Tech

Blanchardville, Wis. - A new study reports high levels of patient satisfaction with a minimally invasive approach to creating vascular access for kidney patients who require hemodialysis. In addition, the researchers found that nearly all the dialysis access sites, or fistulas, were still functional after two years - a significant improvement over surgically created fistulas.

The study marks the first published two-year data for any endovascular fistula procedure. It was recently published online in the Journal of Vascular Access (JVA).

The multi-center study encompassed 105 U.S. patients who had their fistulas created with the Ellipsys® Vascular Access System and had at least two years of follow-up. Patients' responses in the study emphasized the avoidance of surgery, a perceived lack of pain and improved body image when compared to patients who underwent surgery.

Hemodialysis requires access to the patient's bloodstream, which is often created by establishing a permanent connection between an artery and a vein in the arm known as an arteriovenous fistula (AVF). Instead of an open surgical procedure, the innovative Ellipsys system creates a percutaneous AVF using just a small needle puncture and catheter.

"We knew fistulas created with Ellipsys functioned well in the beginning, but patients wanted to know how long their access sites would last. Our goal was to see how many still worked after two years while capturing patients' opinions on this innovative procedure," said Terry Litchfield, a study co-author and President of Access Solutions. "The results were overwhelmingly positive from both a patient and clinical perspective."

According to the survey responses, 93 percent of patients rated their overall satisfaction with the procedure as "excellent" or "very good." The study authors also reported that nearly 92 percent of the fistulas continued to function two years after the Ellipsys procedure. In contrast, less than two-thirds of surgically created fistulas are still functional after two years.

"The dramatic difference in durability between the endovascular fistulas and the surgically created ones is striking," said lead author Gerald Beathard, MD, PhD, a world-renowned interventional nephrologist at University of Texas Medical Branch. "The ability to quickly and easily create a fistula that will last a long time, without surgical trauma or the need for additional procedures, could represent a significant advance in dialysis patient care."

The study was also co-authored by esteemed vascular surgeon William Jennings, MD, University of Oklahoma.

An AVF is the first choice for hemodialysis access because it lowers infection risk, lasts longer and costs less compared to other vascular access methods, such as central venous catheters and grafts. Until recently, the only way to create an AVF was an open surgical procedure that subjects patients to discomfort, longer recovery times and delayed dialysis.

Approved by the FDA in 2018 for patients with end-stage kidney disease, Ellipsys is the first significant innovation in hemodialysis access in over 50 years. It transforms a complex surgery into a minimally invasive procedure that can be performed in a hospital outpatient setting or ambulatory surgical center. A faster recovery allows patients to start hemodialysis sooner. The lack of scars or disfigurement typically associated with surgical fistulas means a more normal cosmetic appearance -- something the study revealed is very important to patients, Litchfield noted.

"I had no surgery - no stitches, no cuts and I wasn't put to sleep. I left with a band aid and went about my day," said Theresa Torres of Mesa, Ariz., who underwent the Ellipsys procedure in 2015 and utilized the fistula for dialysis until her kidney transplant in 2018. "I love the fact that I have no scar on my arm. It was amazing when I'd look at my fistula next to others in the dialysis unit. There was really no comparison."

Litchfield, who has been a patient advocate in the renal community for over 30 years, said patient-reported outcomes are an important piece of the technology innovation puzzle. Relatively few device makers utilize patient perspectives in their development process, which makes both the Ellipsys technology and the two-year data even more meaningful.

"In keeping with the national Advancing American Kidney Health Initiative, this new technology gives kidney patients another choice for vascular access that has the potential to improve their quality of life," she said. "It's exciting to see the push for innovation in dialysis access and even more exciting that patients' voices are being included in the process."

The Ellipsys Vascular Access System is manufactured by Avenu Medical. Nearly 1,000 patients worldwide have had the Ellipsys procedure since 2015.

RICHMOND, Va. (Dec. 5, 2019) -- Patients with nonalcoholic steatohepatitis (NASH), a chronic liver disease and a leading cause for liver transplantation in the U.S., currently lack an approved drug therapy, but this may soon change. A large Phase III clinical trial designed in collaboration with Virginia Commonwealth University is the first to demonstrate the safety and effectiveness of an oral medication to treat the disease.

The drug therapy is pending approval from the Food and Drug Administration. Findings from the interim analysis of the REGENERATE study, sponsored by Intercept Pharmaceuticals, will publish in the medical journal The Lancet this week.

According to the National Institutes of Health, between 7 million and 30 million U.S. adults suffer from NASH, a severe form of fatty liver disease unrelated to alcohol abuse but closely related to obesity and Type 2 diabetes.

"NASH is definitely a modern lifestyle disease and on its way to becoming the leading cause of liver transplantation in the U.S. as early as 2020," said Arun Sanyal, M.D., the senior and corresponding author of the manuscript, and a professor in the Department of Internal Medicine in the VCU School of Medicine. "We hope that this landmark study will lead to the first approved drug therapy for NASH."

In patients suffering from NASH, the buildup of fat in the liver damages cells and causes inflammation. For many, NASH can progress to include scarring, called fibrosis, which prevents the liver from functioning properly. In severe cases, the condition can lead to liver cancer, liver failure or death. The REGENERATE study assesses the safety and efficacy of obeticholic acid in patients with liver fibrosis due to NASH.

