Miracle-dz/UniFAR-FTUs huggingface dataset:
Discover natural compounds as potential phosphodiesterase-4B inhibitors via computational approaches

cAMP, intracellular cyclic adenosine monophosphate, is a ubiquitous second messenger that plays a key role in many physiological processes. PDE4B which can reduce the cAMP level by hydrolyzing cAMP to 5′-AMP has become a therapeutic target for the treatment of human diseases such as respiratory disorders, inflammation diseases, neurological and psychiatric disorders. However, the use of currently available PDE4B inhibitors is restricted due to serious side effects caused by targeting PDE4D. Hence, we are attempting to find out subfamily-selective PDE4B inhibitors from natural products, using computer-aided approaches such as virtual screening, docking, and molecular dynamics simulation. Finally, four potential PDE4B-selective inhibitors (ZINC67912770, ZINC67912780, ZINC72320169, and ZINC28882432) were found. Compared to the reference drug (roflumilast), they scored better during the virtual screening process. Binding free energy for them was −317.51, −239.44, −215.52, and −165.77 kJ/mol, better than −129.05 kJ/mol of roflumilast. The pharmacophore model of the four candidate inhibitors comprised six features, including one hydrogen bond donor, four hydrogen bond acceptors, and one aromatic ring feature. It is expected that our study will pave the way for the design of potent PDE4B-selective inhibitors of new drugs to treat a wide variety of diseases such as asthma, COPD, psoriasis, depression, etc.
What Factors Are Associated With the Development of Pressure Ulcers in a Medical Intensive Care Unit?

Statement of the Problem:Instruments used to determine the risk of pressure ulcer development are universally applied to adult patients. These instruments do not differentiate between intensive and acute care patients. Background:Pressure ulcers contribute to negative outcomes such as increases in pain and discomfort, risk of infection, hospital length of stay and costs, and a decrease in quality of life. Appropriately identifying risk factors is paramount to implementing a targeted care plan to avoid pressure ulcer development as well as pinpointing appropriate treatments if an ulcer develops. Objective:The purpose of this nursing research study was to identify factors associated with pressure ulcer development in a medical intensive care unit. Methods:A 15-month retrospective chart review of patients with pressure ulcers in a medical intensive care unit was performed. Statistics were computed on demographics and variables of interest including: pressure ulcer stage, vasopressor infusion, oxygen requirement, comorbidities, primary diagnosis, length of stay, mortality, age, gender, weight, Braden scores, and albumin level. Results:The characteristics of 76 patients who developed pressure ulcers were evaluated. An equal number of men (n = 38) and women (n = 38) were included. Forty-seven percent had a stage II pressure ulcer. The presence of hemodynamic support with vasopressor administration (P = .016) and the length of stay (P = .021) were noted as the most significant factors in pressure ulcer development in this study. Conclusions:Vasopressor use and length of stay are not factors that are accounted for in current pressure ulcer risk assessment instruments. The administration of vasopressor support and patient length of stay are potential contributory factors that need to be considered when assessing patients. Instruments specific to intensive care unit pressure ulcer risk stratification are warranted and should include the unique characteristics of a critically ill patient.
Developing imidazole analogues as potential inhibitor for Leishmania donovani trypanothione reductase: virtual screening, molecular docking, dynamics and ADMET approach

