Homebrew is a package manager for macOS that helps you easily install PHP and various extensions. There are multiple ways to install the latest PHP version on macOS. MacOS comes prepackaged with PHP but it is normally a little behind the latest stable release. Learn about the built-in, command line web server.To start the server, run the following command from your terminal in your project’s web root: > php -S localhost:8000 With PHP 5.4 or newer, you can start learning PHP without installing and configuring a full-fledged web server. If you are not sure which version a function or feature is in, you can check the PHP documentation on the php.net website. Upgrading is easy, as there are not many backwards compatibility breaks PHP 8.0, PHP 8.1, PHP 8.2. You should try to upgrade to the latest stable version quickly - PHP 7.4 is already End of Life. PHP 8 is a major update of the language and contains many new features and optimizations. The engine has been largely re-written, and PHP is now even quicker than older versions. PHP 8.x adds many new features over the older 7.x and 5.x versions. If you are getting started with PHP, start with the current stable release of PHP 8.2. Help make this website the best resource for new PHP programmers! Contribute on GitHubīack to Top Getting Started Use the Current Stable Version (8.2) The most recent version of PHP: The Right Way is also available in PDF, EPUB and MOBI formats. PHP: The Right Way is translated into many different languages: This is a living document and will continue to be updated with more helpful informationĪnd examples as they become available. Instead offer suggestions for multiple options, when possible explaining the differences This website will also not tell you which tools to use, but To give seasoned pros some fresh ideas on those topics they’ve been doing for years This website aims to introduce new PHPĭevelopers to some topics which they may not discover until it is too late, and aims Quick reference for PHP popular coding standards, links to authoritative tutorialsĪround the Web, and what the contributors consider to be best practices at present. Propagating bad practices and insecure code. There’s a lot of outdated information on the Web that leads new PHP users astray,
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World Light Gray Canvas Base & World Light Gray Canvas Reference World Dark Gray Canvas Base & World Dark Gray Canvas Reference The following raster basemaps will be entering mature support in July 2021 and require a migration for optimal basemap use. Which raster basemaps require migration to vector? Improved personalization options allowing you to customize your basemap appearance and styles based on your needs.Enhanced performance with compact basemaps sizes and more efficient draw times.Optimized to quickly generate and update maps and apps.To ensure you are utilizing the latest and greatest data, it is important to update your basemaps to vector as soon as possible.Įsri vector basemaps have multiple advantages: They will remain available, but they will no longer be updated. At this time, raster basemaps will be placed in Mature Support. Beginning in July 2021, Esri vector basemaps will become the primary basemaps for use in ArcGIS. In July, Esri’s raster basemaps will enter mature support – meaning they will no longer be updated.Įsri raster basemaps will be entering mature support, which means it is important to begin updating your ArcGIS maps and apps to vector basemaps. The frontend still lives at avoid disruption, please begin converting your existing maps and apps built with raster basemaps to vector basemaps before July 2021. Versioned files are here to collaborate around. The project transitioned to Github in 2012. Natural Earth is maintained by Nathaneiel V. Major version X: significatnt integration challenges, either around changed file strucutre, field layout, field values like FeatureCla used in symbolizing data, or significant new additions or significant changes to existing themes.Minor version Y: limited integration challenges.Bug fixes Z: can simply use the new data files, replacing your old files.When we introduce a new version of Natural Earth, you can tell by the version number how much effort you will need to extend to integrate the data with your map implementation. Under this scheme, version numbers and the way they change convey meaning about the underlying code and what has been modified from one version to the next. Bug fixes to shape, attributes in any theme.Minor shape or attribute changes in any theme.Adding, changing FeatureCla field attribute values.Major shape or attribute changes in any theme.Additions, deletions, and any shape or attribute changes in admin-1.Any shape or attribute change in admin-0.Removing FeatureCla field