Along came 1 April and the chance to switch from a textbook that I have been writing (my other life) to the two big projects of 2004: this new and much-needed book on Harry Carter, and our exciting new title on Venetian brickwork (see below). I still had all the type - over sixty galleys - from Stanley Morison & 'John Fell' which I printed last year and it was time to start taking it back to Stan Lane at Gloucester Typesetting who will be setting and casting the type for Harry Carter, Typographer.
Carrying twenty galleys of type up to his workshop from the car was the most exercise I had had for a while and required a breather and mug of tea before returning home on the first of the three trips that I shall have to make to return all the metal. It was also chance to talk about the Carter book and its typesetting. I had been thinking about the typeface for some time, wanting something 20th century in feel and appropriate to Carter. I had first thought of Dante and was close to fixing on it when I saw the piece on John Dreyfus in Matrix 23 from John Randle. It was printed in Romulus and looked lovely. Romulus was originally designed for the Enschedé foundry by Jan van Krimpen and later released by Monotype. It has a sloped roman in place of a true italic, so its 'italics' are rather wide on the body but equally they stand out less than a true italic would. Carter knew Van Krimpen and I'm sure its clean lines would have appealed to Carter. My challenge is to get its qualities onto paper. Stan has now acquired a brand new Romulus diecase - the 15 by 17 set of individual matrices for the typeface - and this book will be the first casting from it. On my second trip with type metal I handed over the copy and went through it with him, discussing the finer points of layout.
Getting the text finalised has been another big challenge. The book is in two parts: the biography and the bibliography. The biography runs to about sixty pages of text, and copy-editing that has been a fairly standard affair. Several people including spouses have given it a going over. The question of when to capitalise 'van/Van' in Dutch names has been a sticking point: authoritative Dutch sources contradict the Oxford Guide to Style which has otherwise been our bible! The bibliography runs to around 200 entries. John Lane collected all the original material, and Anne Rogers and Martyn Thomas have scrupulously checked and painstakingly organised it. John did not restrict himself to Carter's many writings but also collated reviews of Carter's work, and all these reviews appear against the works concerned. Getting the 30pp of the bibliography ready for typesetting has been 'interesting' as we have faced up to all the usual questions of how best to present information which can be looked at from so many different angles. Our solution has included an extensive Index which provides several routes to finding particular works in the bibliography.
We have collected a dozen photographs covering Carter's life, a number having been kindly loaned by the Carter family for the purpose, and others from Oxford University Press of course - Carter's last job was as Archivist at the Press, a role specially created for him in order to have him on board to help Stanley Morison on his great book on John Fell and his types. These have all gone to the Cloister Press near Cambridge for scanning prior to having them separately printed as we did with the photos in Stanley Morison & 'John Fell'. I lay out the photos on a single B2 sheet and then have about 300 of these printed and cut down to yield the tip-ins. (Something apparently as simple as this still has its pitfalls: whichever way the photos are tipped into the book, the grain of the paper they are printed on must go in the same direction as the grain of the paper they are tipped onto, ie parallel to the spine of the book.) Carter also designed some type borders, a Curwen paper, and an 'emerald' type for printing Bibles - we hope to represent all of these in one form or another in the book, to demonstrate the breadth of Carter's output.
Our plans for the de luxe copies are also coming on well. The original thought was to have a portfolio of separate items in the same way that we did for The Fell Revival and Stanley Morison & 'John Fell'. But during their research, Martyn Thomas and Anne Rogers have come across a number of pieces of unpublished writing by Carter and this seems a good opportunity to publish them. So the de luxe copies will probably contain an extra case-bound volume with a selection of these pieces in them.
All in all the book is shaping up very well. When originally conceived it was expected to run to about 60pp, but, as is the way with these things, it now looks more like 120pp! As a result the price has also had to be raised by a third and at the moment our expectation is that standard copies will be around £80 (E135, US$160) and de luxe copies £160 (E270, US$300).
A new study of the brickwork of Venice with over seventy watercolours.
The other big book in our current plans is Peter Harris's study of Venetian brickwork. When I was first sent his draft I was captivated by the watercolours - over seventy of them. His text is authoritative - he spent seven years in La Serenissima - and his images bring to life the qualities he describes in the fifteen chapters.
There is a real advantage to having two books on the go at any one time. One is often waiting for something to happen on a book - a paper order, typesetting, binding, review of drafts etc - and having another project to turn to at such times works well. On The Bricks of Venice I have so far been working on the text, finessing rather than editing. The next challenge - now that the copy for the Harry Carter book is with the typesetter - is to get into the technology of digital printing for the watercolours. When we had Philip Hughes's images for Jump of the Manta Ray printed we had them done on a state-of-the-art Iris printer, an expensive but possibly unsurpassed machine for quality and saturation of colour - Philip's images are very saturated,very intense. Watercolours require a different touch and technology has moved on. It is now a much more practical proposition to print such images on fine papers - the Somerset cotton papers used for Jump of the Manta Ray for instance - using archival inks, and all for a reasonable capital outlay. My computer facilities will be further complemented soon by a top-of-the-range Epson inkjet printer that uses seven cartridges to give the colour range one needs.
I can imagine that the use of these new technologies might feel like a betrayal to some. All of our text will continue to be printed letterpress, and with metal type, for its tactile qualities. But I have always enjoyed colour and think it a shame not to be able illustrate our books with watercolours, for example. My experience with Jump of the Manta Ray was that the combination of letterpress and digital image can produce striking results.
As a first step towards providing the facility to buy our books online from our website, we are now happy to accept payment by PayPal. Our customers in the UK may find it as easy to send us a cheque as always but we hope that customers outside the UK will be saved the nuisance of sending a cheque and instead be able to place an order via the form at our site and then pay by PayPal. If you are not familiar with PayPal why not visit www.paypal.com?
I have recently updated our website to give it (I think) a better feel. One of the developments planned for the near future is to allow online purchases using PayPal. Yes, you might soon be able to drag a virtual shopping cart/trolley around the site! I shall be announcing this in a future newsletter. I hope that customers outside the UK in particular will find this a much more convenient way of dealing with us, removing the need to send us cheques/checks and speeding things up considerably, whilst preserving everyone's financial security in the transaction.
For some years I have offered a discount to anyone (or any library) willing to take one copy of each book I do. It does help to know that there is a certain take-up that is guaranteed. I've decided to raise the discount to 15%. If you would like to take advantage of this please let me know. I generally aim to publish at least one and possibly two substantial books each year, with the occasional slighter title - such as the recent Fedor Tiutchev - dropped into the schedule as things permit. I also print the occasional booklet exclusively for Subscribers and friends of the Press. The most recent was an essay on the future of the book by controversial philosopher Ted Honderich. Future plans include a text on paper-making by hand.


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GNSS Enabling New Capabilities in Space on the TechDemoSat-1 Satellite
Martin Unwin, P. Jales, S. Duncan, A. Palfreyman, C. Gommenginger, G. Foti, Philip Moore, Jing Guo, Josep Rosello
Abstract: This paper describes the status of the UK TechDemoSat-1 (TDS-1) and its experimental GNSS receiver payload, the SGRReSI, and an overview of its recent operations and experiments. TDS-1 is a 160 kg satellite that was launched in July 2014. The SGR-ReSI continues to be operated on an experimental basis 2 days out of 8 collecting significant volumes of reflected GPS signals off the Earth's surface. Once corrections are made for the antenna pattern, and radiometric corrections for the system gain, the signal strength is related to the roughness of the reflection surface. Researchers at NOC have developed algorithms for inverting the measurements into estimates of the wind speed, and have been validating these models against other measurements of wind. While primarily an L1 single frequency experiment, the SGR-ReSI can operate at L2 and has been programmed in orbit to acquire and track GPS L2C signals. SSTL has been working with Newcastle University to recover the precise orbit using both L1 and L2C signals. Extra zenith GPS antennas have been used for providing extra platform attitude measurements, and for the first time, Galileo E1 signals are being tracked in orbit. In mid-summer, TDS-1 reaches the end of its nominal operating life, but plans are being made to extend the life, and move towards a higher level of service with partners experimenting with a pilot service. Beyond TDS-1, opportunities are being formulated for future opportunity flights of GNSS reflectometry on SSTL's satellites, and a new generation of instrument is being developed that supports both reflectometry and radio occultation.
Cite this article: Unwin, Martin, Jales, P., Duncan, S., Palfreyman, A., Gommenginger, C., Foti, G., Moore, Philip, Guo, Jing, Rosello, Josep, "GNSS Enabling New Capabilities in Space on the TechDemoSat-1 Satellite," Proceedings of the 30th International Technical Meeting of the Satellite Division of The Institute of Navigation (ION GNSS+ 2017), Portland, Oregon, September 2017, pp. 4066-4079.

redpajama_set_name: RedPajamaCommonCrawl


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These talking dog toys will give your dog hours of entertainment. Your dog will be captivated. We have a huge selection.
Really smart dogs need a lot of stimulation or they get bored and you know what can happen then. These talking dog toys are wonderful for their brains.
Collect the talking toys. Teach your dog each toys name by starting with one toy. Call that toy by a specific name that never changes, ie Shark. Then ask the dog to bring the toy to you. When he brings Shark give him a treat. Then say Catch Shark and toss the talking dog toy to him. Praise him when he gives it to you. Then ask him to bring it to you again by name. Gradually add the other toys by name. One of our dogs knows the names of 18 talking toys! Asking him to bring the toys to us and praising him is a fun game for all of us but also it uses his energy and allows him to get a good rest later. A fifteen minute brain game equals an hour walk outside. It's a great alternative when the weather is cold or wet. Also, it's a great party trick!


