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A moderate amount of a peptide-enhanced, biological cancer drug goes a long way in treating breast cancers that metastasize to the bone.
A study by scientists at Rice University and Baylor College of Medicine demonstrated the effective treatment of such cancers in rodent models, bringing hope for new therapies to treat bone metastases.
The open-access study, to appear on the cover of the American Chemical Society journal ACS Central Science, advances techniques pioneered by Rice chemist Han Xiao and his co-author at Baylor, biologist Xiang Zhang.
They discovered through extensive testing that engineering “bone-homing” peptides and attaching them to a common breast cancer drug, the antibody trastuzumab, effectively targets and attacks bone tumors.
The researchers reported their surprise that injecting more of the drug compound doesn’t make it better. The drug contains an engineered peptide that finds and binds to bone, but worked best when a moderate amount was delivered.
“The negative charge of the peptide has an affinity for the positively charged bone cancer niche,” said Xiao, whose lab created a library of modified antibodies for testing. “We found the therapeutic efficacy is best with the antibody that has mediocre affinity. That’s a really big discovery.”
As many as 40% of breast cancer survivors eventually experience metastases to distant organs, most often to the bone. Xiao noted bone tumors are notoriously difficult to treat, given the hard nature of the material and its limited vascular network. Delivering a low amount of a drug, he said, can also help tumors develop resistance.
The study showed that peptide-enhanced antibodies also prevented secondary metastases from bone to other organs.
The researchers hope to find collaborators to move the strategy toward human trials.
Rice postdoctoral fellow Zeru Tian and graduate student Chanfei Yu are co-lead authors of the paper. Co-authors are Baylor postdoctoral fellows Weijie Zhang and Zhan Xu and postdoctoral associate Ling Wu; Rice graduate students Kuan-Lin Wu, Chenhang Wang and Yuda Chen, and Rice alumna Ruchi Gupta, now a graduate student at Yale School of Medicine.
Xiao is the Norman Hackerman-Welch Young Investigator and an assistant professor of chemistry, biosciences and bioengineering. Zhang is an associate professor of molecular and cellular biology and the McNair Scholar in the Lester and Sue Smith Breast Center at Baylor.
The Cancer Prevention Research Institute of Texas (RR170014), the National Institutes of Health (R35-GM133706, R21-CA255894, R01-AI165079, CA221946), the Robert A. Welch Foundation (C-1970), the Department of Defense (W81XWH-21-1-0789, DAMD W81XWH-16-1-0073), the John S. Dunn Foundation and a Hamill Innovation Award supported the research.
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Materials provided by Rice University. Original written by Mike Williams. Note: Content may be edited for style and length.

A new study by researchers from the University of Kent and the Goethe University Frankfurt shows that the SARS-CoV-2 Omicron variant is less effective than Delta at blocking a cellular defence mechanism against viruses, the so-called “interferon response.” Moreover, cell culture findings indicate that eight important COVID-19 drugs and drug candidates remain effective against Omicron.
The SARS-CoV-2 Omicron variant causes less severe disease than Delta although it is better at escaping immune protection by vaccinations and previous infections. The reasons for this have so far remained elusive.
A new study by a research team with scientists from the University of Kent and the Goethe-University Frankfurt has now shown that Omicron variant viruses are particularly sensitive to inhibition by the so-called interferon response, an unspecific immune response that is present in all body cells. This provides the first explanation of why COVID-19 patients infected with the Omicron variant are less likely to experience severe disease.
The cell culture study also showed that Omicron viruses remain sensitive to eight of the most important antiviral drugs and drug candidates for the treatment of COVID-19. This included: EIDD-1931 (active metabolite of molnupiravir), ribavirin, remdesivir, favipravir, PF-07321332 (nirmatrelvir, active ingredient of paxlovid), nafamostat, camostat, and aprotinin.
Prof Martin Michaelis, School of Bioscience, University of Kent, said: “Our study provides for the first time an explanation, why Omicron infections are less likely to cause severe disease. This is due to Omicron, in contrast to Delta, does not effectively inhibit the host cell interferon immune response.”
Prof. Jindrich Cinatl, Institute of Medical Virology at the Goethe-University, added: “Although cell culture experiments do not exactly reflect the more complex situation in a patient, our data provide encouraging evidence that the available antiviral COVID-19 drugs are also effective against Omicron.”
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Materials provided by Goethe University Frankfurt. Note: Content may be edited for style and length.

