Tag: X-Ray

  • Antibiotics ineffective for cough treatment in lower respiratory tract infections

    Antibiotics ineffective for cough treatment in lower respiratory tract infections

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    Use of antibiotics provided no measurable impact on the severity or duration of coughs even if a bacterial infection was present, finds a large, prospective study of people who sought treatment in U.S. primary or urgent care settings for lower-respiratory tract infections.

    The study by researchers at Georgetown University Medical Center and colleagues appeared April 15, 2024, in the Journal of General Internal Medicine.

    Upper respiratory tract infections usually include the common cold, sore throat, sinus infections and ear infections and have well established ways to determine if antibiotics should be given. Lower respiratory tract infections tend to have the potential to be more dangerous, since about 3% to 5% of these patients have pneumonia. But not everyone has easy access at an initial visit to an X-ray, which may be the reason clinicians still give antibiotics without any other evidence of a bacterial infection. Plus, patients have come to expect antibiotics for a cough, even if it doesn’t help. Basic symptom-relieving medications plus time brings a resolution to most people’s infections.”


    Dan Merenstein, MD, professor of family medicine at Georgetown University School of Medicine

    The antibiotics prescribed in this study for lower tract infections were all appropriate, commonly used antibiotics to treat bacterial infections. But the researchers’ analysis showed that of the 29% of people given an antibiotic during their initial medical visit, there was no effect on the duration or overall severity of cough compared to those who didn’t receive an antibiotic.

    “Physicians know, but probably overestimate, the percentage of lower tract infections that are bacterial; they also likely overestimate their ability to distinguish viral from bacterial infections,” says Mark H. Ebell, MD, MS, a study author and professor in the College of Public Health at the University of Georgia. “In our analysis, 29% of people were prescribed an antibiotic while only 7% were given an antiviral. But most patients do not need antivirals as there exist only two respiratory viruses where we have medications to treat them: influenza and SARS-COV-2. There are none for all of the other viruses.”

    To determine if there was an actual bacterial or viral infection present, beyond the self-reported symptoms of a cough, the investigators confirmed the presence of pathogens with advanced lab tests to look for microbiologic results classified as only bacteria, only viruses, both virus and bacteria, or no organism detected. Very importantly, for those with a confirmed bacterial infection, the length of time until illness resolution was the same for those receiving an antibiotic versus those not receiving one – about 17 days.

    Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash along with about a 4% chance of serious adverse effects including anaphylaxis, which is a severe, life-threatening allergic reaction; Stevens-Johnson syndrome, a rare, serious disorder of the skin and mucous membranes; and Clostridioides difficile-associated diarrhea. Another significant concern of the overuse of antibiotics is resistance. The World Health Organization released a statement on April 4, 2024, stating: “Uncontrolled antimicrobial resistance [due to the overuse of antibiotics] is expected to lower life expectancy and lead to unprecedented health expenditure and economic losses.”

    “We know that cough can be an indicator of a serious problem. It is the most common illness-related reason for an ambulatory care visit, accounting for nearly 3 million outpatient visits and more than 4 million emergency department visits annually,” says Merenstein. “Serious cough symptoms and how to treat them properly needs to be studied more, perhaps in a randomized clinical trial as this study was observational and there haven’t been any randomized trials looking at this issue since about 2012.”

    In addition to Merenstein and Ebell, the other co-author is Bruce Barrett MD, PhD at the University of Wisconsin, Madison,

    This work was supported by an AHRQ grant R01HS025584.

    Source:

    Journal reference:

    Merenstein, D.J., et al. (2024) Antibiotics Not Associated with Shorter Duration or Reduced Severity of Acute Lower Respiratory Tract Infection. Journal of General Internal Medicine. doi.org/10.1007/s11606-024-08758-y.

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  • Bruker showcases high-performance solutions at Analytica 2024 for research and analysis in applied, industrial and biopharma laboratories

    Bruker showcases high-performance solutions at Analytica 2024 for research and analysis in applied, industrial and biopharma laboratories

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    Bruker Corporation is showcasing some of its latest innovations at Analytica 2024:

    EVOQ DART-TQ+. Image Credit: Bruker

    EVOQ DART-TQ+. Image Credit: Bruker

    Applied and industrial markets solutions

    The new EVOQ DART-TQ⁺ mass spectrometer simplifies high-throughput testing with its integrated DART ion source, eliminating the need for upfront chromatography. With a 20-second analysis time per sample, it provides a fast solution for routine food and environmental testing. By bypassing traditional chromatography methods, it enhances productivity and uptime while lowering the cost of ownership. It offers a quick switch to LC-MS for conventional water and food testing. https://www.bruker.com/en/products-and-solutions/mass-spectrometry/triple-quads/evoq-dart-tq-plus.html

    The ecTOF is a novel GC-HRMS that records EI and CI spectral data in one GC run. It combines parent ion data (via soft CI) and NIST-searchable fragment ion spectra (70 eV EI) to reduce false positives and identify unknown compounds in complex samples. The ecTOF also improves analysis speed, instrument uptime, and expedites data post-processing. This elevates the analysis of complex samples in targeted, suspect, and non-targeted GC-HRMS.