Ajay is a co-founder and CEO of EduBrite Systems Inc. Ajay comes with back-ground of building large scale enterprise systems for companies like eBay, NASA, eTouch Systems, Cisco, HP, Kaplan, and e*Trade.
CPhT: Brittany has worked in a pharmacy setting for more than 12 years. She is a Nationally Certified Pharmacy Technician.
Christopher Edwards works for KRM Associates, Inc. and part of the OSEHRA team as the Manager of Product Certification and Release Support.
Cyndi Shields - Currently a Senior CAC/Radiology ADPAC with DSS, Inc., the vxVistA Open Source experts. Cyndi came to DSS, Inc. with over 31 years experience with the Veterans Administration, 24 of those in the Radiology Service.
David Wicksell, the Chief Operating Officer at Fourth Watch Software, LC, has five years of experience supporting VistA systems. This includes GT.M database administration, Linux system administration, and software development.
Jason Li, Software Process Engineers for OSEHRA and R&D Engineer at Kitware.
Jean Snead - Clinical Applications Coordinator for 11 ½ years. RN with critical care and cardiology experience.
Johnny Tu - Senior Trainer at CustomWare, presented at the 2011 Atlassian Summit conference, worked with the products for over four years.
Kassi Goodman is Licensed Professional Counselor and an Internationally Certified Alcohol and Drug Counselor. I have a Master of Arts degree in Counseling and an Educational Specialist degree in Professional Counseling.
Training Manager: Margie has more than 7 years healthcare experience working with the VistA system. Margie is currently the Manager of the vxTraining team.
Mike Stark is an independent contractor who has worked in the healthcare information technology field for 20 years.
Tobias Anstett is co-founder of K15t Software. Based on Web 2.0 concepts and technologies he develops products and solutions for wiki-based documentation and communication.


This was extremely apparent when discussing business ethics with Steve Mitchell and Kassie Jorgenson, the Bank President and the Chief Operating Officer. Steve and Kassie did not work together until Arbor Bank but alongside one another have created a company culture that contrasts what many would assume could exist and succeed in a bank. The focus on empowering employees to make the right decisions is one of its biggest highlights. Additionally, the company has an impressive track record of providing support to clients and employees going through difficult situations; many other banks or employers would consider Arbor Bank's actions to be out of the scope of their work if faced with similar circumstances. These actions in turn have produced loyal employees and lifelong customers.
Both Steve and Kassie received their bachelor degrees at the University of Nebraska-Lincoln College of Business Administration. Steve started banking in 1992. He moved to Arizona for 10 years before returning to Nebraska. He has a wide range of experience, from working in large regional banks to starting up a new bank. Kassie started her career as a CPA at Arthur Andersen's Omaha office. The timing collided with the notorious Enron scandal and Arthur Andersen was Enron's auditor, a complicit member of the iconic scandal. Kassie worked in audit but did not work on the Enron audit while at Arthur Andersen; however, this impacted her view on business and ethical decision-making early on. She started at Arbor Bank three years before Steve.
How do you instill ethics in your organization?
What does "ethics" mean to you as Omaha business leaders?
With 90 percent of the bank's customers located in Nebraska, it is apparent that Arbor Bank's strong values and integrity in their work helps maintain a positive reputation in the local area. Steve and Kassie believe that if you have an organization built on strong values, profits will follow no matter what. Structuring it the other way will only lead to a short-term gain; therefore, the focus must always be building the culture and instilling values.
Can you describe an ethical situation in your career and how you handled it?
A tornado came through Oakland, Iowa a couple years back, where Arbor Bank has a branch. The bank did not experience damage; however, many of its employees had damage to their houses. The bank leadership made the ethical decision to close the branch for the day, risking potential profit loss, in order to give employees time needed to clean up and repair. Steve along with other branch employees traveled to Oakland to assist in the efforts.
Additionally, Arbor Bank had a longtime customer face a fraud issue. The bank quickly moved to help him retain almost all the money by having a special team formed and contacted all the related banks to recover the money back. The FBI shared with Arbor Bank that they have never had this much of a recovery in similar situations and they commended their team on their quick response and action. Protecting customer's assets and the bank's assets in an ethical manner is their main priority.
What are the ethical challenges and opportunities (ethical issues) you see in the business world today?
Steve shared his sentiments on what he sees as both a potential ethical threat and opportunity facing the business world today: millennials not telling the whole truth due to the pressure to succeed throughout their childhoods. Steve has seen this when young professionals are working on projects or in a particular situation and want to succeed so much that they might stretch the truth. Instead, he recommends not to fear failure and to ask for help every time over making an unethical decision on the whim to cover up the lie or over-exaggeration of experience. He also recommends selecting an organization to work for wisely to avoid ending up in a company where ethics are not top of mind and professionals are not provided resources needed to succeed. Additionally, both Steve and Kassie emphasize the importance of mentors and networking in order to establish a good ethical lens early on.


girl with current interest, Mackenzie Foy. . Wallpaper and background images in the Breaking Dawn The Movie club tagged: breaking dawn renesmee carlie cullen.
This Breaking Dawn The Movie photo contains farmer's market, green market, and greenmarket. There might also be grocery store, grocery, food market, market, candied fruit, succade, crystallized fruit, egg yolk, and yolk.


FSU's Library and Information Studies degree program prepared me for my career. I learned a variety of useful skills in a modern online classroom setting. The faculty and students I worked with are still professional contacts today.


Features include: a) Create online manuals & downloadable PDF docs – 1) Use simple codes for bold, italic, etc.; 2) Easily upload, manage and insert images; 3) Localize topics in multiple languages; 4) •Manage multiple manual versions. Share topics between manuals/versions; and 5) Define variables for use in shared topics; b) Publish manuals online, for any screen size – 1) New & edited topics are online instantly; 2) Auto-adapts to device type & screen size; 3) Built-in super-fast search engine; 4) Automatic downloadable PDF versions; 5) Publish "Private" manuals (optional), with user/pass logins for readers; c) Track topic view stats, user ratings & feedback – 1) Automatic stats of manual & topic views; 2) "Was this useful?" voting for readers; 3) Allow readers to comment on topics; 4) Track all user searches to find keywords; 5) Score Topic Quality from user ratings; and 6) Link Google Analytics for more stats. This has been added to the tools section of Research Resources Subject Tracer™ Information Blogs. This will be added to Tutorial Resources Subject Tracer™.


