Background: Geographical and economic barriers limit access to health care services in rural regions of Colombia. In San Vicente del Caguán, the lack of infrastructure and rehabilitation professionals forces patients to travel long distances. Asynchronous telerehabilitation using video broadcasting is a viable strategy to address these challenges. Objective: This study aims to design and validate a telerehabilitation model using asynchronous audiovisual content broadcasting for rural patients, evaluating functionality, usability, and clinical effectiveness. Methods: A 4-stage case study developed and validated the model in San Vicente del Caguán: (1) analysis of telemedicine experiences and video-based therapy; (2) solution design including telecommunications infrastructure (radio links and Wi-Fi), mobile app (HSRehabiAPP), and web platform (HSRehabiWEB); (3) fieldwork with 7 patients receiving physical, occupational, or speech therapy, evaluating functionality (11 criteria), usability (8 criteria), and content quality (5 criteria); and (4) results analysis. The infrastructure connected San Rafael Hospital with remote centers in Los Pozos and Tres Esquinas. Participants (aged 7-68 years) from urban and rural areas had conditions including stroke, shoulder injuries, knee pathologies, hypertension, and attention-deficit hyperactivity disorder. Results: All 7 patients achieved 100% compliance across functional, usability, and audiovisual content criteria. Functional evaluation covered login, navigation, therapy access, session viewing, exercise execution, pain assessment, therapist communication, and satisfaction surveys. Usability assessment evaluated initial access, content location, navigation comfort, instructional guidance, session organization, video playback, instruction clarity, and interface intuitiveness. Content criteria included exercise clarity, step-by-step instructions, visual quality, audio quality, and correct posture demonstration. Patients reported high satisfaction, noting reduced travel costs and time, family convenience, and effective outcomes. Offline functionality proved essential in areas with limited internet connectivity. Conclusions: The asynchronous audiovisual telerehabilitation model is an effective solution for improving access to rehabilitation services in rural areas. It successfully addressed geographical barriers and infrastructure limitations while maintaining clinical effectiveness across therapies. Implementation requires adequate technological infrastructure, user-friendly platforms with offline capabilities, and quality therapeutic content. Future work demands inclusive health policies, professional training, and research with larger sample sizes to assess long-term sustainability in diverse rural contexts.
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Clinicians’ Decisions to Screen for Intimate Partner Violence Use and Experience and Observed Impacts: Qualitative Study
Background: Recent research has found that concurrent intimate partner violence (IPV) experience (ie, victimization) and use (ie, perpetration) may be more common than experiencing or using IPV in isolation. Therefore, screening for IPV experience and use concurrently is needed to provide resources and connect patients to care. Objective: In this work, we explore how clinicians made decisions to use a screening protocol for IPV use and experience and their perceptions of how concurrent screening impacted patients, clinicians, and the health care system. Methods: We conducted qualitative interviews with 19 clinicians (18 women and 1 man) who participated in a 90-day pilot screening implementation initiative, in which they were asked to integrate screening for IPV use and experience concurrently into their daily practice. Most clinicians (17/19, 89.5%) had prior IPV-related training. Interviews focused on clinicians’ experiences implementing the screening tool and were analyzed using thematic analysis. Results: We identified four themes: (1) new screening implementation is challenging, (2) screening for IPV use and experience concurrently can be uncomfortable, (3) pivoting strategies can make screening easier, and (4) screening for IPV use and experience concurrently is impactful. Findings highlighted complexities of implementing new screening protocols, as clinicians spoke about the importance of screening for IPV use and experience concurrently, while pointing out barriers to integrating the screening protocol into their daily clinical routines. Clinicians made adaptations to the screening protocol and the screener itself to assist with adherence to screening efforts. Conclusions: Findings demonstrate the need for and importance of screening concurrently for IPV use and experience, while bringing awareness to difficulties with implementing any new screener. Findings underscore the importance of addressing barriers to increasing screening efforts for IPV use and experience concurrently through increased allotment for screening efforts. The results also highlight opportunities for pivoting strategies and ongoing training and education around managing concurrent IPV use and experience. Future research should explore how decreasing barriers to screening efforts and adaptations to screening practices impact decisions to screen, while also exploring clients’ perspectives on being screened for IPV use and experiences concurrently.
