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JNCCN: Many hospitalized people with advanced cancer struggle with important daily tasks

image: JNCCN June 2020 Cover

Image: 
NCCN

PLYMOUTH MEETING, PA [June 8, 2020] -- New research from Mass General Cancer Center, published in the June 2020 issue of JNCCN--Journal of the National Comprehensive Cancer Network, found 40.2% of hospitalized patients with advanced, incurable cancer were functionally impaired at the time of admission, meaning they needed assistance with activities of daily living (ADLs) like walking, bathing, getting dressed, or other routine tasks. Patients with functional impairment also had higher rates of pain, depression, and anxiety, and were more likely to have longer hospital stays and worse survival.

"Interventions addressing patients' functional impairment and symptom management could help enhance care delivery and outcomes for the highly symptomatic population of hospitalized patients with advanced cancer," said lead researcher Daniel E. Lage, MD, MsC, Mass General Cancer Center. "This highlights the need for efforts to integrate functional assessments into the care of these patients to identify individuals who may benefit from physical therapy, palliative care, and/or other supportive services earlier in their hospital stay. Our finding that individuals with functional impairment experience worse survival could also help guide conversations about goals of care and hospice planning among hospitalized patients with cancer."

"We are also actively exploring interventions to help patients transition from the inpatient to the outpatient setting, which we have identified as a key challenge for patients with functional impairment," added senior researcher Ryan D. Nipp, MD, MPH, Mass General Cancer Center. "Future work is needed to develop novel models of care to enhance access to palliative care services and address barriers that limit appropriate access to palliative care among patients with advanced cancer."

The researchers studied 970 patients age 18-and-older with advanced cancer--defined as those not being treated with curative intent--who experienced an unplanned hospital admission at Mass General Cancer Center between September 2, 2014 and March 31, 2016. They measured functional impairment using nursing documentation collected at intake and stored in electronic health records (EHR), and also collected self-completed questionnaires from the patients. ADL impairment was defined as any need for assistance by another person. Overall, 390 patients (40.2%) had at least one ADL impairment with 14.8% having one or two, and 25.4% experiencing at least three areas of difficulty with daily tasks.

"Oncologists have long appreciated that functional status is a powerful predictor of a number of important outcomes including survival and treatment outcomes," commented Toby Campbell, MD, Chief of Palliative Care at the University of Wisconsin Carbone Cancer Center, who was not involved in this research. "We know that the routine assessment of symptom burden and functional status in the outpatient setting results in improved survival and quality of life."

Dr. Campbell, a Member of the NCCN Guidelines® Panel for Palliative Care, continued: "Dr. Lage and colleagues highlight the important, often-missed, opportunity to routinely use hospitalization as a trigger for a careful assessment of symptoms and functional status. An unplanned hospitalization for an advanced cancer patient is a watershed moment and predicts higher symptoms and shorter survival in patients with and without impaired function. Hospitalization is a crucial opportunity to facilitate critical serious illness care, including comprehensive palliative care and advanced care planning, with the promise of improving the lives of our patients."

Credit: 
National Comprehensive Cancer Network

Spontaneous formation of nanoscale hollow structures could boost battery storage

image: Small batteries were used to study the spontaneous formation of nanoscale hollow structures in the laboratory of Matthew McDowell at Georgia Tech.

Image: 
Matthew McDowell, Georgia Tech

An unexpected property of nanometer-scale antimony crystals -- the spontaneous formation of hollow structures -- could help give the next generation of lithium ion batteries higher energy density without reducing battery lifetime. The reversibly hollowing structures could allow lithium ion batteries to hold more energy and therefore provide more power between charges.

Flow of lithium ions into and out of alloy battery anodes has long been a limiting factor in how much energy batteries could hold using conventional materials. Too much ion flow causes anode materials to swell and then shrink during charge-discharge cycles, causing mechanical degradation that shortens battery life. To address that issue, researchers have previously developed hollow "yolk-shell" nanoparticles that accommodate the volume change caused by ion flow, but fabricating them has been complex and costly.

Now, a research team has discovered that particles a thousand times smaller than the width of a human hair spontaneously form hollow structures during the charge-discharge cycle without changing size, allowing more ion flow without damaging the anodes. The research was reported June 1 in the journal Nature Nanotechnology.

"Intentionally engineering hollow nanomaterials has been done for a while now, and it is a promising approach for improving the lifetime and stability of batteries with high energy density," said Matthew McDowell, assistant professor in the George W. Woodruff School of Mechanical Engineering and the School of Materials Science and Engineering at the Georgia Institute of Technology. "The problem has been that directly synthesizing these hollow nanostructures at the large scales needed for commercial applications is challenging and expensive. Our discovery could offer an easier, streamlined process that could lead to improved performance in a way that is similar to the intentionally engineered hollow structures."

The researchers made their discovery using a high-resolution electron microscope that allowed them to directly visualize battery reactions as they occur at the nanoscale. "This is a tricky type of experiment, but if you are patient and do the experiments right, you can learn really important things about how the materials behave in batteries," McDowell said.

The team, which included researchers from ETH Zürich and Oak Ridge National Laboratory, also used modeling to create a theoretical framework for understanding why the nanoparticles spontaneously hollow -- instead of shrinking -- during removal of lithium from the battery.

The ability to form and reversibly fill hollow particles during battery cycling occurs only in oxide-coated antimony nanocrystals that are less than approximately 30 nanometers in diameter. The research team found that the behavior arises from a resilient native oxide layer that allows for initial expansion during lithiation -- flow of ions into the anode -- but mechanically prevents shrinkage as antimony forms voids during the removal of ions, a process known as delithiation.

The finding was a bit of a surprise because earlier work on related materials had been performed on larger particles, which expand and shrink instead of forming hollow structures. "When we first observed the distinctive hollowing behavior, it was very exciting and we immediately knew this could have important implications for battery performance," McDowell said.

Antimony is relatively expensive and not currently used in commercial battery electrodes. But McDowell believes the spontaneous hollowing may also occur in less costly related materials such as tin. Next steps would include testing other materials and mapping a pathway to commercial scale-up.

