Nanoparticle-delivered COVID-19 vaccine candidate shows promise in preclinical studies

Nanoparticle-delivered COVID-19 vaccine candidate shows promise in preclinical studies

Researchers from Cleveland Clinic’s Global Center for Pathogen Research & Human Health have developed a promising new COVID-19 vaccine candidate that utilizes nanotechnology and has shown strong efficacy in preclinical disease models.

According to new findings published in mBio, the vaccine produced potent neutralizing antibodies among preclinical models and also prevented infection and disease symptoms in the face of exposure to SARS-CoV-2 (the virus that causes COVID-19). An additional reason for the vaccine candidate’s early appeal is that it may be thermostable, which would make it easier to transport and store than currently authorized COVID-19 vaccines.

“Our vaccine candidate delivers antigens to trigger an immune response via nanoparticles engineered from ferritin—a protein found in almost all living organisms,” said Jae Jung, Ph.D., director of the Global Center for Human Health & Pathogen Research and co-senior author on the study. “This protein is an attractive biomaterial for vaccine and drug delivery for many reasons, including that it does not require strict temperature control.”

Added Dokyun (Leo) Kim, a graduate student in Dr. Jung’s lab and co-first author on the study, “This would dramatically ease shipping and storage constraints, which are challenges we’re currently experiencing in national distribution efforts. It would also be beneficial for distribution to developing countries.”

Other benefits of the protein nanoparticles include minimizing cellular damage and providing stronger immunity at lower doses than traditional protein subunit vaccines against other viruses, like influenza.

The team’s vaccine uses the ferritin nanoparticles to deliver tiny, weakened fragments from the region of the SARS-CoV-2 spike protein that selectively binds to the human entry point for the virus (this fragment is called the receptor-binding domain, or RBD). When the SARS-CoV-2 RBD binds with the human protein called ACE2 (angiotensin-converting enzyme 2), the virus can enter host cells and begin to replicate.

The researchers tested their vaccine candidate on a ferret model of COVID-19, which reflects the human immune response and disease development better than other preclinical models. Dr. Jung, a foremost authority in virology and virus-induced cancers, previously developed the world’s first COVID-19 ferret model—a discovery that has significantly advanced research into SARS-CoV-2 infection and transmission.

In this study, the researchers administered an initial dose of the vaccine candidate followed by two booster vaccines given 14 and 28 days later. One group received the vaccines intramuscularly, while another group received them both intramuscularly and intranasally.

After the second booster, all vaccinated models produced strong neutralizing antibodies. This suggests that repeated exposure to the RBD antigen successfully prepared the immune systems to rapidly fight the virus.

A few days after the second booster (31 days after the initial vaccine dose), the researchers exposed the models to high concentrations of SARS-CoV-2. Compared to the placebo group that received adjuvant-only vaccines (adjuvants are added ingredients that help vaccines work better), those that received the RBD-nanoparticle vaccine were better protected from clinical symptoms and lung damage associated with infection. The findings suggest the vaccine candidate helped prevent infection and serious disease.

Combination intramuscular and intranasal immunization showed more potent protective immunity and faster viral clearance than intramuscular immunization alone. Both were significantly more effective than the adjuvant-only vaccine. More research will be important to uncover the mechanisms behind these differential benefits.

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Srudy shows how tissue’s microscopic geometry affects spread of cancer

Oregon State research shows how tissue's microscopic geometry affects spread of cancer

Oregon State University research has revealed a crucial mechanism behind one of humankind’s most deadly physiological processes: the movement of malignant cells from one part of the body to another.

Published in the Proceedings of the National Academy of Sciences, the study led by OSU biophysicist Bo Sun shows the role that tissues’ microscopic geometry plays in cancer metastasis, the internal spreading of the disease that’s responsible for 95% of all cancer deaths.

To develop drugs that effectively combat metastasis, it’s fundamentally important to understand what directs the metastatic process, Sun said.

“Our results show the level of tissue fiber alignment, particularly collagen fiber alignment, is a crucial part of what’s happening,” Sun said.