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STAT+: Trump administration seeks to overhaul federal grantmaking process, alarming researchers
The Trump administration has released a sweeping proposal to overhaul the bedrock regulation for all federal grants, and in doing so is seeking to codify tighter political control of federally funded research.
The changes, laid out in a 400-plus-page document published this week, would deemphasize the role of peer review in determining what work to fund, limit the ability for scientists to use federal funds to publish their research or travel to conferences, and offer political appointees more latitude to terminate grants at will.
The suite of proposed changes aligns in many respects with policies the administration has attempted to implement through executive orders and one-off announcements, sometimes at individual agencies; if formalized, the revised regulation would be in effect across the government and put the regulatory authority of the White House behind it.
Teclistamab Outperforms Standard Therapy in Relapsed Multiple Myeloma
The treatment landscape for multiple myeloma has undergone a dramatic transformation over the past decade, driven by a growing arsenal of immunotherapies that harness the patient’s own immune system to fight cancer. Now, results from a large international Phase III trial suggest that one of the newest entrants to this class, the bispecific antibody teclistamab, may be poised to move even earlier in the treatment paradigm.
The findings, published in the New England Journal of Medicine and presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that teclistamab significantly improved progression-free survival and depth of response compared with standard therapies in patients with relapsed multiple myeloma.
The study represents one of the strongest demonstrations to date that chemotherapy-free immunotherapy can outperform conventional approaches even after only a limited number of prior treatments.
Moving bispecific antibodies earlier in treatment
Teclistamab belongs to a rapidly expanding class of therapies known as bispecific antibodies. Unlike traditional monoclonal antibodies, bispecifics are engineered to bind two targets simultaneously. Teclistamab recognizes both BCMA, a protein expressed on multiple myeloma cells, and CD3 on T cells, effectively bringing immune cells into direct contact with tumor cells and triggering targeted cancer cell killing.
The therapy has already shown substantial activity in heavily pretreated patients with advanced disease. However, investigators wanted to determine whether moving the drug earlier in the disease course could provide even greater benefit.
“Now we have chemotherapy-free immunotherapy options for patients whose myeloma has relapsed for the first time,” said C. Ola Landgren, MD, chief of the Sylvester Myeloma Institute and senior author of the study. “We are seeing very deep responses and long clinical benefit from these therapies. This is part of a much bigger transformation happening in myeloma care.”
Landmark global trial
The Phase III MajesTEC-9 trial enrolled 593 patients across 24 countries. Participants had relapsed multiple myeloma after one to three prior lines of therapy, representing a patient population increasingly encountered in routine clinical practice.
Approximately three-quarters of patients had already become refractory to commonly used treatments, including immunomodulatory drugs such as lenalidomide and anti-CD38 therapies such as daratumumab. These patients typically face diminishing treatment options and shorter durations of disease control.
Patients were randomized to receive either teclistamab or standard treatment regimens.
The results demonstrated a clear advantage for the bispecific antibody.
After 18 months of follow-up, nearly 70% of patients treated with teclistamab remained free from disease progression, compared with only about 27% of patients receiving standard therapies.
The magnitude of benefit exceeded what many clinicians have come to expect in relapsed myeloma, where treatment resistance often emerges rapidly.
Deep remissions become increasingly common
Beyond delaying disease progression, teclistamab produced remarkably deep responses.
Nearly two-thirds of treated patients achieved complete remission, meaning no evidence of disease could be detected using conventional testing methods.
Another highlight was the frequency of minimal residual disease (MRD) negativity, an increasingly important endpoint in multiple myeloma research. MRD testing uses highly sensitive techniques capable of detecting tiny numbers of remaining cancer cells that standard assessments might miss.
Many patients receiving teclistamab achieved MRD-negative status, suggesting that the therapy may be capable of driving deep eradication of disease.
“To see that this drug is so efficacious and so safe across patients from all these locations worldwide is a very strong signal,” Landgren said. “To see that in patients who have been exposed and refractory to commonly used myeloma treatments is very important.”
The broader shift away from chemotherapy
The results reflect a larger evolution occurring throughout multiple myeloma treatment.
For decades, chemotherapy served as the backbone of therapy. Today, however, treatment increasingly revolves around immune-based approaches including monoclonal antibodies, CAR T-cell therapies, and bispecific antibodies.
