Culture

COLUMBUS, Ohio - Instagram users who detect self-promotion or corporate marketing in a post embracing the body positivity movement may be turned off by that dual messaging, new research suggests.

In the study, women viewed experimental Instagram posts that borrowed body positive messages from actual users and contained body positive hashtags, such as #bopo. The posts all featured the same initial body positive sentiment, but some posts also asked viewers to either like and follow their profiles and others advertised products or services.

Researchers found that participants who spotted self-promotion or advertising considered the posts less morally appropriate and not altogether sincere in their support of the body positivity movement in comparison to non-promotional posts.

Self-promotion was consistently perceived by study participants to be less negative than corporate advertising, but the viewers did not go so far as to consider any marketing messages offensive or inappropriate, the findings showed.

"If companies are going to use body positive imagery, it's a balancing act between trying to seem authentic - and hopefully be authentic - with what they're trying to push," said Kyla Brathwaite, lead author of the study and a doctoral student in communication at The Ohio State University.

"But seeing so much body positivity content coupled with advertising might make viewers wary about the movement - or see the movement as something that's appearance-centered."

Brathwaite conducted the study with co-author David DeAndrea, associate professor of communication at Ohio State. The open-access article is published in the journal Communication Monographs.

Before the "body positive" phrase was coined and body positivity-related hashtags emerged on Instagram, the fat acceptance movement advocated for the rights and dignity of fat people. Now, as then, the body positivity movement decries society's fixation on young, thin, white bodies and calls for acceptance and appreciation of bodies of all shapes, sizes, colors, appearances and abilities.

After encountering the "fitspiration" and "thinspiration" messages pushing exercise and dieting on social media and more recently observing the growth of the body positivity movement, Brathwaite "started hearing a voice in my head saying people are co-opting the movement and trying to sell me things."

With millions of hashtagged posts combined with widespread sponsored content on Instagram, the platform became an attractive candidate for study.

"Our hope was to try to speak more broadly to prosocial movements online in general," DeAndrea said. "They're most effective when they seem genuinely grassroots. Then you have companies that recognize this and are trying to piggyback off the goodwill of the movement to help themselves."

The researchers recruited 851 women from TurkPrime (now CloudResearch) ranging in age from 18 to 89.

Each participant viewed a total of 10 experimental Instagram posts, all of which included two body positive messages that functioned as the basis of posts in the study that represented movement-supporting user content: "We won't be distracted by comparison if we are captivated by purpose" and "Be done shrinking your mind, body and soul. Take up space." The messages also featured hashtags such as #allbodiesaregoodbodies and #bopo.

Messages representing user-generated self-promotion added encouragement to like, comment or visit a YouTube channel. Corporate-sponsored messages either focused on appearance-centered items by adding language promoting a fitness plan and "flaw-blurring" facial products or, in a control condition, marketed a clothing line using language that made no mention of appearance.

An analysis of viewer reactions showed that the higher the participants' recognition of promotional cues in the experimental messages, the more likely they were to attribute posters' motivation to something other than an embrace of body positivity.

The researchers also wanted to gauge how images associated with messages influenced viewers' perceptions, and tested this by featuring photos of either average- or plus-sized women in the messages. The more that participants perceived women's bodies on posts to be plus-sized, the more they rated the messages as morally appropriate and believed the messages were exclusively shared to promote body positivity.

"One could assume that consumers viewing a campaign that's talking about body positivity but not featuring women the movement is supposed to support may be questioning the motives of these companies," Brathwaite said.

The researchers noted that the results suggest meshing the movement with marketing has potential pitfalls for both body positivity itself and for companies that give a nod to the movement in their ads.

"The question is whether you can walk that tightrope of promoting the movement while selling the product," DeAndrea said. "It does seem that people didn't find these messages or images inappropriate, but it can still be done in a way that might minimize any degree to which the movement is undermined, and from a company perspective, minimize any chances for blowback based on exploitation of the movement."

In a retrospective study believed to be one of the largest of its kind, researchers say they have successfully charted the health risks, growth patterns, and medical and surgical outcomes of 1,374 people with the most common form of dwarfism, called achondroplasia, seen over a 60-year period at four academic medical centers, including Johns Hopkins Medicine. The findings, according to the researchers, not only affirm some long-standing views and trends in the care of those with the condition, but also offer a standardized baseline, a blueprint investigators hope will serve to speed diagnosis and improve patients' quality of life and health.

Achondroplasia is caused by a rare genetic mutation that alters the activity of the fibroblast growth factor receptor 3 (FGFR3) gene involved in bone growth. Occurring in about 20,000 live births in the U.S. each year, the condition is marked by short stature, bowed legs, disproportionately large head and other musculoskeletal problems that cause pain, sleep problems and other symptoms.

Among other findings, the new study affirms that the vast majority -- at least two-thirds -- of those with the condition are born to parents of normal stature and bone development, meaning that the genetic mutation mostly arises spontaneously and randomly.

"We aimed to provide more uniformity of information about treatments in this field, because more precise information has great potential to improve therapies that alleviate symptoms and health problems among people with achondroplasia," says Julie Hoover-Fong, M.D., Ph.D., director of the Greenberg Center for Skeletal Dysplasias and professor of genetic medicine at the Johns Hopkins University School of Medicine.

A summary of the findings appeared in the May 18 issue of Genetics in Medicine.

Hoover-Fong says she and her colleagues had talked about doing this type of "look-back," or retrospective review of patient information for more than a decade, and began to do so in earnest in 2017. The data included medical records from 1,374 children and adults diagnosed with achondroplasia seen between 1957 and 2017 at one of four medical centers: The Johns Hopkins Hospital, Nemours/A.I. duPont Hospital for Children in Wilmington, Delaware, the University of Texas Health Science Center at Houston and the University of Wisconsin. There were an equal number of females and males, and 77.6% were white, 5.4% each were Black and Asian, 7.5% were Hispanic, 0.07% were Native American, 1.7% were a mix of more than one race or ethnicity, 1.7% were of unknown race or ethnicity and 0.4% were other ethnicities including those of middle eastern, African or South American descent.

