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Genetic Test Found to Save Drug Expense, Boost Adherence

Spilled pills

(frolicsome/Pixabay)

13 August 2015. A genetic test to guide the choice of drugs prescribed to patients with psychiatric disorders was found to reduce the cost of medications to those patients and improve adherence to the drugs prescribed, compared to patients who were not given the test. Results of the study evaluating the GeneSight test, made by Assurex Health in Mason, Ohio, appear in a recent issue of the journal Current Medical Research and Opinion.

The GeneSight test analyzes a patient’s DNA from a mouth swab sample, to better understand how drugs would affect that individual. The analysis looks at genes involved in the body’s reactions to medications, including their absorption, distribution, metabolism. and elimination. The test also covers genes affected by the drugs’ therapeutic mechanisms.

Assurex says its technology assesses the actions of potential drugs on patients, which for neurological and psychiatric medications is important, since drugs for these disorders often work through multiple genetic pathways. The company offers genetic assessments specialized for psychotropic conditions such as depression or PTSD, chronic pain, ADHD, and folate deficiency associated with individuals having depression. Assurex licensed its technology from Mayo Clinic and Cincinnati Children’s Hospital Medical Center.

The study, conducted by Assurex with the pharmacy benefit management company Express Scripts, reviewed insurance claims records from an Express Scripts database over a one-year period. A group of more than 2,100 individuals given the GeneSight test for psychotropic conditions was matched against a group of nearly 11,000 people newly prescribed a psychiatric drug or who switched to a new drug. People in the both groups were participants in the pharmacy benefit plan for at least six months. The research team looked at the number and costs of drugs being prescribed, as well as adherence by patients to their medications, defined as proportion of days covered during a specified period of time.

The results show individuals first receiving the GeneSight test had lower overall costs for their drugs, stayed with prescriptions more than people not receiving the test, and in some cases reduced the number of medications taken. Drug costs for patients tested with GeneSight were on average $1,036 lower than individuals in the comparison group.

In addition, one of five people receiving the GeneSight test were prescribed fewer medications, which helps address the problem of polypharmacy — too many drugs being taken from too many prescriptions — often an issue for the elderly. The findings also show individuals receiving the GeneSight test stayed with their prescription regimens by a 17 percent margin more than people in the comparison group.

The journal article notes some limitations to the study. The analysis covers only a one-year period, so there are no data on longer-term implications. Likewise, the comparison group was chosen only on the basis of demographic characteristics and psychiatric conditions, thus there may be other confounding factors at work.

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Blood Disease Biotech Gains $120 Million in IPO

Red blood cells with sickle cell disease

Red blood cells with sickle cell disease (NCATS.NIH.gov)

12 August 2015. Global Blood Therapeutics, a biotechnology company developing treatments for blood-related disorders, is raising $120 million in its initial public stock offering. The company, in South San Francisco, California and trading on the Nasdaq exchange under the symbol GBT, issued 6 million shares priced at $20.00. Shares closed today trading at $43.50, more than double the IPO price.

Global Blood Therapeutics, founded in 2012 as a spin-off enterprise from University of California in San Francisco, designs treatments for sickle cell disease and related disorders that aim to address the root causes of disease rather than manage disorders. Sickle cell disease is a genetic blood disorder affecting hemoglobin that delivers oxygen to cells in the body. People with sickle cell disease have hemoglobin molecules that cause blood cells to form into an atypical crescent or sickle shape.

That abnormal shape causes the blood cells to break down, lose flexibility, and accumulate in tiny capillaries, leading to anemia and periodic painful episodes, called vaso-occlusive crises. The disease is prevalent worldwide, and affects 70,000 to 80,000 people in the U.S., including about 1 in 500 people of African descent.

Global Blood Therapeutics’ technology aims to change the shape of blood proteins for treating sickle cell diseases and other genetic disorders. The company’s technology platform combines computational biology and modeling of proteins and ligands — signaling molecules that bind to proteins — with medicinal chemistry and empiric screening.