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LIVE FOOTBALL SCORES
Champions League returns!	5/5	(7)
Posted on February 12, 2019 March 18, 2019 by Dejan
Champions League returns with knock out phase! 16 of the best teams in Europe are left to fight it for the lucrative title of the best on the continent!
All contestants left are well known to the general public and used to compete in the latter stages of the competition.
Champions League round of 16 fixtures
I guess you're all informed how the draw works but we're quickly sum it up. Group winners are seeded teams with the advantage to play the return game at home.
Second-placed teams are non-seeded and play first match at home. At this stage two criteria that need to be considered when pairing is:
Clubs that played in the same group can't meet in the round of 16
Clubs from the same country can't meet in the round of 16
The principles really narrowed the possibilities for English clubs since all 4 of them progressed from the group stage. Spanish and German competitors also had limited options left with 3 clubs from each country earning promotion.
France and Italy managed 2 participants each. Last spots were secured by Dutch and Portuguese representative.
This is what the urn in Nyon prepared for us:
Schalke 04 (GER) – Manchester City (ENG)
Atletico Madrid (SPA) – Juventus (ITA)
Manchester United (ENG) – Paris SG (FRA)
Tottenham (ENG) – Borussia Dortmund (GER)
Lyon (FRA) – Barcelona (SPA)
Roma (ITA) – Porto (POR)
Ajax (NED) – Real Madrid (SPA)
Liverpool (ENG) – Bayern Munich (GER)
Final triumph favorites
Based on what we saw till now in Champions League alone front-runners are Juventus and Barcelona.
Juventus didn't have overly tough group even if Manchester United was part of it. But we all know how United performed in the autumn under the previous manager.
Despite some shaky moments and 2 defeats, the Italian giants showed impressive strength in depth and real desire to finally get their hands on the trophy! Well, at least until topspot and qualification were granted.
Healthy advantage in Serie A allows Allegri to rotate his players domestically in order to focus on the Champions League.
In the last few years Juventus was competitive but every time lacked something. That crucial little detail that eventually swings the fortune your way.
That detail has been taken care of in the summer with Ronaldo's acquisition. Now they can't hide anymore. The squad is complete and it's up to the manager to make it perform as it can.
Barcelona is a mainstay in the knock-out stages in the competition for nearly 2 decades. Not much can be said about the Catalans that hasn't been said already. Several times!
Group wasn't the easiest on paper with Tottenham and Inter, returning to Champions League after a prolonged period. PSV rounded it up but never had realistic chances of progression.
Squad on Valverde's disposal is balanced, talented and experienced. Beside the natural will to win every competition they enter, this year additional motivation is to finally dethrone the arch rivals from the Spanish capital.
Whatever domestic success Barcelona accomplished in the last 3 years, Real Madrid overshadowed it by winning Europeans' prime competition.
Real Madrid, as reigning champion, has to be viewed as a favorite. At least in the wider circle.
Losing the technical leader and best scorer along with one of the most successful managers in club's lustrous history left scars. Deep ones! The voids weren't filled adequately and it shows!
There is still abundance of quality in the team, even unused. However, despite recent upturn in form, Real lost some of its fear factor.
Abysmal first part of the season granted group top spot only due to Roma's inability to hit the target from sitters!
Managerial change improved the performances and results, however, hardly enough to regain the crown. Other team are better equipped for final triumph!
It's hard to predict what to expect from Manchester City in Champions League! Dominant and ruthless in Premier League, yet somewhat struggling in international competition.
A balanced group started with a shocking home defeat to Lyon and continued with hard-fought victories against Shakhtar and Hoffenheim.
Nevertheless the Citizens managed to win the group. Final standings would suggest with ease but actually it wasn't easy. At all!
Schalke won't give any indication on City's real strength, the gulf in class is just to big. However in the quarter finals we should have an answer which is the real City.
The one that gives Lyon the only win in Champions League or the one that blows Liverpool and Chelsea away.
Whatever the draw for next stages will say, if anyone beside the mentioned 4 teams wins, it'll be a huge surprise!
Please review this article using the ratings
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SHAREHOLDER ALERT: Pomerantz Law Firm Reminds Shareholders with Losses on their Investment in Micron Technology, Inc. of Class Action Lawsuit and Upcoming Deadline – MU
NEW YORK, March 21, 2019 (GLOBE NEWSWIRE) -- Pomerantz LLP announces that a class action lawsuit has been filed against Micron Technology, Inc. ("Micron" or the "Company") (NASDAQ: MU) and certain of its officers and directors. The class action, filed in United States District Court, Southern District of New York, and indexed under 19-cv-02136, is on behalf of a class consisting of all persons and entities, other than Defendants and their affiliates, who purchased or otherwise acquired Micron securities between September 26, 2017 and November 19, 2018, inclusive (the "Class Period"), seeking to pursue remedies under the Securities Exchange Act of 1934 (the "Exchange Act").
If you are a shareholder who purchased Micron securities during the class period, you have until March 25, 2019, to ask the Court to appoint you as Lead Plaintiff for the class. A copy of the Complaint can be obtained at www.pomerantzlaw.com. To discuss this action, contact Robert S. Willoughby at [email protected] or 888.476.6529 (or 888.4-POMLAW), toll-free, Ext. 9980. Those who inquire by e-mail are encouraged to include their mailing address, telephone number, and the number of shares purchased.
[Click here to join this class action]
Micron purports to sell high-performance memory and storage technologies, including dynamic random access memory or "DRAM".
The complaint alleges that throughout the Class Period, Defendants made materially false and misleading statements regarding the Company's business, operational and compliance policies. Specifically, Defendants made false and/or misleading statements and/or failed to disclose that: (1) the Company engaged in anti-competitive behavior, including artificially restricting supply growth of DRAM; (2) these anti-competitive efforts were reasonably likely to lead to regulatory scrutiny; (3) the Company's anti-competitive efforts artificially boosted its operating metrics; (4) as a result, the Company's financial performance, including revenue, was overstated; and (5) as a result of the foregoing, Defendants' positive statements about the Company's business, operations, and prospects were materially misleading and/or lacked a reasonable basis.
On November 19, 2018, Financial Times reported that Chinese investigators said they had found "'massive evidence' of anti-competitive behavior" by Micron and two other companies. On this news, the Company's share price fell $2.61 per share, nearly 7%, to close at $36.83 per share on November 19, 2018, on unusually heavy trading volume.
The Pomerantz Firm, with offices in New York, Chicago, Los Angeles, and Paris, is acknowledged as one of the premier firms in the areas of corporate, securities, and antitrust class litigation. Founded by the late Abraham L. Pomerantz, known as the dean of the class action bar, the Pomerantz Firm pioneered the field of securities class actions. Today, more than 80 years later, the Pomerantz Firm continues in the tradition he established, fighting for the rights of the victims of securities fraud, breaches of fiduciary duty, and corporate misconduct. The Firm has recovered numerous multimillion-dollar damages awards on behalf of class members. See www.pomerantzlaw.com.
Robert S. Willoughby
Pomerantz LLP
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Research ArticleMinireview
Overview of Current Herb–Drug Interaction Databases
Yufeng Zhang, Chung Man Ip, Yuen Sze Lai and Zhong Zuo
Drug Metabolism and Disposition January 2022, 50 (1) 86-94; DOI: https://doi.org/10.1124/dmd.121.000420
Yufeng Zhang
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
Chung Man Ip
Yuen Sze Lai
Zhong Zuo
An HERB–Drug Interaction (HDI) database is a structured data collection method for HDI information extracted from scattered literatures for quick retrieval. Our review summarized the ten currently available HDI databases, including those databases comprising HDI on the market. A detailed comparison on the scope of monographs, including the nature of content extracted from the original literature and user interfaces of these databases, was performed, and the number of references of fifty popular herbs in each HDI database was counted and presented in a heatmap to give users an intuitive understanding of the focuses of different HDI databases. Since it is well known that the development and maintenance of databases need continuous investment of capital and manpower, the sustainability of these databases was also reviewed and compared. Recently, artificial intelligence (AI) technologies, especially Natural Language Processing (NLP), have been applied to screen specific topics from massive articles and automatically identify the names of drugs and herbs in the literature. However, its application on the labor-intensive extraction and evaluation of HDI-related experimental conditions and results from literature remains limited due to the scarcity of these HDI data and the lack of well-established annotated datasets for these specific NLP recognition tasks. In view of the difficulties faced by current HDI databases and potential expansion of AI application in HDI database development, we propose a standardized format for data reporting and use of Concept Unique Identifier (CUI) for medical terms in the literature to accelerate the structured data collection.
SIGNIFICANCE STATEMENT The worldwide popularity of botanical and/or traditional medicine products has raised safety concerns due to potential HDI. However, the publicly available HDI databases are mostly outdated or incomplete. Through our review of the currently available HDI databases, a clear understanding of the key issues could be obtained and possible solutions to overcome the labour-intensive extraction as well as professional evaluation of information in HDI database development are proposed.
Botanical products and/or traditional medicines are an important supplement to our current medical system and may be called herbs, foods, dietary supplements, nutraceuticals, or traditional Chinese medicine (TCM) under different regulation systems around the world (Trovato and Ballabio, 2018; Alostad et al., 2020). For the sake of simplicity, all these products used for health purposes are collectively referred to as "HERBs" to represent a broader concept than "herbs" in this review. Unlike conventional drugs, most HERBs or their preparations have not undergone rigorous assessment on the safety, efficacy, and quality control before their launch into the market (Glisson and Walker, 2010). These HERBs may be intentionally or unintentionally co-administered with western drugs, raising the potential of pharmacokinetic and/or pharmacodynamic HERB–drug interactions (HDIs) (Izzo and Ernst, 2001; Hu et al., 2005) and leading to major safety concerns, especially for drugs with narrow therapeutic indices [e.g., warfarin (Ge et al., 2014) and digoxin (Cheng, 2006)]. Thus, the collection and evaluation of these reported HDIs would be valuable to both frontline healthcare workers and the public. However, most literature about HDIs are either case reports or limited clinical observations that are not well-documented (Fugh-Berman and Ernst, 2001), which usually result in "unable to be evaluated" based on the established reliability criteria for western drugs. Regardless, HDI undoubtedly exists, and its risk is unavoidable to each individual.