"It would be interesting to test other materials to see if they transform according to a similar hollowing mechanism," he said. "This could expand the range of materials available for use in batteries. The small test batteries we fabricated showed promising charge-discharge performance, so we would like to evaluate the materials in larger batteries."

Though they may be costly, the self-hollowing antimony nanocrystals have another interesting property: they could also be used in sodium-ion and potassium-ion batteries, emerging systems for which much more research must be done.

"This work advances our understanding of how this type of material evolves inside batteries," McDowell said. "This information will be critical for implementing the material or related materials in the next generation of lithium-ion batteries, which will be able to store more energy and be just as durable as the batteries we have today."

Credit: 
Georgia Institute of Technology

Radiocarbon dating pins date for construction of Uyghur complex to the year 777

image: This is an aerial view of Por-Bajin from the west. The complex is situated on an island in a lake. Scientists have pinned its construction on the year 777 CE, using a special carbon-14 dating technique, based on sudden spikes in the carbon-14 concentration.

Image: 
Andrei Panin

Dating archaeological objects precisely is difficult, even when using techniques such as radiocarbon dating. Using a recently developed method, based on the presence of sudden spikes in carbon-14 concentration, scientists at the University of Groningen, together with Russian colleagues, have pinned the date for the construction of an eighth-century complex in southern Siberia to a specific year. This allows archaeologists to finally understand the purpose for building the complex - and why it was never used. The results were published in Proceedings of the National Academy of Sciences on 8 June.

The Por-Bajin complex, on the border of the Russian Federation and Mongolia, measures 215 x 162 metres and has outer walls of twelve metres high. All of the walls are made of clay (Por-Bajin translates as 'clay house') on a foundation of wooden beams. The complex was created by nomadic Uyghurs, sometime in the eighth century. But archaeologists did not know the purpose of the complex and why it appears to never have been used.

Khans

'In order to understand this, the exact construction date was required to find out which local leader, or khan, gave the orders for the construction,' explains Margot Kuitems, a postdoctoral researcher at the Centre for Isotope Research at the University of Groningen. She currently works on the Exact Chronology of Early Societies (ECHOES) project, funded by the European Research Council and led by Assistant Professor of Isotope Chronology Michael Dee, who is also an author on the PNAS paper.

For the early mediaeval period, radiocarbon dating is generally precise to a few decades. This is good enough for most applications. However, as khans came and went during the eighth century, the exact construction date was required to link it to a specific leader. Within the ECHOES project, Kuitems applied a recently developed method to date her samples exactly.

Spike

Carbon-14 (a radioactive isotope of carbon) is created in the upper atmosphere. Plants absorb carbon dioxide, which includes a tiny amount of carbon-14. When the plant - or the animal that ate the plant - dies, the carbon uptake stops and the carbon-14 slowly decays. Every 5,730 years, half of the carbon-14 decays. Therefore, the carbon-14 concentration tells you how old the object (animal, plant or any other organic material) is.

Production rates of carbon-14 in the atmosphere are not constant. However, changes in atmospheric carbon-14 were believed to show little variation from one year to the next. Then, in 2013, the Japanese Professor Fusa Miyake analysed individual tree rings and found a spectacular spike in carbon-14 content in the year 775. 'When you find wood at an archaeological site from that period, you can look for the spike by measuring the carbon-14 content of subsequent tree rings,' explains Kuitems. The spike tells you which tree ring grew in the year 775. And when the sample includes the bark, it is even possible to determine when the tree was felled.

Chinese princess

This approach was used to analyse a beam taken from the very foundation of the Por-Bajin complex. The sample that they used had 45 rings, followed by the bark. Measurements showed that the spike that dated to the year 775 was present in the 43rd ring. 'So, we knew the tree was felled in 777. Tree ring specialist and co-author Petra Doeve determined that the final, partial ring was created in the spring.' In southern Siberia, there is a clear distinction between summer and winter wood.

Russian archaeologists previously reported that the entire complex was completed in a very short time, about two years. Por-Bajin is situated on an island in a lake and it was determined that the trees came from the surrounding area. 'We are fairly certain that they were felled for the construction of the complex, and it is therefore highly likely that construction took place around 777.' Previously, the site had been dated to 750, based on a runic inscription on a monument called the 'Selenga Stone', which described the construction of a large complex. In 750, Bayan-Chur Khan ruled the Uyghurs. He was married to a Chinese princess and this may explain why some Chinese influences were found in the Por-Bajin complex. 'However, previous radiocarbon dating attempts already suggested that the buildings might be slightly younger.'

Manichaeism

In the year 777, Tengri Bögü Khan was in charge. He had converted to Manichaeism, a gnostic religion that was strongly opposed. Indeed, Bögü Khan was killed during an anti-Manichaean rebellion in 779. 'All this ties in neatly with the archaeological evidence,' explains Kuitems. It is likely that the complex was built to serve as a Manichaean monastery. 'This explains why it was never used after the anti-Manichaeans defeated Bögü Khan. If it had been a palace or a fortress, it is more likely that the victors would have moved in.'

The study shows how carbon-14 spikes can help to solve archaeological conundrums, says Kuitems: 'This technology can be really useful in cases where an exact date is required.' And as ever more spikes are identified, their uses will become more widespread.

Simple Science Summary

At the border between the Russian Federation and Mongolia stands a large clay complex of buildings called Por-Bajin. Archaeologists are not sure who built it and what its purpose was. They do know that it was never used. Scientists have used a promising method to pinpoint the construction date. Normal carbon dating of wood leads to a range of a few decades at best. However, sometimes a spike in carbon-14 levels can be found in one particular tree ring, all across the world. These spikes have been dated to the year by counting the rings in continuous records from known-age wood from tree-ring archives. In the complex, the scientists found a beam with a spike from the year 775. As they were able to ascertain that the tree was felled two years later, the complex must have been constructed in 777. Shortly before this, the local leader (khan) had converted to the Manichaean religion but he was killed by anti-Manichaeans in 779. It was concluded that the complex was built as a Manichaean monastery but was never used since anti-Manichaeans took control of the area.