The lead product from the company, code-named GBT440, is designed as an oral preventative medication taken once a day. GBT440 is designed to block the process of hemoglobin in its de-oxygenated state to cause red blood cells to clump together and form into abnormal sickle shapes. Currently, two early and intermediate stage clinical trials are recruiting healthy volunteers and individuals with sickle cell disease to test the safety, chemical activity, and biological effects of GBT440.

Global Blood Therapeutics’ founders include three biomedical researchers from University of California in San Francisco — pharmaceutical chemist Matthew Jacobson, computational biologist Andrej Sali, and pharmacologist Jack Taunton. In addition to its scientific founders, the company was started  by biotechnology entrepreneurs Charles Homcy and Craig Muir, with Third Rock Ventures partner Charles Homcy. Third Rock Ventures provided early financing for the company, as reported by Science & Enterprise.

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Protein Gels Being Devised to Simulate Human Functions

Jin Kim Montclare

Jin Kim Montclare (New York University)

12 August 2015. New York University’s engineering school is developing a new type of protein-based gel materials that respond to and replicate natural biochemical processes. The three-year project, led by chemical and biomolecular engineering professor Jin Kim Montclare, is funded by a $368,000 grant from the U.S. Army Research Laboratory.

Montclare and colleagues, at NYU’s Polytechnic School of Engineering in Brooklyn, New York, are investigating ways of making hydrogels from engineered proteins derived from E. coli bacteria that can then be refined into substances imitating natural processes to help heal wounds, detect changes in vital signs, or deliver drugs. Hydrogels are networks of material that contain primarily water, but maintain enough substance to form into 3-D gelatinous structures. The body naturally forms some materials, such as vitreous humor in the eyes and cartilage, with hydrogels made of proteins.

One function of these new hydrogels would be adhering to skin and other human surfaces to help wounds heal faster. In this case, hydrogels would be shaped into patterns similar to the feet of geckos that enable the reptile to stick to vertical walls and overhangs, yet release when necessary. Other planned uses include sensing and controlling the flow of fluids in the body, and as well as controlling delivery of drugs to specific organs.

Most previous work in developing materials that simulate natural functions worked with synthetic polymers and other substances. Because these new materials are based on proteins, they can respond to the same natural biochemical stimuli as humans, such as pH levels or temperature.

Montclare’s lab is not alone in devising hydrogels based on natural chemistries. Researchers at Kansas State University are studying development of hydrogels with peptides, simple protein compounds, for medical purposes, reported last November in Science & Enterprise. The team at Kansas State also founded a company, PepGel LLC, to commercialize their research for tissue engineering and regenerative medicine.

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University Faculty Design Mood-Tracking Mobile App

MoodTrek app

MoodTrek smartphone app (University of Missouri Health System)

11 August 2015. Faculty at University of Missouri in psychiatry and computer science built a smartphone app that allows people with depression to track their moods and share the data with their psychiatrists. The app, known as MoodTrek, is available free of charge on Android phones. An iPhone version is planned for the future.

The University of Missouri team, in Columbia, headed by psychiatry professor Ganesh Gopalakrishna, aim to find a way for people with depression to track their moods more frequently and accurately, combined with sleep patterns and activity levels, and report that information to their therapists. According to National Institute of Mental Health, some 16 million people in the U.S., about 7 percent of the adult population, suffer from a major depressive episode at least once a year. And while only a small percentage of people with depression receive treatment for the disorder, visits to therapists happen infrequently, often about every two to three months.

As a result Gopalakrishna and colleagues created a smartphone app, with Missouri computer science professor Sriram Chellappan and Tiger Institute Health Alliance, a partnership between the university and Cerner Corporation, a developer of health information technology solutions including electronic health records. “People tend to forget what their moods were like just a few days ago,” says Gopalakrishna in a university statement, “but through this app, I can now see that data and can use it to provide the best care possible.”

With MoodTrek, individuals can track their moods on a scale of 1 to 5, with smiley-face icons representing their feelings at any time. Data from MoodTrek are integrated with records of sleep and exercise from Fitbit activity monitors, which are shared with the individual’s therapist. If the person’s health care provider uses a Cerner system, data can be captured in those electronic health records as well.

