Miracle-dz/UniFAR-FTUs huggingface dataset:
Two effects of GATA2 enhancer repositioning by 3q chromosomal rearrangements

Chromosomal inversion and translocation between 3q21 and 3q26 [inv (3)(q21.3q26.2) and t(3;3)(q21.3;q26.2), respectively] give rise to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), which have poor prognoses. The chromosomal rearrangements reposition a GATA2 distal hematopoietic enhancer from the original 3q21 locus to the EVI1 (also known as MECOM) locus on 3q26. Therefore, the GATA2 enhancer from one of two GATA2 alleles drives EVI1 gene expression in hematopoietic stem and progenitor cells, which promotes the accumulation of abnormal progenitors and induces leukemogenesis. On the other hand, one allele of the GATA2 gene loses its enhancer, which results in reduced GATA2 expression. The GATA2 gene encodes a transcription factor critical for the generation and maintenance of hematopoietic stem and progenitor cells. GATA2 haploinsufficiency has been known to cause immunodeficiency and myeloid leukemia. Notably, reduced GATA2 expression suppresses the differentiation but promotes the proliferation of EVI1‐expressing leukemic cells, which accelerates EVI1‐driven leukemogenesis. A series of studies have shown that the GATA2 enhancer repositioning caused by the chromosomal rearrangements between 3q21 and 3q26 provokes misexpression of both the EVI1 and GATA2 genes and that these two effects coordinately elicit high‐risk leukemia.
MicroRNA-137 Inhibits Cancer Progression by Targeting Del-1 in Triple-Negative Breast Cancer Cells

MicroRNAs (miRNAs) can be used to target a variety of human malignancy by targeting their oncogenes or tumor suppressor genes. The developmental endothelial locus-1 (Del-1) might be under miRNA regulation. This study investigated microRNA-137 (miR-137) function and Del-1 expression in triple-negative breast cancer (TNBC) cells and tissues. Del-1 mRNA and miRNA-137 levels were determined via qRT-PCR in breast cancer cells (MDA-MB-231, MCF7, SK-BR3, and T-47D) and tissues from 30 patients with TNBC. The effects of miR-137 on cell proliferation, migration, and invasion were determined using MTT assays, wound healing, and Matrigel transwell assays. The luciferase reporter assay revealed direct binding of miR-137 to the 3′-UTR of Del-1. miR-137 inhibited cell proliferation, migration, and invasion of MDA-MB-231 cells. Among the 30 TNBC specimens, miR-137 was downregulated and Del-1 level in plasma was significantly elevated relative to normal controls. It is concluded that miR-137 regulates Del-1 expression in TNBC by directly binding to the Del-1 gene and cancer progression. The results implicate miR-137 as a new therapeutic biomarker for patients with TNBC.
Randomized, Phase II Study Prospectively Evaluating Treatment of Metastatic Esophageal, Gastric, or Gastroesophageal Cancer by Gene Expression of ERCC1: SWOG S1201.

PURPOSE Platinum-based therapy is the standard of care in patients who have HER2-negative, advanced esophagogastric cancer (AEGC). Retrospective data suggest that intratumoral ERCC1 levels may determine platinum sensitivity. A randomized, phase II study was performed in patients with AEGC to explore whether the efficacy of a platinum-based therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) versus a non-platinum-containing regimen of irinotecan and docetaxel (IT) differed according to ERCC1 levels. PATIENTS AND METHODS Overall, 202 untreated patients with HER2-negative AEGC and a Zubrod performance status of 0-1 were evaluated prospectively for mRNA expression of ERCC1 level and then randomly assigned to FOLFOX or IT, stratified by the intratumoral statuses of ERCC1 low (< 1.7) or high (≥ 1.7). Objectives were to assess progression-free survival (PFS) and overall survival (OS) in all patients treated with FOLFOX compared with IT, stratified by low and high ERCC1 levels, and to assess for interactive effects between ERCC1 expression and treatment arm. RESULTS Eighty-six percent of patients had ERCC1 values < 1.7. Thus, evaluation of the ERCC1-high subgroup was limited. Grade ≥ 3 anemia, dehydration, diarrhea, and fatigue were greater in patients with IT. Occurrences of grade ≥ 3 neuropathy and decreased neutrophils were greater in patients with FOLFOX. In all patients, FOLFOX had a statistically superior median PFS compared with IT (5.7 v 2.9 months; hazard ratio, 0.68; P = .02). In patients with ERCC1 levels < 1.7 receiving FOLFOX, PFS and response rate were statistically superior to IT, with no significant difference in OS. CONCLUSION The evaluation of ERCC1 in patients with upper GI tumors was thwarted by an overwhelming predominance of low ERCC1 mRNA expression. Nonetheless, distribution of treatment effects on PFS did not vary with expression. For all patients and for those with low ERCC1 expression, FOLFOX was superior in efficacy to IT.
Botulinum Toxin Therapy Combined with Rehabilitation for Stroke: A Systematic Review of Effect on Motor Function