Visceral leishmaniasis (VL) affects Indian subcontinent, African and South American continent, and it covers 70 countries worldwide. Visceral form of leishmaniasis is caused by Leishmania donovani in Indian subcontinent which is lethal if left untreated. Extensive resistance to antileishmanial drugs such as sodium stibogluconate, pentamidine and miltefosine and their decreased efficacy has been reported in the endemic region. Amphotericin B drug has shown good antileishmanial activity with significant toxicity, but its cost of treatment has limited the outreach of this treatment to affected people living in endemic zone. So, there is an urgent need to identify new antileishmanial drugs with excellent activity and minimal toxicity issues. Trypanothione reductase, a component of antioxidant system, is necessary for parasite growth and survival to raise infection. To develop potential inhibitor, we docked nine hundred and eighty-four 5-nitroimidazole analogues along with clomipramine which is a well-known inhibitor for TR. Total one hundred and forty-seven 5-nitroimidazole analogues with better docking score than clomipramine were chosen for ADMET and QikProp studies. Among these imidazole analogues, total twenty-four imidazole analogues and clomipramine were chosen on the basis of their ADMET, QikProp, and prime MM-GBSA study. Later on, two analogues with best MM-GBSA dG bind were undergone molecular dynamic simulation to ensure protein–ligand interactions. Using above approach, we confirm that ethyl 2-acetyl-5-[4-butyl-2-(3-hydroxypentyl)-5-nitro-1H-imidazol-1-yl]pent-2-enoate can be a drug candidate against L. donovani for the treatment of VL in the Indian subcontinent.
Molecular dynamics simulation of the effects of single (S221P) and double (S221P and K216E) mutations in the hemagglutinin protein of influenza A H5N1 virus: a study on host receptor specificity

Avian influenza viruses of subtype H5N1 circulating in animals continue to pose threats to human health. The binding preference of the viral surface protein hemagglutinin (HA) to sialosaccharides of receptors is an important area for understanding mutations in the receptor binding site that could be the cause for avian-to-human transmission. In the present work, we studied the effect of two receptor binding site mutations, S221P singly and in combination with another mutation K216E in the HA protein of influenza A H5N1 viruses. Docking of sialic acid ligands corresponding to both avian and human receptors and molecular dynamics simulations of the complexes for wild and mutant strains of H5N1 viruses were carried out. The H5N1 strain possessing the S221P mutation indicated decreased binding to α2,3-linked sialic acids (avian receptor, SAα2,3Gal) when compared to the binding of the wild-type strain that did not possess the HA-221 mutation. The binding to α2,6-linked sialic acids (human receptor, SAα2,6Gal) was found to be comparable, indicating that the mutant strain shows limited dual receptor specificity. On the other hand, the S221P mutation in synergism with the K216E mutation in the binding site, resulted in increased binding affinity for SAα2,6Gal when compared to SAα2,3Gal, indicative of enhanced binding to human receptors. The in-depth study of the molecular interactions in the docked complexes could explain how co-occurring mutations in the HA viral protein can aid in providing fitness advantage to the virus, in the context of host receptor specificity in emerging variants of H5N1 influenza viruses.
Steered molecular dynamics study reveals insights into the function of the repetitive B region of collagen- and fibrinogen-binding MSCRAMMs

MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) are modular proteins covalently anchored in the bacterial cell wall of many Gram-positive bacteria. The N-terminal region of most MSCRAMMs carries the ligand-binding domains (A region) which specifically target the host extracellular matrix (ECM) proteins such as collagen, fibrinogen and fibronectin. In Staphylococcus aureus Cna, the prototype collagen-binding MSCRAMM, the A region is followed by a repetitive B region which is found to be conserved among many Gram-positive bacteria. This conservation signifies an important functional role for the B region which is made of repetitive domains. It was suggested that this region could act as a ‘stalk’ as well as a ‘spring’ to present the ligand-binding A region, away from the bacterial surface. But there is no clear functional implication of this region available till date. Each repetitive domain in the B region possesses a variant of the Ig fold called the CnaB fold. Additionally, the B repeats are also paired and the pairs are clustered together. To investigate if the B domains have a function similar to the Ig domains in the I-band region of the giant muscle protein, titin, steered molecular dynamics simulations of one, two and four B repeats of Cna were carried out. The results of the simulations suggest that the B region could provide mechanical stability, extensibility and elasticity to Cna due to the CnaB fold as well as the clustered arrangement of their domains. This study thus provided further insights into the biological underpinnings of adhesin–host interaction.
Efficacy of a balloon‐expandable vascular access system in transfemoral TAVI patients

