of stem cells per crypt is of the order of five to six, or about 5% of the cell population of a single crypt.
Variations in the Botulinum Neurotoxin Binding Domain and the Potential for Novel Therapeutics

Botulinum neurotoxins (BoNTs) are categorised into immunologically distinct serotypes BoNT/A to /G). Each serotype can also be further divided into subtypes based on differences in amino acid sequence. BoNTs are ~150 kDa proteins comprised of three major functional domains: an N-terminal zinc metalloprotease light chain (LC), a translocation domain (HN), and a binding domain (HC). The HC is responsible for targeting the BoNT to the neuronal cell membrane, and each serotype has evolved to bind via different mechanisms to different target receptors. Most structural characterisations to date have focussed on the first identified subtype within each serotype (e.g., BoNT/A1). Subtype differences within BoNT serotypes can affect intoxication, displaying different botulism symptoms in vivo, and less emphasis has been placed on investigating these variants. This review outlines the receptors for each BoNT serotype and describes the basis for the highly specific targeting of neuronal cell membranes. Understanding receptor binding is of vital importance, not only for the generation of novel therapeutics but also for understanding how best to protect from intoxication.
THE ROLE OF DISGUST AS AN EMOTIONAL MEDIATOR OF ADVERTISING EFFECTS

This research examines an emotion that advertising researchers have largely neglected. In particular, we explore in two parallel experiments the role of disgust in the context of fast-food restaurant advertising. A follow-up study then determines that the theoretical concept of disgust captures only a narrow aspect of the meaning this term holds for laypeople. Both the narrow and broadened notions of disgust hold implications for advertising theory and practice.
Anterior Segment Biometry and Their Correlation with Corneal Biomechanics in Caucasian Children

ABSTRACT Purpose: To assess the relationship between the corneal biomechanical parameters and the anterior segment parameters in Caucasian children. Methods: This study included 293 eyes from 293 healthy children aged between 6 and 17 years. Corneal hysteresis (CH) and corneal resistance factor (CRF) were evaluated with the Ocular Response Analyzer, axial length (AL) with IOLMaster and the anterior segment with Pentacam. Anterior segment parameters obtained were the following: central corneal thickness (CCT), corneal volume (CV), anterior chamber depth (ACD), anterior chamber volume (ACV) and mean anterior and posterior keratometry. Two multiple linear regression models were constructed to assess the association between CH and CRF with anterior segment parameters. A value of p < 0.05 was taken as the criterion for statistical significance in all analyses. Results: The mean CH and CRF were 12.12 ± 1.71 and 12.30 ± 1.89 mmHg, respectively. Multiple linear regression revealed that CH and CRF were associated negatively with AL in both models, and positively with CCT and CV in the first and second model, respectively. Meanwhile ACD, ACV or mean keratometry did not correlated with CH and CRF. Moreover, when CCT was in the model, it explained more variability for both CH (22.1%) and CRF (30.9%) than when CV was included (16.2% for CH and 16.5% for CRF). Conclusions: CH and CRF were correlated positively with CCT and CV, and negatively with AL in healthy Caucasian children. Moreover, corneal parameters were the most contributory variables to CH and CRF changes.
How to train your MAML

The field of few-shot learning has recently seen substantial advancements. Most of these advancements came from casting few-shot learning as a meta-learning problem. Model Agnostic Meta Learning or MAML is currently one of the best approaches for few-shot learning via meta-learning. MAML is simple, elegant and very powerful, however, it has a variety of issues, such as being very sensitive to neural network architectures, often leading to instability during training, requiring arduous hyperparameter searches to stabilize training and achieve high generalization and being very computationally expensive at both training and inference times. In this paper, we propose various modifications to MAML that not only stabilize the system, but also substantially improve the generalization performance, convergence speed and computational overhead of MAML, which we call MAML++.
Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, in cynomolgus monkeys

Abstract Trastuzumab deruxtecan (DS-8201a) is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) conjugated to a topoisomerase I inhibitor (DXd) at a drug-to-antibody ratio (DAR) of 7-8. Here, we examined the pharmacokinetic (PK) profiles of DS-8201a and DXd in cynomolgus monkeys, a cross-reactive species. Following intravenous (iv) administration of DS-8201a, the linker was stable in plasma, and systemic DXd exposure was low. DXd was rapidly cleared following iv dosing. Biodistribution studies revealed that intact DS-8201a was present mostly in the blood without tissue-specific retention. The major pathway of excretion for DXd was the faecal route following iv administration of radiolabelled DS-8201a. The only detectable metabolite in the urine and faeces was unmetabolized DXd. DXd is a substrate of organic anion transporting polypeptides, P-gp, and breast cancer resistance protein. In conclusion, the stable linker in circulation and the high clearance of DXd upon release resulted in the low systemic exposure to DXd. Furthermore, the minimal tissue-specific retention and rapid excretion of DXd into faeces as its unmetabolized form with potentially limited impact on drug − drug interaction as a victim were also critical elements of the PK profile of DS-8201a.
Action and Intention Recognition of Pedestrians in Urban Traffic

Action and intention recognition of pedestrians in urban settings are challenging problems for Advanced Driver Assistance Systems as well as future autonomous vehicles to maintain smooth and safe traffic. This work investigates a number of feature extraction methods in combination with several machine learning algorithms to build knowledge on how to automatically detect the action and intention of pedestrians in urban traffic. We focus on the motion and head orientation to predict whether the pedestrian is about to cross the street or not. The work is based on the Joint Attention for Autonomous Driving (JAAD) dataset, which contains 346 videoclips of various traffic scenarios captured with cameras mounted in the windshield of a car. An accuracy of 72% for head orientation estimation and 85% for motion detection is obtained in our experiments.
Morphological features of the yolk processing pattern in the eastern fence lizard, Sceloporus undulatus (Phrynosomatidae)