"We collected everything we could find about patients who had been seen in our achondroplasia clinics, including archives, hard-copy charts and electronic medical records," says Hoover-Fong, who noted that medical centers transitioned through many types of medical record-keeping systems during the 60-year timeframe. The research team focused on four specific areas of study: anthropometry (growth), surgical history, sleep-disordered breathing and radiographic studies completed.

The challenge, says Hoover-Fong, was to identify comparable patterns and measures of physical traits, symptoms, therapies and outcomes.

One focus was on patterns of growth, including weight gain and head circumference among the patients from birth through adulthood, says Hoover-Fong, which are important for clinicians who need to know if their patients are growing as they should and for ensuring that different populations are evaluated appropriately in clinical trials of new therapies. Their database could be further improved by conducting similar analyses of information in people with achondroplasia worldwide.

The findings also confirmed evidence from previous studies that children with achondroplasia are more likely than the general population to be born preterm. Some 12.7% (174 of 1,374) of the study population was born prematurely. In the overall U.S. population, preterm births occur approximately 9.8% of the time. Most of the premature achondroplasia patients were born to mothers of average stature.

"Premature births in this population could be due at least partially to the large size of the fetus' head," says Hoover-Fong.

Analysis of trends in treatments revealed that limb-lengthening surgeries and use of growth hormone were relatively uncommon among patients, at only 1.2%. The surgeries can have a high complication rate, and are more common outside the U.S. where there are few or less-stringent laws providing protections and accommodations afforded by the Americans with Disabilities Act, says Hoover-Fong. Growth hormone, which come with the risk of serious side effects such as weight gain and diabetes, are not typically used among people with achondroplasia in the U.S. or most other countries except Japan.

By contrast, nearly 80%, or 1,094 of the patients in the study, had undergone at least one surgical procedure on ears, nose and throat, brain, foramen magnum (the opening at the base of the skull), spine or extremities to relieve pain, pressure, fluid buildup or other symptoms. More than half the achondroplasia patients had surgeries to insert pressure-equalizing tubes in the ears or to remove tonsils and adenoids. Such procedures are far less frequent in the general population of children of average stature (between 0.7 and 6.8%).

Among the achondroplasia patients, there were a "tremendous number" of X-rays and MRIs -- 10,727 -- likely a factor of the high number of surgical procedures, Hoover-Fong says.

Sleep apnea occurred among 38.4% of the achondroplasia patients, likely due to distorted bone growth in the head and throat. The prevalence of apnea among those with average stature is also high -- as much as 22%, according to some studies. "Medical professional societies have given resounding evidence and support that a series of evaluations, including an overnight stay at a sleep center, are necessary to properly assess sleep apnea in people with craniofacial differences, including those with achondroplasia. Yet, clinicians meet a lot of resistance from insurance companies to reimburse these evaluations," says Hoover-Fong.

The researchers' data also shows that, with the availability of molecular diagnostic tools, fewer patients with achondroplasia are going undiagnosed in recent times. Still, some children go a day, even up to a month without a diagnosis.

"Because those born with achondroplasia need early interventions, clinicians should have an immediate, definitive diagnosis right away," says Hoover-Fong. "We still have a lot of education to do so that more health care professionals can provide continual care for achondroplasia patients."

According to Hoover-Fong, more long-term, prospective studies are needed to improve pain management and well-being in patients, while reducing health care costs and increasing access to care.

A method for making ultrathin sensors for monitoring the health of crops could help farmers grow more food without putting extra demands on the land.

Intensive agriculture is already contributing to widespread biodiversity loss and climate change, yet growing populations continue to put pressure on farmers to produce more food. The challenge now lies in increasing agricultural output without clearing more land or applying excessive fertilizers. Precision farming is a promising solution that involves real-time monitoring of plant needs and responding to them with just the right amount of water, light or nutrients.

"Precision farming typically relies on soil-based sensors or drones fitted with special cameras," says Ph.D. student Abdullah Bukhamsin, "but they cannot capture changes in the plant early enough to enable intervention." Previous research has shown that measuring bioimpedance -- how easily an electrical current passes through organic tissues -- can reveal physiological information about a plant, from its nitrogen and water content to the presence of fungal infections or metal contaminants.

Plants, however, have a thick outer layer that blocks electrical signals, and bioimpedance sensors must pierce the surface without affecting the properties they wish to measure. It remains difficult to manufacture instruments tiny and thin enough to do this job.

Now, an efficient method for making silicone molds that can be used to manufacture such ultrathin microneedles has been developed by Bukhamsin and a multidisciplinary team of KAUST researchers led by Khaled Salama. These delicate needles can be released intact by submerging the mold in trichloromethane. "The swelling causes the mold to expand ever so slightly, thereby gently pushing the trapped structure out," says Bukhamsin.

The reusable molds could enable cost-effective, mass-production of microneedles in various plant-friendly polymers. When the team tested their microneedle on an Arabidopsis thaliana leaf, the puncture hole sealed within four days and the plant was not harmed.

"In our tests, the impedance measurements were closely related to how much light a plant has been exposed to and how dehydrated it is," says Bukhamsin. "This bioimpedance data could be used alongside shading technologies and an irrigation system that responds to the actual needs of the crops, thereby avoiding overwatering." Unexpectedly, this relationship was almost identical in other crops, including date palm and barley. "This is promising as it highlights the versatility of the approach and its potential applicability across different plants," he adds.

"Next, we will explore what other environmental factors affect the impedance of plants," says Salama, "and how we can use electrochemical measurements to quantify hormone levels in different plant species." Such detailed data could feed into even more finely tuned precision farming in the future.

Research has found that training stroke survivors to walk at a faster speed during recovery can help improve the brain function that enables people to walk and perform another task simultaneously, known as dual-task walking. The research, led by academics at Oxford Brookes University, was funded by the Stroke Association.

People who've had a stroke often struggle to walk and do tasks that involve thinking at the same time, for example, activities such as walking and holding a conversation, or planning what to do next. To effectively walk in the community, cognitive effort is needed to navigate safely and deal with distractions. Many people fail to regain this ability after a stroke.

