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FDA grants Enhertu accelerated approval for HER2-mutated non-small cell lung cancer


August 12, 2022

2 min read


Disclosures: Li reports uncompensated advisory services provided to Daiichi Sankyo and AstraZeneca.

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The FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki for treatment of adults with HER2-mutated unresectable or metastatic non-small cell lung cancer.

The approval applies to patients with activating HER2 (ERBB2) mutations detected by an FDA-approved test who received a prior systemic therapy.

Abstract lung image
Source: Adobe Stock.

Fam-trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo) is a novel antibody-drug conjugate with three components: a humanized anti-HER2 immunoglobulin G1 monoclonal antibody with the same amino acid sequence as trastuzumab (Herceptin, Genentech); a topoisomerase 1 inhibitor payload; and a tetrapeptide-based cleavable linker. It is the first drug to receive FDA approval for HER2-mutant NSCLC, according to an FDA press release.

The FDA based on the accelerated approval on results of the randomized, multicenter phase 2 DESTINY-Lung02 trial, which enrolled 152 patients with HER2-mutant metastatic NSCLC who experienced disease recurrence or progression during or following at least one prior anticancer therapy regimen that contained a platinum -based chemotherapy.

The trial’s primary efficacy population included 52 patients (median age, 58 years; 69% women; 79% Asian) who received fam-trastuzumab deruxtecan at a dose of 5.4 mg/kg via IV every 3 weeks until disease progression or unacceptable toxicity.

Major efficacy outcomes included confirmed objective response rate per blinded independent central review and duration of response.

Results of an interim efficacy analysis showed a confirmed ORR of 57.7% (95% CI, 43.2-71.3) and median duration of response of 8.7 months (95% CI, 7.1 to not estimable).

The most common adverse events included nausea, decreased white blood cell count, increased aspartate aminotransferase, increased alanine aminotransferase, fatigue, increased constipation, decreased appetite, vomiting, alkaline phosphatase and alopecia.

The prescribing information includes a boxed warning about risk for interstitial lung disease and embryo-fetal toxicity.

Bob Li, MD

Bob T. Li

“The approval of trastuzumab deruxtecan in non-small cell lung cancer is an important milestone for patients and the oncology community,” Bob T. Li, MD, PhD, MPH, medical oncologist and physician-scientist at Memorial Sloan Kettering Cancer Center, said in a company press release. After 2 decades of research into the role of targeting HER2 in lung cancer, the approval of the first HER2-directed treatment option validates HER2 as an actionable target in lung cancer and marks an important step forward for treating this patient population with unmet medical needs .”

Results of DESTINY-Lung02 will be presented at a future medical meeting, according to the company press release.

FDA also approved two companion diagnostics for fam-trastuzumab deruxtecan — Oncomine Dx Target Test (Life Technologies Corp.) for tissue and Guardant360 CDx (Guardant Health Inc.) for plasma. If a mutation is not detected in a plasma specimen, the tumor tissue should be tested, according to the FDA press release.

Fam-trastuzumab deruxtecan already had been approved in the United States for treatment of adults with metastatic HER2-positive breast cancer who received prior anti-HER2-based therapies, as well as adults with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received a prior trastuzumab-based regimen. Last week, the FDA approved the agent for treatment of patients with unresectable or metastatic HER2-low breast cancer who received prior chemotherapy in the metastatic setting or whose disease progressed during or within 6 months of adjuvant chemotherapy.


Enhertu approved in the US as the first HER2 directed therapy for patients with previously treated HER2 mutant metastatic non-small cell lung cancer (press release). Available at: www.businesswire.com/news/home/20220811005803/en/ENHERTU%C2%AE-Approved-in-the-US-as-the-First-HER2-Directed-Therapy-for-Patients-with-Previously -Treated-HER2-Mutant-Metastatic-Non-Small-Cell-Lung-Cancer. Published Aug. 11, 2022. Accessed Aug. 11, 2022.
FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer (press release). Available at: www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-her2-mutant-non-small-cell-lung?utm_medium=email&utm_source =govdelivery. Published Aug. 11, 2022. Accessed Aug. 11, 2022.

Major Giants AXA, Allianz, AIG, Generali, PICC – InsuranceNewsNet


New JerseyNJ — (SBWIRE) — 08/12/2022 — Worldwide Multi-car Insurance Market In-depth Research Report 2022, Forecast to 2027 is latest research study released by HTF MI evaluating the market risk side analysis, highlighting opportunities and leveraged with strategic and tactical decision-making support (2022-2027) . The study is a perfect mix of qualitative and quantitative Market data collected and validated majorly through primary data and secondary sources. The report provides information on market trends and development, growth drivers, technologies, and the changing investment structure of the Worldwide Multi-car Insurance Market. Some of the key players profiled in the study are AXA, Allstate Insurance, Berkshire Hathaway, AllianzAIG, Generali, State Farm InsuranceMunich Reinsurance, Metlife, Nippon Life InsurancePing An, PICC, China Life Insurance.

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Worldwide Multi-car Insurance Market Overview:

The study provides a comprehensive outlook vital to keep market knowledge up to date segmented by Insurance Intermediaries, Insurance CompanyBank, Insurance Broker & Others, , Multi-car Insurance markets by type, Theft Insurance, Fire Insurance & Others and 18+ countries across the globe along with insights on emerging & major players. If you want to analyze different companies involved in the Worldwide Multi-car Insurance industry according to your targeted objective or geography we offer customization according to requirements.

Worldwide Multi-car Insurance Market: Demand Analysis & Opportunity Outlook 2027

Worldwide Multi-car Insurance research study defines market size of various segments & countries by historical years and forecast the values ​​for next 6 years. The report is assembled to comprise qualitative and quantitative elements of Worldwide Multi-car Insurance industry including: market share, market size (value and volume 2017-2021, and forecast to 2027) that admires each country concerned in the competitive marketplace. Further, the study also caters and provides in-depth statistics about the crucial elements of Worldwide Multi-car Insurance which includes drivers & restraining factors that help estimate future growth outlook of the market.