After realizing the clinical importance of HDI, a handful of researchers and companies started to build HDI databases using various information technologies (IT) in the late 1990s (Bailey, 2011; Lin, 2011; Vardell, 2015; Kluwer, 2018; Wu et al., 2019; Birer-Williams et al., 2020; Wang et al., 2020; UW, 2021; Zhang and Zuo, 2021). Nowadays, these HDI databases could be divided into two categories based on their availability to the public: (1) freely accessible databases and (2) commercially available databases. In general, building a professional database, including HDI databases, consists of three key steps. The first step is to identify the data sources from which to collect the needed information; the second step is to grab/digitize and save the data locally for further processing; and the third step is to obtain structured data through extraction and evaluation of the original data. The first two steps are usually the major work in the early stages of database development and require both the opinions of experts/specialists and IT support. However, the third step consists of the most time-consuming and labor-consuming work, which exists throughout the life cycle of database development and maintenance. Thus, the third step on how to obtain structured data from text materials written in natural languages is a rate-limiting step for the database development. HDI information is buried in all kinds of natural language texts, such as abstracts, journal papers, books, or drug evaluation reports. Only well-trained researchers with a medical background can fulfill this kind of work. For freely accessible databases, they tend to stop updating after their publication due to a lack of continuous funding support. On the other hand, successful commercially available databases could cover all related costs for database development and maintenance by charging annual fees. Recently, to solve the labor- and time-consuming problems in HDI database development, artificial intelligence (AI) technologies have been used to automatically extract HDI information from the literature and displaying the obtained evidence on SUPP.AI (Wang et al., 2020). The application of AI highlights the rate-limiting step of HDI database development, although AI is still far from serving as a substitute for the work of experienced medical researchers in extracting and evaluating HDI information from literature.
In this review, we provided a summary of the coverage of HERBs, main features, source, search and export method, and content update frequency for the ten most popular freely accessible and commercially available HDI databases in Table 1 and illustrated as follows. To further facilitate the choice of HDI database from user point of view, we also compared the number of HDI-related references for 50 selected popular herbs among these databases as shown in Fig. 1. Those databases focused on drug-drug interactions (DDI), such as Cortellis Drug Discovery Intelligence, DrugBank, Medscape, ONCHigh, PharmaPendum, and WebMD, were not covered in this review.
Comparison of HDI database coverage for the selected 50 herbs. Numbers of references larger than zero were marked at the intersection of herbs and HDI databases.
Comparison of the properties from the ten most popular HDI databases.
2. Freely Accessible HDI Databases
2.1. The Chi Mei Search System (CMSS).
CMSS was developed by the Department of Pharmacy, Taiwan Chi Mei Medical Center in October 2004 (Chimei, 2004), and version 2 is its most updated interface. The database embedded a search box for searching herb names, brand, or chemical names of western drugs. A total of 139 herbs and 52 traditional Chinese Medicine (TCM) formulae were included, which resulted in 6,173 interaction pairs with western drugs (Table 1). In addition, possible mechanisms of interaction, clinical manifestations, and recommendations were summarized for each herb/TCM-drug interaction pair. CMSS covers a relatively large number of herbs/TCM and their interactions, but no sources of these interactions were provided, and it is hard for others to re-evaluate those potential HDI interactions.
2.2. The Chinese–Western Medicine Integrative Information Network (CWMIIN).
The CWMIIN was developed by Prof. Lin from China Medical University with grant support from the Ministry of Health and Welfare of Taiwan (Lin, 2011) and was first published in 2004, followed by subsequent updates in 2008 and 2011. The coverage in the current version 2011 system is 30 TCM formulae, 72 herbs, 12 foods, and 4 herbal components, which interacted with 171 western drugs from 607 references (Table 1). Unlike those interaction pairs listed in CMSS, all records in CWMIIN have a link to the source of the HDI information. Users can perform HDI searches by entering an herb list and a drug list or browse all HDI entities from the predefined lists of TCM formulae, herbs, or drugs. The search results include a brief summary of the HDI with the names of the herbs and drugs involved.
2.3. Drug Herb Interaction Query Website (DHIQW).
The DHIQW was the outcome of a collaboration between Prof. CS Wu (National Formosa University) and Prof. ZH Wu (Taipei Medical University), with grant support from the Ministry of Science and Technology of Taiwan (Wu et al., 2019). Current popular front-end and back-end frameworks, such as Vue.js and Node.js, were used for the database development, resulting in a user-friendly and responsive platform. The HDI information extracted from literature in DHIQW were rewritten by pharmacists to render the information easy to be understood by general public. Until now, only three herbs (Ginseng, Ginkgo and Dong Quai) and 300 pairs of HDIs were included in this database as shown in Table 1. Two types of searches, including single search and smart search, are allowed. The former only requires either the name of an herb or a drug, while the latter allows users to search for HDIs of multiple herb-drug pairs. In the search results, the HDIs are bilingually summarized with a few phrases in both the English and Chinese languages. Other information, such as details of the study that lead to the conclusions on HDI, mechanism behind the HDI, implication of HDI, and details about the sources, are also given in the search results.
2.4. Center of Excellence for Natural Product-Drug Interaction Research (NaPDI).
NaPDI is a data repository for pharmacokinetic natural product–drug interactions developed by the National Institutes of Health National Center for Complementary and Integrative Health (Birer-Williams et al., 2020). This database is still under development, and as of July 2021, interactions of 7 herbs with 259 compounds have been included as indicated in Table 1. The unique feature of NaPDI is that structured data, including experimental conditions and pharmacokinetic parameters of in-vitro and in-vivo studies, are extracted for four experiment type categories to guarantee FAIR (Findability, Accessibility, Interoperability and Reusability) data in NaPDI. In addition to supporting refined searches, data in NaPDI can be browsed by the titles of Natural Products, Studies, or Compounds. In addition to the published reports included in NaPDI, there are also six unpublished studies in the current database.
2.5. Probot Chinese Medicine–Drug Interaction Database (Probot).
Probot aims to collect all published evidence about interactions between Chinese Medicine and drugs to provide factual data for clinicians and the public. This database, supported by Healthy Power Limited and Innovation and Technology Commission, Hong Kong, is still under development (Zhang and Zuo, 2021). As of July 2021, 6,292 interactions between 193 herbs and 726 western drugs originated from 4,342 references are included (Table 1). Probot supports bilingual display and query in Chinese and English. For the maintenance of the website, abstracts from PubMed, Wanfang, and CNKI are automatically retrieved by in-house programs and screened for their relevance to HDI using a Naive Bayes model (Precision=0.78, Recall=0.91, F1-score=0.84). Only those HDI-related abstracts are further processed by experienced pharmacists. Such an approach improves the automation of database development so as to allow more focus on manual extraction and evaluation of detailed information from literature that AI may not be able to perform effectively.
2.6. SUPP.AI.
In 2019, a team from the Allen Institute for Artificial Intelligence (AI2) developed the SUPP.AI database, with the aim of providing scientific evidence for supplement-drug interactions by automatically extracting supplement information from the scientific literature (Wang et al., 2020). Apart from searching evidence on supplement-drug interactions, users can also download their dataset, as well as access programmatically with their Application Program Interface (API). As shown in Table 1, the database contains information about 60,000 interactions, with 195,000 evidence sentences extracted from 22 million articles. Specifically, about 2,044 supplements and about 2,842 drugs are involved in these interactions as of July 2021. Users can perform searches with keywords, such as the name of an herb. The search results include possible HDIs at the entity page and the relevant evidence sentences at the interaction page, and the herbs and drugs are highlighted in each evidence sentence. The sources of the evidence sentence, as well as links to further details of the sources provided by the semantic scholar database, are also given. An important advantage of this database is its automated approach to extract evidence sentences, which not only saves time and avoids manual efforts, but also provides convenience for users to process data with customized computer programs for specific purposes. This database covers a relatively large number of supplements and their interactions with drugs. Limitations of the methods for providing the HDI information are discussed in the paper published by the developers (Wang et al., 2020). The arbitrary distinction between drugs and supplements, the lack of a standardized terminology for supplements, and the weakness of the natural language processing (NLP) tools employed by SUPP.AI all seem to limit SUPP.AI's capability to identify potential HDI information from literature.
3. Commercially Available HDI Databases
3.1. UW Drug Interaction Database (DIDB).
The DIDB was founded by Dr. René Levy at the University of Washington in the late 1990s, and the subscription program was started in 2002 (Hachad et al., 2010). DIDB has the largest manually curated collection of in vitro and clinical data related to drug interactions in humans (no data from animal studies), including interacting co-medications, excipients, food products, herbals, tobacco, organ impairment, and genetics, which can affect drug exposure in humans. This database integrates information from the literature, drug labels, FDA drug approval review packages for new drug applications (NDAs), and biologics license applications (BLAs). Relevant information from these resources is manually extracted and presented in DIDB in a well-structured manner based on the mediated mechanism(s), e.g., enzyme or transporter inhibition or induction. Both in vitro kinetic and clinical pharmacokinetic parameters as well as detailed experimental conditions, study design, and dosing regimen are curated. Clinical outcome of each interaction includes pharmacokinetic, pharmacodynamic, and safety. The content in DIDB is validated by experts and updated daily. The database can be searched not only using basic keywords (i.e., drug name, enzyme, transporter, therapeutic class, etc.) but also using more specific parameters of interest, such as in vitro parameters, changes in exposure, QT prolongation, etc. A menu of over 70 pre-formulated queries allows users to search and integrate preclinical and clinical data across multiple studies. In addition to data curation, the database also provides drug monographs for recently marketed drugs, with a detailed DDI summary based on available data. Of note, HDI information is a growing fraction of the DIDB. As of June 2021, the application contains a total of 2,539 natural products (herbal medications and food products), with 15,864 drug interaction experiments/studies (Table 1).
3.2. Lexicomp Drug Interactions (LDI).
Information regarding HDI can be accessed by using the interaction module of the Lexicomp database (Kluwer, 2018). This module is part of UpToDate, which is under Wolters Kluwer, a global provider of professional information for a wide variety of sectors. UpToDate has been marketed as "the most trusted evidence-based clinical decision support resource at the point of care". The target users are medical professionals who need to provide medical advice to clients on a regular basis. Clinical evidence was pre-processed by a team of authors and editors. Data in LDI are mostly for DDI as those in DIDB. Among the 2,096 entities included by LDI, only 85 were herbs, and the total number of herb–drug or herb–herb interaction pairs were 295 which were from 902 references. One of the following interaction ratings is assigned to each interaction: "Avoid combination", "Monitor therapy", "No known interaction", "Consider therapy modification", and "No action needed". LDI organizes all interactions under "Interacting Members", and the member compounds in the same "Interacting Members" are thought to have the same interaction although there is no publication to support.