Credit: 
University of Groningen

Global oncology pharmacists face restricted access to essential PPE items

image: "We have to make sure cancer healthcare workers - in this case, pharmacists and technicians involved in cancer care - continue to be well safeguarded with PPEs and have what they need to do their jobs well," says UCI's Alexandre Chan.

Image: 
Maurisa Jones, UCI

Irvine, Calif., June 8, 2020 -- Oncology pharmacy practitioners around the globe are fighting to provide cancer patients high quality cancer care with increasingly limited and sometimes restricted personal protective equipment supply as well as impaired access to essential anticancer medication, according to University of California, Irvine-led study.

In the Journal of Oncology Pharmacy Practice, Alexandre Chan, department chair and professor clinical pharmacy practice, and Canadian and Australian colleagues of the International Society of Oncology Pharmacy Practitioners surveyed 42 pharmacy practice groups in 28 countries and regions (in both developed and developing countries) to determine pain points that this global pandemic has created for oncology pharmacy practitioners.

The study's abstract can be accessed at: https://journals.sagepub.com/doi/10.1177/1078155220927450

Half of those surveyed reported that PPE was difficult to access or was restricted in supply. These are necessary pieces of equipment for practitioners that are preparing chemotherapy in order to avoid exposure to toxins, which can cause mutagenic and carcinogenic effects. The study reveals that practitioners have had to find ways to preserve PPE supply, such as extending chemotherapy compounding shifts to avoid an excess of PPE changing. In addition, practitioners in 43 percent of the surveyed countries reported impaired access to drugs, including anti-infective agents, anticancer medications and supportive care medications that are essential to treatment of cancer patients, with the largest portion of this problem occurring in African countries.

"We have to make sure cancer healthcare workers - in this case, pharmacists and technicians involved in cancer care - continue to be well safeguarded with PPEs and have what they need to do their jobs well," Chan said. "Oncology pharmacists are important frontline healthcare workers who are involved in the care of patients that are vulnerable."

Moving forward, the group will continue to monitor the long-term impact of COVID-19 on the delivery of cancer care and to identify opportunities to learn from experiences to ensure pharmacy services can prioritize initiatives and workforce activities. This will help with the effort to ensure the continued supply of critical medications and safety of patients on high-risk, complex and narrow therapeutic drug regimens during a pandemic or other resource-constrained environment.

Marliese Alexander, Jennifer Jupp, Grace Chazan and Shaun O'Connor of the International Society of Oncology Pharmacy Practitioners also contributed to the study.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 222 degree programs. It's located in one of the world's safest and most economically vibrant communities and is Orange County's second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.

Credit: 
University of California - Irvine

Physicists study mirror nuclei for precision theory test

image: A precision measurement of helium and hydrogen mirror isotopes reveals new questions in understanding of nuclear structure.

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DOE's Jefferson Lab

NEWPORT NEWS, VA - It's not often in nuclear physics that you can clearly get both sides of the story, but a recent experiment allowed researchers to do just that. They compared very similar nuclei to each other to get a clearer view of how the components of nuclei are arranged and found that there's still more to learn about the heart of matter. The research, carried out at the Department of Energy's Thomas Jefferson National Accelerator Facility, was recently published as an editors' suggested read in Physical Review Letters.

"We want to study nuclear structure, which is basically how protons and neutrons behave inside a nucleus," explains Reynier Cruz-Torres, a postdoctoral researcher at DOE's Lawrence Berkeley National Lab who worked on the experiment as a graduate student at the Massachusetts Institute of Technology. "To do that, we can measure any nucleus that we want. But to do a high-precision test of nuclear theory, we are limited to light nuclei that have precision calculations. Measuring these light nuclei is a benchmark for understanding nuclear structure in general."

For this measurement, the researchers focused on two of the simplest and lightest nuclei in the universe: helium and hydrogen. They focused on an isotope of helium called helium-3, so called because it contains just three major components: two protons and one neutron. The isotope of hydrogen that they tested, tritium, is also composed of three components: one proton and two neutrons.

"They are mirror nuclei. So, you can assume that the protons in helium-3 are basically the same as the neutrons in tritium and vice versa," says Florian Hauenstein, a joint postdoctoral researcher at Old Dominion University and MIT.

According to the researchers, by comparing these relatively simple nuclei, they can get a window into the strong nuclear interactions that can't be duplicated elsewhere. That's because as some of the lightest and least complicated of the nuclei in the universe, these nuclei are excellent examples for comparing with the state-of-the-art theories that describe the basic structures of different nuclei.

"The theory calculations have been there for a while, but we didn't know how good they are," explains Dien Nguyen, a postdoctoral researcher at MIT and incoming Nathan Isgur Fellow in Nuclear Experiment at Jefferson Lab. "So, with this research, we are able to quantitatively say how good the calculation is. I think that is a really important step."

To make the comparison, the researchers measured both nuclei in high-precision experiments in the Continuous Electronic Beam Accelerator Facility (CEBAF), a DOE User Facility based at Jefferson Lab.

Electrons from CEBAF were aimed at the nuclei of tritium and helium-3, where some interacted with the nuclei's protons. The struck protons and the interacting electrons were then captured and measured in large detectors called spectrometers in Jefferson Lab's Experimental Hall A.

"We use the spectrometers to study the properties of those final-state particles and look back to the nucleus and try to understand what was happening inside the nucleus before the reaction took place," says Cruz-Torres.

This experiment was challenging and groundbreaking in that it was conducted at a wider range of energies with unprecedented precision. In addition, the tritium data are the very first ever for these studying these reactions.

The researchers then compared the full range of data from the experiments to theory calculations on the structures of the nuclei of helium-3 and tritium. They found that the data generally matched theory well for both nuclei to the precision allowed by experiment, a feat that was described by one researcher as a triumph of modern-day nuclear physics. However, differences were also observed relative to some of the calculations, indicating that further refinements in the theoretical treatments are required.

"We expected that the helium-3 calculations at the end would easily match the data, but it actually turned out that the tritium cross section fit very well the theory calculation, and the helium-3 not so much through the whole range. So, we need to go back and look at helium-3," explains Hauenstein.

Dien confirms that this unexpected result is now the impetus for continuing these high-precision studies of light nuclei in earnest.