Researchers are not only developing new immunotherapies but also moving them earlier into treatment algorithms, where the immune system may be more intact and capable of mounting stronger anti-tumor responses.
The success of teclistamab in earlier-relapse patients supports this strategy and raises the possibility that bispecific antibodies could eventually become standard components of frontline treatment.
Managing infection risk remains critical
Despite the encouraging efficacy results, teclistamab is not without challenges.
Because the therapy activates T cells and alters immune function, infection remains one of the most important safety considerations. The risk is particularly pronounced during the first several months of treatment, when immune suppression can occur as part of the therapeutic response.
To mitigate this risk, patients typically receive antiviral and antibiotic prophylaxis, undergo routine monitoring of immunoglobulin levels, and may receive supplemental immunoglobulin infusions when necessary.
Investigators reported that these risks were manageable with appropriate monitoring and supportive care, consistent with previous studies of bispecific antibodies.
Looking toward curative strategies
The success of teclistamab is part of a broader effort to transform multiple myeloma from a chronic relapsing disease into one that can potentially be controlled for extended periods, or perhaps one day cured.
Researchers are already investigating whether teclistamab and related bispecific antibodies can be incorporated into even earlier treatment settings, including newly diagnosed disease.
“For me, the goal is to develop curative strategies,” Landgren said. “We are working toward treatments that can either eliminate the disease entirely or control it for very long periods while minimizing the burden on patients and preserving quality of life.”
As bispecific antibodies continue to demonstrate increasingly durable responses, the field is moving closer to that goal. The MajesTEC-9 results suggest that immune-based therapies are no longer merely alternatives to conventional treatment, they may be emerging as the new standard for many patients with relapsed multiple myeloma.
The post Teclistamab Outperforms Standard Therapy in Relapsed Multiple Myeloma appeared first on Inside Precision Medicine.
AI Chatbots Do Not Consistently Deliver Accurate Health Responses
A study into the responses of AI chatbots to everyday medical questions found that nearly 76% of the responses were accurate, according to investigators at Penn State University. Their research, published as a preprint in arXiv, found that while the AI chatbots could deliver useful information, the error rates remain high enough that they shouldn’t replace physicians for either diagnosing or suggesting treatments.
“Our work focuses explicitly on healthcare scenarios that the average internet user might ask AI, which is a perspective that prior research into large language models (LLMs) and healthcare hasn’t covered,” said the study’s senior author Amulya Yadav, PhD, associate professor of informatics and intelligent systems at Penn State. “We wanted to understand that if people are using LLMs like ChatGPT as a symptom health checker, like historically we’ve used Google, how accurate is the LLM in answering those queries, and how harmful could those responses be?”
The study examined a shift in how people seek healthcare information online. According to the researchers, “over half of U.S. adults consult online resources for medical advice,” a trend that is particularly prominent in younger adults, with near one-quarter of people under 30 using AI for health-related guidance.
The research was designed to evaluate AI performance in real-world everyday health communication, rather than in controlled testing environments that rely on medical licensing exams or clinical case studies. The researchers wrote that earlier studies “fail to account for the unstructured and often ambiguous nature of general-purpose everyday health inquiries.”
To conduct the study, the Penn State team organized a weeklong “Diagnose-a-thon” competition involving 34 participants, including faculty, staff, undergraduate students and graduate students. Participants submitted 212 prompts describing real or imagined health concerns from both patient and physician perspectives. They were allowed to use one of four publicly accessible AI models: ChatGPT-4o, ChatGPT-3.5, Gemini-1.5 Pro or Llama3-8b.
“One of the strengths of our study is we’re essentially trying to replicate real-world usage of LLMs by telling participants to choose the LLM of their choice and use it as they would on a normal day,” said lead author Bonam Mingole, a doctoral candidate in information sciences and technology at Penn State. “This type of participatory research is so important for understanding how the public uses AI in their daily life.”
Nine board-certified physicians evaluated the AI-generated responses to the prompts using a six-point scale to measure validity, quality of information, understanding and reasoning, and potential harm. About 76% of responses were considered accurate overall and showed that ChatGPT-4o was the most accurate at 84.62%, while Llama3-8b had the lowest at 50%.