The segments and sub-section of Worldwide Multi-car Insurance market is shown below:

The Study is segmented by following Product/Service Type: Multi-car Insurance markets by type, Theft Insurance, Fire Insurance & Others

Major applications/end-users industry are as follows: Insurance Intermediaries, Insurance CompanyBank, Insurance Broker & Others

Some of the key players involved in the Market are: AXA, Allstate Insurance, Berkshire Hathaway, AllianzAIG, Generali, State Farm InsuranceMunich Reinsurance, Metlife, Nippon Life InsurancePing An, PICC, China Life Insurance

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Important years considered in the Worldwide Multi-car Insurance study:
Historical year – 2017-2021; Base year – 2021; Forecast period** – 2022 to 2027 [** unless otherwise stated]

If opting for the Global version of Worldwide Multi-car Insurance Market; then below country analysis would be included:
North America (USA, Canada and Mexico)
Europe (Germany, Francethe United Kingdom, Netherlands, ItalyNordic Nations, Spain, Switzerland and Rest of Europe)
Asia-Pacific (China, Japan, Australia, New Zealand, South Korea, India, Southeast Asia and Rest of APAC)
South America (Brazil, Argentina, Chile, ColombiaRest of countries etc.)
Middle East and Africa (Saudi Arabia, United Arab Emirates, Israel, Egypt, Turkey, Nigeria, South AfricaRest of MEA)

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Key Questions Answered with this Study
1) What makes Worldwide Multi-car Insurance Market feasible for long term investment?
2) Know value chain areas where players can create value?
3) Teritorry that may see steep rise in CAGR & YOY growth?
4) What geographic region would have better demand for product/services?
5) What opportunity emerging territory would offer to established and new entrants in Worldwide Multi-car Insurance market?
6) Risk side analysis connected with service providers?
7) How influencing factors driving the demand of Worldwide Multi-car Insurance in next few years?
8) What is the impact analysis of various factors in the Worldwide Multi-car Insurance market growth?
9) What strategies of big players help them acquire share in mature market?
10) How Technology and Customer-Centric Innovation is bringing big change in Worldwide Multi-car Insurance Market?

Browse Executive Summary and Complete Table of Content @ https://www.htfmarketreport.com/reports/3701153-worldwide-multi-car-insurance-market-1

There are 15 Chapters to display the Worldwide Multi-car Insurance Market
Chapter 1, Overview to describe Definition, Specifications and Classification of Worldwide Multi-car Insurance market, Applications [Insurance Intermediaries, Insurance Company, Bank, Insurance Broker & Others]Market Segment by Types , Multi-car Insurance markets by type, Theft Insurance, Fire Insurance & Others;
Chapter 2, objective of the study.
Chapter 3, Research methodology, measures, assumptions and analytical tools
Chapter 4 and 5, Worldwide Multi-car Insurance Market Trend Analysis, Drivers, Challenges by consumer behaviour, Marketing Channels, Value Chain Analysis
Chapter 6 and 7, to show the Worldwide Multi-car Insurance Market Analysis, segmentation analysis, characteristics;
Chapter 8 and 9, to show Five forces (bargaining Power of buyers/suppliers), Threats to new entrants and market condition;
Chapter 10 and 11, to show analysis by regional segmentation [The United States, Canada, Germany, France, UK, Italy, Russia, China, Japan, Korea, Southeast Asia, India, Australia, Brazil, Mexico, Argentina, Chile, Colombia, Egypt, Saudi Arabia, United Arab Emirates, Nigeria & South Africa], comparison, leading countries and opportunities; Customer Behaviour
Chapter 12, to identify major decision framework accumulated through Industry experts and strategic decision makers;
Chapter 13 and 14, about competition landscape (classification and Market Ranking)
Chapter 15, deals with Worldwide Multi-car Insurance Market sales channel, research findings and conclusions, appendix and data source.

Thanks for showing interest in Worldwide Multi-car Insurance Industry Research Publication; you can also get individual chapter wise section or region wise report version like North AmericaLATAM, United StatesGCC, Southeast Asia, EuropeAPAC, United Kingdom, India or China etc

About Author:
HTF Market Intelligence consulting is uniquely positioned empower and inspire with research and consulting services to empower businesses with growth strategies, by offering services with extraordinary depth and breadth of thought leadership, research, tools, events and experience that assist in decision making.

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Your Work Deserves a .photography Domain


If you’re trying to establish your name as a professional photographer, building the right website and choosing a proper domain name for your business is essential to your success.

Full disclosure: This article was sponsored by Identity Digital.

Building your brand as a photographer can be an overwhelming task. The identity you land on will set the tone for your clients and their expectations of you and your work. Effectively the brand will build the set of expectations, stories, memories, and relationships that account for a customer’s decision to choose you over someone else. This is why your work deserves a .photography domain.

The idea of ​​making your photography business a brand might seem offputting since most people associate “brand” with large corporations like Amazon, Apple, or Microsoft. This is an incorrect line of thinking since it is incredibly important for creatives to have a name that stands out to potential photography clients, and a custom .photography domain can help them do just that since it tells your visitors exactly what you do.


Reasons To Use a .Photography Domain

Brings clarity to your website and makes it more relevant to potential customers

Whether you are a beginner or a seasoned professional, once you decide to set yourself apart from the pack, the right domain name can help bring clients to your business.

Wedding Photographer Dani Brown says “When my photography business became a full-time career I knew I needed a better domain name. I’d heard of descriptive domains at a seminar and purchased daniellebrown.photography on GoDaddy. My .photography domain helps me build my business brand and improves my SEO.”

Portrait and Fine Art photographer Ken Sandberg says “The .photography domain matched my company name and gave me a shorter URL, so it was an easy choice for me. Not to mention, my email address [email protected] looks much more professional than [email protected]

Tells the world what you do and reaffirms your commitment to the craft

The .photography domain eliminates any ambiguity as to what you do and what services you offer. It provides instant recognition of your brand, services, and skillsets offered. Sending someone a link to www.stevesweatpants.com may leave people with questions as to who they are and what they do, but sending them to www.stevesweatpants.photography sends a pretty clear message.


Norway-based photographer Paul Edmundson says “Recently I rebranded my website using Squarespace and their amazing domain search tool suggested fjord.photography. We love it because it’s a visual mark that immediately says what we do and where we do it. We believe people searching for our services are more likely to click, and we prominently place it in our online ads.”


South Africa-based photographer Natalie Field says “When I discovered I could have nataliefield.photography I just knew I had it for our rebranded website. People always comment on how apt it is to have a domain that specifies my services. My social media channels use the same format, so I have a consistent brand for my entire online presence. I think it has assisted with SEO. At the very least, when people see the domain name there is no ambiguity on what they will find when they click on the link.”

A .photography domain is easy to remember and harder to forget

Even though the .photography domains have been around for several years, custom “targetted” websites are still rather new to many people. Sending someone to this domain will make a lasting impression of who you are and what your business is.

Netherlands-based portrait photographer Hugo Onink says “I started my photography business as a student and wanted to make sure my website and domain name appeared professional. Lifeshots.photography was part of that strategy. I quickly learned that using a .photography was new to most people, so it became a conversation starter which made my domain name easy to remember. And it matches my instagram handle so that helps my online brand.”