Dual-task training did not directly improve ability

To improve the ability to walk and think at the same time, rehabilitation approaches have been to directly practice walking and doing something that requires thinking at the same time, known as dual-task training. A previously-run randomised controlled trial led by Oxford Brookes University and the University of Oxford found that this training did not improve people's ability to dual-task walk any more than just walking training.

Researchers believed that a reason why people struggle with dual-task walking after a stroke may be linked to their walking automaticity - the pattern our brains run which means we don't have to think about walking. This pattern is linked to the cyclic pattern of walking whereby one step 'signals' the next step to follow. If someone walks very slowly this pattern could be disrupted so that walking becomes more like independent steps, rather than a cycle.

Secondary analysis found faster walkers improved dual-task walking

The new research analysed data from the previously-run trial to compare how people who walked slowly and people who walked at faster speeds responded to dual-task training.

"When we compared slower walkers and people who walked at a faster pace - still slower, but closer to walking speeds we expect to see in people who have not had a stroke - both increased their walking speeds after the training," said Dr Johnny Collett, Senior Clinical Research Fellow in the Centre for Movement, Occupational and Rehabilitation Sciences at Oxford Brookes University.

"However, those who could walk faster at the beginning of the training also improved their ability to walk and think at the same time."

Advanced brain imaging tracked responses to training

As part of the new research, scientists at the University of Oxford used advanced imaging to track how people's brains responded to the training. Changes found in the brain supported the findings that people with stroke who walked slower, had a less automatic control of walking. Those who walked at a faster pace had changes in the brain consistent with adaptations that may be necessary for controlling gait in more complex environments.

"These findings show that, for those who walk slowly, initially focusing on improving walking speed may increase their capacity to improve dual-task walking," added Dr Collett. "Greater consideration of walking automaticity may help to better tailor intervention and direct a staged approach of increasing complexity to make people better able to walk in the community."

An important part of rehabilitation

Dr Rubina Ahmed, Director for Research and Policy at the Stroke Association said "Stroke strikes every 5 minutes and has devastating physical and mental impacts. Whilst four out of five stroke survivors recover the ability to walk, most find it hard outside of hospital which has a big impact on their well-being and independence. By funding this research our charity has helped to highlight that training focused on walking speeds could be an important part of rehabilitation for some stroke survivors' recoveries. Research like this is key to finding new treatments and improving stroke care, so that stroke survivors can regain the mobility and independence they need to rebuild their lives."

The paper, Dual-task walking and automaticity after Stroke: Insights from a secondary analysis and imaging sub-study of a randomised controlled trial, is published in Clinical Rehabilitation.

The research team used data from world renowned health study Children of the 90s, to answer three research questions:

Is school enjoyment patterned by biological sex at birth, socioeconomic background of cognition?

How does school enjoyment relate to GCSE achievement?

Does school enjoyment relate to social or sex differences in GCSE achievement?

The team found that pupil's school enjoyment measured at six years old is patterned by their sex and cognitive ability but not their family's socioeconomic background. For example, girls were twice as likely to report enjoying school than boys. School enjoyment strongly related to GCSE achievement at age 16 even after consideration of their socioeconomic background and cognitive ability. Pupils who reported enjoying school at age 6 went on to score on average 14.4 more GCSE points, equivalent to almost a three-grade increase across all GCSE's and were 29 per cent more likely to obtain five plus GCSE's grade A*- Cs including Maths and English than those who did not enjoy school.

Lead author Dr Tim Morris said: "While it is intuitive that a pupil's school enjoyment relates to their education, it is quite remarkable that school enjoyment as early as age six is so strongly linked to GCSE's 10 years later. That this link persists even after considering family and pupil factors provides support that a lack of school enjoyment may have long lasting effects on pupil's educational outcomes."

"Research into methods for improving school enjoyment and the effectiveness of interventions in this area could have beneficial effects for children."

Professor Nic Timpson, Principal Investigator for Children of the 90s said: "This is an important piece of research which shows how Children of the 90s data has helped inform our understanding of educational attainment as well as health/wellbeing."

Scientists studying a common childhood cancer have made a major breakthrough which could lead to a cure for some youngsters who would not have survived the condition.

An international study, involving Newcastle University, UK, has for the first time found a genetic marker in tumours from patients with high-risk neuroblastoma.

Research, published in the Journal of Clinical Oncology, has identified that alterations in the neuroblastoma's ALK (anaplastic lymphoma kinase) gene are associated with a significantly poorer prognosis for children with high-risk disease.

Experts say that by identifying this important genetic marker it means patients should be put on ALK inhibitors at the time of diagnosis with the hope of a cure.

Personalised treatment

Professor Deborah Tweddle, from the Newcastle University Centre for Cancer and Honorary Consultant at The Newcastle Hospitals NHS Foundation Trust, led the UK part of the study.

She said: "By identifying ALK as a genetic marker associated with the likelihood of a poorer outcome within the high-risk group of patients, it means we can treat these patients differently from the outset.

"Most excitingly there are new treatments that target the ALK protein itself, used in other cancers that can now be used for patients with high-risk neuroblastoma with ALK gene abnormalities.

"This research is an excellent example of personalised medicine. By treating those patients with an ALK genetic abnormality with an ALK inhibitor we are tailoring the treatment to the patients' individual tumour type.

"By combining an ALK inhibitor with the other treatments we currently give for high-risk neuroblastoma we hope to be able to cure more patients with this aggressive childhood cancer."

Neuroblastoma is a cancer of the nervous system that mainly affects children under five. It often begins in the adrenal gland, but in around half of cases has spread throughout the body when it is diagnosed - in these high-risk cases survival is only approximately 50 percent.

Sadly, barely half of the children live beyond five years after diagnosis, despite treatment including high dose chemotherapy, surgery, radiotherapy and immunotherapy.

Several European countries took part in the study and the UK-arm of the trial has been based at Newcastle University with the test being carried out within the Newcastle Genetics Lab, supported by grants from Solving Kids Cancer and Neuroblastoma UK.

Study's findings

Experts carried out ALK testing on as many neuroblastomas as possible from patients treated on the high-risk trial and pooled this data with that from national genetic reference labs from 19 other countries.