The results also showed significant differences across medical specialties. Obstetrics and gynecology and otolaryngology generated the strongest AI performance, with high validity scores and low harm scores. Internal medicine, neurology, and dermatology produced the weakest results, including lower validity and higher risk of harmful responses.
The responses also shined a light on a continuing problem in healthcare research that leads to disparities in care. “The lower quality LLM-generated responses for underrepresented patient populations and rare medical conditions raises concerns about the potential of LLMs to inadvertently exacerbate existing healthcare disparities,” the researchers wrote. They added that addressing these issues “requires more than technical mechanisms, it calls for a broader commitment to equity in the data collection, model development, and evaluation processes.”
How the prompts were written also influenced AI performance. Queries between 60 and 250 characters produced the most accurate responses, while very specific prompts also improved output quality. Interestingly, the physician reviewers perceived greater risk of harm in responses generated from prompts that attempted to be written from a medical professional’s perspective.
To test whether specialized medical training could improve the answer generated by AI, the investigators enhanced the LLMs using Retrieval-Augmented Generation, by training them with medical textbooks, clinical guidelines and peer-reviewed research that is typically included in medical school curriculums.
Performance of the LLMs trained in this way were mixed. The physician reviewers preferred the baseline versions of Gemini and Llama over their medically trained counterparts, while no meaningful preference emerged for the ChatGPT models.
The researchers will now look to expand their study by collecting larger and more balanced datasets of crowdsourced health prompts and looking for ways to discourage overreliance on AI-generated medical advice.
“Like it or not, people will continue to use AI for diagnosing their health problems,” said study co-author S. Shyam Sundar, PhD, a professor in the Center for Socially Responsible AI at Penn State. “By understanding their use patterns and testing the validity of AI performance, our project helps advance literacy on the best and worst uses of AI for medical advice.”
The post AI Chatbots Do Not Consistently Deliver Accurate Health Responses appeared first on Inside Precision Medicine.
AI-Powered Pan-Cancer Map Reveals Tertiary Lymphoid Structures
Researchers at The University of Texas MD Anderson Cancer Center have developed a spatial atlas of specialized immune structures known as tertiary lymphoid structures (TLSs), across multiple cancer types, revealing how key features vary across tumor types and influence patient outcomes. Led by Linghua Wang, MD, PhD, professor of genomic medicine, executive director and head of the Center for Cellular Language Intelligence, associate member of the James P. Allison Institute
, and focus area co-lead with the Institute for Data Science in Oncology at UT MD Anderson, the team developed scalable artificial intelligence (AI) frameworks to detect, profile and classify TLSs from spatial omics data and routine pathology slides.
Tumors can contain TLSs with very different levels of organization, cellular composition and spatial relationships within tumor cells and the researchers’ newly reported study showed that these differences carry important biological and clinical information. The team suggests that their first-of-its-kind atlas indicates that TLS maturation state, spatial location, and composition within tumors may provide clinically meaningful information about cancer prognosis and treatment response. They also created a composite scoring system to more effectively stratify patients by prognosis and treatment response across different cancer types and treatment contexts.
“Prior to this study, most of the focus on TLSs as biomarkers was simply on whether or not they were present and, in some cases, whether they were mature,” Wang said. “Here, we show that we can go much deeper. TLSs in tumor tissues are much more complex than that. Their maturation state, spatial location and composition within tumors can tell us critical information about the tumor immune microenvironment, treatment response and clinical outcomes.”
Wang is senior author of the team’s published paper in Science, Titled “Pan-cancer spatial atlas of tertiary lymphoid structures.” In their paper the team concluded, “Together, this work provides a comprehensive landscape of TLS heterogeneity across cancers and establishes spatially defined TLS features and artificial intelligence (AI)–driven TLS classification as scalable tools for precision immuno-oncology.”
The immune system’s response to a tumor is a highly coordinated effort taking place within the tumor microenvironment (TME), the authors explained. In some tumors, immune cells come together to form organized structures called tertiary lymphoid structures, or TLSs. These structures operate as local immune “hubs,” bringing together B cells, T cells, antigen-presenting cells and other supporting cells that help coordinate antitumor immune responses. “TLSs frequently develop within the tumor microenvironment (TME) and have been observed across a broad range of human solid tumors, where they contribute to lymphocyte activation, B cell immunity, and regulation of antitumor immune responses,” they noted.