Two blood proteins have been shown by scientists to influence how long and healthy a life we live, research suggests.
Developing drugs that target these proteins could be one way of slowing the ageing process, according to the largest genetic study of ageing.
As we age, our bodies begin to decline after we reach adulthood, which results in age-related diseases and death. This latest research investigates which proteins could influence the ageing process.
Many complex and related factors determine the rate at which we age and die, and these include genetics, lifestyle, environment and chance. The study sheds light on the part proteins play in this process.
Some people naturally have higher or lower levels of certain proteins because of the DNA they inherit from their parents. These protein levels can, in turn, affect a person’s health.
University of Edinburgh researchers combined the results of six large genetic studies into human ageing — each containing genetic information on hundreds of thousands of people,
Among 857 proteins studied, researchers identified two that had significant negative effects across various ageing measures.

Researchers at the University of Missouri have developed a new framework that they believe will help identify people previously overlooked for alcohol use disorder (AUD). This framework focuses on 13 risk factors, such as impulsive behavior, reward sensitivity, and punishment sensitivity, that could lead to someone developing an AUD.
“We know from decades of research that there are a lot of different pathways to alcohol use disorder,” said Cassie Boness, a former graduate student at MU in the Department of Psychological Sciences. “So, we want to make sure that we are targeting people’s specific pathways as accurately as possible in order to be most effective in identifying and treating AUD.”
Throughout her career, Boness has been interested in the causes, diagnosis and assessment of substance use disorders, including AUD, a chronic medical condition characterized by ongoing alcohol use despite adverse consequences. For Boness, it’s personal — after seeing her loved ones stigmatized for their addiction to alcohol, and then watching them struggle to get connected with treatment, she wanted to help reduce the amount of suffering people may experience with AUD.
While today’s assessment tools, such as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) can help health care professionals diagnose someone with AUD, Boness believes the current methods are too narrowly focused on the consequences of someone’s actions, rather than incorporating a broad list of potential risk factors that may lead to an AUD diagnosis.
Boness, who is now a research assistant professor at the University of New Mexico, hopes their framework can be a step forward toward a comprehensive diagnosis of AUD throughout the health care community. However, she stresses that this tool is not meant to be the only solution, but rather a way for other researchers like her to build upon and enhance the existing research on the subject.
“Eventually, we’d like to see assessment tools that more comprehensively capture the factors articulated in our framework so that we can identify individual profiles of risk and potentially intervene during earlier stages of addiction,” Boness said.
“The etiologic, theory-based, ontogenetic hierarchical framework of alcohol use disorder: a translational systematic review of reviews,” was published in Psychological Bulletin. Other authors on the study include Ashley Watts, Kimberly Moeller and Ken Sher at MU. Funding was provided by grants from the National Institutes of Health (F31AA026177, K99AA028306, R01-AA024133 and T32AA13526). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
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Materials provided by University of Missouri-Columbia. Note: Content may be edited for style and length.