attribute values.Changing existing data column (field) names.Bug fixes not affecting the file and field names, patch version Z will be incremented.Backwards compatible additions/changes, increment the minor version Y.Backwards incompatible changes, increment the major version X.For our project, the data layout is the API. SemVer is a simple set of rules and requirements around version numbers. Natural Earth is a big project with hundreds of files that depend on each other and the total weighs in at several gigabytes. The 2.0 release in 2012 marked the project's shift from so-called marketing versions to semantic versioning. Other attributes facilitate faster map production, such as width attributes assigned to river segments for creating tapers. Most data contain embedded feature names, which are ranked by relative importance. The data attributes are equally important for mapmaking. Natural Earth, however, is more than just a collection of pretty lines. For example, where rivers and country borders are one and the same, the lines are coincident. Natural Earth was built from the ground up so you will find that all data layers align precisely with one another. The carefully generalized linework maintains consistent, recognizable geographic shapes at 1:10m, 1:50m, and 1:110m scales. Because your time is valuable, Natural Earth data comes ready-to-use. In a time when the web is awash in geospatial data, cartographers are forced to waste time sifting through confusing tangles of poorly attributed data to make clean, legible maps. Natural Earth solves a problem: finding suitable data for making small-scale maps. Natural Earth was built through a collaboration of many volunteers and is supported by NACIS (North American Cartographic Information Society), and is free for use in any type of project (see our Terms of Use page for more information). Featuring tightly integrated vector (here) and raster data ( over there), with Natural Earth you can make a variety of visually pleasing, well-crafted maps with cartography or GIS software. Natural Earth is a public domain map dataset available at 1:10m, 1:50m, and 1:110 million scales. No, really! This readme is a poor substitute for the live site. At the same time, upon seeing their hypnotized principal run around as Captain Underpants, Harold laughs and admits he's "kind of loving this", and George agrees. When Captain Underpants escapes and goes out to fight nonexistent crime, George and Harold realize that that probably won't turn out well and they need to stop him.In this case, Professor Poopypants reuses a voice that's similar to Senor Feeture. Actor Allusion: Like the previous two theatrical animated films he has starred in, Nick Kroll reuses a voice he used for one of his live action characters for Professor Poopypants.Acrofatic: Captain Underpants, even more so than his original iteration from the novels.Tra-la-la! Captain Underpants: The First Epic Movie contains examples of: Released on June 2, 2017, Captain Underpants is the final DreamWorks Animation film to be distributed by Twentieth Century Fox after the former's acquisition by NBCUniversal and before the latter's acquisition by Disney and its renaming into 20th Century Studios, all DreamWorks Animation movies from How to Train Your Dragon: The Hidden World onward were distributed by Universal. Krupp's love interest) and Nick Kroll as the insidious villain, Professor Poopypants. Rounding out the cast is Jordan Peele as Melvin Sneedly, the nerdy nemesis of George and Harold Kristen Schaal as Edith, the school lunch lady (and Mr. Krupp ( Ed Helms) into their comic book character - Captain Underpants - their elementary school life suddenly becomes anything but elementary. But when they accidentally turn their megalomaniacal principal Mr. George Beard ( Kevin Hart) and Harold Hutchins ( Thomas Middleditch) are two scheming fourth graders whose goals are to play pranks, hide in their secret treehouse and write comic books. Captain Underpants: The First Epic Movie is a DreamWorks Animation film based on the Captain Underpants book series by Dav Pilkey. This browser-based game is perfect for hanging out with friends or meeting new people. The only way is to kill each other in order to gain more resources and stay alive! This is a battle royale game that features full 3D graphics and various weapons to choose from. A plane crashed nearby but it's now out of fuel and there's no way to get back to civilization. This chapter contains a variety of fish species and evolutionary stages. You're a group of survivors stranded on an island, caught up in the middle of nowhere. Stabfish 2 is the sequel to Stabfish.io, a shark-themed io battleground game. In this game, you and your friends have been stranded on a remote island after a plane crash. We had no choice but