Antibody injections could become more affordable with new production method

Antibody injections are a highly desirable treatment for people with chronic diseases such as cancer, psoriasis, Crohn’s disease and arthritis. And recently, antibodies have been in the news as a promising treatment for severe cases of COVID-19.
But the costly, time-consuming manufacturing process to produce antibodies prevents these treatments from being accessible to most patients.
Andrew Zydney, Bayard D. Kunkle Chair and professor of chemical engineering at Penn State, has identified a new method to manufacture antibodies, which could drive down the production cost. His research results were recently published in Biotechnology Progress.
“If you look at the top 10 best-selling medications, by annual sales, eight are in the category of monoclonal antibodies,” Zydney said. “And every year, individuals and insurance companies spend upwards of $100 billion on antibodies, with costs to treat a single patient often exceeding $50,000. There remains a huge unmet need for these products in treating a growing range of diseases.”
Known as precipitation, Zydney’s new protein purification process involves adding zinc chloride and polyethylene glycol, a water-soluble polymer, to a solution containing the antibody. This causes the antibody to precipitate so that the impurities can be washed away.
Though the precipitation process has been used for 70 years in blood plasma processing, it has never been used for the commercial production of antibodies, according to Zydney.

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Coronavirus: Third wave will 'wash up on our shores', warns Johnson

SharecloseShare pageCopy linkAbout sharingBoris Johnson has warned the effects of a third wave of coronavirus will “wash up on our shores” from Europe.The PM said the UK should be “under no illusion” we will “feel effects” of growing cases on the continent. One of his ministers, Lord Bethell, also warned the UK might put “all our European neighbours” on the red list of countries, where arrivals are either banned or put in quarantine hotels. The comments come amid a row over Covid-19 vaccine supplies in the EU.The president of the European Commission, Ursula von der Leyen has warned the EU could “forbid” doses made in the bloc from being exported to the UK.EU leaders will hold a virtual meeting on Thursday to discuss their plans. Officials confirmed the PM spoke to German Chancellor Angela Merkel and French President Emmanuel Macron on Sunday about the ongoing issue, which would affect exports of the Oxford-AstraZeneca vaccine made in Europe. Mr Johnson said he “talked to EU friends repeatedly” during the pandemic and had been “reassured… over the last few month they don’t want to see blockades”.Downing Street also said President von der Leyen, had told Mr Johnson earlier this year that the EU was not intending to restrict exports of vaccines.PM hails record-breaking day with 844,285 jabsEU should not ‘build walls’ around vaccinesWhy is the EU having vaccine problems?EU legislation allows measures to be taken “if severe difficulties arise in the supply of certain products” – which, in theory, could include export bans and the waiving of patent and intellectual property rights on vaccines.But earlier, Mrs von der Leyen’s chief spokesman, Eric Mamer, insisted that Brussels was not seeking to ban vaccine exports, but wanted pharmaceutical firms to meet their contractual obligations to the bloc.Mr Mamer said: “In that context, the president has said that, of course, we see that, actually, companies that manufacture doses in the EU have been exporting very widely – which is in itself a good thing – but that we want to see reciprocity and proportionality in these exports.”image copyrightReutersAsked if he was worried about the row, Mr Johnson told reporters: “I am reassured by talking to EU partners over the last few months that they don’t want to see blockades.”But he went on to issue a warning about what the growing infections in Europe could mean for the UK.The PM said: “On the continent right now you can see, sadly, there is a third wave under way.”And people in this country should be under no illusions that previous experience has taught us that when a wave hits our friends, I’m afraid it washes up on our shores as well.”He added: “I expect we will feel those effects in due course. That’s why we’re getting on with our vaccination programme as fast as we can.”Later, Health Minister Lord Bethell warned how the rising cases and issues with vaccines could affect travel to European countries going forward. He told the House of Lords: “I don’t know how that will play out and it’s certainly above my pay grade to speculate, but we are all aware that the possibility lies that will have to red list all of our European neighbours – but that would be done with huge regret.” On Monday, the UK reported 17 deaths over the last 24 hours of people who had tested positive for Covid-19 in the past 28 days. A further 5,342 cases were also confirmed, while another 367,006 people received their first vaccination – along with 52,612 who got their second jab. Meanwhile, the long-awaited results of the US trial of the Oxford-AstraZeneca vaccine, which involved more than 32,000 volunteers, show that the jab is safe and highly effective.Several European leaders paused rollout of the vaccine amid concerns of a possible link with blood clots. UK and EU regulators said there was no evidence the vaccine causes blood clots.European leaders have faced criticism for the slow pace of the vaccine rollout on the continent.Less than 12% of the EU’s population is reported to have received the vaccine, compared with nearly 40% in the UK – although the bloc has 446 million citizens, compared to almost 67 million in the UK.The EU has encountered production problems with the Pfizer-BioNTech, Moderna and Oxford-AstraZeneca vaccines.British-Swedish manufacturer AstraZeneca said the fact that EU contracts were signed later than with the UK caused problems with supplying their vaccine.Downing Street has previously said that it does not believe that vaccine supply issues will affect the current road map for easing lockdown restrictions.Irish Taoiseach Michael Martin said it is vital that supply chains were kept open, telling RTE: “Once you start putting up the barriers, other people start putting up barriers globally and it could lead to everybody losing. We’d all lose in that situation.”Labour leader Sir Keir Starmer also said the UK government was right to say that contractual obligations need to be honoured, telling LBC that the EU was not “helping itself”.The Guardian says a report by data analysts Airfinity suggests that if an export ban was applied to all vaccines – including those from Moderna and Johnson & Johnson that have yet to be deployed in the UK – it would see the offer of a first vaccine to every adult completed in late August rather than the target date of 31 July.But Mr Johnson said the UK had already vaccinated over half of the adults in the country, adding: “We’ll just bash on with the road map we’ve set out.” The prospect of a third coronavirus wave won’t engulf anyone with joy. So why did Boris Johnson highlight this danger today?Privately and publicly ministers are making it clear that they don’t want to delay the dates in England’s roadmap out of lockdown.There will be a vote in Parliament on coronavirus restrictions later this week. So by stressing the risk that the virus still poses, the PM may be hoping to convince restless backbenchers that he can’t go any quicker. He may also be trying to persuade vaccinated people with itchy feet that booking spring or summer holidays would still be premature.He is preparing us, too, for the strong possibility that cases could rise in the coming weeks – not just because of “incoming” risks, but because rules here are being slowly relaxed.But by stressing the shared threat from the coronavirus – i.e. the sooner the EU population is vaccinated, the less chance of importing a third wave – his comments could be also be clearing the way for more UK/EU vaccine co-operation, and the dousing down of an inflammatory row with Brussels.The latest point of contention between the UK and the EU appears to be over vaccine doses being manufactured at a plant in the Netherlands.An EU official told Reuters news agency that those doses should be distributed among member states, and not sent to Britain.SUPPORT BUBBLES: What are they and who can be in yours?FACE MASKS: When do I need to wear one?SCHOOLS: What will happen if children catch coronavirus?TESTING: What tests are available?JOBS: How will I be kept safe at work?”I WAS SO SICK, IN SO MUCH PAIN”: Understanding endometriosisYOUR QUESTIONS ANSWERED: Covid vaccine trials for children

