Nevin Manimala

Database (Oxford). 2021 Sep 3;2021:baab055. doi: 10.1093/database/baab055.

ABSTRACT

Peptides have attracted attention during the last decades due to their extraordinary therapeutic properties. Different computational tools have been developed to take advantage of existing information, compiling knowledge and making available the information for common users. Nevertheless, most related tools available are not user-friendly, present redundant information, do not clearly display the data, and usually are specific for particular biological activities, not existing so far, an integrated database with consolidated information to help research peptide sequences. To solve these necessities, we developed Peptipedia, a user-friendly web application and comprehensive database to search, characterize and analyse peptide sequences. Our tool integrates the information from 30 previously reported databases with a total of 92 055 amino acid sequences, making it the biggest repository of peptides with recorded activities to date. Furthermore, we make available a variety of bioinformatics services and statistical modules to increase our tool’s usability. Moreover, we incorporated a robust assembled binary classification system to predict putative biological activities for peptide sequences. Our tools’ significant differences with other existing alternatives become a substantial contribution for developing biotechnological and bioengineering applications for peptides. Peptipedia is available for non-commercial use as an open-access software, licensed under the GNU General Public License, version GPL 3.0. The web platform is publicly available at peptipedia.cl. Database URL: Both the source code and sample data sets are available in the GitHub repository https://github.com/ProteinEngineering-PESB2/peptipedia.

PMID:34478499 | DOI:10.1093/database/baab055

Bioinformatics. 2021 Sep 3:btab615. doi: 10.1093/bioinformatics/btab615. Online ahead of print.

ABSTRACT

SUMMARY: Quantitative interpretation of single-molecule FRET experiments requires a model of the dye dynamics to link experimental energy transfer efficiencies to distances between atom positions. We have developed FRETraj, a Python module to predict FRET distributions based on accessible-contact volumes (ACV) and simulated photon statistics. FRETraj helps to identify optimal fluorophore positions on a biomolecule of interest by rapidly evaluating donor-acceptor distances. FRETraj is scalable and fully integrated into PyMOL and the Jupyter ecosystem. Here we describe the conformational dynamics of a DNA hairpin by computing multiple ACVs along a molecular dynamics trajectory and compare the predicted FRET distribution with single-molecule experiments. FRET-assisted modeling will accelerate the analysis of structural ensembles in particular dynamic, non-coding RNAs and transient protein-nucleic acid complexes.

AVAILABILITY: FRETraj is implemented as a cross-platform Python package available under the GPL-3.0 on Github (https://github.com/RNA-FRETools/fretraj) and is documented at https://RNA-FRETools.github.io/fretraj.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34478493 | DOI:10.1093/bioinformatics/btab615

Bioinformatics. 2021 Sep 3:btab592. doi: 10.1093/bioinformatics/btab592. Online ahead of print.

ABSTRACT

MOTIVATION: Combining the results of different experiments to exhibit complex patterns or to improve statistical power is a typical aim of data integration. The starting point of the statistical analysis often comes as sets of p-values resulting from previous analyses, that need to be combined in a flexible way to explore complex hypotheses, while guaranteeing a low proportion of false discoveries.

RESULTS: We introduce the generic concept of composed hypothesis, which corresponds to an arbitrary complex combination of simple hypotheses. We rephrase the problem of testing a composed hypothesis as a classification task, and show that finding items for which the composed null hypothesis is rejected boils down to fitting a mixture model and classify the items according to their posterior probabilities. We show that inference can be efficiently performed and provide a thorough classification rule to control for type I error. The performance and the usefulness of the approach are illustrated on simulations and on two different applications. The method is scalable, does not require any parameter tuning, and provided valuable biological insight on the considered application cases.

AVAILABILITY: The QCH methodology is implemented in the qch R package hosted on CRAN.

PMID:34478490 | DOI:10.1093/bioinformatics/btab592

Bioinformatics. 2021 Sep 3:btab627. doi: 10.1093/bioinformatics/btab627. Online ahead of print.