    The new BEAM FT-NIR uses Bruker’s RockSolid interferometer for accuracy and stability. Designed for quality control, it is IP65-protected and suitable for solid and semi-solid materials, and can be fitted on pipelines, hoppers, or conveyor belts. The BEAM improves manufacturing process control and minimizes variations. Its single-point FT-NIR process analyzer allows quick analysis in process environments, ensuring long-term stability for minimizing waste and rework. https://www.bruker.com/en/products-and-solutions/infrared-and-raman/ft-ir-nir-for-process-control/beam.html

    The D6 PHASER makes advanced XRD methods accessible for cleantech markets.

    We are heavily invested in the development of electrocatalytic coatings that will form the beating heart of the next generation of water electrolyzers in the green energy transition. Bruker’s D6 PHASER provides us with the extraordinary power, flexibility, and accuracy needed to push our coating development forward. We will have access to advanced X-ray techniques crucial for material science that were previously not available in a compact benchtop system. https://www.bruker.com/en/products-and-solutions/diffractometers-and-x-ray-microscopes/x-ray-diffractometers/d6-phaser.html

    Dr. Jan Vos, Researcher at Magneto Special Anodes

     

    The Fourier 80 X-optimized 1H/7Li system facilitates battery research by examining lithium-based materials essential for better batteries.

    As we transition from fundamental materials development towards implementing new materials in prototypes and pilot lines, benchtop systems with lithium NMR can be a great tool.” The collaboration between Bruker and Dragonfly Energy accelerates pioneering battery technology research, showcasing the versatility of the Fourier 80 benchtop FT-NMR platform. https://www.bruker.com/en/products-and-solutions/mr/nmr/fourier80.html

    Dr. Vick Singh, Director of Research & Development for Dragonfly Energy

    Bruker’s Avance Chemical Profiling Module for NMR, provides data processing, interpretation, and reporting, improving quality and efficiency in diverse QC processes. It simplifies NMR analysis, offering a tool to identify and quantify various compounds in a mixture with a single measurement. Its user-friendly interface and driven workflow make it a practical NMR solution for routine analysis in manufacturing settings. https://www.bruker.com/en/products-and-solutions/mr/nmr-epr-td-nmr-industrial-solutions/fourier-80-chemlab-mixture-profiler.html

    Bruker presents the MGA series, a laser-based gas analyzer from MIRO Analytical AG to simultaneously measure various pollutants and greenhouse gases with high precision. It can detect gases such as CO, NO, NO2, NH3, O3, SO2, CO2, CH4, and N2O. Its compact size and rapid measurements are suitable for mobile monitoring. Its Quantum Cascade Lasers enable precise gas detection, contributing to our understanding of air pollution. https://www.bruker.com/en/products-and-solutions/infrared-and-raman/gas-analysis/mga-series.html

    Gracing Incidence X-ray Fluorescence (GIXRF) for the S4 T-STAR® excites a flat sample by changing the beam angle. The resulting signal profiles vary based on sample type, mass, and thickness. GIXRF offers non-destructive material analysis with a compact benchtop TXRF spectrometer, used for quick qualitative assessments of structures such as nanoparticles, monolayers, or layered systems. This enables the monitoring of diffusion in multilayer systems and the study of metal dopant depth profiles in substrates. https://www.bruker.com/en/products-and-solutions/elemental-analyzers/txrf-spectrometers/s4-t-star.html

    Biopharma solutions

    The Fourier 80 benchtop FT-NMR is now equipped with the synTQ NMR PAT adapter, enhancing Process Analytical Technologies by structural insights, accurate quantification, and efficient process QC. The adapter synchronizes with soft sensors and techniques like IR and Raman, integrating data streams for thorough process understanding. The Fourier PAT is useful in distributed API manufacturing, collecting reaction data for AI-driven process optimization. This setup advances API production, supports distributed and on-demand manufacturing, and improves safety, environmental impact, and cost-effectiveness. https://www.bruker.com/en/products-and-solutions/process-analytical-technology/fourier-pat.html

