Why Shares of Structure Therapeutics Rose

 Shares of Structure Therapeutics (GPCR 0.07%) closed up 18.35% on Monday after the clinical-stage biotech received what is perceived to be good news from Pfizer and a boost from an analyst. The stock went public in February with an initial public offering.

Structure focuses on oral therapies that treat diseases, especially those of the metabolic, cardiovascular, and pulmonary systems. Its lead product candidate, GSBR-1290, targets type 2 diabetes and obesity. The drug recently entered phase 2 trials to treat type 2 diabetes and obesity and is a small molecule agonist of the GLP-1 receptor (GLP-1-RA). 

Structure's stock may have benefited Monday because Pfizer said it was discontinuing clinical trials for lotiglipron, an oral GLP-1-RA candidate, in favor of continuing with another GLP-1-RA therapy, danuglipron. Patients who took lotiglipron showed higher liver enzymes, so safety was a concern. 

The move was unpopular with Pfizer's investors and means a little less competition for GSBR-1290. On top of that, Structure just picked up an analyst's rating, and that can influence investors. On Monday, Evan Seigerman of BMO Capital gave Structure a Buy rating with a price target of $40. Last month, Jefferies Financial Group initiated coverage on Structure Therapeutics with a price target between $34 and $41.

While Structure just went public this year and doesn't have any marketed products yet, GSBR-1290 showed promise in phase 1 trials to treat two relatively large patient populations of diabetics and obese patients. 

Before going all-in on Structure, however, it is important to note the company lost $18 million in the first quarter and had, as of the end of the first quarter, $240.9 million in cash. That was enough, it said, to fund operations through the end of 2025. There's a good chance the company will have to raise funds to continue its operations before it starts making any profits from products.

https://www.fool.com/investing/2023/06/26/why-shares-of-structure-therapeutics-rose-monday/

Genelux, TVAX: US patent covers combination of adoptive T cell therapy/oncolytic viral cancer treatment

 V2ACT Therapeutics™, LLC is a joint venture between Genelux Corporation and TVAX Biomedical, Inc.

- V2ACT Immunotherapy is a proprietary immuno-oncology modality composed of Olvi-Vec (oncolytic viral immunotherapy) and TVAX Immunotherapy® (vaccine-enhanced adoptive T cell therapy).

- The patent expiry for the combination, prior to any patent term extension, will be in 2036.

 Genelux Corporation (NASDAQ: GNLX) and TVAX Biomedical, Inc. today announced that the United States Patent and Trademark Office granted a patent claiming methods of combining vaccine-enhanced adoptive T cell therapy with oncolytic virus adjunct therapy.

The patent has been exclusively licensed to V2ACT Therapeutics, LLC, a joint venture between Genelux and TVAX that was established for the purpose of developing and testing V2ACT Immunotherapy. The patent expiry, prior to any patent term extension, will be in 2036 and will add substantial intellectual property protection for V2ACT Immunotherapy.

The rationale for V2ACT Immunotherapy stems from compelling scientific evidence that vaccination generates an immune response which increases the number of neoantigen-specific T cells in the body and that Olvi-Vec induces an acute inflammatory response that increases cancer tissue receptivity for the clinical effects of adoptively transferred neoantigen-specific effector T cells. This generates compelling support for the view that V2ACT Immunotherapy may safely achieve superior efficacies against a wide range of cancers.

