bayesynergy: flexible Bayesian modelling of synergistic interaction effects in in vitro drug combination experiments.

The effect of cancer therapies is often tested pre-clinically via in vitro experiments, where the post-treatment viability of the cancer cell population is measured through assays estimating the number of viable cells. In this way, large libraries of compounds can be tested, comparing the efficacy of each treatment. Drug interaction studies focus on the quantification of the additional effect encountered when two drugs are combined, as opposed to using the treatments separately. In the bayesynergy R package, we implement a probabilistic approach for the description of the drug combination experiment, where the observed dose response curve is modelled as a sum of the expected response under a zero-interaction model and an additional interaction effect (synergistic or antagonistic). Although the model formulation makes use of the Bliss independence assumption, we note that the posterior estimates of the dose-response surface can also be used to extract synergy scores based on other reference models, which we illustrate for the Highest Single Agent model. The interaction is modelled in a flexible manner, using a Gaussian process formulation. Since the proposed approach is based on a statistical model, it allows the natural inclusion of replicates, handles missing data and uneven concentration grids, and provides uncertainty quantification around the results. The model is implemented in the open-source Stan programming language providing a computationally efficient sampler, a fast approximation of the posterior through variational inference, and features parallel processing for working with large drug combination screens.

A comprehensive comparative assessment of 3D molecular similarity tools in ligand-based virtual screening.

Three-dimensional (3D) molecular similarity, one major ligand-based virtual screening (VS) method, has been widely used in the drug discovery process. A variety of 3D molecular similarity tools have been developed in recent decades. In this study, we assessed a panel of 15 3D molecular similarity programs against the DUD-E and LIT-PCBA datasets, including commercial ROCS and Phase, in terms of screening power and scaffold-hopping power. The results revealed that (1) SHAFTS, LS-align, Phase Shape_Pharm and LIGSIFT showed the best VS capability in terms of screening power. Some 3D similarity tools available to academia can yield relatively better VS performance than commercial ROCS and Phase software. (2) Current 3D similarity VS tools exhibit a considerable ability to capture actives with new chemotypes in terms of scaffold hopping. (3) Multiple conformers relative to single conformations will generally improve VS performance for most 3D similarity tools, with marginal improvement observed in area under the receiving operator characteristic curve values, enrichment factor in the top 1% and hit rate in the top 1% values showed larger improvement. Moreover, redundancy and complementarity analyses of hit lists from different query seeds and different 3D similarity VS tools showed that the combination of different query seeds and/or different 3D similarity tools in VS campaigns retrieved more (and more diverse) active molecules. These findings provide useful information for guiding choices of the optimal 3D molecular similarity tools for VS practices and designing possible combination strategies to discover more diverse active compounds.

Web repositories of natural agents promote pests and pathogenic microbes management.

The grand challenge to meet the increasing demands for food by a rapidly growing global population requires protecting crops from pests. Natural active substances play a significant role in the sustainable pests and pathogenic microbes management. In recent years, natural products- (NPs), antimicrobial peptides- (AMPs), medicinal plant- and plant essential oils (EOs)-related online resources have greatly facilitated the development of pests and pathogenic microbes control agents in an efficient and economical manner. However, a comprehensive comparison, analysis and summary of these existing web resources are still lacking. Here, we surveyed these databases of NPs, AMPs, medicinal plants and plant EOs with insecticidal, antibacterial, antiviral and antifungal activity, and we compared their functionality, data volume, data sources and applicability. We comprehensively discussed the limitation of these web resources. This study provides a toolbox for bench scientists working in the pesticide, botany, biomedical and pharmaceutical engineering fields. The aim of the review is to hope that these web resources will facilitate the discovery and development of potential active ingredients of pests and pathogenic microbes control agents.

Association between media attention and presentation of vaccination information on Canadian chiropractors' websites: a prospective mixed-methods cohort study.

