Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-Cancer Effects of CKD-581, a Potent Histone Deacetylase Inhibitor against Diffuse Large B-Cell Lymphoma

Double-hit lymphoma (DHL) and double-expressor lymphoma (DEL) are aggressive forms of lymphoma that require better treatments to improve patient outcomes. CKD-581 is a new histone deacetylase (HDAC) inhibitor that exhibited a better safety profile in clinical trials compared to other HDAC inhibitors. Here, we demonstrate that CKD-581 inhibited the class I–II HDAC family via histone H3 and tubulin acetylation. CKD-581 treatment also up-regulated the phosphorylation of histone H2AX (γH2AX, DNA double-strand break marker), and reduced levels of MYC and anti-apoptotic proteins such as BCL-2, BCL-6, BCL-XL, and MCL-1 in DH/DE-diffuse large B cell lymphoma (DLBCL) cell lines. Ultimately, CKD-581 also induced apoptosis via poly(ADP ribose) polymerase 1 (PARP1) cleavage. In a DLBCL SCID mouse xenograft model, CKD-581 exhibited anti-cancer effects comparable with those of rituximab (CD20 mAb). Our findings suggest that CKD-581 could be a good candidate for the treatment of DLBCL.
Predispersal reproductive ecology of Gronovia scandens L. (Loasaceae), a plant from disturbed habitats1

Abstract Raimúndez-Urrutia, E. (Departamento de Biología de Organismos, División de Ciencias Biológicas, Universidad Simón Bolívar, Caracas, Venezuela) and C. Varela (Postgrado en Ciencias Biológicas, Universidad Simón Bolívar, Caracas, Venezuela). Predispersal reproductive ecology of Gronovia scandens L. (Loasaceae), a plant from disturbed habitats. J. Torrey Bot. Soc. 132: 581–589. 2005. —Gronovia scandens is a short-lived climbing herb that lives in disturbed sites and has become a weed in crop lands as a result of its rapid vegetative expansion and population growth, although it can also develop in late succesional stages. Study of its predispersal reproductive ecology showed that this plant is a self-compatible outcrossing annual with delayed autogamy; i.e., it exhibits a mixed mating system in which outcrossing has a temporal advantage over selfing. The outcrossing advantage is revealed by the high biomass allocation to male structures and pollinator attractants in the flower and the high pollen/ovule ratio. The delayed autogamy is mainly due to the fact that the anthers adhere to the stigma at the end of anthesis allowing seed production when outcrossing fails. The hymenopterans that were captured and identified as pollinators made non-specialized foraging movements and loaded scarce pollen on their bodies, although the body areas with pollen made contact with the stigma. Nevertheless, the presence of a single ovule per flower, delayed autogamy and a relatively low fruit cost related with the flower cost, favor a high efficiency in fruit (seed) production.
Induction of Cellular Oxidative Stress by the β-amyloid Peptide Involved in Alzheimers disease

β-amyloid, the 39-43 amino acid peptide fragment originating from amyloid precursor protein, is today, generally accepted as the biological entity responsible for causing the debilitating human disorder Alzheimer's disease. Understanding the exact biological effects of β-amyloid in vitro and in vivo is clearly important to provide therapeutic strategies for the disease. Recent in vitro studies have focused on the production of reactive oxygen species by aggregating β- amyloid, but the cellular effects of β-amyloid induced reactive oxygen species production have not been fully elucidated.
On-line anxiety level detection from biosignals: Machine learning based on a randomized controlled trial with spider-fearful individuals

We present performance results concerning the validation for anxiety level detection based on trained mathematical models using supervised machine learning techniques. The model training is based on biosignals acquired in a randomized controlled trial. Wearable sensors were used to collect electrocardiogram, electrodermal activity, and respiration from spider-fearful individuals. We designed and applied ten approaches for data labeling considering individual biosignals as well as subjective ratings. Performance results revealed a selection of trained models adapted for two-level (low and high) and three-level (low, medium and high) classification of anxiety using a minimal set of six features. We obtained a remarkable accuracy of 89.8% for the two-level classification and of 74.4% for the three-level classification using a short time window length of ten seconds when applying the approach that uses subjective ratings for data labeling. Bagged Trees proved to be the most suitable classifier type among the classification models studied. The trained models will have a practical impact on the feasibility study of an augmented reality exposure therapy based on a therapeutic game for the treatment of arachnophobia.
Assessment of structural lesions, synovitis and bone marrow lesions in erosive hand osteoarthritis on MRI (0.3T) compared to the radiographic anatomical Verbruggen-Veys score