Collagen is a protein that serves as the primary component of human connective tissue, which supports, protects and provides structure for other tissues and organs in the body. Collagen is also a key part of the extracellular matrix, the non-cellular part of tissues and organs that acts as a scaffold and also performs important biochemical and biomechanical functions.

“Clinical studies have shown that the microscopic geometry of tissue is significantly correlated with the progression of breast cancers,” Sun said. “Our study reveals the underlying biophysical mechanism. In the era of precision medicine, we think taking into account the physical properties of a patient’s tissue can be critical for the prediction and treatment of metastatic disease.”

The correlation is due to a cellular phenomenon known as “contact guidance,” which is analogous to a back-country hiker trying to pick a route based on the contours of the terrain and the network of downed trees on the ground.

“In navigating the three-dimensional extracellular matrix, where the fibers aren’t necessarily parallel, cells have to integrate multiple guidance cues that aren’t always clear and sometimes are conflicting,” Sun said. “Understanding the mechanisms and limitations of cell responses to imperfect guidance signals is pivotal for predicting and engineering cell behaviors—i.e., providing a patient with a precise diagnosis, prognosis and treatment.”

¬¬In this research, Sun and collaborators at OSU, the University of California San Diego and Northeastern University found that a breast cancer cell can switch between two distinct states: the mesenchymal, in which the cell shape is elongated, and the amoeboidal, in which it’s more round.

“In the mesenchymal state, a cell follows the orientation of tissue fibers, and the effect is strongest when the level of fiber alignment is highest,” Sun said. “In the amoeboidal state, the same cell moves rather randomly. Another part of it is that the transition rate between the two states is also determined by the level of tissue fiber alignment—strong alignment leads to a stronger tendency for a cell to stay in the mesenchymal state.”

Collaborating with Sun were graduate research assistant Jihan Kim and Ph.D. candidate Christopher Eddy of OSU’s Department of Physics, Yuansheng Cao and Wouter-Jan Rappel of UC San Diego, and Youyuan Deng and Herbert Levine of Northeastern.

The U.S. Department of Defense, the National Science Foundation and the National Institute of General Medical Sciences supported this study, which builds on earlier research by Sun that showed human cells, including cancer cells, could mechanically and permanently remodel their surroundings—and thus affect an array of physiological processes from metastasis to wound healing to embryo development.

In that research, Sun found that a single pair of breast cancer cells could increase the local fiber density of reconstituted collagen matrices by more than 150%.

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Close-Up! Kylie Jenner Shows Off Her Curves in Barely There String Bikini

Still got it! Kylie Jenner put her enviable body on display in a barely there blue string bikini.

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The reality star, 23, posted a close-up photo in her swimwear via Instagram on Friday, February 5. She also shared a video of herself holding a bottle. “SPF body oil @kylieskin,” she wrote.

https://www.instagram.com/p/CK7mGeHneUl/

A post shared by Kylie 🤍 (@kyliejenner)

Jenner’s sisters praised her in the comments section. “We get it! We get it!!! You’re perfect,” Khloé Kardashian replied, while Kim Kardashian responded with four fire emojis.

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In a video on her Instagram Story, the Kylie Cosmetics founder sprayed the Kylie Skin oil on herself and gave another look at her getup, accessorized by a gold body chain and her long, dark hair. She then posted a clip on Saturday, February 6, that showed her walking around a house in the swimsuit and a pink coverup. “Yesterday,” she captioned the video.

While Jenner has followed in her siblings’ footsteps of sharing sultry snaps via social media, Kendall Jenner opened up in April 2019 about feeling insecure about her own body. “My sisters are a lot curvier than me,” the model, 25, told The Telegraph at the time. “They have boobs and I don’t have boobs. Growing up being this little twiggy girl, I saw my sisters and always thought, ‘Oh, no. Am I supposed to be more sexy like them?’”

Kendall confessed that she “almost felt like [she] didn’t fit in” with her family but eventually embraced her unique features. “I like that I have a different vibe to everyone. I like to do different things. And that’s OK.”

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Kylie, for her part, welcomed daughter Stormi in February 2018. One year later, she addressed speculation that she had plastic surgery.