to run via boat, and it was all thanks to some quick thinking that I got us there in time. En este juego online repleto de acción, tomas el control de un mortífero pez puñal y entablas intensos combates submarinos. Suddenly, I saw a giant shark coming out of the water and quickly planning our escape route. Stabfish.io se sumerge en las profundidades del océano, ofreciendo una emocionante y competitiva experiencia multijugador en la que los jugadores se enfrentan como temibles depredadores acuáticos. After several hours of trying to collect food and building our base, we had finally started collecting some bait to use later on. I was playing a game of survival with my friends in the sea. This is a fun and exciting game that is suitable for all ages, including children and teens. You will also be given the opportunity to collect items and earn money that can be used to buy more items or upgrade your weapons. The game is played in an arena-like setting with friends. Stabfish 2 is a fun survival game, you play as a brave character in a fantasy world where you’ll be battling against hordes of undead monsters. 30 Then the word of the Lord came to Jeremiah: 31 “Send this message to all the exiles: ‘This is what the Lord says about Shemaiah ( AZ) the Nehelamite: Because Shemaiah has prophesied to you, even though I did not send ( BA) him, and has persuaded you to trust in lies, 32 this is what the Lord says: I will surely punish Shemaiah the Nehelamite and his descendants. ( AW) Therefore build ( AX) houses and settle down plant gardens and eat what they produce.’”Ģ9 Zephaniah ( AY) the priest, however, read the letter to Jeremiah the prophet. 27 So why have you not reprimanded Jeremiah from Anathoth, who poses as a prophet among you? 28 He has sent this message ( AV) to us in Babylon: It will be a long time. You said to Zephaniah, 26 ‘The Lord has appointed you priest in place of Jehoiada to be in charge of the house of the Lord you should put any maniac ( AT) who acts like a prophet into the stocks ( AU) and neck-irons. Message to ShemaiahĢ4 Tell Shemaiah the Nehelamite, 25 “This is what the Lord Almighty, the God of Israel, says: You sent letters in your own name to all the people in Jerusalem, to the priest Zephaniah ( AS) son of Maaseiah, and to all the other priests. I know ( AQ) it and am a witness ( AR) to it,” declares the Lord. 22 Because of them, all the exiles from Judah who are in Babylon will use this curse: ‘May the Lord treat you like Zedekiah and Ahab, whom the king of Babylon burned ( AO) in the fire.’ 23 For they have done outrageous things in Israel they have committed adultery ( AP) with their neighbors’ wives, and in my name they have uttered lies-which I did not authorize. 21 This is what the Lord Almighty, the God of Israel, says about Ahab son of Kolaiah and Zedekiah son of Maaseiah, who are prophesying lies ( AN) to you in my name: “I will deliver them into the hands of Nebuchadnezzar king of Babylon, and he will put them to death before your very eyes. ( AL) And you exiles have not listened either,” declares the Lord.Ģ0 Therefore, hear the word of the Lord, all you exiles whom I have sent ( AM) away from Jerusalem to Babylon. 19 For they have not listened to my words,” ( AJ) declares the Lord, “words that I sent to them again and again ( AK) by my servants the prophets. 18 I will pursue them with the sword, famine and plague and will make them abhorrent ( AF) to all the kingdoms of the earth, a curse ( AG) and an object of horror, ( AH) of scorn ( AI) and reproach, among all the nations where I drive them. I will gather you from all the nations and places where I have banished you,” declares the Lord, “and will bring you back to the place from which I carried you into exile.” ( AC)ġ5 You may say, “The Lord has raised up prophets for us in Babylon,” 16 but this is what the Lord says about the king who sits on David’s throne and all the people who remain in this city, your fellow citizens who did not go with you into exile- 17 yes, this is what the Lord Almighty says: “I will send the sword, famine and plague ( AD) against them and I will make them like figs ( AE) that are so bad they cannot be eaten. ( AA) 14 I will be found by you,” declares the Lord, “and will bring you back ( AB) from captivity. 13 You will seek ( Z) me and find me when you seek me with all your heart. ( V) 12 Then you will call ( W) on me and come and pray ( X) to me, and I will listen ( Y) to you. 11 For I know the plans ( T) I have for you,” declares the Lord, “plans to prosper ( U) you and not to harm you, plans to give you hope and a future. I have not sent ( O) them,” declares the Lord.