How artificial intelligence can explain its decisions

Artificial intelligence (AI) can be trained to recognise whether a tissue image contains a tumour. However, exactly how it makes its decision has remained a mystery until now. A team from the Research Center for Protein Diagnostics (PRODI) at Ruhr-Universität Bochum is developing a new approach that will render an AI’s decision transparent and thus trustworthy. The researchers led by Professor Axel Mosig describe the approach in the journal Medical Image Analysis, published online on 24 August 2022.
For the study, bioinformatics scientist Axel Mosig cooperated with Professor Andrea Tannapfel, head of the Institute of Pathology, oncologist Professor Anke Reinacher-Schick from the Ruhr-Universität’s St. Josef Hospital, and biophysicist and PRODI founding director Professor Klaus Gerwert. The group developed a neural network, i.e. an AI, that can classify whether a tissue sample contains tumour or not. To this end, they fed the AI a large number of microscopic tissue images, some of which contained tumours, while others were tumour-free.
“Neural networks are initially a black box: it’s unclear which identifying features a network learns from the training data,” explains Axel Mosig. Unlike human experts, they lack the ability to explain their decisions. “However, for medical applications in particular, it’s important that the AI is capable of explanation and thus trustworthy,” adds bioinformatics scientist David Schuhmacher, who collaborated on the study.
AI is based on falsifiable hypotheses
The Bochum team’s explainable AI is therefore based on the only kind of meaningful statements known to science: on falsifiable hypotheses. If a hypothesis is false, this fact must be demonstrable through an experiment. Artificial intelligence usually follows the principle of inductive reasoning: using concrete observations, i.e. the training data, the AI creates a general model on the basis of which it evaluates all further observations.
The underlying problem had been described by philosopher David Hume 250 years ago and can be easily illustrated: No matter how many white swans we observe, we could never conclude from this data that all swans are white and that no black swans exist whatsoever. Science therefore makes use of so-called deductive logic. In this approach, a general hypothesis is the starting point. For example, the hypothesis that all swans are white is falsified when a black swan is spotted.
Activation map shows where the tumour is detected
“At first glance, inductive AI and the deductive scientific method seem almost incompatible,” says Stephanie Schörner, a physicist who likewise contributed to the study. But the researchers found a way. Their novel neural network not only provides a classification of whether a tissue sample contains a tumour or is tumour-free, it also generates an activation map of the microscopic tissue image.
The activation map is based on a falsifiable hypothesis, namely that the activation derived from the neural network corresponds exactly to the tumour regions in the sample. Site-specific molecular methods can be used to test this hypothesis.
“Thanks to the interdisciplinary structures at PRODI, we have the best prerequisites for incorporating the hypothesis-based approach into the development of trustworthy biomarker AI in the future, for example to be able to distinguish between certain therapy-relevant tumour subtypes,” concludes Axel Mosig.
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New treatment could result in more donor lungs

A large amount of lungs donated cannot be used for transplantation. Researchers at Lund University in Sweden and Skåne University Hospital have conducted an animal study bringing hope that more donor lungs could be used in the future. The researchers have launched a pilot study to investigate whether the treatment will have the same positive effects on human beings.
About 190 organs are donated in Sweden every year. Due to injuries to the lungs, only about 30 percent of them can be used for transplantation. Adding to that, the mortality rate is high: about half of the patients pass away within five years of transplant.
“The results from our study indicate that a certain treatment can help us use a larger part of a donor lung, and that there is an improved outcome during the first two days after surgery,” says Sandra Lindstedt, senior consultant in thoracic surgery at Skåne University Hospital and adjunct professor at Lund University.
In their study on pigs, the researchers investigated the effects of reducing the levels of cytokines in lungs. Cytokines are small proteins that are produced by specific cells of immune system.
The function of the lungs was reduced before transplant so that the lungs developed acute respiratory distress syndrome (ARDS). By doing this, the lungs acquired injuries similar to those of donor lungs in humans. In ten cases the donor lung was treated — either before and after transplant or only after transplant. Six cases composed a control group and were not given any treatment.
“The results show that the lung function was restored to a higher capacity than before thanks to the reduced levels of cytokines. We could also see that the lungs were functioning better after the transplant and that complications during the first 48 hours after transplant was reduced,” says Sandra Lindstedt.
About 50 to 60 lung transplants are performed each year at Skåne University Hospital in Lund and Sahlgrenska University Hospital in Gothenburg. The hope is that the number will increase thanks to the new treatment.
“This will not work on all donor lungs but if we can use it on some of the donor lungs that are discarded today, it could be of great significance for patients on the waiting list for a transplant. We hope to create the needed prerequisites to save more patients,” Sandra Lindstedt says.
To be able to conduct the study, a special unit was created within the Department of Cardiothoracic and Vascular Surgery, Anaesthesia and Intensive Care at Skåne University Hospital. The unit brought together all the competencies needed for the study.
“This study would not be possible without the great efforts of different clinical specialities, such as thoracic surgeons, anaesthesiologists, perfusionists, operating room nurses and anaesthesiology nurses.”
The study results, which are published in Nature Communications, are the basis of a newly started clinical pilot study.
“We have started to include the first patients in the pilot study at Skåne University Hospital in Lund. The whole study consists of 20 transplants, half of which will be treated to reduce the cytokine levels, and the rest will be treated in the conventional way. If we get positive results, we will expand the study and include 120 transplants nationally,” Sandra Lindstedt concludes.
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COVID rekindled an appreciation of nature for many