ABSTRACT

MOTIVATION: Metabolomics studies aim at reporting a metabolic signature (list of metabolites) related to a particular experimental condition. These signatures are instrumental in the identification of biomarkers or classification of individuals, however their biological and physiological interpretation remains a challenge. To support this task, we introduce FORUM: a Knowledge Graph (KG) providing a semantic representation of relations between chemicals and biomedical concepts, built from a federation of life science databases and scientific literature repositories.

RESULTS: The use of a Semantic Web framework on biological data allows us to apply ontological based reasoning to infer new relations between entities. We show that these new relations provide different levels of abstraction and could open the path to new hypotheses. We estimate the statistical relevance of each extracted relation, explicit or inferred, using an enrichment analysis, and instantiate them as new knowledge in the KG to support results interpretation/further inquiries.

AVAILABILITY: A web interface to browse and download the extracted relations, as well as a SPARQL endpoint to directly probe the whole FORUM knowledge graph, are available at https://forum-webapp.semantic-metabolomics.fr. The code needed to reproduce the triplestore is available at https://github.com/eMetaboHUB/Forum-DiseasesChem.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34478489 | DOI:10.1093/bioinformatics/btab627

PLoS One. 2021 Sep 3;16(9):e0257137. doi: 10.1371/journal.pone.0257137. eCollection 2021.

ABSTRACT

OBJECTIVES: High-speed tooth preparation requires effective cooling to avoid thermal damage, which generates spray mist, which is a mixture of an aerosol, droplets and particles of different sizes. The aim of this experimental study was to analyze the efficacy of spray mist reduction with an intraoral high-volume evacuation system (HVE) during simulated high-speed tooth preparation for suboptimal versus optimal suction positions of 16 mm sized cannulas and different flow rates of the HVE.

MATERIAL AND METHODS: In a manikin head, the upper first premolar was prepared with a dental turbine, and generated particles of 5-50 microns were analyzed fifty millimeters above the mouth opening with the shadow imaging technique (frame: 6.6×5.3×1.1 mm). This setup was chosen to generate a reproducible spray mist in a vertical direction towards an imaginary operator head (worst case scenario). The flow rate (FR) of the HVE was categorized into five levels (≤120 l/min up to 330 l/min). The number of particles per second (NP; p/s) was counted, and the mass volume flow of particles per second (MVF; μg/s*cm3) was calculated for 10 sec. Statistical tests were nonparametric and two-sided (p≤0.05).

RESULTS: With increasing flow rate, the NP/MVF values decreased significantly (eta: 0.671/0.678; p≤0.001). Using a suboptimally positioned cannula with an FR≤160 l/min, significantly higher NP values (mean±SD) of 731.67±54.24 p/s (p≤0.019) and an MVF of 3.72±0.42 μg/s*cm3 (p≤0.010) were measured compared to those of the optimal cannula position and FR≥300 l/min (NP/MVF: 0/0). No significant difference in NP and MVF was measurable between FR≥250 l/min and FR>300 l/min (p = 0.652, p = 0.664).

CONCLUSION: Within the limitations of the current experimental study, intraoral high-flow rate suction with ≥300 l/min with an HVE effectively reduced 5-50 μm sized particles of the spray mist induced by high-speed tooth preparation with a dental turbine.

PMID:34478480 | DOI:10.1371/journal.pone.0257137

PLoS One. 2021 Sep 3;16(9):e0257109. doi: 10.1371/journal.pone.0257109. eCollection 2021.

ABSTRACT

INTRODUCTION: Health care workers are the most affected part of the world population due to the COVID-19 pandemic. Countries prioritize vaccinating health workers against COVID-19 because of their susceptibility to the virus. However, the acceptability of the vaccine varies across populations. Thus, this study aimed to determine the health care worker’s intentions to accept the COVID-19 vaccine and its associated factors in southwestern Ethiopia, 2021.

METHODS: A facility-based cross-sectional study was conducted among health care workers in public hospitals in southwestern Ethiopia from March 15 to 28, 2021. A simple random sampling method was used to select 405 participants from each hospital. Data were collected using self-administered questionnaires. Descriptive statistics, such as frequency and percentage, were calculated. Multivariable logistic regression was also performed to identify factors associated with health care worker’s intention to accept the COVID-19 vaccine. Statistically significant variables were selected based on p-values (<0.05) and the adjusted odds ratio was used to describe the strength of association with 95% confidence intervals.