South Carolina-based wedding photographer Sol Basconcillo says “Honestly, I found sol.photography randomly and it’s one of the best things that has happened for my business. It’s clear and concise. I often have quick conversations with people and share my URL. When I say sol.photography people usually say “Wow, that’s it?! It’s so easy to remember.” I’m really glad I chose it.”

Take The Next Step

By building your website on a .photography domain you will join the ranks of many other working professionals who have made their brand and business clear including some of the world’s best photographers like Sean Tucker (UK), Masters of Photography (including Steve McCurry and Albert Watson), and Steven John Irby (SteveSweatPants). Not only will the .photography domain state your purpose of being for potential clients, but it is also an SEO-Optimized domain that can be found fast by anyone seeking a professional photographer.

Using a .photography domain will allow you to leverage both sides of the “dot” for search engines, giving you a leg up on the competition. Learn more at buildyour.photography

Full disclosure: This article was sponsored by Identity Digital. .Photography is part of the Identity Digital portfolio of domain extensions.

Image credits: Header illustration photo from 123RF

Shopify Review | HTMLGoodies.com


Is Shopify the ideal e-commerce platform for you and your online store? We will help you figure that out in this review that will break down Shopify’s pros and cons, features, and pricing.

Looking to learn how to build your own website and online store? Check out our list of the Top WordPress Online Courses to get started.

What Is Shopify?

When it comes to e-commerce platforms, you will be hard-pressed to find one more popular or chock full of features than Shopify. Thanks to its loads of apps and integrated features, you can use Shopify to build your own online store without any extensive tech skills, scale it, and build your brand while you boost your bottom line. And, while you can snag plenty of sales directly through your Shopify store, the platform also gives you the power to sell via social media and other online marketplaces.

Shopify’s Pros And Cons

Where does Shopify excel as an e-commerce platform, and where could it improve? Let us look at that now with these lists of pros and cons.

Shopify Pro

Here is a list of what we consider to be Shopify’s pros for people building online stores and web developers:

  • A massive app library – You do not need to hire an expensive programmer to give your online store all of the bells and whistles you desire, as Shopify integrates with over 3,000 third-party apps and extensions to extend the functionality of your site.
  • Sell ​​across various platforms – There is no need to limit your sales to just your store, as Shopify allows for multi-platform selling that lets you expand your reach via other sales channels like Amazon, eBay, Facebook, and Instagram.
  • A plethora of payment options – If your payment options are limited, you could miss out on sales. That will not be an issue with Shopify since it has its own gateway (Shopify Payments) and supports over 100 other payment options.
  • Tons of templates – You can hit the ground running thanks to Shopify’s impressive catalog of free and premium templates that eliminate the need to waste a ton of time on designing your site.
  • Supports large stores – With Shopify’s robust inventory system and backend editor, you can scale and manage your online store without worry.
  • Superb support – Even the slightest site hiccup could result in a significant loss of revenue. You can enjoy the peace of mind that comes with Shopify’s 24/7 support should any problems arise.

Read: SEMRush SEO Tool Review

Shopify Cons

Here is a list of what we consider to be Shopify’s cons as an e-commerce and website building platform:

  • Hefty transaction fees – Some of your profits could get swallowed up by transaction fees if you elect to use something besides Shopify Payments to run your store. Add in other payment gateway expenses, and you could experience sticker shock.
  • User-friendliness – The phrase “practice makes perfect” applies to Shopify’s editor, as it can take some time to get used to, especially if you do not have experience with similar software.
  • Cost On the surface, Shopify seems cheap. Once you factor in transaction fees and the cost to use some apps, however, Shopify can chew up a nice chunk of your store’s monthly budget.
  • A need for apps – Shopify’s extensive integration with apps is one of the platform’s pros, but it is also a weakness. Why? Because you may find yourself relying on many apps to get the job done, and some of them come with separate costs.

Shopify Features

Although the entire list of Shopify’s features is too long to list here, we will do our best to showcase the main highlights and features.


It does not matter how many features Shopify has if they are too complicated to use. Luckily, that is not an issue since Shopify is, for the most part, user-friendly, provided you invest some time to get used to it.

The Shopify interface is simple and relatively straightforward. As such, even beginners should not have too much trouble finding their way around the platform. Setting up the basics of your online store should not be too difficult, although it probably will not be up and running in under 10 minutes. As long as you can get past the possible initial intimidation that comes with building your own online store, you will find Shopify user-friendly and not as hard as it looks.

On the other hand, do not be surprised if you are a bit frustrated when using Shopify at first.

A common complaint is that the interface can be clunky when switching between the front and back end to change the design, edit product displays, and so forth.


Shopify Themes

Shopify’s themes – or templates – look great and are varied enough that you can find the right fit for your brand with ease. More importantly, they are highly functional and responsive, whether your customers or browsing your store on a desktop or shopping on the go via a mobile device or tablet.

And, if you want to tweak a Shopify theme to fit your precise needs, you can do so since they are customizable.

While each theme has its own set of features to draw your eyes to it, you can count on such standard features as free updates, stock photos at no cost, varying color palettes and styles, mobile-friendliness, drop-down navigation, customizable content sections, and built-in SEO tools.

Product Management

Shopify Product Manager

Shopify makes it simple to manage your products via:

  • An inventory management feature that lets you update product listings, monitor orders, and track stock levels.
  • Quickly customizable product variations that differ in terms of color, size, material, weight, price, etc.


You can choose from over 100 payment gateways with Shopify to ensure your customers can purchase products without difficulty. To enjoy the lowest transaction fees and sell in multiple currencies, you will need to pick Shopify Payments.

Multi-Channel Selling

Shopify lets your store reach its full profit potential by allowing you to sell across various online channels like Amazon, eBay, Facebook, and Instagram.

Digital Sales

You do not need a physical product to sell to make cash with Shopify, as you can sell digital products and services through the platform once you install an app like Shopify Digital Downloads.


Shopify Apps Feature

Speaking of apps, if there is a feature you want to add to your store, you can probably do so via an app. Shopify offers well over 1,000 free and paid apps in its store to extend your site’s functionality.

Abandoned Cart Recovery

One of Shopify’s top integrated features is its abandoned car recovery, which can urge customers to make a purchase once they leave your site by sending them emails, offering discount codes, etc. This feature alone can help you recover up to 15 percent of your customers.


A critical part of e-commerce is shipping, and Shopify makes it as simple as can be via partnerships with UPS, USPS, DHL, and more. Whether you want to change your shipping rates or print labels, you can do it all via Shopify’s shipping features.


Is your site performing up to its potential? Shopify’s reporting tools can give you that answer, so you get insights into your sales, customer retention rate, and more.

Email Marketing

If you are not emailing your customers, you are potentially leaving a ton of cash on the table. Shopify integrates with third-party email apps like Klayivo and Constant Contact so you can execute this essential part of e-commerce.

