Regioselective modification at the 2,3- and 6-positions of chitosan with phenylcarbamates for chromatographic enantioseparation.

Chitosan derivatives with two different phenylcarbamate pendants at the 6-position and 2,3-positions of the glucosamine unit were synthesized by triphenylmethyl as a protective group. The regioselective chitosan derivatives were prepared corresponding to coated-type chiral packed materials (CPMs), which were evaluated with thirteen chiral compounds by high-performance liquid chromatography (HPLC). The regioselective chitosan derivatives (4aⅠ/4aⅡ, 4bⅠ/4bⅡ) bearing electron-withdrawing 3,5­chloro or 4­chloro at the 6-position can recognize 7 or 8 of the 13 enantiomers and achieve baseline separation for enantiomers 5 and 7. They exhibited better chiral recognition abilities than the other derivatives with different substituents at the 6-position and the same 3,5-dimethylphenyl substituent at the 2,3-postion. In comparison to Chit-1 featuring a 3,5-dimethylphenyl substituent at the 2,3- and 6-positions, it was observed that the combination of both an electron-withdrawing and an electron-donating substituent of the regioselective chitosan derivatives (4aⅠ/4aⅡ, 4bⅠ/4bⅡ) showed better or similar enantioseparation abilities for racemic Compounds 7 and 6, respectively. The molecular weight-performance relationship of the regioselective chitosan derivatives was investigated in detail. It was found that with increasing molecular weight, the derivatives 4aⅡ and 4bⅡ all possessed greater enantioseparation power for 4 enantiomers, such as enantiomers 4, 7, 11, and 15, than the corresponding derivatives with low molecular weights. The molecular docking simulation results showed that excellent enantioseparation power significantly depended on the combination and interaction of multiple factors, such as steric hindrance, and polarity of the substituents on the CPMs and enantiomers.

Digital health and Clinical Patient Management System (CPMS) platform utility for data sharing of neuromuscular patients: the Italian EURO-NMD experience.

BACKGROUND: The development of e-health technologies for teleconsultation and exchange of knowledge is one of the core purposes of European Reference Networks (ERNs), including the ERN EURO-NMD for rare neuromuscular diseases. Within ERNs, the Clinical Patient Management System (CPMS) is a web-based platform that seeks to boost active collaboration within and across the network, implementing data sharing. Through CPMS, it is possible to both discuss patient cases and to make patients' data available for registries and databases in a secure way. In this view, CPMS may be considered a sort of a temporary storage for patients' data and an effective tool for data sharing; it facilitates specialists' consultation since rare diseases (RDs) require multidisciplinary skills, specific, and outstanding clinical experience. Following European Union (EU) recommendation, and to promote the use of CPMS platform among EURO-NMD members, a twelve-month pilot project was set up to train the 15 Italian Health Care Providers (HCPs). In this paper, we report the structure, methods, and results of the teaching course, showing that tailored, ERN-oriented, training can significantly enhance the profitable use of the CPMS. RESULTS: Throughout the training course, 45 professionals learned how to use the many features of the CPMS, eventually opening 98 panels of discussion-amounting to 82% of the total panels included in the EURO-NMD. Since clinical, genetic, diagnostic, and therapeutic data of patients can be securely stored within the platform, we also highlight the importance of this platform as an effective tool to discuss and share clinical cases, in order to ease both case solving and data storing. CONCLUSIONS: In this paper, we discuss how similar course could help implementing the use of the platform, highlighting strengths and weaknesses of e-health for ERNs. The expected result is the creation of a "map" of neuromuscular patients across Europe that might be improved by a wider use of CPMS.

SeqCP: A sequence-based algorithm for searching circularly permuted proteins.