The next generation of soft robotics, smart clothing and biocompatible medical devices are going to need integrated soft sensors that can stretch and twist with the device or wearer. The challenge: most of the components used in traditional sensing are rigid.
Now, researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a soft, stretchable, self-powered thermometer that can be integrated into stretchable electronics and soft robots.
“We have developed soft temperature sensors with high sensitivity and quick response time, opening new possibilities to create new human-machine interfaces and soft robots in healthcare, engineering and entertainment,” said Zhigang Suo, the Allen E. and Marilyn M. Puckett Professor of Mechanics and Materials at SEAS and senior author of the paper.
The research is published in the Proceedings of the National Academy of Sciences.
The thermometer consists of three simple parts: an electrolyte, an electrode, and a dielectric material to separate the two. The electrolyte/dielectric interface accumulates ions while the dielectric/electrode interface accumulates electrons. The charge imbalance between the two sets up an ionic cloud in the electrolyte. When the temperature changes, the ionic cloud changes thickness and a voltage is generated. The voltage is sensitive to temperature, but insensitive to stretch.
“Because the design is so simple, there are so many different ways to customize the sensor, depending on the application,” said Yecheng Wang, a postdoctoral fellow at SEAS and first author of the paper. “You can choose different materials, arranged in different ways and optimized for different tasks.”
By arranging the electrolyte, dielectric, and electrode in different configurations, the researchers developed four designs for the temperature sensor. In one test, they integrated the sensor into a soft gripper and measured the temperature of a hot hard boiled egg. The sensors are more sensitive than traditional thermoelectric thermometers and can respond to changes in temperature within about 10 milliseconds.
“We demonstrated that these sensors can be made small, stable, and even transparent,” said Wang.
Depending on the materials used, the thermometer can measure temperatures upwards of 200 degrees Celsius or as cold as -100 degrees Celsius.
“This highly customizable platform could usher in new developments to enable and improve the internet of everything and everyone,” said Suo.
The research was co-authored by Kun Jia, Shuwen Zhang, Hyeong Jun Kim, Yang Bai and Ryan C. Hayward. The research was supported in part by the National Science Foundation through the Harvard University Materials Research Science and Engineering Center under grant DMR2011754.
Video of stretchable thermometer: https://youtu.be/AJN6OTZAe14

Researchers at the University of Washington have developed a new test for COVID-19 that combines the speed of over-the-counter antigen tests with the accuracy of PCR tests that are processed in medical labs and hospitals.
The Harmony COVID-19 test is a diagnostic test that, like PCR tests for COVID-19, detects genetic material from the SARS-CoV-2 virus. But whereas conventional PCR tests can take several hours, the Harmony kit can provide results in less than 20 minutes for some samples and with similar accuracy.
“We designed the test to be low-cost and simple enough that it could be used anywhere,” said Barry Lutz, a UW associate professor of bioengineering and investigator with the Brotman Baty Institute for Precision Medicine. “We hope that the low cost will make high-performance testing more accessible locally and around the world.”
Lutz is senior author on a paper published Dec. 15 in Science Advances that describes the Harmony COVID-19 test kit. The researchers developed Harmony to be simple and easy-to-use, employing ready-to-use reagents. The test uses a “PCR-like” method to detect the presence of the SARS-CoV-2 RNA genome in a nasal swab sample with the aid of a small, low-cost detector, which was also designed by Lutz’s group. A smartphone is used to operate the detector and read the results. The detector can handle up to four samples at a time and would fit into a standard car’s glove compartment.
The accuracy of COVID-19 tests has been a pressing matter throughout the pandemic. Many at-home antigen kits for COVID-19, which detect pieces of the proteins the virus creates instead of its genetic material, are 80-85% accurate, though accuracy may drop with the omicron variant, which harbors a relatively high number of mutations not found in other strains. PCR tests are generally 95% accurate or better — a key FDA benchmark — but require expensive equipment and a long wait for results.
Initial results reported in the paper show that the Harmony kit is 97% accurate for nasal swabs. The Harmony kit detects three different regions of the virus’ genome. If a new variant has many mutations in one region, the new test can still detect the other two. It can, for example, detect the omicron variant, which has dozens of mutations in the region of the genome that encodes the so-called spike protein.

Americans’ use of common outpatient health services dipped sharply at the outset of the COVID-19 pandemic, then rebounded to near-normal levels by the end of 2020, only to decline again during the second surge in January-February 2021, according to a new UCLA-led study.
But the 2020 recovery in care wasn’t equal for all, researchers found. Some of the most socioeconomically disadvantaged patients — those with Medicaid or Medicare-Medicaid dual eligibility insurance — were far less likely than those with other insurance plans to return to using outpatient services at rates approaching normal, pre-pandemic levels.
The study, published this week in the Journal of the American Medical Association and based on data on 14.5 million adults in the U.S., raises concerns about patients missing treatments for acute illnesses, delaying preventive care and lacking a clear understanding of when to seek help during the pandemic, said lead author Dr. John Mafi, an associate professor of medicine and practicing general internist at the David Geffen School of Medicine at UCLA.
“The worsening access to care we observed among socioeconomically disadvantaged Americans is particularly concerning,” Mafi said, “because it suggests that the pandemic is widening inequities in access to vital health services such as emergency care, preventive cancer screening and behavioral health services.”
For the study, the researchers looked at the use of six ambulatory care services: emergency department visits, doctors office visits (including for urgent care), behavioral health services, colonoscopy screenings, mammogram screenings, and HIV screenings or contraception counseling. They compared the utilization of those services among patients with commercial insurance, Medicare Advantage, Medicare fee-for-service insurance, and those with Medicaid or Medicare-Medicaid dual eligibility insurance between Jan. 1, 2019, and Feb. 28, 2021. (Patient data was drawn from the Milliman MedInsight Emerging Experience research database and included data on patients from all U.S. states.)
They found that during the initial COVID-19 surge in March-April 2020, overall use of the six ambulatory care services dropped to just 67% of levels that would be expected had the pandemic not occurred.