The pandemic has impacted our lives in a multitude of ways, many of which will no doubt be felt for years to come. While many of those effects are clearly negative, UConn researchers have identified at least one positive impact — our perception of natural spaces changed. The findings are published in Nature Scientific Reports.
As people flocked to outdoor spaces for recreation in the spring of 2020, Sohyun Park, assistant professor in UConn’s College of Agriculture, Health and Natural Resources Department of Plant Science and Landscape Architecture, noticed some interesting trends: more people were on the trails, and many of those people had traveled from far away to enjoy nature.
Park was also part of the team for the Connecticut Trail Census and co-wrote a paper about the trends.
Sohyun Park of the Department of Plant Science and Landscape Architecture in her office in the W.B. Young Building. Mar. 8, 2022. (Jason Sheldon/UConn Photo)
“What’s interesting was rural trail use increased compared to urban trails,” Park says. “I wanted to try to find out how people were changing their mindset or their attitudes or perceptions.”
To do this, Park and co-authors Seungman Kim and Jaehoon Lee of Texas Tech University, and Biyoung Heo of James Corner Field Operations, looked to social media data and machine learning techniques to help make sense of the vast quantities of information on Twitter and try to find a pattern among those data, says Park. They utilized Twitter’s Application Programming Interface (API), which allows researchers to obtain aggregated data from Twitter posts.

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Arterial stiffness raises blood pressure in adolescents via insulin resistance

In the young population, arterial stiffness, an emerging risk factor for hypertension, indirectly raises blood pressure via an increase in insulin resistance but not via an increase in body fat, a paper published in Frontiers in Cardiovascular Medicine concludes.
There is a global effort aimed at screening, identification, and early diagnosis of hypertension in order to prevent this “silent killer disease” and its sequelae from early life. There remain missing gaps in knowledge on pathways through which blood pressure is raised even in normal-weight populations who are physically active and have healthy lifestyle choices.
It is well known that obesity increases the risk of hypertension. Researchers have recently shown that arterial stiffness, which has been established as a causal risk factor for hypertension in adults, is also implicated in the young population. Arterial stiffness may also cause increased insulin resistance in adolescents and young adults. Unfortunately, clinical trials to lower arterial stiffness in adults have not been promising, and clinical trials in the young population are ongoing.
In the new study, researchers examined whether arterial stiffness raises blood pressure via increased body fat or insulin resistance in a largely normal-weight adolescent population. This is because clinical trials in the young population have shown that lifestyle intervention could lower body fat and insulin resistance. Therefore, should arterial stiffness indirectly raise blood pressure through any of these pathways, it could be clinically relevant to intercept that path.
“We found that arterial stiffness indirectly raised blood pressure in adolescence via the insulin resistance pathway. It is nonetheless surprising that increased body fat was not a pathway through which arterial stiffness raised blood pressure in this general population of adolescents. Until results from clinical trials on reducing arterial stiffness in adolescents are available, it may be important for pediatricians and public health experts to focus on encouraging healthy lifestyle choices that lower insulin resistance thereby potentially lowering blood pressure. Increasing physical activity, reducing screen time, quitting smoking or vaping, reducing salt and sugar intake, increasing vegetable and fibre portion of diet, and having optimal daily sleep are healthy lifestyle choices,” says Andrew Agbaje, a physician and clinical epidemiologist at the University of Eastern Finland.
Dr Agbaje’s research group (urFIT-CHILD) is supported by research grants from Jenny and Antti Wihuri Foundation, the Finnish Cultural Foundation Central Fund, the Finnish Cultural Foundation North Savo Regional Fund, the Orion Research Foundation sr, the Aarne Koskelo Foundation, the Antti and Tyyne Soininen Foundation, the Paulo Foundation, the Yrjö Jahnsson Foundation, the Paavo Nurmi Foundation, the Finnish Foundation for Cardiovascular Research and the Foundation for Pediatric Research.
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Untangled blinking: Fluorescence patterns aid medical diagnostics