Objective To evaluate prevalence of structural lesions, synovitis and bone marrow lesions (BMLs) on MRI performed with a 0.3T imaging system in patients with erosive hand osteoarthritis (EHOA) and to compare them to the anatomic radiographic Verbruggen-Veys score (VV). Design For this Cross-sectional study, fifty-five EHOA patients were studied with 0.3T contrast-enhanced MRI and radiography (RX) of their dominant hand. Structural lesions were scored according to the OMERACT Hand Osteoarthritis MRI Scoring System as follows: osteophytes and erosions were graded from 0 to 3. On joint destruction lesion synovitis and BMLs were graded from 0 to 1. And on MRI, we evaluated the presence of several structural features: N: normal, O: osteophytic lesions, E: erosive lesions, E/O: osteophytic and erosive lesions and D: joint destruction. RX was scored according to the VV system. Relations between MRI features and VV stages were analysed. Results MRI identified more structural lesions than RX (77.3% versus 74.8%) and particularly more erosive lesions (E or E/O) than VV Phase E (33.5% versus 20.2%). E/O and D were mostly found on MRI. Synovitis and BMLs were significantly associated with E/O and D with the following odds ratios (ORs): 8.4 (95% CI 1.8–13.6); OR: 13.7 (95% CI 2.9–21.0); OR: 15.7 (95% CI 3.2–23.5); OR: 38.5 (95% CI 9.5–57.0), respectively. Conclusion MRI 0.3T appears completely relevant for EHOA lesion analysis. First, MRI shows more erosive lesions than RX in EHOA; second, it allows for the analysis of synovitis and BMLs to be associated with more specific structural MRI features (E/O and D).
High Biological Value Compounds Extraction from Citrus Waste with Non-Conventional Methods

Citrus fruits are extensively grown and much consumed around the world. Eighteen percent of total citrus cultivars are destined for industrial processes, and as a consequence, large amounts of waste are generated. Citrus waste is a potential source of high biological value compounds, which can be used in the food, pharmaceutical, and cosmetic industries but whose final disposal may pose a problem due to economic and environmental factors. At the same time, the emerging need to reduce the environmental impact of citrus waste and its responsible management has increased. For these reasons, the study of the use of non-conventional methods to extract high biological value compounds such as carotenoids, polyphenols, essential oils, and pectins from this type of waste has become more urgent in recent years. In this review, the effectiveness of technologies such as ultrasound assisted extraction, microwave assisted extraction, supercritical fluid extraction, pressurized water extraction, pulsed electric field, high-voltage electric discharges, and high hydrostatic pressures is described and assessed. A wide range of information concerning the principal non-conventional methods employed to obtain high-biological-value compounds from citrus waste as well as the most influencing factors about each technology are considered.
Challenges Affecting Access to Health and Social Care Resources and Time Management among Parents of Children with Rett Syndrome: A Qualitative Case Study

Rare diseases face serious sustainability challenges regarding the distribution of resources geared at health and social needs. Our aim was to describe the barriers experienced by parents of children with Rett Syndrome for accessing care resources. A qualitative case study was conducted among 31 parents of children with Rett syndrome. Data were collected through in-depth interviews, focus groups, researchers’ field notes and parents’ personal documents. A thematic analysis was performed and the Standards for Reporting Qualitative Research (SRQR) guidelines were followed. Three main themes emerged from the data: (a) essential health resources; (b) bureaucracy and social care; and (c) time management constraints. Parents have difficulties accessing appropriate health services for their children. Administrative obstacles exist for accessing public health services, forcing parents to bear the financial cost of specialized care. Time is an essential factor, which conditions the organization of activities for the entire family. Qualitative research offers insight into how parents of children with Rett syndrome experience access to resources and may help improve understanding of how Rett syndrome impacts the lives of both the children and their parents.
Aeromedical evacuations during the COVID-19 pandemic: practical considerations for patient transport