Features of embryonic development in birds traditionally have been assumed to be shared by sauropsids in general. Herein, we document a pattern of yolk processing and cellularization in the Eastern fence lizard (Sceloporus undulatus) that is fundamentally different from that of birds. In the avian pattern, cells of the yolk sac lining phagocytose, and digest yolk material. These cells release products of digestion into underlying blood vessels for transport back to the embryo. In contrast, microscopic examination of the developing eggs of S. undulatus reveals that the yolk mass is converted into vascularized, “spaghetti‐like” strands that fill the yolk sac cavity. Three successive developmental stages are involved. First, the liquid yolk is invaded by proliferating endodermal cells, which phagocytose and digest the yolk material. These cells form clumps that progressively fill the yolk sac cavity. Second, small blood vessels derived from the yolk sac vasculature invade the yolk sac cavity. Third, the endodermal cells become organized in monolayers around these vessels. This arrangement provides a means by which large numbers of endodermal cells can digest yolk, with each cell being positioned to release products of digestion into an adjacent blood vessel for transport to the embryo. The mechanism of yolk processing in this lizard species is similar to that of recently studied snakes. From its phylogenetic distribution, we infer that this pattern probably is ancestral for squamate sauropsids.
Current and future options for opioid use disorder: a survey assessing real-world opinion of service users on novel therapies including depot formulations of buprenorphine

Purpose Integrated treatment for opioid use disorder (OUD) includes opioid agonist therapy (OAT) such as methadone and buprenorphine with well-evidenced benefits. Treatment with typical existing oral medications is associated with burdens and limits to successful outcomes (frequent dosing, attendance for collection/consumption, difficulty in achieving optimal dosing, misuse, diversion, accidental exposure, and stigma from the treatment process). Novel medications include injected depot formulations with less frequent administration, providing consistent drug levels after dosing. This survey assesses the opinion of those with OUD treatment services lived experience to inform future medication choices. Patients and methods A survey of people with experience of OUD pharmacotherapy – the treatment system – was completed. Participants reviewed statements describing elements of OUD care using 7-point Likert scales to indicate their level of agreement or disagreement. Data were assessed using descriptive analysis. Results In total, 35 people (16 in treatment; 19 with previous history of treatment) completed the survey. Average drug-use duration, 20 years, commonly included injected opioids. The majority agreed treatment was effective, but not tailored to their individual needs and limited normal day-to-day activities. Opinions on novel depot medications included the following: agreement on its potential to make life easier, reduce stigma, free-up time for preferred activities. Participants did not report concerns over the effectiveness and safety of depot medications, nor about reduced contact with treatment services that could be associated with less frequent dosing. Conclusion This survey provides a useful initial record of the opinions of people experienced in OUD treatment services on novel depot medications, which may result in important benefits. Care providers and policy makers should continue to work with those with lived experience to understand the specific opportunity provided by such innovation.
Quantitative analysis of somatically acquired and constitutive uniparental disomy in gastrointestinal cancers

Somatically acquired uniparental disomies (aUPDs) are frequent events in solid tumors and have been associated with cancer‐related genes. Studies assessing their functional consequences across several cancer types are therefore necessary. Here, we aimed at integrating aUPD profiles with the mutational status of cancer‐related genes in a tumor‐type specific manner. Using TCGA datasets for 1,032 gastrointestinal cancers, including colon (COAD), rectum (READ), stomach (STAD), esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), we show a non‐random distribution of aUPD, suggesting the existence of a cancer‐specific landscape of aUPD events. Our analysis indicates that aUPD acts as a “second hit” in Knudson's model in order to achieve biallelic inactivation of tumor suppressor genes. In particular, APC, ARID1A and NOTCH1 were recurrently inactivated by the presence of homozygous mutation as a consequence of aUPD in COAD and READ, STAD and ESCC, respectively. Furthermore, while TP53 showed inactivation caused by aUPD at chromosome arm 17p across all tumor types, copy number losses at this genomic position were also frequent. By experimental and computationally inferring genome ploidy, we demonstrate that an increased number of aUPD events, both affecting the whole chromosome or segments of it, were present in highly aneuploid genomes compared to near‐diploid tumors. Finally, the presence of mosaic UPD was detected at a higher frequency in DNA extracted from peripheral blood lymphocytes of patients with colorectal cancer compared to healthy individuals. In summary, our study defines specific profiles of aUPD in gastrointestinal cancers and provides unequivocal evidence of their relevance in cancer.
Adversarial Learning of Answer-Related Representation for Visual Question Answering

Visual Question Answering (VQA) aims to learn a joint embedding of the question sentence and the corresponding image to infer the answer. Existing approaches learn the joint embedding don't consider the answer-related information, which results in that the learned representation is not effective to reflect the answer of the question. To address this problem, this paper proposes a novel method, i.e., Adversarial Learning of Answer-Related Representation (ALARR) for visual question answering, which seeks an effective answer-related representation for the question-image pair based on adversarial learning between two processes. The embedding learning process aims to generate modality-invariant joint representations for the question-image and question-answer pairs, respectively. Meanwhile, it tries to confuse the other process, embedding discriminator, which tries to discriminate the two representations from different modalities of pairs. Specifically, the joint embedding of the question-image pair is learned by a three-level attention model, and the joint representation of the question-answer pair is learned by a semantic integration model. Through the adversarial leaning, the answer-related representation are better preserved. Then an answer predictor is proposed to infer the answer from the answer-related representation. Experiments conducted on two widely used VQA benchmark datasets demonstrate that the proposed model outperforms the state-of-the-art approaches.