“People think I fully went under the knife and completely reconstructed my face, which is completely false,” she told Paper magazine in February 2019. “I’m terrified! I would never. They don’t understand what good hair and makeup and, like, fillers can really do.”

Kylie is not the only member of her famous family to show off her physique in recent weeks. Khloé, 36, posted an Instagram photo of her stretch marks on January 30, writing: “I love my stripes.”

Although social media users called out the Revenge Body host in May 2020 for her changing look, a source exclusively told Us Weekly the following month that she was unbothered by the backlash she received. “She thinks she looks great,” the insider revealed. “And actually [she] does not care what people think as long as she’s happy.”

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Study shows safety of adaptive radiotherapy in non small cell lung cancer patients

lung

The NRG Oncology and the American College of Radiology Network (ACRIN) multicenter, phase II trial, NRG-RTOG 1106/ACRIN 6697, is the first randomized trial to demonstrate the feasibility and safety of performing adaptive radiotherapy (RT) escalation in patients with locally advanced non-small cell lung cancer (NSCLC). The improvement of in-field tumor control appeared similar to the level (1% improvement with 1Gy dose escalation) of the single institutional study of adaptive radiotherapy performed at University of Michigan, and different from that of RTOG617 with non-adaptive high dose radiation in stage III NSCLC. The results were presented at the virtual edition of the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer, Singapore.

The NRG Oncology randomized phase III trial NRG-RTOG 0617 offered the insight that a higher dose of radiotherapy delivered with chemoradiotherapy actually worsened tumor control and survival for this patient population. NRG-RTOG 1106/ACRIN 6697 was designed to bridge this treatment gap by testing adaptive radiotherapy dose escalation with chemotherapy to see if this treatment could enhance two-year local-regional tumor control compared to the 60 Gy standard dose of radiotherapy this patient population typically receives. The use of fluorodeoxyglucose-positron emission tomography (FDG-PET/CT) imaging would help identify resistant aggressive tumor identified mid-treatment and adapt personalized treatment plans per each individual’s tolerance.

Patients with Stage III NSCLC were randomly assigned in a 2:1 ratio to receive either the standard radiotherapy at 60 Gy (Standard Arm) or the adaptive radiotherapy treatment that resulted in a median dose escalation of 11 Gy (Adaptive Arm). Patients on both treatment arms received FDG-PET/CT imaging at mid-treatment for radiation. The Standard Arm included 43 eligible patients whereas the Adaptive Arm included 84 eligible patients. The Standard Arm had a median follow up of 3.7 years for surviving patients with acceptable overall radiotherapy compliance rates (92.9% and 50% per protocol). The 2-year overall local-regional progression free rate was 59.5% (95% CI: 37.9, 75.7). Median local-regional progression free time was 27.5 months (95% CI: 14.3, not reached) in the Standard Arm. The Adaptive Arm had a median follow up of 3.4 years for surviving patients with acceptable overall radiotherapy compliance rates (95.8% for the initial course of treatment and 32.4% for adaptive course per protocol) and 2-year overall local-regional progression free rates were 54.6% (95% CI: 39.9, 67.0). Median local-regional progression free time was 28.4 months (95% CI: 19.1, not reached) in the Adaptive Arm. There were no significant differences in grade 3 or worse toxicity of lung, esophagus, and heart or overall survival, progression-free survival, and lung cancer specific survival between treatment arms. Adaptive radiotherapy did increase in-field local-regional tumor control by 11% and in-field primary tumor control by 17% during the trial.

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April Love Geary Shows Postpartum Body in Lingerie 6 Weeks After Son's Birth

Postpartum pride! April Love Geary posed in black lingerie less than two months after giving birth to her and Robin Thicke’s son, Luca.

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“Six weeks postpartum,” the model, 26, captioned her Wednesday, January 27, Instagram selfie rocking a lacy bra and underwear set and wavy hair. “Loose skin, tight friendships.”

Geary and the Masked Singer judge, 43, welcomed their third child together in December 2020. The little one joined big sisters Mia, 2, and Lola, 23 months, as well as Thicke’s 10-year-old son, Julian, with ex-wife Paula Patton.