ġ0 This is what the Lord says: “When seventy years ( P) are completed for Babylon, I will come to you ( Q) and fulfill my good promise ( R) to bring you back ( S) to this place. ( M) 9 They are prophesying lies ( N) to you in my name. Do not listen to the dreams ( L) you encourage them to have. Pray ( I) to the Lord for it, because if it prospers, you too will prosper.” 8 Yes, this is what the Lord Almighty, the God of Israel, says: “Do not let the prophets ( J) and diviners among you deceive ( K) you. ( G) 7 Also, seek ( H) the peace and prosperity of the city to which I have carried you into exile. Increase in number there do not decrease. 6 Marry and have sons and daughters find wives for your sons and give your daughters in marriage, so that they too may have sons and daughters. 4 This is what the Lord Almighty, the God of Israel, says to all those I carried ( E) into exile from Jerusalem to Babylon: 5 “Build ( F) houses and settle down plant gardens and eat what they produce. The systems model of creativity: The collected works of Mihaly Csikszentmihalyi. Cambridge University Press.Ĭsikszentmihalyi, M. Sternberg (Ed.), Handbook of creativity (pp. Implications of a systems perspective for the study of creativity. Creativity: Flow and the psychology of discovery and invention. Flow: The psychology of optimal experience. Sternberg (Ed.), The nature of creativity: Contemporary psychological perspectives (pp. Society, culture and person: A systems view of creativity. University of Canberra, Canberra, ACT.Ĭsikszentmihalyi, M. Making Sense: Data, Publics and Storytelling, The Annual Australian and New Zealand Communication Association Conference. The constrabling nature of internet radio. Macleod (Eds.), Tourists and tourism: Identifying with people and places (pp. More than the Beatles: Popular music, tourism and urban regeneration. The systems view of life: A unifying vision. Brown Partworks Ltd.Ĭapra, F., & Luisi, P. The rules of art: Genesis and structure of the literary field. Music Radar: The No 1 Website for Musicians. Paul McCartney’s 12 greatest Beatles bass performances. The creative mind: Myths and mechanisms (2nd ed.). This chapter explores the scalability of creative systems by examining the recording and production of the Beatles’ ‘Paperback Writer’ (1966), principally written by Paul McCartney and exposes some of the creative processes operating at an individual level, the sharing of ideas and knowledge between the creative group that worked within Studio Three of EMI’s Abbey Road studio, all of which was situated within a temporally and spatially located sociocultural system.īeatles, T. We use the concepts of holons and holarchies to show that not only are the systems of audio engineering deeply connected horizontally to the system of record producing and the system of studio musicianship, but these related holons are linked vertically to the broader system of popular record production and at a different scale again to the system of western popular music. Despite these appearances though, systems still depend upon other systems, which all exist as multi-layered systems within systems. A system, such as a system of musical recordings, can sometimes appear to operate independently with apparent well-defined boundaries around it. "I arrived at Weybridge and told John I had this idea of trying to write off to a publishers to become a paperback writer, and I said, 'I think it should be written like a letter.' I took a bit of paper out and I said it should be something like 'Dear Sir or Madam, as the case may be.' and I proceeded to write it just like a letter in front of him, occasionally rhyming it."Ī history of the song from Beatles Music History quotes McCartney as saying he always loved the word "paperback.As explored in a prior chapter in Paul McCartney and His Creative Practice: The Beatles and Beyond, the way a song like ‘Yesterday’ emerged clearly shows that nothing exists in isolation. McCartney explains how he wrote the song in this quote from Paul McCartney: Many Years From Now by Barry Miller. The Beatles Bible also notes that McCartney wrote the song after reading an article in the Daily Mail about an aspiring writer. Why did The Beatles decide to pen a song about become a paperback writer? The Beatles Bible reports that one reason is McCartney wanted to write a song that was based on a single chord. It could make a million for you overnight If you really like it you can have the rights The query says the paperback could make a million dollars: I could make it longer if you like the style It's a thousand pages, give or take a few The lyrics also say the manuscript is about a thousand pages so far: It took me years to write, will you take a look? "Paperback Writer" begins:ĭear Sir or Madam, will you read my book? The repeats the words paperback writer in the chorus. Another interesting aspect of the song is how McCartney wrote it like a query letter. It is about wanting to become a novelist. "Paperback