"Before, we thought we had a very good understanding of the calculations," says Nguyen. "But now, the result is what is driving us to do an even more detailed measurement, because we want to make sure that we have a good agreement with the theory."

Credit: 
DOE/Thomas Jefferson National Accelerator Facility

Researchers develop ultra-sensitive device for detecting magnetic fields

PROVIDENCE, R.I. [Brown University] -- A team of Brown University physicists has developed a new type of compact, ultra-sensitive magnetometer. The new device could be useful in a variety of applications involving weak magnetic fields, the researchers say.

"Nearly everything around us generates a magnetic field -- from our electronic devices to our beating hearts -- and we can use those fields to gain information about all these systems," said Gang Xiao, chair of the Brown Department of Physics and senior author of a paper describing the new device. "We have uncovered a class of sensors that are ultra-sensitive, but are also small, inexpensive to make and don't use much power. We think there could be many potential applications for these new sensors."

The new device is detailed in a paper published in Applied Physics Letters. Brown graduate student Yiou Zhang and postdoctoral researcher Kang Wang were the lead authors of the research.

A traditional way of sensing magnetic fields is through what's known as the Hall effect. When a conducting material carrying current comes into contact with a magnetic field, the electrons in that current are deflected in a direction perpendicular to their flow. That creates a small perpendicular voltage, which can be used by Hall sensors to detect the presence of magnetic fields.

The new device makes use of a cousin to the Hall effect -- known as the anomalous Hall effect (AHE) -- which arises in ferromagnetic materials. While the Hall effect arises due to the charge of electrons, the AHE arises from electron spin, the tiny magnetic moment of each electron. The effect causes electrons with different spins to disperse in different directions, which gives rise to a small but detectable voltage.

The new device uses an ultra-thin ferromagnetic film made of cobalt, iron and boron atoms. The spins of the electrons prefer to be aligned in the plane of the film, a property called in-plane anisotropy. After the film is treated in a high-temperature furnace and under a strong magnetic field, the spins of the electrons develop a tendency to be oriented perpendicular to the film with what's known as perpendicular anisotropy. When these two anisotropies have equal strength, electron spins can easily reorient themselves if the material comes into contact with an external magnetic field. That reorientation of electron spins is detectable through AHE voltage.

It doesn't take a strong magnetic field to flip the spins in the film, which makes the device quite sensitive. In fact, it's up to 20 times more sensitive than traditional Hall effect sensors, the researchers say.

Key to making the device work is the thickness of the cobalt-iron-boron film. A film that's too thick requires stronger magnetic fields to reorient electron spins, which decreases sensitivity. If the film is too thin, electron spins could reorient on their own, which would cause the sensor to fail. The researchers found that the sweet spot for thickness was 0.9 nanometers, a thickness of about four or five atoms.

The researchers believe the device could have widespread applications. One example that could be helpful to medical doctors is in magnetic immunoassay, a technique that uses magnetism to look for pathogens in fluid samples.

"Because the device is very small, we can put thousands or even millions of sensors on one chip," Zhang said. "That chip could test for many different things at one time in a single sample. That would make testing easier and less expensive."

Another application could be as part of an ongoing project in Xiao's lab supported by the National Science Foundation. Xiao and his colleagues are developing a magnetic camera that can make high-definition images of magnetic fields produced by quantum materials. Such a detailed magnetic profile would help researchers better understand the properties of these materials.

"Just like a regular camera, we want our magnetic camera to have as many pixels as possible," Xiao said. "Each magnetic pixel in our camera is an individual magnetic sensor. The sensors need to be small and they can't consume too much power, so this new sensor could be useful in our camera."

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Brown University

New tool helps nanorods stand out

image: Rice University scientists have created an open-source algorithm, SEMseg, that simplifies nanoparticle analysis using scanning electron microscope images.

Image: 
Landes Research Group/Rice University

HOUSTON - (June 8, 2020) - Rice University scientists have developed an easy and affordable tool to count and characterize nanoparticles.

The Rice labs of chemists Christy Landes and Stephan Link created an open-source program called SEMseg to acquire data about nanoparticles, objects smaller than 100 nanometers, from scanning electron microscope (SEM) images that are otherwise difficult if not impossible to analyze.

The size and shape of the particles influences how well they work in optoelectronic devices, catalysts and sensing applications like surface-enhanced Raman spectroscopy.

SEMseg is described in a study led by Landes and Rice graduate student Rashad Baiyasi in the American Chemical Society's Journal of Physical Chemistry A.

The program is available for download from GitHub at https://github.com/LandesLab?tab=repositories.

SEMseg -- for SEM segmentation -- springs from the team's study in Science last year that showed how proteins can be used to push nanorods into chiral assemblies. "This work was one result of that," Landes said. "We realized there was no good way to quantitatively analyze SEM images."

Counting and characterizing individual or aggregate nanorods is usually done with complex and expensive transmission electron microscopes (TEM), manual measurement that is prone to human bias or programs that fail to distinguish between particles unless they're far apart. SEMseg extracts pixel-level data from low-contrast, low-resolution SEM images and recombines it into sharp images.

SEMseg can quickly distinguish individual nanorods in closely packed assemblies and aggregates to determine the size and orientation of each particle and the size of gaps between them. That allows for a more efficient statistical analysis of aggregates.

"In a matter of minutes, SEMseg can characterize nanoparticles in large datasets that would take hours to measure manually," Baiyasi said.

Segmenting nanoparticles, he said, refers to isolating and characterizing each constituent particle in an aggregate. Isolating the constituent nanoparticles lets researchers analyze and characterize the heterogenous structure of aggregates.

Baiyasi said SEMseg can be adapted for such other imaging techniques as atomic force microscopy and could be extended for other nanoparticle shapes, like cubes or triangles.

Credit: 
Rice University

Kidney problems more prevalent in NYC COVID-19 patients

NEW YORK, NY (June 8, 2020) --- Hospitalized COVID-19 patients at a New York City medical facility had higher rates of kidney complications than other COVID-19 patient groups in different areas of the U.S. and other countries, according to a new study from researchers at Columbia University Irving Medical Center and NewYork-Presbyterian.