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“My Luca Patrick, you are so perfect,” the California native captioned her baby boy’s Instagram debut. “Mommy and Daddy love you so much.”

Geary’s eldest daughter was immediately a big fan of Luca, she went on to write via Instagram. “I was NOT expecting her to bet his happy,” Geary wrote at the time. “She keeps saying, ‘He’s so cute,’ ‘He loves me so much,’ and ‘Can I pet him?’ She’s the best big sis.”

As for Lola, Geary shared sweet videos of the toddler babbling at her baby brother and carefully touching his head. “My heart is so full,” Geary wrote alongside the footage.

Us Weekly broke the news in September 2020 that Thicke was expecting baby No. 4. His fiancée confirmed the news the following month, showing off her bikini bump during a beach trip.

“Sorry we can’t hang out, there’s a pandemic and I’m pregnant again,” Geary captioned an October 2020 Instagram photo. “We love consistency.”

She went on to write on her Instagram Story that she and the Grammy winner were done expanding their family. “With Julian, it’ll be four total and I love even numbers,” Geary explained.

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As for whether her pregnancy was planned, Geary said it wasn’t, but that she and the Canada native had “decided to roll with it.”

The couple started dating in 2014, the same year Thicke split from Patton, 45. They got engaged in December 2018. “YES YES 1000x YES,” the bride-to-be wrote via Instagram following her restaurant proposal.

The couple welcomed Mia and Lola in February 2018 and February 2019, respectively. Two months after giving birth to her second daughter, Geary showed her postpartum stomach.

“I’ve been getting a bunch of DMs saying things like, ‘How could you support abortion when you’re a mother yourself?’ so this is MY body, MY body after having an abortion in 2014, a miscarriage in 2017, delivering a baby in 2018 & 2019,” she captioned a May 2019 Instagram post. “I’m glad I was able to make decisions about MY body without facing any type of punishment.”

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New research shows the importance of consuming enough vitamin B12 in pregnancy

pregnancy

A new study published in Nutrition Research has found that children born to a mother with low intake of vitamin B12 during pregnancy were at increased risk of adverse development specific to certain speech and mathematical abilities.

The study, from Professor Jean Golding and colleagues at the University of Bristol, used data from the renowned long-term health study Children of the 90s.

Information on details of the diets of almost 14,000 pregnant women was collected by the Children of the 90s study (also known as the Avon Longitudinal Study of Parents and Children or ALSPAC), based in Bristol, UK. Their children have been followed over the years and their abilities tested at various time points. A publication in the journal Nutrition Research reports on the results of comparing the children born to women who were eating a diet relatively low in vitamin B12 with children whose mothers ate a diet higher in the vitamin.

Professor Golding explained: “Many nutrients in pregnancy have beneficial effects on the brain of the unborn child, with resulting improved childhood abilities in regard to intelligence and educational abilities. However, it is unclear whether vitamin B12 has a similar effect.

“Vitamin B12 is found in foods such as meat, fish, eggs, cheese, milk and some fortified breakfast cereals. For vegans and vegetarians, Marmite is a rich source of vitamin B12 and other B vitamins.”

Researchers compared 29 different test results of which 26 were shown to differ with levels of vitamin B12, a far higher amount than would have been expected.

However, the mothers who had a diet low in vitamin B12 differed from the rest of the population in 9 different independent features. Once these factors had been taken into account there were no residual effects with social class or any other socioeconomic measure. These nine variables were all taken into account when assessing the possible effects of the mother’s diets during pregnancy on her offspring’s abilities.

Whilst many of the differences such as reading and spelling abilities, as well as aspects of IQ could be explained by other background factors, there were six associations which could not be explained away. These indicated that the children born to women with the lowest intake of vitamin B12 were at increased risk of poor vocabulary at 24 months, reduced ability at combining words at 38 months, poor speech intelligibility at six years, poor mathematics comprehension at school years four and six (ages eight to nine and 10-11 years), and poor results on the national mathematics tests (age 13). There were no significant associations with mental arithmetic, indicating that the mathematics results were specific to a reasoning component rather than computational abilities.