As people transitioned to working from home at the onset of the coronavirus pandemic, journal submissions from academics increased across the board. But a new study from Northwestern University found as men’s scholarly productivity increased, women physicians were submitting less.
The research reflects wider trends in academic publishing and is the first study to find such patterns in family medicine. The study contributes to a growing body of evidence that the pandemic caused unique career disruptions for women as they became stretched thin during remote work, causing stress, burnout and anxiety.
“The worry is that these problems will compound,” said Katherine Wright, the paper’s corresponding author and the director of research in the department of family and community medicine at Northwestern University Feinberg School of Medicine. “As men were able to submit more, they may benefit from more citations, promotions, funding and career opportunities as women fall further behind.”
The paper, “COVID-19 and Gender Differences in Family Medicine Scholarship,” will be published Jan. 24 in the journal Annals of Family Medicine.
Wright said the study was conceived in part because of observations about her own department, where she saw roles changing dramatically and many doctors attempting to play dual roles between childcare or eldercare and work. Santina Wheat, co-first author and program director of the Northwestern-McGaw family medicine residency at Erie Family Health Center in Humboldt Park, emphasized the impact of shifting schedules on her own life.
“All of a sudden we were doing telehealth at all hours of the day, and hours of the clinics shifted significantly and quickly,” Wheat said. “There was also always the sense you may need to cover for someone else, which impacted your ability to think about the academic side — or mentor others to do the same.”
To conduct the study, the team performed a bibliometric analysis of journal submissions to see how submission rates changed during the pandemic. With access to the last five years of submission data from the Annals of Family Medicine, the top-ranked primary care journal, the scientists reviewed submission data before and during the pandemic. They examined submission volume by gender in addition to distribution of author’s gender by submission type (such as original research versus special reports, which impact tenure differently).