Standard medical imaging readily detects most solid brain cancers, one third of which are gliomas. Unfortunately, two complex surgeries are often necessary. But now, researchers from Japan may have devised a way to perform the initial biopsy, lab tests, and subsequent tumor removal during one surgical procedure.
During the first operation for a glioma, a surgical biopsy, the surgeon collects a sample of the suspect tissue. A lab then runs tests on the sample to diagnose the type of cancer (i.e., whether it is benign or not) and to determine what type of malignancy. Depending on the resulting treatment plan, you might then need a second surgical operation. However, in a study recently published in Chem, researchers from Osaka University and collaborating partners have used an advanced DNA-based fluorescence technique that could help bring real-time cancer diagnostics to medical practice. This study answers long-standing basic science questions and could open up new directions in medical care.
Photo-induced electron transfer is the basis of many DNA-based biosensors. Researchers’ understanding of the kinetics (i.e., rate) of this process is based on the average behavior of many molecules, known as ensemble measurements. “Such measurements obscure the single-molecule behavior that’s foundational to the kinetics of electron transfer,” explains Shuya Fan, lead author, “but our research clears this obscurity. We used fluorescence correlation spectroscopy to measure transient fluorescence patterns — fluorescence blinking — and in so doing uncovered single-molecule chemistry that will advance diagnostic applications.”
The researchers measured the relationship between the kinetics of electron transfer in single molecules of DNA with the distance and sequence of the DNA. The basis of their work was to photo-irradiate a fluorescent molecule, which initiated electron transfer from the DNA. A mathematical technique known as autocorrelation analysis indicated that a greater distance between fluorescent molecule and an electron donor (a hole acceptor) corresponded to a decreased speed of fluorescence blinking.
“Unexpectedly, the electron transfer rate for any given DNA sequence was a unique range of values — a pattern, rather than a precise value,” says Kiyohiko Kawai, senior author. “We used the corresponding fluorescence blinking to detect an mRNA glioma point mutation in cultured cells.”
An immediate extension of this research is an increased understanding of how point mutations spread in the body. Furthermore, the researchers’ approach is compatible with real-time glioma diagnosis during a surgical biopsy. Thus, targeted cancer therapy without the need for multiple surgeries is an additional realistic extension of this research development. Perhaps based on this research, cancer surgery will be simpler, faster, and more effective than today.
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New omicron BA.2.75 is as susceptible to antibodies as the currently dominant variant, findings suggest

In a recent study, researchers from Karolinska Institutet in Sweden, and others, have characterised the new omicron variant BA.2.75, comparing its ability to evade antibodies against current and previous variants. The study, published in the journal The Lancet Infectious Diseases, suggests that BA.2.75 is not more resistant to antibodies than the currently dominating BA.5, which is positive news.
In May 2022, a new variant of omicron, BA.2.75, was detected, which is driving a wave of infections in India, and has spread internationally. In the last few weeks, BA.2.75 has also been detected in Sweden.
“Identifying how vulnerable the population is, right now, to emerging variants is crucial,” says Daniel Sheward, researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and the study’s first author. “By producing a pseudovirus for BA.2.75, we were able to test its sensitivity to antibodies present in blood donors.”
Tests were carried out using 40 random blood samples taken in Stockholm, both before and after the first omicron wave.
“Our study shows that omicron BA.2.75 has approximately the same level of resistance to antibodies as the dominant variant BA.5, which is reassuring news if we were to suffer a BA.2.75 wave in Sweden,” says Ben Murrell, assistant professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and the study’s senior author.
The researchers from Karolinska Institutet, University of Cape Town, South Africa, ETH Zürich, Switzerland, Karolinska University Hospital, and Imperial College London, Great Britain, have also investigated whether antiviral monoclonal antibodies, which are used clinically to treat already infected patients, lose their effect against omicron BA.2.75, compared to BA.5. Here, too, the researchers found no alarming differences.
Ben Murrell’s lab will continue to monitor new mutations that are arising in omicron sublineages that may undermine vaccines.
The study was funded by the SciLifeLab’s Pandemic Laboratory Preparedness program, the Erling Persson Foundation, the European Union’s Horizon 2020 research and innovation programme. Daniel J. Sheward, Gunilla B. Karlsson Hedestam and Ben Murrell have intellectual property rights associated with antibodies that neutralise omicron variants.
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Establishing a novel strategy to tackle Huntington's disease