The numbers involved in these results were as follows: 24 month vocabulary (n=9140); combining words at 38 months (n=8833), poor speech intelligibility at six years (n=7,647), poor mathematics comprehension at school years four and six (ages eight to nine (n=4,093) and 10-11 years (n=6,142), and poor results on the national mathematics tests (age 13 (n=8,215).

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Saying ‘I understand’ makes a real difference, study shows

Showing support for a person who is upset over something they’ve experienced can help boost their positive feelings, new research shows.

Just saying “I understand why you feel that way” makes a difference, according to Ohio State University researchers who explored positive and negative emotions in more than 300 students.

Three experiments assessed the effects of both supportive and critical comments (validation and invalidation) on what clinicians call positive and negative affect. Positive affect refers to emotions and expression that foster curiosity, connection and flexible thinking. Negative affect engenders feelings of disgust, fear or sadness.

Students completed questionnaires about positive and negative affect at the start and end of the study. They also reported their overall mood during the experiments.

They were asked to think and write for five minutes about a time when they were intensely angry and then to describe those feelings out loud.

The researcher either validated or invalidated their angry feelings with phrases that included: “Of course you’d be angry about that,” or “Why would that make you so angry?”

When they thought or wrote about being angry, everyone had a drop off in positive affect. Those whose feelings were validated saw their moods restored to normal. Those who were not validated did not recover while talking with researchers and their moods generally got worse.

No significant difference was found in participants’ negative emotions. That speaks to the value of protecting positivity, said senior author Jennifer Cheavens, a professor of psychology.

“We spend so much time thinking about how to remedy negative emotions, but we don’t spend much time thinking about helping people harness and nurture positive emotions,” she said in a university news release. “It’s really important to help people with their depression, anxiety and fear, but it’s also important to help people tap into curiosity, love, flexibility and optimism. People can feel sad and overwhelmed, and also hopeful and curious, in the same general time frame.”

Researchers plan to apply the results in a therapy setting, but the findings are also valuable for relationships, Cheavens said.

“Validation protects people’s affect so they can stay curious in interpersonal interactions and in therapy,” she said. “Adding validation into therapy helps people feel understood, and when we feel understood we can receive feedback on how we also might change. But it’s not a uniquely clinical thing—often the same ways you make therapy better are ways you make parenting, friendships and romantic relationships better.”

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Study in mice shows genes may be altered through drug repurposing

Researchers at the University of Illinois Chicago have published a study showing a promising approach to using drug repurposing to treat genetic diseases.

A team from the UIC Department of Ophthalmology and Visual Sciences published the article, “Gene dosage manipulation alleviates manifestations of hereditary PAX6 haploinsufficiency in mice” in the journal Science Translational Medicine.

Nearly all the genes in human DNA have two copies, one inherited from the mother and one from the father. There are some genetic diseases where only one copy is normal and the other one is non-functional due to a mistake in the DNA. The idea behind this study was to see if the normal copy can be enhanced to make up for the non-functional copy, said Ali Djalilian, UIC professor of ophthalmology and corresponding author of the paper.

Researchers used a mouse model of the human disease aniridia, an eye disorder that affects the iris and causes substantial visual impairment and can also be associated with systemic abnormalities. In aniridia, one copy of the gene PAX6 is normal and the other copy is non-functional. The PAX6 gene is important in eye development and patients with aniridia and PAX6 deficiency are born with eye problems, which limit their vision and can progress throughout life, Djalilian said.

The investigators screened drugs that can enhance PAX6 and found a particular class of drugs known as MEK inhibitors can stimulate PAX6 expression in the eye. They tested this drug in newborn PAX6 deficient mice and found that either topical or oral administration of the drug enhanced PAX6 and partially normalized their eye development. Mice treated with topical MEK inhibitor had clearer corneas (less scarring) and could see better.

“Patients with aniridia can develop progressive loss of their corneal stem cells which is a challenging clinical problem. Our research in the Corneal Regenerative Medicine Laboratory is aimed at regenerating healthy corneal cells, which we hope can help these and similar patients,” said Mark Rosenblatt, dean of the UIC College of Medicine and a co-author on the study.