The study showed that ALK mutations are present in about 14% of patients newly diagnosed with high-risk neuroblastoma, and nearly 4% have amplification of this gene.

More importantly, these abnormalities are associated with a lower rate of survival and they are therefore important prognostic markers that could be targeted by treatment.

Professor Tweddle added: "As part of the next European clinical trial for high-risk neuroblastoma, we are going to treat all patients with an ALK abnormality found in their tumour with an ALK inhibitor in addition to standard treatment."

The breakthrough comes at the launch of the Newcastle University Cancer Fund, a new fundraising effort to inspire the next generation of cancer researchers to train and work at Newcastle for the benefit of people living with cancer locally as well as sending their research worldwide.

The Fund will work with cancer researchers at the very earliest stages of their studies and see them through to the point where they become established cancer researchers.

Patient case study

Happy schoolboy, Alexander Mohammed, is living life to the full as he enjoys fishing and outdoor activities with his family.

But five years ago, it was a very different story as the youngster, of Gosforth, Newcastle, was given the devastating diagnosis of neuroblastoma.

For almost two years Alexander had intensive treatment which included many aggressive cycles of chemotherapy at the Great North Children's Hospital in Newcastle.

The 10-year-old is now in remission and is monitored every six months under the care of Professor Deborah Tweddle.

Alexander's dad Raphael, a doctor, 43, said: "When Alexander was diagnosed with cancer it was such a shock and not something that we were expecting as he did not have the classic symptoms of neuroblastoma.

"It was difficult to watch him go through the intensive treatment, but he was so brave and to see how well he is doing now is fantastic as he has been in remission for four years.

"To hear of this major breakthrough into the treatment of the condition for children offers real hope of personalised treatment options in the future so that more youngsters lives can be saved."

Researchers from the German Center for Infection Research (DZIF) at Charité - Universitätsmedizin Berlin and the University of Bonn have examined the way in which SARS-CoV-2 reprograms the metabolism of the host cell in order to gain an overall advantage. According to their report in Nature Communications*, the researchers were able to identify four substances which inhibit SARS-CoV-2 replication in the host cell: spermine and spermidine, substances naturally found in the body; MK-2206, an experimental cancer drug; and niclosamide, a tapeworm drug. Charité is currently conducting a trial to determine whether niclosamide is also effective against COVID-19 in humans.

Viral replication depends on host cell machinery and the use of the host's molecular building blocks. In order to avoid detection by the immune system, viruses also have to ensure that they can evade cellular surveillance systems. To do this, they manipulate various processes in the infected host cell - and every virus pursues a different strategy. This is why a team of researchers led by PD Dr. Marcel Müller of Charité's Institute of Virology and Dr. Nils Gassen of the Psychiatry and Psychotherapy Clinic and Outpatient Clinic at the University Hospital Bonn (UKB) have investigated the way in which SARS-CoV-2 reprograms host cells for its own benefit. Their key finding was as follows: The new coronavirus slows down the cell's own recycling mechanism, a process known as autophagy. The purpose of this 'auto-digestion' mechanism is to enable the cell to dispose of damaged cell materials and waste products while recycling usable molecular building blocks for incorporation into new cellular structures.

"In our study, we were able to show that at the same time as using the cell's building blocks for its own benefit, SARS-CoV-2 deceives the cell by simulating a nutrient-rich status, thereby slowing cellular recycling," explains first author Dr. Gassen. As part of this work, the researchers undertook a detailed analysis of SARS-CoV-2 infected cells and the lung tissue of COVID-19 patients, studying cellular metabolism and the processing of molecular signals. "It is likely that SARS-CoV-2 uses this to avoid dismantling by the cell. After all, viruses are also subject to autophagic disposal," adds the study's last author, DZIF researcher PD Dr. Müller. He adds: "The same reprogramming strategy is also used by the MERS coronavirus, whose autophagy-inhibiting action we were able to demonstrate more than a year ago. However, there are other coronaviruses which, quite in contrast to this, induce autophagy. These mainly infect animals."

When results from the study suggested that the recycling mechanism might be a potential target for COVID-19 therapy, the researchers tested whether substances which induce cellular recycling also reduce the replication of SARS-CoV-2 inside infected cells. Interestingly, the researchers found four substances which proved effective - all of them already in use in humans. These included the polyamine spermidine, an autophagy-enhancing metabolite which is produced in all human cells and by bacteria in the human gut. It occurs naturally in foods such as wheat germ, soya, mushrooms, and mature cheese and is freely available as a food supplement. When the researchers added spermidine to cells infected with SARS-CoV-2, this resulted in an 85 percent reduction in the numbers of virus particles produced. Similar results were produced by spermine, another polyamine which occurs naturally in the body. This derivative of spermidine was found to reduce viral replication by more than 90 percent in human lung cells and in a human gut model comprising clusters of cells known as 'organoids'.

"The obvious effects produced by spermidine and, in particular, spermine are certainly encouraging. For one thing, substances which occur naturally in the body are less likely to induce side effects," says PD Dr. Müller. "Having said that, we worked with pure forms of these substances which are not suitable for medical use. Spermidine, in particular, has to be used at relatively high concentrations to achieve an appreciable effect in cell culture. Many questions therefore remain to be answered before we can consider polyamines as a potential treatment against COVID-19: When used in the body, will it be possible to achieve blood levels high enough to inhibit viral replication in the respiratory tract? And, if yes: would administration before or during the infection be advisable? Are there any side effects? Even so, our findings from cell culture are a good starting point for research involving animal models. Self-medication is not advisable, one of the reasons being that viruses also use polyamines to help boost replication; the correct dosage is therefore crucial. The same applies to fasting, which can stimulate the body's autophagy process. Given that the body needs energy to mount an immune response, it remains unclear whether fasting is advisable in SARS-CoV-2 infected patients."

The third substance to prove effective against SARS-CoV-2 was the 'AKT inhibitor' MK-2206. The substance is currently at the clinical trial stage and undergoing testing for its tolerability and efficacy against a range of different cancers. In the current study, MK-2206 reduced the production of infectious SARS-CoV-2 virus by approximately 90%. It did so at plasma concentrations which had already been achieved during a previous study. "Based on our data, I would consider MK-2206 as an interesting treatment candidate against COVID-19 which, after a careful analysis of risks and benefits, would justify further study in clinical trials," explains PD Dr. Müller.

