Publisher Health

Researchers at the University of Turku, Finland, showed that the antibody treatment reactivates the immune defense in patients with advanced-stage cancer. The treatment alters the function of the body’s phagocytes and facilitates extensive activation of the immune system.
The immune defense is the body’s own defense system equipped to combat cancer. However, cancer learns to hide from immune attacks and harnesses this system to promote its own growth. Therefore, it would be beneficial to be able to return the immune defense back to restricting the advancement of cancer.
Macrophages, a type of white blood cell, are central in the fight against cancer. Cancer educates macrophages to subdue the defense system and renders many treatments targeting the immune system ineffective.
Academy Research Fellow Maija Hollmén’s research group has searched for means of altering the activity of macrophages in order to direct the immune defense to attack cancer. The antibody bexmarilimab, developed based on this research and in collaboration with Faron Pharmaceuticals, is currently undergoing clinical trials in patients. Hollmén’s group has studied the changes occurring in the defense systems of patients with cancer following antibody treatment.
“In the majority of patients, the antibody treatment activated killer T cells, which are the body’s strike force against cancer. Additionally, the antibody treatment successfully lowered the suppressive potential of macrophage precursors travelling in the blood circulation. The patients also showed increases in certain mediators of inflammation and types of white blood cell in the blood,” describes Hollmén.
“The activation of the killer T cells is a very promising demonstration of the antibody’s capability to boost the defense system against cancer. The treated patients had very advanced and poorly treatable cancers, which highlights the significance of the results,” says Doctoral Candidate Jenna Rannikko.

Airway mucus consists of various proteins such as long mucins MUC5AC and MUC5B, both of which contribute greatly to the proper gel-like consistency of this most essential bodily fluid. UNC School of Medicine researchers led by mucin expert Mehmet Kesimer, PhD, had previously discovered that the total mucin concentrations in the lungs are associated with COPD disease progression and could be used as diagnostic markers of chronic bronchitis, a hallmark condition for patients with COPD. Kesimer and colleagues now report that one of these mucins, MUC5AC, is more closely and reliably associated with the development of COPD than is its brother, MUC5B.
The research, published in The Lancet Respiratory Medicine, shows that MUC5AC is found at elevated levels in smokers who had not yet developed COPD but whose lung function wound up decreasing over the course of the three-year study. Former smokers at-risk for COPD, on the other hand, had normal levels of MUC5AC at the start of the study and maintained proper lung function over three years. MUC5AC hyperconcentration in the lungs may be a key factor in predicting the risks and rates of progression to more severe disease, according to the study.
Recent nationwide efforts have focused on early- or pre-COPD to predict the risks of progression to COPD amongst smokers.
“Currently, we cannot forecast which individuals in the at-risk smokers group will progress to COPD because we don’t have an objective biological marker to underpin the disease-causing pathways. Our research shows that MUC5AC could be a predictor of who will develop COPD from the large group of aging “at-risk” smokers,” said Kesimer, senior author of the study, professor in the UNC Department of Pathology and Laboratory Medicine, and member of the UNC Marsico Lung Institute. “We think MUC5AC could be a new biomarker for COPD prognosis and it could be a biomarker for testing the effectiveness of therapeutic strategies.”
MUC5AC could also become a target for pharmaceutical developers whose goal it is to halt COPD disease progression and help patients live more normal, active lives.
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease that causes obstructed airflow from the lungs and affects about 16 million people in the United States. Symptoms include breathing difficulty, coughing, mucus production, and wheezing. It’s typically caused by long-term exposure to irritants, such as particulate matter like cigarette smoke. The two main conditions that contribute to COPD are chronic bronchitis, an inflammation of the lining of the bronchial tubes due to chronic mucin/mucus accumulation; and emphysema, when the tiny air sacs at the end of the smallest air passages of the lungs are destroyed.
There are some treatment options for COPD to attempt to slow disease progression and reduce symptoms, but treatments often don’t work well, especially during late stages of the condition, and there is no cure.
The Kesimer Lab in the UNC Marsico Lung Institute uses various techniques, including mass spectrometry, to identify and measure the different biological mechanisms involved in lung conditions. For this study, the UNC team of scientists were able to measure the concentrations of MUC5AC and MUC5B in different groups of people, including people who had never smoked cigarettes, who had quit smoking, and who continue to smoke with or without COPD.