3.3. Natural Medicines Comprehensive Database (NMCD).
The NMCD was developed by the Therapeutic Research Center (TRC), an organization set up in 1985 with the aim to "positively impact patient care and reduce medication errors in the U.S and beyond". This database is marketed as "the most authoritative resource available on dietary supplements, herbal medicines, and complementary and integrative therapies" (Yacobucci, 2016). NMCD is in fact a collection of databases, and to search for HDI information, users would need to use the "Food, Herbs and Supplements" database. As of July 2021, this database has included more than 1200 products for food, herbs, and supplements as indicated in Table 1. Users can either access information by performing keyword-based searches and/or select from a list of food, herbs, and supplements. In the HDI section of each monograph, the interactions are characterized by the interaction rating, severity, likelihood of occurrence, and level of evidence, followed by a description of the interaction. Apart from the rather comprehensive coverage of herbs, this database also provides easy-to-understand monographs that are specifically prepared for consumers rather than professionals. For each monograph, an image of the item, e.g., herb is provided, which gives the users an idea of the appearance of the searched items, or the sources of the searched items. Users may also find products that contain the particular searched items by using the links provided in the "commercial products" section. In addition, each monograph is reviewed at least once per year, and the date of review and any update are given at the bottom of the monograph. Information in the database should be reliable since it is processed and validated by health professionals licensed to practice in their specialty area. Consumer information about herbs and HDIs are also available in French and Spanish as well as from English. Some of the monographs are still under development; thus, users will find "insufficient reliable information available" in some sections.
3.4. Stockley's Herbal Medicines Interactions (SHMI).
As one of the databases from MedicinesComplete, published by the UK Royal Pharmaceutical Society, SHMI has been an important online platform for exploring HDI information since its launching in 2004 (Bailey, 2011; Rice, 2014). SHMI aims to provide quick and easy access to core and specialist resources at the point of care. The database contains monographs of about 216 herbal medicines, dietary supplements, and nutraceuticals originating from about 2,000 references as shown in Table 1. The general information page of each 216 HERBs includes its synonyms, constituents, indications, pharmacokinetics, and interaction monographs. Under the section of interaction monographs for each herb, all drugs or drug categories having interactions with that HERB are listed with hyperlinks to the HDI monograph for each HDI pair. The database also offers quick access to "related content" of the queried HDI, so users can conveniently look up other relevant HDIs, such as those involving the herb of the queried HDI. This database covers a relatively large number of herbs, and information is regularly updated, processed, and validated. Some pedagogic guidance on the usage and relevant scientific principles are available, which facilitate users' understanding of herbal medicines and potential risks.
4. Summary and Perspectives
4.1. Coverage of Herbs and References.
For fair comparison, only HDI-related information were included in Table 1 and Fig. 1, with those interactions between a single herbal component and drugs or two drugs being excluded. An ideal HDI database is to include all HERBs and all HDI-related references; however, no currently available HDI databases meet such requirement. In general, commercial (DIDB, LDI, NMCD, and SHMI) and newly developed (Probot) databases have broader coverage than free ones. To visually compare the coverage of herbs and HDI-related references in the ten reviewed databases, we selected 50 popular herbs from 616 herbs in 2015 China Pharmacopoeia based on number of research papers obtained in Wanfang and PubMed, the two well-known abstract databases for English and Chinese articles, respectively. As a result, the top 50 herbs were identified as shown in Fig. 1. To find whether there is a match for each herb, the plant/herb name as well as their synonyms in both English and Chinese were searched in the ten HDI databases. For example, the matched terms for Licorice were (1) "Licorice" in DIDB, LDI, NMCD, NaPDI, and SUPP.AI; (2) "Licorice" in SHMI; (3) "甘草" in CMSS, CWMIIN, and Probot; (4) "Gan Cao" in Probot. The search results for the 50 selected herbs were summarized in Fig. 1. Since no source is available for CMSS, the number of HDI entries were used to represent the number of references instead. It is noted that CMSS, Probot, and SUPP.AI had a better coverage of popular herbs than other HDI databases. Although NMCD and SHMI are also good sources for HDI, their relatively lower reference numbers could be mainly due to the insufficient inclusion of literature written in Chinese in PubMed, the source of these two databases. Despite low coverage of herbs, DHIQW and NaPDI are still very useful for HDI information of their included herbs due to unique features, such as structured data for experimental conditions and results.
4.2. Nature of Content Extracted from the Original Literature.
Except for CMSS, all other databases provide source links where applicable, and most of the data appears to come from PubMed as indicated in Table 1. Some databases also include prescribing information, books, conference papers, even regulatory documents, although these are not common since alternative data sources might be less accessible than PubMed. Many databases use data from post-processed original literature. The post-processing work is typically performed by health professionals and researchers, for the sake of validating raw data and simplifying technical details which would otherwise be difficult for general audiences to understand. An exception is SUPP.AI, in which evidence sentences are extracted directly from original references without further rephrasing nor validation by professionals. The advantage is that it reduces manual effort: however, the quality of the HDI information extracted without verification by professionals might be questionable.
4.3. Content Update Frequency, Sustainability and Liability.
Data entities in professional databases need to be constantly revised, supplemented, and added to present the users with comprehensive and correct information at all times. If the information in databases is not updated in time, it may cause users to make wrong judgments, thereby harming the health of patients. Update frequencies of the reviewed ten databases were given in Table 1. Three databases (CMSS, CWMIIN, and DHIQW) have, however, already abandoned continuous update, which might be attributed to the costly manual update of their content. LDI, NaPDI, and SUPP.AI have not updated their content for at least several months. Only NMCD, SHMI, DIDB, and Probot have published recent updates. DIDB, NMCD, and SHMI belong to commercial databases, and annual subscriptions are needed for users to access their data, which could be used to cover the high cost of regular updates. Therefore, user-paid access may facilitate the sustainability of these databases. In addition, SUPP.AI offers an automatic protocol for updating the database once in several months, which may serve as a solution for database developers to provide continuous updates without sufficient resources.
Data provided in these HDI databases should be used with care since some databases did not undergo a strict review process and it is suggested to verify the information with their provided original sources before making a crucial decision. It was also noted that most HDI databases lacked convenient ways for users to point out errors in their databases. It is not expected that all the HDI databases can replace health professionals to provide HDI information in the near future. Currently, many HDI databases include a disclaimer or warning to indicate that information provided by the databases should not be used as a substitute for advice from healthcare professionals. The disclaimer on Stockley's database states that the publisher is not be responsible for errors and omissions, and it is the responsibility of practitioners to interpret SHMI in light of professional knowledge and relevant circumstances. SUPP.AI has also included a disclaimer to indicate that "the information contained herein should not be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider".
4.4. User Interfaces.
All databases support keyword-based searches. The keywords that users must provide are typically either the name of the herbs or the drugs or both. Some databases provide alphabetical indexes to facilitate searches (e.g., NMCD and SHMI), while analogous indexes for herbs and drugs in Chinese are available in CWMIIN. Almost none of the databases considered provide a search function that allows query based solely on the characteristics of the HDI without explicitly stating the herbs and drugs involved. An exception appears to be DIDB, in which study results of HDI can be retrieved without necessarily providing drug names.
Recently, there has been a surge in the use of graph databases, which allows searches to be performed based on descriptors of relationships. Potentially, a graph database can enhance the search function and some other technical aspects of a typical relational-type HDI database and remove the limitation of confining keywords to be the names of herbs and drugs in HDIs. A graph database stores data in the form of nodes and relationships, which are fundamental elements of graphs. In the context of HDI, the graph can be a representation based on herbs and drugs as nodes and interactions as relationships. The implication of an HDI graph database is that, if users only have knowledge of the symptoms and are ignorant about herbs and drugs, and these symptoms describe the relationships, i.e., the interactions, users might still be able to make use of the database and discover potential herb–drug pairs that cause the symptoms.
Some databases provide advanced search options to facilitate filtration of undesirable search results. NMCD, for example, allows users to exclude certain fields for a particular query. Both NMCD and SHMI are collections of sub-categorized databases of smaller sizes, and both databases allow users to search only a subset of the collection. Surprisingly, few databases provide the functions to allow users to download a record of the search results in a format, e.g., .CSV, which can be electronically edited with ease. Seemingly only NaPDI, DIDB, and SUPP.AI offer this type of function. SUPP.AI is the only database that provides an API for programmatic access of data. Such a feature is particularly convenient for data analysis that requires customization with user-developed computer programs.
4.5. Role of AI in HDI Database Development.
The subset of AI that is particularly relevant to the development of HDI database, which typically requires understanding and organizing a large amount of biomedical text data from a large corpus of scientific articles and reports, is NLP (Rodriguez-Esteban, 2009). With the aid of NLP, the expected outcome is that these text data can be efficiently and accurately classified, extracted, translated, and interpreted, minimizing the manual efforts and time required to develop and maintain these HDI databases. Some of the applications of NLP for developing an HDI database include the recognition of HDI-related articles, the recognition of named entities, e.g., herbs and drugs, the recognition of relationships e.g., the interactions between a pair of herb and drug, and to draw conclusions from a piece (or a large corpus) of text. In the context of HDI, the last task can be interpreted as extracting the conclusion of HDI. This is not the same as drawing a conclusion from several studies for a particular HDI, which is desirable for an HDI database as this would produce certainty with regard to the HDI information offered, but difficult to achieve with confidence even done manually by professionals. Databases such as DrugBank (Wishart et al., 2006) and NMCD would use metrics, such as evidence levels, to represent the reliability of the information on HDI and DDI.