"The treatment tested can reverse the course of NASH," Sanyal said. "Obeticholic acid showed an ability to successfully reverse liver scarring in patients most at risk for irreversible liver damage when evaluated 18 months into the study. The study will also follow the patients long term to see if these changes seen on a liver biopsy translate into improved clinical outcomes."

Given the silent nature of the disease, many patients progress to cirrhosis without being diagnosed. While developing an approved therapy is critical, it also will be important to develop simple diagnostic tools that can be used in clinics, Sanyal said. He currently is engaged in studies to develop such diagnostics. In the U.S. alone, the prevalence of NASH is expected to increase by 63% between 2015 and 2030.

A decade ago, Sanyal helped establish the scientific foundation for what may soon become the first approved drug therapy for NASH at the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research, where he serves as education core director. The scientific understanding of how bile acids enhance glucose disposal, which is a critical element of a condition called insulin resistance, led to a successful, federally funded Phase II FLINT trial in 2015, paving the way for the REGENERATE trial.

"Obeticholic acid, the new investigational drug submitted for FDA approval, is in essence a more potent, chemically modified version of a naturally occurring bile acid that plays a key role in our metabolism and also has anti-fibrotic effects," Sanyal said.

On average, countries implemented just under half of the 18 non-communicable disease (NCD) policies recommended by WHO in 2017, and implementation is slowly improving over time.

NCDs include cardiovascular disease, diabetes, cancer and chronic respiratory disease and are responsible for 73% of all global deaths.

The application of all 18 policies increased except for those targeting alcohol and physical activity.

Iran and Costa Rica score highest in the world for the number of policies they implemented by 2017. USA lags behind middle-income countries for implementing policies to reduce non-communicable diseases. UK is joint second with Norway, while Haiti and South Sudan come last.

The first analysis of WHO-recommended policies to prevent and control non-communicable diseases (NCDs) finds that implementation is slowly improving, but on average just over half get no further than being endorsed, according to results from 151 countries published in The Lancet Global Health journal. The current study is the first to analyse what progress was made in putting 18 policies into practice worldwide between 2015 and 2017.

In 2015, 193 countries committed to reduce premature NCD deaths by a third by 2030 as part of the UN's sustainable development goals. WHO member states have endorsed a set of interventions to help reduce the four main risk factors for NCDs: tobacco use, the harmful use of alcohol, unhealthy diets and physical inactivity. In 2018, the WHO's independent high-level commission on NCDs, of which The Lancet is a partner, called for bold actions from heads of state to prevent and treat NCDs and to promote mental health and wellbeing.

"The WHO has provided a road map to help governments respond to the challenge of reducing preventable premature deaths from non-communicable diseases, and we set out to see whether it's being followed in practice and, if not, why that might be," says Dr Luke Allen from the University of Oxford, UK. [1]

For their analysis, the authors used progress reports released by the WHO in 2015 and 2017, which monitored the extent to which 18 NCD policies were implemented in 151 countries. To score countries on how well they had implemented the policies, they awarded a point for every policy fully implemented, half a point for partial implementation, and zero for no implementation, or when there was no data (this was then converted into a percentage). The authors ranked countries according to the percentage of policies they had applied.

The new study found that overall, implementation improved from an average of 42% in 2015 to 49% in 2017, so the percentage of policies implemented remained just under half. 109 countries increased the number of NCD policies implemented, but in 32 countries progress reversed. In South Sudan and Haiti, only 5% of policies were implemented in 2017, while Costa Rica and Iran had the joint highest implementation scores, at nearly 87%.

On average, implementation improved for 14 out of 18 policies. The most commonly implemented were the introduction of clinical guidelines, graphic warnings on tobacco packaging and surveys on national NCD risk factors. The least widely implemented were market-related policies, including tobacco taxation, tobacco mass-media campaigns and alcohol advertising bans, as well as providing cardiovascular drug therapy. Many countries took a step backwards on promoting physical activity through mass-media campaigns (on average, implementation fell from 61% to 54%) and on imposing restrictions on the sale and promotion of alcohol (implementation of alcohol advertising bans fell by 10% between 2015 and 2017; from 43% to 33%).

The researchers analysed associations between the extent of implementation and seven political, geographic, economic and mortality indicators such as each nation's democracy index, World Bank income group and risk of premature death from NCDs. The results suggest that more policies were implemented in democratic centre-left countries. The authors say that, in theory, democracies are more responsive to their populations, although they point out that they might also be less likely to impose measures that constrain industry profits. For example, the USA performed poorly on market-related policies and came 50th out of 151 countries overall for the percentage of all policies it had implemented.

Many high-income countries were in the top 20 for implementation, while scores were lowest in low-income countries. For example, 17 of the bottom 20 countries were in sub-Saharan Africa. However, some countries defied this trend. For example, the highest implementation scores were achieved by two middle-income countries, Iran and Costa Rica, while Moldova ranked joint fifth overall for NCD policy implementation despite coming 130th out of the 151 countries in terms of gross national income.

"Although financial resources are helpful, putting NCD policies into effect is not necessarily expensive, and some - like taxes - can actually generate revenue, adding to a country's balance sheet rather than being a drain," says Beatrice Yeung from the University of Oxford, UK. [1]

The authors highlight several limitations to their study. For example, some policies are more effective than others at combating NCDs but the implementation scores treat them as equivalent. Meanwhile, the analysis of possible explanations for the wide variability in implementation was able to identify associations, but these cannot be seen as causes.

A new study finds more than two-fold differences between counties with the lowest and highest rates of surgery for patients with early stage lung cancer, with socioeconomic and healthcare delivery factors contributing to the gap. The study appears in the journal Chest.