We have a great tutorial that highlights some of the best Email Marketing Tips.

SEO and Digital Marketing

Your store will not succeed if it is hidden in the search engine results or poorly optimized. Shopify addresses this issue with a wide range of SEO tools to ensure your site gets seen and positioned in the SERPs so you can make sales.

Want to learn more about search engine optimization? Check out our SEO section for a whole slew of digital marketing tutorials and tips.

Point Of Sale

Do you sell in person more than online? Use the Shopify POS app to accept credit card payments in-store, sell gift cards, and more.


If your store follows the dropshipping model, Shopify will suffice as long as you install one of its dropshipping apps like Oberlo or AliExpress.


You do not have to be an accountant to run your online business, as Shopify can help with its integrated tax calculation tool.

What Does Shopify Cost?

Shopify offers five pricing plans made to fit varying needs:

  • Basic Gives you all the essentials to build your store, process payments, and ship products for $29 per month.
  • Shopify – Offers Basic’s features with added staff accounts and professional reporting to grow your online business for $79 per month.
  • Advanced – Supplies you with “the best of Shopify” while giving you the lowest transaction fees and custom reporting.
  • Starter – An alternative solution that lets you sell products online via messaging apps and social media for $5 per month.
  • Shopify Plus Another alternative solution designed for high-volume businesses seeking enterprise power. It is by far the most expensive Shopify plan, priced at $2,000 per month.

Once again, remember that the actual price of using those plans can fluctuate greatly depending on your transaction fees and the number of apps you decide to use.

Looking for an e-commerce solution or online website builder other than Shopify? Check out our list of Shopify Alternatives for more online store options.

Disclaimer: We may be compensated by vendors who appear on this page through methods such as affiliate links or sponsored partnerships. This may influence how and where their products appear on our site, but vendors cannot pay to influence the content of our reviews. For more info, visit our Terms of Use page.

Why Cyber ​​Security Is Essential For Digital Marketers & PR Specialists? – Latest Hacking News


Why should a marketer and PR specialist always keep the importance of cybersecurity in mind? The matter is that marketing and cybersecurity are directly interconnected. In the case of digital marketing, the potential threat from it is practically as essential as the possible benefit. Despite all the benefits, digital marketing strategies can become the source of some risks like loss of reputation, leakage of personal data of customers, and unfair competition. That’s why marketers and PR managers should take care of cybersecurity issues as well, manage the risks and follow the best data protection practices.

Protecting Customer Data Is Your Responsibility

If you don’t protect your customers’ data, your company’s data, your information resources, your reputation and your career are at risk. Both small and large companies are at cyber security risk and the number of cyberattacks is constantly increasing.

The Internet has penetrated so deeply that it would be foolish to deny the power and scope of this tool in the process of conquering markets and customers. After all, it is not at all necessary to be a professional hacker to hack into the Google account of a digital marketer or PR specialist and gain access to the information of more than one company. In just one account, there can be gigabytes of information that will bring a lot of trouble for both the specialist, the company and the clients.

Data Leak Risks When Delegating Marketing Tasks

Delegation is another potential data breach threat. And here, we are talking about both the threat of cooperation with unscrupulous contractors and the risks from outside. There is a need to recognize the issue of cyber security in advertising and other directions. Therefore, when choosing partners, you should pay attention to the approach to security. Marketers should work with a website promotion service for SEO that have a good reputation and level of trust. First, it minimizes security risks. Secondly, it will allow you to get backlinks from quality platforms that will bring more value than 10 links from sites with poor quality. The links from trusted resources are what will help every marketer.

Special Vulnerability to Hacker Attacks

In the hands of marketers and PR specialists are the keys to many doors. Oftentimes, marketers and PR professionals are the least protected. Since, in fact, it is an open gate between the company and the virtual world.

The marketer and PR specialist work in cyberspace constantly. This is the working environment of such specialists. Therefore, it is important to understand that what you do constantly within the framework of your profession constantly immerses you in the risk zone of cyber attacks. For example, such a trick as setting a weak password for your Hubspot account or following a link from a phishing email can bring a lot of trouble.

You Are a Potential Phishing Target

The most insecure channel is, of course, email. Phishing emails are still common. Of course, any worker can open an infected email but even here, marketers and PR specialists are clearly more likely to fall into the trap. They are more active than others in communicating with the outside world, getting in touch with consumers, all kinds of contractors, and so on. A marketer or PR specialist is a link between the company and the digital world. Therefore, the issue of cybersecurity is extremely acute for such professionals.

Email hacking provides attackers with access to the contact database. This is enough to lose customers and permanently tarnish the company’s reputation. To avoid such situations, always be aware of the potential risks and check the accuracy of the information in the email.

Must Do List For Improving Cyber ​​Security

So, what is important for a marketing specialist to do for better cybersecurity protection? Below you will find a list that will help you solve your security issue at a basic level. If your company does not have a security specialist, then make sure to follow the tips below to protect your reputation, the reputation of your company and sensitive business data:

  • Always lock your laptop or smartphone. Danger can be not only inside your devices but also outside.
  • Do not link all accounts to one mailbox. Create multiple accounts so that in case of hacking, attackers could not access the data. It is especially recommended not to mix business matters with personal ones. Therefore, be sure to create work and mail for personal use.
  • Use strong passwords and change them regularly (for email, Google account, social media accounts, CRM system, etc.). Updating passwords is extremely important. Also, do not use the same combination for different accounts.
  • Use random password generators instead of creating the passwords on your own. Never use the personal names, names of celebrities, countries or cities, as well as birthdates and other commonly known combinations of numbers.
  • Enable two-factor authentication wherever possible. For example, you can use Google Authenticator and other free online services to secure your profiles.
  • Use a password manager. There are various software that will allow you to manage your passwords and receive notifications promptly if there are any threats.
  • Store work information on network drives to ensure its availability in case of loss of access.
  • Give preference to devices with hardware encryption or use online file exchangers.
  • Consult with cybersecurity experts. Types of threats are constantly changing, which means that some actions may no longer be effective in the context of cybersecurity. There is a need to know about the last innovations in this area.
  • Always be aware of potential risks and your vulnerability.
  • Do not click on suspicious links in social networks, messengers and emails.
  • Use specialized software that will provide you with safe web surfing and will also check your files and emails for hacker threats. For example, you can use a tool like Office 365 Advanced Threat Protection.


The issue of cyber security is especially essential for marketing and PR specialists since they mostly work in a digital environment. Hackers and cyber attackers, in turn, are constantly coming up with new and new tricks, so make sure to follow the tips we have shared above to decrease the risk of sensitive data leakage.

Delicious Green Bay pools digital marketing resources of restaurants


Michael Newby of De Pere has been in the advertising industry since 2000. During those years, he worked with national and local businesses to help them promote their brands. He found that national companies were well-versed in digital media and promotion while smaller businesses often struggled.