The study, using data from electronic health records and published recently in the British Medical Journal, also found the need for mechanical ventilation was greatest at two different points after symptom onset.

The study offers a detailed look at the clinical course of the first 1,000 COVID-19 patients treated at NewYork-Presbyterian/Columbia University Irving Medical Center between March 1 and April 5, 2020.

Patients in the study had higher rates of underlying chronic conditions than reported in other patient populations; the most common were hypertension (60%) and diabetes (37%). More than half of patients hospitalized for COVID-19 were male, and the median age was 63.

Nearly 34% of the patients admitted for COVID-19 developed acute kidney injury, versus 15% of patients in a recent report from China and 19% of patients in a report from Washington State. Almost 80% of patients in the ICU developed acute kidney injury.

The researchers also found that more than 95% of patients who were intubated required mechanical ventilation within the first 14 days, at either 3-4 days or 9 days after symptom onset.

"The finding that there were two points in time to intubation for critically ill COVID-19 patients tells us when we might need to be most vigilant," says George Hripcsak, MD, MS, chair and Vivian Beaumont Allen Professor of Biomedical Informatics at Columbia University Vagelos College of Physicians and Surgeons and co-corresponding author of the study. "Knowing that intubation is much less likely to be needed after 15 days can help clinicians decide if it is safe for a patient to return home." Dr. Hripcsak is also director of medical informatics services for NewYork-Presbyterian/Columbia University Irving Medical Center.

The median length of stay for COVID-19 patients in the current study was 6 days, similar to that of patients in a recent report from China. However, in the current study patients in the ICU had a median hospital stay of 23 days, compared with 8 days for critically ill patients in the Chinese study. More than a third of the critically ill patients remained hospitalized at the end of the study.

"Our study provides valuable details about the clinical course of hospitalized COVID-19 patients from one of the largest epicenters of the pandemic," says RuiJun Chen, MD, a postdoctoral research fellow in biomedical informatics at Columbia University Irving Medical Center, clinical assistant professor of medicine at Weill Cornell Medicine, and co-corresponding author of the study. "As the pandemic continues to spread around the globe, our findings may have implications for planning and resource allocation to accommodate the needs of critically ill patients, and for de-escalation of care, rehabilitation, and follow-up care after prolonged stays on a ventilator or in the ICU."

The overall mortality rate, around 21%, was similar to other patient cohorts. The mortality rate among ICU patients was 43.6%.

"Describing our COVID-19 patient population is the first step toward identifying important risk factors for experiencing severe disease," says Hripcsak. "Additional studies are needed to tease out what is actually causing the differences we saw in our population versus other populations."

The paper is titled "Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series."

Credit: 
Columbia University Irving Medical Center

Scientists identify targets for COVID-19 vaccine using cancer immunotherapy tools

Philadelphia, June 8, 2020--Cancer researchers at Children's Hospital of Philadelphia (CHOP) have harnessed tools used for the development of cancer immunotherapies and adapted them to identify regions of the SARS-CoV-2 virus to target with a vaccine, employing the same approach used to elicit an immune response against cancer cells to stimulate an immune response against the virus. Using this strategy, the researchers believe a resulting vaccine would provide protection across the human population and drive a long-term immune response.

The strategy is described in Cell Reports Medicine.

"In many ways, cancer behaves like a virus, so our team decided to use the tools we developed to identify unique aspects of childhood cancers that can be targeted with immunotherapies and apply those same tools to identify the right protein sequences to target in SARS-CoV-2," said senior author John M. Maris, MD, a pediatric oncologist in CHOP's Cancer Center and the Giulio D'Angio Professor of Pediatric Oncology at the Perelman School of Medicine at the University of Pennsylvania. "By adapting the computational tools developed and now refined by lead author Mark Yarmarkovich, PhD in the Maris Lab, we can now prioritize viral targets based on their ability to stimulate a lasting immune response, predicted to be in the vast majority of the human population. We think our approach provides a roadmap for a vaccine that would be both safe and effective and could be produced at scale."

The COVID-19 pandemic has led to an urgent need for the development of a safe and effective vaccine against SARS-CoV-2, the virus that causes the COVID-19 disease. An optimally designed vaccine maximizes a long-lasting immune response, while minimizing adverse reactions, autoimmunity, or disease exacerbation.

To increase the likelihood that a vaccine is both safe and effective, the research team prioritized parameters in identifying regions of the virus to target. The researchers looked for regions that would stimulate a memory T-cell response that, when paired with the right B cells, would drive memory B cell formation and provide lasting immunity and do so across the majority of human genomes. They targeted regions of SARS-CoV-2 that are present across multiple related coronaviruses, as well as new mutations that increase infectivity, while also ensuring that those regions were as dissimilar as possible from sequences naturally occurring in humans to maximize safety.

The researchers propose a list of 65 peptide sequences that, when targeted, offer the greatest probability of providing population-scale immunity. As a next step, the team is testing various combinations of a dozen or so of these sequences in mouse models to assess their safety and effectiveness.

"With the third epidemic in the past two decades underway, all originating from the coronavirus family, these viruses will continue to threaten the human population and necessitate the need for prophylactic measures against future outbreaks," said Dr. Yarmarkovich. "A subset of the sequences selected in our study are derived from viral regions that are very similar to other coronaviruses, and thus our approach, if successful, could lead to protection against not only SARS-CoV-2 but also other coronaviruses that might emerge in the future."

Credit: 
Children's Hospital of Philadelphia

Countries must work together on CO2 removal to avoid dangerous climate change

The Paris Agreement lays out national quotas on CO2 emissions but not removal, and that must be urgently addressed, say the authors of a new study.

The Paris Agreement aims to keep global temperature rise this century well below 2°C above pre-industrial levels and to pursue efforts to limit it to 1.5°C. Reaching these targets will require mitigation - lowering the carbon dioxide (CO2) emitted through changes such as increased use of renewable energy sources, and removal of CO2 from the atmosphere through measures such as reforestation and carbon capture and storage.

However, while countries signed up to the Paris Agreement have individual quotas they need to meet in terms of mitigation and have individual plans for doing so, there are no agreed national quotas for CO2 removal.