BACKGROUND: Historically, some chiropractors have been critical of vaccination, and this has been the subject of recent media attention in Canada. We explored the association between media attention and public dissemination of vaccination information on Canadian chiropractors' websites. METHODS: In 2016, we identified all Canadian chiropractors' websites that provided information on vaccination by extracting details from the regulatory college website for each province using the search engine on their "find a chiropractor" page. We assessed the quality of information using the Web Resource Rating Tool (scores range from 0% [worst] to 100% [best]), determined whether vaccination was portrayed in a positive, neutral or negative manner, and conducted thematic analysis of vaccination content. We revisited all identified websites in 2019 to explore for changes to posted vaccination material. RESULTS: In July 2016, of 3733 chiropractic websites identified, 94 unique websites provided information on vaccination: 59 (63%) gave negative messaging, 19 (20%) were neutral and 16 (17%) were positive. The quality of vaccination content on the websites was generally poor, with a median Web Resource Rating Tool score of 19%. We identified 4 main themes: there are alternatives to vaccination, vaccines are harmful, evidence regarding vaccination and health policy regarding vaccination. From 2012 to 2016, there was 1 Canadian newspaper story concerning antivaccination statements by chiropractors, whereas 51 news articles were published on this topic between 2017 and 2019. In April 2019, 45 (48%) of the 94 websites we had identified in 2016 had removed all vaccination content or had been discontinued. INTERPRETATION: In 2016, a minority of Canadian chiropractors provided vaccination information on their websites, the majority of which portrayed vaccination negatively. After substantial national media attention, about half of all vaccination material on chiropractors' websites was removed within several years.

Use of GoFundMe® to crowdfund complementary and alternative medicine treatments for cancer.

PURPOSE: Complementary and alternative medicine (CAM) use is common amongst cancer patients. However, there is growing concern about its safety and efficacy. Online crowdfunding campaigns represent a unique avenue to understand the cancer patient's perspective for using CAM or declining conventional cancer therapy (CCT). METHODS: Five hundred GoFundMe campaigns from 2012 to 2019 detailing financial need for cancer treatment were randomly selected and reviewed for endorsement of CAM use, reasons for using CAM, and reasons for declining CCT. Descriptive statistics were used to compare patient and campaign characteristics between 250 CAM users and 250 non-CAM users. RESULTS: Compared to non-CAM users, CAM users were more likely to be female (70% vs. 54%, p < 0.01), to report more stage IV cancer (54% vs. 12%, p < 0.01), and to have a history of delayed, missed, or misdiagnosis (10% vs. 4%, p < 0.01). Reasons for using CAM include endorsing curative/therapeutic effects 212 (85%), pain/stress reduction 137 (55%), and dissatisfaction with current or past medical treatment options 105 (42%). 87 (35%) CAM users that declined CCT reported that they wanted to try to fight off cancer using CAM first 57 (61%), that CCT was too "toxic" to the body 39 (42%), and cancer was already too advanced, so that CCT would be futile or too aggressive 25 (27%). CONCLUSION: Cancer patients on GoFundMe using CAM highly value quality of life, comfort, and autonomy. Physicians should educate themselves on CAM to set realistic expectations and provide comprehensive counseling of the risks and benefits of CAM usage to patients who choose to use CAM to either augment or completely replace CCT.

Practical Application of "About Herbs" Website: Herbs and Dietary Supplement Use in Oncology Settings.

The Integrative Medicine Service at Memorial Sloan Kettering Cancer Center developed and maintains About Herbs (www.aboutherbs.com), which provides summaries of research data including purported uses, adverse effects, and herb-drug interactions for about 284 dietary supplements. Using Google Analytics, we found the website registered more than 26,317,000 hits since November 2002. The 10 most searched-for herbs/supplements of 2018 are chaga mushroom, turmeric, ashwagandha, reishi mushroom, graviola, Active Hexose-Correlated Compound, boswellia, dandelion, green tea, and Coriolus versicolor. Here we discuss their safety, herb-drug interactions, and appropriate uses in the oncology setting, based on literature searches in PubMed. Over the past 16 years, the evidence for use of these supplements is based mostly on preclinical findings, with few well-designed studies and limited trials conducted in cancer patients. It is important to familiarize health care professionals about popular supplements, so patients can be informed to make decisions that maximize benefits and minimize risks.

