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  • Landscape for AML Patients Evolving Rapidly as Research Discoveries Advance New Treatments

    Landscape for AML Patients Evolving Rapidly as Research Discoveries Advance New Treatments

    Newswise — MIAMI, FLORIDA (EMBARGOED UNTIL DEC. 10, 2023, AT 7:30 P.M. ET) – The treatment landscape for acute myeloid leukemia (AML) is evolving rapidly, as research discoveries at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine and other academic cancer centers advance new, more effective therapies for this aggressive blood cancer. 

    “We’ve seen more progress during the past 10 years than the previous four decades combined,” said Justin M. Watts, M.D., Sylvester hematologist, associate professor of medicine, and Pap Corps Early Career Endowed Professor in Leukemia, “especially when it comes to treating older AML patients.”

    Watts, who serves as chief of the leukemia section at Sylvester, will highlight new drugs, such as Venetoclax plus Azacitidine, and new targeted therapies resulting from research advances when he leads an educational session at ASH 2023, the annual meeting of the American Society of Hematology in San Diego, Dec. 9-12.

    The session is designed to update community-based physicians who treat AML patients on current standards of care for using these new drugs sequentially or in triplet combinations with targeted inhibitors.  

    Background

    Acute myeloid leukemia is a cancer characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood-cell production. It’s one of the most common leukemia types in adults, although it’s fairly rare, accounting for about 1% of all cancers.

    It tends to afflict older adults, with 68 being the median age when first diagnosed, according to the American Cancer Society. Men are slightly more at risk than women.

    Typically, AML patients have been treated with intensive chemotherapy and a bone-marrow or stem-cell transplant. Those therapies are generally more effective in people under age 60. “We can cure about 60% of younger patients now, which is significantly better than just two decades ago,” said Watts. “But older patients, depending on their fitness level, don’t usually tolerate these treatments and historically less than 10 percent were cured, but this is now pushing 30% with the advent of venetoclax plus azacitidine and targeted inhibitors.”

    Until recently, next steps for these patients were limited to supportive care and blood transfusions, he added.

    Targeted Therapies for Mutations

    However, the outlook has improved, especially for older patients, with the emergence of new drugs and targeted inhibitors for the mutations driving AML, Watts says.

    “AML is almost always driven by mutations acquired over time,” he explained. “That’s why the risk of AML increases as we age.”

    Although there are hundreds of mutations that can cause this blood cancer, and most patients have more than one, there are five more common ones that are targetable: IDH1, IDH2, FLT3, NPM1 and MLL, Watts said. All of these now have approved therapies – or ones in development – thanks to ongoing research at Sylvester and other cancer centers.

    The results are encouraging. “We’re seeing very promising results in our studies and trials, combining Venetoclax, Azacitidine and targeted therapies, often as frontline therapy for AML,” he noted.

    Watts said the combination of Venetoclax and Azacitidine is producing good outcomes in about 52% of older patients, and the median survival is more than 2 years in these patients, with some patients living much longer.  

    Additionally, targeted therapies are proving effective, even in relapsed patients, and these treatments are also better tolerated than chemotherapy.

    Now, researchers like Watts and his colleagues must determine the best way to combine venetoclax and targeted therapies to produce the best outcomes. “That includes designing clinical trials to help us identify the optimal combinations for the right patients with specific mutations,” he explained, “and determining when we stop therapy for patients in a long remission.”

    On the Horizon

    Watts said that up to 50% of AML patients have a mutation for which there is no current targeted therapy. “We have to expand our targeted therapies to treat AML patients with harder to target mutations,” he explained, citing TP53 and RAS mutations as two common pathways for treatment resistance. “We currently have few approved therapies that are effective for these patients, especially if they are older.”

    Watts believes the future direction for AML treatment will involve targeted therapy combined with the “best backbone we have, possibly chemotherapy for younger patients or the drugs like venetoclax and azacitidine generating good results for older adults.”

    One of the biggest things that may come into play is immunotherapy, he said. “I can see us getting the immune system more involved in treating these blood cancers, as it has done with solid tumors and lymphoma.”

    Disclosures

    Dr. Watts serves on the consulting/advisory boards of Rigel, Servier, Celgene/BMS, Daiichi Sankyo, Aptose and Ativarre. He receives research funding from Takeda, Immune Systems Key Ltd, and Rigel.

    # # # 

    ASH Presentation Title:

    “The Future Paradigm of HMA + VEN or Targeted Inhibitor Approaches: Sequencing or Triplet Combinations in AML Therapy”

    Presentation Date/Time:

    Sunday, Dec. 10, 2023, 7:30 to 8:45 pm ET (4:30 to 5:45 pm PT)

    # # #

    Sylvester Comprehensive Cancer Center

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  • ASH: Novel combination therapy significantly reduces spleen volume in patients with myelofibrosis

    ASH: Novel combination therapy significantly reduces spleen volume in patients with myelofibrosis

    Newswise — SAN DIEGO ― Combining the JAK inhibitor ruxolitinib with the BCL-xL inhibitor navitoclax was twice as effective in reducing enlarged spleens – a major indicator of clinical improvement – compared with standard-of-care ruxolitinib monotherapy for adult patients with intermediate or high-risk myelofibrosis, a rare bone marrow cancer, according to results of the Phase III TRANSFORM-1 trial reported by researchers from The University of Texas MD Anderson Cancer Center.

    Data from the global, randomized, placebo-controlled clinical trial were presented today at the 2023 American Society of Hematology (ASH) Annual Meeting by Naveen Pemmaraju, M.D.,  professor of Leukemia. At the time of data cut-off, 63.2% of patients who received ruxolitinib and navitoclax achieved a spleen volume reduction of at least 35% within 24 weeks, compared to 31.5% of patients receiving ruxolitinib plus placebo, meeting the study’s primary endpoint.

    “By adding a second drug to an approved therapy, we were able to improve spleen volume reduction compared to the current standard of care. This is an important measurement of the clinical benefits of this novel drug combination because treatments can be less effective when the spleen remains enlarged,” Pemmaraju said. “If we can treat myelofibrosis earlier on in the disease course, we may have an opportunity to impact overall disease modificationimprove patient outcomes and reduce symptom burden.”

    Currently, there are few Food and Drug Administration-approved drugs for the treatment of myelofibrosis. Available options provide patients with spleen and symptom improvement, but a substantial unmet need remains for therapies that provide durable spleen size reduction and other longer-term clinical. Allogenic stem cell transplants are an effective treatment option, but not all patients qualify.

    This international trial enrolled 252 patients with intermediate or high-risk myelofibrosis and measurable spleen enlargement who had not received prior JAK inhibitor treatment. The trial randomized 125 patients to receive the navitoclax and ruxolitinib combination and 127 patients to receive ruxolitinib plus placebo. Most patients were male (57%) and the median age was 69.

    The trial met its primary endpoint of spleen volume reduction at 24 weeks. Spleen volume reduction at any time was achieved by 77% of patients on the combination arm and 42% of patients on the control arm. The median time to first spleen volume reduction response was 12.3 weeks with the combination and 12.4 weeks with monotherapy. At 24 weeks, there were no significant differences between the groups in a myeloproliferative neoplasm symptom assessment, a secondary endpoint of the study.

    Patients treated with the combination therapy, patients experienced side effects that were manageable and consistent with previous trials. The most common treatment-related side effects were thrombocytopenia, anemia, diarrhea and neutropenia. Serious adverse events were experienced by 26% of patients on the combination arm and 32% on the control arm.

    “This study marks a notable achievement in the field of myelofibrosis, as one of the first reported global Phase III frontline randomized combination clinical trials in our field,” Pemmaraju said. “This dataset now opens the door for additional research and investigation into combination therapies to treat myelofibrosis and, importantly, highlights a potential new era of investigating disease modification for patients. Additional data from the TRANSFORM-1 study is being evaluated.”

    The trial was funded by AbbVie. Pemmaraju receives research support from AbbVie. A full list of co-authors and their disclosures may be found here.

    Read this press release in the MD Anderson Newsroom.

    University of Texas MD Anderson Cancer Center

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  • ASH: Targeted oral therapy reduced disease burden and improved symptoms for patients with rare blood disorder

    ASH: Targeted oral therapy reduced disease burden and improved symptoms for patients with rare blood disorder

     Newswise — SAN DIEGO ― The targeted therapy bezuclastinib was safe and rapidly reduced markers of disease burden while also improving symptoms for patients with a rare blood disorder called nonadvanced system mastocytosis, according to results of the Phase II SUMMIT trial reported by researchers at The University of Texas MD Anderson Cancer Center.

    The findings, presented today at the 2023 American Society of Hematology (ASH) Annual Meeting, demonstrate that all participants treated with bezuclastinib achieved at least a 50% reduction in markers of disease burden and 63% reported their disease symptoms eased within 12 weeks. That number increased to 78% after an additional eight weeks of treatment, at which time all patients also reported an improvement in pain symptoms.

    “The era of targeted therapy offers hope, not just for alleviating symptoms but for getting to the root of the condition,” said principal investigator Prithviraj Bose, M.D., professor of Leukemia. “Bezuclastinib provides precision targeting without the typical central nervous system or bleeding side effects often associated with similar drugs.”

    Systemic mastocytosis (SM) is a rare disease marked by the buildup of malignant mast cells in the bone marrow and other tissues. These high levels of abnormal mast cells can lead to a multitude of symptoms due to the release of chemicals called mediators. SM can range from non-advanced (NonAdvSM) to advanced disease (AdvSM), with symptoms that can include brain fog and skin rashes to gut issues and life-threatening anaphylaxis.

    In up to 95% of patients, SM is driven by the KIT D816V gene mutation. Treatments targeting this mutated kinase have been used for AdvSM variants, but they are known to have off-target activity that can cause toxicities that restrict dosing and, therefore, limit efficacy.

