New Methods to Improve Protein Structure Modeling

Proteins are considered the central compound necessary for life, as they play a crucial role in governing several life processes by performing the most essential biological and chemical functions in every living cell. Understanding protein structures and functions will lead to a significant advance in life science and biology. Such knowledge is vital for various fields such as drug development and synthetic biofuels production. Most proteins have definite shapes that they fold into, which are the most stable state they can adopt. Due to the fact that the protein structure information provides important insight into its functions, many research efforts have been conducted to determine the protein 3-dimensional structure from its sequence. The experimental methods for protein 3-dimensional structure determination are often time-consuming, costly, and even not feasible for some proteins. Accordingly, recent research efforts focus more and more on computational approaches to predict protein 3-dimensional structures. Template-based modeling is considered one of the most accurate protein structure prediction methods. The success of template-based modeling relies on correctly identifying one or a few experimentally determined protein structures as structural templates that are likely to resemble the structure of the target sequence as well as accurately producing a sequence alignment that maps the residues in the target sequence to those in the template. In this work, we aim at improving the template-based protein structure modeling by enhancing the correctness of identifying the most appropriate templates and precisely aligning the target and template sequences. Firstly, we investigate employing inter-residue contact score to measure the favorability of a target sequence fitting in the folding topology of a certain template. Secondly, we design a multi-objective alignment algorithm extending the famous Needleman-Wunsch algorithm to obtain a complete set of alignments yielding Pareto optimality. Then, we use protein sequence and structural information as objectives and generate the complete Pareto optimal front of alignments between target sequence and template. The alignments obtained enable one to analyze the trade-offs between the potentially conflicting objectives. These approaches lead to accuracy enhancement in template-based protein structure modeling

The motor effects of 0.25% bupivacaine vs 0.19 bupivacaine in ultrasound-guided axillary brachial plexus block in pediatrics undergoing below-elbow orthopedic surgeries: A randomized controlled study

ABSTRACTBackground The standard dose of bupivacaine used in axillary brachial plexus block (ABPB) in pediatrics is 0.5 ml/kg of bupivacaine 0.25%. However, bupivacaine (0.19%) is still to be investigated for peripheral nerve block in pediatrics regarding the efficacy and adequacy of intra- and postoperative analgesia and degree of motor affection. We aimed to compare different concentrations (0.25%, 0.19%) of bupivacaine plus dexmedetomidine mixture to perform US-ABPB in pediatrics undergoing upper limb surgery distal to the elbow regarding affecting the postoperative motor power and adequacy of intra- and postoperative analgesia.Methods This prospective, randomised-controlled, double-blinded work was performed on 60 pediatric individuals presenting for upper limb orthopedic surgeries in the wrist, hand, and elbow distal to cubital fossa with surgical time planned to not exceed 1 h. 0.25% bupivacaine plus 1 µg/kg dexmedetomidine (Group A) or 0.19% bupivacaine in addition to 1 µg/kg dexmedetomidine (Group B) were given at random to participants. Motor power and pain were assessed using the Modified Bromage scale, Face, Legs, Activity, Cry, and Consolability (FLACC) score, respectively.Results A highly substantial variation was recorded between the two groups in Bromage 0 till Bromage 60 with higher values in group (B), and no substantial variation was found in Bromage 90 till Bromage 180 existed between the two groups. No substantial variation existed among the two groups with regard to FLACC score in FLACC0 (immediately after recovery), 1st hour after recovery, and 12th hour after recovery, and FLACC was significantly more (p < 0.05) in group B contrasted to group A in the 4th hour after recovery and 8th hour after recovery.Conclusion Using a lower concentration of bupivacaine (0.19%) plus dexmedetomidine (1 µg/kg) was associated with regain of postoperative motor power with the same postoperative analgesic efficacy compared to the standard concentration (0.25%) bupivacaine plus dexmedetomidine (1 µg/kg) in the early postoperative period in US-ABPB

Identifying At-Risk Students for Early Interventions—A Time-Series Clustering Approach

The purpose of this paper is to identify at-risk online students earlier, more often, and with greater accuracy using time-series clustering. The case study showed that the proposed approach could generate models with higher accuracy and feasibility than the traditional frequency aggregation approaches. The best performing model can start to capture at-risk students from week 10. In addition, the four phases in student’s learning process detected holiday effect and illustrate at-risk students’ behaviors before and after a long holiday break. The findings also enable online instructors to develop corresponding instructional interventions via course design or student–teacher communications

Conformational Clusters of Phosphorylated Tyrosine

Tyrosine phosphorylation plays an important role in many cellular and intercellular processes including signal transduction, subcellular localization, and regulation of enzymatic activity. In 1999, Blom et al., using the limited number of protein data bank (PDB) structures available at that time, reported that the side chain structures of phosphorylated tyrosine (pY) are partitioned into two conserved conformational clusters (Blom, N.; Gammeltoft, S.; Brunak, S. J. Mol. Biol. 1999, 294, 1351−1362). We have used the spectral clustering algorithm to cluster the increasingly growing number of protein structures with pY sites, and have found that the pY residues cluster into three distinct side chain conformations. Two of these pY conformational clusters associate strongly with a narrow range of tyrosine backbone conformation. The novel cluster also highly correlates with the identity of the <i>n</i> + 1 residue, and is strongly associated with a sequential pYpY conformation which places two adjacent pY side chains in a specific relative orientation. Further analysis shows that the three pY clusters are associated with distinct distributions of cognate protein kinases

The educational value of ward rounds as a learning and teaching opportunity for house officers, medical officers, and registrars in Sudanese hospitals: a multi-center cross-sectional study

Abstract Background Ward rounds are a cornerstone in the educational experience of junior doctors and an essential part of teaching patient care. Here, we aimed to assess the doctors’ perception of ward rounds as an educational opportunity and to identify the obstacles faced in conducting a proper ward round in Sudanese hospitals. Method A cross-sectional study was conducted from the 15th to the 30th of January 2022 among house officers, medical officers, and registrars in about 50 teaching and referral hospitals in Sudan. House officers and medical officers were considered the learners, while specialist registrars were considered the teachers. Doctors’ perceptions were assessed using an online questionnaire, with a 5-level Likert scale to answer questions. Results A total of 2,011 doctors participated in this study (882 house officers, 697 medical officers, and 432 registrars). The participants were aged 26.9 ± 3.2 years, and females constituted about 60% of the sample. An average of 3.1 ± 6.8 ward rounds were conducted per week in our hospitals, with 11.1 ± 20.3 h spent on ward rounds per week. Most doctors agreed that ward rounds are suitable for teaching patient management (91.3%) and diagnostic investigations (89.1%). Almost all the doctors agreed that being interested in teaching (95.1%) and communicating appropriately with the patients (94.7%) make a good teacher in ward rounds. Furthermore, nearly all the doctors agreed that being interested in learning (94.3%) and communicating appropriately with the teacher (94.5%) make a good student on ward rounds. About 92.8% of the doctors stated that the quality of ward rounds could be improved. The most frequently reported obstacles faced during ward rounds were the noise (70%) and lack of privacy (77%) in the ward environment. Conclusion Ward rounds have a special value in teaching patient diagnosis and management. Being interested in teaching/learning and having good communication skills were the two major criteria that make a good teacher/learner. Unfortunately, ward rounds are faced with obstacles related to the ward environment. It is mandatory to ensure the quality of both ward rounds' teaching and environment to optimize the educational value and subsequently improve patient care practice