Aeromedical evacuation systems around the world face new challenges in light of coronavirus disease 2019 (COVID-19). These challenges include unprecedented demand for patient transfers, as well as increased risk of exposure to aircraft crew due to prolonged close contact with contagious patients. Our organization, Service d’évacuations aéromédicales du Québec (EVAQ, Quebec Aeromedical Evacuation Services) is the medical evacuation service for the Province of Quebec. Every year, over 2000 critical care patients are transferred by our service. Since the declaration of the COVID-19 pandemic by the World Health Organization on March 11, 2020, EVAQ has organized transfers for 50 COVID-19 confirmed or suspected patients. We would like to share some practical considerations from our experience with aeromedical transfer of COVID-19 patients. These concepts are relevant not only to aeromedical transfer crews, but also to the referring and receiving emergency medical teams.
A grounded theory of adoption and maintenance of physical activity among autistic adults

Background: Although a growing body of literature has explored the physical activity experiences from the perspective of children on the autism spectrum, the perspective of autistic adults remains largely unheard. Due to this absence of perspective, there exists limited knowledge of the appropriateness and generalizability of current models and theories of physical activity for this population. Methods: A constructivist grounded theory study was conducted to explore the experiences of adoption and maintenance of physical activity from the direct perspective of autistic adults. Autistic adults (n = 23) from the United States and the United Kingdom were recruited. Results: A total of 29 codes emerged from the coding process. These codes were formed into four broad categories: (1) individual attributes; (2) environmental factors; (3) social relationships; and (4) social experiences. The interconnectedness of these four categories was explored. Conclusions: The findings and presented model highlight the importance of building successful experiences for young children on the autism spectrum, so that they are more likely to continue physical activity into their adult life. Furthermore, findings emphasize the importance of creating noncompetitive, sensory-friendly physical activity experiences for autistic adults that offer flexibility in social engagement. Lay abstract Little is known about how autistic adults experience physical activity. To begin to change this, we interviewed 23 autistic adults from the United State and the United Kingdom about their past and current experiences of physical activity participation. The interviewees told us about how their physical activity experiences were highly influenced by their individual strengths, the setting in which the activity took place, the presence of people to support their physical activities, and the sensory experiences they had while in physical activity. Through these interviews, we were able to create a model that represented the physical activity experiences discussed. Based on the model that emerged from this study, we recommend physical activity opportunities are made available that are noncompetitive, sensory-friendly, and that allow for participants to socialize as they prefer.
Digestibility studies with cows given whole and rolled cereal grains

The susceptibility of whole and rolled cereal and legume seeds to microbial attack within the rumen of cows was examined by incubating seeds in nylon bags in the rumen for 24,48 and 72 hr. With whole, intact seeds the husked cereal grains were less susceptible than naked grains and legume seeds. Inter-varietal differences were observed with maize, oats and barley. Breaking the cereal grains before incubation considerably increased the losses of dry matter. Digestibility trials with non-lactating cows confirmed that barley, sorghum, wheat and oats were poorly digested when given whole, and considerable variation was recorded between individual cows in their ability to digest whole grains. Rolling the grains before feeding made the greatest improvement in digestibility with sorghum, wheat and barley and the least with oats.
Programming in Natural Language with fuSE: Synthesizing Methods from Spoken Utterances Using Deep Natural Language Understanding