Lung cancer is the leading cause of cancer-related death in the United States, with non-small cell lung cancer (NSCLC) accounting for about 85% of cases. Surgery is the standard treatment for early-stage (I or II) disease, but studies have documented variations in receipt of curative-intent surgery by race, facility type, and geography.

The authors of the current study recently reported substantial state-level variations in receipt of curative-intent surgery for NSCLC in the United States. For the current study, investigators at the American Cancer Society and Baptist Cancer Center, Memphis , led by Helmneh Sineshaw, M.D., MPH, looked at county-level variations within states to gain a sharper picture of the extent of care delivery problems.

A total of 179,189 patients 35 and older diagnosed with stage I/II NSCLC between 2007-2014 in 2,263 counties were identified from 39 states, the District of Columbia, and Detroit population-based cancer registries compiled by the North American Association of Central Cancer Registries. The percentage of patients who underwent surgery was calculated for each county with 20 or more cases of NSCLC.

The authors found surgery rates ranged from 12.8% to 48.6% in the 10% of counties with the lowest surgery rates to 74.3% to 91.7% in the 10% of counties with the highest rates of surgery. Pockets of low surgery rate-counties within each state were also identified. For example, there was a 25% absolute difference between the lowest and highest surgery receipt rate-counties in Massachusetts. Overall, counties in the lowest quartile for receipt of surgery were those with high proportion of non-Hispanic blacks, high poverty and uninsured rate, low surgeon-to-population ratio, and nonmetropolitan status.

"Receipt of curative-intent surgery for early-stage NSCLC varied substantially across counties in the United States with pockets of low receipt counties, even within states with high surgical resection rates," write the authors. "Area-level socioeconomic and healthcare delivery factors partially contributed to these variations, suggesting that concerted policy interventions targeting low access and high poverty counties may reduce variations in receipt of curative-intent surgery."

The authors say further studies are needed to identify and address gaps in access to surgical treatment of early-stage NSCLC, such as more direct evaluation of patient-, provider-, institution-, and community-level factors influencing access to and choice for or against curative-intent treatment modalities.

Researchers in Finland are "training" pieces of plastic to walk under the command of light. The method developed, published December 4 in the journal Matter, is the first time a synthetic actuator "learns" to do new "tricks" based on its past experiences, without computer programming.

These plastics, made from thermo-responsive liquid crystal polymer networks and a coat of dye, are soft actuators that can convert energy into mechanical motion. Initially, the actuator is only respondent to heat, but by associating light with heat, it learns to respond to light. In response, the actuator similarly bends itself as a human curls its index finger. By irradiating the actuator periodically, it "walks" like an inchworm with a speed of 1 mm/s, about the same pace of a snail.

"Our research is essentially asking the question if an inanimate material can somehow learn in a very simplistic sense," says senior author Arri Priimägi (@APriimagi), of Tampere University. "My colleague, Professor Olli Ikkala from Aalto University, posed the question: Can materials learn, and what does it mean if materials would learn? We then joined forces in this research to make robots that would somehow learn new tricks." The research team also includes postdoctoral researchers Hao Zeng, Tampere University, and Hang Zhang, Aalto University.

The conditioning process, which associates light with heat, allows the dye on the surface to diffuse throughout the actuator, turning it blue. The phenomenon increases the overall light absorption, which boosts the photothermal effect and raises the actuator's temperature. It then "learns" to bend upon irradiation.

"This study that we did was inspired by Pavlov's dog experiment," says Priimägi. In the experiment, a dog salivates in response to seeing food. Pavlov then rang the bell before giving the dog food. After a few repetitions, the dog associated food with the bell and started salivating upon hearing the bell. "If you think about our system, heat corresponds to the food, and the light would correspond to the bell in Pavlov's experiment."

"Many will say that we are pushing this analogy too far," says Priimägi. "In some sense, those people are right because compared to biological systems, the material we studied is very simple and limited. But under right circumstances, the analogy holds." The next step for the team is to increase the level of complexity and controllability of the systems, in order to find the limits of the analogies that can be drawn to biological systems. "We aim at asking questions which maybe allow us to look at inanimate materials from a new light."

But besides walking, the systems can also "recognize" and respond to different wavelengths of light that correspond to the coating of its dye. This characteristic makes the material a tunable soft micro-robot that can be remotely controlled, an ideal material for biomedical applications.

"I think there's a lot of cool aspects there. These remotely controlled liquid crystal networks behave like small artificial muscles," says Priimägi. "I hope and believe there are many ways that they can benefit the biomedical field, among other fields such as photonics, in the future."

Conditioning is a method made famous by Ivan Pavlov's experiments with dogs. Pavlov trained a dog by ringing a bell every time the dog was fed. The dog learned to associate the bell with food, and then drooled when it heard the bell ring, even if it didn't see anything to eat. In an earlier study, researchers at Aalto University and Tampere University succeeded in conditioning a solid gel so that it melted to become liquid under the influence of light alone. Now, the same researchers have taught a liquid crystal polymer to move, and to stick to an object of a given colour.

'At first, the liquid crystal polymer did not react to light at all, but during the process, it learned to move and grab objects under the guidance of light. The idea is the same as in the previous study, but now the conditioning includes tangible functions', Professor Olli Ikkala from Aalto University explained.

The plastic used in the study contains liquid crystal molecules whose positioning relative to one another is important for flexibility and transformation.