Now, in a paper published today in Nature Climate Change, an international group of researchers have argued that to meet the Paris Agreement's targets, CO2 removal quotas cannot be allocated in such a way that any one country can fulfil its obligations alone.

Cross-border cooperation

The team, from Imperial College London, the University of Girona, ETH Zürich and the University of Cambridge, say countries need to start working together now to make sure enough CO2 is removed in a fair and equitable way. This should involve deciding how quotas might be allocated fairly and devising a system where countries that cannot fulfil their obligations alone can trade with countries with greater capacity to remove CO2.

Co-author Dr Niall Mac Dowell, from the Centre for Environmental Policy and the Centre for Process Systems Engineering at Imperial, said: "Carbon dioxide removal is necessary to meet climate targets, since we have so far not done enough to mitigate our emissions. Both will be necessary going forward, but the longer we wait to start removing CO2 on a large scale, the more we will have to do.

"It is imperative that nations have these conversations now, to determine how quotas could be allocated fairly and how countries could meet those quotas via cross-border cooperation. It will work best if we all work together."

Co-author Dr David Reiner, from Judge Business School at the University of Cambridge, added: "Countries such as the UK and France have begun to adopt binding 'net-zero targets' and whereas there has been extensive focus on greenhouse gas emissions and emissions reductions, meeting these targets will require greater attention to the negative emissions or carbon dioxide removal side of the equation."

Allocating quotas

A critical element in any negotiations will be to determine the fairest way to allocate quotas to different nations. Different methods have been used for determining previous quotas, such as the ability of a country to pay and its historic culpability (how much CO2 it has emitted), with a blend of methods often used implicitly or explicitly in any final agreement.

The team modelled several of these different methods and applied them to countries across Europe. While the quotas varied significantly, they found that only a handful of countries could meet any of the quotas using only their own resources.

Co-lead author Dr Ángel Galán-Martín, from ETH Zürich, said: "The exercise of allocating CO2 removal quotas may help to break the current impasse, by incentivising countries to align their future national pledges with the expectations emerging from the fairness principles."

Carbon dioxide removal can be achieved in several ways. Reforestation uses trees as natural absorbers of atmospheric CO2 but takes time to reach its full potential as the trees grow. Carbon capture and storage (CCS) takes CO2 out of the atmosphere and stores it in underground geological formations.

CCS is usually coupled with a fossil fuel power station to take the CO2 out of the emissions before they reach the atmosphere. However, it can also be coupled to bioenergy - growing crops to burn for fuel. These systems have the double benefit of the crops removing CO2 from the atmosphere, and the CCS capturing any CO2 from the power station before it is released.

Beginning the process

However, different countries have varying abilities to deploy these CO2 removal strategies. For example, small but rich countries like Luxembourg might incur a heavy CO2 removal burden but not have the geological capacity to implement large-scale CCS or have the space to plant enough trees or bioenergy crops.

The authors therefore suggest, after quotas have been determined, that a system of trading quotas could be established. For example, the UK has abundant space for CCS thanks to favourable geological formations in the North Sea, so could sell some of its capacity to other countries.

This system would take a while to set up, so the authors urge nations to begin the process now. Co-lead author Dr Carlos Pozo from the University of Girona, said: "By 2050, the world needs to be carbon neutral - taking out of the atmosphere as much CO2 as it puts in. To this end, a CO2 removal industry needs to be rapidly scaled up, and that begins now, with countries looking at their responsibilities and their capacity to meet any quotas.

"There are technological solutions ready to be deployed. Now it is time for international agreements to get the ball rolling so we can start making serious progress towards our climate goals."

Credit: 
Imperial College London

Novel eco-friendly electrochemical reaction can synthesize useful semiconductor materials

image: Electrochemical setup for the synthesis of thienoacene derivatives.

Image: 
2020 Okayama University

Organic solar cells have a variety of applications in the field of electronics, especially in the development of novel electronic devices like wearable devices. Often, these batteries are composed of organic semiconductor molecules, which are light and robust. Thus, finding novel strategies for the development of these semiconductor molecules has been the goal of many scientists globally. But usually, synthesizing these molecules involves the use of expensive rare metal catalysts. Not only does this result in a high manufacturing cost, but the possibility of the metal catalysts being contaminated makes the process challenging.

To this end, in a new study published in Angewandte Chemie International Edition, a research group at Okayama University, including Professor Seiji Suga and Associate Professor Koichi Mitsudo, developed a novel reaction system to synthesize thienoacene derivatives--key building blocks in organic semiconductor synthesis. The scientists focused on constructing carbon-sulfur (C-S) bonds through organic electrolysis, which is an environment-friendly reaction. Prof Suga explains, "We focused on C-S bonds, as they are an abundant and significant in the field of pharmaceuticals and materials science, such as in certain antidepressant and antifungal medications. "

Conventionally, C-S bonds are constructed via a method called "transition metal-catalyzed cross-coupling," which requires the use of rare metal catalysts. This makes the reaction expensive and, thus, infeasible. Thus, in this study, the scientists focused on a different approach, called "electrochemical carbon-heteroatom bond formation," which is an eco-friendly reaction requiring mild conditions. Although several novel electrochemical carbon-heteroatom coupling reactions have been reported in the past, these reactions had never been used to synthesize thienoacenes until now. Prof Suga says, "Over the past several years, we were interested in the development of new methods for thienoacene synthesis, acene derivatives that have a good track record in organic electrochemistry and are attractive candidates for useful organic materials ."

Having established the basis of their study, the scientists then dug deeper to find novel electrochemical methods for thienoacene synthesis. They found that the desired C-S bond formation occurred smoothly in the presence of a "bromide" ion, which acts as a powerful promoter of the reaction. Using this strategy, the scientists successfully synthesized types of thienoacene derivatives called the "π-expanded thienoacene derivatives." Interestingly, this study is the first to report successful C-S bond formation for the synthesis of thienoacene derivatives. Prof Suga explains, "Our study was the first to report an electro-oxidative dehydrogenative reaction to produce C-S bonds for thienoacenes. We found that bromide ion, which catalytically promotes the reaction as a halogen mediator, is essential to the reaction ."