    There are two variants within NonAdvSM: indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM). ISM, which affects the majority of patients with SM, is characterized mostly by symptoms related to mast cell degranulation and mediator release. SSM is identified by a higher mast cell burden, marked by high levels of blood enzymes like serum tryptase, but without resulting organ damage.

    Bezuclastinib is a potent type-1 tyrosine kinase inhibitor that blocks mutant KIT D816V activity while sparing other kinases, minimizing the potential for off-target side effects. In a separate, prior studies, the drug demonstrated minimal brain penetration in animals and no central nervous system toxicities in patients with AdvSM.

    The first part of the SUMMIT trial followed 20 patients with NonAdvSM for a median duration of seven months. The majority were female (75%) with a median age of 50. Seventy-five percent of patients had the KIT D816V mutation, and all had moderate-severe symptoms. Patients were treated with either 100 or 200 mg of bezuclastinib or with placebo. All patients continued to receive their baseline anti-mediator treatments throughout the trial.

    Researchers evaluated the efficacy of bezuclastinib through multiple patient-reported outcome measures and changes in markers of disease burden, such as serum tryptase, bone marrow mast cell percentage and KIT D816V mutation allele burden.

    Patients who received the 100 mg dose experienced a median reduction in symptoms of 48.5% after 12 weeks. During this period, none of the patients in the placebo group reported significant improvement in their overall symptoms. However, after transitioning those patients to bezuclastinib treatment, 67% reported an improvement in their symptoms after four weeks. 

    After 20 weeks, more patients observed greater improvements in dermatological symptoms (78%), gastrointestinal symptoms (33%) and cognitive symptoms (33%) compared to the 12-week mark.

    Adverse events generally were mild and reversible, with the most frequent being a change in hair color, nausea and peripheral edema. No serious adverse events related to bezuclastinib were reported in the 100 mg or 200 mg cohorts.

    “This drug may offer great promise in the treatment of non-advanced systemic mastocytosis,” Bose said. “As we move forward, our aspiration is to optimize the dosage while maintaining a robust safety profile.”

    To futher assess the drug’s efficacy in patients with NonAdvSM, next steps for the SUMMIT trial include comparing bezuclastinib against placebo once the optimal dose is determined. Part Ib of the trial will investigate 100mg and 150 mg daily doses that use a different formulation of the drug, and those results are expected in 2024, Bose explained.

    The SUMMIT trial was sponsored by Cogent Biosciences. Bose reports relationships with Cogent Biosciences, GSK, Novartis, Karyopharm, AbbVie, PharmaEssentia, Jubilant, Morphic, Kartos, Telios, Disc, Jassen, Geron, Ionis, Incyte, Bristol Myers Squibb, Sobi, MorphoSys, Blueprint and Sumitomo. A full list of co-authors and disclosures can be found with the abstract.

    Read this press release in the MD Anderson Newsroom.

    University of Texas MD Anderson Cancer Center

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  • ASH: Novel menin inhibitors show promise for patients with advanced acute myeloid leukemias

    ASH: Novel menin inhibitors show promise for patients with advanced acute myeloid leukemias

    Newswise — Two clinical trials led by researchers from The University of Texas MD Anderson Cancer Center demonstrated early positive results from novel therapies targeting menin for the treatment of relapsed or refractory acute leukemias with specific genetic alterations. Results from the studies were shared today in oral presentations at the 2023 American Society of Hematology (ASH) Annual Meeting. More information on all ASH Annual Meeting content from MD Anderson can be found at MDAnderson.org/ASH.

    Menin inhibitor monotherapy reduces disease burden in majority of relapsed or refractory acute leukemia patients (Abstract 57) According to data from a Phase I trial led by Elias Jabbour, M.D., professor of Leukemia, the menin inhibitor JNJ-75276617 showed early clinical activity in patients with relapsed or refractory acute leukemias and genetic alterations in KMT2A or NPM1, which are associated with poor clinical outcomes.

    Among 66 patients able to be evaluated after one month of treatment, JNJ-75276617 monotherapy reduced bone marrow disease burden in 71%, and 33 of those patients had a decrease in bone marrow blasts of more than 50%. Median time to first response was less than two months. Similar response rates were observed across patient groups with both genetic alterations.  

    “Patients with relapsed or refractory leukemias and KMT2A or NPM1 alterations often do poorly on currently available therapies, so there is a need to advance more effective options,” Jabbour said. “We are encouraged by the antileukemic activity of this monotherapy, which mimics what we saw in the preclinical setting.”

    In the multi-center clinical trial, researchers took a stepwise approach in evaluating the safety and efficacy of JNJ-75276617, a potent and selective inhibitor of the interaction between the scaffolding protein menin and the methyltransferase KMT2A. Eighty-six patients who had acute leukemias with NPM1 & KTM2A genetic alterations were included in the trial.

    Patients received the therapy orally on a 28-day cycle. Fifty-six percent of evaluable patients had AML with KMT2A alterations and 43% of evaluable patients had NPM1 alterations. The median age of trial participants was 63 years, while the median number of prior therapies was two.

    Differentiation syndrome was the most common side effect in patients, but was overcome with step-up dosing. The trial is ongoing to determine the recommended Phase II dose.

    The trial is sponsored by Janssen Pharmaceuticals. A complete list of collaborating authors and their disclosures can be found with the abstract.

    Oral therapy combination shows promising results for advanced acute leukemias (Abstract 58) The Phase I/II SAVE trial, led by Ghayas Issa, M.D., assistant professor of Leukemia, combined the menin inhibitor revumenib with venetoclax and hypomethylating agent ASTX727, yielding encouraging responses in adult and pediatric patients with relapsed or refractory advanced acute myeloid leukemia (AML) with KMT2A or NUP98 rearrangements or NPM1 mutations.

    The overall response rate among nine evaluable patients was 100%. Three patients achieved complete remission, one patient achieved complete remission with partial hematologic recovery, and three patients had complete remission with incomplete platelet count recovery. In addition, one patient had a partial response and one had a morphologic leukemia-free state. Measurable residual disease was undetectable in six of the patients. 

    “These advanced and acute leukemias often are very difficult to treat and currently have no approved targeted therapies. We believe these early results suggest this treatment will be highly effective in advanced leukemias,” Issa said. “This is our first look at an entirely oral combination therapy using menin inhibitors, and the results are very encouraging. If sustained in further trials, this could lead to a change in the standard of care for this patient population, with great potential to improve their quality of life.”

    Revumenib is a potent, oral, selective inhibitor of the menin-KMT2A interaction. To date, nine patients aged 12 years and older have been enrolled in the trial. Of those, five patients had KMT2A rearrangements, three had NUP98 rearrangements and one had mutant NPM1. On average, patients had received three prior lines of therapy.

    Side effects were manageable and consistent with previous studies. The trial is ongoing, with plans to establish the recommended Phase II dose and optimize delivery of the combination before enrolling patients in the Phase II cohort.

    This investigator-initiated study was supported by Syndax and Astex. A complete list of collaborating authors and their disclosures can be found with the abstract.

    Read this press release in the MD Anderson Newsroom.

    University of Texas MD Anderson Cancer Center

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  • First-in-human clinical trial of CAR T cell therapy with new binding mechanism shows promising early responses

    First-in-human clinical trial of CAR T cell therapy with new binding mechanism shows promising early responses

    Newswise — SAN DIEGO – Early results from a Phase I clinical trial of AT101, a new CAR T cell therapy that uses a distinct binding mechanism to target CD19, show a 100 percent complete response (CR) rate at the higher dose levels studied in the trial, according to researchers from the University of Pennsylvania Perelman School of Medicine and Penn Medicine’s Abramson Cancer Center. The findings were published today in Molecular Cancer and presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 2096).

    CAR T cell therapy has revolutionized treatment for many people with blood cancers who had run out of other treatment options. While some patients experience long-term responses to CAR T cell therapy, it doesn’t work–or the cancer eventually returns–for others. The CD19 CAR T cell therapies that are currently approved all target CD19 through the same epitope (FMC63). To try and make CD19 CAR T cell therapy more effective for more patients, Marco Ruella, MD, an assistant professor of Hematology-Oncology and Scientific Director of the Lymphoma Program, and his research team, along with the Korean company AbClon Inc, co-developed a CAR T product (AT101), using cells originating from the same patient, that targets CD19 through a different epitope, located closer to the cell membrane, via a novel antibody (h1218). In preclinical studies, the team previously demonstrated that h1218-CART19 had decreased T cell exhaustion and improved control compared to FMC63-CART19.

    The Phase I first-in-human clinical trial (NCT05338931) was conducted in South Korea and enrolled 12 patients with relapsed or refractory B cell non-Hodgkin’s lymphoma (NHL). The study was designed to increase the dose level of AT101 after safety was confirmed in the first six patients. After a median follow-up of 6.5 months, all six patients who received dose level 2 or higher experienced a complete response and their cancer has not relapsed.  

    “We’ve learned that the way you design your CAR really matters. Designing a different CAR might drastically change the way the T cells work, potentially allowing that CAR T cell product to work where other CAR T cell products have failed,” Ruella said. “We were not expecting such a drastic early difference in this study. The CART19 products that are already FDA-approved are very effective, and it’s not easy to do better. While there is not a randomized trial of this product yet, the initial results seem very promising, and we look forward to moving into the planned Phase II portion of the study.”

    The drug was found to be safe, with manageable side effects, including cytokine-release syndrome in four patients and immune-cell-related neurotoxicity syndrome in three patients. One patient experienced grade 3 sepsis that resolved; the same patient later developed fatal neutropenic septic shock outside the dose-limiting toxicity time frame.

    The Phase I study enrolled patients who had not previously received any other CAR19 therapy. In the Phase II expansion, the study will also include patients who have previously received CAR19 therapy.

    Editor’s Note: The study was funded by AbClon Inc; Ruella is a paid consultant for the company and has a Sponsored Research Agreement with them.