Previous studies have shown that TLSs—particularly those that are more mature—are often associated with better patient outcomes and improved responses to immunotherapy across a variety of cancer types. “The presence of TLSs has been linked to favorable responses to immune checkpoint blockade (ICB) and prolonged survival across multiple cancer types, fueling interest in TLSs as predictive biomarkers, prognostic indicators, and potential therapeutic targets. However, the presence of TLSs alone does not tell the whole story,” the scientists noted. “While it is well acknowledged that TLSs are important in cancer, our understanding of their cellular and molecular heterogeneity has remained limited, especially in their natural spatial context across large cohorts of human tumor samples.”
“Although TLS presence has been associated with enhanced immune activity and improved outcomes in several settings, their maturation states, spatial locations relative to tumors, and context-dependent associations have not been systematically characterized at a pan-cancer scale, limiting a unified view of TLS biology and clinical utility,” they stated.
For their reported study the team developed scalable computational frameworks to precisely detect, comprehensively profile and classify TLSs from spatial omics data. Leveraging this framework, the team built a pan-cancer spatial atlas of TLSs across 340 samples from 12 cancer types. This atlas allowed them to examine the TLS landscape in tumor tissues, to define how TLSs vary in key features, and identify transcriptional programs associated with TLS maturation. “By integrating transcriptomic, spatial, histopathological, and clinical data, we systematically characterized TLS abundance, spatial distribution, size, maturation states, and transcriptomic programs in 340 ST samples across 12 cancer types and examined their interactions with tumor cells and the surrounding TME,” they wrote in summary.
The study found that TLSs vary substantially across tissues. As TLSs mature, they become more organized and undergo coordinated changes in immune, stromal, and vascular components. Further, their proximity to tumor cells is associated with spatial gradients of tumor signaling. These findings suggest that TLS maturation and spatial context are linked to distinct tumor signaling environments and may reflect important features of the tumor immune microenvironment.
To make these insights more scalable, the team developed an AI framework to rapidly identify and classify TLSs from hematoxylin and eosin (H&E) whole-slide images (WSIs), pathology images that are routinely used in daily clinical care. Training this AI model makes the process of analyzing TLSs more easily translatable to the clinic, while also making the process significantly faster and more scalable. The AI framework enabled the researchers to go one step further, evaluating 25,088 TLSs from more than 3,000 whole-slide images across 10 independent cohorts and developing a TLS “composition score” for a given patient’s tumor. “By developing a scalable AI-enabled framework to detect and classify TLSs directly from routine H&E WSIs, we have extended TLS analysis from limited spatial datasets to thousands of tumors,” the team noted.
This composition score captures not only the number of TLSs, but also their maturation states within a tumor. This method significantly outperformed conventional TLS measures in stratifying patients by prognosis and treatment response, suggesting that a more detailed view of TLS biology, accounting for maturation state, may provide more clinically meaningful information than TLS presence alone. “… we developed a data-driven, unsupervised TLS-based patient stratification framework that outperformed existing approaches in prognostic evaluation,” they commented.
The TLS composite scoring approach must be validated in prospective clinical trials. If successful, the framework could support broader integration of TLS profiling into routine pathology workflows, since it uses routine pathology images. “Together, this work establishes generalizable and clinically scalable frameworks for TLS profiling and highlights TLS state composition as a key dimension of tumor immune organization with translational relevance. It also provides a foundation for prospective evaluation of TLS-informed biomarkers in clinical settings,” they stated.
The findings raise important biological and therapeutic questions, the researchers suggest. One important observation from the study is that many TLSs in tumor tissues remain immature, and some are located away from tumor regions rather than within or adjacent to tumor cells. This suggests that future studies should investigate how to promote TLSs toward more mature and functional states, and how to enhance their spatial interaction with tumor cells and the broader tumor microenvironment.
These efforts may help identify therapeutic strategies to promote effective TLS formation and maturation and enhance TLS-associated anti-tumor immune responses. In their paper the team concluded, “Prospective studies should test whether TLS composition improves risk and response modelling beyond established clinicopathologic and molecular predictors, and whether TLS-informed stratification can guide clinical trial design or therapeutic modulation strategies.”