V2ACT capitalizes on the lead assets of both Genelux and TVAX as a combination therapy. Olvi-Vec has demonstrated systemic immunomodulation, an excellent safety profile, powerful immune modulation of the cancer microenvironment and well-documented anti-cancer effects over a wide range of cancers both in preclinical and Phase 2 clinical trials. TVAX Immunotherapy provides a unique neoantigen-specific adoptive T cell therapy, with an excellent safety profile and powerful anti-cancer effects on a wide range of cancers demonstrated in preclinical and Phase 2 clinical trials.

https://finance.yahoo.com/news/genelux-corporation-tvax-biomedical-inc-110000785.html

Jin, Sdoma in electric scooter JV

 JIN MEDICAL INTERNATIONAL LTD. (the "Company" or “JinMed”) (NASDAQ: ZJYL), a Cayman Islands holding company with Chinese operating entities that manufacture and develop wheelchairs and living aids products, today announced that the Company’s variable interest entity, Changzhou Zhongjin Medical Equipment Co. Ltd., has entered into an investment agreement (the “Agreement”) with Shanghai Sdoma Smart Technology Co. (“Sdoma”) to form a joint venture (the “JV”) dedicated to the production and sales of a range of high-quality electric wheelchair and mobility scooter products. Sdoma specializes in research and development, production, and sales of elderly mobility scooters and daily living aids products under the brand name “Sdoma”, which is a top-ranked brand in China based on its online traffic measured by monthly visits to its online store, according to SYCM.com, an e-commerce analytics platform in China. On June 28, 2023, JinMed and Sdoma held a formal signing ceremony at JinMed’s headquarters in Changzhou, China.

Pursuant to the Agreement, the JV will be established in Shanghai, with an estimated investment amount of up to RMB50 million in the next three years, 60% of which shall be contributed by JinMed and the remaining 40% shall be contributed by Sdoma.

Pursuant to the Agreement, JinMed shall be responsible for the design and production of the electric wheelchairs and mobility scooter products, while Sdoma shall be responsible for the sales of the products, brand marketing, and overall operation of the JV.

The JV is expected to synthesize the strengths of JinMed and Sdoma in the electric mobility scooter industry, with a focus on expanding both companies’ product lines, market penetration, and sales channels, both online and offline. JinMed and Sdoma, through the JV, plan to establish more than 30 offline stores in major cities in China within the next three years.

https://finance.yahoo.com/news/jin-medical-international-ltd-announces-120000140.html

'Bacteria use a sugar in the intestinal mucus layer to infect the gut'

 A new study by researchers at the University of British Columbia (UBC) and BC Children's Hospital shows the sugar sialic acid, which makes up part of the protective intestinal mucus layer, fuels disease-causing bacteria in the gut.

The findings, published in PNAS, suggest a potential treatment target for intestinal bacterial infections and a range of chronic diseases linked to gut bacteria, including inflammatory bowel disease (IBD), celiac disease, irritable bowel syndrome and short bowel syndrome.

"Bacteria need to find a place in our intestines to take hold, establish and expand, and then they need to overcome all the different defenses that normally protect our gut," says Dr. Bruce Vallance, a professor in the department of pediatrics at UBC and investigator at BC Children's Hospital. "In the future, we can potentially target this sugar, or how pathogens sense it, to prevent clinically important disease."

Inflammatory diseases such as IBD are on the rise in children, and because of their immature immune systems, kids are more susceptible to gut bacterial infections. Dr. Vallance and his team, including lead author and UBC graduate student Qiaochu Liang and UBC research associate Dr. Hongbing Yu, sought to understand what enables these bacterial pathogens to survive and expand inside our intestines.

For the study, the researchers examined Citrobacter rodentium, an intestinal bacterial pathogen of mice that's used to model infections with human E. coli. The team discovered that the bacteria have genes involved in sialic acid consumption, and when these genes are removed, the bacteria's growth is impaired.

Further investigation revealed that upon consuming the sugars, the bacteria produced two special virulence proteins that help the bacteria cross the colonic mucus layer and stick to the underlying epithelial cells. The findings reveal how the bacteria can change over time and actually worsen disease.

"You start off with IBD, your microbes change, they start digging their way into the cells lining your gut, causing more inflammation, and that may be one reason why IBD becomes chronic," says Dr. Vallance. "Specific nutrients such as sialic acid or other sugars might be Achilles heels for them in terms of things you could target to remove dangerous bacteria from the intestine."