Smoking cigarettes has long been known to be a major risk factor for COPD, but Kesimer’s work suggests that quiting smoking decreases the odds of developing COPD as we age.
“Our data indicate that increased MUC5AC concentrations in the airways may contribute to the initiation of COPD, as well as disease progression, symptom exacerbation, and how the disease progesses over time, in general,”Kesimer said. “We did not observe the same association with MUC5B.”
The best thing an aging person can do to avoid the inevitable decline associated COPD is quit smoking immediately before airway obstruction sets in due to mucin/mucus accumulation. Through Kesimer’s work, though, it might be possible to pinpoint which individuals are at the highest immediate risk for developing COPD soon.

Building on their previous findings, scientists from the Immuno-Pharmacology and Interactomics group at the Department of Infection and Immunity of the Luxembourg Institute of Health (LIH), in collaboration with the Center for Drug Discovery at RTI International (RTI), a nonprofit research institute, have demonstrated that conolidine, a natural painkiller derived from the pinwheel flower and traditionally used in Chinese medicine, interacts with the newly identified opioid receptor ACKR3/CXCR7 that regulates opioid peptides naturally produced in the brain. The researchers also developed a synthetic analogue of conolidine, RTI-5152-12, which displays an even greater activity on the receptor. These findings, which were published on June 3rd in the international journal Signal Transduction and Targeted Therapy (Nature publishing group), further advance the understanding of pain regulation and open alternative therapeutic avenues for the treatment of chronic pain.
Opioid peptides are small proteins that mediate pain relief and emotions, including euphoria, anxiety, stress and depression, by interacting with four classical receptors (“molecular switches”) in the brain. Dr Andy Chevigné, Head of Immuno-Pharmacology and Interactomics, and his team had previously identified the chemokine receptor ACKR3 as a novel fifth atypical opioid receptor, with high affinity for various natural opioids (Nature Communications, Meyrath et al. 2020). ACKR3 functions as a ‘scavenger’ that ‘traps’ the secreted opioids and prevents them from binding to the classical receptors, thereby dampening their analgesic activity and acting as a regulator of the opioid system.
In the current study, the researchers identified ACKR3 as the most responsive target for conolidine, an alkaloid with analgesic properties, by screening over 240 receptors for their ability to be activated or inhibited by this molecule.
“We confirmed that conolidine binds to the newly identified opioid receptor ACKR3, while showing no affinity for the other four classical opioid receptors. By doing so, conolidine blocks ACKR3 and prevents it from trapping the naturally secreted opioids, which in turn increases their availability for interacting with classical receptors. We believe that this molecular mechanism is at the basis of the beneficial effects of this traditionally used medicine on pain relief,” said Dr Martyna Szpakowska, first author of the publication and scientist within the LIH Immuno-Pharmacology and Interactomics group.
In parallel to characterising the interaction between conolidine and ACKR3, the two teams went a step further. The scientists developed a modified variant of conolidine — which they called “RTI-5152-12” — which exclusively binds to ACKR3 with an even higher affinity. Like LIH383, a patented compound previously developed by Dr. Andy Chevigné and his team, RTI-5152-12 is postulated to increase the levels of opioid peptides that bind to classical opioid receptors in the brain, resulting in heightened painkilling activity. The LIH-RTI research teams established a collaboration agreement and filed a joint patent application in December 2020.
“The discovery of ACKR3 as a target of conolidine further emphasises the role of this newly discovered receptor in modulating the opioid system and, consequently, in regulating our perception of pain,” said Dr. Chevigné, corresponding author of the publication and leader of the LIH Immuno-Pharmacology and Interactomics group.
“Our findings could also mean that conolidine, and potentially also its synthetic analogues, could carry new hope for the treatment of chronic pain and depression, particularly given the fact that conolidine was reported to trigger fewer of the detrimental side-effects — namely addiction, tolerance and respiratory problems — associated with commonly used opioid drugs like morphine and fentanyl.”