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Co-Designing a Text Messaging Intervention for Youth Transitioning From Child to Adult Mental Health Services: Participatory Design Jam Study
<strong>Background:</strong> The transition from child to adult mental health services is a vulnerable period marked by service disengagement, care gaps, and worsening mental health outcomes. Although planned, developmentally appropriate transition processes can improve functioning, youths report insufficient preparation, limited continuity of care, and unmet expectations for support. Existing transition supports remain underevaluated and require further adaptation for mental health contexts. Youth consistently report needing clearer information, concrete support, and sustained connection. Digital tools, particularly SMS text messaging, which is widely used, accessible, and acceptable to youth, offer a promising way to deliver timely transition supports. Yet most digital mental health tools are developed without meaningful youth involvement, highlighting the need for participatory approaches to ensure relevance, usability, and uptake. <strong>Objective:</strong> This study aimed to co-design and refine prototypes for a transition-focused SMS text messaging intervention by engaging youth with lived experience in a participatory co-design activity (design jam) to identify priority content, key functionality, and implementation enablers to support the transition from child to adult mental health services. <strong>Methods:</strong> We conducted a 3-hour mixed methods, participatory design jam to co-design transition-focused SMS text messaging prototypes, recruiting youth aged 16-26 years in Canada who had recently transitioned to, or were approaching transitioning to, adult mental health services. Data sources included workshop artifacts, observational field notes, and audio recordings from structured activities involving evidence review, brainstorming, rapid prototyping, brief team pitches, and evaluation. Rapid qualitative analysis, integrating open coding, content analysis of visual prototypes, and the rapid identification of themes from audio recordings, was used to identify priority content, key functionality, and implementation enablers. Findings were refined through a member-checking debrief with youth participants. <strong>Results:</strong> Seven youths aged 19-24 years participated in the design jam. Across two teams, participants generated 54 content ideas and 50 feature ideas. Two distinct prototypes were developed: one emphasizing long-term affirmation, self-advocacy, self-care, and profile-based customization, and the other prioritizing shorter-term informational support, navigation resources, and flexible message frequency. Youth across both groups highlighted the importance of interactive and visually engaging elements. Analysis revealed 3 thematic tensions shaping youth design preferences: balancing autonomy with ongoing support (roaming/reconnecting), balancing personalization with the need for simplicity (customization/convention), and balancing knowledge delivery with motivation for action (learning/living). Participants rated the design jam positively. <strong>Conclusions:</strong> Youth meaningfully contributed to co-designing an SMS text messaging intervention to support transition from child to adult mental health services, generating concrete content, functionality, and implementation priorities. Their prototypes highlighted the need to balance autonomy with support, personalization with simplicity, and information with motivational guidance. These findings demonstrate the value of participatory co-design in developing youth-centered digital transition supports and underscore the importance of evaluating such prototypes in real-world settings to determine feasibility and impact.
Antibiotic Design Strategy Overcomes Efflux-Mediated Resistance in Preclinical Study
Researchers headed by a team at King’s College London have developed a new way of designing antibiotics that could support the discovery of new treatments for drug-resistant infections.
Designed to overcome one of the ways bacteria escape antibiotic treatment, the Efflux Resistance Breaker (ERB) approach allows researcher to chemically redesign antibiotics so that they are less easily removed from the cells by bacterial efflux pumps. The technology could also help revive antibiotics that have lost effectiveness due to the evolution of efflux-mediated resistance.
Study lead Professor Khondaker Miraz Rahman, PhD, a professor of medicinal chemistry at King’s College London, said: “Antimicrobial resistance is rising, but the number of truly new antibiotics in development remains worryingly low. Our work shows that we can redesign antibiotics so they stay inside bacterial cells at higher concentrations and overcome resistance mechanisms that would normally make them ineffective. This approach could help us design better new antibiotics, but it could also help revive existing antibiotic classes that bacteria have learned to defeat.”
Rahman is senior author of the team’s published paper in Journal of Medicinal Chemistry, titled “Designing Antibiotics with Inherent Resistance to Efflux as a Strategy to Revive Discovery against Multidrug-Resistant Pathogens.”
Worldwide increase in antimicrobial resistance (AMR) is threatening new developments in antibiotics, the authors noted. “The development and approval of new antibiotics are currently being outpaced by the emergence of resistance to existing drugs, a trend that must be reversed to ensure the long-term effectiveness of antibiotics.”