Dr. Vallance and his team are now examining the role other sugars in the gut may play in feeding pathogenic bacteria. They're also looking for resident good bacteria (probiotics) that could out-compete the dangerous bacteria, stealing the sugars away from them.

They also plan to explore potential interactions between resident and pathogenic bacteria. Pathogenic bacteria can't access the sugars on their own and thus, some of the normally harmless resident bacteria must serve as accomplices.

"Basically, these accomplices cut the sugar off the mucus, and then either they hand it to the dangerous bacteria or the dangerous bacteria have come up with a way of stealing it from them," he explains.

A better understanding of these interactions could provide new ways to block pathogenic bacteria, something Dr. Vallance says is urgently needed.

"In the past, our ancestors were constantly assaulted by dangerous bacteria," says Dr. Vallance. "With the advent of more and more antibiotic resistance in bacteria, these bacterial infections are going to become a growing problem again. Without new antibiotics, we need to come up with novel ways to fight these bacteria, like starving them."

More information: Liang, Qiaochu et al, Sialic acid plays a pivotal role in licensing Citrobacter rodentium's transition from the intestinal lumen to a mucosal adherent niche, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2301115120. doi.org/10.1073/pnas.2301115120

https://medicalxpress.com/news/2023-07-pathogenic-bacteria-sugar-intestinal-mucus.html

'Long COVID not caused by COVID-19 immune inflammatory response: new research'

 Long COVID, which affects nearly two-million people in the UK, is not caused by an immune inflammatory reaction to COVID-19, University of Bristol-led research finds. Emerging data demonstrates that immune activation may persist for months after COVID-19.

In this new study, published in eLife, researchers wanted to find out whether persistent immune activation and ongoing inflammation response could be the underlying cause of long COVID.

To investigate this, the Bristol team collected and analyzed immune responses in blood samples from 63 patients hospitalized with mild, moderate or severe COVID-19 at the start of the pandemic and before vaccines were available.

The team then tested patients' immune responses at three months and again at eight and 12 months post hospital admission. Of these patients, 79% (82%, 75%, and 86% of mild, moderate, and severe patients, respectively) reported at least one ongoing symptom with breathlessness and excessive fatigue being the most common.

Dr. Laura Rivino, Senior Lecturer in Bristol's School of Cellular and Molecular Medicine and the study's lead author, explained, "Long COVID occurs in one out of 10 COVID-19 cases, but we still don't understand what causes it. Several theories proposed include whether it might be triggered by an inflammatory immune response towards the virus that is still persisting in our body, sending our immune system into overdrive or the reactivation of latent viruses such as human cytomegalovirus (CMV) and Epstein Barr virus (EBV)."

The team found patients' immune responses at three months with severe symptoms displayed significant dysfunction in their T-cell profiles indicating that inflammation may persist for months even after they have recovered from the virus. Reassuringly, results showed that even in severe cases inflammation in these patients resolved in time. At 12 months, both the immune profiles and inflammatory levels of patients with severe disease were similar to those of mild and moderate patients.

Patients with severe COVID-19 were found to display a higher number of long COVID symptoms compared to mild and moderate patients. However, further analysis by the team revealed no direct association between long COVID symptoms and immune inflammatory responses, for the markers that were measured, in any of the patients after adjusting for age, sex and disease severity.

Importantly, there was no rapid increase in immune cells targeting SARS-CoV-2 at three months, but T-cells targeting the persistent and dormant Cytomegalovirus (CMV)—a common virus that is usually harmless but can stay in your body for life once infected with it— did show an increase at low levels.

This indicates that the prolonged T-cell activation observed at three months in severe patients may not be driven by SARS-CoV-2 but instead may be "bystander driven" i.e. driven by cytokines.

Dr. Rivino added, "Our findings suggest that prolonged immune activation and long COVID may correlate independently with severe COVID-19. Larger studies should be conducted looking at both a larger number of patients, including if possible vaccinated and non-vaccinated COVID-19 patients, and measuring a larger range of markers and cytokines.