Geneticists have revealed why some people with obesity remain relatively healthy, whilst others suffer from life-changing ailments such as type 2 diabetes and heart disease.
Anyone with a BMI over 30 is considered obese rather than just overweight and although people with obesity all have a few extra kilos in common, two people with the same BMI can have very different amounts of fat, and that fat can be distributed in different places throughout the body. Fat stored under the skin, like a paunch or a double chin, is considered less harmful than fat stored around organs such as the liver and heart, and it’s the genes we’re born with that determine how and where this fat is stored — what scientists refer to as having ‘favourable’ or ‘unfavourable’ adiposity.
“Some people have unlucky fat genes, meaning they store higher levels of fat everywhere, including under the skin, liver and pancreas. That’s associated with a higher risk of diseases such as type 2 diabetes,” said Dr Hanieh Yaghootkar, a lecturer in biosciences at Brunel University London, who led the research. “Others are luckier and have genes that mean higher fat under the skin but lower liver fat and a lower risk of diseases like type 2 diabetes.”
Using a technique known as Mendelian randomisation, the team found that of the 37 diseases they tested, 12 — including coronary artery disease, stroke and type 2 diabetes — were directly related to the genes that determine whether or not a person has a ‘favourable adiposity,’ whilst nine could be said to be unrelated to someone’s adiposity and were most likely a result of simply carrying too much weight, such as having deep vein thrombosis or arthritic knees.
However, the researchers caution that regardless of whether someone has a favourable or unfavourable adiposity, being obese is a serious hazard to a person’s health, with even those with a favourable adiposity still at a heightened risk of diseases such as gallstones, adult-onset asthma and psoriasis.
They also found some other diseases previously thought to be related to someone’s weight, such as Alzheimer’s, appear to be unconnected.
“To better prevent and measure risk of disease, it is important to understand if obesity is a casual risk factor and if it is causal, which consequences of it — be they metabolic, mechanical or psychological — are deriving the risk,” said Dr Yaghootkar.
She added: “Our results also provide evidence that everyone will benefit from losing their extra fat even if they are metabolically healthy.”
The researchers say the results will help medical doctors determine if they should be targeting the adverse effects of someone’s obesity, or be trying to get them to shed a few pounds. “For example, there are many treatments that can lower the high-fat levels in the blood and around the organs that do not affect the extra weight a person carries,” said Prof Timothy Frayling, Professor of Human Genetics at the University of Exeter.
“In contrast, for other conditions, it may be more important to reduce the extra weight as much as, or more than, the damaging high sugar and fat levels in the blood.”
The study, published in the journal eLife, funded by Diabetes UK, and run in collaboration with the University of Winchester, used data from Finland’s FinnGen project and the UK Biobank, which collected information from 500,000 individuals aged 37 to 73 between 2006 and 2010 from across the UK. One in four are already considered by the NHS to be ‘very overweight’ and at increased risk of getting seriously ill.
Dr Susan Martin, a postdoctoral research fellow at Exeter who was involved in the research, said: “Whilst it’s important that we identify the causes of obesity-related disease, good genes is still no substitute for a healthy lifestyle. A favourable adiposity will only go so far — if you’re obese, the advice is to still try and shift the excess weight where you can.”

People with dementia who see the same GP each time have lower rates of health complications and fewer emergency hospital admissions, according to a new study.
The research, led by the University of Exeter and published in the British Journal of General Practice (BJGP) analysed more than 9,000patient records of people diagnosed with dementia in the Clinical Practice Research Datalink. The team found that people with dementia who were consistently seen by the same GP over the course of one year were given fewer medicines and were less likely to be given medicines that can cause problems like incontinence, drowsiness and falls. Those seeing the same GP over time were 35 per cent less likely to develop delirium, a state of confusion commonly experienced in dementia. Those who consistently saw the same GP were also 58 per cent less likely to experience incontinence, and almost ten per cent less likely to have an emergency hospitalisation, compared to those who had the most variation in GPs treating them.
The research was conducted in anonymised patient records of people with dementia aged 65 and over in 2016, who were followed-up for one year. This study includes people who visited a GP at least three times in the previous year.
Lead author Dr João Delgado, of the University of Exeter, said: “The number of people with dementia has been rising steadily and it is now one of the leading causes of death in the UK. In the absence of a cure, long-term care is particularly important. Treating people with dementia can be complex, because it often occurs together with other common diseases. Our research shows that seeing the same general practitioner consistently over time is associated with improved safe prescribing and improved health outcomes. This could have important healthcare impacts, including reduced treatment costs and care needs.”
Delirium (an episode of more severe confusion) is common in dementia, and patients who develop delirium are more likely to die. Delirium and incontinence are very distressing for individuals, and require additional NHS resource. Extra hospital admissions are a high cost for the NHS.
Sir Denis Pereira Gray, co-author and GP researcher at the St Leonard’s Practice, said: “These new findings show that GP continuity is associated with important benefits for patients. Whilst national policy makers have for years discouraged continuity, general practices can still provide good GP continuity through their internal practice organisation, for example, by using personal lists.”
Dr Richard Oakley, Associate Director of Research at Alzheimer’s Society said: “For the 900,000 people living with dementia in the UK, it’s likely dementia isn’t the only condition they’re getting treatment for.
“It’s clear from this study that consistently seeing the same GP has real benefits for people living with dementia — better management and treatment of conditions, and lower risk of complications like delirium and incontinence, leading to improved quality of life.
“The pandemic has put GP services under immense pressure, so while we might not be able to get consistent GP care for everyone with dementia tomorrow, policymakers should absolutely be working with the NHS to build this into their plans as we emerge from the pandemic.”
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Materials provided by University of Exeter. Note: Content may be edited for style and length.