'Conditioning can teach materials new tricks, such as recognising colours or moving in conditions where they don't originally move,' said Professor Arri Priimägi from Tampere University.

Video: https://www.youtube.com/watch?v=05t9gV_zFH0&feature=youtu.be

'For material to learn, it must have a memory. When the material is heated, the dye originally spread on the surface of the liquid crystal polymer penetrates into the material, thus forming the memory. Different dyes react to different wavelengths of light, so the initially neutral stimulus (color of light) can be controlled by the dye applied onto it. Additionally, when designing the material, molecules must be positioned so that the material reacts as desired when heated,' Olli Ikkala said.

Soft robotics and adaptive materials

Soft robots copy nature and the human body. 'If you give a typical mechanical robot a strawberry it might crush it. So, we need robots that can grasp things very softly. Traditional robots also often need a power cord or a large, heavy battery. Soft robotics aims at lightweight, external control, for example by using light,' said Olli Ikkala.

According to Olli Ikkala, new kinds of materials with the ability to "learn" can be useful in soft robotics already now, even though the functions are still limited.

Arri Priimägi's team has specialised in soft robotics research for a few years now. According to Priimägi, this research can also open up new opportunities in materials technology. It may be possible in the future to create coating materials that change their function under different conditions.

'The concept of conditioning is not only tied to this experimental setting, but can be extended to other areas as well. But at the moment, conditioning is only achieved through the combined effect of light and heat,' Priimägi said.

Next, the researchers want to determine whether the materials can also be conditioned with completely independent signals. Light and heat are not completely independent because light also produces heat.

'Since functional materials can be controlled by a variety of other stimuli, such as electric and magnetic fields, humidity changes, or chemicals, in addition to light and heat, there are many alternatives to further developing this concept. The material must also have a memory which is activated by a signal,' Arri Priimägi said.

In addition to Olli Ikkala and Arri Priimägi, the research group includes postdoctoral researchers Hang Zhang from Aalto University and Hao Zeng from Tampere University. The research was carried out at the Academy of Finland's Centre of Excellence in Molecular Engineering of Biosynthetic Hybrid Materials (HYBER), and it is part of the Academy of Finland Flagship Programme on photonics (PREIN). The project has been funded by the European Research Council's projects DRIVEN and PHOTOTUNE. The research is being published in the journal Matter, and is available online here https://doi.org/10.1016/j.matt.2019.10.019.

Nearly six million Americans have heart failure, a leading driver of health care costs in the United States. The "stiff heart" heart failure variant accounts for about half of all cases and the vast majority of such patients take beta-blocker medications despite unclear benefit from their regular use. A new publication in JAMA Network Open links use of beta-blockers to heart failure hospitalizations among those with this common "stiff heart" heart failure subtype.

Heart failure occurs when the heart cannot meet the body's demands. About half of patients have heart failure characterized by a normal squeeze but impaired relaxation of the heart muscle from a "stiff heart". This is also known as heart failure with preserved ejection fraction. The other half of cases are due to a "weak heart" with an abnormal squeeze, also known as heart failure with reduced ejection fraction. Beta-blockers--medications that lower the heart rate and blood pressure--are strongly recommended in national guidelines for treatment of "weak heart" heart failure because of their clear benefit.

"A big problem with 'stiff heart' heart failure is that we don't have effective medical therapies," says coauthor Timothy Plante, M.D., an assistant professor of medicine at the Larner College of Medicine at the University of Vermont. "So, instead, we use the same medications that work for 'weak heart' heart failure. Because beta-blockers save lives in 'weak heart' heart failure, we assume they are also effective in 'stiff heart' heart failure patients--this assumption may be wrong."

Plante, lead author Daniel Silverman, M.D., senior author Markus Meyer, M.D., and colleagues analyzed data from the National Institutes of Health-funded TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) study, a trial of the medication spironolactone in patients with "stiff heart" heart failure. About four out of five study participants were on beta-blockers.

The researchers found beta-blocker use to be a risk factor for hospitalizations for heart failure among these patients with "stiff heart" heart failure.

"Beta-blocker use was associated with a 74 percent higher risk of heart failure hospitalizations among participants with heart failure and a normal pump function," says Meyer, an associate professor of medicine at the University of Minnesota Medical School.

Despite their common use, the authors note that beta-blocker use in "stiff heart" heart failure has not been sufficiently studied. This publication extends their prior work, which found that halting beta-blockers markedly improves levels of the heart failure blood test known as BNP among patients with "stiff heart" heart failure.

"In 'stiff heart' heart failure, the heart is less able to relax and fill with blood. Beta-blockers appear to increase pressures inside the heart. This may lead to symptoms like worsening shortness of breath and retention of fluid," says Silverman, a cardiology fellow and clinical instructor in medicine at the University of Vermont Medical Center and Larner College of Medicine.

"Even people without heart failure will have more shortness of breath and less exercise capacity. This has been a known class side effect for decades," says Meyer. "It is important to understand that our findings are not proof that beta-blockers are harmful among patients with 'stiff heart' heart failure - it is just a concerning signal."

They believe their findings warrant a clinical trial to evaluate the safety and effects of beta-blockers in patients with "stiff heart" heart failure. "There are some big next steps, like reproducing this finding in other studies and testing if there is a benefit of stopping beta-blockers in patients with 'stiff heart' heart failure," says Silverman.