Many bacteria use molecular pumps, known as efflux pumps, to push antibiotics out of the cell before the drugs can reach levels high enough to kill them. This reduces the amount of antibiotic inside the bacteria and allows resistant infections to survive. Previous strategies have tried to combine antibiotics with separate efflux pump inhibitors (EPIs), the team continued. “Efflux pump inhibitors (EPIs) have been pursued as adjunct therapies to safeguard approved antibiotics prone to efflux-based resistance.” However, no EPI has yet been approved. “As well as a lack of mechanistic insight and biochemical information regarding efflux pumps, we opine that this failure is rooted in a fundamental flaw in the EPI-antibiotic combination approach: that the antibiotics remain unmodified substrates and can be effluxed by different pumps despite the presence of EPIs,” the authors noted.
The study by Rahman and colleagues has now shown that antibiotics can be chemically redesigned so they are less easily removed by these pumps. Their approach builds resistance-breaking properties directly into the antibiotic molecule, meaning that the antibiotic is designed to protect itself from being pumped out, allowing it to remain inside the bacterial cell at higher concentrations, and so restoring its ability to kill bacteria even when resistance mechanisms are present.
Importantly, the work shows that the ERB approach could support a new way of developing antibiotics by building resistance-breaking properties directly into their design. In their reported study the team developed ERB-modified fluoroquinolones and demonstrated their effectiveness against multiple bacterial pathogens, and in mouse infection models. The study provides an important proof of concept for antibiotic discovery, showing that maintaining high intracellular antibiotic concentration can help overcome resistance, including in bacteria that already show reduced susceptibility to existing antibiotics. “This study demonstrates that ERB modification enhances intracellular accumulation, reduces efflux susceptibility, and preserves antibacterial potency, as supported by complementary mechanistic, biochemical, and in vivo evidence,” the scientists concluded.
Added J. Mark Sutton, PhD, at the UK Health Security Agency, a key collaborator on this project, “Efflux pumps are a major cause of antibiotic resistance because they reduce the concentration of drug inside the bacterial cell. This study shows that rational chemical design can be used to overcome that problem. By building efflux resistance directly into the antibiotic, we may be able to restore activity against bacteria that are no longer controlled by current drugs.”
The researchers believe the ERB platform could be used as a general strategy to design antibiotics with built-in resilience to efflux-mediated resistance. Their team describes the ERB technology as a framework for developing next-generation antibiotics and for revitalizing existing drugs. “Beyond revitalizing existing drugs, ERB technology provides a general framework for designing next-generation antibiotics with built-in resilience to efflux-mediated resistance at the earliest stages of discovery,” they stated.
The team says it will work towards commercializing the ERB technology and advancing antibiotics developed using this strategy towards clinical development, with the aim of translating this discovery into new treatment options for drug-resistant infections.
The post Antibiotic Design Strategy Overcomes Efflux-Mediated Resistance in Preclinical Study appeared first on GEN – Genetic Engineering and Biotechnology News.