The key to effortless end-user programming is natural language. We examine how to teach intelligent systems new functions, expressed in natural language. As a first step, we collected 3168 samples of teaching efforts in plain English. Then we built fuSE, a novel system that translates English function descriptions into code. Our approach is three-tiered and each task is evaluated separately. We first classify whether an intent to teach new functionality is present in the utterance (accuracy: 97.7% using BERT). Then we analyze the linguistic structure and construct a semantic model (accuracy: 97.6% using a BiLSTM). Finally, we synthesize the signature of the method, map the intermediate steps (instructions in the method body) to API calls and inject control structures (F1: 67.0% with information retrieval and knowledge-based methods). In an end-to-end evaluation on an unseen dataset fuSE synthesized 84.6% of the method signatures and 79.2% of the API calls correctly.
Semisynthetic Modification of Tau Protein with Di-Ubiquitin Chains for Aggregation Studies

Ubiquitin, a protein modifier that regulates diverse essential cellular processes, is also a component of the protein inclusions characteristic of many neurodegenerative disorders. In Alzheimer’s disease, the microtubule associated tau protein accumulates within damaged neurons in the form of cross-beta structured filaments. Both mono- and polyubiquitin were found linked to several lysine residues belonging to the region of tau protein that forms the structured core of the filaments. Thus, besides priming the substrate protein for proteasomal degradation, ubiquitin could also contribute to the assembly and stabilization of tau protein filaments. To advance our understanding of the impact of ubiquitination on tau protein aggregation and function, we applied disulfide-coupling chemistry to modify tau protein at position 353 with Lys48- or Lys63-linked di-ubiquitin, two representative polyubiquitin chains that differ in topology and structure. Aggregation kinetics experiments performed on these conjugates reveal that di-ubiquitination retards filament formation and perturbs the fibril elongation rate more than mono-ubiquitination. We further show that di-ubiquitination modulates tau-mediated microtubule assembly. The effects on tau protein aggregation and microtubule polymerization are essentially independent from polyubiquitin chain topology. Altogether, our findings provide novel insight into the consequences of ubiquitination on the functional activity and disease-related behavior of tau protein.
General and Target-Specific DExD/H RNA Helicases in Eukaryotic Translation Initiation

DExD (DDX)- and DExH (DHX)-box RNA helicases, named after their Asp-Glu-x-Asp/His motifs, are integral to almost all RNA metabolic processes in eukaryotic cells. They play myriad roles in processes ranging from transcription and mRNA-protein complex remodeling, to RNA decay and translation. This last facet, translation, is an intricate process that involves DDX/DHX helicases and presents a regulatory node that is highly targetable. Studies aimed at better understanding this family of conserved proteins have revealed insights into their structures, catalytic mechanisms, and biological roles. They have also led to the development of chemical modulators that seek to exploit their essential roles in diseases. Herein, we review the most recent insights on several general and target-specific DDX/DHX helicases in eukaryotic translation initiation.
Barriers and Strategies for Improving Medication Adherence Among People Living With COPD: A Systematic Review

BACKGROUND: While medication is an integral component of the effective management of COPD, contemporary studies report that more than half of all people who are prescribed medication for the management of their COPD do not adhere to therapy. Enhancing medication adherence and improving health outcomes for those living with COPD are among the key challenges for the global health community. This systematic review aims to identify the rate of nonadherence among people who are prescribed controller medication for the management of their COPD, and identifies the barriers and facilitators that influence their medication use behavior. METHODS: A systematic search of medical databases (ie, MEDLINE, CINHAL, and EMBASE) was conducted using key words to identify literature in the English language, published between January 2003 and December 2019. Included studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. RESULTS: A total of 1,474 studies were identified from the initial database search, of which 38 met the inclusion criteria. Of these 38 studies, 37 reported on rates of nonadherence (ranging from 22% to 93%), 30 reported on barriers to adherence, 24 reported on enablers to adherence, and 16 reported on both. The majority (33) of the studies were conducted in high-income nations. The quality of articles ranged from 47% to 90%. Medication-taking behavior was reported to be influenced by several factors such as subjects’ beliefs about medication, their experiences of and satisfaction with medication effectiveness, their concerns regarding medication side effects, their personal circumstances, habits and health status, and their relationships with health care providers. CONCLUSIONS: Adherence to COPD medication was generally low, with the majority of studies identifying the presence of depression and subjects’ concern about the harmful effects of the medicine as barriers to adherence. Variability exists on the reported rates of nonadherence, possibly due to different measures utilized to assess adherence. Future research in low-income nations is needed.
Wedge resection as an alternative treatment for octogenarian and older patients with early-stage non-small-cell lung cancer.