    The new Triceratops SPR #64 enhances real-time, label-free molecular interaction characterization. Its innovative microfluidics allows 64 sensor spots, pushing the boundaries of SPR capabilities. It offers industry-leading throughput without sacrificing data quality. Its user-friendly touchscreen and automation features, including robot integration make it convenient for SPR biopharma research. https://www.bruker.com/en/products-and-solutions/surface-plasmon-resonance/spr-64.html

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  • LAG-3 protein structure may be the key to unlocking new cancer treatments

    LAG-3 protein structure may be the key to unlocking new cancer treatments

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    A molecular “snapshot” of a protein can be critical to understanding its function. Scientists at Stanford and NYU have published and investigated a new structure of the protein LAG-3 which could enable the development of new cancer treatments.

    Some cancerous tumors hijack proteins that act as “brakes” on our immune system and use them to form a sort of shield against immune recognition. Immunotherapy treatments have been created that turn off these “brakes” and allow our body to attack foreign-looking cancer cells. To further advance such treatments, researchers at Stanford University and New York University have published a new structure of one of these brake proteins, LAG-3. Their work contains key details of the molecule’s structure, as well as information about how the LAG-3 protein functions.

    Although over a dozen immunotherapies targeting LAG-3 are in development, and one is already FDA approved, knowledge of LAG-3’s structure and function has been incomplete.

    “Given the amount of time and resources being put into developing therapeutics that target LAG-3, it is astounding that we don’t yet have a full understanding of how this protein functions,” said Jennifer Cochran, the Addie and Al Macovski Professor in the School of Engineering and professor of bioengineering, and co-senior author on the study detailing LAG-3, published in Proceedings of the National Academy of Sciences.

    Getting a clear image of a protein might not seem like a big deal, but when it comes to proteins, form often begets function. If you know what a protein looks like at the atomic scale, you can begin to understand how it interacts with other molecules and design experiments to further deduce how it works. Studies like these are crucial to developing drugs that can optimally block their target’s function.

    A key structure

    Proteins like LAG-3, called immune checkpoints, exist to stop our immune system from attacking things they shouldn’t. In theory, our immune system should naturally recognize tumor cells as foreign. But a checkpoint protein shield can give cancer cover.

    Current immunotherapies aren’t chemical drugs, they’re lab-manufactured antibodies that attach to certain parts of these checkpoints, and essentially turn them off. Once the checkpoint is turned off, our immune system can recognize and target the cancer again.

    There are already approved antibody treatments that target two checkpoint proteins: CTLA-4 and PD-1. Both turn off our immune systems but in different ways. Because CTLA-4 and PD-1 were the first two checkpoint proteins found, they are quite well studied, and different approaches to inhibiting them for cancer therapy earned scientists the 2018 Nobel Prize in physiology or medicine.

    LAG-3 seems to work in an entirely different way. Scientists hope that those differences might make it a better or complementary target to treat certain types of cancer, said Jack Silberstein, the Stanford immunology PhD student who co-led the work.

    Because of that, Silberstein said, “there was all this excitement in the field. Groups rushed to make antibodies against LAG-3, without knowing entirely how LAG-3 or those antibodies functioned.”

    Silberstein and colleagues, including those in Stanford’s ChEM-H Macromolecular Structure Knowledge Center and the SLAC National Accelerator Laboratory, began working on LAG-3’s structure in 2019. A structure of LAG-3 was published by a different group in 2022 providing an initial glimpse of the protein, but it lacked crucial detail around sugar molecules that are key to LAG-3’s function, and detailed information on how the LAG-3 structure related to its biological activity.

    A painstaking process

    When Silberstein first started this project, “I quickly realized why there was no published structure. It’s a tremendously difficult protein to work with.”

    And the technique Silberstein used to get the structure, called X-ray crystallography, is extremely finicky. First, Silberstein had to grow a crystal made entirely out of LAG-3 protein. Then, in collaboration with Irimpan Mathews at the SLAC National Accelerator Laboratory, they fired X-ray beams at the crystal to create a 3D image of the molecule.

    LAG-3 is a spindly, flexible protein, so it’s difficult to get the molecules to stack in an orderly way. Silberstein estimates he made more than 10,000 crystals, of which 3,000 were fired with X-rays before the team finally solved the structure.

    It was a very intense, grind-it-out-for-three-years, bang-your-head-against-the-wall kind of thing.”


    Jack Silberstein, Stanford immunology PhD student

    But it paid off. The team’s structure confirmed that LAG-3 exists as a dimer, with two LAG-3 molecules coming together to form the functional checkpoint protein. The sugar residue that was elusive in previous structural efforts is a key element in the LAG-3 dimer interface and helps promote a different orientation of the LAG-3 protein.