A recent analysis offers estimates of the changes in incidence of Alzheimer's disease in the United States, confirming previous reports of a declining trend. The analysis, which is published in the Journal of the American Geriatrics Society, also highlights considerable geographic variation in incidence rates across the country.

The retrospective analysis of administrative claims data for a 5% random sample of Medicare beneficiaries aged 65 years or older revealed that the diagnosed incidence of Alzheimer's disease in the United States decreased from 1.53% in 2007 to 1.09% in 2014. The trend over time was similar for most geographical areas; however, in 2014, the estimates of Alzheimer's disease incidence varied considerably by region--from 0% to more than 3%, with the highest incidence rates observed in areas of the Midwest and the South. ?

"Although additional research is needed to understand the reasons behind the observed trends in the incidence of Alzheimer's disease, our findings underscore the need to consider regional factors when contemplating policy directives aimed at improving the identification and management of people with cognitive impairment," said corresponding author Urvi Desai, PhD, of Analysis Group, Inc.

New research indicates that social media is leading young adolescent girls and boys down a worrying path towards developing body image issues and eating disorder behaviours - even though they are smartphone savvy.

The Australian research, published in the International Journal of Eating Disorders (Wiley), found platforms with a strong focus on image posting and viewing such as Instagram and Snapchat are the most used and the most risky.

Flinders and University of Western Australia researchers surveyed 996 Year 7 and 8 'middle school' adolescents on their use of Instagram, Facebook, Tumblr and Snapchat.

Behaviours related to disordered eating were reported by 51.7% of girls, and 45% of the boys, with strict exercise and meal skipping to lose weight or prevent weight gain being the most common.

A total of 75.4% of girls and 69.9% of boys had at least one social media account, with Instagram the most common. This was despite half the sample being younger than 13-years-old, the recommended minimum age for these platforms.

The more social media accounts, and greater time spent using them, were associated with a higher likelihood of disordered eating thoughts and behaviours, says lead author Dr Simon Wilksch, a Senior Research Fellow in Psychology at Flinders University.

The study is believed to be the first to examine the relationship between specific social media platforms and disordered eating behaviours and thoughts in young adolescents.

Dr Wilksch believes the findings are cause for concern.

"A key component of preventing eating disorders is to give the message that our self-worth should be defined by a mix of our abilities, values and relationships," he says.

"Social media seems to encourage young people to focus strongly on their appearance and the way it is judged or perceived by others.

"To find these clear associations between disordered eating and social media use in young adolescent girls and boys suggests that much more needs to be done to increase resilience in young people to become less adversely impacted by social media pressures," says Dr Wilksch, who is launching an Australia-wide trial of Media Smart Online program designed to combat such pressures in people of any gender aged between 13 and 25 years old.

The program is backed by positive findings from the first trial with 18-25 year old women where Media Smart Online reduced eating disorder onset by 66% (in those not meeting diagnosis at study start point) and increased eating disorder recovery by 75% (for those starting with disordered eating), relative to controls.

A range of other risk factors also improved along with lowering the likelihood of onset of depressive symptoms and thoughts about self-harm.

"We were very pleased with the outcomes of the first trial, and are excited to expand the program to a wider age range and people of any gender in this new research, since we know these concerns are not limited to females."

A key message of the program is for young people to "make up their own mind" on what relationship they want to have with social media and how their media use fits with their personal values.

The cooperation of two Prague research institutes - Institute of Organic Chemistry and Biochemistry and Institute of Microbiology of the Czech Academy of Sciences and the Brno based start-up CF Plus Chemicals, a spin-off of ETH Zurich, has brought a new technology called CF LINK for site-selective bioconjugation of proteins and also their structural characterization. The recently published, patent-pending technology, allows to selectively prepare protein conjugates via their tryptophan residues and perform posttranslational modification of aromatic amino acids. Furthermore, it can also be used as a tool for the mapping of protein surfaces and studies of protein-protein interactions.

The company CF Plus Chemicals, an ETH Zurich spin-off founded in 2014, is based on almost ten years of cooperation of the group of Dr. Petr Beier at the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague) and Dr. Václav Matoušek, a Ph.D. alumnus of Prof. Dr. Antonio Togni at ETH Zurich.

Reagents based on cyclic hypervalent iodine-perfluoroalkyl compounds, nowadays also termed as the Togni reagents, have become widely used and popular tools in organic synthesis, especially in medicinal chemistry for preparation of new fluorinated drug candidates, in-line with the growing demand for fluorinated scaffolds in drug design. While in the early 1990s fluorinated molecules accounted for 5% of the total number of approved drugs, now it is 15% and roughly 30% for newly approved therapeutics.

This family of chemical compounds was subsequently expanded in 2013 in collaboration of ETH Zurich and Dr. Petr Beier from IOCB to a new generation of patented Togni reagents that carry a more complex RCF2CF2 group instead of a simple CF3 group.[1] The new family of these chemicals shares not only the rich reactivity of the first generation of Togni reagents, but also brings an extra dimension due to the virtually unlimited structural variability of the β-substituted tetrafluoroethyl group which they are able to transfer to a variety of substrates relevant to medical chemistry of small molecules.

In 2017, the application potential of the second generation of Togni reagents was extended to proteins.[2 ] Their high affinity towards the thiol group allows to perform selective bioconjugation through cysteines to form stable conjugates which, unlike maleimide conjugates, are not subject to slow deconjugation and thiol exchange.