OBJECTIVE Anatomical resection with lymph node dissection is the standard treatment for early non-small cell lung cancer, whereas wedge resection is considered as a compromise. We aimed to determine whether wedge resection without lymph node dissection could be a treatment option for patients aged ≥80 years. METHODS We assessed 669 patients with clinical stage IA non-small cell lung cancer, whole tumour sizes ≤2 cm and a consolidation to tumour ratio of >0.5 who underwent R0 resection at three institutions between 2010 and 2016. We selected 58 of them who were aged ≥80 years and analysed their clinicopathological findings and prognosis after surgical procedures over a median follow-up of 38 months. Propensity scores for surgical procedures were calculated using age, gender, smoking status and solid tumour size on computed tomography. RESULTS Three-year overall and recurrence-free survival rates after wedge resection and after segmentectomy + lobectomy for patients aged ≥80 years did not significantly differ (overall survival: 88.9% [95% confidence interval, 69.4-96.3%] vs. 75.5% [95% confidence interval, 51.5-88.8%], P = 0.95; recurrence-free survival: 85.2% [95% confidence interval: 65.2-94.2%] vs. 68.0% [95% confidence interval, 44.4-83.2], P = 0.57). Multivariable Cox regression analysis of overall survival with propensity scores revealed that surgical procedure was not an independent predictor of a poor prognosis (hazard ratio: 0.86 (0.28-2.6), P = 0.78) in patients aged ≥80 years. CONCLUSIONS Wedge resection might be an alternative to lobectomy or segmentectomy with lymph node dissection for patients aged ≥80 years with early non-small cell lung cancer.
Embryonic Regulation of Integrins β3,α 4, and α1 in Human Endometrial Epithelial Cells in Vitro1

In the present study, we examined the embryonic regulation ofβ 3 integrin in human endometrial epithelial cells (EEC) at the protein level and analyzed putative embryonic factors responsible for this regulation. The model employed is based on a clinical in vitro fertilization program in which single human embryos were cocultured with EEC until blastocyst stage and then transferred back to the uterus. After embryo transfer, EEC wells were divided according to the embryonic status reached: EEC with embryos that achieved the blastocyst stage, EEC with arrested embryos, and EEC without embryos. Immunostaining for β3 was positive in plasma membrane of EEC. Flow cytometry showed a mean percentage ofβ 3-stained cells of 24.1 ± 5.7 in EEC cocultured with embryos that achieved the blastocyst stage (n = 13) vs. 9.5 ± 1.6 (P < 0.05) in those EEC cultured with arrested embryos (n = 12). Immunostaining for α1 and α4 integrins was negative in EEC monolayers studied, regardless of the presence or absence of embryos, and.
Lack of DLAD mutations in age-related nuclear cataract

DNase II like acid DNase (DNase IIβ, DLAD) is expressed in human and murine cells in the lens. Studies in mice have reported that abnormal degeneration of cellular organelles by DLAD reduced lens transparency and that the DLAD gene may be involved in cataract formation. The aim of the present study was to search for possible genetic alterations in the DLAD gene in human senile cataract. Anterior lens capsule material was collected during surgery from 55 patients with senile cataract, with or without a subcapsular component. Total DNA was extracted, amplified by polymerase chain reaction and sequenced for exon 3 (n = 51) exon 4 (n = 40) and all 6 exons of the DLAD gene (n = 27). No mutation was found. There were genomic polymorphisms in all exons except 3 and 4. Nonsynonymous genomic polymorphisms were detected in exon 1 (rs738573) and exon 2 (rs3754274) and synonymous polymorphisms were detected in exon 5 (rs7511984) and exon 6 (rs3768250). In contrast to findings in mice, based on the limited samples analyzed, this study suggests that human age-related nuclear cataract is not associated with DLAD mutations.