“About five years ago, I started thinking, ‘What would I do if I didn’t work for a company?’ My parents owned an ice cream shop and I had helped with that when I was young and loved small businesses,” Newby said. “With the contacts I had from my advertising career, I though I could start a full-scale digital marketing firm. ”

That vision, and a romantic interest, led him to the Green Bay area where he began to finalize his business plan.

Seattle’s Best Vegan and Plant-Based Restaurants


A decade ago, when national chain Veggie Grill arrived in Seattle, the company was one of many to intentionally use the term “plant-based” to avoid the door connotations some people had with the word “vegan.” But each year, this practice inches more firmly into Seattle’s mainstream. Diners prioritize plants on the plate for a multitude of reasons: lactose intolerance, general health, or environmental concerns about meat’s carbon footprint. Then there are places like Frankie and Jo’s, where flexitarians, vegans, and omnivores line up for a cone just because the ice cream is so dang good.

Most great Seattle restaurants can feed vegans well, though sometimes advance notice helps. But here are our favorite restaurants (and bars, and bakeries) dedicated to plant-based fare.

Plant One on Me:

Plant-Based Restaurants / Vegan Bars / Vegan Burgers / Vegan Sweets

Thoroughly Plant-Based Restaurants

Araya’s Place

Bellevue, Madison Valley, University District

A quarter century ago, Aratana Nualkhair led the way on vegan Thai food in the Northwest. Now Araya’s Place has three Seattle locations and a broad menu filled with finds like avocado curry, tofu satay, and drunken noodles. And yet so many regulars (plant-based eaters and omnivores alike) confess, they can’t get past their regular order of phad thai.

Ba Bar Green

South Lake Union

A window inside the venerable Vietnamese chainlet’s South Lake Union location offers a freestanding menu, mostly plant-based renditions of flavors from across Southeast Asia. Coconut and curry, dan dan noodles, and Lao-style crispy rice salad pack big flavors, as does a choyrizo banh mi that defies geography in the tastiest manner possible.

ChuMinh Tofu and Vegan Deli

Chinatown–International District

Owner Thanh-Nga Nguyen, or Tanya, is a neighborhood treasure, and so is her food: tangy noodle soups, eggless egg rolls, and banh mi with faux crispy pork skin that passes muster with carnivores. Best of all might be ChuMinh’s buffet, a bounty of curry, tofu, braised jackfruit, eggplant, and assorted “meat” that’s the stuff of meatless dreams. You can pay by weight or plunk down a fixed fee for all-you-can-eat.

Cycle Dogs


Nashville-style chicken, a Dick’s Deluxe, even In-N-Out Burger’s animal fries, sans actual animals. This food truck turned counter offers impressive vegan facsimiles of America’s fast food favorites—right down to the kids meal that comes with a tiny STEM toy.

Harvest Beat


Five-course dinners brim with intelligent vegan creations (saffron lobster mushroom bisque, curried cashew paneer) and equally smart wine pairings. You can even order them to-go, or hit up the pandemic-era market stocked with roasted beet garlic hummus, cookies, and creamy salad dressing—a more relaxed insight into the kitchen’s plant-based talents.

Veggie Grill

Downtown, University Village

The fast-casual chain leans into comfort food with buffalo wings, nachos, and fast food-style sandwiches made with Beyond Burger patties, chick’n, even a Good Catch vegan tuna melt and crispy fish sandwich.

Plum Bistro

Capitol Hill

Chef Makini Howell—Seattle’s version of vegan royalty—puts out cultured, plant-based plates at her flagship restaurant. Howell has added multiple dishes to Seattle’s meatless canon (her mac and yease, a properly decadent tofu reuben, some incredible salads) but she also knows when to keep things straightforward, like pan-roasted cauliflower or truffle-topped gnocchi.

Wayward Vegan Cafe


Plant-based eaters need all-day dinner breakfast, too. This bi-level hangout is ready with huge portions of (faux) chicken and waffles, loaded omelets, breakfast burritos, and every possible permutation of biscuits and gravy. Don’t miss the crunch wrap.

Pi Vegan Pizzeria

University District

Seattle’s stalwart vegan pizza tavern has worn booths that look like their own tiny rooms, and a ton of old-school flourishes like cheezy breadsticks, cookie pizza, a calzone option, and the ability to stuff your pizza crust with Teese, one of the better plant-based mozzarellas out there. These are no minimalist pies; toppings proliferate on soft chewy crusts, with a few options by the slice.

Kati Vegan Thai

Kirkland, South Lake Union

Thai’s a natural fit for plant-based dining, but this restaurant duo finds nce and deep flavor in fried oyster mushrooms, garlicky jackfruit, pumpkin curry, pad see ew, and a host of classic dishes. The desserts: unexpectedly great. A new location at the Village at Totem Lake recently joined the handsome original in Amazonia.

Broadfork Cafe

Lower Queen Anne, University District

This sustainably-minded cafe makes veggie-forward breakfast and lunch creations that transcend dietary preferences, like an artichoke melt sandwich on sourdough, piled with sprouts and cucumber. Broadfork goes light on the faux meat—save a little bit of Field Roast—and heavy on veggie bowls, smoothies and juice, and the house cashew cheese sauce.

Vegan Bars

Georgetown Liquor Company


The former owner of Capitol Hill’s beloved meatless dive the Highline resurrected this vegan punk bar in 2020. Some Highline favorites surfaced here, like the french dip and reuben made with house seitan. This is assuredly a bar, serving burgers and nachos in those little plastic baskets, but the kitchen makes an impressive amount of stuff in house.

Life on March

Capitol Hill

That perfect egg white foam atop your cocktail is actually the work of chickpea juice, and the stunning vinyl collection nods to the owners’ deep ties to local music scene (KEXP’s John Richards is a partner). Patrons get to pick records to play, but you might be too busy with the plant-based disco fries, the chop cheese made with Beyond Beef, or the brunch menu that comes with its own slate of careful drinks.

Vegan Burgers

Galaxy Rune Burgers


It’s hard to choose from the deep bench of sandwiches, melts, and an entire section dedicated to (soy-based) pulled pork. But it’s hard to bypass burgers at this compact, black-walled counter spot, thanks to housemade patties with great texture and a proper sear. They come piled with proper fixins, including a smokey house bacon. The soda, dipping sauce, and side order game is equally strong.

Next Level Burger


A classic American burger stand with an enormous menu hides inside the Roosevelt Whole Foods, complete with a rare (and fairly impressive) lineup of milkshakes. The Oregon-based company piles its sandwiches with toppings and flavor, and adorns its packaging with messages about eating better for the planet. A free-standing Seattle location is on the way.