This study offers hope that, in the future, organic semiconductor molecules can be produced using a cost-efficient technique, without the need to use expensive metal catalysts. Prof Suga concludes, "The key to this research lies in the method of 'electrochemical synthesis,' which is a clean and renewable source of energy ." Through these findings, the scientists at Okayama University hope to achieve sustainable organic synthesis with minimal impact on the environment. Thus, this study is also a significant step towards achieving the UN sustainable development goals and hence promoting a better future for humanity.

Credit: 
Okayama University

Viewing the topology of thermonuclear reaction in nuclear landscape from the network perspective

image: The topologies pertaining to the (a) n, (b) p, (c) h and (d) r layers of the 40Ca's nucleus at the nuclear landscape. The network is built on the basis of the substrate-product method

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©Science China Press

How is the universe formed? What's the mechanism of the nucleosynthesis of lighter nuclei to heavier nuclei in the Universe? Where is the limit of the nuclear landscape? These problems have always been hot topics in nuclear astrophysics in which nuclear reactions play an important role. Moreover, much attention has been paid on solving these problems.

To understand the path of nucleosynthesis in the Universe, traditionally, researchers require to solve a set of time-dependent differential equations called nuclear reaction network calculation, which need expensive computer equipment and spend a lot of time, even is prohibitive, and obtain the abundance of element involved in nucleosynthesis.

The REACLIB database, which is continuously updated and snapshotted regularly by the Joint Institute for Nuclear Astrophysics (JINA) Collaboration, is usually used in nuclear reaction network calculation. It contains eight thousand nuclei and eighty thousand reactions, where each reaction includes the information of the type of reaction, parameters needed for calculating reaction rate and Q value, etc.

In recent years, complex network science, as a new interdisciplinary field, has been applied in reactions involved in physics, chemistry and biology to explore their statistical characteristics of the whole reaction system which is challenging. Its basic ideas origin from graph theory, which regard reaction individuals in a real system as node and relationship between two individuals as edge, by doing so the real system is mapped to a network.

Chinese group guided by Yugang Ma combined the REACLIB database with the complex network theory aiming to obtain the topological characteristics of all thermonuclear reactions in the database. The main concept was to identify real interacting nuclide as nodes and determine the relationships between the two nuclides as edges. Using the substrate-product method, a directed, multi-layer nuclear reaction network was formed, which contained four layers, n-, p-, h- and r-, according to the types of reactions involved in neutrons, proton, 4He and the remaining atomic particles, respectively.

For example, each nuclide in n-layer, called `node' X in terms of network concept, the reaction n + Y -> X was considered as 'in-coming' (corresponding to in-degree), the reaction X + n -> Y was regarded as 'out-going' (corresponding to out-degree) and the number of all reactions involved in this node X was called degree that equal to in-degree plus out-degree.

In order to understand this more clearly, figure 1 shows an example of the topological structures of 40Ca nucleus denoted by gold color in the four-layer nuclear reaction network. Where the red arrow and the black arrow represent the consumption and the production of 40Ca, respectively.

In an article published in Scientific Reports (2016) coauthored with Yugang Ma, scholars at Shanghai Institute of Applied Physics, Chinese Academy of Sciences and School of Information Science and Technology, East China Normal University, indicated that "the degree difference and node overlapping coefficient are able to identify the majority of stable nuclides".

Recently, four scholars, guided by Yugang Ma, likewise took advantage of the directed, un-weighted, multi-layer nuclear reaction networks in the study, which is published in the Science China Physics, Mechanics & Astronomy, and revealed that nuclear reaction networks for nucleosynthesis calculations are amenable to many topological properties that have not yet been explored in the theoretical and experimental studies in nucleosynthesis.

Research aimed at finding out the most frequent reaction patterns of interconnections occurring in different nodes, which called 'motif' structure, and calculating the correlation of each two layers.

"All motif structures, regardless of the layer in which they are found, fade away or change shape as the number of protons reaches at or near 82." the researchers wrote in an article titled "Network structure of thermonuclear reactions in nuclear landscape".

"The degree values (i.e. numbers of reactions), for three layers of n-, p-, and h-, have a significant correlation with one another, and their topological structures exhibit a similar regularity. However, the r-layer has a more complex topological structure compared to the other layers." they explained.

"This work provides a novel approach to investigating the nuclear reaction network that prevails in the astrophysical context." wrote the four researchers.

"In the future work, we will focus on improving mapping methods, incorporating the dynamics on the network and a more in-depth analysis of each layer." wrote the four researchers.

Credit: 
Science China Press

Single-cell yolk-shell capsules with high biological activity and stability

image: (a) Schematic illustration of sequential steps for yolk-shell encapsulation of cyanobacterium. (b) SEM micrograph of the encapsulated cyanobacteria with the corresponding EDX mapping for elemental Si and O. Scale bars: 2 μm. (c) Merged CLSM micrograph of encapsulated cyanobacteria, showing encapsulated, red-fluorescent cyanobacteria and green-fluorescent silica shells. Scale bar: 5 μm. (d) TEM micrograph of an encapsulated cyanobacterium, showing intracellular structures and the colloidal packing layer. Scale bar: 500 nm. (e) HAADF-STEM micrograph and FFT (inset) image of an encapsulated cyanobacterium. The FFT image indicates ordered of the colloidal packing. Scale bar: 500 nm.

Image: 
©Science China Press

Recently, the value of the global market for microbes and microbial products is continuously increasing. However, the full exploitation of bacteria towards advanced biotechnology and bio-energetics is impeded by low biological activity and stability in the industrial reactors.

Single-cell nanoencapsulation is an emerging, non-genetic technique to address these limitations. It concerns to create extended cell surface functionalities, provide external stimuli to enhance cell stability and activity, and incorporate new properties. Colloidal packing is a common strategy for single-cell nanoencapsulation through an adsorption-assembly-encapsulation sequence. However, the disordered structure of current generation colloidal packings does not allow well-controlled exchange between a cell and its environment, affecting nutrient, waste and metabolite diffusion and therefore, cell activity and stability. Moreover, such colloidal packing results in direct contact between the shell and the cell surface, which is incompatible with cells and negatively affects their activity and stability even further.