In general, the NLP tasks for HDI data can, in principle, be performed with two types of algorithms, rule-based approaches and statistical models. Rule-based approaches use rules derived from linguistics and/or knowledge of medicines to extract the relevant HDI information. For instance, provided with a dictionary and a set of well-defined rules for the nomenclature of herbs and drugs, matching text strings might suffice the task for Named Entity Recognition (NER), a method that does not require high computational cost. A dictionary-based approach, however, can suffer from problems of term variation. Kang et al. discussed that variations can be eliminated using the Unified Medical Language System (UMLS) (Bodenreider, 2004), and they have derived rules to tackle these problems (Kang et al., 2013). In the same study, researchers have derived rules for other NLP tasks, including coordination, abbreviations, boundary corrections, and filtering, and all the rules are related to the use of a concept normalization system. These rule-based NLP methods were able to improve the recognition of disease from relevant corpus. A linguistic rule-based approach was attempted by Segura-Bedmar et al. to extract DDIs from biomedical text, but in this study, the rules were unable to identify many of the interactions, and the authors suggested that this is due to the variability of natural language expression (Segura-Bedmar et al., 2011). Generally, trouble-shooting is convenient for rule-based approaches, and there is often high flexibility to improve the effect of the rules, i.e., the performance of the NLP methods. It might be difficult, however, to develop rule-based systems if the data sources are articles with different writing styles, and there is a large variability with regard to the content of these articles.
Another approach would be the use of statistical models, which are normally trained with large and annotated datasets. Techniques for text classification and NER are well-developed in the field of biomedical text mining. Many common classification methods, such as Naïve Bayes (NB) classifiers and support vector machines (SVMs), that without the need to extensively experiment with these methods, may be sufficient to produce results with tolerable inaccuracies, provided the dataset is sufficiently large and well-curated. The linear SVM classifier in Sum Kim et al.'s work was able to achieve an F1-score of 0.67 based on the DDIExtraction 2013 corpus (Kim et al., 2015). A feature-based approach combined with an SVM classifier tested by Quoc-Chinh Bui et al. were able to achieve accuracy of over 80% for extracting DDIs (Bui et al., 2014).
The research community generally believes that deep learning techniques can improve the performance of AI in many different applications. Zhang et al. reviewed a large number of these techniques for the extraction of DDIs, which are either based on convolutional neural network (CNN), recurrent neural network (RNN), or recursive neural network (Re-NN) (Zhang et al., 2020). They have shown that some of the models, such as attention-based RNN and deep CNN were able to produce high F1 scores of over 80%. These methods, however, may have stability issues, and the dependencies of these models on other factors, such as data volume and quality, could discourage choosing this type of technique to extract DDIs. In general, statistical models are particularly useful in unstructured data, e.g., articles with different writing styles and contents, but difficult for troubleshooting, and require large amounts of data that can be difficult to prepare and collect.
So far, the most representative example of the application of AI for an HDI database is SUPP.AI. The data collected were pre-processed, including entity recognition and entity linking using the ScispaCy library (Neumann et al., 2019), and the generation and clustering of CUIs based on the UMLS Metathesaurus. This step prepares sentences from a large number of abstracts for further classification. The goal of the subsequent classification is to determine for a sentence if an interaction exists or not. SUPP.AI in this respect uses a Bidirectional Encoder Representations from Transformers (BERT) model, RoBERTa (Liu et al., 2019), that was fine-tuned by pre-trained embedding for DDI classification. The model for identifying supplement–drug interactions (SDIs) is based on the presumption that the model trained for identifying DDI can be transferred to identify SDIs. The relatively sophisticated models in SUPP.AI (Precision=0.82, Recall=0.58, F1-score=0.68) have seemingly outperformed some classic classification methods, such as SVM for the extraction of DDI, but when tested for supplements the performance is not as promising.
It can be concluded that the main advantage of AI is its possibility to process a large amount of data so as to achieve a broader coverage of HDI information. However, a number of limitations for AI application in database development remain. First, there is a strong need to improve the accuracy of methods for performing various NLP tasks. In addition, many studies have explored the performance of NER methods on dataset for DDIs instead of HDIs. To apply such method to extract HDI information, a branch of AI known as transfer learning could serve as a potential solution. Moreover, since the development and improvement of both rule-based and probabilistic methods could be time-consuming and cumbersome, developers of HDI databases are therefore advised to plan ahead and perform extensive testing of methods before implementations.
4.6. Further Development of HDI Database.
As we mentioned in the introduction, the third step, extracting and evaluating the buried information in literature to obtain structured data, is the rate-limiting step in HDI database development. The application of AI seems to achieve promising results in recognizing the names of herbs/drugs and in text classification (e.g., extracting SDI sentences in SUPP.AI and screening HDI-related abstracts in Probot) and could significantly reduce the manual efforts for database maintenance. However, application of AI in other specific tasks, such as recognizing experimental models, conditions, and parameters, would be more challenging due to the lack of annotated training datasets for these tasks. The lack of such datasets is due to not only the huge amount of work required but also the shortage of published HDI reports so far. According to our searches on the HDI databases shown in Table 1, except for SUPP.AI (due to unavailable amount of HDI references), the number of published HDI reports is estimated to be less than 5,000. Even though all the published HDI articles are manually annotated, the resulting datasets may not be sufficient for training NER models for recognizing all kinds of information from literature. Moreover, the annotated datasets are task-specific, and different datasets are needed for different training purposes. Thus, the role of AI in obtaining structured HDI-related data are limited and manual curation is still not dispensable in the near future.
On the other hand, to avoid the difficulty of extracting structured data from HDI literatures, it is suggested that the authors publish their experiments and results in a predefined format, such as those proposed in NaPDI. The data in NaPDI are organized according to "Study" and "Experiment". One "Study" consists of one or more related "Experiments". Each "Experiment" belongs to one of the eleven experiment types with a standard operating procedure (SOPs) for entering data into NaPDI. Apart from this standardized format to reposit research data, we also suggest the authors provide CUIs for related medical terms based on the Unified Medical Language System (UMLS). A CUI contains the letter C followed by seven numbers and the key goal of it is to link different names for herbs, drugs, and experimental models with the same meaning and improve the accuracy in scientific expression. Overall, the sharing of structured data by authors would eliminate the need to develop NLP models as well as the effort of manual curation and thus accelerate the process of HDI database development.
The authors would like to thank Drs. Jingjing Yu and Isabelle Ragueneau-Majlessi from University of Washington Drug Interaction Solutions for providing relevant information about UW DIDB.
Note Added in Proof: An unrelated supplemental Figure 1 was accidentally added to the Fast Forward version of the article published October 25, 2021. The supplementary figure has been removed.
Authorship Contributions
Participated in research design: Zhang, Zuo.
Performed data analysis: Zhang, Ip, Lai.
Contributed to the writing of the manuscript: Zhang, Ip, Zuo.
Received February 10, 2021.
Accepted October 20, 2021.
This work is financially supported by Innovation Technology and Commission of the Hong Kong Special Administrative Region, China (Reference number: ITS/099/18FX).
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CMSS
the Chimei Search System
Concept Unique Identifier
CWMIIN
The Chinese–Western
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Drug–Herb Interaction Query Website Medicine Integrative Information Network
DIDB
UW Drug Interaction Database
Herb–Drug Interaction
Lexicomp Drug interactions
NMCD
Natural Medicines Comprehensive Database
Probot Chinese Medicine–Drug Interaction Database
SHMI
Stockley's Herbal Medicines Interactions
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Overview of the Herb-Drug Interaction Databases
Drug Metabolism and Disposition January 1, 2022, 50 (1) 86-94; DOI: https://doi.org/10.1124/dmd.121.000420
Clinical Pharmacology of FDA-Approved Small Interfering RNAs
Unusual Biotransformation Reactions
Fifty years of AHR research in the pages of DMD
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This entry was posted in Books, Movies and tagged abigail breslin, adaptations, emma watson, hailee steinfield, little women, logan lerman, louisa may alcott. Bookmark the permalink.
← Sci-Fi Month Intro Post!
I am excited about a "Little Women" movie.
I am oblivious to who almost any actress is… I live in a non-music/literary pop culture bubble. That being said, I like the looks of your proposed cast.
I know very little about who bands are too, but I generally have an idea of who actors and actresses are, even if I haven't really seen them in anything. Glad to know someone else is excited about the movie!
You do make a good point that Beth is probably supposed to be more frail, or at least by the end of the movie. Perhaps Dakota or Elle can color their hair to play Beth and the other could be older Amy.
Your casting Emma Watson as Meg is FLAWLESS. Meg is the quintessential Southern Belle society queen, the symbolism of feminine ideals. Meg is the Grace Kelly of Little Women and I cannot WAIT to see Emma rocking her typical English Rose look( strawberry blonde hairand huge green eyes), her Southern accent and her beautiful dresses!!
Your casting is brilliant. However, I prefer: Saoirse Ronan as Jo, Hailee Stanfeild as Meg and Elle Fanning as Amy. Nicholas Hoult can slay the dashing yet scandalous Laurie, Dan Stevens can play John and Colin Firth is the only choice for me as Professor Bhaer.
Needless to say, I CAN'T WAIT! I love Little Women. I love its funny plotlines, its clear, understandable yet moral meanings, the glamorous world in the novel and the March sisters' beautiful dresses.
I wish I had more to say here, but I haven't even read Little Women (I know, I'm a failure). I'm curious to see what becomes of the new adaptation, though. Maybe I'll get off my duff and read the book before it comes out!
So I haven't read Little Women 😦 I plan to, I just haven't.. yet. But that being said, an adaptation is always a good way to get me to read something!
Hopefully it'll get more people interested in reading it!
Do we need a new movie? The old one nailed it! I love Winona as Jo and will find it hard to see anyone else in the role :O Emma as Meg is an interesting choice, I think that would work really well but I could actually see her playing Jo as well.
I thought of Emma as Jo, but I couldn't think of someone else that I thought would nail Meg as well (within the age range I was thinking).
As much as I adore the 1994 version (and I think Wionna Ryder and Christian Bale are both perfect in it!), with it being 20 years I wouldn't mind a newer version. Some stories I love so much I enjoy seeing them reinterpreted in new ways. For instance, I own two different movie versions of Emma plus enjoy Emma Approved. If something's well done, I don't mind a new spin on something after a proper amount of time or in a completely new way.