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Refining the hunt for SARS-CoV-2 in wastewater

There are many ways to test municipal wastewater for signs of the virus that causes COVID-19, but scientists in Houston have determined theirs is the best yet.
A study led by environmental engineer Lauren Stadler of Rice University’s Brown School of Engineering with the aid of the City of Houston Health Department and Baylor College of Medicine compared five processes used by labs around the country to concentrate samples and find the virus in wastewater from six Houston plants.
The process employed at Rice and now Baylor, called “electronegative filtration with bead beating,” proved the most sensitive to signs of the virus as well as the most cost-effective.
The study appears in the Elsevier journal Water Research.
There is no standard test, according to the study, but all of the processes — including electronegative filtration with elution, ultrafiltration, precipitation and direct extraction — are effective to a degree.
“The virus is extremely dilute in wastewater, so we need a way to concentrate it,” Stadler said in explaining the Rice process. “First, we add salt to the wastewater sample to enhance adsorption of the virus to the electronegative filter. After filtration, we physically beat the filter with glass beads to release the virus into a lysate. Even though this process might break up the virus, we only detect tiny fragments of its RNA genome to quantify it.”
Established in spring 2020, the Houston coalition was on the leading edge of what became a nationwide effort to find the SARS-CoV-2 virus in wastewater. The technique quickly proved able to anticipate COVID-19 outbreaks and allowed health officials to ramp up testing where needed.