Aim: The purpose of this study was to examine the effectiveness of botulinum toxin A (BoNT-A) therapy combined with rehabilitation on motor function in post-stroke patients. Methods: The following sources up to December 31, 2018, were searched from inception for articles in English: Pubmed, Scopus, CINAHL, Embase, PsycINFO, and CENTRAL. Trials using injections of BoNT-A for upper and lower limb rehabilitation were examined. We excluded studies that were not performed for rehabilitation or were not evaluated for motor function. Results: Twenty-six studies were included. In addition to rehabilitation, nine studies used adjuvant treatment to improve spasticity or improve motor function. In the upper limbs, two of 14 articles indicated that significant improvement in upper limb motor function was observed compared to the control group. In the lower limbs, seven of 14 articles indicated that significant improvement in lower limb motor function was observed compared to the control group. Conclusions: The effect of combined with rehabilitation is limited after stroke, and there is not sufficient evidence, but results suggest that BoNT-A may help to improve motor function. In future studies, the establishment of optimal rehabilitation and evaluation times of BoNT-A treatment will be necessary for improving motor function and spasticity.
Evaluation of Pattern Recognition Methods for Head Gesture-Based Interface of a Virtual Reality Helmet Equipped with a Single IMU Sensor

The motivation of this paper is to examine the effectiveness of state-of-the-art and newly proposed motion capture pattern recognition methods in the task of head gesture classifications. The head gestures are designed for a user interface that utilizes a virtual reality helmet equipped with an internal measurement unit (IMU) sensor that has 6-axis accelerometer and gyroscope. We will validate a classifier that uses Principal Components Analysis (PCA)-based features with various numbers of dimensions, a two-stage PCA-based method, a feedforward artificial neural network, and random forest. Moreover, we will also propose a Dynamic Time Warping (DTW) classifier trained with extension of DTW Barycenter Averaging (DBA) algorithm that utilizes quaternion averaging and a bagged variation of previous method (DTWb) that utilizes many DTW classifiers that perform voting. The evaluation has been performed on 975 head gesture recordings in seven classes acquired from 12 persons. The highest value of recognition rate in a leave-one-out test has been obtained for DTWb and it equals 0.975 (0.026 better than the best of state-of-the-art methods to which we have compared our approach). Among the most important applications of the proposed method is improving life quality for people who are disabled below the neck by supporting, for example, an assistive autonomous power chair with a head gesture interface or remote controlled interfaces in robotics.
Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance

Preparation and formulation of amorphous solid dispersions (ASDs) are becoming more and more popular in the pharmaceutical field because the dissolution of poorly water-soluble drugs can be effectively improved this way, which can lead to increased bioavailability in many cases. During downstream processing of ASDs, technologists need to keep in mind both traditional challenges and the newest trends. In the last decade, the pharmaceutical industry began to display considerable interest in continuous processing, which can be explained with their potential advantages such as smaller footprint, easier scale-up, and more consistent product, better quality and quality assurance. Continuous downstream processing of drug-loaded ASDs opens new ways for automatic operation. Therefore, the formulation of poorly water-soluble drugs may be more effective and safe. However, developments can be challenging due to the poor flowability and feeding properties of ASDs. Consequently, this review pays special attention to these characteristics since the feeding of the components greatly influences the content uniformity in the final dosage form. The main purpose of this paper is to summarize the most important steps of the possible ASD-based continuous downstream processes in order to give a clear overview of current course lines and future perspectives.
Melatonin-Nitric Oxide Crosstalk and Their Roles in the Redox Network in Plants