Vascular complications (VC) are a serious and frequent complication of transfemoral transcatheter aortic valve implantation (TAVI) and result in increased morbidity and mortality. It has been suggested that newly developed vascular sheaths may increase the ability to perform transfemoral TAVI in patients with normal and access‐limiting peripheral artery disease (PAD) and reduce vascular complications. Aims: We sought to assess the safety and efficacy of the 19 French (F) SoloPath balloon‐expandable transfemoral vascular access system in patients who underwent transfemoral TAVI at our center between 2011 and 2014. Methods and results: Single‐center retrospective study of 90 patients who underwent transfemoral TAVI with the use of the SoloPath sheath. Patients were categorized into two groups according to a sheath to femoral artery ratio (SFAR) of less than or equal to 1.05, or greater than 1.05. Overall, the incidence of major bleeding complications was low, 4.4%. No significant differences were found in technical or procedural success rates (100% in both groups and 100% vs. 91.3; P = 0.09; respectively), total vascular complications (20.8 vs. 21.7; P = 0.92) or total bleeding complications (20.8 vs. 30.4; P = 0.36 between those with SFAR greater or less than 1.05. Conclusions: The use of the SoloPath balloon‐expandable sheath is feasible and safe even in patients with SFAR > 1.05, showing no increased vascular or bleeding complications compared to patients with larger vascular access. © 2016 Wiley Periodicals, Inc.
MANAGEMENT DEVELOPMENT PROGRAM

Program Description Emory Medicine’s Management Development Program seeks to attract, position, develop, and advance talent for management and leadership positions. Within three to five years, participants will progress through the three phases, resulting in the opportunity to fill a permanent leadership position upon completion of the program. Participants have the opportunity to join an emerging leader network group, learn from mentors and executive leaders, and participate in continuing professional development.
Investigating the effect of charged amino acids on DNA conformation in EcoRI–DNA complex: a molecular dynamics simulation study

Sequence-specific binding of proteins to DNA is essential for almost all the cellular processes like transcription, translation, replication, etc. One among the various mechanisms that has been identified so far that contributes to the specificity in protein–DNA interaction is the DNA conformational change. Electrostatic neutralization of the phosphate groups by the positively charged amino acid residues in proteins is thought to bring about such conformational changes in DNA. Here, we employ molecular dynamics simulations to examine the effect of charge on amino acids Lys113, Arg145, and Asp91 which are attached to the scissile phosphate on the conformation of DNA in EcoRI–DNA complex. The results indicate that the charge of these amino acids is essential for maintaining the local conformation of DNA in the EcoRI-bound form. Interestingly, we observe that the positively charged amino acids Lys113 and Arg145 have a long-range influence on the DNA conformation, whereas the negatively charged amino acid Asp91 has only a localized effect on the DNA conformation. The charge on the amino acids also alters the collective dynamics of EcoRI. Collectively, the results shed light on the diversity of the effect of charges on DNA conformation as well as on protein dynamics.
Effect of glycosylation on hydration behavior at the ice-binding surface of the Ocean Pout type III antifreeze protein: a molecular dynamics simulation

Antifreeze proteins (AFPs), found in certain vertebrates, plants, fungi and bacteria have the ability to permit their survival in subzero environments by thermal hysteresis mechanism. However, the exact mechanism of ice growth inhibition is still not clearly understood. Here, four long explicit molecular dynamics (MD) simulations have been carried out at two different temperatures (277 and 298 K) with and without glycan to study the conformational rigidity of the Ocean pout type III antifreeze protein in aqueous medium and the structural arrangements of water molecules hydrating its ice-binding surface. It is found that irrespective of the temperature the ice-binding surface (IBS) of the protein is relatively more rigid than its non ice-binding surface (NonIBS) in its native and glycosylated form. Hydrophilic residues N14, T18 and Q44 are essential to antifreeze activity. Radial distribution, density distribution function and nearest neighbor orientation plots with respect to individual two surfaces confirm that density of water molecule near these binding surface in native and glycosylated form are relatively more than the nonbinding surface. The glycosylated form shows a strong peak than the native one. From rotational auto correlation function of water molecules around ice-binding sites, it is prominent that with increase in temperature, strong interaction between the water oxygen and the hydrogen bond acceptor group on the protein-binding surface decreases. This provides a possible molecular reason behind the ice-binding activity of ocean pout at the prism plane of ice.
Emotional Intelligence: Review of Research and Educational Implications