The present invention[3,4] builds on the previous knowledge of the radical nature of Togni reagent-mediated reactions. In the SME Instrument Horizon 2020 project, supported by the City of Brno and in cooperation with IOCB and Dr. Petr Novák from the Institute of Microbiology of the Czech Academy of Sciences (IMIC), it was showcased that Togni reagents, when mixed with sodium ascorbate, a cheap, non-toxic and biocompatible reducing agent, immediately generate ß-substituted tetrafluoroethyl radicals that selectively attach to sterically accessible tryptophan residues of the protein under transition metal-free conditions.

Once azidofluoroalkyl groups are attached to the protein, various functional groups, such as fluorescent dyes, radionuclides or ADC-toxins for targeted oncotherapy can be subsequently linked via click reaction to afford the corresponding protein conjugates. The disclosed tryptophan-selective bioconjugation method does not disrupt protein disulfide bridges and offers an alternative solution where conventional cysteine conjugation is not possible, for example due to an undesirable disulfide scrambling.

This bioconjugation method can also be extended to other aromatic amino acids and hence to proteins lacking tryptophan. Thus, it was possible to successfully modify human recombinant insulin and attach up to 7 modifications to its aromatic amino acids, demonstrating the potential for post-translational modification of proteins.

The extremely rapid nature of this reaction that targets solvent-accessible aromatic amino acids makes it a convenient tool for mapping protein surfaces and studying protein-protein interactions. Using the example of human carbon anhydrase, it has been demonstrated that the results of surface mapping are in excellent agreement with its published native structure.

The second generation of Togni-CF2CF2R reagents is protected by a worldwide patent owned by ETH Zurich and IOCB and are exclusively licensed by CF Plus Chemicals. The new CF LINK ascorbate technology, a subject of another patent application, further strengthens the intellectual property protection and forms a technology package which is currently offered to licensing to business partners for bioconjugation of diagnostically and therapeutically relevant proteins/antibodies, preparation the corresponding immunoconjugates with fluorescence dyes, radionuclides or ADC-toxins, post-translational protein modification, structural proteomics and study of protein-protein interactions.

Prof. Dr. Martin Fusek, CEO of IOCB Tech: „The basis of successful commercial outcomes from basic research results is excellent scientific work. This is an important result that is not only useful as a tool for basic research but also as a means for the development of new protein-based drugs. The uniqueness, which should rather be the rule, is that the project was created by the cooperation of two academic and one commercial subject. I am very glad that we could have been part of the process, albeit small."

Dr. Petr Beier, Head of a research group at IOCB Prague: "I am glad that we have been able to develop a successful cross-disciplinary collaboration of organic synthesis and biochemistry. It turns out that the specific properties of fluorinated compounds can be utilized not only traditionally in the medical chemistry of small molecules, but as recently showcased also for bioconjugation of proteins and studies of their structure. I believe that in the future we will be able to identify other attractive uses of Togni reagents in biochemistry."

Dr. Petr Novák, Head of a research group at IMIC: „Thanks to Togni reagents we have been able to introduce a fluorinated probe into the protein structure in an aqueous environment in a matter of few seconds. We are now able to use this technology to selectively tag proteins for clinical diagnostics or use to it to identify the interaction interface of proteins with their ligands.

Dr. Václav Matoušek, CEO of CF Plus Chemicals: "I am excited to see that the reactivity of Togni reagents could be extended to aromatic amino acids and aromates in general, thus opening a plethora of potential applications, especially in protein science and protein-based therapeutics. We are now actively looking for established industrial partners who could apply our technology to solve their challenges."

The small-world property is a property of networks in which, despite a large number of nodes, it is possible to find short communication paths between them.

Discovered in the field of social sciences in the 1960s, the phenomenon known as small-world has fascinated popular culture and science for decades. It arose from the observation that in the world, any two people are connected by a short chain of social ties.

A network, whether natural (neural or social) or artificial (communication or transport systems) is an ordered set of elements connected to each other through various methods that share information. The small-world property is a property of networks in which, despite a large number of nodes, it is possible to find short communication paths between them. In recent decades it has been proved that both in natural and artificial systems, many real networks are also small-world. But, are all small-world networks small, and how do they compare to others?

In the physical world we evaluate and compare the size of objects by contrasting them to a common reference, usually a standard metric system defined and agreed by the community. In the case of complex networks, the difference is that every network constitutes its own metric space. Thus, the question of whether a network is smaller or larger than another implies the comparison of two different spaces with each other, rather than the more familiar situation in which two objects are contrasted within the space they share.

Despite the existing variety of small-world networks, it still remains a challenge to make a reliable and comparable measurement of their average length.

The main result of a study published in Nature Communications Physics on 14 November is "the identification of the lower and upper boundaries for the average pathlength and global efficiency for (di)graphs of arbitrary number of nodes and links", assert Gorka Zamora-Lopez, a researcher at the Center for Brain and Cognition (CBC) at the Department of Information and Communication Technologies (DTIC) and Romain Brasselet, a researcher at the International School for Advanced Studies (SISSA) in Trieste (Italy), authors of the work.

"We can now assess the average pathlength of a network--of a given size and density--by evaluating how much it deviates from the smallest and the largest pathlength it could possibly take", Zamora López and Brasselet comment.

These results allow characterizing the length of a network under a natural reference and provide a synoptic representation, without the need to choose between models generated randomly (random graphs) as had been the case to date. In other words, "this theoretical framework allows us to evaluate both empirical networks and graph models together under the same reference framework. While the pathlength of these constructions is comparable, their dynamic properties may differ significantly", they add.