Circular permutation (CP) is a protein sequence rearrangement in which the amino- and carboxyl-termini of a protein can be created in different positions along the imaginary circularized sequence. Circularly permutated proteins usually exhibit conserved three-dimensional structures and functions. By comparing the structures of circular permutants (CPMs), protein research and bioengineering applications can be approached in ways that are difficult to achieve by traditional mutagenesis. Most current CP detection algorithms depend on structural information. Because there is a vast number of proteins with unknown structures, many CP pairs may remain unidentified. An efficient sequence-based CP detector will help identify more CP pairs and advance many protein studies. For instance, some hypothetical proteins may have CPMs with known functions and structures that are informative for functional annotation, but existing structure-based CP search methods cannot be applied when those hypothetical proteins lack structural information. Despite the considerable potential for applications, sequence-based CP search methods have not been well developed. We present a sequence-based method, SeqCP, which analyzes normal and duplicated sequence alignments to identify CPMs and determine candidate CP sites for proteins. SeqCP was trained by data obtained from the Circular Permutation Database and tested with nonredundant datasets from the Protein Data Bank. It shows high reliability in CP identification and achieves an AUC of 0.9. SeqCP has been implemented into a web server available at: http://pcnas.life.nthu.edu.tw/SeqCP/.

A critical evaluation of the EU-virtual consultation platform (CPMS) within the European Reference Network on Rare Endocrine Conditions.

In 2017, the European Commission installed 24 European Reference Networks (ERNs) for different categories of rare and complex conditions to facilitate cross-border health care via virtual case consultations in a secure Clinical Patient Management System (CPMS). The ERN for rare endocrine conditions (Endo-ERN) previously reviewed the CPMS, in which they detailed the difficulties physicians encountered with the system and proposed solutions to these that should enable the system to be used to a greater extent. This paper will further the endeavor of the first by performing a critical evaluation of the CPMS, assessing how these suggested improvements have been implemented, and if these have affected the usage of the system. The evaluation involves an assessment of CPMS usage statistics since its conception that takes into consideration the technical updates and the external factors that may have affected these, including data from a review survey following a training workshop for our new healthcare providers (HCPs) added in January 2022. It appears that the improvements made to the system since the first review, in particular the implementation of the Operational Helpdesk, have had a positive effect in increasing CPMS membership; however, the regular usage of the system continues to fluctuate. Several suggestions are made on how to further facilitate the use of CPMS by our members both individually and network-wide, by integrating CPMS activities with other network initiatives and further integrating these into national health care systems as well as looking for ways to measure patient satisfaction from the CPMS discussions outcomes.

Prevalence of psychiatric disorders among 4 to 14 year age group children in slums of Thiruvananthapuram Corporation.

Introduction: Failure of early identification and timely intervention of psychological disorders adversely affect the development of child to healthy adult. This study was done to estimate the prevalence of psychiatric disorders among 4-14 years age group children in urban slums as well as to find out the socio-demographic factors associated with it. Methods: A cross-sectional study with cluster sampling technique was conducted in urban slums of Thiruvananthapuram Corporation among 1029 participants. For the estimation of prevalence, CPMS was used and the socio-demographic factors were obtained using pretested interviewer-administered semi-structured questionnaire. Data were analysed using proportion with 95% CI, Chi-square, odds ratio and logistic regression. Results: Prevalence of childhood psychiatric disorders was 11.5% [95%CI (9.51-13.49)] and it was significantly associated with age (P =0.000), birth order (P =0.008), birth weight (P =.033), siblings number (P =.004) school performance (P =.000), peer status (P =.012), peer relation (P =.000), disease status (P =.000), maternal education (P =.006), paternal education (P =.000), maternal occupation (P =.000) and paternal occupation (P =.005), parental separation (P =.000), the person looking after the child (P =.000), marital disharmony (P =.000), history of alcohol intake (P =.000) and frequency of drinking (P =.000). By logistic regression, poor performance [odds ratio 12.79 (7.09-23.07)], disease status [odds ratio 4.83 (2.83-8.27)], problem in adjustment with peer [odds ratio 12.3 (1.97-77.55)], history of daily intake of alcohol in fathers [odds ratio 3.15 (1.87-5.29)] and offspring of unskilled mothers [odds ratio [2.07 (1.32-3.27)] constitute the predictors for these disorders. Conclusion: This study findings highlight prevalence and the association of childhood and adolescence psychiatric disorders with several socio-demographic factors, which needs consideration while planning for implementation of mental health programme in the community.