Virtual Ligand Screening Using PL-PatchSurfer2, a Molecular Surface-Based Protein-Ligand Docking Method.

Virtual screening is a computational technique for predicting a potent binding compound for a receptor protein from a ligand library. It has been a widely used in the drug discovery field to reduce the efforts of medicinal chemists to find hit compounds by experiments.Here, we introduce our novel structure-based virtual screening program, PL-PatchSurfer, which uses molecular surface representation with the three-dimensional Zernike descriptors, which is an effective mathematical representation for identifying physicochemical complementarities between local surfaces of a target protein and a ligand. The advantage of the surface-patch description is its tolerance on a receptor and compound structure variation. PL-PatchSurfer2 achieves higher accuracy on apo form and computationally modeled receptor structures than conventional structure-based virtual screening programs. Thus, PL-PatchSurfer2 opens up an opportunity for targets that do not have their crystal structures. The program is provided as a stand-alone program at http://kiharalab.org/plps2 . We also provide files for two ligand libraries, ChEMBL and ZINC Drug-like.

Medicina herbal china ofertada en páginas web en español: calidad de la información y riesgos / Information quality and health risks in Spanish-language retail websites for Chinese herbal medicine

Objetivo: El auge de la venta en Internet propicia el acceso a productos naturales potencialmente tóxicos y la rápida difusión de la información, no necesariamente veraz, que los proveedores ofrecen al consumidor acerca de sus propiedades. El objetivo del presente trabajo ha sido analizar en páginas web en español de venta de medicina herbal china la calidad de la información ofrecida al consumidor y los posibles riesgos derivados de su consumo. Métodos: I) Búsqueda en Google España de sitios web de venta de medicina herbal china y posterior evaluación de la información sobre las propiedades y consumo seguro de los productos ofertados. II) Identificación en los sitios web de plantas III) Cuantificación de las retiradas de productos de medicina herbal china por la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Resultados: 1) Sólo un tercio de las 30 páginas web localizadas cumple con la legislación vigente, ya que las demás incluyen indicaciones terapéuticas occidentales como reclamo para la venta de medicina herbal china en España 2) Cinco páginas aportan información sobre consumo seguro 3) Dos páginas ofertan plantas potencialmente tóxicas y 4) Un importante porcentaje de productos retirados por la AEMPS corresponde a medicina herbal china adulterada con sibutramina, sildenafilo o sus derivados. Conclusión: Nuestros resultados indican que existen motivos suficientes que aconsejan la creación por parte de las autoridades españolas de un sitio web que asesore a quienes pretenden utilizar Internet para comprar medicina herbal china y así permitir que los usuarios tomen decisiones estando bien informados (AU)

Objective: The growing use of purchase online via Internet retailers favours the access to potentially toxic natural products. It also contributes to the quick dissemination of the claims made by the retailers on efficacy and safety, these claims being not always based upon reliable information. Here, we have conducted an online search to find Spanish-language retail websites for Chinese herbal medicine and we have analysed them for the quality of product information and the potential health risks. Methods: I) Online search in Google España to find Spanish-language retail websites for Chinese herbal medicine in which we analysed both the claims regarding possible health benefits and adequate safe use indications II) Identification of potentially toxic herbs in the websites III) Quantification of Chinese herbal medicines withdrawn by the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Results: 1) Only one third of the 30 Spanish-language retail websites found which sell Chinese herbal medicine observe the law, given that the other websites include illegal Western disease claims as marketing tools, 2) Five websites provide some safety information, 3) Two websites offer potentially toxic herbs and 4) Chinese herbal medicine adulterated with sibutramine, silfenafil or their analogues make a considerable percentage of the total products withdrawn by the AEMPS. Conclusion: Online health seekers should be warned about misinformation on retail websites for Chinese herbal medicine and directed to a Spanish government Web site for guidance in safely navigating the Internet for buying Chinese herbal medicine (AU)

Evaluation of a Web-Based Holistic Stress Reduction Pilot Program Among Nurse-Midwives.