    With the structure described, colleagues at New York University, including MD, PhD student Jasper Du and pathology Assistant Professor Jun Wang co-led critical experiments further elucidating LAG-3’s function. Other NYU colleagues, including Kun-Wei Chan and Xiang-Peng Kong, helped conduct electron microscopy studies to detail disruption of dimer formation by LAG-3 antibodies.

    Additional work by the team uncovered, for the first time, that an antibody that has been used for close to 20 years to demonstrate therapeutic efficacy in animal tumor models blocks the activity of LAG-3 by binding to the interface between two LAG-3 molecules, disrupting LAG-3 from forming its functional dimer. Intriguingly, LAG-3 antibodies in clinical development bind to other areas of the protein, away from this dimer interface.

    There will never be just one “cure,” because cancers are all different and involve a number of diverse biochemical pathways. Silberstein and Cochran envision a future where a tapestry of surgical, chemical, and immunological treatment approaches are employed, driven by basic science discoveries and medical innovations. Additional treatments targeting LAG-3 may very well be a part of that picture.

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  • New AI model accurately identifies tumors and diseases in medical images

    New AI model accurately identifies tumors and diseases in medical images

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    Medical diagnostics expert, doctor’s assistant, and cartographer are all fair titles for an artificial intelligence model developed by researchers at the Beckman Institute for Advanced Science and Technology.

    Their new model accurately identifies tumors and diseases in medical images and is programmed to explain each diagnosis with a visual map. The tool’s unique transparency allows doctors to easily follow its line of reasoning, double-check for accuracy, and explain the results to patients.

    The idea is to help catch cancer and disease in its earliest stages -; like an X on a map -; and understand how the decision was made. Our model will help streamline that process and make it easier on doctors and patients alike.”


    Sourya Sengupta, study’s lead author and graduate research assistant at the Beckman Institute

    This research appeared in IEEE Transactions on Medical Imaging.

    Cats and dogs and onions and ogres

    First conceptualized in the 1950s, artificial intelligence -; the concept that computers can learn to adapt, analyze, and problem-solve like humans do -; has reached household recognition, due in part to ChatGPT and its extended family of easy-to-use tools.

    Machine learning, or ML, is one of many methods researchers use to create artificially intelligent systems. ML is to AI what driver’s education is to a 15-year-old: a controlled, supervised environment to practice decision-making, calibrating to new environments, and rerouting after a mistake or wrong turn.

    Deep learning -; machine learning’s wiser and worldlier relative -; can digest larger quantities of information to make more nuanced decisions. Deep learning models derive their decisive power from the closest computer simulations we have to the human brain: deep neural networks.

    These networks -; just like humans, onions, and ogres -; have layers, which makes them tricky to navigate. The more thickly layered, or nonlinear, a network’s intellectual thicket, the better it performs complex, human-like tasks.

    Consider a neural network trained to differentiate between pictures of cats and pictures of dogs. The model learns by reviewing images in each category and filing away their distinguishing features (like size, color, and anatomy) for future reference. Eventually, the model learns to watch out for whiskers and cry Doberman at the first sign of a floppy tongue.

    But deep neural networks are not infallible -; much like overzealous toddlers, said Sengupta, who studies biomedical imaging in the University of Illinois Urbana-Champaign Department of Electrical and Computer Engineering.

    “They get it right sometimes, maybe even most of the time, but it might not always be for the right reasons,” he said. “I’m sure everyone knows a child who saw a brown, four-legged dog once and then thought that every brown, four-legged animal was a dog.”

    Sengupta’s gripe? If you ask a toddler how they decided, they will probably tell you.

    “But you can’t ask a deep neural network how it arrived at an answer,” he said.

    The black box problem

    Sleek, skilled, and speedy as they may be, deep neural networks struggle to master the seminal skill drilled into high school calculus students: showing their work. This is referred to as the black box problem of artificial intelligence, and it has baffled scientists for years.

    On the surface, coaxing a confession from the reluctant network that mistook a Pomeranian for a cat does not seem unbelievably crucial. But the gravity of the black box sharpens as the images in question become more life-altering. For example: X-ray images from a mammogram that may indicate early signs of breast cancer.

    The process of decoding medical images looks different in different regions of the world.

    “In many developing countries, there is a scarcity of doctors and a long line of patients. AI can be helpful in these scenarios,” Sengupta said.