“Our work could therefore set the basis for the development of a new class of drugs with alternative mechanism of action, thereby contributing to tackling the public health crisis linked to the increasing misuse of and addiction to opioid drugs,” says Dr. Ojas Namjoshi, co-corresponding author of the publication and lead scientist on the study at RTI.
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A nasal therapy, built upon on the application of a new engineered IgM antibody therapy for COVID-19, was more effective than commonly used IgG antibodies at neutralizing the COVID-19 virus in animal models, according to research recently published by The University of Texas Health Science Center at Houston (UTHealth), The University of Texas Medical Branch at Galveston (UTMB Health), the University of Houston, and IGM Biosciences, Inc.
The study was published today in Nature.
Researchers engineered IgM antibodies and found that in all cases, these antibodies were significantly more potent than standard IgG antibodies in neutralizing the COVID-19 virus. One of the engineered IgM antibodies, IGM-6268, demonstrated a significantly increased potency against the original SARS-CoV-2 and emerging variants such as the current U.K., South African, and Brazilian variants of concern (VOC) and variants of interest (VOI), as well as the antibody escape mutants for the current Emergency Use Authorization antibodies. Additionally, IGM-6268 was shown to be highly effective for prophylaxis and treatment in mouse models when administered intranasally.
“High viral load in the respiratory tract correlates with severe illness and mortality in patients with COVID-19,” said Zhiqiang An, PhD, director of UTHealth Texas Therapeutics Institute, professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School at UTHealth, and faculty member at MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences and one of the corresponding authors on the study. “Respiratory mucosal antibodies are key to clearing SARS-CoV-2 infection and reducing viral transmission and IgM antibodies are nature’s first line of defense against pathogens such as viruses.”
The current government-approved antibodies, which are all IgG antibodies, are administered intravenously at high doses and don’t directly target the main sites of viral infection.
“SARS-CoV-2 has evolved mutations that severely compromise the neutralizing activities of multiple IgG monoclonal antibodies, including those under clinical trials and authorized for emergency use. Therefore, developing new antibody therapies that can overcome these challenges is an urgent unmet need, and we are pleased with the data published today,” An said.
“Synergizing the strengths of multiple institutions from academia and industry is the key to the rapid translation from ideas to therapeutic candidates. This is another example of such success. The cross-institutional and academic-industry collaborations should be expanded to other disease indications,” said Pei-Yong Shi, PhD, professor and co-senior author of the study from the Department of Biochemistry and Molecular Biology at UTMB Health.
This antibody has been licensed to biotech partner IGM Biosciences for drug development.
“The ability to use potently neutralizing IgM antibodies against SARS-CoV-2 with broad coverage of VOCs, VOIs, and viral escape mutants, is a very exciting application of the IGM platform,” said Fred Schwarzer, CEO of IGM Biosciences. “We are grateful to our collaborators at UTHealth, UTMB Health, and our scientists at IGM for the exceptional work described in Nature today.”
Additional UTHealth authors: Zhiqiang Ku, PhD; Xiaohua Ye, PhD; Wei Xiong, MD, PhD; Junquan Liu, PhD; Ningyan Zhang, PhD; Hang Su, and Hui Deng.
Other authors include Xuping Xie, PhD; Antonio E. Muruato, PhD; Jing Zou, PhD; Yang Liu, PhD; and Vineet D. Menachery, PhD, with UTMB Health; Xinli Liu, PhD; and Sujit Biswas with the University of Houston; and Paul R. Hinton; Dean C. Ng, PhD; Yu-An Cao, PhD; Kevin B. Carlin, PhD; Elizabeth J. Haanes, PhD; Bruce A. Keyt, PhD; Stephen F. Carroll, PhD; Deepal Pandya, and Sachi Rahman with IGM Biosciences.
The work was supported by grants from the Cancer Prevention and Research Institute of Texas, the National Institutes of Health, the Welch Foundation, the Sealy Smith Foundation, the Kleberg Foundation, the John S. Dunn Foundation, the Amon G. Carter Foundation, the Gillson Longenbaugh Foundation, and the Summerfield Robert Foundation.

Researchers at ETH Zurich are developing a new filter membrane that is highly efficient at filtering and inactivating a wide variety of air-​borne and water-​borne viruses. Made from ecologically sound materials, the membrane has an appropriately good environmental footprint.