text:
Bradysia cinerascens is een muggensoort uit de familie van de rouwmuggen (Sciaridae). De wetenschappelijke naam van de soort is voor het eerst geldig gepubliceerd in 1884 door Grzegorzek.

Rouwmuggen

redpajama_set_name: RedPajamaWikipedia


It is like my underwear is giving me permission to eat a brownie.
N: [urgently, and with such deep excitement that when uttered suddenly, might be confused with emergent need] t'pon, OM MY GOD, please come in here NOW, now... OH MY GOD!
t'pon: [running in, a tad frantic -- see aforementioned tone similarity] what, oh my god, N. what, what?!??!?
N: it's a MIRACLE, i can see... I can see YOU, i just woke up..
N: YES! no glasses, no contaaahh...cts... [somewhat pregnant, obviously awkward pause. i may have tapped my foot for effect] ummm, so... never mind, ok.
Anyway,it was a bit of an obsession... a cute obsession. Bean would run around the house, making animal noises in different languages while I struggled to just get him to say anything in English.
And then after a day sometime, it was just irritating. It maybe got so bad that I wished I had never introduced it in the first place. The kind of bad that that makes you want to bang out your ear drums with a meat tenderizer after the 18th time in the last seven minutes you have heard the rooster crow in French.
And so, I unintroduced it. (Like I unintroduced M*ckey M*use Clubhouse when I determined that it was melting my will to live.) And after much gnashing of teeth and tearing of garments, Bean moved onto other Web-based obsessions. For many happy months, the inhabitants of casa t'pon lived a francophone rooster-free existence.
Let me interject here. What I find truly amazing about kids (at least mine) is how they operate like a really funk-dirty sponge. Soaking up everything around them, but only saving up the truly nasty, dirty, germy bits to spread around your counters and table tops for fun later on... Can't get this kid to remember to poop in the poop-can, but he sure can remember to tell everyone in Target that his mommy is tired of cleaning "sh&t" out of his pants... precious. really.
And so it was that a few days ago, the francophone rooster returned. at 5:30 in the MORNING. with a megaphone. attached to a sub-woofer. placed directly inside my BRAIN!
If I were the kind of parent that thought spontaneous bouts of cuteness were charming regardless of the hour or VOLUME... perhaps, I would be a better person all around. But, alas, I find cute to be far more, well cute, with an extra 2 hours of sleep in the morning.
So here's to you... CO CO RICO! I am getting some duct tape and taking a nap!
This is a Flickr badge showing public photos from tpon. Make your own badge here.
my kids LOVE television. And, I am ok with that.