Abstract This article provides a critical review of the research field of emotional intelligence (EI) and examines the usefulness of the construct in the debate on educational policy and practice. The authors examine two approaches to the theory and measurement of EI and summarize the evidence linking EI to life success and academic achievement. Also considered is whether or not EI can be changed or developed, and how it might be facilitated in educational practice. In conclusion, while a distinct construct of EI remains debatable; many of the attributes encompassed by this term do predict that life success and programmes of socio-emotional learning in schools may usefully contribute to the development of these attributes.
The wise radialist's guide to optimal transfemoral access: Selection, performance, and troubleshooting

Transradial access (TRA) has reduced vascular access‐site complication (VASC) and bleeding rates in patients undergoing coronary angiography and intervention. A “radial‐first” approach should be adopted and indications of TRA extended in order to maximize its beneficial effect. However, in certain clinical scenarios, transfemoral access (TFA) is a preferable or a mandatory route to successfully perform the procedure. Since the widespread adoption of TRA, a paradoxical increase in VASC rates has been observed in patients undergoing TFA, which might be attributed to a combination of increased risk profile of both the procedures and the patients, and a loss of skills in securing TFA by those who are now default radial operators. In the present article we provide recommendations on how to optimize patient selection for TRA and TFA, how to manage access site crossover, and how to perform state‐of‐the‐art femoral artery puncture. © 2016 Wiley Periodicals, Inc.
Management of vascular access after TAVR: Let's keep it simple

Bleeding and vascular complications are major causes of morbidity and mortality after transfemoral TAVR. Compared with standard approaches to hemostasis, the catheter balloon occlusion technique CBOT) resulted in significant reduction in major bleeding and vascular complications (18.6% vs. 5.5%, P = 0.042). Femoral crossover could not be achieved in 3.6%, and CBOT led to vessel dissection in 7.2%, major or life‐threatening bleeding in 5.5%, need for transfusion > 2 units in 10.9%, and minor bleeding or hematoma in 21.8% of patients.
An iris recognition approach through structural pattern analysis methods

Abstract: Continuous efforts have been made to improve the robustness of iris coding methods since Daugman's pioneering work on iris recognition was published. Iris recognition is at present used in several scenarios (airport check‐in, refugee control etc.) with very satisfactory results. However, in order to achieve acceptable error rates several imaging constraints are enforced, which reduce the fluidity of the iris recognition systems. The majority of the published iris recognition methods follow a statistical pattern recognition paradigm and encode the iris texture information through phase, zero‐crossing or texture‐analysis based methods. In this paper we propose a method that follows the structural (syntactic) pattern recognition paradigm. In addition to the intrinsic advantages of this type of approach (intuitive description and human perception of the system functioning), our experiments show that the proposed method behaves comparably to the statistical approach that constitutes the basis of nearly all deployed systems.
A hybrid neural network approach for credit scoring

The development of an effective credit scoring model has become a very important issue as the credit industry is confronted with ever‐intensifying competition and aggravating bad debt problems. During the past few years, a substantial number of studies in the field of statistics have been conducted to improve the accuracy of credit scoring models. In order to refine the classification and decrease misclassification, this paper presents a two‐stage model. Focusing on classification, the first stage aims at constructing an artificial neural network (ANN)‐based credit scoring model to categorize applicants into the group of accepted (good) credit and the group of rejected (bad) credit. Switching from classification to reassignment, the second stage proceeds to reduce the Type I error by retrieving the originally rejected good credit applicants to conditional acceptance using the Case‐Based Reasoning (CBR) classification technique. The proposed model (RST–ANN–CBR) is applied to a credit card dataset to verify its effectiveness. As the results indicate, the proposed model is able to achieve more accurate credit scoring than four other methods; more importantly, it is validated to recover potentially lost customers and to increase business revenues.
Hybrid recommendations for mobile commerce based on mobile phone features