    Yunlin Zhang, MS, a research specialist in Ruella’s lab, will present the findings in a poster session on Saturday, Dec. 9, from 5:30 to 7:30 p.m. PT in the San Diego Convention Center Halls G-H.

    ###

    Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

    The Perelman School of Medicine is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

    The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

    Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

    Perelman School of Medicine at the University of Pennsylvania

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  • Mindfulness Could Help Women with Opioid Use Disorder Better Control Drug Urges

    Mindfulness Could Help Women with Opioid Use Disorder Better Control Drug Urges

    BYLINE: Patti Zielinski

    Newswise — Mindfulness-Oriented Recovery Enhancement (MORE) — a behavioral intervention that integrates training in mindfulness, emotion regulation strategies and savoring of natural rewards — could hold the key to mitigating relapse in women undergoing medically assisted opioid use disorder treatment, a Rutgers study found.

    The pilot study published in the journal Explore, is the first to evaluate the potential neural changes that underlie women’s emotion regulation and craving after an eight-week MORE intervention.

    Previous studies have shown that women report higher opioid craving and show a greater inability to control their drug urges than men. Although medications, like buprenorphine, can be effective in mitigating urges in the short-term by limiting biological changes associated with acute withdrawal, it is less effective at long-term adherence in avoiding relapse with other illicit drugs.

    “While these medications help with withdrawal, they do not fully engage the core regulatory and affective processing circuits that give people control over negative emotion and do not help to address opioid craving in a sustainable way,” said the lead author Suchismita Ray, an associate professor at Rutgers School of Health Professions. “This is where complementary therapies, such as MORE, could play a key role.”

    MORE, which was developed by Eric L. Garland at The University of Utah, is centered on three key therapeutic processes:

    • Mindfulness, which trains a person to become aware of when their attention has become fixated on addictive cues, stressors or pain, then to shift from affective to sensory processing of craving, stress or pain sensations and re-orient their attention through mindful breathing.
    • Reappraisal of thoughts to disengage from negative emotions and addictive behaviors and turn toward positive thoughts that promote resilience, meaning and active coping behaviors.
    • Savoring naturally rewarding experiences (nature, time with a loved one) in a mindful way and recognize the positive emotional responses to the experience.

    Researchers studied nine women in residential treatment who were on medications for opioid use disorder and completed an eight-week MORE intervention once a week for two hours. Both before and after the eight-week period, researchers gave participants an emotion regulation questionnaire and then scanned their brains in a magnetic resonance imaging machine while they listening to a 10-minute guided MORE meditation and viewed a picture of an outdoor garden to measure the brain’s communication during the meditation.

    “Prior studies have shown that the inability to handle negative emotion and drug craving are major determinants of drug relapse. We examined the immediate effects of the 10-minute guided MORE meditation on mood and craving, then looked at the effects of the eight-week MORE intervention on brain communication and how well the women regulated their emotions,” Ray said. “The results show that a single 10-minute guided MORE meditation without any prior meditation experience immediately improved participants’ mood. The eight-week MORE intervention boosted their emotional awareness and strengthened their impulse control — factors that are important in preventing relapse.”

    In addition, researchers found that the eight-week MORE intervention resulted in significantly increased communication between the areas of the brain that may help women with opioid use disorder to better control their negative emotion and drug craving.

    “What this could mean is if an opioid user experiences stress or a craving for an opioid, she can immediately practice a 10-minute MORE meditation, which will improve her mood in the moment and potentially prevent her from taking the drug,” Ray said. “If that person also takes part in the eight-week MORE intervention, she could reap additional long-term benefits to control negative emotion and opioid craving and better maintain sobriety.”

    Other Rutgers authors include Jamil Bhanji and Mauricio Delgado (Rutgers–Newark) and Patricia Dooley Budsock and Nina A. Cooperman (Rutgers Robert Wood Johnson Medical School). Eric L. Garland from The University of Utah is also an author on this pilot study.

    The authors would like to acknowledge The Rutgers University Brain Imaging Center in Newark where the subject scanning took place for this pilot study.

    Rutgers University-New Brunswick

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  • Groundbreaking progress in treating severe asthma emerges.

    Groundbreaking progress in treating severe asthma emerges.

    Newswise — A landmark study has shown that severe asthma can be controlled using biologic therapies, without the addition of regular high-dose inhaled steroids which can have significant side effects.

    The findings from the multinational SHAMAL study, published in The Lancet, demonstrated that 92% of patients using the biologic therapy benralizumab could safely reduce inhaled steroid dose and more than 60% could stop all use. 

    The study’s results could be transformative for severe asthma patients by minimising or eliminating the unpleasant, and often serious, side effects of inhaled steroids. These include osteoporosis which leads to increased risk of fractures, diabetes and cataracts.

    Asthma is one of the most common respiratory diseases worldwide – affecting almost 300 million people – and around 3 to 5% of these have severe asthma.  This leads to daily symptoms of breathlessness, chest tightness and cough, along with repeated asthma attacks which require frequent hospitalisation.

    The SHAMAL study was led by Professor David Jackson, head of the Severe Asthma Centre at Guy’s and St Thomas’ and Professor of Respiratory Medicine at King’s College London.

    Professor Jackson said: “Biological therapies such as benralizumab have revolutionised severe asthma care in many ways, and the results of this study show for the first time that steroid related harm can be avoided for the majority of patients using this therapy.” 

    Benralizumab is a biologic therapy that reduces the number of inflammatory cells called eosinophil. This is produced in abnormal numbers in the airway of patients with severe asthma and is critically involved in the development of asthma attacks. Benralizumab is injected every four to eight weeks and is available in specialist NHS asthma centres.

    The SHAMAL study took place across 22 sites in four countries – the UK, France, Italy and Germany.

    The 208 patients were randomly assigned to taper their high dose inhaled steroid by varying amounts over 32 weeks, followed by a 16 week maintenance period. Approximately 90% of patients experienced no worsening of asthma symptoms and remained free of any exacerbations throughout the 48 week study. 

    Similar studies to SHAMAL will be necessary before firm recommendations can be made regarding the safety and efficacy of reducing or eliminating high dose steroid use with other biologic therapies.

    The study was funded by AstaZeneca and carried out by researchers at renowned universities including Queens University Belfast, Université Paris-Saclay and Trinity College Dublin.

    King’s College London

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  • Boosting engagement in heterosexual men may reduce HIV in Uganda

    Boosting engagement in heterosexual men may reduce HIV in Uganda

    Newswise — A study looking at 15 years of HIV transmission and suppression in Uganda reveals how closing gender gaps in treatment could slash infection rates.

    Providing more heterosexual men with easy access to HIV treatment and care could help to suppress the virus and rapidly cut transmission to their female partners, shows a new study published in Nature Microbiology.

    The research, led by scientists from Imperial College London and the Rakai Health Sciences Program in Uganda, analysed 15 years of data from 2003-2018, during which the US President’s Emergency Plan For AIDS Relief (PEPFAR) has delivered an extensive programme of HIV/AIDS testing, prevention, and treatment.

    This included distributing Antiretroviral Therapy (ART) drugs, which supress the virus so a person is no longer infectious. The analysis shows that the PEPFAR program and other services have greatly reduced new infections among young women and heterosexual men, but that reductions were less substantial in women aged 25 and above.

    This is thought to be because women are more likely to reach viral suppression through uptake and effective use of HIV treatment, preventing them from passing HIV to their male partners, but that the same is not true the other way around.

    Gender disparity

    The analysis showed that the number of women reaching and maintaining undetectable (non-transmissible) levels of HIV infection were 1.5 to 2 times higher than men across all ages by the year 2018. The analysis shows that had men reached the same levels of virus suppression as women, around half the new infections that occurred between 2016 and 2018 could have been avoided.

    The team also reconstructed transmission networks based on the genetic code of the virus from thousands of participants, which confirmed that overall, the proportion of transmissions from men is increasing and is now at 63% of all transmissions in the area – even though a greater number of women are living with HIV than men.

    The team say the disparity could be because men need to travel for work, that clinics are closed when they are back home, or for other reasons, including social stigma.

    Dr Oliver Ratmann, senior author of the study from the Department of Mathematics at Imperial, said: “In this evolving battle against HIV, it is critical we adapt our strategies, bridge gaps in care, and ensure that individuals, regardless of their gender, have access to the lifesaving benefits of ART.

    “It is important to design services in a way that everybody who would like to use them is able and feels empowered to do so. By routinely monitoring the changing dynamics of the epidemic and striving for equity in HIV care, we can move closer to the ultimate goal of controlling and, one day, eliminating HIV transmission.”

    Dr Kate Grabowski, a co-author of the study from the Johns Hopkins School of Medicine, added: “The continued success of the President’s Emergency Plan for AIDS Relief (PEPFAR) in reducing infections and saving lives is crucial for ending HIV transmission. With United States Congress currently evaluating PEPFAR funding, our evidence strongly supports the program’s efficacy and provides a clear roadmap to ending the pandemic through enhanced HIV treatment coverage, particularly among men.”

    Closing the gap in transmission

    The team used data from the Rakai Community Cohort Study (RCCS) in southern Uganda, a region where more than 9% of adults are living with HIV – approximately 20 times higher than in the US. Since 2003, a period predating the widespread availability of ART in Africa, RCCS has enrolled nearly 37,000 individuals, tracking changes in HIV infection as new interventions came on board.

    The analysis tracked evolving heterosexual HIV epidemic dynamics in 36 communities over a 15-year span of RCCS surveillance data, including records of new infections, deep sequence HIV genomic data, HIV treatment uptake, viral suppression, and behavioural information.

    Analyses in earlier years showed that the highest number of new HIV cases in southern Uganda was among adolescent girls and young women aged 15-24 years. In more recent years tracked in the new study, women 25-34 years old have become a new focal group, experiencing a slower decline in new infections than other age groups. This is alongside a significant difference in the declines in new infections between men and women, with those among boys and men declining much faster.