Developing a mechanism of construction project manager's emotional intelligence on project success: A grounded theory research based in China.

A project manager's emotional intelligence (EI) is essential to project success. However, the mechanism in this cause and effect remains a black box in extant literature. China is now the world's largest construction market, and figuring out the mechanism of construction project manager's (CPM's) EI on project success is meaningful for developing the global construction market. This study conducted an in-depth interview with 24 CPMs with more than 5-year experience in construction project management. The grounded theory was employed to profile the application of CPM's EI and to build the multilevel mechanism that explains the influence of CPM's EI on project success. The mechanism framework conforms to the existed input-process-output (IPO) theory. It consists of a team-level mechanism (including the positive team atmosphere, shared vision, and team cohesion) and an individual-level mechanism (i.e., organizational citizenship behavior directed at the organization, perceived supervisor support, trust in leader, and subordinate's psychological and emotional health). This study further proposed that the effect of this mechanism does not work immediately but develops with time passing. Implications for further research and project management practice are discussed in the end.

Protocol for a cluster randomised controlled feasibility study of Prehospital Optimal Shock Energy for Defibrillation (POSED).

Aims: The Prehospital Optimal Shock Energy for Defibrillation (POSED) study will assess the feasibility of conducting a cluster randomised controlled study of clinical effectiveness in UK ambulance services to identify the optimal shock energy for defibrillation. Methods: POSED is a pragmatic, allocation concealed, open label, cluster randomised, controlled feasibility study. Defibrillators within a single UK ambulance service will be randomised in an equal ratio to deliver one of three shock strategies 120-150-200 J, 150-200-200 J, 200-200-200 J. Consecutive adults (≥18 years) presenting with out of hospital cardiac arrest requiring defibrillation will be eligible. The study plans to enrol 90 patients (30 in each group). Patients (or their relatives for non-survivors) will be informed about trial participation after the initial emergency has resolved. Survivors will be invited to consent to participate in follow-up (i.e., at 30 days or discharge).The primary feasibility outcome is the proportion of eligible patients who receive the randomised study intervention. Secondary feasibility outcomes will include recruitment rate, adherence to allocated treatment and data completeness. Clinical outcomes will include Return of an Organised Rhythm (ROOR) at 2 minutes post-shock, refibrillation rate, Return of Spontaneous Circulation (ROSC) at hospital handover, survival and neurological outcome at 30 days. Conclusion: The POSED study will assess the feasibility of a large-scale trial and explore opportunities to optimise the trial protocol.Trial registration: ISRCTN16327029.

Clinical prediction models of fractional flow reserve: an exploration of the current evidence and appraisal of model performance.

BACKGROUND: Invasive fractional flow reserve (FFR) is a standard indicator of coronary stenoses' hemodynamic severity. Clinical prediction models (CPMs) may help differentiate ischemic from non-ischemic lesions without using a pressure wire but by integrating related variables. This approach differs from that of physics-based models. However, it is not yet known which CPMs are the most reliable at detecting hemodynamic significance. METHODS: A systematic review was performed of relevant publications that developed or validated any FFR CPMs from inception to April 2019 in the PubMed, EMBASE, and Cochrane Library databases by two independent authors. The risk of bias and applicability were assessed using the prediction model risk of the bias assessment tool (PROBAST). RESULTS: A total of 11 unique CPMs and 5 subsequent external validation studies were identified. The prevalence of hemodynamically significant lesions (FFR ≤0.80) across the studies had a median of 37.1% (range: 20.7-68.0%). Lesion length, percent diameter stenosis, and minimal lumen diameter were the three most frequently used variables in the CPMs. Of the 11 FFR CPMs, 9 (82%) exhibited strong discrimination [area under the curve (AUC) >0.75], and 5 (45%) had been subject to external validation; however, calibration was only available for 3 models (27%). There was a high degree of applicability; however, none of the studies was assessed as having a low risk of bias. A CPM was identified that had undergone rigorous validation and calibration: the DILEMMA score (three validations; median AUC, 0.83). CONCLUSIONS: Almost half of the existing FFR CPMs had been externally validated. Due to their good discrimination abilities, these FFR CPMs are useful tools that could reduce the need for invasive hemodynamic measurements. Future research that adheres to methodological guidelines should be undertaken to develop high-quality models in this setting. (PROSPERO registration number: CRD42019125011).