The second Saturday of each month head to Awakening Minds Art for a special opportunity – My Grown Up and Me! Perfect for all ages, for parents, grandparents, aunts, uncles, and more. The cost includes a light lunch, juice and all art supplies.
RSVP is required by the Thursday prior to the event. The cost is $40 for two guests, and $10 for each additional!


The previously mentioned Tlacolulokos collective has brought their artistry and social commentary to a wall on the upper floor of the Casa de la Ciudad. The mural, "Con el fuego en las manos" shows two young women, almost mirror images of each other or, perhaps, two sides of the same woman.
The young women/woman wear the traditional clothing of San Bartolome Quialana, a village near Tlacolula de Matamoros, home of the Tlacolulokos collective. Like communities throughout Oaxaca, much of the male population has migrated to the United States, in search of work leaving the women to carry on alone.
As the introduction to the exhibit on the Casa de la Ciudad website explains, With a critical view towards the current cultural context, Tlacolulokos group, headed by Darío Canul and Cosijoesa Cernas, seeks to question the idealized images of the Oaxacan culture, tourism product discourse, and insights from the reality currently experienced by the people of Oaxaca.
One of the trademarks of the Tlacolulokos group is the power their images acquire and the emotion they elicit by limiting the palette to black, white, and grays. For more background and a better understanding of the mural, a video (en español) of the artists discussing their work can be found here.
"Con el fuego en las manos" is scheduled to run until December 2015 at the Casa de la Ciudad (Porfirio Diaz No. 115, at the corner of Morelos in Oaxaca's Historic District). Hours are 9:00 AM to 8:00 PM, Monday through Sunday.
Seen on the same wall in Tlacolula de Matamoros where we were stopped in our tracks by the Tlacolula never dies mural in August. Both were conceived and created by the Tlacolulokos colective.
The artists are known for fusing iconic Mexican imagery with political and social commentary and can be found on Facebook.
These traditional religious standards voice today's messages, "against all governments" and "alive we want them." The latter refers to the disappeared and murdered students from the Escuela Normal Rural Raúl Isidro Burgos, teachers' college in Ayotzinapa, Guerrero, one of whom, Christian Tomás Colón Garnica, is from Tlacolula.
A splash of red to liven up the day.
After five days of being confined to Casita Colibrí — eating, inhaling, and choking on concrete and brick-dust and enduring the throbbing sounds of drills, hammers, and chisels — due to demolition of the old and construction of a new kitchen counter (still not finished), market day in Tlacolula de Matamoros was just what the doctor ordered. Blogger buddy Chris offered and off we went.
The mural is the work of Tlacolulokos, a collective that originated in Tlacolula. According to this article, these self-taught artists explore the subjects of violence, the transformation of traditions, tourism, poverty, and social decay by referencing southern Mexican folk elements. They use a variety of media and techniques, ranging from graffiti, easel painting, graphics and object, to video and sound.
And, Tlacolula worked her magic… We ate, soaked in her color, stopped to listen to a youth band from Santa María Guelac (with a girl tuba player, no less!) play "New York, New York" and "Can-can," and shopped a little (for me, a 5-liter plastic "gas" canister for our next mezcal run and red bananas). Tlacolula never dies and never gets old.


Briteframe GLDA is a phosphor-free chelate and therefore an anti-scalant.
Synonyms: C9H9NO8Na4, L-glutamic acid N,N-diacetic acid, tetra sodium salt Briteframe GLDA is a phosphor-free chelate and therefore an anti-scalant. The raw materials for Briteframe GLDA types are of natural origin (sugar). This makes it even greener than Briteframe MGDA. Briteframe GLDA is a sustainable, OECD301-readily degradable chelant. It functions at high pH. It shows synergy in combination with biocides. It is eco-toxicologically safe and thus a green complex forming anti-scalant, replacing NTA, EDTA and phosphonic acids and phosphonates. It has synergetic effects with biocides. In bleaching systems Briteframe MGDA proofs a stabilizer for SPC.


Drumcannon is on Logainm.ie: Drumcannon.
It is located at 54° 46' 30" N, 7° 40' 6" W.
Curious to see who lived in Drumcannon in the past? Maybe even seeing scans of their handwritten census returns?
Drumcannon was added to OpenStreetMap on 21 Oct 2015 by Stephen_Co_Antrim.


All our rooms are beautifully furnished and are indeed very comfortable with en-suite facilities. We have 3 rooms available of which 2 are double rooms and 1 a twin room. One of our double rooms is located on the ground floor.
We have a No Smoking policy on the premises. We can be flexible with your arrival and departure and this can be confirmed on booking.


The Palm Beach County Library System invites you to the Hispanic Heritage Month Celebration. We celebrate our community's cultural diversity, the beautiful traditions of Latin American countries, and the contributions Hispanics have made to American society. Join us for a wide variety of events for the entire family. Check the calendar for special events at your local branch. Events offered in English and Spanish.
Celebrate childhood and the love of reading with stories and enjoy lively performances by Wayna: Music of the Andes with music from Ecuador, Perú and Bolivia. Todas las edades. All ages. (60 min.) Call (561) 744-2301 to preregister.Se requiere registrarse.
Celebremos la niñez y el amor por la lectura con cuentos, y una maravillosa presentación de Wayna, Música de los Andes, con un repertorio de música tradicional de Ecuador, Perú y Bolivia. Todas las edades. (60 min.) Se requiere registrarse.


The latest of our dryer reviews is this Electrolux dryer with allergen cycle review, featuring the EFME617SIW. It may not offer anything new in terms of drying features or ability, but what it does do it does very well indeed. It's a paired model with the washing machine (EFLS617SIW) that brought a revolution in cleaning performance.
Like its sister washing machine, this dryer's interface is designed around a large and handsome illuminated dial, as if Electrolux have been referring to the Nest design handbook. The dial illuminates with the time remaining in the cycle, and also shows messages such as cleaning and maintenance reminders. To the left of the dial is the power button, and to the right are controls to customize your wash cycle.
The controls are completed by Start/Pause and Cancel buttons. These buttons are super sensitive and easy to operate accidentally, but only the pause button works mid-cycle. This Electrolux dryer has 9 cycles, slightly fewer than many of our favourite dryers.
Options include adding steam to help remove wrinkles and static, Eco mode which adds time but saves energy, a tumble option if you can't empty the dryer immediately, up to 12 hours delayed start, and lock for the controls between cycles.
The dryer learns your favourite settings, and will automatically have them ready: if you always use "air dry" with a timed dry cycle, it will select that before you start. The 8 cubic foot stainless steel drum has a bright light inside that stays on for 3 minutes, giving you enough time to find any stray socks.
Like many dryers, the EFME617SIW is fitted with a moisture sensor to prevent over-drying or under drying of your garments. The manual warns that actual drying time may be longer or shorter than displayed, and sure enough, a smaller than average load of wet clothes is finished sooner than advertised.
The towel cycle, already 91 minutes, is bumped up to 116 if you turn the heat up to sanitize. However, our test load of sheets and a couple of towels was fully dry in under an hour and a half, so the dryer turned itself off. We tried overloading the 15 minute quick cycle with eleven shirts, a cotton hoodie and some underwear, and they used the full cycle and still came out damp. But considering this cycle is meant for very small loads, it did a good job with a big pile of laundry.
Although the drying times are more unpredictable with the moisture sensor, the machine will save energy by stopping a cycle when the contents are dry (which helps it earn Energy Star certification). It won't leave you with a drumful of damp or overheated clothes.
Electrolux offers 3 years' parts and one year labour cover with this dryer.
We're pleased that this Electrolux dryer review is just as positive as for its paired washing machine as other reviews are. The sanitize and allergen options are chief among some very useful options. The moisture sensors worked well and while they made finish times unpredictable, other settings like wrinkle release and delayed start mean you can arrange to be ready to remove your load when it's dry. Our only complaint is the sensitive pause button, and since that's the only fault we can find, it's a clear winner.