    To estimate the likely impact of getting men to the same level of viral suppression, the team applied statistical models based on the data about transmission dynamics. The resulting projections indicate that closing the viral suppression gap in men could have effectively halved rates of new infections among women and eliminated gender disparities in acquiring HIV.

    Dr Joseph Kagaayi, previous director of the Rakai Health Sciences program and senior co-author of the study, said: “Our study findings emphasise the importance of addressing disparities in ART uptake and viral suppression between men and women. By doing so, we can not only reduce HIV infections among women but also work towards closing the gender gap in HIV transmission. Achieving these goals will require concerted efforts, informed policies, and strengthened healthcare services.”

    Imperial College London

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  • Study reveals Zika’s shape-shifting machinery—and a possible vulnerability

    Study reveals Zika’s shape-shifting machinery—and a possible vulnerability

    Newswise — Viruses have limited genetic material—and few proteins—so all the pieces must work extra hard. Zika is a great example; the virus only produces 10 proteins. Now, in a study published in the journal PLOS Pathogens, researchers at Sanford Burnham Prebys have shown how the virus does so much with so little and may have identified a therapeutic vulnerability.

    In the study, the research team showed that Zika’s enzyme—NS2B-NS3—is a multipurpose tool with two essential functions: breaking up proteins (a protease) and dividing its own double-stranded RNA into single strands (a helicase).

    “We found that Zika’s enzyme complex changes function based on how it’s shaped,” says Alexey Terskikh, Ph.D., associate professor at Sanford Burnham Prebys and senior author of the paper. “When in the closed conformation, it acts as a classic protease. But then it cycles between open and super-open conformations, which allows it to grab and then release a single strand of RNA—and these functions are essential for viral replication.”

    Zika is an RNA virus that’s part of a family of deadly pathogens called flaviviruses, which include West Nile, dengue fever, yellow fever, Japanese encephalitis and others. The virus is transmitted by mosquitoes and infects uterine and placental cells (among other cell types), making it particularly dangerous for pregnant women. Once inside host cells, the virus re-engineers them to produce more Zika.

    Understanding Zika on the molecular level could have an enormous payoff: a therapeutic target. It would be difficult to create safe drugs that target the domains of the enzyme needed for protease or helicase functions, as human cells have many similar molecules. However, a drug that blocks Zika’s conformational changes could be effective. If the complex can’t shape-shift, it can’t perform its critical functions, and no new Zika particles would be produced.

    An efficient machineResearchers have long known that Zika’s essential enzyme was composed of two units: NS2B-NS3pro and NS3hel. NS2B-NS3pro carries out protease functions, cutting long polypeptides into Zika proteins. However, NS2B-NS3pro’s abilities to bind single-stranded RNA and help separate the double-stranded RNA during viral replication were only recently discovered.

    In this study, the researchers leaned on recent crystal structures and used protein biochemistry, fluorescence polarization and computer modeling to dissect NS2B-NS3pro’s life cycle. NS3pro is connected to NS3hel (the helicase) by a short amino acid linker and becomes active when the complex is in its closed conformation, like a closed accordion. The RNA binding happens when the complex is open, whereas the complex must transition through the super-open conformation to release RNA.

    These conformational changes are driven by the dynamics of NS3hel activity, which extends the linker and eventually “yanks” the NS3pro to release RNA. NS3pro is anchored to the inside of the host cell’s endoplasmic reticulum (ER)—a key organelle that helps shepherd cellular proteins to their appropriate destinations—via NS2B and, while in the closed conformation, cuts up the Zika polypeptide, helping generate all viral proteins.

    On the other side of the linker, NS3hel separates Zika’s double-stranded RNA and conveniently hands a strand over to NS3pro, which has positively charged “forks” to grab on to the negatively charged RNA.

    “There’s a very nice groove of positive charges,” says Terskikh. “So, RNA just naturally follows that groove. Then the complex shifts to the closed conformation and releases the RNA.”

    As NS3hel reaches forward to grab the double-stranded RNA, it pulls the complex with it; however, since the NS3pro is anchored in the ER membrane, and the linker can only extend so far, the complex snaps into the super-open conformation and releases RNA. The complex then relaxes back to the open conformation, ready for a new cycle.

    Meanwhile, when NS3pro detects a viral polypeptide to cut, it forces the complex into the closed conformation, becoming a protease. The authors call this process “reverse inchworm,” because grabbing and releasing the single-stranded RNA resembles inchworm movements, but backward with the jaws (the protease) trailing behind.

    In addition to providing a possible therapeutic target for Zika, this detailed understanding could be applied to other flaviviruses, which share similar molecular machinery.

    “Versions of the NS2B-NS3pro complex are found throughout the flaviviruses,” says Terskikh. “It could potentially constitute a whole new class of drug targets for multiple viruses.”

    ###

    Additional authors include Sergey A. Shiryaev, Piotr Cieplak, Anton Cheltsov and Robert C. Liddington.

    This study was supported by grants from the National Institutes of Health (5R21AI134581 and R01 NS105969).

    Sanford Burnham Prebys

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  • Advisory panel issues field-defining recommendations for investments in particle physics research

    Advisory panel issues field-defining recommendations for investments in particle physics research

    Newswise — Yesterday marked the release of a highly anticipated report from the Particle Physics Project Prioritization Panel (P5), unveiling an exciting new roadmap for unlocking the secrets of the cosmos through particle physics.

    The report was released by the High Energy Physics Advisory Panel to the High Energy Physics program of the Office of Science of the U.S. Department of Energy (DOE) and the National Science Foundation’s Division of Physics. It outlines particle physicists’ recommendations for research priorities in a field whose projects — such as building new accelerator facilities — can take years or decades, contributions from thousands of scientists and billions of dollars

    The 2023 P5 report represents the major activity in the field of particle physics that delivers recommendations to U.S. funding agencies. This year’s report builds on the output of the 2021 Snowmass planning exercise — a process organized by the American Physical Society’s (APS) Division of Particles and Fields that convened particle physicists and cosmologists from around the world to outline research priorities. This membership division constitutes the only independent body in the U.S. that represents particle physics as a whole.

    “With our state-of-the-art facilities and community of dedicated scientists, Argonne’s contributions are shaping the global trajectory of high-energy physics.” — Rik Yoshida, Argonne High Energy Physics Division Director

    “With our state-of-the-art facilities and community of dedicated scientists, Argonne’s contributions are shaping the global trajectory of high-energy physics.” — Rik Yoshida, Argonne High Energy Physics Division Director

    “The P5 report will lay the foundation for a very bright future in the field,” said R. Sekhar Chivukula, 2023 chair of the APS Division of Particles and Fields and a distinguished professor of physics at the University of California, San Diego. ​“There are extraordinarily important scientific questions remaining in particle physics, which the U.S. particle physics community has both the capability and opportunity to help address, within our own facilities and as a member of the global high energy physics community.”

    The report includes a range of budget-conscious recommendations for federal investments in research programs, the U.S. technical workforce and the technology and infrastructure needed to realize the next generation of transformative discoveries related to fundamental physics and the origin of the universe. For example, the report recommends continued support for the Deep Underground Neutrino Experiment (DUNE), based out of DOE’s Fermilab in Illinois, for CMB-S4, a network of ground-based telescopes designed to observe the cosmic microwave background (CMB), and for the planned expansion of the South Pole’s neutrino observatory, an international collaboration known as IceCube-Gen2, in a facility operated by the University of Wisconsin–Madison.

    Researchers at DOE’s Argonne National Laboratory stand at the forefront of high energy physics and are poised to contribute significantly to the advancement of the field over the next decade. They are exploring the fundamental nature of the universe and pioneering innovative technologies with far-reaching implications. In particular, Argonne’s High Energy Physics (HEP) division leverages the laboratory’s suite of multidisciplinary facilities and equipment — including world-class scientific computing capabilities — to further scientific discovery and advance accelerator technology. For example, Argonne’s contributions to key high energy physics collaborations include the design and fabrication of components for DUNE, the development of cutting-edge detectors for CMB-S4 and more.

    “With our state-of-the-art facilities and community of dedicated scientists, Argonne’s contributions are helping to shape the global trajectory of high-energy physics,” said Rik Yoshida, director of Argonne’s HEP division. ​“This report reflects the collective wisdom of the high energy physics community, and we look forward to leveraging our expertise and capabilities here at Argonne to help uncover the mysteries of the universe, drive innovation, inspire future generations of scientists and bolster our nation’s vital role in the future of particle physics.”

    “In the P5 exercise, it’s really important that we take this broad look at where the field of particle physics is headed, to deliver a report that amounts to a strategic plan for the U.S. community with a 10-year budgetary timeline and a 20-year context. The panel thought about where the next big discoveries might lie and how we could maximize impact within budget, to support future discoveries and the next generation of researchers and technical workers who will be needed to achieve them,” said Karsten Heeger, P5 panel deputy chair and Eugene Higgins Professor and chair of physics at Yale University.

    New knowledge, and new technologies, set the stage for the most recent Snowmass and P5 convenings. ​“The Higgs boson had just been discovered before the previous P5 process, and now our continued study of the particle has greatly informed what we think may lie beyond the standard model of particle physics,” said Hitoshi Murayama, P5 panel chair and the MacAdams Professor of physics at the University of California, Berkeley. ​“Our thinking about what dark matter might be has also changed, forcing the community to look elsewhere — to the cosmos. And in 2015, the discovery of gravitational waves was reported. Accelerator technology is changing too, which has shifted the discussion to the technology R&D needed to build the next-generation particle collider.”

    The U.S. participates in several major international scientific collaborations in high energy physics and cosmology, including the European Council for Nuclear Research (CERN), which operates the Large Hadron Collider, where the Higgs boson was discovered in 2012. The P5 report recommends that the U.S. support a significant in-kind contribution to a new international facility, the ​“Higgs factory,” to further our understanding of the Higgs boson.