In addition to structured and statistical data, MoodTrek can also capture free-form notes that clients can share with their therapists. The app also can connect directly to the National Suicide Prevention Lifeline. Individuals can access their data and download reports for their own use or their clinicians.

Kody Ihnat, a student at Missouri and a MoodTrek user since January 2015, reports an improvement in her mental well-being since using the app. “It forces you to take time for self-analysis and really reflect to find out why you’re feeling the way you do,” notes Ihnat in a university statement. “My family is very much comforted,” she adds, “by the fact that I have something in my pocket that is looking out for me and allows me to be in touch with my doctor.”

Ihnat and Gopalakrishna tell more about MoodTrek in the following video.

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Trial Shows Fertility Treatment Boosts IVF Pregnancy Rate

Pregnant woman

(Greyerbaby, Pixabay)

11 August 2015. A clinical study of cellular treatments for women using in-vitro fertilization shows the treatments increased pregnancy rates compared to women receiving standard IVF alone. Findings from the study that tested treatments developed by IVF technology company OvaScience Inc. in Cambridge, Massachusetts are scheduled to be published on 25 August in the Journal of Fertilization: In Vitro– IVF-Worldwide Reproductive Medicine, Genetic & Stem Cell Biology.

OvaScience says IVF often fails due to poor egg health, with the decline in egg health largely due to a reduction in the eggs’ energy production. The company, founded in 2011, designs and commercializes treatments that use precursor, or early-forming, eggs found in the ovarian lining, for women whose natural egg development is compromised. The technology is based on research by molecular biologist Jonathan Tilly, chair of the biology department at Northeastern University and professor of reproductive biology at Harvard Medical School.

OvaScience’s lead product, known as Augment, was tested in the study. Augment extracts the mitochondria or energy components of precursor egg cells to improve the quality of a patient’s fully-formed eggs, increase the eggs’ energy levels, and increase the likelihood of fertilization and a healthy birth. Augment treatments are now available in a few fertility clinics in Canada, Europe, and Middle East (not yet in the U.S.).

The study, conducted at Fakih IVF clinic in United Arab Emirates, recruited 25 clients with a poor prognosis for IVF success and no history of live births. Eggs from participants in the trial were assigned to receive Augment treatments combined with IVF, or standard IVF alone. Embryo quality was then evaluated with examination of physical properties, such as fragmentation and symmetry, that are factors in selecting embryos for transfer. Embryos also received standard preimplantation genetic diagnosis and screening.

After these assessments, the highest quality embryos were selected for transfer and placement. The company says more eggs treated first with Augment were selected and transferred for placement than eggs receiving only standard IVF treatments, by a statistically reliable margin. In addition, embryos receiving the the Augment treatments resulted in more pregnancies than those from standard IVF, again by a statistically reliable margin.

Zeev Shoam, editor of the journal publishing the paper says in a company statement, “Declining mitochondrial function is one of the reasons why women’s egg fertilization and embryo development efficacy decreases, impacting pregnancy rates, and the Augment treatment is addressing these potential energy deficiencies.”

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Astronauts to Eat Space-Grown Vegetables

Red romaine lettuce on space station

Red romaine lettuce grown on the International Space Station (NASA)

10 August 2015. Astronauts in Expedition 44 on the International Space Station plan to eat fresh leafy vegetables today grown in their own lab. The red romaine lettuce on their menus is grown in a plant system, nicknamed Veggie — officially known as Veg-01 — and marks the first crops both grown and consumed in space.

Growing food crops in microgravity is nothing new, but in previous experiments the crops were returned to Earth for analysis. The Veggie technology, if successful, will provide a sustainable source for food production for space flights of long durations, where storing food for the entire mission is impractical.

The space-grown leafy vegetables are the culmination of R&D by NASA and partners going back to 2010. Since that time, researchers experimented with hydroponic plants, grown entirely in water instead of soil and stacked in shelves, and later advanced into aeroponic crop production, where plants were suspended in air, do not need soil, and grow faster than comparable plants in soil.