The most pronounced antiviral effect was associated with niclosamide, which the researchers had shown to be effective against the MERS coronavirus during an earlier study. The tapeworm drug was found to reduce the production of infectious SARS-CoV-2 particles by more than 99 percent. "Niclosamide showed the strongest effect in our cell culture-based experiments. What is more, it has been licensed for use against tapeworm infections in humans for a very long time and is well tolerated at potentially relevant doses," says PD Dr. Müller. He adds: "Out of the four new candidate substances, we consider it to be the most promising one. This is why we are now conducting a clinical trial at Charité to test whether niclosamide might also have a positive effect on people with COVID-19. I am delighted at this development. It shows how quickly findings from basic research can reach patients if research and clinical practice are closely interlinked and work together in an efficient manner."

The Phase II clinical trial - entitled 'NICCAM' - is being led by Prof. Dr. Martin Witzenrath, Deputy Head of Charité's Department of Infectious Diseases and Respiratory Medicine. The study will test the safety, tolerability, and efficacy of niclosamide combined with camostat (another licenced drug) in patients recently (within the last few days) diagnosed with COVID-19. The study is currently recruiting and looking for participants. Potential participants wishing to find out more information on the study should contact the team at 'Charité Research Organisation' on +49 30 450 539 210 or by emailing patienten@charite-research.org.

In humans, adenoviruses can infect the cells of the respiratory tract, while herpes viruses can infect those of the skin and nervous system. In most cases, this does not lead to the production of new virus particles, as the viruses are suppressed by the immune system. However, adenoviruses and herpes viruses can cause persistent infections that the immune system is unable to completely suppress and that produce viral particles for years. These same viruses can also cause sudden, violent infections where affected cells release large amounts of viruses, such that the infection spreads rapidly. This can lead to serious acute diseases of the lungs or nervous system.

Automatic detection of virus-infected cells

The research group of Urs Greber, Professor at the Department of Molecular Life Sciences at the University of Zurich (UZH), has now shown for the first time that a machine-learning algorithm can recognize the cells infected with herpes or adenoviruses based solely on the fluorescence of the cell nucleus. "Our method not only reliably identifies virus-infected cells, but also accurately detects virulent infections in advance," Greber says. The study authors believe that their development has many applications - including predicting how human cells react to other viruses or microorganisms. "The method opens up new ways to better understand infections and to discover new active agents against pathogens such as viruses or bacteria," Greber adds.

The analysis method is based on combining fluorescence microscopy in living cells with deep-learning processes. The herpes and adenoviruses formed inside an infected cell change the organization of the nucleus, and these changes can be observed under a microscope. The group developed a deep-learning algorithm - an artificial neural network - to automatically detect these changes. The network is trained with a large set of microscopy images through which it learns to identify patterns that are characteristic of infected or uninfected cells. "After training and validation are complete, the neural network automatically detects virus-infected cells," explains Greber.

Reliably predicting severe acute infections

The research team has also demonstrated that the algorithm is capable of identifying acute and severe infections with 95 percent accuracy and up to 24 hours in advance. Images of living cells from lytic infections, in which the virus particles multiply rapidly and the cells dissolve, as well as images of persistent infections, in which viruses are produced continuously but only in small quantities, served as training material. Despite the great precision of the method, it is not yet clear which features of infected cell nuclei are recognized by the artificial neural network to distinguish the two phases of infection. However, even without this knowledge, the researchers are now able to study the biology of infected cells in greater detail.

The group has already discovered some differences: The internal pressure of the nucleus is greater during virulent infections than during persistent phases. Furthermore, in a cell with lytic infection, viral proteins accumulate more rapidly in the nucleus. "We suspect that distinct cellular processes determine whether or not a cell disintegrates after it is infected. We can now investigate these and other questions," says Greber.

Hypoxia, or the inadequate oxygenation of a tissue, is a condition occurring frequently in all solid tumours such as melanoma skin cancer. Melanoma cells are not only able to survive oxygen deprivation, but also to use it to their own advantage by hijacking the anti-tumour immune response and developing resistance mechanisms to conventional anti-cancer therapies. A key gene responsible for cancer cell adaptation to hypoxia is HIF-1α (Hypoxia Inducible Factor-1 alpha). Led by Dr Bassam Janji, head of the Tumor Immunotherapy and Microenvironment (TIME) research group at the Luxembourg Institute of Health (LIH) and in collaboration with Gustave Roussy Cancer Center in France and the Thumbay Research Institute of Precision Medicine at Gulf Medical University in the United Arab Emirates, the team used gene editing technologies to show how targeting HIF-1α could not only inhibit tumour growth, but also drive cytotoxic (toxic to cells) immune cells to the cancer tissue. This discovery provided a valuable new target to make resistant melanomas more vulnerable to available anti-cancer treatments. Their findings were recently published in the reputable Oncogene Journal.

Melanoma is a type of skin cancer that develops from melanocytes, cells that are responsible for the production of pigments. Melanomas become harder to treat if not detected early, with emerging treatment resistance being an important barrier to their effective management. Due to their rapid growth rate and low blood supply, solid tumours including melanoma often exhibit areas of hypoxia. Hypoxia, or the decrease of oxygen in the tumour microenvironment, would normally cause tumour cell death. "However, certain solid tumours have evolved to survive this hostile microenvironment by activating HIF-1α, a gene reported to be a major factor mediating the adaptive response to changes in tissue oxygen level," explains Dr Janji. William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza were awarded the Nobel Prize in Physiology or Medicine in 2019 for their discovery of HIF-1? and how cells use it to sense hypoxia. Hypoxia has also been reported to be responsible for the failure of tumour response to conventional anti-cancer therapies and can prevent the infiltration of immune cells into the tumour. It is therefore crucial to understand the mechanisms by which cancer cells overcome this hypoxic environment to improve the effectiveness of available anti-cancer therapies.