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Image analysis based on machine learning reliably identifies haematological malignancies

Myelodysplastic syndrome (MDS) is a disease of the stem cells in the bone marrow, which disturbs the maturing and differentiation of blood cells. Annually, some 200 Finns are diagnosed with MDS, which can develop into acute leukemia. Globally, the incidence of MDS is 4 cases per 100,000 person years.
To diagnose MDS, a bone marrow sample is needed to also investigate genetic changes in bone marrow cells. The syndrome is classified into groups to determine the nature of the disorder in more detail.
In the study conducted at the University of Helsinki, microscopic images of MDS patients’ bone marrow samples were examined utilising an image analysis technique based on machine learning. The samples were stained with haematoxylin and eosin (H&E staining), a procedure that is part of the routine diagnostics for the disease. The slides were digitised and analysed with the help of computational deep learning models.
The study was published in the Blood Cancer Discovery, a journal of the American Association for Cancer Research, and the results can also be explored with an interactive tool: http://hruh-20.it.helsinki.fi/mds_visualization/.
By employing machine learning, the digital image dataset could be analysed to accurately identify the most common genetic mutations affecting the progression of the syndrome, such as acquired mutations and chromosomal aberrations. The higher the number of aberrant cells in the samples, the higher the reliability of the results generated by the prognostic models.
Diagnosis supported by data analysis
One of the greatest challenges of utilising neural network models is understanding the criteria on which they base their conclusions drawn from data, such as information contained in images. The recently released study succeeded in determining what deep learning models see in tissue samples when they have been taught to look for, for example, genetic mutations related to MDS. The technique provides new information on the effects of complex diseases on bone marrow cells and the surrounding tissues.
“The study confirms that computational analysis helps to identify features that elude the human eye. Moreover, data analysis helps to collect quantitative data on cellular changes and their relevance to the patient’s prognosis,” says Professor Satu Mustjoki.
Part of the analytics carried out in the study was implemented using the Helsinki University Hospital (HUS) data lake environment, which enables the efficient collection and analysis of extensive clinical datasets.
“We’ve developed solutions to structure and analyse data stored in the HUS data lake. Image analysis helps us analyse large quantities of biopsies and rapidly produce diverse information on disease progression. The techniques developed in the project are suited to other projects as well, and they are perfect examples of the digitalizing medical science,” says doctoral student Oscar Bruck.
“[This] study provides new insights into the pathobiology of MDS and paves the way for increased use of artificial intelligence for the assessment and diagnosis of hematological malignancies,” says PhD Olivier Elemento from the Caryl and Israel Englander Institute for Precision Medicine in his commentary to the article in Blood Cancer Discovery, a journal of the American Association for Cancer Research.
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Materials provided by University of Helsinki. Original written by Anu Koivusipilä. Note: Content may be edited for style and length.

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Predicting who may do best with psychedelic-assisted therapy

As psychedelics gain ground as a potential therapy for mental health disorders, there remains a pressing concern that patients in clinical trials may have adverse effects to the drugs.
New research identifies personality traits that have been associated with positive and negative experiences on psychedelics in previous studies, information that could help predict how future clinical trial participants will respond to the drugs.
The findings suggest that people more open to new experiences and willing to surrender to the unknown may be best positioned to have a positive experience on psychedelics, and individuals who tend to be preoccupied or apprehensive could be more likely to have a negative, or challenging, experience.
These predictions could be used by scientists to help hesitant clinical trial patients feel more open to the potential therapy, possibly by offering lower doses as a starting point, researchers say — though such a concept remains speculative.
“The findings point to interesting testable things we can look at in future research,” said Alan Davis, assistant professor of social work at The Ohio State University and senior author of the review. “It might be plausible to use threshold doses that are smaller than those used in a trial as a first exposure so people have less anxiety, experience the benefit and, from that, go into a higher dose later.”
The study is published online in the journal ACS Pharmacology & Translational Science.

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Widening political rift in U.S. may threaten science, medicine

The lightning speed with which scientists developed and tested the COVID-19 vaccine is a true scientific triumph — one that would not have been possible without the more than 70,000 volunteers who participated in clinical trials of the vaccine.
Public participation is critical to the success of any medical research. Yet recruiting volunteers for trials is increasingly challenging. New research from Washington University in St. Louis suggests the widening ideological gap in the U.S. may contribute to these challenges.
Researchers found evidence that Americans approach opportunities to contribute to medical research with either a general aversion or an inclination to participate. This research concludes that propensity is driven, at least in part, by political ideology.
While much attention has been given to Black people’s distrust in the medical system and research in particular, the current study — published in Scientific Reports — is the first to demonstrate the effect of political ideology on willingness to trust science and participate in medical research.
“Our research shows that conservatives are less willing to participate in medical research than are liberals. This difference is due, in part, to ideological differences in trust in science,” said Matthew Gabel, professor of political science in Arts & Sciences.
There are potential consequences to this divide.