Vegan Sweets

Frankie and Jo’s

Ballard, Capitol Hill, University Village

Three plant-filled shops offer a mind-blowing lineup of vegan scoops—crazy decadent, deeply flavored, and in no way a dietary consolation prize. Flavors like dirty horchata, date-sweetened chocolate, or pickled blueberry channel Southern California; sorbets step away from the nut milks with combos like beet-strawberry-rose. Every last scoop, chocolate sauce topping, and vanilla-maple waffle cone is both vegan and gluten-free. (F&J pints are also available at some local grocery stores.)

Lazy Cow Bakery


Vegan croissants are a rarity, but a plant-based bakery in the heart of Fremont pulls off a commendable version (classic, almond, and the occasional chocolate) thanks to the magic of vegan butter. Lazy Cow also makes tasty retro-looking layer cakes. The bakery supports mutual aid organization La Casa del Xoloitzcuintle and operates a community fridge and food pantry inside its large space.

Dough Joy

Ballard, Capitol Hill, Alaska Junction

These newcomers (two brick-and-mortar, plus a truck in Ballard) have cascaded across town, bringing doughnuts in a rainbow of flavors that sparkle—sometimes literally thanks to edible glitter. The all-vegan dough isn’t as light as a typical brioche doughnut; They almost resemble King’s Hawaiian buns, but make a worthwhile canvas for birthday cake, strawberry lemonade, everything bagel, or lemon poppyseed. Coffee drinks come with a wee doughnut, skewered on a stir stick.

Flying Apron

West Seattle

There are butter-based bakeries in town whose pastry cases look skimpy next to Flying Apron’s legendary counter lineup of cookies, cakes, muffins, bon bons, sticky buns, scones, even the occasional beignet. Everything is plant-based and gluten free, including a savory menu of pizza, tofu scrambles, and mac and chez. These goods also show up at groceries and coffee shops around town.

Mighty-O Donuts


This longtime staple found its way to plant-based recipes after setting out to make organic, consciously sourced doughnuts. Donuts are mostly of the cake variety (plus the requisite raised twists, bars, and fritters), full of familiar, yet finessed flavors like chocolate topped with peanut butter, or raspberry-glazed vanilla. Early experiments pouring chai into doughnut mix yielded the popular french toast flavor.


Capitol Hill

As the name implies, this North American chain specializes in cinnamon rolls piled with frosting, sprinkles, pie crumbles, chocolate sauce, and all manner of edible flair. But anyone craving vegan, gluten-free junk food should also investigate the edible cookie dough.

Janel Smith Obituary (2022 – 2022) – Rexburg, ID


Janel May Drake Smith, 87, of Rexburg, died Thursday, August 11, 2022, at Homestead Assisted Living. She was born in Nampa, ID on April 19th, 1935, to Harriet May Kelly and Edgar LeRoy Drake. The only daughter of five children, she was cherished by her parents and brothers.

Janel grew up in Nampa ID with annual summer education/vacations at the family cabin in Warm Lake Idaho where she developed her love of the mountains and nature. Janel attended BYU, studying music for 3 years before deciding to pursue Dietetics. She graduated as a certified Dietician, a profession she maintained until her retirement. In later life, she completed her Master’s degree at BYU, graduating on her 50th birthday. For her degree, she completed research on the Nutritional Status of Palestinian Arab Children in the State of Israel.

Janel married her first husband, Ron Madsen in 1957while at BYU. They moved to California shortly thereafter, where they were blessed with four children: Terry Madsen of Bountiful UT, Michelle Getz and Shawna Madsen of Houston TX, and Brian Madsen of NY, NY. She later moved to New Jersey for a short time and then to Houston in 1968. In addition to her four children, she has13 beautiful grandchildren and four great-grandchildren.

Janel worked as a Dietician for a time in Houston, before moving to Rexburg, ID in 1980where she taught Foods and Nutrition at Ricks College from 1980 to 2000. She served as Department Chair for several years.

Janel and Norm Smith met at a church dance in 1983. They had a whirlwind romance and were married in 1984 in the LDS Idaho Falls Temple. Janel and Norm had a very happy marriage and shared many adventures and world travels including Russia and French Polynesia.

They served four missions for the church of Jesus Christ of Latter-Day Saints, including twice at Martins Cove in WY where they educated visitors about the pioneers. They also served in South Chicago where they supported the local congregation and guided young missionaries. In later years, they served a humanitarian mission in Rexburg, counseling and supporting members in crisis.

Janel served many callings throughout her life including Choir Director, Primary teacher, and Relief Society President. Her love of music led her to be called to direct the music in Sacrament meeting in nearly every ward she attended.

Janel enthusiastically celebrated the holidays, preparing elaborate dinners, baking cookies, and making it a memorable and magical time of the year for all. Her love of family, adventure, and fun will be greatly missed by her husband Norm, her family, and all who knew her.

Funeral services will be held at 2:00 pm Monday, August 15th at the Rexburg 15th Ward Chapel, 166 South 1st East, Rexburg, Idaho. The family will receive friends Sunday evening from 5:00 to 6:30 pm at Flamm Funeral Home and then again Monday from 1:00 to 1:45 pm at the church prior to services. Interment will in the Victor Cemetery. In lieu of flowers donations may be made to Four Paws, 119 South 4th West Rexburg.

Services may be viewed at: https://my.gather.app/remember/janel-smith

Published by Post Register on Aug. 12, 2022.

To plant trees in memory, please visit the Sympathy Store.

Parents sound alarm on CMV, little-known virus that can cause birth defects


In August 2019, when Corey Clem was pregnant with her daughter, she caught a cold with a “pretty bad cough,” she told TODAY. She visited her doctor to make sure everything was OK and received a prescription for cough medicine. The next month, she gave birth to her daughter, Ellie, and noticed some unexpected things about the newborn.

When Ellie was born, she was small and experienced petechiae. She later lost her hearing. Doctors discovered that CMV contributed.Courtesy Corey Clem

“She was a lot smaller than we thought she was going to be, and she had this petechiae, these little red spots all over her,” Clem, 32, from New Home, Texas, said. “She was otherwise healthy.”Doctors did some bloodwork to try to understand why she had petechiae, and they found that Ellie’s platelet count was low. She also failed her newborn hearing test twice, but they reassured Clem that happens sometimes, especially when babies have fluid on her ears. Four days after the family returned home, they learned what was wrong.

“Our doctor called to give us the news that she had CMV. The first thing our pediatrician said was, ‘Do not Google it,’” Clem said. “That was the first time I had ever heard of it.”

What is CMV?

CMV stands for cytomegalovirus. It’s such common virus that half of all adults have had it by the time they turn 40, according to the US Centers for Disease Control and Prevention. Most people never know they have it because it’s often asymptomatic. In others, it feels like the “common cold.”