RESULT: Among the respondents, 48.4% [95% CI: 38.6, 58.2] of health care workers intended to accept COVID-19. Intention to accept COVID-19 vaccination was significantly associated with physicians (AOR = 9.27, 95% CI: 1.27-27.32), professionals with a history of chronic illness (AOR = 4.07, 95% CI: 2.02-8.21), perceived degree of risk of COVID-19 infection (AOR = 4.63, 95% CI: 1.26-16.98), positive attitude toward COVID-19 prevention (AOR = 6.08, 95% CI: 3.39-10.91) and good preventive practices (AOR = 2.83, 95% CI: 1.58-5.08).

CONCLUSION: In this study, the intention of health care workers to accept the COVID-19 vaccine was low. Professional types, history of chronic illness, perceived degree of risk to COVID-19 infection, attitude toward COVID-19 and preventive practices were found to be factors for intention to accept COVID-19 vaccine in professionals. It is important to consider professional types, history of chronic illness, perceived degree of risk to COVID-19, attitude of professionals and preventive behaviors to improve the intention of professionals’ vaccine acceptance.

PMID:34478470 | DOI:10.1371/journal.pone.0257109

J Clin Res Pediatr Endocrinol. 2021 Sep 3. doi: 10.4274/jcrpe.galenos.2021.2021.0169. Online ahead of print.

ABSTRACT

BACKGROUND: No meta-analysis is available which has analysed role of letrozole in constitutional delay in growth and puberty (CDGP).

METHODS: Electronic databases were searched for RCTs involving children with CDGP receiving letrozole. Primary outcome were changes in predicted adult height (PAH) and pubertal progression. Secondary outcomes were alterations in bone age, hormonal markers of puberty, bone mineral density and side-effects.

RESULTS: One hundred-thirty articles were reviewed, from which 7 RCTs which fulfilled all criteria were analysed. Letrozole was superior to placebo [mean difference (MD) 4.63cm (95% CI: 3.90 – 5.36); P<0.01; I2=0%] but not testosterone [MD 2.21cm (95% CI: -1.71 – 6.16); P=0.27; I2=98%] with regards to improvement in PAH after 12-months use. Letrozole was superior to both placebo [MD 4.80ml (95% CI: 0.57 – 9.03); P=0.03] and testosterone [MD 3.36ml (95% CI: 0.58 – 6.75); P=0.02; I2=0%] with regards to improvement in testicular volume after 12-months use. Letrozole was superior to testosterone [MD -0.84 years (95% CI: 2.83 – 8.18); P=0.06; I2=0%] with regards to slowing in bone age progression after 12-months use, which approached statistical significance. Serum LH, FSH, testosterone and inhibin-B were significantly higher after 6-months letrozole use compared to active as well as passive controls. No increased occurrence of adverse events, spinal deformities were noted with letrozole.

CONCLUSION: Letrozole is safe and effective for improving height and pubertal outcomes in CDGP, and is better than testosterone with regards to improvement in testicular volume and delaying bone-age progression.

PMID:34477355 | DOI:10.4274/jcrpe.galenos.2021.2021.0169

Q J Nucl Med Mol Imaging. 2021 Sep 3. doi: 10.23736/S1824-4785.21.03387-2. Online ahead of print.

ABSTRACT

BACKGROUND: The most important cause of heart transplant loss is early acute allograft rejection, caused by the infiltration of lymphocytes, development of edema and myocardial necrosis. It has been propagated that [68Ga]DOTA-TATE PET might be suitable to quantify the presence of SSTR over-expressing lymphocytes. With heterotopic allogenic heart transplant models in the rat readily available, we aimed to investigate, if monitoring and quantification of acute allograft rejection after heterotopic allogenic heart transplantation was feasible by non-invasive serial [68Ga]DOTA-TATE PET.

METHODS: 17 Lewis rats (9 for serial PET imaging, 8 for histological correlation) received allogenic heterotopic heart transplants from 17 Brown-Norway rats. On days 4, 6 and 7 a [68Ga]DOTA-TATE PET scan was performed.