    When time and talents are in high demand, automated medical image screening can be deployed as an assistive tool -; in no way replacing the skill and expertise of doctors, Sengupta said. Instead, an AI model can pre-scan medical images and flag those containing something unusual -; like a tumor or early sign of disease, called a biomarker -; for a doctor’s review. This method saves time and can even improve the performance of the person tasked with reading the scan.

    These models work well, but their bedside manner leaves much to be desired when, for example, a patient asks why an AI system flagged an image as containing (or not containing) a tumor.

    Historically, researchers have answered questions like this with a slew of tools designed to decipher the black box from the outside in. Unfortunately, the researchers using them are often faced with a similar plight as the unfortunate eavesdropper, leaning against a locked door with an empty glass to their ear.

    “It would be so much easier to simply open the door, walk inside the room, and listen to the conversation firsthand,” Sengupta said.

    To further complicate the matter, many variations of these interpretation tools exist. This means that any given black box may be interpreted in “plausible but different” ways, Sengupta said.

    “And now the question is: which interpretation do you believe?” he said. “There is a chance that your choice will be influenced by your subjective bias, and therein lies the main problem with traditional methods.”

    Sengupta’s solution? An entirely new type of AI model that interprets itself every time -; that explains each decision instead of blandly reporting the binary of “tumor versus non-tumor,” Sengupta said.

    No water glass needed, in other words, because the door has disappeared.

    Mapping the model

    A yogi learning a new posture must practice it repeatedly. An AI model trained to tell cats from dogs studying countless images of both quadrupeds.

    An AI model functioning as doctor’s assistant is raised on a diet of thousands of medical images, some with abnormalities and some without. When faced with something never-before-seen, it runs a quick analysis and spits out a number between 0 and 1. If the number is less than .5, the image is not assumed to contain a tumor; a numeral greater than .5 warrants a closer look.

    Sengupta’s new AI model mimics this setup with a twist: the model produces a value plus a visual map explaining its decision.

    The map -; referred to by the researchers as an equivalency map, or E-map for short -; is essentially a transformed version of the original X-ray, mammogram, or other medical image medium. Like a paint-by-numbers canvas, each region of the E-map is assigned a number. The greater the value, the more medically interesting the region is for predicting the presence of an anomaly. The model sums up the values to arrive at its final figure, which then informs the diagnosis.

    “For example, if the total sum is 1, and you have three values represented on the map -; .5, .3, and .2 -; a doctor can see exactly which areas on the map contributed more to that conclusion and investigate those more fully,” Sengupta said.

    This way, doctors can double-check how well the deep neural network is working -; like a teacher checking the work on a student’s math problem -; and respond to patients’ questions about the process.

    “The result is a more transparent, trustable system between doctor and patient,” Sengupta said.

    X marks the spot

    The researchers trained their model on three different disease diagnosis tasks including more than 20,000 total images.

    First, the model reviewed simulated mammograms and learned to flag early signs of tumors. Second, it analyzed optical coherence tomography images of the retina, where it practiced identifying a buildup called Drusen that may be an early sign of macular degeneration. Third, the model studied chest X-rays and learned to detect cardiomegaly, a heart enlargement condition that can lead to disease.

    Once the mapmaking model had been trained, the researchers compared its performance to existing black-box AI systems -; the ones without a self-interpretation setting. The new model performed comparably to its counterparts in all three categories, with accuracy rates of 77.8% for mammograms, 99.1% for retinal OCT images, and 83% for chest x-rays compared to the existing 77.8%, 99.1%, and 83.33.%

    These high accuracy rates are a product of the deep neural network, the non-linear layers of which mimic the nuance of human neurons.

    To create such a complicated system, the researchers peeled the proverbial onion and drew inspiration from linear neural networks, which are simpler and easier to interpret.

    “The question was: How can we leverage the concepts behind linear models to make non-linear deep neural networks also interpretable like this?” said principal investigator Mark Anastasio, a Beckman Institute researcher and the Donald Biggar Willet Professor and Head of the Illinois Department of Bioengineering. “This work is a classic example of how fundamental ideas can lead to some novel solutions for state-of-the-art AI models.”

    The researchers hope that future models will be able to detect and diagnose anomalies all over the body and even differentiate between them.

    “I am excited about our tool’s direct benefit to society, not only in terms of improving disease diagnoses, but also improving trust and transparency between doctors and patients,” Anastasio said.

    Source:

    Journal reference:

    Sengupta, S., et al. (2024) A Test Statistic Estimation-based Approach for Establishing Self-interpretable CNN-based Binary Classifiers. IEEE Transactions on Medical Imaging. doi.org/10.1109/TMI.2023.3348699.