Melatonin, an amine hormone highly conserved during evolution, has a wide range of physiological functions in animals and plants. It is involved in plant growth, development, maturation, and aging, and also helps ameliorate various types of abiotic and biotic stresses, including salt, drought, heavy metals, and pathogens. Melatonin-related growth and defense responses of plants are complex, and involve many signaling molecules. Among these, the most important one is nitric oxide (NO), a freely diffusing amphiphilic biomolecule that can easily cross the cell membrane, produce rapid signal responses, and participate in a wide variety of physiological reactions. NO-induced S-nitrosylation is also involved in plant defense responses. NO interacts with melatonin as a long-range signaling molecule, and helps regulate plant growth and maintain oxidative homeostasis. Exposure of plants to abiotic stresses causes the increase of endogenous melatonin levels, with the consequent up-regulation of melatonin synthesis genes, and further increase of melatonin content. The application of exogenous melatonin causes an increase in endogenous NO and up-regulation of defense-related transcription factors, resulting in enhanced stress resistance. When plants are infected by pathogenic bacteria, NO acts as a downstream signal to lead to increased melatonin levels, which in turn induces the mitogen-activated protein kinase (MAPK) cascade and associated defense responses. The application of exogenous melatonin can also promote sugar and glycerol production, leading to increased levels of salicylic acid and NO. Melatonin and NO in plants can function cooperatively to promote lateral root growth, delay aging, and ameliorate iron deficiency. Further studies are needed to clarify certain aspects of the melatonin/NO relationship in plant physiology.
Establishing a Field-Effect Transistor Sensor for the Detection of Mutations in the Tumour Protein 53 Gene (TP53)—An Electrochemical Optimisation Approach

We present a low-cost, sensitive and specific DNA field-effect transistor sensor for the rapid detection of a common mutation to the tumour protein 53 gene (TP53). The sensor consists of a commercially available, low-cost, field-effect transistor attached in series to a gold electrode sensing pad for DNA hybridisation. The sensor has been predominantly optimised electrochemically, particularly with respect to open-circuit potentiometry as a route towards understanding potential (voltage) changes upon DNA hybridisation using a transistor. The developed sensor responds sensitively to TP53 mutant DNA as low as 100 nM concentration. The sensor responds linearly as a function of DNA target concentration and is able to differentiate between complementary and noncomplementary DNA target sequences.
The Importance of the Microbiome in Critically Ill Patients: Role of Nutrition

Critically ill patients have an alteration in the microbiome in which it becomes a disease-promoting pathobiome. It is characterized by lower bacterial diversity, loss of commensal phyla, like Firmicutes and Bacteroidetes, and a domination of pathogens belonging to the Proteobacteria phylum. Although these alterations are multicausal, many of the treatments administered to these patients, like antibiotics, play a significant role. Critically ill patients also have a hyperpermeable gut barrier and dysregulation of the inflammatory response that favor the development of the pathobiome, translocation of pathogens, and facilitate the emergence of sepsis. In order to restore the homeostasis of the microbiome, several nutritional strategies have been evaluated with the aim to improve the management of critically ill patients. Importantly, enteral nutrition has proven to be more efficient in promoting the homeostasis of the gut microbiome compared to parenteral nutrition. Several nutritional therapies, including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, are currently being used, showing variable results, possibly due to the unevenness of clinical trial conditions and the fact that the beneficial effects of probiotics are specific to particular species or even strains. Thus, it is of great importance to better understand the mechanisms by which nutrition and supplement therapies can heal the microbiome in critically ill patients in order to finally implement them in clinical practice with optimal safety and efficacy.
Elemental analysis in living human subjects using biomedical devices

