Miracle-dz/UniFAR-FTUs huggingface dataset:
MIND-BEST: Web server for drugs and target discovery; design, synthesis, and assay of MAO-B inhibitors and theoretical-experimental study of G3PDH protein from Trichomonas gallinae.

Many drugs with very different affinity to a large number of receptors are described. Thus, in this work, we selected drug-target pairs (DTPs/nDTPs) of drugs with high affinity/nonaffinity for different targets. Quantitative structure-activity relationship (QSAR) models become a very useful tool in this context because they substantially reduce time and resource-consuming experiments. Unfortunately, most QSAR models predict activity against only one protein target and/or they have not been implemented on a public Web server yet, freely available online to the scientific community. To solve this problem, we developed a multitarget QSAR (mt-QSAR) classifier combining the MARCH-INSIDE software for the calculation of the structural parameters of drug and target with the linear discriminant analysis (LDA) method in order to seek the best model. The accuracy of the best LDA model was 94.4% (3,859/4,086 cases) for training and 94.9% (1,909/2,012 cases) for the external validation series. In addition, we implemented the model into the Web portal Bio-AIMS as an online server entitled MARCH-INSIDE Nested Drug-Bank Exploration & Screening Tool (MIND-BEST), located at http://miaja.tic. udc.es/Bio-AIMS/MIND-BEST.php . This online tool is based on PHP/HTML/Python and MARCH-INSIDE routines. Finally, we illustrated two practical uses of this server with two different experiments. In experiment 1, we report for the first time a MIND-BEST prediction, synthesis, characterization, and MAO-A and MAO-B pharmacological assay of eight rasagiline derivatives, promising for anti-Parkinson drug design. In experiment 2, we report sampling, parasite culture, sample preparation, 2-DE, MALDI-TOF and -TOF/TOF MS, MASCOT search, 3D structure modeling with LOMETS, and MIND-BEST prediction for different peptides as new protein of the found in the proteome of the bird parasite Trichomonas gallinae, which is promising for antiparasite drug targets discovery.
Removal of methylene blue from aqueous solutions using polyaniline/graphene oxide or polyaniline/reduced graphene oxide composites

ABSTRACT The polymeric nanocomposites polyaniline/graphene oxide (PANI/GO) and polyaniline/reduced graphene oxide (PANI/RGO) were synthesized for effective dye removal through the adsorption process. Synthesized composites were characterized by XRD, SEM, TEM and FTIR analyses. The sorption of methylene blue dye (MB) on the PANI/GO or (PANI/RGO) composites were studied as a function of contact time, concentration, temperature, adsorbent dosage and pH, and the results showed that MB sorption was dependent on pH value. The optimum concentration of the dye and the contact time for sorption of MB on PANI/GO or PANI/RGO was determined to be 270 min and 50 mg/L, respectively while the adsorbent dosage of PANI/GO and PANI/RGO were determined to be 0.4 and 0.3 g, respectively. At optimum conditions, the nature of the adsorption process have been investigated by kinetic and isotherm models. The results showed that the adsorption process followed the pseudo first-order kinetics this noticed from the higher value of correlation coefficient (R 2 = 0.991) and was best suited to the Langmuir model. The maximum dye adsorption capacity of PANI/GO and PANI/RGO were estimated to be 14.2 and 19.2 mg g−1 respectively. From the results, it can be assured that the PANI/RGO is more effectively than PANI/GO for the removal of dye pollutants in water. GRAPHICAL ABSTRACT
Single Synapse Indicators of Impaired Glutamate Clearance Derived from Fast iGluu Imaging of Cortical Afferents in the Striatum of Normal and Huntington (Q175) Mice