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  • Early detection may help Kentucky tamp down its lung cancer crisis

    Early detection may help Kentucky tamp down its lung cancer crisis

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    Anthony Stumbo’s heart sank after the doctor shared his mother’s chest X-ray.

    “I remember that drive home, bringing her back home, and we basically cried,” said the internal medicine physician, who had started practicing in eastern Kentucky near his childhood home shortly before his mother began feeling ill. “Nobody wants to get told they’ve got inoperable lung cancer. I cried because I knew what this meant for her.”

    Now Stumbo, whose mother died the following year, in 1997, is among a group of Kentucky clinicians and researchers determined to rewrite the script for other families by promoting training and boosting awareness about early detection in the state with the highest lung cancer death rate. For the past decade, Kentucky researchers have promoted lung cancer screening, first recommended by the U.S. Preventive Services Task Force in 2013. These days the Bluegrass State screens more residents who are at high risk of developing lung cancer than any state except Massachusetts — 10.6% of eligible residents in 2022, more than double the national rate of 4.5% — according to the most recent American Lung Association analysis.

    The effort has been driven by a research initiative called the Kentucky LEADS (Lung Cancer Education, Awareness, Detection, and Survivorship) Collaborative, which in 2014 launched to improve screening and prevention, to identify more tumors earlier, when survival odds are far better. The group has worked with clinicians and hospital administrators statewide to boost screening rates both in urban areas and regions far removed from academic medical centers, such as rural Appalachia. But, a decade into the program, the researchers face an ongoing challenge as they encourage more people to get tested, namely the fear and stigma that swirl around smoking and lung cancer.

    Lung cancer kills more Americans than any other malignancy, and the death rates are worst in a swath of states including Kentucky and its neighbors Tennessee and West Virginia, and stretching south to Mississippi and Louisiana, according to data from the Centers for Disease Control and Prevention.

    It’s a bit early to see the impact on lung cancer deaths because people may still live for years with a malignancy, LEADS researchers said. Plus, treatment improvements and other factors may also help reduce death rates along with increased screening. Still, data already shows that more cancers in Kentucky are being detected before they become advanced, and thus more difficult to treat, they said. Of total lung cancer cases statewide, the percentage of advanced cases — defined as cancers that had spread to the lymph nodes or beyond — hovered near 81% between 2000 and 2014, according to Kentucky Cancer Registry data. By 2020, that number had declined to 72%, according to the most recent data available.

    “We are changing the story of families. And there is hope where there has not been hope before,” said Jennifer Knight, a LEADS principal investigator.

    Older adults in their 60s and 70s can hold a particularly bleak view of their mortality odds, given what their loved ones experienced before screening became available, said Ashley Shemwell, a nurse navigator for the lung cancer screening program at Owensboro Health, a nonprofit health system that serves Kentucky and Indiana.

    “A lot of them will say, ‘It doesn’t matter if I get lung cancer or not because it’s going to kill me. So I don’t want to know,’” said Shemwell. “With that generation, they saw a lot of lung cancers and a lot of deaths. And it was terrible deaths because they were stage 4 lung cancers.” But she reminds them that lung cancer is much more treatable if caught before it spreads.

    The collaborative works with several partners, including the University of Kentucky, the University of Louisville, and GO2 for Lung Cancer, and has received grant funding from the Bristol Myers Squibb Foundation. Leaders have provided training and other support to 10 hospital-based screening programs, including a stipend to pay for resources such as educational materials or a nurse navigator, Knight said. In 2022, state lawmakers established a statewide lung cancer screening program based in part on the group’s work.

    Jacob Sands, a lung cancer physician at Boston’s Dana-Farber Cancer Institute, credits the LEADS collaborative with encouraging patients to return for annual screening and follow-up testing for any suspicious nodules. “What the Kentucky LEADS program is doing is fantastic, and that is how you really move the needle in implementing lung screening on a larger scale,” said Sands, who isn’t affiliated with the Kentucky program and serves as a volunteer spokesperson for the American Lung Association.

    In 2014, Kentucky expanded Medicaid, increasing the number of lower-income people who qualified for lung cancer screening and any related treatment. Adults 50 to 80 years old are advised to get a CT scan every year if they have accumulated at least 20 pack years and still smoke or have quit within the past 15 years, according to the latest task force recommendation, which widened the pool of eligible adults. (To calculate pack years, multiply the packs of cigarettes smoked daily by years of smoking.) The lung association offers an online quiz, called “Saved By The Scan,” to figure out likely eligibility for insurance coverage.

    Half of U.S. patients aren’t diagnosed until their cancer has spread beyond the lungs and lymph nodes to elsewhere in the body. By then, the five-year survival rate is 8.2%.