A Novel Circular RNA circITSN2 Targets the miR-218-5p/LMO7 Axis to Promote Chicken Embryonic Myoblast Proliferation and Differentiation.

Circular RNA (circRNA) is a class of endogenous non-coding RNAs without 5' and 3' ends; an increasing number of studies show that circRNA is involved in skeletal muscle development. From our previous sequencing data, the circRNAome in breast muscle of two chicken lines with a distinct rate of muscle development, which included a fast muscle growing broiler (FMGB) and a slow muscle growing layer (SMGL), we found a novel differentially expressed circRNA generated by intersectin 2 (ITSN2) gene (named circITSN2). We verified that circITSN2 is a skeletal muscle-enriched circRNA that promotes chicken primary myoblast (CPM) proliferation and differentiation. Further molecular mechanism analysis of circITSN2 in chicken myogenesis was performed, and we found circITSN2 directly targeting miR-218-5p. Besides, miR-218-5p inhibits CPM proliferation and differentiation, which is contrary to circITSN2. Commonly, circRNAs act as a miRNA sponge to alleviate the inhibition of miRNAs on mRNAs. Thus, we also identified that a downstream gene LIM domain 7 (LMO7) was inhibited by miR-218-5p, while circITSN2 could block the inhibitory effect of miR-218-5p by targeting it. Functional analysis revealed that LMO7 also accelerates CPM proliferation and differentiation, which was similar to circITSN2 but contrary to miR-218-5p. Taken together, these results suggested that circITSN2 promotes chicken embryonic skeletal muscle development via relieving the inhibition of miR-218-5p on LMO7. Our findings revealed a novel circITSN2/miR-218-5p/LMO7 axis in chicken embryonic skeletal muscle development, which expands our understanding of the complex muscle development regulatory network.

CPMS-improving patient care in Europe via virtual case discussions.

PURPOSE: The core task of European Reference Networks (ERNs) is to reduce health care inequalities throughout Europe for all patients with rare and complex conditions. A secure web-based application for virtual consultations, the Clinical Patient Management System (CPMS), was developed by the EU to provide expert specialized care for all these patients. This review analyses the opportunities and difficulties that the implementation of this virtual network implies for physicians as well as for the patients. METHODS: European Reference Network on Rare Endocrine Conditions (Endo-ERN) installed an Operational Helpdesk (OH) to support their members in using CPMS. The OH initiated several actions to facilitate and increase the usage of CPMS. Satisfaction with the system and reasons for low participation rates in virtual case discussions were analyzed by different surveys. RESULTS: The number of CPMS users increased constantly, but the active usage of the system remains insufficient. Main reasons were technical difficulties, lack of time and insufficient awareness about CPMS in experts and patients throughout Europe. Still, outcomes of the virtual discussions are considered useful by involved experts and the discussions have provided topics for educational webinars and research. CONCLUSIONS: CPMS is a secure system with many advantages compared to previous ways of consulting experts but also difficulties that need to be overcome with future strategies. By facilitating its use and increasing awareness among all relevant European experts and patients, CPMS can help to make the existing expertise available for all patients with rare (endocrine) conditions throughout Europe as it was intended.

α-Amylase action on starch in chickpea flour following hydrothermal processing and different drying, cooling and storage conditions.