Writer" is an interesting song because it is not use a common song theme like love, war or loss. A person is less likely to say they want to become a "paperback writer" today in the era of ebooks, but people will still know what you mean by the term. Becoming a published author is still a dream of many people today. The 1966 song was written by Paul McCartney. "Paperback Writer" is a hit song from The Beatles that wannabe writers can certainly appreciate. ***Current Online Coupons (enter coupon code when checking out. *If online ordering is disabled, please call us at 35 to place your order during business hours. You can also order delivery through the third-party services of (until 10 PM), GrubHub (until 12 AM), and DoorDash (available during all business hours) (may be subject to a higher miniumum and/or minimum gratuity). *If you are outside our delivery area, you are more than welcome to call to see if we can deliver there *Pricing/fees may be different for deliveries through online ordering. *If you are ordering for someone else, please include the recipient's name/phone number as an added note (located when you add an item to your order). Online ordering is available (during business hours only)! CLICK HERE TO PLACE AN ONLINE ORDER.ĭelivery/takeout times are estimates and may vary based on how busy we are. WE ARE HIRING! CLICK HERE for information on how to apply!įollow us on Facebook for up-to-date changes in operating days. Still have trouble, call us at 35 to place your order.Ī Gainesville Originally, known for our creative flavors of cookies, all made in-store and always baked fresh right when you order for pickup and delivery. Refer to and click the dorm, then scroll down and you’ll find the address (most, but not all will work for our online ordering.). We are working to solve the problem, but we do offer delivery to ALL of UF’s dorms. Hi! WE DELIVER ALL OVER THE UNIVERSITY OF FLORIDA CAMPUS, but it’s come to our attention that our online ordering for deliveries is having some problems finding dorms at UF’s campus. Retrieved May 4, 2021.WE WILL BE CLOSED OCTOBER 23-25 (Monday-Wednesday). ^ "Insomnia Cookies celebrates National Ice Cream Day".^ "Insomnia Cookies Nutritional Facts Guide" (PDF)."There's a Cookie Speakeasy in Philadelphia - If You Know Where to Look". "Insomnia Cookies launches unlimited cookie membership". "JAB Holdings to Acquire Insomnia Cookies". ^ "Insomnia Cookies to Open Real Estate Search to All 48 States in the Continental U.S." (Press release).^ "Insomnia Cookies feeds SU for 5 years".^ "An Interview with Seth Berkowitz | How the Founder of Insomnia has Revolutionized the College Experience Armed Only with Cookies"."Insomnia Cookies Opens Its 200th Store In Exton". ^ "Insomnia Cookies Opens University of Illinois Location to Satisfy Cravings All Day and Late into the Nigh"."Midnight munchies? Insomnia Cookies has your back". "Another place to get a cookie at 3 in the morning". ^ a b c Van Allen, Peter (March 8, 2013).Other products include cookie cakes, brownies, milk, ice cream, and ice cream sandwiches. Insomnia Cookies sells 17 types of classic cookies, including vegan options, and a variety of deluxe cookies. In October 2023, the company partnered with Universal Pictures and Scott Cawthon Productions to release the 'Freddy Fazbear's Cookie Pizza' in promotion of the Five Nights at Freddy's movie. In June 2021, the company opened its 200th store in Exton, Pennsylvania. In April 2021, the company opened its first store with an experimental CookieLab section, a "cookie speakeasy" that offers customizable cookies and a bar with milk and milkshake options. A subscription costs $9.99 per month and provides members with a free classic cookie every day, free local delivery from Insomnia Cookies locations, and other perks. The company launched the "CookieMagic" membership service in March 2021. In 2018 Krispy Kreme, financed by JAB Holding Company, acquired Insomnia Cookies the company continues to operate independently. The company has expanded throughout the continental U.S., opening its 100th store in 2016. Monday-Friday, and from noon until 3:00 a.m. Insomnia Cookies bakeries are typically located near college and university campuses to target students who wish to order cookies past the closing time of traditional bakeries. Insomnia Cookies is based in New York City and Philadelphia. The first retail store opened in 2003 in Syracuse, New York. From there the concept of cookie delivery grew. Berkowitz began baking and delivering cookies from a dorm room to students on campus late at night. The company was co-founded by Jared Barnett and Seth Berkowitz in 2003 while attending the University of Pennsylvania in Philadelphia. Many stores are located in close proximity to university campuses and cater to students