In this context, the team led by Dr Janji sought to inactivate the functionality of the HIF-1α gene using CRISPR gene editing technology and investigate the impact of such inactivation on tumour growth, immune cell infiltration and response to immunotherapy in a preclinical melanoma mouse model.

"Our study revealed that blocking the activity of HIF-1α significantly inhibited melanoma growth and amplified the infiltration of immune cells into the tumour microenvironment by increasing the release of CCL5, a well-defined mediator involved in driving cytotoxic immune cells to the tumour battlefield", summarises Dr Audrey Lequeux, first author of the publication. Importantly, the study also showed that combining a drug devised to stop hypoxia significantly improves melanoma immunotherapy. When the results were validated retrospectively in a cohort of 473 melanoma patients, the hypoxic signature of tumours was correlated to worsened outcomes and the lack of immune cell infiltration into tumours, which is considered as a major characteristic of tumour resistance to immunotherapies.

"Together, our data strongly argue that therapeutic strategies disrupting HIF-1α would be able to modulate the tumour microenvironment to permit the infiltration of immune cells. Such strategies could be used to improve vaccine-based and immune checkpoint blockade-based cancer immunotherapies in non-responder melanoma patients," conclude Dr Chouaib and Dr Janji from Gulf Medical University and Luxembourg Institute of Health, respectively.

A research group led by Professor Sachie Hiratsuka, Institute for Biomedical Research, Shinshu University, has found that a specific sequence of messenger RNA (mRNA), which exists outside cells, binds to receptors on the surface of natural killer (NK) cells and is taken up into the nucleus. The group found that NK cells with mRNA uptake are able to enhance their migration activity and interferon gamma production. Furthermore, NK cells incorporating the mRNA showed an inhibitory effect on cancer metastasis in animal experiments.

In recent years, the results of cancer treatment have been improving with the increase of medical technology. However, it is still difficult to effectively prevent cancer metastasis, so there is a need to develop new treatment methods. Cancer metastasis occurs when cancer cells in the body metastasize to other organs and grow again in those organs. The process is extremely complex, with various reactions occurring simultaneously, and it is difficult to say that we have enough basic knowledge at present.

In cancer metastasis, the cancer cells themselves undergo changes that increase their malignant potential, such as invasion of the surrounding tissues. At the same time, the target organ is in a condition to accept metastasizing cancer cells. Therefore, in order to prevent cancer metastasis, basic research is being conducted for a method that not only works directly on cancer cells but also works on the target organs.

Professor Hiratsuka's research team has been conducting basic research on the role of immune cells and pulmonary vascular endothelial cells in lung metastasis using a mouse model of cancer metastasis. It was found that in the mice with a primary tumor transplanted subcutaneously, some NK cells stimulated by cancer tissue migrate from the liver to the lung. Furthermore, these cells were found to have the function of suppressing cancer metastasis in the lungs, and these cells were named "anti-metastatic cells," but their molecular mechanism was not unknown. Therefore, the team decided to conduct research to elucidate the activation mechanism of anti-metastatic cells.

Messenger RNA exists inside the cell and is the blueprint for protein synthesis. Until now, it has been unclear whether mRNA also exists outside the cell, or if it does, whether it has any function other than making proteins. In this study, the group first showed the presence of mRNA in tissue-cultured medium. At the same time, they demonstrated anti-metastatic cells isolated from mice incorporated mRNA into their cells. The uptake of mRNA was attributed to the action of the ZC3H12D protein, which binds strongly to a specific part of the RNA called the AU-rich region. It was also found that the incorporated RNA was transported to the cell nucleus. Mouse anti-metastatic cells showed increased expression of genes resistant to death, activation of cell migration ability, and production of interferon gamma after incorporation of RNA. Furthermore, when the RNA-incorporated anti-metastatic cells were injected into mice, they inhibited cancer metastasis. These results indicate that some mRNAs are taken up by cells and transported to the nucleus, which may inhibit cancer metastasis. (Figure)

Special diets, exercise programs, supplements and vitamins, there is everywhere something supposed to help us live longer. Whether it actually works has not always been shown, but the average life expectancy of people has increased over the last 150 years. A study by an international team of researchers, including Claudia Fichtel and Peter Kappeler, scientists in the Behavioral Ecology and Sociobiology Unit at the German Primate Center (DPZ) - Leibniz Institute for Primate Research in Göttingen, indicates that we probably cannot slow down aging. The comparative studies with humans and non-human primates, indicates that it is not the rate at which humans age that slows down, but that the survival rate of younger individuals has changed over time (Nature Communications).

The team of scientists led by biologist Susan Alberts from Duke University, North Carolina, USA, compared data from nine human populations and 30 populations of non-human primates. Claudia Fichtel and Peter Kappeler participated in this study with data collected over 25 years from ten sifaka groups, a lemur species from Madagascar. The researchers have been conducting behavioral studies on lemurs for over 25 years at the DPZ Kirindy Forest field station on the west coast of the island.

The research team, comprising scientists from 14 different countries, analyzed patterns of births and deaths, looking at the relationship between life expectancy and lifespan equality.

Lifespan equality tell us how much the age of death varies in a population. If everyone tends to die at around the same age - for instance, if almost everyone can expect to live a long life and die in their 70s or 80s - lifespan equality is very high. If death could happen at any age - because of disease, for example - lifespan equality is very low.

In humans, lifespan equality is closely related to life expectancy: people from populations that live longer also tend to die at a similarly old age, while populations with shorter life-expectancies tend to have deaths distributed across a wider range of ages.

To understand if this pattern is uniquely human, the researchers turned to our closest relatives: non-human primates. What they found is that the tight relationship between life expectancy and lifespan equality is widespread among primates as well as humans. But why?

In most mammals, risk of death is high at very young ages, relatively low at adulthood, then it increases again after the onset of aging. Could higher life-expectancy be due to individuals ageing slower and living longer?

The primate populations tell us that the answer is probably no. Instead, the main sources of variation in the average age of death in different primate populations were infant, juvenile and young adult deaths. In other words, life expectancy and lifespan equality are not driven by the rate at which individuals senesce and become old, but by how many children and young adults die of reasons that have nothing to do with old age.