The implications of these results transcend the purely structural study of networks. Applying this theoretical framework to empirical examples of three categories (neural, social and transportation) shows that, while most real networks display a pathlength comparable to that of random graphs, when contrasted against the upper and lower boundaries, only the neural networks, i.e., the cortical connectomes, prove to be ultra-short.

The authors conclude that network optimization problems involve the maximization of a variety of parameters. The results they have obtained are the solutions to the simplest case with a minimal set of constraints. These solutions can serve as the starting point for studying more complex problems which include additional constraints beyond the number of nodes and links.

The cover for issue 63 of Oncotarget features Figure 6, "Inverse relationship between ETV7 and SERPINE1 in OSCC," by Salameti, et al.

In this study, the research team investigated NOTCH1 mutations in keratinocyte lines derived from OSCC biopsies that had been subjected to whole exome sequencing.

One line, SJG6, was found to have truncating mutations in both NOTCH1 alleles, resulting in loss of NOTCH1 expression.

Overexpression of the NOTCH1 intracellular domain in SJG6 cells promoted cell adhesion and differentiation, while suppressing proliferation, migration and clonal growth, consistent with the previously reported tumour suppressive function of NOTCH1 in OSCC.

Dr. Fiona M. Watt from the Centre for Stem Cells and Regenerative Medicine, King's College London, Tower Wing, Guy's Hospital, London, UK said "Notch1 is a heterodimeric and multifunctional transmembrane receptor that regulates key cellular processes, including cell fate determination, maintenance of stem cells, cell survival, proliferation and apoptosis."

Notch1 is a heterodimeric and multifunctional transmembrane receptor that regulates key cellular processes, including cell fate determination, maintenance of stem cells, cell survival, proliferation and apoptosis.

The majority of NOTCH1 mutations occur in the EGF-like ligand binding domain of the NECD, and prevent ligand binding and downstream signaling.

The detection of NOTCH1 mutations in dysplastic regions, and reduced expression of NOTCH1 in pre-neoplastic and cancerous skin lesions, suggests its potential gate-keeper properties.

Some studies have implicated Notch1 signaling in angiogenesis and therapy resistance in HNSCC, while in vitro studies have pointed to the role of NOTCH1 in promoting keratinocyte differentiation.

The Watt Research Team concluded that their study indicates that the tumour suppressive role of NOTCH1 in OSCC is manifested, at least in part, by ETV7-mediated suppression of SERPINE1.

Diffractive deep neural network is an optical machine learning framework that blends deep learning with optical diffraction and light-matter interaction to engineer diffractive surfaces that collectively perform optical computation at the speed of light. A diffractive neural network is first designed in a computer using deep learning techniques, followed by the physical fabrication of the designed layers of the neural network using e.g., 3D printing or lithography. Since the connection between the input and output planes of a diffractive neural network is established via diffraction of light through passive layers, the inference process and the associated optical computation does not consume any power except the light used to illuminate the object of interest.

Developed by researchers at UCLA, diffractive optical networks provide a low power, low latency and highly-scalable machine learning platform that can find numerous applications in robotics, autonomous vehicles, defense industry, among many others. In addition to providing statistical inference and generalization to classes of data, diffractive neural networks have also been used to design deterministic optical systems such as a thin imaging system.

In these earlier demonstrations, diffractive networks models were developed to process information through a single wavelength and therefore required a monochromatic and coherent illumination source, unlike for example the ambient light which is incoherent and composed of a continuum of wavelengths, making it broadband. Addressing this limitation, UCLA researchers have designed diffractive networks that can process information using a continuum of wavelengths, expanding this all-optical computation framework into broadband optical signals. Published in Light: Science & Applications, a journal of the Springer Nature, UCLA researchers demonstrated the success of this new framework by creating a series of optical components that filter broadband input light into desired sub-bands. These deep learning-based diffractive systems also control the precise location of each filtered band of radiation at the output plane, demonstrating spatially-controlled wavelength de-multiplexing in terahertz (THz) part of the electromagnetic spectrum.

After their design in a computer, these broadband diffractive networks were fabricated with a 3D-printer and tested using a pulsed THz source emitting a continuum of wavelengths between 60 and 3,000 micrometers. The experimental results obtained with these 3D-printed diffractive networks showed a very good agreement with their corresponding numerical designs, highlighting the experimental robustness of broadband diffractive optical networks.

This research was led by Dr. Aydogan Ozcan, UCLA Chancellor's Professor of electrical and computer engineering (ECE) and associate director of the California NanoSystems Institute (CNSI). The other authors of this work are graduate students Yi Luo, Deniz Mengu, Muhammed Veli, post-doctoral researcher Dr. Nezih T. Yardimci, Adjunct Professor Dr. Yair Rivenson, as well as Professor Mona Jarrahi, all with the ECE department at UCLA.

"Simultaneously analyzing and processing light across many wavelengths present unique opportunities to enhance the inference and generalization capabilities of diffractive optical networks to perform machine learning tasks such as all-optical object recognition, as well as to design deterministic and task-specific optical components, expanding the optical design space beyond the human intuition" said Prof. Ozcan.

This new method is also broadly applicable to different parts of the electromagnetic spectrum, including the visible band, and thus, represents a critical milestone for diffractive optical networks toward their widespread utilization in modern day optical components and machine learning systems, covering a wide range of applications in for example robotics, autonomous vehicles and surveillance.