Changes in the balance between glutamate (Glu) release and uptake may stimulate synaptic reorganization and even synapse loss. In the case of neurodegeneration, a mismatch between astroglial Glu uptake and presynaptic Glu release could be detected if both parameters were assessed independently and at a single-synapse level. This has now become possible due to a new imaging assay with the genetically encoded ultrafast Glu sensor iGluu. We report findings from individual corticostriatal synapses in acute slices prepared from mice of either sex that were >1 year of age. Contrasting patterns of short-term plasticity and a size criterion identified two classes of terminals, presumably corresponding to the previously defined IT (intratelencephalic) and PT (pyramidal tract) synapses. The latter exhibited a higher degree of frequency potentiation/residual Glu accumulation and were selected for our first iGluu single-synapse study in Q175 mice, a model of Huntington's disease (HD). In HD mice, the decay time constant of the perisynaptic Glu concentration (TauD), as an indicator of uptake, and the peak iGluu amplitude, as an indicator of release, were prolonged and reduced, respectively. Treatment of WT preparations with the astrocytic Glu uptake blocker TFB-TBOA (100 nm) mimicked the TauD changes in homozygotes. Considering the largest TauD values encountered in WT, ∼40% of PT synapses tested in Q175 heterozygotes can be classified as dysfunctional. Moreover, HD but not WT synapses exhibited a positive correlation between TauD and the peak amplitude of iGluu. Finally, EAAT2 (excitatory amino acid transport protein 2) immunoreactivity was reduced next to corticostriatal terminals. Thus, astrocytic Glu transport remains a promising target for therapeutic intervention. SIGNIFICANCE STATEMENT Alterations in astrocytic Glu uptake can play a role in synaptic plasticity and neurodegeneration. Until now, the sensitivity of synaptic responses to pharmacological transport block and the resulting activation of NMDA receptors were regarded as reliable evidence for a mismatch between synaptic uptake and release. But the latter parameters are interdependent. Using a new genetically encoded sensor to monitor extracellular glutamate concentration ([Glu]) at individual corticostriatal synapses, we can now quantify the time constant of perisynaptic [Glu] decay (as an indicator of uptake) and the maximal [Glu] elevation next to the active zone (as an indicator of Glu release). The results provide a positive answer to the hitherto unresolved question of whether neurodegeneration (e.g., Huntington's disease) associates with a glutamate uptake deficit at tripartite excitatory synapses.
Comparison of Immune Responses to Different Versions of VLP Associated Stabilized RSV Pre-Fusion F Protein

Efforts to develop a vaccine for respiratory syncytial virus (RSV) have primarily focused on the RSV fusion protein. The pre-fusion conformation of this protein induces the most potent neutralizing antibodies and is the focus of recent efforts in vaccine development. Following the first identification of mutations in the RSV F protein (DS-Cav1 mutant protein) that stabilized the pre-fusion conformation, other mutant stabilized pre-fusion F proteins have been described. To determine if there are differences in alternate versions of stabilized pre-fusion F proteins, we explored the use, as vaccine candidates, of virus-like particles (VLPs) containing five different pre-fusion F proteins, including the DS-Cav1 protein. The expression of these five pre-F proteins, their assembly into VLPs, their pre-fusion conformation stability in VLPs, their reactivity with anti-F monoclonal antibodies, and their induction of immune responses after the immunization of mice, were characterized, comparing VLPs containing the DS-Cav1 pre-F protein with VLPs containing four alternative pre-fusion F proteins. The concentrations of anti-F IgG induced by each VLP that blocked the binding of prototype monoclonal antibodies using two different soluble pre-fusion F proteins as targets were measured. Our results indicate that both the conformation and immunogenicity of alternative VLP associated stabilized pre-fusion RSV F proteins are different from those of DS-Cav1 VLPs.
Effect of Fixed Orthodontic Treatment on Salivary Nickel and Chromium Levels: A Systematic Review and Meta-Analysis of Observational Studies

Nickel and chromium ions released from fixed orthodontic appliances may act as allergens. This study aimed to systematically review the effect of fixed orthodontic treatment on salivary levels of these ions by doing a meta-analysis on cross-sectional and cohort studies. The Web of Science, Scopus, Cochrane Library, and PubMed databases were searched for articles on salivary profile of nickel or chromium in patients under fixed orthodontic treatment published from January 1983 to October 2017. A random-effect meta-analysis was done using Review Manager 5.3 to calculate mean difference (MD) and 95% confidence interval (CI), and the quality of questionnaire was evaluated by the Newcastle–Ottawa scale. Fourteen studies were included and analyzed in this meta-analysis. Salivary nickel level was higher in periods of 10 min or less (MD = −11.5 µg/L, 95% CI = −16.92 to −6.07; P < 0.0001) and one day (MD = −1.38 µg/L, 95% CI = −1.97 to −0.80; P < 0.00001) after initiation of treatment compared to baseline (before the insertion of appliance). Salivary chromium level was higher in periods of one day (MD = −6.25 µg/L, 95% CI = −12.00 to −0.49; P = 0.03) and one week (MD = −2.07 µg/L, 95% CI = −3.88 to −0.26; P = 0.03) after the initiation of treatment compared to baseline. Corrosion of fixed orthodontic appliances leads to elevated salivary nickel and chromium concentrations early after initiation of orthodontic treatment. Randomized clinical trials controlling for factors affecting the saliva composition are recommended on a higher number of patients and among different ethnicities.
Eyelid Spontaneous Blink Analysis and Age-Related Changes Through High-Speed Imaging.