"Understanding whether inflammation and immune activation associate with long COVID would allow us to understand whether targeting these factors may be a useful therapy for this debilitating condition."

More information: Marianna Santopaolo et al, Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months, eLife (2023). DOI: 10.7554/eLife.85009

https://medicalxpress.com/news/2023-07-covid-covid-immune-inflammatory-response.html

'Unstructured 5-minute break can help restore attention'

 Researchers from University of Sydney set out to discover which common attention hacks really work. They found a 5-minute break from thinking is all you need to get your concentration back. There is no need for a walk along a river, or a lengthy video of bamboo forests swaying in the wind (although that could be nice). A five-minute total break will do the trick.

New research has found a simple, unstructured five-minute break from a complex task is all you need to get your concentration back or restore attention.

Rest is increasingly recognized as important for performance, well-being and learning. Whether it's a two-week holiday, one good night's sleep, a walk in a park for an hour, or a few minutes spent getting up from your desk for a coffee, rest breaks come in different shapes and sizes. In workplaces and study environments, methods such as the Pomodoro Technique—setting a timer to take a short five-minute break after 25 minutes of concentrated work—are gaining popularity as reminders to recharge.

Spending time in nature has been found to restore attention in a range of studies since the 1980s. But not many of us can pop out to do some "forest bathing" to take a break from essay writing or learning a new skill at work. Some studies suggest simply looking at a video of a natural scene offers the same restorative effect.

"If you want your work or study to be more productive, you need to build in simple five-minute breaks of doing nothing," said Associate Professor Paul Ginns, an expert in educational psychology at University of Sydney. "You need to be doing something different for five minutes. Move away from your computer or device, do some breathing or just sit quietly to rest your brain from the task. Scrolling through social media does not count as rest—you need to take a break from devices."

Associate Professor Ginns said we need to use our brain to create attention so we can learn or solve problems, but attention is finite and can be quickly depleted.

"Our attentions spans differ individually, and we can be influenced by the time of day or by blood sugar levels or caffeine intake, so it is complicated," he said. "But we wanted to test how we can restore attention and it's delightful that it can be as simple as a five-minute rest break. It's an easy productivity hack that is accessible to everyone."

How the study worked

In the study, published in Educational and Developmental Psychologist, 72 Australian university students first completed a difficult mental mathematics pre-test under speeded testing conditions, in order to exhaust students' attentional resources. This part of the experiment was designed to last around 20 minutes.

Students in the control (no rest) group then continued straight on to study a short lesson on how to mentally multiply two two-digit numbers (e.g., 34 x 67). The second group of students took a five-minute unstructured rest break, with a simple count-down on a computer screen showing how much of the break time was left.

The third group watched a first-person perspective video of a walk in an Australian rainforest for five minutes. The study called this "nature-based rest" even though it was simply watching a video.

All students then completed a "directed attention" short survey on the extent to which they experienced distracting thoughts during the mental mathematics lesson, responding to questions such as "My attention was directed towards things other than the lesson" and "I found it hard to maintain my concentration for more than a short time." Lastly, students completed a 20-question problem-solving test to see how well they could apply the mental mathematics strategy.

Comparing results across the three groups, students in the unstructured rest group reported higher average levels of directed attention than those in the no rest control group. On the problem-solving test, both the unstructured rest group and the nature-based rest group outperformed the control group.

While the nature-based rest group solved more problems on average than the unstructured rest group (60% vs. 53% correct), the difference between the two rest groups was not statistically significant.

Why rest helps learning

"Many skills—including cognitive skills like mathematics—take a lot of concentration to master, but our cognitive resources become depleted when we use our minds to solve problems or study," said Associate Professor Paul Ginns, the academic supervisor and co-author of the paper. "It may seem counter-intuitive to interrupt a study break to help learning, but short rest breaks—whether they're unstructured or watching 'virtual' nature videos—seem to be well-worth the time, helping students to concentrate better and learn more effectively. This could also be applied for workers learning a new skill or concentrating on a complex task."