Climate worries go hand in hand with CO2 emissions concerns. Emissions hit an all-time high last year. The CO2 level in the atmosphere may be higher than it's been in 3 million years.

Carbon capture will most likely be necessary to reduce the level of CO2 in the atmosphere. To accomplish that, we need the technology and materials to do the job. Recently a promising and surprising new candidate has emerged.

"The results are first and foremost important in terms of climate change," says Professor Liyuan Deng at the Norwegian University of Science and Technology's (NTNU) Department of Chemical Engineering.

Professor Deng is leading the work of the membrane research group at NTNU, and their results are gaining attention.

Power plants that use fossil fuels require a membrane that can filter the emissions and separate out the carbon. These membranes need to be both permeable for CO2 and also separate the CO2 from the other gases, such as nitrogen.

"We didn't think this membrane material was going to be suitable," says Deng.

But a simple move changed that. The hopeless membrane candidate needed another substance to work properly. This second substance was simply - water.

By lowering the membrane into water and then drying it out again, the membrane underwent a change. CO2 penetrated the membrane much more efficiently, and the membrane was somewhat better at filtering out nitrogen.

NPG Asia Materials, a journal in the Nature group, recently published an article on the NTNU research. The authors wrote that "these nanostructured membranes constitute promising candidates for gas separation technologies aimed at CO2 capture."

TESET

The material in question is a polymer. Polymers are relatively inexpensive and easy to make. Many researchers therefore regard them as promising candidates for separating different gases on the large scale that will be needed to cope with climate change. The membranes must also be stable and durable.

A polymer is a substance composed of long-chain molecules. Many plastics are polymers, but they are also found in nature as proteins, cellulose and glass, for example.

This particular polymer bears the name poly[tert-butylstyrene-b-(ethylene-alt-propylene)-b-(styrene-r-styrenesulfonate)-b-(ethylene-alt-propylene)-b-tert-butylstyrene].

Fortunately, someone gave it the nickname TESET instead. The material is already in commercial use and is therefore readily available.

"The company holding the patent is interested in this new field of application," says Deng.

The Membrane Research Laboratory at NTNU hosts the only group in Norway that is studying membranes from polymers that can be used to filter CO2 from the air. Some individual scientists are working with the same materials, while other groups are looking at inorganic membranes. The research on membranes in Norway as a whole is quite advanced, and perhaps even cutting edge, according to the professor.

This particular research is part of Horizon 2020, the EU's Framework Programme for Research and Innovation.

The group is also working on other promising candidates for CO2 filtration. Among these are membranes made of graphene oxide. Graphene is the world's thinnest and strongest material. It consists of one layer of carbon atoms organized in a hexagonal pattern. The material has many exciting properties, and several groups at NTNU are looking at the practical fields of application for it.

All the published results and articles from the membrane research group associated with Horizon 2020 are freely accessible for the public, and the Trondheim laboratory is open to researchers from around the world to carry out experiments, as long as they receive permission and support from the EU ECCSEL project.

It is incompletely understood which factors in patients with multiple sclerosis (MS) act as a trigger for the immune system to attack the brain and spinal cord. A potential factor is described by a research team in the journal Proceedings of the National Academy of Sciences, PNAS. The medical researchers used an animal model to show that the protein Smad7 mobilises immune cells in the intestines which, in turn, trigger inflammation in the central nervous system. Analyses of intestinal tissue samples taken from MS patients confirmed the results, which were published online on 4 December 2019.

The study was conducted at the Department of Neurology and the Centre of Neuroimmunology at St. Josef-Hospital, university hospital of Ruhr-Universität Bochum. The Bochum-based group with biologist Dr. Steffen Haupeltshofer and neurologists Professor Simon Faissner and Professor Ingo Kleiter, formerly at the Bochum university hospital, currently at Marianne-Strauß-Klinik in Berg, collaborated with other colleagues from Bochum, Bremen, Mainz, Düsseldorf, Jülich and Rome.

Protein Smad7 activates immune cells in the intestines

The research team initially analysed the signal protein Smad7 in intestinal immune cells in mice, or more precisely: in T-cells. The researchers compared genetically modified mice with a normal and those with a particularly high quantity of Smad7 in T-cells as well as mice without any Smad7 in T-cells. They monitored if the animals developed opticospinal encephalomyelitis - a disease that mimics MS in humans.

The strongest clinical MS-like symptoms occurred in animals with an increased Smad7 level in T-cells. In their intestines, T-cells were more frequently activated, which then migrated into the central nervous system where they triggered inflammation. Moreover, the ratio of protective regulatory T-cells to pathogenic autoreactive T-cells had changed. In mice that didn't have any Smad7 protein, no clinical signs of a MS-like disease occurred.

Results confirmed using tissue samples from patients

In the next step, the researchers analysed tissue samples taken from the intestines of 27 MS patients and compared them with samples taken from 27 healthy individuals. In the patients, they identified changes similar to those in the animal model: the signal protein Smad7 occurred more frequently in intestinal mucosa samples of MS patients than in those of healthy individuals; in addition, an abnormal ratio of regulatory to pathogenic mechanisms was identified in intestinal mucosa samples in patients.

"For other autoimmune diseases such as Crohn's and other inflammatory bowel diseases, researchers are already aware that Smad7 offers a promising therapeutic target; our results suggest that the same is true for multiple sclerosis," says Ingo Kleiter. "Researchers are increasingly exploring intestinal involvement in the development and progression of MS," adds Simon Faissner.