    It also recommends that the U.S. study the possibility of hosting the next most-advanced particle collider facility to reinforce the country’s leading role in international high energy physics for decades to come.

    Activities of the P5 are supported in part by the APS’s Division of Particles and Fields.

    The American Physical Society is a nonprofit membership organization working to advance and diffuse the knowledge of physics through its outstanding research journals, scientific meetings, and education, outreach, advocacy, and international activities. APS represents more than 50,000 members, including physicists in academia, national laboratories, and industry in the United States and throughout the world.

    Argonne National Laboratory

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  • Michigan Ross Professor Yesim Orhun Explores Information Preference and Avoidance in New Research

    Michigan Ross Professor Yesim Orhun Explores Information Preference and Avoidance in New Research

    Newswise — In her recently published research, Yesim Orhun, associate professor of marketing and Michael R. and Mary Kay Hallman Fellow, explores unique insights into what information individuals seek when making important decisions and how policymakers, medical professionals, and business leaders should communicate anxiety-provoking news.  

    Recently published in the American Economic Review, “Intrinsic Information Preferences and Skewness” was co-authored by Orhun and two collaborators – Yusufcan Masatiloglu from the University of Maryland and Collin Raymond from Cornell University.

    Orhun’s research extends precursory research that documents information avoidance. Previous studies have shown that individuals avoid obtaining information in some contexts, even when information can be useful for making better decisions. Information avoidance generally arises in anxiety-provoking situations where the information can be good or bad. For example, in deciding to take a test that will determine whether one will develop a debilitating disease later in life. To protect themselves against the emotional blow of getting bad news, people may choose to remain in the dark instead. Orhun and her collaborators tested the implications of these theories with a focus on the kinds of information people prefer.

    The team conducted experiments on informational preferences in medical testing, intelligence testing, and lotteries. First, they tested a new kind of preference — a preference for skewness. Positively skewed information sources present bad news frequently but with low precision. When they deliver good news, which happens infrequently, you can count on it being generally accurate. Negatively skewed information sources present good news frequently but with low precision, and when they deliver bad news, it’s with higher certainty. Their findings showed that when given the choice, people overwhelmingly prefer positively skewed information sources and often avoid negatively skewed information sources.

    “When we started this project, I expected the majority of people to prefer the negatively skewed information sources over the positively skewed ones because I do. I do not like to get my hopes up high only to get disappointed by reality later. In fact, much of the early discussions about this project related to medical tests I was willing to endure as an expectant mom and my inability to fathom why my husband would not share the same informational preferences. The data settled the debate, which showed that I am in the minority,” said Orhun.

    The team then focused on individuals who rejected obtaining precise information that perfectly predicted the outcome. They found that some information-avoidant individuals will agree to receive positively skewed information. “The most important insight from our paper is that more precise information does not always mean more informed decision-making. People manage their emotions about anxiety-provoking events in the future by choosing the beliefs they want to carry, which is partially managed by which information sources they want to expose themselves to,” said Orhun.

    On avenues for future research, Orhun said, “Our findings raise two fundamental questions for me. First, would people pick different information sources if they had better coping mechanisms for dealing with the emotional impact of reality, such as more social support? Secondly, how should we think about the welfare implications of information? We care about one’s emotional well-being and physical and economic well-being. Information generally leads to better decision-making. Should we force information onto people when they want to avoid it? I think this is where knowing that positively skewed information may increase information uptake really comes in handy.”

    University of Michigan Ross School of Business

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  • Bird feeding may give humans something to chirp about

    Bird feeding may give humans something to chirp about

    BYLINE: Travis Williams

    Newswise — Ashley Dayer hopes to peck away at the notion that bird feeding is simply for the birds.

    An associate professor in the Department of Fish and Wildlife Conservation at Virginia Tech, Dayer is the lead author of an article published in People and Nature that argues not only for the acknowledgment of the activity’s benefit to humans, but that it should play a role in public guidance and policy.

    “Wildlife agencies and others making decisions on managing bird feeding need to be considering not only what the science is behind what’s going on with birds, but also the science behind what’s going on with people,” Dayer said.

    The article also encourages additional research to better understand how human well-being is impacted by regularly feeding birds, and Dayer and a team of researchers both in and outside of Virginia Tech are leading the way. The group is conducting what is perhaps the first large-scale bird feeding research that also incorporates observing humans.

    “People are not only reporting what they see at their bird feeders, but also their emotional responses to it,” Dayer said. “It’s pretty fun because most citizen science projects focus just on the natural or physical science, but we’re now able to look at the human piece of it.”

    Funded recently as part of a more than $1.5 million National Science Foundation grant led by Dayer and Dana Hawley, professor of biological sciences, the four-year project aims to engage more than 10,000 bird feeders across the United States.

    Other collaborators on the article and project include

    • Christy Pototsky, a graduate student studying fish and wildlife conservation at Virginia Tech
    • Richard Hall, associate professor at the University of Georgia
    • Alia Dietsch, associate professor at Ohio State University
    • Tina Phillips, David Bonter, Emma Greig, and Wesley Hochachka of the Cornell Lab of Ornithology

    Dayer said interest in the topic began in 2021, when the researchers began to notice state agencies advising people to stop feeding birds in response to various avian disease outbreaks. After looking into it, they found that 23 states had made such recommendations without evidence it would decrease disease spread, with varying levels of pushback, and with no real method of gauging compliance, much less its impact on people.

    The new project is an extension of the work Dayer and Hawley began about six years ago with the help of a joint seed grant from the Global Change Center of the Fralin Life Sciences Institute and the Institute for Society, Culture, and the Environment.

    Hawley said the lack of information about humans related to bird feeing was something she’d not previously considered, and she found it a strong motivator for this project.

    “In all my years of studying how bird feeding impacts wild birds, I didn’t give much thought to how it can also impact the people that spend their time and money feeding and watching birds,” Hawley said. “I get calls every year from people who see a sick bird at their feeder and want to know how they can help prevent disease spread. All in all, this made me wonder about how policy decisions that aim to minimize disease spread can inadvertently impact the people who feed the birds.”

    To help find those answers, the research team will utilize Project FeederWatch’s existing network of bird enthusiasts. Operated by the Cornell Lab of Ornithology and Birds Canada, FeederWatch has tasked people with asks participants to observe and report what they see at their feeders from November to April for the past 37 years.

    “FeederWatch is such a versatile data set even though, at its core, it is based on simple bird counts,” said Emma Greig, co-author and project leader for FeederWatch. “When you overlay information about behavior, disease, habitat, and climate change with those bird counts, we can get amazing insights into ecology and evolution.”

    During this project, FeederWatch participants also will be asked to observe their own well-being. Dayer said about 8,000 submissions came in in from the first week of this season alone.

    Such passion for birds is something Dayer understands very well. She said her mother always made sure they had bird feeders outside their family’s home, and when she became an “empty nester,” the birds became almost like children.

    “She’ll go on vacation and cut the vacation short because she needs to go home and feed her birds,” Dayer said. “So I’ve lived with someone who was really into bird feeding and have seen how important it can be to them.”

    But Dayer believes the positive impact of bird feeding isn’t limited to enthusiasts and is important in proving one of the most widely accessible connection to wildlife.

    “People in urban areas can feed birds. People with just a deck can feed birds. People with a wide range of physical abilities can feed birds. So it’s just a great way to keep that human connection to wildlife,” Dayer said.

    Hawley agreed with that sentiment, and said she hopes their work helps advance policies that will foster both health and healthy relationships.

    “In a world where so many of us live in cities or suburbs, having birds visit feeders in our yards or on our balconies is one of the only ways we get to connect daily with wildlife. But people want to be able to feed birds in ways that keep wild bird populations healthy and thriving,” Hawley said. “Our work will ideally help us develop guidelines for bird feeding that minimize risk to wild birds and maximize the benefits to the people that feed them.”

    The Department of Fish and Wildlife Conservation is in the College of Natural Resources and Environment. The Department of Biological Sciences is in the College of Science.
     

    Virginia Tech

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  • First Study of its Kind Reveals Impact of River Sediment on US Coastline

    First Study of its Kind Reveals Impact of River Sediment on US Coastline

    Newswise — As sea level continues to rise, threatening ecosystems, communities and infrastructure, experts are searching for ways to better understand how coastal environments may change in the future. A new research breakthrough published in Science reveals a novel way to study these changes by measuring how much sediment from the nation’s rivers makes it to the coastline. 

     

    Measuring, Mapping and Modeling 

    After testing many approaches in many different watersheds, UNCW Department of Earth and Ocean Sciences Professor Joanne Halls and co-authors Scott Ensign (Stroud Water Research Center) and Erin Peck (Northeast Climate Adaptation Science Center and USGS Woods Hole Coastal and Marine Science Center) developed a solution to measure the rate of river sediment accumulation across all watersheds of the contiguous United States.

    Using her expertise in Geographic Information Science (GIS), Halls developed a new web application called Sediment Pancakes. The app uses publicly available geospatial data to create digital models and interactive maps of the entire continental U.S. coast, including 4,972 rivers and streams. This is the first continent-wide examination of its kind. 

    “We tend to know much more about our large rivers and very little about the amount of river sediment in the smaller creeks and tributaries, even though these smaller systems are the majority of the landscape,” Halls said. “To our knowledge, this new web application is the only tool that provides local estimates of riverine sediment for all rivers of the contiguous U.S.”  

    The published paper, “Watershed Sediment Cannot Offset Sea Level Rise in Most US Tidal Wetlands,” concluded that 72% of all rivers do not provide adequate sediment, on an annual basis, to keep up with current estimates of sea level rise. In other words, river-borne sediment alone is insufficient to provide the elevation gain needed to offset increasing sea levels found in tidal wetlands like marshes, swamps and bogs. 