Today, patients undergoing dialysis are at low risk for aluminum-induced dementia. Workers are unlikely to experience cadmium-induced emphysema and the public’s exposure to lead is an order of magnitude lower than in 1970. The research field of in vivo elemental analysis has played a role in these occupational and environmental health improvements by allowing the effects of people’s chronic exposure to elements to be studied using non-invasive, painless, and relatively low-cost technology. From the early 1960s to the present day, researchers have developed radiation-based systems to measure the elemental content of organs at risk or storage organs. This reduces the need for (sometimes painful) biopsy and the risk of infection. Research and development has been undertaken on forty-nine in vivo measurement system designs. Twenty-nine different in vivo elemental analysis systems, measuring 22 different elements, have been successfully taken from design and testing through to human measurement. The majority of these systems employ either neutron activation analysis or x-ray fluorescence analysis as the basis of the measurement. In this review, we discuss eight of the successful systems, explaining the rationale behind their development, the methodology, the health data that has resulted from application of these tools, and provide our opinion on potential future technical developments of these systems. We close by discussing four technologies that may lead to new directions and advances in the whole field.
Leaf Morphological and Biochemical Responses of Three Potato (Solanum tuberosum L.) Cultivars to Drought Stress and Aphid (Myzus persicae Sulzer) Infestation

Drought stress on plants can cause cellular water deficits and influence the physiology of host plants, which alter the performance of insect pests. This study was conducted to determine the effect of drought and aphid (Myzus persicae Sulzer) infestation on three potato (Solanum tuberosum L.) genotypes under greenhouse conditions. A factorial experiment involving three potato genotypes, two levels of drought, and two levels of aphid infestation was conducted. The potato genotypes possessed different levels of tolerance to drought and are described as tolerant (Qingshu 9), moderately tolerant (Longshu 3), and sensitive (Atlantic). Sixty-day-old potato plants were infested with aphid nymphs and monitored for 20 d. There was a significant variety × drought × aphid interaction effect on the parameters measured. The genotype Atlantic, which is sensitive to drought, exhibited greater tolerance to aphid infestation under drought or no drought conditions than the other genotypes. This genotype also exhibited poor host acceptance and the aphid survival rate, colonization success, and average daily reproduction were low. Qingshu 9, which is tolerant to drought, was highly susceptible to aphid infestation and exhibited high host acceptance and greater aphid survival rate, colonization success, and average daily reproduction compared to the other genotypes. This study demonstrates that the biochemical and morphological traits that confer drought tolerance in potato do not necessarily confer aphid tolerance.
Exclusive Breastfeeding Rates and Associated Factors in 13 “Economic Community of West African States” (ECOWAS) Countries

Exclusive breastfeeding (EBF) has important protective effects on child survival and also increases the growth and development of infants. This paper examined EBF rates and associated factors in 13 “Economic Community of West African States” (ECOWAS) countries. A weighted sample of 19,735 infants from the recent Demographic and Health Survey dataset in ECOWAS countries for the period of 2010–2018 was used. Survey logistic regression analyses that adjusted for clustering and sampling weights were used to determine the factors associated with EBF. In ECOWAS countries, EBF rates for infants 6 months or younger ranged from 13.0% in Côte d’Ivoire to 58.0% in Togo. EBF decreased significantly by 33% as the infant age (in months) increased. Multivariate analyses revealed that mothers with at least primary education, older mothers (35–49 years), and those who lived in rural areas were significantly more likely to engage in EBF. Mothers who made four or more antenatal visits (ANC) were significantly more likely to exclusively breastfeed their babies compared to those who had no ANC visits. Our study shows that EBF rates are still suboptimal in most ECOWAS countries. EBF policy interventions in ECOWAS countries should target mothers with no schooling and those who do not attend ANC. Higher rates of EBF are likely to decrease the burden of infant morbidity and mortality in ECOWAS countries due to non-exposure to contaminated water or other liquids.
Aberrant reward prediction error during Pavlovian appetitive learning in alexithymia