PURPOSE: Work-related stress among midwives results in secondary traumatic stress, posttraumatic stress disorder, and job attrition. The purpose of this pilot project was to evaluate the effectiveness of a holistic, web-based program using holistic modalities for stress reduction and improved coping among certified nurse-midwives. DESIGN AND METHOD: A convenience sample of 10 midwives participated in a web-based holistic stress reduction intervention using yoga, mindfulness-based stress reduction, and meditation for four days each week over 4 weeks. Participants completed pre- and postintervention questionnaires (Perceived Stress Scale [PSS] and the Coping Self-Efficacy Scale [CSES]) for evaluation of effectiveness. FINDINGS: The PSS means showed improvement in midwives' stress (16.4-12.3). The CSES means showed improvement in coping (174.8-214.5). Improvement was shown in each subscale of the CSES ("uses problem-focused coping": 19.2%; "stops unpleasant thoughts and emotions": 20.3%; and "gets support from family and friends": 16.6%). CONCLUSION: Findings suggest the potential for stress reduction and improved coping skills after using holistic techniques in a web-based format within a cohort of nurse-midwives. Further research of web-based, holistic intervention for stress reduction among midwives is warranted.

CSCD: a database for cancer-specific circular RNAs.

Circular RNA (circRNA) is a large group of RNA family extensively existed in cells and tissues. High-throughput sequencing provides a way to view circRNAs across different samples, especially in various diseases. However, there is still no comprehensive database for exploring the cancer-specific circRNAs. We collected 228 total RNA or polyA(-) RNA-seq samples from both cancer and normal cell lines, and identified 272 152 cancer-specific circRNAs. A total of 950 962 circRNAs were identified in normal samples only, and 170 909 circRNAs were identified in both tumor and normal samples, which could be further used as non-tumor background. We constructed a cancer-specific circRNA database (CSCD, http://gb.whu.edu.cn/CSCD). To understand the functional effects of circRNAs, we predicted the microRNA response element sites and RNA binding protein sites for each circRNA. We further predicted potential open reading frames to highlight translatable circRNAs. To understand the association between the linear splicing and the back-splicing, we also predicted the splicing events in linear transcripts of each circRNA. As the first comprehensive cancer-specific circRNA database, we believe CSCD could significantly contribute to the research for the function and regulation of cancer-associated circRNAs.

Growth of Integrative Medicine at Leading Cancer Centers Between 2009 and 2016: A Systematic Analysis of NCI-Designated Comprehensive Cancer Center Websites.

Background: Cancer centers have increasingly offered integrative medicine therapies in response to their patients' unmet needs. We evaluated the growth of integrative medicine in leading academic cancer centers in the United States as reflected by their public-facing websites. Methods: We performed a systematic review of 45 National Cancer Institute (NCI)-designated comprehensive cancer center websites. Two researchers independently evaluated whether the websites provided information regarding integrative medicine modalities and, if so, whether the services were provided in the same health system. They compared the proportion of cancer centers providing the information on each modality in 2016 with the data from the prior study in 2009. Results: The most common integrative medicine therapies mentioned on the 45 NCI-designated comprehensive cancer center websites were exercise (97.8%) and acupuncture and meditation (88.9% each), followed by yoga (86.7%), massage (84.4%), and music therapy (82.2%). The majority of the websites also provided information on nutrition (95.6%), dietary supplements (93.3%), and herbs (88.9%). The most common therapies offered in the health systems were acupuncture/massage (73.3% each), meditation/yoga (68.9% each), and consultations about nutrition (91.1%), dietary supplements (84.4%), and herbs (66.7%). Compared with 2009, there was a statistically significant increase in the number of websites mentioning acupuncture, dance therapy, healing touch, hypnosis, massage, meditation, Qigong, and yoga (all P < .05). Conclusions: Leading US cancer centers increasingly present integrative medicine content on their websites, and the majority of them provide these services to patients in the same health systems.