"In our research area in Madagascar, female sifakas have an average life expectancy of about 5 years, although some females can live up to 23 years," says Claudia Fichtel. "Because infant mortality is very high - about 65 percent of infants die within the first year of life - only few females manage to live to such an advanced age. Most juveniles are probably preyed upon by the fossa, the largest predator living in Madagascar."

Susan Alberts, professor of biology and evolutionary anthropology at Duke University and senior author of the study, adds: "Populations get older and older mostly because more and more individuals get through those early stages of life. Early life used to be so risky for humans, whereas now we prevent most early deaths."

TEL AVIV, Israel and RALEIGH, NC, June 21, 2021, RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced presentation of the positive Phase 2 safety and efficacy data for oral opaganib (Yeliva®, ABC294640) in hospitalized patients with COVID-19 pneumonia at the World Microbe Forum (WMF) 2021 (poster #: 5574).

Results and post hoc analyses of data from the 40-patient U.S. Phase 2 study were presented in a poster entitled, "Opaganib, an Oral Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: A Randomized, Double-blind, Placebo-controlled Phase 2A Study, in Adult Subjects Hospitalized with SARS-CoV-2 Positive Pneumonia (NCT: 04414618)" . Patients in the study were randomized to receive either opaganib or placebo in addition to standard of care (SoC), predominantly including dexamethasone and/or remdesivir. Findings include:

50% of patients treated with opaganib (n=22) reached room air by Day 14 compared to 22% in the placebo group (n=18). The benefit of reaching room air by Day 14 for patients on opaganib was maintained regardless of whether the patients were receiving dexamethasone and/or remdesivir

86.4% of patients treated with opaganib were discharged from hospital by Day 14 compared to 55.6% of patients treated with placebo

Median time to discharge was 6 days for the opaganib group compared to 7.5 days for the placebo group

81.8% of opaganib patients achieved a 2-point improvement in the WHO Ordinal Scale compared to 55.6% of patients in the placebo group - achieved in a median time of 6 days versus 7.5 days, respectively

No significant differences in safety-related measures between the two groups (with diarrhea being the main treatment-emergent difference in tolerability)

"The need for an effective oral therapy to treat COVID-19 is clear. Such a therapy would greatly improve our ability to manage this pandemic," said Kevin Winthrop, MD, MPH, Professor of Infectious Diseases at Oregon Health & Science University, who presented the findings at WMF. "These data, from this proof-of-concept clinical study of opaganib in patients with severe COVID-19, suggest a potential role of SK2 inhibition in combating the effects of this virus. With much more data on opaganib expected in the coming weeks, we could make some real progress toward having access to a much-needed oral therapy for patients who currently have a paucity of options available to them."

"Presentation of these positive data from our exploratory Phase 2 study support our growing confidence that opaganib could be the first novel, oral therapy to demonstrate efficacy in the treatment of COVID-19 in a large late-stage study. With the recent completion of enrollment of our 475-patient global Phase 2/3 study, we will have a clearer picture of that in the very near future," said Mark L. Levitt, MD, Ph.D., Medical Director at RedHill. "Opaganib acts on both the cause and effect of COVID-19 via a unique dual antiviral and anti-inflammatory mode of action. Being host-targeted, opaganib is also expected to maintain effect against the emerging SARS-CoV-2 variants, which continue to threaten the progress being made against the pandemic and underscore the urgent need for effective COVID-19 therapeutics."

The global 475-patient Phase 2/3 study of opaganib in severe COVID-19 has been approved in 10 countries and completed enrollment, through 57 participating sites, on June 6th. The primary endpoint of the study is the proportion of patients breathing room air without oxygen support by Day 14. Additional important outcome measures, such as time to discharge from hospital, improvement according to the World Health Organization Ordinal Scale for Clinical Improvement and incidence of intubation and mortality, will also be captured in the follow-up period of up to 6 weeks. The study received four independent DSMB recommendations to continue following unblinded safety reviews and a futility review. Additionally, an evaluation of the blinded blended intubation and mortality rates to date was encouraging as compared to reported rates of mortality from large platform studies such as RECOVERY, and other studies in similar patient populations .

Extreme heat waves in urban areas are much more likely than previously thought, according to a new modeling approach designed by researchers including University of Illinois Urbana-Champaign Civil and Environmental Engineering (CEE) assistant professor Lei Zhao and alumnus Zhonghua Zheng (MS 16, PhD 20). Their paper with co-author Keith W. Oleson of the National Center for Atmospheric Research, "Large model structural uncertainty in global projections of urban heat waves," is published in the journal Nature Communications.

Urban heat waves (UHWs) can be devastating; a 1995 heat wave in Chicago caused more than 1,000 deaths. Last year's heat wave on the west coast caused wildfires. Global warming is expected to increase the incidence and severity of UHWs, but if cities fully understand their risk, they can prepare better with forecasts and warnings, safety guidance and improving access to health facilities like cooling centers and hospitals. Longer-term strategies include adaptation practices, which help cities adapt to the warmer temperatures induced by climate change - such as highly reflective roofs and pavements and green infrastructure - and mitigation practices, which help reduce the carbon emission - like renewable energy.

In recent years, though, an increase in record-breaking UHWs has caused concerns that the computer models used to predict them are flawed, leading to a systematic underestimation of their frequency and severity. Without accurate models, cities may dramatically misjudge their risk and fail to prepare accordingly, putting their citizens at greater risk as the world heats up.

Zhao's team has developed a model that closes two major gaps in urban climate modeling. First, most traditional climate models effectively ignore cities entirely. Urban areas make up only 2-3 percent of the earth's land, so their effect on global models is negligible, but more than half of the world's population lives in urban areas, so their impact is significant. The team's new modeling approach addresses that by providing urban-specific climate signals.

Second, because of this lack of urban representation in state-of-the-art climate models, there were no global-scale, multi-model projections for urban climates. The multi-model projections are critical to characterize the robustness and uncertainty of the projections, which is very important for estimating the climate-driven risks, for example, the likelihood of climate extremes. The new model provides global multi-model projections of local urban climates.