who want to order cookies late at night. The company has more than 240 stores, located throughout the continental U.S. Based in New York and Philadelphia, it was started in 2003 by Jared Barnett and Seth Berkowitz, both students at the University of Pennsylvania. Insomnia Cookies is a chain of bakeries in the United States that specializes in delivering warm cookies, baked goods, and ice cream. Parks, attractions, or entertainment may: close due to refurbishing, capacity, weather or special events change operating hours and otherwise change or be discontinued without notice and without liability to the owners of Universal Orlando Resort (“Universal”). Valid only during normal operating hours. ^Tickets are nonrefundable, non-transferable, and must be used by the same person on all days. Additional restrictions may apply and subject to change without notice. One offer per package, not valid with other discounts, promotions or prior purchases. Valid for bookings now – 12/12/18 with travel now – 12/31/19. §Savings based on the travel dates of the Splash, Stay and Play vacation package from Universal Parks & Resorts Vacations™. Additional hotels, rates and travel dates available. Reservation must be made 72 hours in advance. Subject to availability, room type, hotel, and travel dates selected. Rate is per adult, per night, tax inclusive and based on double adult occupancy on a 5-Night stay at the Rosen Inn International, Standard Room. Errors will be corrected where discovered, and Universal Orlando and Universal Parks & Resorts Vacations reserve the right to revoke any stated offer and to correct any errors, inaccuracies or omissions, whether such error is on this website or any print or other advertisement relating to these products and services. I am ready to book now! All prices, package inclusions & options are subject to availability and to change without notice and additional restrictions may apply. Access to select live entertainment venues˄ at Universal CityWalk™.Includes Early Park Admission◊ one hour before the theme parks open to one (1) Universal Orlando™ theme park as determined by Universal Orlando (valid theme park admission required.).3-Park Admission^ to Universal Studios Florida™, Universal’s Islands of Adventure™ and Universal’s Volcano Bay™.5-Night Accommodations at a Universal Partner Hotel. Plus, save up to $100** with select travel. The best way to experience all Universal Orlando™ has to offer with this epic 3-Park vacation package starting from only $99* per adult, per night, tax inclusive. If you'd rather not have WhatsApp saving every photo and video you receive to your camera roll, taking up space and cluttering up your own photos, disable autosave. Ask someone to send you a new WhatsApp message: This should automatically refresh the message count. Tap Notifications, then turn on Notification dot on app. Group Chats will still use read receipts, however. Ensure the notification dot is enabled on your device: Open device Settings. Now tap the green toggle next to images, to fully disable the app, tap the. Tap that button, tap Edit in the top left corner, tap the - icon next to images, and tap Remove from Favorites. Note: Turning this feature off will also prevent you from seeing when a friend has read your message. Open the Messages app on your iPhone and swipe left on the apps list at the bottom of the screen until you see a button with three dots. Go to your devices settings, find the 'Apps' or. Clear app cache: If restarting the app didnt work, you can try clearing the cache. Close WhatsApp completely and then relaunch it to see if the GIF and other app options reappear. Your device will warn you to backup your data. Restart the app: Sometimes, a simple restart can help refresh the apps interface and restore missing options. Now select the ' Factory Data Reset ' option. Sometimes it's found under Additional Settings in some other models. Solution 7: Use Dr.Fone System Repair to Fix Any Software Issue with iPhone. Here is how to factory reset your phone on Android. Solution 6: Reset All Settings on your iPhone. Solution 5: Disable the Automatic Offloading of Apps. Solution 4: Find the Missing Apps via Siri. Open Settings > Account > Privacy and uncheck the box or slide the switch next to Read Receipts to the Off position. Solution 3: Update or Install the Missing Apps on your iPhone. This will prevent fellow users from knowing you have read a message. Then, trust the computer on your device and you should wait for the program to detect the iOS device. Step 2: Tap on Settings to bring up WhatsApp settings. Going one step further, you can disable read receipts in WhatsApp. Step 1: Open WhatsApp on your phone and tap on the three-dot menu in the top-right corner. This help isolate the behavior youre experiencing further and helps improve the. In addition, youll want to make sure your iPhone is updated to the latest iOS update of 13.3. Check to see if 'Emoji' appears in the keyboard. This may help you to recover the missing chat and media. We suggest to restore your chat history from WhatsApp. We can help point you in the right direction. Then pick from Everyone, My Contacts or Nobody. If so, youll want to open the Messages app, then with your finger, hold the globe icon for a few seconds and let go. We understand youre missing data from WhatsApp, and youd like recover that information. Sometimes it's too much pressure knowing that people can see when you were last online and it makes you feel like you have to reply to pending messages.