    But regular screening boosts those odds. When a CT scan detects lung cancer early, patients have an 81% chance of living at least 20 years, according to data published in November in the journal Radiology.

    Some adults, like Lisa Ayers, didn’t realize lung cancer screening was an option. Her family doctor recommended a CT scan last year after she reported breathing difficulties. Ayers, who lives in Ohio near the Kentucky border, got screened at UK King’s Daughters, a hospital in far eastern Kentucky. The scan didn’t take much time, and she didn’t have to undress, the 57-year-old said. “It took me longer to park,” she quipped.

    She was diagnosed with a lung carcinoid tumor, a type of neuroendocrine cancer that can grow in various parts of the body. Her cancer was considered too risky for surgery, Ayers said. A biopsy showed the cancer was slow-growing, and her doctors said they would monitor it closely.

    Ayers, a lifelong smoker, recalled her doctor said that her type of cancer isn’t typically linked to smoking. But she quit anyway, feeling like she’d been given a second chance to avoid developing a smoking-related cancer. “It was a big wake-up call for me.”

    Adults with a smoking history often report being treated poorly by medical professionals, said Jamie Studts, a health psychologist and a LEADS principal investigator, who has been involved with the research from the start. The goal is to avoid stigmatizing people and instead to build rapport, meeting them where they are that day, he said.

    “If someone tells us that they’re not ready to quit smoking but they want to have lung cancer screening, awesome; we’d love to help,” Studts said. “You know what? You actually develop a relationship with an individual by accepting, ‘No.’”

    Nationally, screening rates vary widely. Massachusetts reaches 11.9% of eligible residents, while California ranks last, screening just 0.7%, according to the lung association analysis.

    That data likely doesn’t capture all California screenings, as it may not include CT scans done through large managed care organizations, said Raquel Arias, a Los Angeles-based associate director of state partnerships at the American Cancer Society. She cited other 2022 data for California, looking at lung cancer screening for eligible Medicare fee-for-service patients, which found a screening rate of 1%-2% in that population.

    But, Arias said, the state’s effort is “nowhere near what it needs to be.”

    The low smoking rate in California, along with its image as a healthy state, “seems to have come with the unintended consequence of further stigmatizing people who smoke,” said Arias, citing one of the findings from a 2022 report looking at lung cancer screening barriers. For instance, eligible patients may be reluctant to share prior smoking habits with their health provider, she said.

    Meanwhile, Kentucky screening efforts progress, scan by scan.

    At Appalachian Regional Healthcare, 3,071 patients were screened in 2023, compared with 372 in 2017. “We’re just scratching the surface of the potential lives that we can have an effect on,” said Stumbo, a lung cancer screening champion at the health system, which includes 14 hospitals, most located in eastern Kentucky.

    The doctor hasn’t shed his own grief about what his family missed after his mother died at age 51, long before annual screening was recommended. “Knowing that my children were born, and never knowing their grandmother,” he said, “just how sad is that?”




    Kaiser Health NewsThis article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

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  • Researchers identify a new approach to controlling bacterial infections

    Researchers identify a new approach to controlling bacterial infections

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    Researchers at the Icahn School of Medicine at Mount Sinai have identified a new approach to controlling bacterial infections. The findings were described in the February 6 online issue of Nature Structural & Molecular Biology [DOI # 10.1038/s41594-024-01220-x].

    The team found a way to turn on a vital bacterial defense mechanism to fight and manage bacterial infections. The defense system, called cyclic oligonucleotide-based antiphage signaling system (CBASS), is a natural mechanism used by certain bacteria to protect themselves from viral attacks. Bacteria self-destruct as a means to prevent the spread of virus to other bacterial cells in the population.

    We wanted to see how the bacterial self-killing CBASS system is activated and whether it can be leveraged to limit bacterial infections. This is a fresh approach to tackling bacterial infections, a significant concern in hospitals and other settings. It’s essential to find new tools for fighting antibiotic resistance. In the war against superbugs, we need to constantly innovate and expand our toolkit to stay ahead of evolving drug resistance.”


    Aneel Aggarwal, PhD, Co-Senior Author, Professor of Pharmacological Sciences at Icahn Mount Sinai

    According to a 2019 report by the Centers for Disease Control and Prevention, more than 2.8 million antimicrobial-resistant infections occur in the United States each year, with over 35,000 people dying as a result.

    As part of the experiments, the researchers studied how “Cap5,” or CBASS-associated protein 5, is activated for DNA degradation and how it could be used to control bacterial infections through a combination of structural analysis and various biophysical, biochemical, and cellular assays. Cap5 is a key protein that becomes activated by cyclic nucleotides (small signaling molecules) to destroy the bacterial cell’s own DNA.