The paper also highlights four high-stakes regions - the Great Lakes region, southern Europe, central India and north China - and finds that cities in those areas had dramatically lower probabilities of risk with a single-model approach than with the researchers' multi-model approach. For example, the researchers found that using only traditional models, the Great Lakes region was expected to experience an extreme heat event only once in 10,000 years; with the researchers' new modeling technique, such events could be expected once every four years.

"This work highlights the critical importance of having multi-model projections to accurately estimate the likelihood of extreme events that will occur in the future under climate change," Zhao said.

An increasing number of studies on artificial intelligence (AI) are published in the dental and oral sciences but aspects of these studies suffer from a range of limitations. Standards towards reporting, like the recently published CONSORT-AI extension, can help to improve studies in this emerging field. Watch authors Falk Schwendicke and Joachim Krois of the Charité - Universitätsmedizin Berlin, Germany, discuss the Journal of Dental Research (JDR) article "Better Reporting of Studies on Artificial Intelligence: CONSORT-AI and Beyond," moderated by JDR Editor-in-Chief Nicholas Jakubovics, Newcastle University, England.

Watch: https://bit.ly/3zBpRUW
View article: https://bit.ly/2SHWf81

For AI studies in healthcare, only a limited number of randomized controlled trials are available, many studies are low quality and reporting is often insufficient to fully comprehend and possibly replicate these studies. Reporting standards such as the CONSORT (Consolidated Standards of Reporting Trials) statement, which provides evidence-based recommendations for reporting of randomized controlled trials, have been widely adopted by journals and have been shown to increase reporting quality. The new CONSORT-AI extension specifically addresses issues relating to the use of AI in clinical trials.

Randomized controlled trials are often used to inform decision-makers in health policy, regulatory, and clinical care, comprehensive and systematic reporting, allowing to gauge a trial's methodology, validity and bias as well as facilitating replication, is crucial. With the rapid expansion of AI as a tool to enhance clinical trials and other research studies, it is critical that steps are made to standardize reporting in this area.

"Given the emergence of studies on AI in dentistry, action is needed," said Jakubovics. "Standards like the recently published CONSORT-AI extension will improve reporting of AI studies in dentistry. The Journal of Dental Research encourages authors, reviewers and readers to adhere to these standards. A range of further aspects along the AI lifecycle should be considered when conceiving, conducting, reporting or evaluating studies on AI in dentistry."

Forces of nature have been outsmarting the materials we use to build our infrastructure since we started producing them. Ice and snow turn major roads into rubble every year; foundations of houses crack and crumble, in spite of sturdy construction. In addition to the tons of waste produced by broken bits of concrete, each lane-mile of road costs the U.S. approximately $24,000 per year to keep it in good repair.

Engineers tackling this issue with smart materials typically enhance the function of materials by increasing the amount of carbon, but doing so makes materials lose some mechanical performance. By introducing nanoparticles into ordinary cement, Northwestern University researchers have formed a smarter, more durable and highly functional cement.

The research was published today (June 21) in the journal Philosophical Transactions of the Royal Society A.

With cement being the most widely consumed material globally and the cement industry accounting for 8% of human-caused greenhouse gas emissions, civil and environmental engineering professor Ange-Therese Akono turned to nanoreinforced cement to look for a solution. Akono, the lead author on the study and an assistant professor in the McCormick School of Engineering, said nanomaterials reduce the carbon footprint of cement composites, but until now, little was known about its impact on fracture behavior.

"The role of nanoparticles in this application has not been understood before now, so this is a major breakthrough," Akono said. "As a fracture mechanics expert by training, I wanted to understand how to change cement production to enhance the fracture response."

Traditional fracture testing, in which a series of light beams is cast onto a large block of material, involves lots of time and materials and seldom leads to the discovery of new materials.

By using an innovative method called scratch testing, Akono's lab efficiently formed predictions on the material's properties in a fraction of the time. The method tests fracture response by applying a conical probe with increasing vertical force against the surface of microscopic bits of cement. Akono, who developed the novel method during her Ph.D. work, said it requires less material and accelerates the discovery of new ones.

"I was able to look at many different materials at the same time," Akono said. "My method is applied directly at the micrometer and nanometer scales, which saves a considerable amount of time. And then based on this, we can understand how materials behave, how they crack and ultimately predict their resistance to fracture."

Predictions formed through scratch tests also allow engineers to make changes to materials that enhance their performance at the larger scale. In the paper, graphene nanoplatelets, a material rapidly gaining popularity in forming smart materials, were used to improve the resistance to fracture of ordinary cement. Incorporating a small amount of the nanomaterial also was shown to improve water transport properties including pore structure and water penetration resistance, with reported relative decreases of 76% and 78%, respectively.

Implications of the study span many fields, including building construction, road maintenance, sensor and generator optimization and structural health monitoring.

By 2050, the United Nations predicts two-thirds of the world population will be concentrated in cities. Given the trend toward urbanization, cement production is expected to skyrocket.

Introducing green concrete that employs lighter, higher-performing cement will reduce its overall carbon footprint by extending maintenance schedules and reducing waste.

Alternately, smart materials allow cities to meet the needs of growing populations in terms of connectivity, energy and multifunctionality. Carbon-based nanomaterials including graphene nanoplatelets are already being considered in the design of smart cement-based sensors for structural health monitoring.

Akono said she's excited for both follow-ups to the paper in her own lab and the ways her research will influence others. She's already working on proposals that look into using construction waste to form new concrete and is considering "taking the paper further" by increasing the fraction of nanomaterial that cement contains.

"I want to look at other properties like understanding the long-term performance," Akono said. "For instance, if you have a building made of carbon-based nanomaterials, how can you predict the resistance in 10, 20 even 40 years?"

The study, "Fracture toughness of one- and two-dimensional nanoreinforced cement via scratch testing," was supported by the National Science Foundation Division of Civil, Mechanical and Manufacturing Innovation (award number 18929101).

Akono will give a talk on the paper at The Royal Society's October meeting, "A Cracking Approach to Inventing Tough New Materials: Fracture Stranger Than Friction," which will highlight major advances in fracture mechanics from the past century.