Viruses can spread not only via droplets or aerosols like the new coronavirus, but in water, too. In fact, some potentially dangerous pathogens of gastrointestinal diseases are water-borne viruses.
To date, such viruses have been removed from water using nanofiltration or reverse osmosis, but at high cost and severe impact on the environment. For example, nanofilters for viruses are made of petroleum-based raw materials, while reverse osmosis requires a relatively large amount of energy.
Environmentally friendly membrane developed
Now an international team of researchers led by Raffaele Mezzenga, Professor of Food & Soft Materials at ETH Zurich, has developed a new water filter membrane that is both highly effective and environmentally friendly. To manufacture it, the researchers used natural raw materials.
The filter membrane works on the same principle that Mezzenga and his colleagues developed for removing heavy or precious metals from water. They create the membrane using denatured whey proteins that assemble into minute filaments called amyloid fibrils. In this instance, the researchers have combined this fibril scaffold with nanoparticles of iron hydroxide (Fe-O-HO).

A Cleveland Clinic study shows that survivors of COVID-19 who have moderate or severe obesity may have a greater risk of experiencing long-term consequences of the disease, compared with patients who do not have obesity. The study was recently published online in the journal of Diabetes, Obesity and Metabolism.
Multiple studies have identified obesity as a risk factor for developing a severe form of COVID-19 that may require hospital admission, intensive care, and ventilator support in the early phase of the disease. Obesity, which is a complex disease caused by multiple factors, is associated with an increased risk for cardiovascular disease, blood clots and lung conditions. In addition, obesity weakens the immune system and creates a chronic inflammatory state. Those conditions can lead to poor outcomes after an infection with SARS-CoV-2, which is the virus that causes COVID-19.
“To our knowledge, this current study for the first time suggests that patients with moderate to severe obesity are at a greater risk of developing long-term complications of COVID-19 beyond the acute phase,” said Ali Aminian, M.D., director of Cleveland Clinic’s Bariatric & Metabolic Institute and principal investigator of the research.
In this observational study, researchers used a registry of patients who tested positive for SARS-CoV-2 infection within the Cleveland Clinic health system in a five-month period from March 2020 to July 2020, with follow-up until January 2021.
Researchers examined three indicators of possible long-term complications of COVID-19 — hospital admission, mortality, and need for diagnostic medical tests — that occurred 30 days or later following the first positive viral test for SARS-CoV-2. The outcomes were compared among five groups of patients based on their body mass index (BMI): 18.5-24.9 (normal), 25-29.9 (overweight), 30-34.9 (mild obesity), 35-39.9 (moderate obesity), and 40 or greater (severe obesity). Obesity is a disease classified as having a BMI of 30 or greater.
A total of 2,839 patients who did not require ICU admission and survived the acute phase of COVID-19 were included in the final results of this study. The normal BMI group was considered as a reference.
The study found that a health condition called post-acute sequelae of SARS-CoV-2 infection (PASC) is an extremely common problem in COVID-19 survivors. Specifically, during a 10-month follow-up after the acute phase of COVID-19, 44% of the study participants had required hospital admission and 1% died. Furthermore, results show that compared with patients with normal BMI, the risk of hospital admission was 28% and 30% higher in patients with moderate and severe obesity, respectively. The need for diagnostic tests to assess different medical problems, compared with patients with normal BMI, was 25% and 39% higher in patients with moderate and severe obesity, respectively.
More specifically, the need for diagnostic tests to assess cardiac, pulmonary, vascular, renal, gastrointestinal, and mental health problems was significantly higher in patients with a BMI of 35 or greater, compared with normal BMI patients.
“The observations of this study can possibly be explained by the underlying mechanisms at work in patients who have obesity, such as hyper-inflammation, immune dysfunction, and comorbidities,” said Bartolome Burguera, M.D, Ph.D., chair of Cleveland Clinic’s Endocrinology & Metabolism Institute and co-investigator of the study. “Those conditions can lead to poor outcomes in the acute phase of COVID-19 in patients with obesity and could possibly lead to an increased risk of long-term complications of COVID-19 in this patient population.”