Through an international joint research effort involving ProQR Therapeutics of the Netherlands, Université Grenoble Alpes of France, and KTH Royal Institute of Technology of Sweden, Professor Ji-Soon Song’s research team in the Department of Biological Sciences and KAIST Institute for BioCentury of KAIST, established a noble strategy to treat Huntington’s disease. The new works showed that the protein converted from disease form to its disease-free form maintains its original function, providing new roadblocks to approach Huntington’s disease.
This research, titled, “A pathogenic-proteolysis resistant huntingtin isoform induced by an antisense oligonucleotide maintains huntingtin function,” co-authored by Hyeongju Kim, was published in the online edition of Journal of Clinical Investigation Insight on August 9, 2022.
Huntington’s disease is a dominantly inherited neurodegenerative disease and is caused by a mutation in a protein called ‘huntingtin’, which adds a distinctive feature of an expanded stretch of glutamine amino acids called polyglutamine to the protein. It is estimated that one in every 10,000 have Huntington’s disease in United States. The patients would suffer a decade of regression before death, and, thus far, there is no known cure for the disease.
The cleavage near the stretched polyglutamine in mutated huntingtin is known to be the cause of the Huntington’s disease. However, as huntingtin protein is required for the development and normal function of the brain, it is critical to specifically eliminate the disease-causing protein while maintaining the ones that are still normally functioning. The research team showed that huntingtin delta 12, the converted form of huntingtin that is resistant to developing cleavages at the ends of the protein, the known cause of the Huntington’s disease (HD), alleviated the disease’s symptoms while maintaining the functions of normal huntingtin.
This work was supported by a Global Research Lab grant from the National Research Foundation of Korea (NRF) and by a EUREKA Eurostars 2 grant from European Union Horizon 2020.
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Toxins in old toys an obstacle for circular economy

Letting children play with hand-me-down plastic toys could constitute a health risk. When researchers at the University of Gothenburg tested a large number of old toys and dress-up items made of plastic, 84 per cent of the items were found to contain toxins that can disrupt growth and development and reproductive capacities in children. These toxins are an obstacle for the circular economy in the future involving reuse and recycling, the researchers explain.
The current use-and-discard behaviour is wasteful with resources and a drain on the Earth’s finite resources. In 2021, the European Parliament adopted a Circular Economy Action Plan. It encourages the re-use, repair and recycling of products and materials. But the question is whether all products are good to reuse again?
Researchers from the University of Gothenburg have recently published an article in the Journal of Hazardous Materials Advances which shows that old toys and dress-up items may contain toxic chemicals that can cause cancer, damage DNA or disrupt the future reproductive capacities of children.
Toxic chemicals in most old toys
The hazardous chemicals that were discovered included phthalates and short chain chlorinated paraffins used as plasticizers and flame retardants in toys.
Professor Bethanie Carney Almroth at the University of Gothenburg conducts research on the environmental impact of plastics and plastic-related chemicals, and has led the research study conducted at the interdisciplinary Centre for Future Chemical Risk Assessment and Management Strategies (FRAM). For the study, researchers selected 157 different toys, new and old, and measured their chemical content.
The study showed that most of the older toys and items (84 per cent) contained quantities of chemicals that exceed current legal limits. A total of 30 per cent of the newer toys and items also exceeded the legal limits. By far however, the older toys were significantly worse.
“The concentrations of toxic substances were significantly higher in the older items. For example, many of the old balls were found to have concentrations of phthalates totalling more than 40 per cent of the toy’s weight, which is 400 times over the legal limit,” says Bethanie Carney Almroth.
Toxins an obstacle to a circular economy
EU legislation on the chemical content of toys, known as the Toy Safety Directive, regulates the permissible quantities of a number of chemical substances found in toys in an attempt to protect the health and safety of children. At present, the permissible limit values for new toys under the Toy Safety Directive are 0.1 per cent by weight for phthalates and 0.15 per cent by weight for short chain chlorinated paraffins.
“The study indicates that reuse and recycling is not always automatically a good thing. The transition to a more circular economy requires bans and other policy measures that get rid of hazardous chemicals from plastic and other materials. Although the Toy Safety Directive has been crucial in reducing the incidence of hazardous chemicals in toys, it has only been applicable to new toys, not old ones,” explains Daniel Slunge, Environmental Economist at the University of Gothenburg.
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Mystery pneumonia: Argentina investigates three deaths