Structure-Based Virtual Screening.

Structure-based virtual screening (SBVS) is a computational approach used in the early-stage drug discovery campaign to search a chemical compound library for novel bioactive molecules against a certain drug target. It utilizes the three-dimensional (3D) structure of the biological target, obtained from X-ray, NMR, or computational modeling, to dock a collection of chemical compounds into the binding site and select a subset of these compounds based on the predicted binding scores for further biological evaluation. In the present work, we illustrate the basic process of conducting a SBVS with examples using freely accessible tools and resources.

SOHPRED: a new bioinformatics tool for the characterization and prediction of human S-sulfenylation sites.

Protein S-sulfenylation (SOH) is a type of post-translational modification through the oxidation of cysteine thiols to sulfenic acids. It acts as a redox switch to modulate versatile cellular processes and plays important roles in signal transduction, protein folding and enzymatic catalysis. Reversible SOH is also a key component for maintaining redox homeostasis and has been implicated in a variety of human diseases, such as cancer, diabetes, and atherosclerosis, due to redox imbalance. Despite its significance, the in situ trapping of the entire 'sulfenome' remains a major challenge. Yang et al. have recently experimentally identified about 1000 SOH sites, providing an enriched benchmark SOH dataset. In this work, we developed a new ensemble learning tool SOHPRED for identifying protein SOH sites based on the compositions of enriched amino acids and the physicochemical properties of residues surrounding SOH sites. SOHPRED was built based on four complementary predictors, i.e. a naive Bayesian predictor, a random forest predictor and two support vector machine predictors, whose training features are, respectively, amino acid occurrences, physicochemical properties, frequencies of k-spaced amino acid pairs and sequence profiles. Benchmarking experiments on the 5-fold cross validation and independent tests show that SOHPRED achieved AUC values of 0.784 and 0.799, respectively, which outperforms several previously developed tools. As a real application of SOHPRED, we predicted potential SOH sites for 193 S-sulfenylated substrates, which had been experimentally detected through a global sulfenome profiling in living cells, though the actual SOH sites were not determined. The web server of SOHPRED has been made publicly available at for the wider research community. The source codes and the benchmark datasets can be downloaded from the website.

TarNet: An Evidence-Based Database for Natural Medicine Research.

BACKGROUND: Complex diseases seriously threaten human health. Drug discovery approaches based on "single genes, single drugs, and single targets" are limited in targeting complex diseases. The development of new multicomponent drugs for complex diseases is imperative, and the establishment of a suitable solution for drug group-target protein network analysis is a key scientific problem that must be addressed. Herbal medicines have formed the basis of sophisticated systems of traditional medicine and have given rise to some key drugs that remain in use today. The search for new molecules is currently taking a different route, whereby scientific principles of ethnobotany and ethnopharmacognosy are being used by chemists in the discovery of different sources and classes of compounds. RESULTS: In this study, we developed TarNet, a manually curated database and platform of traditional medicinal plants with natural compounds that includes potential bio-target information. We gathered information on proteins that are related to or affected by medicinal plant ingredients and data on protein-protein interactions (PPIs). TarNet includes in-depth information on both plant-compound-protein relationships and PPIs. Additionally, TarNet can provide researchers with network construction analyses of biological pathways and protein-protein interactions (PPIs) associated with specific diseases. Researchers can upload a gene or protein list mapped to our PPI database that has been manually curated to generate relevant networks. Multiple functions are accessible for network topological calculations, subnetwork analyses, pathway analyses, and compound-protein relationships. CONCLUSIONS: TarNet will serve as a useful analytical tool that will provide information on medicinal plant compound-affected proteins (potential targets) and system-level analyses for systems biology and network pharmacology researchers. TarNet is freely available at http://www.herbbol.org:8001/tarnet, and detailed tutorials on the program are also available.

BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM's diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients' target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ's cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the "multi-component, multi-target and multi-pathway" combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM's molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.

TargetFreeze: Identifying Antifreeze Proteins via a Combination of Weights using Sequence Evolutionary Information and Pseudo Amino Acid Composition.

Antifreeze proteins (AFPs) are indispensable for living organisms to survive in an extremely cold environment and have a variety of potential biotechnological applications. The accurate prediction of antifreeze proteins has become an important issue and is urgently needed. Although considerable progress has been made, AFP prediction is still a challenging problem due to the diversity of species. In this study, we proposed a new sequence-based AFP predictor, called TargetFreeze. TargetFreeze utilizes an enhanced feature representation method that weightedly combines multiple protein features and takes the powerful support vector machine as the prediction engine. Computer experiments on benchmark datasets demonstrate the superiority of the proposed TargetFreeze over most recently released AFP predictors. We also implemented a user-friendly web server, which is openly accessible for academic use and is available at http://csbio.njust.edu.cn/bioinf/TargetFreeze. TargetFreeze supplements existing AFP predictors and will have potential applications in AFP-related biotechnology fields.

PredHydroxy: computational prediction of protein hydroxylation site locations based on the primary structure.

Compared to well-known and extensively studied protein phosphorylation, protein hydroxylation attracts much less attention and the molecular mechanism of the hydroxylation is still incompletely understood. And yet annotation of hydroxylation in proteomes is a first-critical step toward decoding protein function and understanding their physiological roles that have been implicated in the pathological processes and providing useful information for the drug designs of various diseases related with hydroxylation. In this work, we present a novel method called PredHydroxy to automate the prediction of the proline and lysine hydroxylation sites based on position weight amino acids composition, 8 high-quality amino acid indices and support vector machines. The PredHydroxy achieved a promising performance with an area under the receiver operating characteristic curve (AUC) of 82.72% and a Matthew's correlation coefficient (MCC) of 69.03% for hydroxyproline as well as an AUC of 87.41% and a MCC of 66.68% for hydroxylysine in jackknife cross-validation. The results obtained from both the cross validation and independent tests suggest that the PredHydroxy might be a powerful and complementary tool for further experimental investigation of protein hydroxylation. Feature analyses demonstrate that hydroxylation and non-hydroxylation have distinct location-specific differences; alpha and turn propensity is of importance for the hydroxylation of proline and lysine residues. A user-friendly server is freely available on the web at: .

methylC Track: visual integration of single-base resolution DNA methylation data on the WashU EpiGenome Browser.

SUMMARY: We present methylC track, an efficient mechanism for visualizing single-base resolution DNA methylation data on a genome browser. The methylC track dynamically integrates the level of methylation, the position and context of the methylated cytosine (i.e. CG, CHG and CHH), strand and confidence level (e.g. read coverage depth in the case of whole-genome bisulfite sequencing data). Investigators can access and integrate these information visually at specific locus or at the genome-wide level on the WashU EpiGenome Browser in the context of other rich epigenomic datasets. AVAILABILITY AND IMPLEMENTATION: The methylC track is part of the WashU EpiGenome Browser, which is open source and freely available at http://epigenomegateway.wustl.edu/browser/. The most up-to-date instructions and tools for preparing methylC track are available at http://epigenomegateway.wustl.edu/+/cmtk. CONTACT: twang@genetics.wustl.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.