Future studies are planned to confirm findings of this study that obesity is a major risk factor for the development of PASC and determine the long-term and rigorous follow-up that patients with obesity need after a SARS-CoV-2 infection.
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A different type of surge may be on the way more than a year into the pandemic — a baby surge.
The COVID-19 shutdown initially seemed to hit pause on pregnancy and birth rates, new research from one major hospital system suggests, but that trend is quickly reversing.
“Birth rates declined early on in the pandemic, but we expect a dramatic rebound soon,” says lead author Molly Stout, M.D., MSci, maternal fetal medicine director at Michigan Medicine Von Voigtlander Women’s Hospital.
“We’re already seeing signs of a summer baby surge.”
While infectious disease experts have been modelling COVID cases to project surge trends, Stout and her team have been doing the same for pregnancy trends.
Using electronic health records for a cohort of pregnancies at Michigan Medicine, researchers were able to model pregnancy episodes and accurately project anticipated changes in pregnancy volumes over the last year during pandemic societal changes.

A group of researchers have discovered the detailed inner workings of the molecular motor that packages genetic material into double-stranded DNA viruses. The advance provides insight into a critical step in the reproduction cycle of viruses such as pox- herpes- and adeno-viruses. It could also give inspiration to researchers creating microscopic machines based on naturally occurring biomotors.
The research was conducted by scientists from Duke University, the University of Minnesota, the University of Massachusetts and the University of Texas Medical Branch (UTMB). The results appear online in a trilogy of papers published in Science Advances, Proceedings of the National Academy of Sciences and Nucleic Acids Research.
“There were several missing pieces of information that prevented us from understanding how these kinds of DNA packaging motors work, which hindered our ability to design therapeutics or evolve new technologies,” said Gaurav Arya, professor of mechanical engineering and materials science, biomedical engineering, and chemistry at Duke. “But with new insights and simulations, we were able to piece together a model of this fantastic mechanism, which is the most detailed ever created for this kind of system.”
Viruses come in many varieties, but their classification generally depends upon whether they encode their genetic blueprints into RNA or single- or double-stranded DNA. The difference matters in many ways and affects how the genetic material is packaged into new viruses. While some viruses build a protein container called a capsid around newly produced RNA or DNA, others create the capsid first and then fill it with the genetic material.
Most double-stranded DNA viruses take the latter route, which presents many challenges. DNA is negatively charged and does not want to be crammed together into a small space. And it’s packaged into an extremely dense, nearly crystalline structure, which also requires a lot of force.
“The benefit of this is that, when the virus is ready to infect a new cell, the pressure helps inject DNA into the cell once it’s punctured,” said Joshua Pajak, a doctoral student working in Arya’s laboratory. “It’s been estimated that the pressure exceeds 800 PSI, which is almost ten times the pressure in a corked bottle of champagne.”
Forcing DNA into a tiny capsid at that amount of pressure requires an extremely powerful motor. Until recently, researchers only had a vague sense of how that motor worked because of how difficult it is to visualize. The motor only assembles on the virus particle, which is enormous compared to the motor.

A new method to monitor epidemics like COVID-19 gives an accurate real-time estimate of the growth rate of an epidemic by carefully evaluating the relationship between the amount of viruses in infected people’s bodies, called the viral load, and how fast the number of cases is increasing or decreasing.
“This new method, which effectively links what we know about how the virus grows within the body to the dynamics of how the virus spreads across a population, provides a brand new metric that public health officials, policy makers, and epidemiologists will be able to use to get up-to-date real-time information on the epidemic,” said Michael Mina, assistant professor of epidemiology at Harvard T.H. Chan School of Public Health and a core member of the Center for Communicable Disease Dynamics.
Mina is the senior author of a paper that describes the method, published June 3, 2021 in the journal Science.
Monitoring epidemics is essential for public health response to understand how well interventions like masks, lockdowns, or vaccines are working, and to know where to distribute extra resources when cases are rising.