     

    Planning for the Future 

    As many local government agencies are building coastal resilience plans, and researchers nationwide are designing monitoring strategies to study and protect the coastal environments, the Sediment Pancakes app is a tool they can use to inform their planning.  

    “The more we leverage the enormous amount of map data toward principles of ‘smart growth,’ the better we can make our local communities,” Halls said. “My goal is to deliver map tools that assist local residents and planners so that we empower people to be engaged, exchange ideas in a meaningful and equitable way, and inspire students to be creative problem-solvers.” 

    University of North Carolina Wilmington

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  • UC Irvine researchers discover a mechanism that controls the identity of stem cells

    UC Irvine researchers discover a mechanism that controls the identity of stem cells

    Newswise — Irvine, Calif., Dec. 7, 2023 — University of California, Irvine, researchers discovered a mechanism that controls the identity of stem cells. When this mechanism fails, embryonic stem cells revert back in time and become totipotent. When a cell becomes totipotent, this rare change enables the cells the ability to differentiate into hundreds of cell types, and then go on to form every part of our body. This contrasts with pluripotent stem cells which can divide into various cell types but are unable to become an entire organism solely on their own.

    The study, Nuclear RNS catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation, was published Dec. 7, 2023, in Molecular Cell.

    “In a dish of embryonic stem cells, the majority of stem cells are pluripotent. However, one out of 1,000 cells are different from the rest, and are totipotent,” said Ivan Marazzi, PhD, director of the at UCI School of Medicine. “Totipotent cells are the only cells that have unlimited potential and can give rise to all parts of our body. We discovered the mechanism that allows this change from pluripotent to totipotent.”

    The ability to change the identity of stem cells allows researchers to delve into the fundamental aspect of development, specifically what happens when two cells meet and give rise to an embryo. Moreover, many disorders like cancer and neurodegenerative disease are characterized by cells “going back in time,” a process called cellular dedifferentiation.

    “Factors that control this ’reversion’ from stem cell to totipotent cell are mutated in humans with cancer and neurodegenerative disease,” said Marazzi, professor in the Department of Biological Chemistry at UCI School of Medicine.” We think there is a special susceptibility of brain and cancer cells to be vulnerable to this mechanism, which could help us in the future as we treat patients with these conditions.”

    The study was funded by the NIH and UCI.

     

    UCI School of Medicine:

    Each year, the UCI School of Medicine educates more than 400 medical students and nearly 150 PhD and MS students. More than 700 residents and fellows are trained at the UCI Medical Center and affiliated institutions. Multiple MD, PhD and MS degrees are offered. Students are encouraged to pursue an expansive range of interests and options. For medical students, there are numerous concurrent dual degree programs, including an MD/MBA, MD/MPH, or an MD/MS degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Program in Medical Education for Leadership Education to Advance Diversity-African, Black and Caribbean (PRIME LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit medschool.uci.edu.

     

    CITATION:

    Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation.

    Torre D, Fstkchyan YS, Ho JSY, Cheon Y, Patel RS, Degrace EJ, Mzoughi S, Schwarz M, Mohammed K, Seo JS, Romero-Bueno R, Demircioglu D, Hasson D, Tang W, Mahajani SU, Campisi L, Zheng S, Song WS, Wang YC, Shah H, Francoeur N, Soto J, Salfati Z, Weirauch MT, Warburton P, Beaumont K, Smith ML, Mulder L, Villalta SA, Kessenbrock K, Jang C, Lee D, De Rubeis S, Cobos I, Tam O, Hammell MG, Seldin M, Shi Y, Basu U, Sebastiano V, Byun M, Sebra R, Rosenberg BR, Benner C, Guccione E, Marazzi I.Mol Cell. 2023 Nov 14:S1097-2765(23)00903-6. doi: 10.1016/j.molcel.2023.10.036. Online ahead of print.PMID: 37995687

     

     

    Conflict of Interest Disclosures: Author has no conflict of interest to disclose.

    DOI: doi: 10.1016/j.molcel.2023.10.036.

    University of California, Irvine

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  • Fossil plant revealed as a baby turtle fossil.

    Fossil plant revealed as a baby turtle fossil.

    Newswise — From the 1950s to the 1970s, a Colombian priest named Padre Gustavo Huertas collected rocks and fossils near a town called Villa de Levya. Two of the specimens he found were small, round rocks patterned with lines that looked like leaves; he classified them as a type of fossil plant. But in a new study, published in the journal Palaeontologia Electronica, researchers re-examined these “plant” fossils and found that they weren’t plants at all: they were the fossilized remains of baby turtles.

    “It was truly surprising to find these fossils,” says Héctor Palma-Castro, a paleobotany student at the Universidad Nacional de Colombia.

    The plants in question had been described by Huertas in 2003 as Sphenophyllum colombianum. The fossils come from Early Cretaceous rocks, between 132 and 113 million years ago, during the dinosaurs’ era. Fossils of Sphenophyllum colombianum were surprising at this time and place— the other known members of the genus Sphenophyllum died out more than 100 million years prior. The plants’a ge and locality piqued the interest of Fabiany Herrera, the Negaunee assistant curator of fossil plants at the Field Museum in Chicago, and his student, Palma-Castro.

    “We went to the fossil collection at the Universidad Nacional de Colombia in Bogotá and started looking at the plants, and as soon as we photographed them, we thought, ‘this is weird,’” says Herrera, who has been collecting Early Cretaceous plants from northwestern South America, an area of the world with little paleobotanical work.

    At first glance, the fossils, about 2 inches in diameter, looked like rounded nodules containing the preserved leaves of the plant Sphenophyllum. But Herrera and Palma-Castro noticed key features that weren’t quite right.

    “We spent days searching through wooden cabinets for fossil plants. When we finally found this fossil, deciphering the shape and margin of the leaf proved challenging,” says Palma-Castro.

    “When you look at it in detail, the lines seen on the fossils don’t look like the veins of a plant— I was positive that it was most likely bone,” says Herrera. So he reached out to an old colleague of his, Edwin-Alberto Cadena.

    “They sent me the photos, and I said, “This definitely looks like a carapace’— the bony upper shell of a turtle,” says Cadena, a paleontologist who focuses on turtles and other vertebrates at the Universidad del Rosario in Bogotá. When he saw the scale of the photos, Cadena recalls, “I said, ‘Well, this is remarkable, because this is not only a turtle, but it’s also a hatchling specimen, it’s very, very small.”

    Cadena and his student, Diego Cómbita-Romero of the Universidad Nacional de Colombia, further examined the specimens, comparing them with the shells of both fossil and modern turtles. “When we saw the specimen for the first time I was astonished, because the fossil was missing the typical marks on the outside of a turtle’s shell,” says Cómbita-Romero. It was a little bit concave, like a bowl. At that moment we realized that the visible part of the fossil was the other side of the carapace, we were looking at the part of the shell that is inside the turtle.”

    Details in the turtle’s bones helped the researchers estimate how old it was at death. “Turtle growth rates and sizes vary,” says Cómbita-Romero, so the team looked at features like the thickness of its carapace and the spots where its ribs were knitting together into solid bone. “This is a feature uncommon in hatchlings but observed in juveniles. All this information suggests that the turtle likely died with a slightly developed carapace, between 0 to 1 years old, in a post-hatchling stage,” he says.

    “This is actually really rare to find hatchlings of fossil turtles in general,” says Cadena. “When the turtles are very young, the bones in their shells are very thin, so they can be easily destroyed.”

    The researchers say that the rarity of fossilized baby turtles makes their discovery an important one. “These turtles were likely relatives of other Cretaceous species that were up to fifteen feet long, but we don’t know much about how they actually grew to such giant sizes,” says Cadena.

    The researchers don’t fault Padre Huertas for his mistake— the preserved shells really do resemble many fossil plants. But the features that Huertas thought were leaves and stems are actually the modified rib bones and vertebrae that make up a turtle’s shell. Cómbita-Romero and Palma-Castro nicknamed the specimens as “Turtwig,” after a Pokémon that’s half-turtle, half-plant.

    “In the Pokémon universe, you encounter the concept of combining two or more elements, such as animals, machines, plants, etc. So, when you have a fossil initially classified as a plant that turns out to be a baby turtle, a few Pokémon immediately come to mind. In this case, Turtwig, a baby turtle with a leaf attached to its head,” says Palma-Castro.” In paleontology, your imagination and capacity to be amazed are always put to the test. Discoveries like these are truly special because they not only expand our knowledge about the past but also open a window to the diverse possibilities of what we can uncover.”

    The scientists also note the importance of these fossils in the larger scheme of Colombian paleontology. “We resolved a small paleobotanical mystery, but more importantly, this study shows the need to re-study historical collections in Colombia. The Early Cretaceous is a critical time in land plant evolution, particularly for flowering plants and gymnosperms. Our future job is to discover the forests that grew in this part of the world,” says Herrera.

    This project was supported by the National Geographic Society, grant (EC-96755R-22) Discovering Early Cretaceous Floras from Northern South America & the Negaunee Integrative Research Center, Field Museum.

     

    Field Museum

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  • Lessons Learned From ADLM’s COVID Immunity Study Could Improve Research on Future Pandemics

    Lessons Learned From ADLM’s COVID Immunity Study Could Improve Research on Future Pandemics

    Newswise — WASHINGTON – A special report published today in the Association for Diagnostics & Laboratory Medicine’s (ADLM’s, formerly AACC’s) The Journal of Applied Laboratory Medicine describes the design, operations, and methodology of the COVID Immunity Study, a large-scale scientific study by ADLM that took place in September 2021. By detailing the design of this novel study, the special report aims to facilitate similar studies by other scientific societies. These could fill in gaps in infectious disease research and potentially improve the global response to future pandemics.   