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Heritable traits that appear in teen years raise risk for adult cannabis use

While some youth experiment with marijuana but don’t go on to long-term use, others develop a problematic pot habit that continues into adulthood. A major new analysis shows that at least a small portion of the risk for developing into an adult marijuana user may be related to inherited behaviors and traits that appear during adolescence.
The journal Addiction published the findings by researchers at Brown University and Emory University.
“Our analysis suggests that some early adolescent behaviors and traits — like depression, neuroticism and acting out — can be indicative for cannabis use later in life,” says Rohan Palmer, senior author of the paper and assistant professor in Emory’s Department of Psychology, where he heads the Behavioral Genetics of Addiction Laboratory.
“Decades of research has shown that behaviors can have a genetic component,” adds Leslie Brick, lead author and assistant professor in the Department of Psychiatry and Human Behavior in Brown’s Alpert Medical School. “And while there is not one genetically-influenced trait that determines whether you’re going to be a long-term cannabis user, our paper indicates that there are polygenic effects across multiple inherited behaviors and traits that show a propensity for increased risk.”
Brick, a long-time collaborator with Rohan, also holds an adjunct faculty appointment in Emory’s Department of Psychology.
The Transmissible Liability Index is a well-known measure for a constellation of heritable traits that may appear during the developmental years that are associated with the risk of a substance use disorder. For the current paper, the researchers wanted to tease out which of these heritable characteristics might be associated with repeated marijuana use later in life.

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COVID-19 pandemic severely impacts mental health of young people

The Covid-19 pandemic severely impacted the mental health of young people, with increased levels of clinical depression being identified, a new study published in the journal Psychiatry Research reports. A decrease in alcohol consumption was also identified amongst young people during the pandemic.
During this unique study researchers from the University of Surrey surveyed 259 young people pre- pandemic (autumn 2019) and in the midst of initial lockdown measures (May/June 2020) on their levels of depression, anxiety, wellbeing, alcohol use and sleep quality.
Researchers found evidence of a substantial impact on the mental health of these young adults due to the Covid-19 pandemic, with a significant rise in depression symptoms and a reduction in overall wellbeing during lockdown compared to the previous autumn. Levels of clinical depression in those surveyed were found to have more than doubled, rising from 14.9 per cent in autumn 2019 to 34.7 per cent in May/June 2020.
Sleep quality was not seen to decline in the overall sample but, importantly, a correlation was seen between the rise in depression and lower sleep quality under lockdown. Also of concern, researchers identified a significant shift towards ‘eveningness’ (a preference to go to sleep and wake later), which has previously been associated with higher levels of anxiety and a greater prevalence of minor psychiatric disorders.
Interestingly, despite reports of rising worldwide sales of alcohol during the first lockdown, researchers identified a significant decrease in alcohol consumption amongst the group that could be attributed to social restrictions in place during this period. Researchers were encouraged by this finding as it suggests that young people were not using alcohol as a coping strategy during that time.
Findings from this study highlight the substantial impact of the Covid-19 pandemic on young people’s mental health. The link to sleep quality could help inform strategies to support their wellbeing as the Covid-19 situation continues to evolve.
Dr Simon Evans, Lecturer in Neuroscience at the University of Surrey, said: “For many years there has been a rise in the number of young people experiencing problems with their mental health, and it is concerning to find that this has been significantly exacerbated due to Covid-19. Supporting the mental health of young people and ensuring they can access the support they need is vital to ensure their overall wellbeing. As social restrictions continue in response to the pandemic, it is crucial that we take steps to protect their mental health.”
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Materials provided by University of Surrey. Original written by Natasha Meredith. Note: Content may be edited for style and length.

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Cells burn more calories after just one bout of moderate aerobic exercise, OSU study finds

In a recent study testing the effects of exercise on overall metabolism, researchers at Oregon State University found that even a single session of moderate aerobic exercise makes a difference in the cells of otherwise sedentary people.
Mitochondria are the part of the cell responsible for the biological process of respiration, which turns fuels such as sugars and fats into energy, so the researchers focused only on mitochondria function.
“What we found is that, regardless of what fuel the mitochondria were using, there were mild increases in the ability to burn off the fuels,” said Matt Robinson, lead author on the study and an assistant professor in the College of Public Health and Human Sciences.
OSU researchers recruited participants who do not follow a regular exercise routine and had them ride a stationary bike for an hour at a moderate intensity. They biopsied their muscles 15 minutes later to test how efficient the mitochondria were after the exercise was completed and compared those results with a resting day.
Post-exercise, study participants’ mitochondria burned 12-13% more fat-based fuel and 14-17% more sugar-based fuel. While the effects were not drastic, they were consistent, Robinson said.
“It’s pretty remarkable that even after just one hour of exercise, these people were able to burn off a little more fuel,” he said.