Published34 minutes agoSharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesA third person has died this week in Argentina from an unexplained type of pneumonia that has affected nine people in total so far. All of the cases centre around a private medical clinic in northwestern Tucuman province. Authorities say they have ruled out Covid and common types of flu but are continuing other infection checks. Tests on the local water supply and air conditioners are also being done in the hunt for the cause. The third victim was a 70-year-old woman who had been admitted to the clinic for a surgical procedure.Doctors believe she may have been “patient zero” for the respiratory illness. The others who have fallen ill with the lung condition were medical staff at the centre. Their close contacts are under follow-up but none have developed symptoms to date. The mystery disease claimed its first victim among workers at the clinic on Monday and a second two days later. Both, like the 70-year-old woman, had other underlying health conditions. The first six patients started showing symptoms between August 18 and 23.Tucuman health minister Luis Medina Ruiz said on Wednesday the patients were struck with “a severe respiratory condition with bilateral pneumonia…very similar to Covid”.Symptoms included a high fever, body aches and difficulty breathing. Hector Sale, president of the Tucuman provincial medical college, told local reporters: “We are not dealing with a disease that causes person-to-person transmission” as no cases have been identified among close contacts of any of the patients.The Pan American Health Organization is monitoring the situation along with the Argentina health authorities.Related Internet LinksPan American Health OrganizationThe BBC is not responsible for the content of external sites.

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Circadian rhythm disruption found to be common among mental health disorders

Anxiety, autism, schizophrenia and Tourette syndrome each have their own distinguishing characteristics, but one factor bridging these and most other mental disorders is circadian rhythm disruption, according to a team of neuroscience, pharmaceutical sciences and computer science researchers at the University of California, Irvine.
In an article published recently in the Nature journal Translational Psychiatry, the scientists hypothesize that CRD is a psychopathology factor shared by a broad range of mental illnesses and that research into its molecular foundation could be key to unlocking better therapies and treatments.
“Circadian rhythms play a fundamental role in all biological systems at all scales, from molecules to populations,” said senior author Pierre Baldi, UCI Distinguished Professor of computer science. “Our analysis found that circadian rhythm disruption is a factor that broadly overlaps the entire spectrum of mental health disorders.”
Lead author Amal Alachkar, a neuroscientist and professor of teaching in UCI’s Department of Pharmaceutical Sciences, noted the challenges of testing the team’s hypothesis at the molecular level but said the researchers found ample evidence of the connection by thoroughly examining peer-reviewed literature on the most prevalent mental health disorders.
“The telltale sign of circadian rhythm disruption — a problem with sleep — was present in each disorder,” Alachkar said. “While our focus was on widely known conditions including autism, ADHD and bipolar disorder, we argue that the CRD psychopathology factor hypothesis can be generalized to other mental health issues, such as obsessive-compulsive disorder, anorexia nervosa, bulimia nervosa, food addiction and Parkinson’s disease.”
Circadian rhythms regulate our bodies’ physiological activity and biological processes during each solar day. Synchronized to a 24-hour light/dark cycle, circadian rhythms influence when we normally need to sleep and when we’re awake. They also manage other functions such as hormone production and release, body temperature maintenance and consolidation of memories. Effective, nondisrupted operation of this natural timekeeping system is necessary for the survival of all living organisms, according to the paper’s authors.

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