PURPOSE To analyze the spontaneous eyelid blink and sphincter closure activity of the orbicularis oculi by measuring the horizontal eyelid movement. METHODS Individuals 18+ years of age, any ethnicity, and gender were recruited. Participants completed a questionnaire to determine eligibility. Exclusion criteria included the following: history of facial trauma, nerve palsy, surgery, use of periorbital neuromodulators or filler within the past year, thyroid eye disease, and eyelid or ocular surface disease. Data were collected from participants by decade. Eyelid blinks were recorded using the FPS 1000HD. The motions of 3 spontaneous blinks in primary gaze were recorded. All blinks were reviewed and one chosen for most accurate analysis. Horizontal palpebral fissure width and its changes of open and closed eye measurements were taken using National Institute of Health ImageJ software version 2.0. The data were subjected to SAS version 9.4 analysis using paired t test, t test, and linear models. RESULTS One hundred thirty-six patients were recruited. Fourteen patients were excluded; 122 patients were used in analysis. Ages ranged from 22 to 90 years. Participants were divided into 6 groups according to age (20-29, 30-39, 40-49, 50-59, 60-69, and 70+ years of age). The average horizontal fissure length across all ages was 24.23 mm. Average change in horizontal fissure length decreased 1.42 mm among all ages. There was a statistically significant difference comparing age 20-29 decade to age 70+ decade. CONCLUSIONS Horizontal fissure length changes with eyelid blink and defines 1 component of the eyelid sphincter.
NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor–Positive Breast Cancer

Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor–positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design: Eligible patients with clinical stage II/III ER+/HER2− breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1–21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 > 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%). Results: Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, P < 0.001). Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and PIK3CA status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression. Conclusions: Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. Clin Cancer Res; 23(15); 4055–65. ©2017 AACR.
Preferences for Feeding Tube Use and Their Determinants Among Cognitively Intact Nursing Home Residents in Wuhan, China: A Cross-Sectional Study

Introduction: Standard advance care planning practice is yet to be established in Mainland, China, and little is known about feeding tube preferences among Chinese nursing home residents. The purpose of the study was to examine preferences for feeding tube use and its predictors among frail and cognitively competent nursing home residents in Wuhan, China. Method: A cross-sectional sample of 682 nursing home residents were interviewed face-to-face using a structured questionnaire from 2012 to 2014. Results: A total of 54.5% of participants would accept feeding tube. Participants who reported greater quality of life (odds ratio [OR] = 2.67), having health insurance (OR = 2.09) were more willing to accept feeding tube. Participants with greater impairment in physical health (OR = 0.94) were less willing to accept it. Discussion: Health care professionals need to routinely assess nursing home residents’ feeding tube preferences. It is imperative to consider sociocultural perspectives in understanding Chinese older adults’ decision making for end-of-life care.
Dried fruit and public health – what does the evidence tell us?

Abstract A scientific workshop held in the UK explored the potential contribution of traditional dried fruits to public health, identified gaps in the evidence and addressed priorities for research. Presentations considered the categorisation and composition of dried fruits; dried fruit and gastrointestinal health; the polyphenol content of dried fruits and their potential contribution to health; dried fruit and appetite in relation to the psychology of snacking and obesity; dried fruit and dental health including its role as a snack; and conflicts in public health advice for dried fruits. A round table discussion explored the contribution of dried fruit to “five a day” fruit and vegetable intake and fibre intake, whether dried fruits have equivalence with fresh in terms of dietary advice, advice on snacking in relation to dental health and appetite control, informing the public about different types of dried fruits and avoiding consumer confusion, and future research requirements.
Opioid Use in Pregnant Women and Neonatal Abstinence Syndrome—A Review of the Literature

Opiate use during pregnancy has been an increasing problem over the last two decades, making it an important social and health concern. The use of such substances may have serious negative outcomes in the newborn, and clinical and cognitive conditions have been reported, including neonatal abstinence syndrome, developmental problems, and lower cognitive performance. These conditions are common when opiates are used during pregnancy, making the prescription of these kinds of drugs problematic. Moreover, the mother may develop opiate addiction, thus, increasing the likelihood of the infant being born with any of those conditions. This paper reviews the use of opiates during pregnancy and focuses mainly on the neonatal abstinence syndrome. First, the commonly prescribed opiates will be identified, namely those usually involved in cases of addiction and/or neonatal abstinence syndrome. Second, published approaches to deal with those problems will be presented and discussed, including the treatment of both the mother and the infant. Finally, we will outline the treatments that are safest and most efficient, and will define future goals, approaches, and research directions for the scientific community regarding this problem.
Minichromosome Maintenance Proteins MCM-3, MCM-5, MCM-7, and Ki-67 as Proliferative Markers in Adrenocortical Tumors