    View the full report here: https://academic.oup.com/jalm/advance-article/doi/10.1093/jalm/jfad089/7416439

    The COVID Immunity Study is the first scientific study performed by a professional association that combines an online health survey, on-site blood collection, off-site testing and analysis, provision of SARS-CoV-2 testing results to participants, and sample banking to address questions of SARS-CoV-2 immunity. Large-scale epidemiological studies such as this are crucial for understanding how viruses evolve and for making informed public health decisions. Because these types of studies demand tremendous resources, they are typically conducted by government agencies or as collaborative efforts by academic research groups. As the COVID Immunity Study shows, though, scientific societies also have the resources and expertise to perform large-scale epidemiological studies. These organizations are also in a position to investigate potentially important lines of inquiry that traditionally funded research can’t look into. While several papers that were either recently published or in preparation focus on the results of the COVID Immunity Study, this special report discusses the methodology of the study and unique challenges it encountered with the goal of providing a model for other scientific societies to follow.

    The COVID Immunity Study was mainly conducted at the 2021 AACC Annual Scientific Meeting in Atlanta. Blood was drawn on-site from 698 participants, who provided consent and completed general health and COVID-19 questionnaires beforehand. A portion of each sample was sent to Quest Diagnostics for T-cell function analysis, while serum and plasma were obtained from the remaining samples, which were stored at Centers for Disease Control and Prevention (CDC) facilities in Atlanta and made available to medical and research communities. Partnerships between ADLM staff and subject-matter experts such as clinical laboratory scientists and immunologists, as well as state and local health departments, were crucial to the success of the study.

    The study group encountered several logistical and practical challenges during the execution of the COVID Immunity Study, including staffing shortages due to the pandemic, the lack of prior on-site facilities for a scientific study, unavailable and back-ordered supplies, and the large number of participants required to donate blood. Though the COVID Immunity Study was successfully planned and executed in 6 months, the paper’s authors recommend a 12-month or longer period for such a study, especially if conducted in pandemic conditions.

    “ADLM believes that the unique makeup of scientific societies positions them well to ask and answer pressing questions in their fields that might otherwise not fall into a clear area of interest by traditional research funding sources,” the report authors said. “We hope that this paper will serve as a reference — and set a precedent — for member-based organizations to contribute to future such scientific studies.”

    About the Association for Diagnostics & Laboratory Medicine (ADLM)

    Dedicated to achieving better health through laboratory medicine, ADLM (formerly AACC) brings together more than 70,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, ADLM has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.myadlm.org.

    The Journal of Applied Laboratory Medicine (academic.oup.com/jalm) is published online by ADLM. This international, peer-reviewed publication showcases applied research on clinically relevant laboratory topics as well as commentary on the practice of clinical chemistry and laboratory medicine.

     

     

     

     

     

    Association for Diagnostic and Laboratory Medicine (ADLM (formerly AACC))

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  • New Case Western Reserve University study finds diabetes drug may reduce risk for colorectal cancer

    New Case Western Reserve University study finds diabetes drug may reduce risk for colorectal cancer

    Newswise — CLEVELAND—A groundbreaking study by researchers at Case Western Reserve University suggests a class of medications used to treat type 2 diabetes may also reduce the risk of colorectal cancer (CRC).

    The findings, published today (Dec. 7) in the journal JAMA Oncology, support the need for clinical trials to determine whether these medications could prevent one of the deadliest types of cancers. Eventually, the medications may also show promise in warding off other types of cancer associated with obesity and diabetes.

    “Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular anti-diabetic drugs, such as Metformin or insulin, at preventing the development of CRC,” said Nathan Berger, the Hanna-Payne Professor of Experimental Medicine at the Case Western Reserve School of Medicine and the study’s co-lead researcher.

    Glucagon-like peptide-1 receptor agonists, or GLP-1 RAs, are medications to treat type 2 diabetes. Usually given by injection, they can lower blood-sugar levels, improve insulin sensitivity and help manage weight. They’ve also been shown to reduce the rates of major cardiovascular ailments.

    Importantly the protective effect of GLP-1 RAs are noted in patients with or without overweight/obesity.

    “To our knowledge,” said co-lead researcher Rong Xu, a professor at the School of Medicine, “this is the first indication this popular weight-loss and anti-diabetic class of drugs reduces incidence of CRC, relative to other anti-diabetic agents.”

    Berger and Xu are members of the Case Comprehensive Cancer Center.

    National health problem

    Being overweight or obese or having diabetes are risk factors for increasing incidence of CRC and for making its prognosis worse.

    The National Institutes of Health (NIH) defines being overweight and obese as an increase in size and amount of fat cells in the body above certain levels. These conditions are common nationally and are caused by several factors—among them diet, lack of sleep or physical activity, genetics and family history.

    Healthcare providers use body mass index to measure body fat based on height and weight. Nearly 75% of adults ages 20 or older in the United States are either overweight or obese, and nearly 20% of children and teens ages 2 to 19 have obesity, according to the NIH.

    Obesity is a chronic health condition that raises the risk for heart disease—the leading cause of death in the United States—and is linked to many other health problems, including type 2 diabetes and cancer.

    The American Cancer Society estimates CRC is the third-leading type of cancer in both sexes, with 153,000 new cases per year. It is also the second-leading cause of cancer mortality with 52,550 deaths per year.

    The study

    Since GLP-1 RAs have been shown to be effective anti-diabetic and weight-loss agents, the researchers hypothesized they might reduce incidence of CRC.

    Using a national database of more than 100 million electronic health records, the researchers conducted a population-based study of more than 1.2 million patients. These individuals had been treated with anti-diabetic agents from 2005-19; the CWRU team examined the effects of GLP-1 RAs on their incidence of CRC, as compared to those prescribed other anti-diabetic drugs.

    Population-based research means matching as many people as possible with the same characteristics—sex, race, age, socio-economic determinants of health and other medical conditions—to accurately compare the drug’s effects.

    Among 22,572 patients with diabetes treated with insulin, there were 167 cases of CRC. Another 22,572 matched patients treated with GLP-1 RAs saw 94 cases of CRC. Those treated with GLP-1 RAs had a 44% reduction in incidence of CRC.

    In a similar comparison of 18,518 patients with diabetes treated with Metformin, compared to 18,518 patients with diabetes treated with GLP-1 RAs, had a 25% reduction in CRC.

    “The research is critically important for reducing incidence of CRC in patients with diabetes, with or without overweight and obesity,” Berger said.

     

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    (Initial data for this manuscript was developed last summer by Lindsey Wang and William Wang, Orange High School students whose work was sponsored by the Case Comprehensive Cancer Center and National Cancer Institute-funded Scientific Enrichment Opportunity/Youth Engaged in Science Program. Lindsey Wang is now a first-year undergraduate at Case Western Reserve in the pre-professional scholars program, planning to enroll at the Case Western Reserve School of Medicine.)

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    Case Western Reserve University is one of the country’s leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 6,200 undergraduate and 6,100 graduate students comprise our student body. Visit case.edu to see how Case Western Reserve thinks beyond the possible.

     

    Case Western Reserve University

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  • Acne sufferers encounter social and professional stigma, study reveals.

    Acne sufferers encounter social and professional stigma, study reveals.

    • Brigham researchers found that individuals with darker skin tones and more severe acne were likely to face greater stigma 

    • Researchers note the importance of treating acne as a medical problem and ensuring access to treatment 

     
    Newswise — A new study highlights how stigmatizing attitudes about individuals with acne may influence social and professional perceptions. Led by investigators from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, the study found that individuals with acne face stigmatizing attitudes from the general public in professional and social scenarios. The researchers also found that more severe acne and darker skin tones were associated with a greater degree of stigma. These results, published in JAMA Dermatology, highlight the need to identify ways to reduce stigmatizing attitudes and increase access to care in order to improve the experience of individuals with acne. 
     

    “Our findings show that stigmatizing attitudes about acne can impair quality of life, potentially by affecting personal relationships and employment opportunities,” said corresponding author John Barbieri, MD, MBA, of the Department of Dermatology. “Acne is often wrongly perceived as merely a cosmetic issue. It’s important that people with this medical problem get access to treatment, just like any other condition.” 

    Most teenagers and many adults experience acne at some point in their lifetimes. While previous studies have examined how acne impacts the psychological well-being of individuals, not much is known about public perception and attitudes towards them. 

    ​​​For this study, Barbieri and his team obtained stock portraits of four adults, including males and females of either light or dark skin tone. The researchers digitally altered these pictures to create two additional versions of each with mild and severe acne, resulting in a total pool of 12 portraits. They then performed a cross-sectional internet survey of 1357 participants, who were randomly shown one of the 12 images and asked a set of questions regarding stigmatizing attitudes about the pictured individual. The answer scores for images with acne were compared with the corresponding original image without acne as baseline.  

    The team found that participants were less likely to want to be friends, have close contact, or post a photograph on social media with individuals with severe acne, compared to those without acne. Participants reported a greater desire to socially distance themselves from individuals with acne, particularly if the pictured individual had a darker skin tone. 

    The authors also observed that respondents were more likely to agree with stereotypes about individuals with severe acne, tending to perceive them as unhygienic, unattractive, unintelligent and untrustworthy. This stereotype endorsement was also higher in individuals with darker skin. 

    Participants with past or current acne had less stigmatizing attitudes and only 26.4% believed that acne was a cosmetic issue. Most agreed that acne does not affect only teenagers. 

    The study has some limitations. It was not possible to control for comparisons between images with differences in sex or skin tone (for example, female with light skin tone with severe acne versus male with dark skin tone and no acne). Therefore, the results regarding differences by skin tone could be due to other factors and should be interpreted cautiously. The survey population was mostly white and highly educated, limiting the generalizability of the results.  

    Further studies are required to better understand if the relationship between darker skin tones and stigmatizing attitudes result from underlying structural racism or other factors.  