The Veggie system contains collections of seeds in pods known as pillows to develop their roots, in this case containing romaine seeds with a set of zinnias, delivered to the space station in April 2014. The modular system that includes a panel of multi-colored LEDs to encourage plant growth was designed and built by NASA and Orbital Technologies Corp. in Madison, Wisconsin. The multi-color LEDs give off red and blue light that encourages plant growth, but also green tones to help the romaine lettuce look more appetizing to humans.

Since the space station crew has much more to do than grow vegetables, the project also employed sensors attached to the plants that tell crew members when the crops need watering. The sensors measure leaf thickness that indicates water content, and are monitored by one of the space station’s computers. When the sensors find the plants need water, the system sends text messages to the crew.

Another problem was the build up of ethylene, a natural gaseous hormone given off by plants as they grow. Ethylene accelerates the ripening process, but if it accumulates can also cause the growing crops to spoil. Greenhouses on earth can vent the gas, but not those in space. Air scrubbers, first developed for NASA by KES Science and Technology in Georgia, remove not only ethylene, but also other gaseous compounds, bacteria, mold, viruses, and odors.

An earlier crew grew a test crop of Veggie plants in 33 days, which were returned to earth for safety analysis. The current crew activated the new seed pillows on 8 July and also grew the romaine lettuce plants for 33 days. The following brief (15 second) video shows crew members enjoying their harvest.

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Intrexon Acquires Oxitec, Partners on Genetic Disorder

Diamondback moth

Diamondback moth (Olaf Leillinger, Wikimedia Commons)

10 August 2015. Intrexon Corp., a biotechnology company specializing in synthetic biology, is acquiring Oxitec Ltd., a designer of genetically modified insects to control the spread of disease-bearing and agricultural pests for $160 million. Intrexon is also partnering with Synthetic Biologics Inc. to develop therapies for phenylketonuria, a genetic metabolic disorder.

Intrexon, in Gaithersburg, Maryland develops genetically engineered products for the pharmaceutical, food, energy, environmental, and consumer markets. The company operates several technologies derived from computational models and software that assemble DNA-based solutions on a commercial scale.

Oxitec, in Oxford, U.K., is a spin-off enterprise from Oxford University that develops genetically engineered insect varieties. Under the merger, Oxitec shareholders will receive $80 million in cash and another $80 million in Intrexon stock. The deal is expected to be completed by the end of 2015.

In July 2015, Oxitec released results of controlled tests in greenhouses that show its genetically engineered diamondback moth could prevent females of the species from maturing, and quickly reduce populations of this destructive agricultural pest. Caterpillars from the diamondback moth eat brassica or crucifer vegetable crops including popular items such as broccoli, Brussels sprouts, cabbage, cauliflower, collard greens, and kale. Controlling the diamondback up to now relied on pesticides, but in recent years, the moth developed a resistance to synthetic, biological, and plant-expressed pesticides, as well as some types of crops genetically engineered to survive the moth.

Also in July, an Oxitec-designed mosquito, engineered to produce offspring that die before maturity, was found to reduce the dengue mosquito population in a city in Brazil by 95 percent, well below the level needed to spread the disease.  Dengue is viral disease transmitted by infected mosquitoes (not person-to-person) that occurs most frequently in tropical urban regions of the world. World Health Organization estimates from 50 to 100 million dengue infections occur each year, with half of the world’s population at risk.

In a separate deal, Intrexon and Synthetic Biologics Inc. in nearby Rockville, Maryland, agreed to an exclusive channel collaboration to develop therapies for phenylketonuria, an inherited metabolic disorder. Exclusive channel collaborations give Intrexon partners an exclusive license to develop new products from Intrexon technologies, move those products through regulatory processes, and conduct marketing and sales. Financial terms of the collaboration were not disclosed.

Phenylketonuria is a rare disorder where an amino acid called phenylalanine builds up in the body, particularly when the individual eats foods high in protein. The condition is caused by a defect in the gene that creates a liver enzyme to control phenylalanine and results in delayed development, intellectual disabilities, behavioral and emotional problems, psychiatric disorders, and neurological problems including seizures.

The agreement with Synthetic Biologics gives the company a license to therapy candidates from Intrexon’s ActoBiotics platform that develops therapies from engineered microbes commonly used to produce yogurt and cheese. The company modifies the organisms to produce therapeutic peptides and proteins that it says are taken orally, produced efficiently, and released in the gastrointestinal tract.