In response to this challenge, inspired by the yolk-shell structure of eggs and the structural ordering of cell surfaces in the evolution, the living materials team led by Prof. Bao-Lian Su from Wuhan University of Technology and the University of Namur proposed highly stable single cyanobacterium capsules with an ordered yolk-shell structure of uniformly organized and tunable nanoporosity shaped by protein-assisted, hydrophilic colloidal silica packing. The void between the ordered nanoporous shell and cell is created by the controlled internalization of protamine, which could subsequently be filled by nutrients. Shells thus constructed are not only biocompatible but also endow introduction of new and unprecedented cell surface functionalities, such as specific size-dependent permeability and defined molecular recognition abilities. Owing to the presence of the buffering interstitial hollow space filled by nutrient between the ordered nanoporous shell and the cell surface, cyanobacterial activity, and stability evolving from this yolk-shell encapsulation technology are highly enhanced. Because of the specific size-dependent permeability stemming from uniformly organized nanoporosity, the survival ability of yolk-shell encapsulated cyanobacteria against toxic chemical environments is significantly strengthened. In addition, this yolk-shell structure can also be equipped with molecular recognition abilities.

It is envisioned single cells encapsulated in their ordered yolk-shell structures have a broad scope in a wide range of applications with specific functionalities, including in photobioreactors, biochips, biosensors, biocatalysis, biofuel reactors, and controlled delivery therapeutics.

Credit: 
Science China Press

New treatment target verification for myelodysplastic syndrome

image: RUNX3 suppresses the expression level a gene in the same family, RUNX1, that is essential for hematopoiesis. RUNX3 also cooperates with the strong oncogene MYC to grow MDS cells.

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Dr. Goro Sashida

A research group from Kumamoto University, Japan analyzed the pathophysiology of myelodysplastic syndrome (MDS), a blood cancer that presents often in the elderly, and found the presence of the transcription factor RUNX3, thereby revealing a cancer growth function for what had been considered a tumor suppressor. Additional analyses of human MDS cells and model mice found an abnormal gene expression mechanism linked to the initiation and propagation of MDS stem cells, and confirmed RUNX3 as a new therapeutic target.

MDS is a refractory cancer that is resistant to anticancer drugs. It originates from hematopoietic stem cells and causes hematopoietic failure. Recent advances in comprehensive DNA sequencing analysis have largely revealed the major genetic mutations within MDS but much remains unknown about the mechanisms that cause it. Thus, the International Research Center for Medical Sciences (IRCMS) research group turned their focused toward the transcription factor RUNX3 and investigated its role in the development of MDS.

They first analyzed the correlation between RUNX3 expression levels in human MDS cells and life prognosis, and confirmed that patients with higher RUNX3 expression had a worse prognosis. Next, since RUNX3 expression in human MDS cells has a high frequency of mutation in TET2 gene, they created RUNX3-expressing MDS model mice deficient in the TET2 gene. RUNX3-expressing TET2-deficient MDS cells were found to suppress the expression level and function of RUNX1, a transcription factor in the same gene family as RUNX3 and is essential for normal hematopoiesis. This indicates a new mechanism of cancer development that suppresses normal functions through interactions between family genes. The researchers also found that RUNX3 cooperates with the MYC gene, a known oncogene, to grow MDS cells. Inhibition of MYC function significantly suppressed the proliferation of RUNX3-expressing cells.

"Further progress in future research is expected to lead to the development of new therapeutic methods targeting the transcription factor RUNX3 in the refractory cancer myelodysplastic syndrome," said Professor Goro Sashida who lead this study. "Our results are also expected to be beneficial in the study of other hematological cancers where the transcription factor RUNX plays an important role such as Down's syndrome-related leukemia."

Credit: 
Kumamoto University

'Social distancing' saves frogs: New approach to identify individual frogs noninvasively

image: A Beautiful stream frog (Amolops formosus) in a Himalayan torrent stream.

Image: 
Naitik Patel

Globally, 41% amphibian species are regarded as threatened with extinction. However, when it comes to the case of India, the majority of the species falls in the Data Deficient group, according to the criteria of the International Union for Conservation of Nature's (IUCN) Red List of Threatened Species.

This means that we hardly have any population data for Indian amphibians, which leads to a serious conservation bottleneck, especially when you are dealing with elusive herpiles. Therefore, there is the pressing priority to obtain demographic trends to prompt and support conservation actions for endemic and habitat-dependent species.

While demographics of natural populations is best estimated with the mark-recapture technique, used in animals, where individuals have distinct body markings, such as the stripes in a tiger, the dots in a whale shark and the fingerprints in a human. In the meantime, while frogs are well known for their individual-specific markings and colour patterns, this kind of technique has never been used in amphibians, even though they have long been recognised as some of the most vulnerable animals on Earth.

On the other hand, it is hardly possible to capture and mark individual frogs in the wild. So, Naitik Patel and Dr Abhijit Das of the Wildlife Institute of India came up with one of the very first non-invasive approaches to identify individual frogs using photos from their natural habitats, which are then processed with the animal recognition software HotSpotter. Their unique method is described in the open-access, peer-reviewed scientific journal Herpetozoa.

"Capturing each frog is not possible in the field, so to address this problem, we conducted a short study on Beautiful stream frogs (Amolops formosus), a species that, just like many other amphibians, has variable body markings amongst individuals. As this species inhabits the Himalayan torrent stream, which is difficult to access, we tried our best to photograph each frog from a distance to avoid any kind of physical contact," explains Naitik Patel, a PhD student at the Wildlife Institute of India.

Having concluded their study with a success rate of 94.3%, the research team is hopeful that their protocol could be effectively implemented in rapid population estimation for many endangered species of frogs.

"We conducted photographic documentation to capture the unique markings of each frog, and then compared them, using computer-assisted individual identification. With this method, the number of individuals can be counted to estimate the population structure. This study is exceptional, owing to the minimal disturbance it causes to the frogs. Such a technique has rarely been tried on amphibians and is a promising method to estimate their numbers. It can also be used in citizen science projects," comments senior scientist Dr Abhijit Das.

Credit: 
Pensoft Publishers