“Usually, it’s not a problem in the sense that you don’t get long-term health consequences,” Dr. Allison August, vice president of clinical development for infectious diseases at Moderna, told TODAY. “If you are immune compromised, then you are more at risk for having a severe case. And it’s particularly concerning for pregnant women, specifically if they get CMV for the first time.”

Pregnant people’s babies are at risk for congenital CMV, which can lead to life-long health problems. CMV is the No. 1 cause of birth defects due to an infection, according to the CDC.

“Every 30 minutes in the United States, there is a baby born affected with CMV, and one in five of those babies have long-term health consequences,” August said. “Despite these statistics, 91% of women have never heard of CMV.”

Andy Jones and his wife were part of that predominantly. The couple had two daughters and decided to have a third child, secretly hoping for a boy. During her third pregnancy, Jones’ wife visited the doctor at 35 weeks pregnant for a routine screening. Then Jones received a frantic call.

“My wife said they were taking her down for an emergency C-section. Ross’s heart tones were low,” Jones, 35, of Birmingham, Alabama, told TODAY. “Honestly, I didn’t even know what that meant at the time.”

After Ross was born, he briefly opened his eyes while dad Andy Jones visited him.  It was the only times Jones saw his son's eyes.
After Ross was born, he briefly opened his eyes while dad Andy Jones visited him. It was the only times Jones saw his son’s eyes.Courtesy Andy Jones

He rushed to the hospital and waited without answers for a while.

“A doctor came out and said that my son, Ross, had been born alive but was not breathing,” Jones said. “They were able to resuscitate him, but it took, they estimated, about two to three minutes. So there was always the specter of, ‘Was there brain damage? Or how damaged were any of his organs?”

Doctors were unsure why Ross was so ill.

“He was really critical and down in the (neonatal intensive care unit),” Jones said. “I went to see him. (It was) just unbelievable how small and frail and sick he looked. He opened his eyes super briefly, and that actually turned out to be the only time I saw his eyes.”

For the next three and a half days, Ross clung to life. It seemed like his organs were recovering, but then doctors rushed in with a crash cart to revive him. By the fourth day, medical staff exhausted all the interventions they had.

“His heart just stopped, and we let him go,” Jones said. “I still never heard the word CMV.”

Six weeks later following an autopsy, they learned why Ross died.

“They said my wife must have gotten a CMV infection in her first trimester that passed onto Ross, and it had six or seven months to grown and spread because what they found was that virtually every one of his organs was fully infected with CMV,” Jones said. “They think he was probably just dying (at the 35-week scan).”

Doctors believe that Andy Jones' wife contracted CMV early in the pregnancy and it infected baby Ross as he developed in utero.  By the time he was born, he had been fighting the virus for months.
Doctors believe that Andy Jones’ wife contracted CMV early in the pregnancy and it infected baby Ross as he developed in utero. By the time he was born, he had been fighting the virus for months.Courtesy Andy Jones

Raising awareness

Like the others, Kristen Spytek had never encountered CMV until doctors detected some “abnormal ultrasound findings” when she was pregnant with her daughter,” she told TODAY.

“When my child was born, it was the neonatologist who whisked her away and said, ‘I think that this is congenital CMV,’” Spytek, the CEO of the CMV Foundation, said. “She was 3 pounds 14 ounces. She had microcephaly.”

The doctors gave Spytek’s daughter antivirals to treat her.

“(These treatments) do not retroactively restore what has been lost or different, but it will help improve outcomes,” Spytek explained. “We find testing to be very, very important either during pregnancy or after so these babies have a chance for early intervention and other treatments.”

Spytek’s daughter had hearing loss, cortical visual impairment, epilepsy and hypotonia, meaning she couldn’t sit on her own. She struggled to eat and underwent surgery for a feeding tube. She died after that procedure at 21 months old.

“Given the chance again, I would absolutely do the treatment each and every time,” Spytek said.

Spytek hopes that a vaccine could prevent what happened to her daughter from happening to other families.

“We’re really pushing for a CMV vaccine,” she said.

Ellie is deaf in her left ear and has hearing loss in her right.  Thanks for early intervention, she's thriving even though she was born with CMV.
Ellie is deaf in her left ear and has hearing loss in her right. Thanks for early intervention, she’s thriving even though she was born with CMV.Courtesy Corey Clem

There’s currently no vaccine for CMV, and that’s why raising awareness of it remains so essential, August and Spytek said.

“The best that we have in terms of counseling is prevention,” August said. “The more education everyone has about how to prevent CMV, then that is one very important way that we can really conquer and certainly, at a minimum, decrease the spread.”

To prevent the spread, August recommends that parents who are pregnant or have contact with a pregnant person do the following:

  • Don’t share food, utensil or drinks with children
  • Don’t put a child’s pacifier in your mouth
  • Don’t share toothbrushes
  • Avoid contact with saliva such as kissing a child

Moderna has a vaccine in phase 3 clinical trials and researchers are still recruiting people for it, August said. Until then, Spytek emphasizes what she calls a “knowledge vaccine.”

“We try and educate on the risks while pregnant,” she said. “(People are) not talking about CMV, and that’s concerning to us because it is so very common.”

Association between long-term weight-change trajectory and cardiovascular disease risk by physical activity level


Data and study subjects

This study was conducted using data from the community-based cohort (Ansung-Ansan cohort) in the Korean Genome and Epidemiology Study (KoGES). Detailed information regarding the KoGES has been published elsewhere23. This community-based cohort study began in 2001–2002 to investigate risk factors for chronic diseases among Koreans. This prospective cohort included residents (aged 40–69 years) living in two communities in Gyeonggi Province: Ansung, a rural region (n = 5018), and Ansan, an industrial region (n = 5012). The 10,030 participants completed the baseline survey in 2001–2002. Biennial follow-up assessments were conducted by trained technicians and interviewers and are still ongoing. The follow-up assessments include questionnaires, anthropometric measurements, blood sampling (collected after overnight fasting), urine tests, and biomarker measurements. This study included data up to the eighth follow-up (conducted in 2017–2018; follow-up rate = 61.4%). There were no significant differences between follow-up participants and non-participants, except in smoking status, total calories, and fasting blood glucose levels23.