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Nicotine Destroying Drug Candidate Discovered

Lighting a cigarette

(Pakura, Pixabay)

7 August 2015. Biochemists at Scripps Research Institute reported on an enzyme derived from naturally-occurring bacteria that shows in lab tests can remove nicotine in the blood, with potential as a drug to help smokers quit. The team from the lab of chemistry professor Kim Janda at Scripps’s La Jolla, California campus described their findings earlier this week in Journal of the American Chemical Society (paid subscription required).

Janda’s group investigates catalytic enzymes, including those with potential for treating nicotine addiction. In their study Janda and colleagues studied NicA2, an enzyme derived from Pseudomonas putida, bacteria found in soil and fresh water that digest and break down organic matter as part of the carbon cycle. This property also gives the microbes an ability to break down organic toxins, which at one time attracted the attention of conservationists as a method for cleaning up toxic wastes.

Cigarette smoking continues to involve large numbers of people in the U.S., with 42 million adults currently using tobacco. Centers for Disease Control and Prevention says the percentage of Americans smoking cigarettes declined from 21 percent in 2005 to 18 percent in 2013, but smoking is still the leading cause of preventable disease and death in the U.S., causing more than 480,000 deaths a year. Also, some 16 million Americans are living with a smoking-related disease. Despite sophisticated behavioral techniques and chemical aids, getting smokers to quit is difficult, with multiple relapses common among people trying to stop smoking.

The Scripps team tested the enzyme NicA2, derived from Pseudomonas putida, as a way to break down and destroy nicotine in the bloodstream before it reaches the brains of people who smoke, thus blocking its addictive mechanism and helping people break the habit. In the lab, researchers mixed the equivalent amount of nicotine found in a cigarette with blood serum from a mouse, then added NicA2. They found that before adding NicA2, nicotine has an active lifetime of 4 to 6 hours, but after adding the enzyme, the nicotine lasts only 18 to 30 minutes.

The researchers then looked into other properties of NicA2 as a potential drug candidate. They discovered the enzyme remains stable for more than 3 weeks at a temperature of 98 degrees F. In addition, the team found degraded nicotine does not generate toxic byproducts from its reaction to NicA2.

Despite these findings, an important issue remains, namely the bacterial components of the enzyme, which could trigger an immune reaction in humans and would need to be neutralized. Nonetheless, the researchers believe they identified a treatment candidate with a favorable biochemical profile that could open up a new strategy for smoking cessation.

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Peanut Allergy Therapy Company Raises $160 Million in IPO

Peanuts

(National Institute of Food and Agriculture, USDA)

6 August 2015. Aimmune Therapeutics Inc., a developer of treatments for peanut and other food allergies, raised $160 million from its initial public stock offering, pricing its 10 million shares at $16.00. Shares in the Brisbane, California company trade on the Nasdaq exchange under the symbol AIMT. Shares closed today (6 August), priced at $24.10 a share, up 51 percent for the day, while the overall Nasdaq fell by 1.62 percent.

Aimmune Therapeutics was founded in 2011 as Allergen Research Corporation, partially in response to a scientific conference that year calling for more oral-administered immunotherapy drugs to treat food allergies. The company received seed funding from the not-for-profit organization Food Allergy Research and Education, and licensed technologies from research labs at Duke University, Stanford University, and University of Arkansas. Aimmune was later financed by 2 venture rounds, the latest in March 2015 raising some $97 million.

Allergies to peanuts and other foods are a result of the body’s immune system misinterpreting certain foods as pathogens, and responding by the release of histamines, chemicals in the body causing the allergy symptoms. In most cases, the symptoms are mild, such as runny nose and itching, but people with peanut allergies face a real and elevated risk of anaphylaxis, a life-threatening condition constricting airways, swelling the throat, and causing a sharp drop in blood pressure. Food Allergy Research and Education says some 15 million people in the U.S. and 17 million people in Europe have a food allergy, with growing numbers of people reporting an allergy.