The current approaches to monitoring epidemics rely almost entirely on following case counts or hospitalization rates over time, and looking at test positivity rates and deaths. Throughout the COVID-19 pandemic, for example, daily case data like that published by the New York Times has been crucial for public health officials and researchers to evaluate how well states and countries are controlling the spread of the SARS-CoV-2 virus that causes COVID-19. However, these types of data can often be of only limited use because of variable testing practices or poor reporting. For example, a growing epidemic might look like it is leveling off if testing capacity is maxed out or if reporting is delayed because resources are being focused elsewhere. These pitfalls of monitoring case reports over time can adversely impact appropriate public health responses.
Because outbreaks grow or fall exponentially, when cases are growing, most people who are positive at any moment in time will have been recently infected and will thus have higher viral loads — as measured in PCR (polymerase chain reaction) tests — at the time that they are tested. This is because the virus is at its peak amount in the body early after infection and then falls to very low but still detectable levels in PCR tests over weeks or even months after infection. When the outbreak is slowing down and cases are falling, the average person who is detected as positive in surveillance testing will have been infected potentially weeks before testing and thus will have lower viral loads at the time of testing.
To better track pandemic hotspots, researchers at Harvard Chan School developed a mathematical tool that carefully evaluates the relationship between viral load — measured from the PCR test in a value called the cycle threshold (Ct value) — and how fast cases are increasing or decreasing. Using even the relatively small number of 30 SARS-CoV-2 positive samples taken from surveillance testing on a single day can give an accurate real-time estimate of the growth rate of the epidemic. When Ct values are available from multiple time points, the researchers discovered that they can use even a very limited amount of positive results to reconstruct the epidemic curve and estimate how many people have been infected over time.
Even viral amounts detected in positive PCR test samples collected from one location at just a single point in time can help estimate the growth or decay rate of an outbreak across a population, the researchers found.
In the U.S. and in much of the world, the PCR Ct values — the values that show how much virus is collected on the swab from someone’s nose — are often discarded and the results of the PCR test returned with a simple “positive” or “negative” result.
“Our work demonstrates just how valuable the Ct values are and why we should not only stop our current practice of throwing them away, but why we should instead make them a key piece of data to collect for our pandemic response,” said Mina, who has previously published on the use of PCR Ct values to aid in clinical decision making and who has been a leader in developing new approaches for using COVID-19 tests to limit the disease’s spread.
James Hay, who co-led the research as a postdoctoral researcher in Mina’s lab, stressed that the new technique is not COVID-19-specific but is a method that will be valuable for monitoring outbreaks and epidemics of other viruses in the future. “This tool is not just for COVID, but rather provides a new approach to estimating epidemic trajectories of many types of viruses, and is an approach that does not rely on potentially biased approaches like counting cases over time and will not be reliant on accurate reporting of cases or hospitalization,” he said.
Other Harvard Chan School researchers who contributed to the study include Lee Kennedy-Shaffer and Marc Lipsitch.

When bringing technologies into the workplace, it pays to be realistic. Often, for instance, bringing new digital technology into an organization does not radically improve a firm’s operations. Despite high-level planning, a more frequent result is the messy process of frontline employees figuring out how they can get tech tools to help them to some degree.
That task can easily fall on overburdened workers who have to grapple with getting things done, but don’t always have much voice in an organization. So isn’t there a way to think systematically about implementing digital technology in the workplace?
MIT Professor Kate Kellogg thinks there is, and calls it “experimentalist governance of digital technology”: Let different parts of an organization experiment with the technology — and then centrally remove roadblocks to adopt the best practices that emerge, firm-wide.
“If you want to get value out of new digital technology, you need to allow local teams to adapt the technology to their setting,” says Kellogg, the David J. McGrath Jr. Professor of Management and Innovation at the MIT Sloan School of Management. “You also need to form a central group that’s tracking all these local experiments, and revising processes in response to problems and possibilities. If you just let everyone do everything locally, you’re going to see resistance to the technology, particularly among frontline employees.”
Kellogg’s perspective comes after she conducted an 18-month close ethnographic study of a teaching hospital, examining many facets of its daily workings — including things like the integration of technology into everyday medical practices.
Some of the insights from that organizational research now appear in a paper Kellogg has written, “Local Adaptation Without Work Intensification: Experimentalist Governance of Digital Technology for Mutually Beneficial Role Reconfiguration in Organizations,” recently published online in the journal Organization Science.