ĭon't want friends or random contacts to know your "Last Seen" time? Open Settings > Account > Control your privacy and export conversations. Any information that could lead to patient identity was eliminated, and all data included in this research were anonymized thus, the need for informed consent has been waived. This research protocol was approved by the Medical Ethics Committee of Wenzhou Medical University’s First Affiliated Hospital, Wenzhou, China, and was conducted following the Declaration of Helsinki. However, the correlation between serum AGR and IBD has not been established.Ĭonsidering the vital role of inflammation in IBD and the strong association between inflammatory responses and AGR, we speculated that serum AGR is closely related to the development and severity of IBD, and serum AGR might hold potential for distinguishing IBD from other GI symptoms and evaluating disease activity. 14, 24 The decreased albumin and increased globulin will substantially reduce AGR (calculated as albumin/globulin), suggesting its potential predictive value in inflammatory disease (such as IBD). 25 Current research has pointed out that globulin was positively associated with the severity of chronic inflammation 26 and increased in the progressive IBD. 24 Globulin, another abundant serum protein, plays an essential part in immunity and inflammation. 21, 22 As the main protein in human serum, albumin reflects nutritional status and acute-phase response to inflammation, 23 and its levels decrease after the inflammatory stimulus. AGR was negatively associated with chronic inflammation. 19, 20 In the last few years, several studies have demonstrated that serum AGR is a reliable indicator of poor prognosis in inflammatory disease and malignancy. 17, 18Īs mentioned previously, one of the critical characteristics of IBD is the deficit in the resolution of intestinal inflammation with extraintestinal involvement. However, its prediction value in UC and postoperative recurrence of CD was limited. 9 Besides, CRP, as a non-specific reactant, was reported to discriminate IBD from IBS accurately. 15 Whereas, the elevated levels of FC were not observed in CD patients even with large ulcers 16 and were not a good predictor for IBD activity. 12–14 FC and CRP have been widely studied and play a possible role in discriminating IBD from irritable bowel syndrome (IBS), evaluating disease activity, monitoring medication response, and so on. Currently, various biomarkers have been reported, including fecal calprotectin (FC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, and so on. 11 Thus, developing a non-invasive method that is more convenient, tolerable, reliable, economical, and faster for accurately diagnosing IBD and monitoring IBD activity is of great importance. 10 However, endoscopy tends to be least tolerable due to its considerable cost, inconvenience, and invasive risk, especially when routinely re-evaluated. 9 The cross-sectional imaging offers complementary information of small bowel, which the endoscope can hardly reach. 8 Endoscopy with pathological examination is the gold standard for diagnosing IBD and evaluating disease activity. 6 In contrast, delays in referral and diagnosis seem prevalent in IBD. 4–7 Moreover, IBD has a notable impact on patients’ physical and psychological health, making it critical to diagnose and treat as quickly as possible. 2, 3 IBD has become a global public health problem that generates significantly higher morbidity and an enormous burden for health care systems. It is thought to be due to the interaction of commensal bacteria (or their products), susceptibility genes, environmental factors (such as diet), and immune deficiencies. 1 The pathogenesis of IBD is undefined, complex, and not yet fully understood. Inflammatory bowel disease (IBD), which consists of ulcerative colitis (UC) and Crohn’s disease (CD), is a chronically relapsing inflammatory intestinal disorder with an incidence continuously ascending in recent years, especially in developing countries. |
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