In this study, participants with a history of cancer, myocardial infarction, coronary artery disease, cerebrovascular disease, or congestive heart failure at baseline were excluded (n = 410). In addition, participants had to have completed at least one follow-up survey to be included in the analysis. After exclusions, this study included 8774 participants (4161 males and 4613 females). The excluded individuals were slightly older, had a higher prevalence of diabetes and hypertension, and had lower physical activity levels than those who were included; However, there were no differences in mean BMI, weight, or current-smoking percentage (data not shown). Our study followed the STROBE guidelines. The study was conducted according to the guidelines of the Declaration of Helsinki and the study protocol was also approved by the Institutional Review Board (IRB) of Ewha Womans University Hospital (IRB no. EUMC 2017-06-041/EUMC 2021-03-008 ). Review board requirement for written informed consent was waived by the IRB of Ewha Womans University Hospital because this study used an anonymous dataset.

Cardiovascular diseases assessment

As an outcome, newly identified cases during the follow-up period were considered. For the conditions diagnosed by physicians, self-reported questionnaires for myocardial infarction, coronary artery disease, cerebrovascular disease, and congestive heart failure were used to determine the incidence of non-fatal CVD. If a medical diagnosis was confirmed during follow-up, the event was considered to have occurred on the date of follow-up; the follow-up time was then calculated. Thus, follow-up commenced on study entry and ended when the physician-diagnosed disease was confirmed or on the date of the last follow-up. Fatal CVD was determined based on the cause of death of each subject as of December 31, 2019 by linking the death certificate data from the Korean National Statistical Office and cohort data. Fatal CVD was defined as codes of I00-I79 based on the International Classification of Disease, 10th Revision24, and confirmed deaths due to myocardial infarction (I21–I22), coronary artery disease (I20–I25), cerebrovascular disease, (I60–69) and congestive heart failure (I50). The validity of the data was assessed by comparing self-reported diagnoses with the diagnoses reported in the medical records, and 93% agreement between self-reported diagnoses and the medical records was observed among 30 cases25.

Weight-change and body-composition assessment

The average number of measurements of weight for participants was 6.7 ± 2.6. Using weight values ​​before CVD development, bodyweight change was calculated by subtracting baseline weight from the weight at each follow-up time point.

Total skeletal-muscle mass (SMM) and body fat mass were measured using multi-frequency bioelectrical impedance analysis (MF-BIA; InBody 3.0; Biospace, Seoul, Korea). Body was measured at each follow-up composition and data were collected.


Several demographic factors collected at baseline were included as covariates including age, sex, study region (industrial/rural), and educational level at baseline. Additional potential risk factors for CVD including body mass index (BMI) (continuous), current smoking, alcohol intake (no alcohol, < 15 g/day, 15–24.9 g/day, ≥ 25 g/day)27, and sex-specific quartile of physical activity (PA) at baseline were also considered. The intensity and duration of PA over the past year were assessed using the metabolic equivalent of task (MET)-hours per week based on the International Physical Activity Questionnaire28. Additionally, since several prevalent conditions are associated with weight change and CVD risk, diabetes, hypertension, dyslipidemia, and arthritis were considered covariates. The condition was defined taking into account clinically relevant data or self-reported information for physician-diagnosed illnesses, collected as part of the baseline survey. Using clinically related data, diabetes was defined as a fasting blood glucose level ≥ 126 mg/dL, and hypertension was defined as a systolic or diastolic blood pressure of 140/90 mmHg or higher. Dyslipidemia was defined as triglyceride levels > 150 mg/dL or high-density lipoprotein-cholesterol levels < 40 mg/dL for men and < 50 mg/dL for women.

Statistical analysis

All statistical analyzes were conducted using SAS software (ver. 9.4; SAS Institute, Cary, NC, USA). Two-tailed p-values ​​< 0.05 were considered statistically significant.

Participants were categorized into distinct subgroups based on their specific pattern of weight change over time using the Proc Traj procedure in SAS software for group-based trajectory modeling26. A group-based trajectory model is an statistical technique for longitudinal data13 that has several advantages, including the discovery of unexpected and potentially meaningful trajectories and graphical representation of the results for better understanding13. Each trajectory can be specified individually, allowing the best-fitting polynomial form. The optimal fit model is chosen based on Bayesian Information Criterion (BIC) values, with each trajectory containing at least 5% of the predicted sample size12. To compare two models with different numbers of groups, we calculated the logged Bayes factor (2 × ΔBIC). The five-pattern model did not satisfy the group size requirements. Therefore, the four-pattern model was selected as the optimal model based on the logged Bayes factor (eTable 1). We then refined the four-pattern model until the highest polynomial coefficient for each trajectory group was statistically significant. Therefore, the highest polynomials for each group were quadratic, quadratic, linear, and quadratic, respectively (Fig. 1). For the selected model, based on the highest posterior probability, each individual was assigned to a specific trajectory group. The probability of belonging to a particular group can depend on the covariates, which can affect the model coefficients. Thus, sex and age were included in the model as covariates. The four groups were named ‘gradual weight loss’, ‘slight weight loss’, ‘stable weight’, and ‘gradual weight gain’ based on the features of their weight-change patterns.

Figure 1

Weight changes by trajectory group derived from group-based modeling over the 16-year study duration. The solid line indicates the estimated average value.

Basic group characteristics were summarized as means with standard deviations for numerical data and a number of participants with percentages for categorical data. Differences in basic characteristics among groups were tested using a generalized linear model and Chi-square test. Basic characteristics with significant differences between groups were included as covariates in the analysis.

The association between weight-trajectory patterns and CVD risk was evaluated using Cox proportional hazard regression modeling. We evaluated whether the influence of the trajectory patterns differed by PA quartile regarding CVD risk and observed significant interactions (pinteraction< 0.05). Thus, subsequent analyzes were stratified by the PA quartile. The relationship between trajectory patterns and the CVD risk was estimated using hazard ratios (HRs) with 95% confidence intervals (95% CI). The multiple regression model included sex, age, study region, educational level, BMI, smoking status, alcohol intake, any history of diabetes, hypertension, dyslipidemia, or arthritis at baseline, and skeletal muscle mass change during follow-up. Furthermore, multiple models were stratified by obesity at baseline (BMI ≥ 25.0 kg/m2 or BMI < 25.0 kg/m2) and sex. Additionally, associations were evaluated in subjects with low-muscle mass and high-fat mass that were defined using the median of SMM and body fat mass.

A mixed-model analysis was performed to estimate the relationship between weight-change patterns and SMM or body fat mass. A random-intercept model was constructed to include group (ie, weight-change patterns), measurement time point, the interaction between group and measurement time point as fixed effects, as well as the covariates. Sex, age, study region, education level, physical activity (MET), current smoking, alcohol intake, disease history of diabetes, hypertension, dyslipidemia, and arthritis at baseline, height (the residual from a regression model in which height is the independent variable and SMM is the dependent variable at each follow up)29, mutually adjusted for body fat mass (in the SMM model), and SMM (in the body fat mass model) at each follow up were included as covariates. Covariance structure was determined according to BIC values. The results were indicated as least-square means with 95% CIs.