Aimmune Therapeutics develops therapies for food allergies using a technology it calls characterized oral desensitization immunotherapy, or Codit. The technology exposes people with food allergies to increasing amounts of the allergens over a period of months, thereby desensitizing the individuals to the allergen. Codit, says Aimmune, enhances conventional oral immunotherapies by precisely controlling the amount of offending food protein ingested by people with food allergies and establishing treatment routines that start with very small amounts of the offending food protein and gradually increasing the amounts over time.

The company’s lead product, code-named AR101, is a treatment designed to provide people with peanut allergies convenient and consistent concentrations of peanut proteins, as capsules in dosages from 0.5 to 300 milligrams for desensitization and eventually maintenance therapies. In June 2015, U.S. Food and Drug Administration assigned breakthrough status to AR101, providing expedited review of new treatments offering substantial improvement over current therapies for serious or life-threatening conditions.

FDA granted breakthrough designation based on results of an intermediate-stage clinical trial with 55 individuals, about half of them children, testing AR101 against a placebo. The trial measured ability to ingest peanut protein over 6 to 9 months, and found 78 percent of participants receiving AR101 could ingest a cumulative amount of 1,043 milligrams and all AR101 participants could ingest 443 milligrams. Aimmune says a late-stage clinical trial is planned for early in 2016.

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Computer Model Provides Early Sepsis Alert

Suchi Saria and Katherine Henry

Suchi Saria, right, with first author Katherine Henry (Will Kirk, Homewood Photo, Johns Hopkins University)

6 August 2015. Researchers at Johns Hopkins University wrote a computer model that gives clinicians an early and accurate warning that a patient is developing sepsis, a life-threatening complication of infections. The team of medical researchers, computer scientists, and mathematicians published its findings yesterday in the journal Science Translational Medicine (paid subscription required).

Sepsis results from an immune-system reaction to chemicals released by the body to fight infection, including infections from medical equipment such as catheters. The inflammatory responses can occur anywhere in the body and generate a series of further reactions, including blood clots and leaking blood vessels, causing organ damage and failure. If sepsis develops into septic shock, blood pressure drops sharply, often causing death. Centers for Disease Control and Prevention says the number of people in U.S. hospitals with sepsis rose from 621,000 in 2000 to more than 1.1 million in 2008, with death resulting in 28 to 50 percent of cases.

The Johns Hopkins team, led by computer scientist and health policy professor Suchi Saria, is seeking tools for identifying potential sepsis cases earlier in their development, before they progress to septic shock. Current diagnostic methods, say the authors, can spot sepsis only in advanced stages, when there is little time for clinicians to respond. Current tools also cannot predict if sepsis cases will progress to septic shock.

Saria and colleagues identified 27 factors from a pool of 54 candidates that reliably predict sepsis development, and combined those factors into a machine-learning algorithm. The team then ran the algorithm with a database of more than 13,000 electronic medical records (without identifying information) of intensive-care patients at Beth Israel Deaconess Medical Center in Boston from 2001 to 2007 to refine the model, which they call Targeted Real-time Early Warning Score, or TREWScore. The electronic records include data captured from real-time vital sign monitors and lab reports.

The researchers tested the model with another 3,053 patient records from the same database, and compared the results with current tools for identifying risk of sepsis. The results show the TREWScore model performed with greater statistical certainty — identifying cases that develop into septic shock versus those that do not  — than the current method, Modified Early Warning Score. TREWScore identified septic shock cases in advance by a median of 28 hours, with a sensitivity, or true positive rate, of 85 percent. In addition, TREWScore identified 59 percent more patients before signs of organ failure were noticed.

The researchers still need to devise workable processes for building the model into the systems and procedures of health care providers. “Our methods are reaching a point where they can be a real aid to clinicians,” says Saria in a university statement, “especially in noticing subtle hints, buried deep in a chart, that a problem is developing.” Saria notes, however, “we have to do this in a way that it is well-integrated into the existing clinical workflow and does not cause alarm fatigue.”

The authors note that with the Affordable Care Act, more opportunities will arise for constructing real-time predictive models like TREWScore. The Affordable Care Act requires health plans and providers to standardize billing and adopt electronic health records for cutting costs and reducing medical errors.

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