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Snow Cute! Katy Perry Shows Off Adorable Baby Gift From Ariana Grande

The perfect present! Ariana Grande sent Katy Perry and Orlando Bloom’s 3-month-old daughter, Daisy, a Givenchy snowsuit on Sunday, December 6.

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The American Idol judge, 36, unboxed the white outfit in an Instagram Story video captioned, “Ily.”

In the footage, the “I Kissed a Girl” singer showed a note from Grande, 27. “Katy and Orlando, Congrats and I adore you both. Love, Ariana,” the message read.

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Perry and Bloom, 43, welcomed their baby girl in August. While Daisy is the California native’s first child, the actor became a dad in 2011 when his then-wife, Miranda Kerr, gave birth to their son, Flynn, now 9.

The English star gushed the following month that his son is the “best” big brother. “He’s very well-versed in little babies,” the Lord of the Rings star told Ellen DeGeneres in October, referencing Kerr and Evan Spiegel’s sons, Hart, 2, and Myles, 13 months. “For the first time, he has a sister. His mom has a couple. He’s wonderful.”

Bloom added at the time: “We’re at home a lot [amid the coronavirus pandemic], so there’s been a lot of time for nesting and getting him to pick up his room and take care of the baby sort of.”

Daisy sleeps through the night, the Carnival Row star went on to say during The Ellen DeGeneres Show appearance. He called himself a “baby whisperer,” but his fiancée said on Friday, December 4, that finding time for rest has been “a challenge.”

The Grammy nominee explained during a “Meditate America” event that while her daughter is “a gift,” Perry isn’t sure how to “get [back] those six hours that [she] used to get.”

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She and Bloom have become “closer” as a couple since their infant’s arrival, a source exclusively told Us Weekly last month.

“Orlando has made Daisy his priority and slashed a lot of his work time to stay home for the holidays,” the insider said in November. “Orlando is so happy about being a new dad again. He has been doing the night feeds and helping out however he can. … At first, they were concerned that Katy was going to have to jump straight back into work, but she’s been fully focused on being a mom and happy staying home and spending time with Daisy.”

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Pregnant Sadie Robertson Shows 17-Week Baby Bump in Bathing Suit: 'in Awe'

She’s at 17 weeks! Pregnant Sadie Robertson showed her baby bump progress during a Tuesday, November 24, beach trip.

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“Wow wow wow wow,” the Duck Dynasty alum, 23, captioned an Instagram slideshow of herself cradling her budding belly in a striped one-piece. “It’s just absolutely miraculous that my body is daily changing to grow this life inside of me. I cannot miss the intentionally of a creator behind the scenes. I love thinking about her every single day. What she’s going to be like, what’s she going to look like, what will her favorite hobby be.”

The former reality star added, “The greatest thing to think of is that before I will ever know these things God knows her. He knows the hairs forming on her head, and he knows the heart she has that is beating so strongly. He is making her beautiful and wonderful and I can’t wait to be captivated by the design. I’m in awe and wonder.”

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In the same bathing suit, the Louisiana native recreated a throwback photo with her husband, Christian Huff, that her parents, Korie Robertson and Willie Robertson, took at the beach ahead of her 1997 arrival. “Mom and Dad your pose was truly timeless,” the pregnant star wrote via Instagram.

“Oh, my gosh, this is incredible,” Little People, Big World’s Audrey Roloff commented on the social media upload.

Sadie announced last month that she and Huff, 21, are expecting their first child. “SCREAMING WITH EXCITEMENT TO SHARE THIS NEWS,” the Dancing With the Stars alum captioned her Instagram reveal in October. “Baby we already adore you. What I’ve learned from you already – God has still been creating. God is still believing in us. God is still bringing forth LIFE. Hope is still to come. How we choose to live will affect your generation to come, so I want to live my life to the fullest and be loud for you.”

The pregnant star was hospitalized following her announcement after she tested positive for the coronavirus. “Wow, these symptoms are wild,” the former A&E Network personality wrote via Instagram. “I’ve definitely struggled through this one.”

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Earlier this month, she and Huff announced the sex of their baby-to-be with the help of pink paint.

The pair tied the knot in November 2019 in Louisiana, five months after their engagement.

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