Starch is present in many prepared 'ready-meals' that have undergone processing and/or storage in frozen or chilled state. Hydrothermal processing greatly increases starch digestibility and postprandial glycaemia. Effects of different heating/drying and cooling regimes on amylolysis have received little attention. Hence, we examined the effects of different processing treatments on in vitro digestibility of starch in chickpea flour. Solid-state 13C NMR was used to estimate ordered double-helical structure in the starch. Native starch with 25 % double-helical content was the most resistant to digestion but hydrothermal processing (gelatinisation) resulted in >95 % loss of order and a large increase in starch digestibility. Air-drying of pre-treated flour produced slowly-digestible starch (C∞, 55.9 %). Refrigeration of gelatinised samples decreased ease of amylolysis coincident with increase in double-helical content. Freezing maintained the same degree of digestibility as freshly gelatinised material and produced negligible retrogradation. Chilling may be exploited to produce ready-meals with a lower glycaemic response.

Boundary crash data assignment in zonal safety analysis: An iterative approach based on data augmentation and Bayesian spatial model.

Boundary effect refers to the issue of ambiguous allocation of crashes occurred on or near the boundaries of neighboring zones in zonal safety analysis. It results in bias estimates for associate measure between crash occurrence and possible zonal factors. It is a fundamental problem to compensate for the boundary effect and enhance the model predictive performance. Compared to conventional approaches, it might be more reasonable to assign the boundary crashes according to the crash predisposing agents, since the crash occurrence is generally correlated to multiple sources of risk factors. In this study, we proposed a novel iterative aggregation approach to assign the boundary crashes, according to the ratio of model-based expected crash number in adjacent zones. To verify the proposed method, a case study using a dataset of 738 Traffic Analysis Zones (TAZs) from the county of Hillsborough in Florida was conducted. Using Bayesian spatial models (BSMs), the proposed approach demonstrated the capability in reasonably compensating for the boundary effect with better model estimation and predictive performance, as compared to three conventional approaches (i.e., half and half ratio method, one to one ratio method, and exposure ratio method). Results revealed that several factors including the number of intersections, road segment length with 35 mph speed limit, road segment length with 65 mph speed limit and median household income, were sensitive to the boundary effect.

Pre-procedural risk models for patients undergoing transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) has emerged as the standard treatment option for patients with symptomatic aortic stenosis who are considered intermediate to high surgical risk. Nonetheless, optimal clinical outcomes following the procedure require careful consideration of procedural risk by the Heart Team. While this decision-making could be supported through the development of TAVI-specific clinical prediction models (CPMs), current models remain suboptimal. In this review paper, we aimed to outline the performance of several recently derived TAVI CPMs that predict mortality and present some future research directions. We discuss how the existing risk models have achieved only moderate discrimination but highlight that some of the models are well calibrated across multiple populations, indicating the feasibility of using them to aid benchmarking analyses. Moreover, we suggest that future work should focus on the development of CPMs in cohorts of patients with aortic stenosis that include multiple treatment modalities. Supported by appropriate modelling of 'what if' scenarios, this would allow the Heart Teams to predict and compare outcomes across surgical aortic valve replacement, medical management and TAVI, thereby allowing one to personalise treatment decisions to the individual patient. Such a goal could be facilitated by considering novel risk factors, shifting the focus to endpoints other than mortality, and through collaborative efforts to combine the evidence base and existing models across wider populations.

Determination of triterpenic acids in fruits by a novel high performance liquid chromatography method with high sensitivity and specificity.

A novel and interesting pre-column derivatisation method was developed for the analysis of triterpenic acids by high-performance liquid chromatography (HPLC) with fluorescence detection. Each triterpenic acid produced two HPLC peaks with similar peak areas after derivatising with chiral 1-(9H-carbazol-9-yl) propan-2-yl-methanesulfonate (CPMS), while the fatty acid derivative of CPMS had only one peak. This phenomenon greatly increased the confidence in analyte confirmation. Compound with only one peak or two peaks differing greatly in their peak areas could be excluded from the target compound list. CPMS was compared with five other derivatising reagents, four of which produced only one peak for one triterpenic acid, to study the possible mechanism. Analytes with different behaviours were also studied to better interpret the mechanism. The proposed method also showed the merits of high sensitivity and less sample consumption. It was successfully applied to the analysis of triterpenic acids in fruit peels and flesh. There is no prior report on the two peak phenomenon of triterpenic acids. The information provided in this study will be helpful for those who are also engaged in derivatisation study.