    “In our study, we started by identifying which of the many cyclic nucleotides could activate the effector Cap5 of the CBASS system,” says co-senior author Olga Rechkoblit, PhD, Assistant Professor of Pharmacological Sciences at Icahn Mount Sinai. “Once we figured that out, we looked closely at the structure of Cap5 when it’s bound to these small signaling molecules. Then, with expert help from Daniela Sciaky, PhD, a researcher at Icahn Mount Sinai, we showed that by adding these special molecules to the bacteria’s environment, these molecules could potentially be used to eliminate the bacteria.”

    The researchers found that determining the structure of Cap5 with cyclic nucleotides posed a technical challenge, requiring expert help from Dale F. Kreitler, PhD, AMX Beamline Scientist at Brookhaven National Laboratory. It was achieved by using micro-focused synchrotron X-ray radiation at the same facility. Micro-focused synchrotron X-ray radiation is a type of X-ray radiation that is not only produced using a specific type of particle accelerator (synchrotron) but is also carefully concentrated or focused on a tiny area for more detailed imaging or analysis.

    Next, the researchers will explore how their discoveries apply to other types of bacteria and assess whether their method can be used to manage infections caused by various harmful bacteria.

    The paper is titled “Activation of CBASS-Cap5 endonuclease immune effector by cyclic nucleotides.”

    Other authors who contributed to this work are Angeliki Buku, PhD, and Jithesh Kottur, PhD, both with Icahn Mount Sinai.

    The work was funded by National Institutes of Health grants R35-GM131780, P41GM111244, KP1605010, P30 GM124165, S10OD021527, GM103310, and by the Simons Foundation grant SF349247.

    Source:

    Journal reference:

    Rechkoblit, O., et al. (2024). Activation of CBASS Cap5 endonuclease immune effector by cyclic nucleotides. Nature Structural & Molecular Biology. doi.org/10.1038/s41594-024-01220-x.

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  • XRCC1 shows potential as a prognostic and immunological pan-cancer biomarker

    XRCC1 shows potential as a prognostic and immunological pan-cancer biomarker

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    A new research paper was published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 16, Issue 1, entitled, “XRCC1: a potential prognostic and immunological biomarker in LGG based on systematic pan-cancer analysis.”

    X-ray repair cross-complementation group 1 (XRCC1) is a pivotal contributor to base excision repair, and its dysregulation has been implicated in the oncogenicity of various human malignancies. However, a comprehensive pan-cancer analysis investigating the prognostic value, immunological functions, and epigenetic associations of XRCC1 remains lacking.

    In this new study, researchers Guobing Wang, Yunyue Li, Rui Pan, Xisheng Yin, Congchao Jia, Yuchen She, Luling Huang, Guanhu Yang, Hao Chi, and Gang Tian from Southwest Medical University, The Affiliated Hospital of Southwest Medical University, Yibin Hospital of T.C.M, Medical School of Nanchang University, Fourth Military Medical University, and Ohio University aimed to address this knowledge gap by conducting a systematic investigation employing bioinformatics techniques across 33 cancer types.

    “Our analysis encompassed XRCC1 expression levels, prognostic and diagnostic implications, epigenetic profiles, immune and molecular subtypes, Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), immune checkpoints, and immune infiltration, leveraging data from TCGA, GTEx, CELL, Human Protein Atlas, Ualcan, and cBioPortal databases.”

    Notably, XRCC1 displayed both positive and negative correlations with prognosis across different tumors. Epigenetic analysis revealed associations between XRCC1 expression and DNA methylation patterns in 10 cancer types, as well as enhanced phosphorylation. Furthermore, XRCC1 expression demonstrated associations with TMB and MSI in the majority of tumors. 

    Interestingly, XRCC1 gene expression exhibited a negative correlation with immune cell infiltration levels, except for a positive correlation with M1 and M2 macrophages and monocytes in most cancers. Additionally, the researchers observed significant correlations between XRCC1 and immune checkpoint gene expression levels. Lastly, their findings implicated XRCC1 in DNA replication and repair processes, shedding light on the precise mechanisms underlying its oncogenic effects. 

    “Overall, our study highlights the potential of XRCC1 as a prognostic and immunological pan-cancer biomarker, thereby offering a novel target for tumor immunotherapy.”

    Source:

    Journal reference:

    Wang, G., et al. (2024). XRCC1: a potential prognostic and immunological biomarker in LGG based on systematic pan-cancer analysis. Aging. doi.org/10.18632/aging.205426.

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