Abstract Extensive literature shows that alexithymia, a subclinical trait defined by difficulties in identifying and describing feelings, is characterized by multifaceted impairments in processing emotional stimuli. Nevertheless, its underlying mechanisms remain elusive. Here, we hypothesize that alexithymia may be characterized by an alteration in learning the emotional value of encountered stimuli and test this by assessing differences between individuals with low (LA) and high (HA) levels of alexithymia in the computation of reward prediction errors (RPEs) during Pavlovian appetitive conditioning. As a marker of RPE, the amplitude of the feedback-related negativity (FRN) event-related potential was assessed while participants were presented with two conditioned stimuli (CS) associated with expected or unexpected feedback, indicating delivery of reward or no-reward. No-reward (vs reward) feedback elicited the FRN both in LA and HA. However, unexpected (vs expected) feedback enhanced the FRN in LA but not in HA, indicating impaired computation of RPE in HA. Thus, although HA show preserved sensitivity to rewards, they cannot use this response to update the value of CS that predict them. This impairment may hinder the construction of internal representations of emotional stimuli, leaving individuals with alexithymia unable to effectively recognize, respond and regulate their response to emotional stimuli.
Type I Interferons and Cancer: An Evolving Story Demanding Novel Clinical Applications

The first report on the antitumor effects of interferon α/β (IFN-I) in mice was published 50 years ago. IFN-α were the first immunotherapeutic drugs approved by the FDA for clinical use in cancer. However, their clinical use occurred at a time when most of their mechanisms of action were still unknown. These cytokines were being used as either conventional cytostatic drugs or non-specific biological response modifiers. Specific biological activities subsequently ascribed to IFN-I were poorly considered for their clinical use. Notably, a lot of the data in humans and mice underlines the importance of endogenous IFN-I, produced by both immune and tumor cells, in the control of tumor growth and in the response to antitumor therapies. While many oncologists consider IFN-I as “dead drugs”, recent studies reveal new mechanisms of action with potential implications in cancer control and immunotherapy response or resistance, suggesting novel rationales for their usage in target and personalized anti-cancer treatments. In this Perspectives Article, we focus on the following aspects: (1) the added value of IFN-I for enhancing the antitumor impact of standard anticancer treatments (chemotherapy and radiotherapy) and new therapeutic approaches, such as check point inhibitors and epigenetic drugs; (2) the role of IFN-I in the control of cancer stem cells growth and its possible implications for the development of novel antitumor therapies; and (3) the role of IFN-I in the development of cancer vaccines and the intriguing therapeutic possibilities offered by in situ delivery of ex vivo IFN-stimulated dendritic cells.
Mancozeb exposure during development and lactation periods results in decreased oocyte maturation, fertilization rates, and implantation in the first-generation mice pups: Protective effect of vitamins E and C

This study aimed to evaluate the mancozeb (MNZ) impact on oocyte maturation of first-generation mice pups as well as their fertilization rate, embryo development, and implantation along with the preventative effect of vitamins E and C. Pregnant mice were randomly divided into six groups: control, vehicle, and MNZ (500 mg/kg body weight (BW)), vitamin E (200 mg/kg BW), MNZ plus vitamin E, MNZ plus vitamin C (100 mg/kg BW), and MNZ plus two vitamins. All treatments were conducted by oral gavage every 2 days from the second day of gestation until the end of lactation. Vitamin treatment was initiated 30 min before receiving MNZ. After birth, first-generation mice pups were kept until adulthood (8–10 W). Adult female mice pups superovulated and then the collected oocytes were examined for nuclear maturity status. After in vitro fertilization of metaphase II oocytes with sperm of the first-generation male mice pups, fertilization rate and embryo development were evaluated over 24 h. Also, the fecundity rate and the number of implanted embryos in vivo were studied on the eighth day of pregnancy. MNZ exposure during embryo development and lactation significantly decreased the total number of collected oocytes, oocyte maturation, fertilization rate, implantation rate, fecundity rate, and embryo development compared with the control group in the first-generation pups. In contrast, vitamin treatments significantly increased these parameters compared to the MNZ group. Reduction in the quality of oocyte, the rate of fertilization, embryo implantation, and development following MNZ exposure could decrease female reproductive success, while coadministration of vitamins E and C could prevent these complications.