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Bacteria may aid anti-cancer immune response

Cancer immunotherapy may get a boost from an unexpected direction: bacteria residing within tumor cells. In a new study published in Nature, researchers at the Weizmann Institute of Science and their collaborators have discovered that the immune system “sees” these bacteria and shown they can be harnessed to provoke an immune reaction against the tumor. The study may also help clarify the connection between immunotherapy and the gut microbiome, explaining the findings of previous research that the microbiome affects the success of immunotherapy.
Immunotherapy treatments of the past decade or so have dramatically improved recovery rates from certain cancers, particularly malignant melanoma; but in melanoma, they still work in only about 40% of the cases. Prof. Yardena Samuels of Weizmann’s Molecular Cell Biology Department studies molecular “signposts” — protein fragments, or peptides, on the cell surface — that mark cancer cells as foreign and may therefore serve as potential added targets for immunotherapy. In the new study, she and colleagues extended their search for new cancer signposts to those bacteria known to colonize tumors.
Using methods developed by departmental colleague Dr. Ravid Straussman, who was one of the first to reveal the nature of the bacterial “guests” in cancer cells, Samuels and her team, led by Dr. Shelly Kalaora and Adi Nagler (joint co-first authors), analyzed tissue samples from 17 metastatic melanoma tumors derived from nine patients. They obtained bacterial genomic profiles of these tumors and then applied an approach known as HLA-peptidomics to identify tumor peptides that can be recognized by the immune system.
The research was conducted in collaboration with Dr. Jennifer A. Wargo of the University of Texas MD Anderson Cancer Center, Houston, Texas; Prof Scott N. Peterson of Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; Prof Eytan Ruppin of the National Cancer Institute, USA; Prof Arie Admon of the Technion — Israel Institute of Technology and other scientists.
The HLA peptidomics analysis revealed nearly 300 peptides from 41 different bacteria on the surface of the melanoma cells. The crucial new finding was that the peptides were displayed on the cancer cell surfaces by HLA protein complexes — complexes that are present on the membranes of all cells in our body and play a role in regulating the immune response. One of the HLA’s jobs is to sound an alarm about anything that’s foreign by “presenting” foreign peptides to the immune system so that immune T cells can “see” them. “Using HLA peptidomics, we were able to reveal the HLA-presented peptides of the tumor in an unbiased manner,” Kalaora says. “This method has already enabled us in the past to identify tumor antigens that have shown promising results in clinical trials.”
It’s unclear why cancer cells should perform a seemingly suicidal act of this sort: presenting bacterial peptides to the immune system, which can respond by destroying these cells. But whatever the reason, the fact that malignant cells do display these peptides in such a manner reveals an entirely new type of interaction between the immune system and the tumor.
This revelation supplies a potential explanation for how the gut microbiome affects immunotherapy. Some of the bacteria the team identified were known gut microbes. The presentation of the bacterial peptides on the surface of tumor cells is likely to play a role in the immune response, and future studies may establish which bacterial peptides enhance that immune response, enabling physicians to predict the success of immunotherapy and to tailor a personalized treatment accordingly.
Moreover, the fact that bacterial peptides on tumor cells are visible to the immune system can be exploited for enhancing immunotherapy. “Many of these peptides were shared by different metastases from the same patient or by tumors from different patients, which suggests that they have a therapeutic potential and a potent ability to produce immune activation,” Nagler says.
In a series of continuing experiments, Samuels and colleagues incubated T cells from melanoma patients in a laboratory dish together with bacterial peptides derived from tumor cells of the same patient. The result: T cells were activated specifically toward the bacterial peptides.
“Our findings suggest that bacterial peptides presented on tumor cells can serve as potential targets for immunotherapy,” Samuels said. “They may be exploited to help immune T cells recognize the tumor with greater precision, so that these cells can mount a better attack against the cancer. This approach can in the future be used in combination with existing immunotherapy drugs.”
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Materials provided by Weizmann Institute of Science. Note: Content may be edited for style and length.

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