    “Many insurers poorly cover acne and rosacea treatments, claiming that it’s cosmetic,” Barbieri said. “Our study highlights the need for that narrative to change and for ​​identifying approaches to reduce stigmatizing attitudes in the community.” 

    Authorship: Additional Mass General Brigham co-authors include Ali Shields (BWH), Sophia Ly (BWH), Priya Manjaly (BWH) and Arash Mostaghimi (BWH). 

    Other authors include Michael R. Nock. 

    Disclosures: Dr Mostaghimi reported personal fees from hims & hers, AbbVie, Sun Pharmaceutical Industries, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN Pharmaceuticals, Boehringer Ingelheim, Fig.1 Beauty, Acom Healthcare, and Olaplex outside the submitted work. Dr Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr Barbieri is Associate Editor and Evidence-Based Practice Editor of JAMA Dermatology but was not involved in any of the decisions regarding review of the manuscript or its acceptance. 
     
    Funding: This study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. 

    Paper cited: Shields, Ali et al. “Evaluation of Stigma Toward Individuals With Acne” JAMA Dermatology DOI:10.1001/jamadermatol.2023.4487 

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    Brigham and Women’s Hospital

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  • Chemists craft colorful organic molecules.

    Chemists craft colorful organic molecules.

    Newswise — CAMBRIDGE, MA — Chains of fused carbon-containing rings have unique optoelectronic properties that make them useful as semiconductors. These chains, known as acenes, can also be tuned to emit different colors of light, which makes them good candidates for use in organic light-emitting diodes.

    The color of light emitted by an acene is determined by its length, but as the molecules become longer, they also become less stable, which has hindered their widespread use in light-emitting applications.

    MIT chemists have now come up with a way to make these molecules more stable, allowing them to synthesize acenes of varying lengths. Using their new approach, they were able to build molecules that emit red, orange, yellow, green, or blue light, which could make acenes easier to deploy in a variety of applications.

    “This class of molecules, despite their utility, have challenges in terms of their reactivity profile,” says Robert Gilliard, the Novartis Associate Professor of Chemistry at MIT and the senior author of the new study. “What we tried to address in this study first was the stability problem, and second, we wanted to make compounds where you could have a tunable range of light emission.”

    MIT research scientist Chun-Lin Deng is the lead author of the paper, which appears today in Nature Chemistry.

    Colorful molecules

    Acenes consist of benzene molecules — rings made of carbon and hydrogen — fused together in a linear fashion. Because they are rich in sharable electrons and can efficiently transport an electric charge, they have been used as semiconductors and field-effect transistors (transistors that use an electric field to control the flow of current in a semiconductor).

    Recent work has shown that acenes in which some of the carbon atoms are replaced, or “doped,” with boron and nitrogen have even more useful electronic properties. However, like traditional acenes, these molecules are unstable when exposed to air or light. Often, acenes have to be synthesized within a sealed container called a glovebox to protect them from air exposure, which can lead them to break down. The longer the acenes are, the more susceptible they are to unwanted reactions initiated by oxygen, water, or light.

    To try to make acenes more stable, Gilliard decided to use a ligand that his lab has previously worked with, known as carbodicarbenes. In a study published last year, they used this ligand to stabilize borafluorenium ions, organic compounds that can emit different colors of light in response to temperature changes.

    For this study, Gilliard and his co-authors developed a new synthesis that allowed them to add carbodicarbenes to acenes that are also doped with boron and nitrogen. With the addition of the new ligand, the acenes became positively charged, which improved their stability and also gave them unique electronic properties.

    Using this approach, the researchers created acenes that produce different colors, depending on their length and the types of chemical groups attached to the carbodicarbene. Until now, most of the boron, nitrogen-doped acenes that had been synthesized could emit only blue light.

    “Red emission is very important for wide-ranging applications, including biological applications like imaging,” Gilliard says. “A lot of human tissue emits blue light, so it’s difficult to use blue-fluorescent probes for imaging, which is one of the many reasons why people are looking for red emitters.”

     

    Better stability

    Another important feature of these acenes is that they remain stable in both air and water. Boron-containing charged molecules with a low coordination number (meaning the central boron atom has few neighbors) are often highly unstable in water, so the acenes’ stability in water is notable and could make it feasible to use them for imaging and other medical applications.

    “One of the reasons why we’re excited about the class of compounds that we’re reporting in this paper is that they can be suspended in water. That opens up a wide range of possibilities,” Gilliard says.

    The researchers now plan to try incorporating different types of carbodicarbenes to see if they can create additional acenes with even better stability and quantum efficiency (a measure of how much light is emitted from the material).

    “We think it will be possible to make a lot of different derivatives that we haven’t even synthesized yet,” Gilliard says. “There are a lot of optoelectronic properties that can be dialed in that we have yet to explore, and we’re excited about that as well.”

    Gilliard also plans to work with Marc Baldo, an MIT professor of electrical engineering, to try incorporating the new acenes into a type of solar cell known as a single-fission-based solar cell. This type of solar cell can produce two electrons from one photon, making the cell much more efficient.

    These types of compounds could also be developed for use as light-emitting diodes for television and computer screens, Gilliard says. Organic light-emitting diodes are lighter and more flexible than traditional LEDs, produce brighter images, and consume less power.

    “We’re still in the very early stages of developing the specific applications, whether it’s organic semiconductors, light-emitting devices, or singlet-fission-based solar cells, but due to their stability, the device fabrication should be much smoother than typical for these kinds of compounds,” Gilliard says.

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    The research was funded by the Arnold and Mabel Beckman Foundation and the National Science Foundation Major Research Instrumentation Program.

    Massachusetts Institute of Technology (MIT)

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  • Investigation of degradation mechanism for all-solid-state batteries takes another step toward commercialization

    Investigation of degradation mechanism for all-solid-state batteries takes another step toward commercialization

    Newswise — Often referred to as the ‘dream batteries’, all-solid-state batteries are the next generation of batteries that many battery manufacturers are competing to bring to market. Unlike lithium-ion batteries, which use a liquid electrolyte, all components, including the electrolyte, anode, and cathode, are solid, reducing the risk of explosion, and are in high demand in markets ranging from automobiles to energy storage systems (ESS). However, devices that maintain the high pressure (tens of MPa) required for stable operation of all-solid-state batteries have problems that reduce the battery performance, such as energy density and capacity, and must be solved for commercialization.

    Dr. Hun-Gi Jung and his team at the Energy Storage Research Center at the Korea Institute of Science and Technology (KIST) have newly identified degradation factors that cause rapid capacity degradation and shortened lifespan when operating all-solid-state batteries at pressures similar to those of lithium-ion batteries. Unlike previous studies, the researchers confirmed for the first time that degradation can occur inside the cathode as well as outside, showing that all-solid-state batteries can be operated reliably even in low-pressure environments in the future.

    In all-solid-state batteries, the cathode and anode have a volume change during repeated charging and discharging, resulting in interfacial degradation such as side reaction and contact loss between active materials and solid electrolytes, which increase the interfacial resistance and worsen cell performance. To solve this problem, external devices are used to maintain high pressure, but this has the disadvantage of reducing energy density as the weight and volume of the battery increase. Recently, research is being conducted on the inside of the all-solid-state cell to maintain the performance of the cell even in low-pressure environments.

    The research team analyzed the cause of performance degradation by repeatedly operating a coin-type all-solid-state battery with a sulfide-based solid electrolyte in a low-pressure environment of 0.3 MPa, similar to that of a coin-type Li-ion battery. After 50 charge-discharge cycles, the NCM cathode layer had expanded in volume by about two times, and cross-sectional image analysis confirmed that severe cracks had developed between the cathode active material and the solid electrolyte. This newly revealed that in addition to the interfacial contact loss, cracking of the cathode material and irreversible cathode phase transformation are the causes of degradation in low-pressure operation.

    Furthermore, after replacing the lithium in the cathode with an isotope (6Li) to distinguish it from the lithium present in the solid electrolyte, the team used time-of-flight secondary ion mass spectrometry (TOF-SIMS) to identify for the first time the mechanism by which lithium consumption in the cathode contributes to the overall cell capacity reduction. During repeated charge-discharge cycles, sulfur, a decomposed product of the solid electrolyte, infused the cracks in the cathode material to form lithium sulfide, a byproduct that is non-conductive. This depleted the active lithium ions and promoted cathode phase transformation, reducing the capacity of the all-solid-state batteries.

    By clearly identifying the cause of the degradation of all-solid-state batteries in low-pressure operating environments, these analytical methods provide a clue to solving the problem of poor cycling characteristics compared to conventional lithium-ion batteries. If this problem is solved, it is expected that the economics of all-solid-state batteries can be secured by eliminating external auxiliary devices, which have been a major cause of rising production costs.

    “For the commercialization of all-solid-state batteries, it is essential to develop new cathode and anode materials that can be operated in a pressure-free or low-pressure environment rather than the current pressurized environment,” said Dr. Hun-Gi Jung of KIST. “When applying low-pressure-working all-solid-state batteries to medium and large-scale applications such as electric vehicles, it will be expected to make full use of established lithium-ion battery manufacturing facilities.”

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    KIST was established in 1966 as the first government-funded research institute in Korea. KIST now strives to solve national and social challenges and secure growth engines through leading and innovative research. For more information, please visit KIST’s website at https://eng.kist.re.kr/

    This research was supported by the Korea Institute of Science and Technology institutional program funded by the Ministry of Science and ICT of Korea (Minister Lee Jong-ho), by the Development Program of Core Industrial Technology funded by the Ministry of Trade, Industry and Energy (Minister Bang, Moon Kyu), and by the Technology Development Program to Solve Climate Changes funded by the National Research Foundation (President Lee, Kwang-bok). The research results were published as a front cover article in the latest issue of Advanced Energy Materials (IF 27.8, top 2.5% in JCR), an international journal in the field of energy materials.

    National Research Council of Science and Technology

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