What you can do to restore attention

Build in five-minute breaks after 20 minutes of complex cognitive work. This could be in classrooms or university settings. It could also be applied to a range of workplaces or at home doing complex cognitive tasks such as tax returns

"The Pomodoro Technique method—where people work for 25 minutes and then break for five minutes—is a popular life hack and we may have just found the first evidence for it working," said Associate Professor Ginns. "Other hacks, such as deep breathing or finding a sense of stillness are centuries old. Whatever you choose to do, offer your brain a total break for just five minutes and see how your attention improves."

More information: Paul Ginns et al, Rest breaks aid directed attention and learning, Educational and Developmental Psychologist (2023). DOI: 10.1080/20590776.2023.2225700

https://medicalxpress.com/news/2023-07-unstructured-minute-attention.html

'One night of total sleep deprivation shown to have antidepressant effect for some'

 A study led by the Perelman School of Medicine, University of Pennsylvania, Philadelphia, has investigated a seemingly contradictory phenomenon of sleep deprivation leading to mood improvement in patients with depressive disorders.

In a paper, "Enhanced amygdala–cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation," published in PNAS, the research team mapped brain region activity through resting-state-functional magnetic resonance imaging to see why some people receive a healthy boost from an otherwise negative public health epidemic.

The study finds that one night of total sleep deprivation enhanced amygdala connectivity to the anterior cingulate cortex, which correlated with better mood in some healthy and depressed individuals.

In sleep deprivation experiments conducted on both healthy individuals (n=38) and patients with major depressive disorder (n=30), along with 16 controls who were allowed uninterrupted sleep, researchers explored the effects of total sleep deprivation (TSD) on mood and functional connectivity networks.

The experiments were performed in the Clinical Translational Research Center laboratory at the University of Pennsylvania Hospital for five consecutive days. All participants underwent three rs-fMRI scanning sessions. A total of 210 fMRI images were acquired per participant.

Participants underwent three resting-state fMRI scanning sessions over the five days. The first scan came after a normal night's sleep on the morning of day two as the baseline. In the TSD groups, participants had their second scanning session on the morning of day three after no sleep.

Then participants were allowed two nights of restful sleep and had their final scanning session on the morning of day five. All participants completed a 37-item shortened version of the Profile of Mood States every two hours during days two to five.

As expected, most participants showed a worsening mood immediately after missing a night's sleep. Thirteen out of 30 (43%) depressed participants experienced mood improvement, and the remaining 17 participants experienced mood worsening or no change after one night of TSD.

After one night of restful sleep, 20 major depressive disorder participants experienced mood improvement, and the remaining participants experienced mood worsening or no change.

Amygdala to anterior cingulate cortex connectivity increased significantly in patients with improved mood but less in those with unimproved mood. The amygdala is the core of the fight or flight response, processing fearful or threatening stimuli and signaling other parts of the brain for a response action.

The anterior cingulate cortex (ACC) brain region is involved with both the "emotional" limbic system and the "cognitive" prefrontal cortex. Among other things, it plays a significant role in the ability to control and manage emotional states or affect regulation.

The findings suggest that amygdala–ACC network connectivity may reflect the neural resilience to mood disruption after sleep loss and thus may be a potential target for antidepressant interventions.

According to the researchers, one potential explanation for the individual differences in TSD influence may reside in the rapid eye movement (REM) sleep duration.

Major depression has previously been associated with abnormalities in REM sleep. Excess REM sleep would diminish noradrenaline, resulting in decreased binding to the ɑ-2 receptor in the medial frontal lobes comprised of the ACC and the medial prefrontal cortex. The absence of REM sleep with TSD may give some participants a break to improve top-down control of the amygdala, resulting in an antidepressant effect.

More information: Ya Chai et al, Enhanced amygdala–cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2214505120

https://medicalxpress.com/news/2023-07-night-total-deprivation-shown-antidepressant.html