RESULTS: Imaging of acute transplant rejection until 7 days after allogenic heart transplantation in the rat is feasible. Heterotopic allografts showed significantly increased tracer uptake on day 4 until day 7 after transplantation, reflecting the process of histologically detected myocardial lymphocytic infiltration. Both the area of infarction and the amount of necrosis increased over the course of 7 days, with necrosis reaching statistical significance.

CONCLUSIONS: We purport that the detected PET signal is primarily a specific marker of lymphocyte infiltration and only to a lesser extent an unspecific marker of infarction and necrosis. Thus, [68Ga]DOTA-TATE PET might be a suitable tool for serial imaging and quantification of lymphocyte infiltration as a direct mediator of acute allograft rejection at an early stage after heart transplantation.

PMID:34477347 | DOI:10.23736/S1824-4785.21.03387-2

Q J Nucl Med Mol Imaging. 2021 Sep 3. doi: 10.23736/S1824-4785.21.03366-5. Online ahead of print.

ABSTRACT

AIM: To assess the detection rate of 18F-choline PET/CT in non-metastatic hormone-sensitive prostate cancer (hsPCa) and non-metastatic castrate resistant prostate cancer (CRPCa), based on the criteria proposed in the phase III SPARTAN trial and with high Gleason Score (GS).

METHODS: Between October 2008 and September 2019, data from a retrospective multicenter study (n=4 centers), involving patients undergoing 18F-choline PET/CT scans for a biochemical recurrence of PCa, were collected. The following inclusion criteria were used: 1) histologically proven PCa, 2) a non-metastatic disease in accordance with conventional imaging findings; 3) a PSA doubling time (PSAdt) <10 months, 4) a GS > 8 and 5) no pelvic node > 2 cm. The group of hsPCa and CRPCa patients, were compared by using a non-parametric statistical analysis. Moreover, a logistic regression analysis and ROC curves were used.

RESULTS: 140 patients were included. Of these, 82 patients were affected by hsPCa, and 58 had a CRPCa. Overall, 18F-Choline PET/CT was positive in 99/140 (70.7%). It was positive in 55/82 (67.1%) hsPCa patients and in 44/58 (75.9%) CRPCa subjects, respectively. The site of recurrence at 18F-Choline PET/CT were: 16 (27.6%) and 20 (24.4%) in prostatic bed, 25 (43.1%) and 24 (29.3%) in loco-regional lymph nodes and in 27 (46.6%) and 28 (34.1%) in distant organs, respectively for CRPCa and hsPCa patients. The optimal cut-off values for PSA at the time of PET/CT for the prediction or recurrence were 0.5 vs. 2.5 ng/mL for all site of recurrence (AUC: 0.70 vs. 0.72), 0.48 vs. 3.4 ng/mL for prostatic bed (AUC: 0.60 vs. 0.59), 0.5 vs. 1.5 for loco-regional lymph nodes (AUC: 0.62 vs. 0.57) and 2.2 vs. 2.8 ng/mL for distant metastasis (AUC: 0.74 vs. 0.71), respectively in CRPCa and hsPCa (all p=NS). Sensitivities and specificities of 18F-Choline PET/CT for the identification of recurrence disease in all patient population, in hsPCa and CRPCa were 83.7% and 87.5%, 78.9% and 88.9%, 91.4% and 85.7%, respectively.

CONCLUSIONS: the rate of positive 18F-Choline PET/CT is similar in patients with a hsPCa and CRPCa, in case of low PSAdt and high GS. Therefore, non-metastatic PCa patients should be assessed by molecular imaging, in order to adapt the most appropriate therapeutic approach.

PMID:34477346 | DOI:10.23736/S1824-4785.21.03366-5

Arthritis Care Res (Hoboken). 2021 Sep 3. doi: 10.1002/acr.24777. Online ahead of print.

ABSTRACT

We thank Dr Lai for their interest in our study (1). While we did not show a statistically significant link between the use of allopurinol and mortality in people with gout, we agree that Allopurinol Hypersensitivity Syndrome (AHS) is the most serious side-effect of allopurinol, particularly in populations with South East Asian ancestry, leading to the recommendation to screen people of South East Asian descent for the HLA-B*5801 allele prior to starting treatment with allopurinol (2,3).

PMID:34477323 | DOI:10.1002/acr.24777