Background/Aim: Morphological features, combined with Ki-67 proliferative index, remain the standard for discriminating benign and malignant adrenocortical tumors. The aim of this study was to evaluate the role of minichromosome maintenance proteins MCM-3, MCM-5, MCM-7, and Ki-67 as proliferative markers in adrenocortical tumors. Materials and Methods: Specimens of 81 adrenocortical adenomas and 3 adrenocortical carcinomas were stained with antibodies against MCM-3, 5, 7 and Ki-67. Results: Malignant tumors were characterized by a greater size (p=0.017), volume (p=0.017), and higher levels of Ki-67 (p=0.005), MCM-3 (p=0.005), MCM-7 (p=0.008), but not MCM-5 (p=0.069). The markers' levels were independent from the tumors' size and volume, the patient's age and hormonal status. ROC curves showed Ki-67 (AUC 0.984), MCM-3 (AUC 0.984), and MCM-7 (AUC 0.950), but not MCM-5 (AUC 0.820) to be reliable markers. Conclusion: Ki-67, MCM-3, and MCM-7, but not MCM-5 are reliable proliferative and diagnostic markers in discerning benign and malignant adrenocortical tumors.
Transmission phenotype of Mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology

In a study of household contacts (HHC), households were categorized into High (HT) and Low (LT) transmission groups based on the proportion of HHC with a positive tuberculin skin test. The Mycobacterium tuberculosis (Mtb) strains from HT and LT index cases of the households were designated Mtb-HT and Mtb-LT, respectively. We found that C3HeB/FeJ mice infected with Mtb-LT strains exhibited significantly higher bacterial burden compared to Mtb-HT strains and also developed diffused inflammatory lung pathology. In stark contrast, a significant number of mice infected with Mtb-HT strains developed caseating granulomas, a lesion type with high potential to cavitate. None of the Mtb-HT infected animals developed diffused inflammatory lung pathology. A link was observed between increased in vitro replication of Mtb-LT strains and their ability to induce significantly high lipid droplet formation in macrophages. These results support that distinct early interactions of Mtb-HT and Mtb-LT strains with macrophages and subsequent differential trajectories in pathological disease may be the mechanism underlying their transmission potential.
Persistence of recipient-type endothelium after allogeneic hematopoietic stem cell transplantation

Background The possibility that allogeneic hematopoietic stem cell transplantation performed across the ABO blood group-barrier is associated with an increase of graft-versus-host disease, in particular endothelial damage, has not been elucidated so far. For this reason, we investigated the level of endothelial cell chimerism after allogeneic hematopoietic stem cell transplantation in order to delineate the role of hematopoietic stem cells in endothelial replacement. Design and Methods The frequency of donor-derived endothelial cells was analyzed in 52 hematopoietic stem cell transplant recipients, in 22 normal skin biopsies, in 12 skin samples affected by graft-versus-host disease, various tissues from five autopsies and four secondary solid tumors by ABH immunohistochemistry, XY fluorescence in situ hybridization and short tandem repeat analysis of laser captured endothelial cells. Results Skin biopsies from two patients transplanted with minor ABO-incompatible grafts (i.e. O in A) showed 3.3% and 0.9% H antigen-positive donor-derived endothelial cells by ABH immunohistochemistry. Tumor biopsies from two recipients showed 1.2% and 2.5% donor-derived endothelial cells by combined immunohistochemistry/ fluorescence in situ hybridization. All other skin samples, heart, liver, bone-marrow, and tumor tissues failed to reveal donor-type endothelial cells up to several years after ABO-incompatible hematopoietic stem cell transplantation. Conclusions Endothelial cell replacement by bone marrow-derived donor cells after allogeneic hematopoietic stem cell transplantation is a rare event. It does not seem to represent a major mechanism of physiological in vivo blood vessel formation, tumor neoangiogenesis, vascular repair after graft-versus-host disease episodes or acceptance of ABO-incompatible grafts.
Exploiting Self-Capacitances for Wireless Power Transfer

Conventional approaches for wireless power transfer rely on the mutual coupling (near-field or far-field) between the transmitter and receiver transducers. As a result, the power-transfer efficiency of these approaches scales non-linearly with the cross-sectional area of the transducers and with the relative distance and respective alignment between the transducers. In this paper, we show that when the operational power-budget requirements are in the order of microwatts, a self-capacitance (SC)-based power delivery has significant advantages in terms of the power transfer-efficiency, receiver form-factor, and system scalability when compared to other modes of wireless power transfer (WPT) methods. We present a simple and a tractable equivalent circuit model that can be used to study the effect of different parameters on the SC-based WPT. In this paper, we have experimentally verified the validity of the circuit using a cadaver mouse model. We also demonstrate the feasibility of a hybrid telemetry system where the microwatts of power, which can be harvested from SC-based WPT approach, is used for back-scattering a radio-frequency (RF) signal and is used for remote sensing of in vivo physiological parameters such as temperature. The functionality of the hybrid system has also been verified using a cadaver mouse model housed in a cage that was retrofitted with 915 MHz RF back-scattering antennas. We believe that the proposed remote power-delivery and hybrid telemetry approach would be useful in remote activation of wearable devices and in the design of energy-efficient animal cages used for long-term monitoring applications.