Mobile data communications have evolved as the number of third generation (3G) subscribers has increased. The evolution has triggered an increase in the use of mobile devices, such as mobile phones, to conduct mobile commerce and mobile shopping on the mobile web. There are fewer products to browse on the mobile web; hence, one‐to‐one marketing with product recommendations is important. Typical collaborative filtering (CF) recommendation systems make recommendations to potential customers based on the purchase behaviour of customers with similar preferences. However, this method may suffer from the so‐called sparsity problem, which means there may not be sufficient similar users because the user‐item rating matrix is sparse. In mobile shopping environments, the features of users' mobile phones provide different functionalities for using mobile services; thus, the features may be used to identify users with similar purchase behaviour. In this paper, we propose a mobile phone feature (MPF)‐based hybrid method to resolve the sparsity issue of the typical CF method in mobile environments. We use the features of mobile phones to identify users' characteristics and then cluster users into groups with similar interests. The hybrid method combines the MPF‐based method and a preference‐based method that uses association rule mining to extract recommendation rules from user groups and make recommendations. Our experiment results show that the proposed hybrid method performs better than other recommendation methods.
A multi‐resolution multi‐classifier system for speaker verification

This paper describes a Speaker Verification System based on the use of multi resolution classifiers in order to cope with performance degradation due to natural variations of the excitation source and of the vocal tract. The different resolution representations of the speaker are obtained by considering multiple frame lengths in the feature extraction process and from these representations a single Pseudo‐Multi Parallel Branch (P‐MPB) Hidden Markov Model is obtained. In the verification process, different resolution representations of the speech signal are classified by multiple P‐MPB systems: the final decision is obtained by means of different combination techniques. The system based on the Weighted Majority Vote technique considerably outperforms baseline systems: improvements are between 15% and 38%. The execution time of the verification process is also evaluated and it proves to be very acceptable, thus allowing the use of the approach for applications in real time systems.
Steered molecular dynamics for studying ligand unbinding of ecdysone receptor

Ecdysone receptor (EcR) is an important target for pesticide design. Ligand binding regulates EcR transcriptional activity similar to other nuclear receptors; however, the pathways by which ligands enter and leave the EcR remain poorly understood. Here, we performed computational studies to identify unbinding pathways of an ecdysone agonist [the selective ecdysone agonist, BYI06830] from the EcR ligand binding domain (EcR LBD). BYI06830 can dissociate from EcR LBD via four different pathways with little effect on receptor structure. By comparing the potential of mean force (PMF) of four pathways, path 2 was considered to be the most likely exit path for BYI06830, which was located in the cleft formed by the H3-H4 loop, H6-H7 loop, and the H11 C-terminus. Furthermore, structural features along path 2 were analyzed and the structural snapshots of the metastable and transition states were isolated to illustrate the unbinding mechanism of ecdysone agonist from EcR LBD.
Renal Ultrasound Correlates with Renal Nuclear Scan in Upper Tract Surveillance of Spinal Cord-Injured Patients

Purpose: Renal ultrasound (RUS), renal nuclear scan (RNS), and intravenous pyelogram (IVP) are the most common studies used for surveillance of upper urinary tracts of spinal cord-injured (SCI) patients with neurogenic bladder (NGB). There is lack of consensus regarding which upper urinary tract studies should be incorporated in the routine surveillance protocol of SCI/NGB patients. We sought to determine if it is necessary to include both RUS and RNS as part of routine upper tract surveillance in SCI patients. Materials and Method: We retrospectively reviewed the medical records, including RUS and RNS reports, of 178 SCI patients treated at the Miami VA Medical Center during the years 1996-2001. The mean age was 56 years (range, 22-84 years). Of these 178 patients, 162 had a total of 478 paired and matched RUS and RNS studies (i.e., one RUS and one RNS, generally scheduled within 48 hours of each other) suitable for analysis. 16 patients were omitted from the study because they lacked paired and matched .