Wearable- and Mobile App–Based Activity Pacing and Fatigue Management in Post–COVID-19 Condition: Exploratory Observational Study
<strong>Background:</strong> Post–COVID-19 fatigue affects millions worldwide; yet, evidence-based management strategies remain limited. Activity pacing, regulating activity to match available energy and minimize symptom exacerbation, may support symptom management, although optimal pacing approaches remain unclear. <strong>Objective:</strong> This study aimed to explore associations between activity pacing strategies delivered through a mobile app and daily fatigue levels in individuals with post–COVID-19 fatigue. <strong>Methods:</strong> In this exploratory observational study, 19 adults with post–COVID-19 fatigue used wearable devices (Fitbit Inspire 3) for objective activity monitoring and a mobile app (FatigueSense) to self-report daily symptoms (fatigue and energy levels) and optionally select activity pacing goals (light, balanced, or active) over a period of 3 months. We examined associations between pacing strategies and symptom outcomes by using mixed-effects linear models with random intercepts. Same-day outcomes (fatigue and energy reported on the day of goal selection) were analyzed controlling for age and sex. Next-day outcomes (fatigue and energy reported the day following goal selection) were analyzed controlling for age, sex, and prior-day symptoms. <strong>Results:</strong> Across 2182 observation days, participants self-selected pacing goals on 816 (37.4%) days, demonstrating symptom-responsive behavior with higher baseline fatigue on pacing days (mean score 1.74, SD 0.59 vs 1.58, SD 0.54 on nonpacing days on a 0-3 scale where 0=“none” and 3=“severe”; <i>P</i>=.004). On pacing days (584/816, 71.6% with complete data from 18 participants), active pacing was associated with reduced same-day fatigue (β=−0.34, 95% CI −0.49 to −0.19; <i>P</i><.001) and increased same-day energy (β=8.8, 95% CI 4.7-12.9; <i>P</i><.001) compared to light pacing. Balanced pacing also showed significant reductions in fatigue (β=−0.15; <i>P</i>=.008) and increases in energy (β=5.8; <i>P</i><.001) compared to light pacing. Next-day effects were attenuated and nonsignificant (fatigue: β=−0.05, <i>P</i>=.53; energy: β=1.1, <i>P</i>=.61). Individual heterogeneity was substantial, with an intraclass correlation coefficient of 0.32, indicating that 32% of the variance was attributable to between-person differences. Among participants trying multiple strategies, 58.3% (7/12) showed meaningful responses (≥0.3-point fatigue reduction) to structured pacing strategies. <strong>Conclusions:</strong> Structured activity pacing strategies (active and balanced) were associated with improved same-day symptom management in individuals with post–COVID-19 fatigue. However, substantial confounding by indication (self-selection of pacing based on symptom state) and individual heterogeneity limit causal interpretation. These exploratory findings warrant testing in randomized controlled trials to establish efficacy and identify responder characteristics. <strong>Trial Registration:</strong>
Illumina Announces MRD Kit Ahead of ASCO Meeting
Ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, kicking off this weekend, Illumina has announced a new molecular residual disease (MRD) product. The distributed kit enables solid tumor MRD and blood cancer genomic profiling and, the company says, will enable more labs to adopt MRD detection for clinical research.
It is the first in a new portfolio of WGS oncology research offerings, with additional solutions in development leveraging the latest advancements of the NovaSeq X. Illumina’s MRD research solution is available today for early access to select partners and will launch for global customers next year.
“In precision healthcare, early and accurate detection of molecular residual disease is critical to monitoring patients during and after cancer treatment,” said Todd Christian, senior vice president of Services, Arrays, and Genomic Access at Illumina. “Illumina’s MRD solution for clinical research leverages the advanced sensitivity of whole-genome sequencing, coupled with unparalleled analysis, to enable our customers to more easily deliver the most precise information to advance MRD research. We aim to make WGS in oncology more accessible and scalable to support the integration of precision solutions into the standard of care.”
The MRD solution supports fingerprinting through solid tumor samples, and MRD detection using blood samples, all compatible on NovaSeq Systems. The end-to-end research workflow can be completed in as fast as five days and is optimized for analytical sensitivity as low as 10 ppm, particularly important for early-stage and low-shedding tumors, including breast, ovarian, and renal.
Illumina’s DRAGEN MRD analysis connects each fingerprint to serial circulating tumor DNA (ctDNA). The new MRD solution has been optimized across thousands of samples to develop and demonstrate a ctDNA detection algorithm with 99.5% analytical specificity to distinguish true tumor signals from background noise.
Mayo Clinic evaluated the solution on a small sample cohort and found high concordance among previously characterized paired samples. The results were also highly correlated with clinical and imaging results over time. The team is planning to expand the cohort for additional research with Mayo Clinic and other academic partners.
“We are looking forward to participating in early access and evidence generation for a tumor-informed, non-bespoke whole-genome sequencing approach to MRD,” said Gang Zheng, MD, PhD and professor of Laboratory Medicine and Pathology at Mayo Clinic. “We have seen early pilot results across several solid tumor clinical samples that demonstrated the potential utility of highly sensitive solid tumor MRD detection, and we continue to pilot technologies that help us efficiently progress in our ability to analyze and translate complex genomic arrays.”
Built on recently announced NovaSeq X advancements, including 35B output and Q70 quality scores, a complementary research workflow that will deliver ultra-sensitive MRD detection in the single-digit ppm range leveraging duplex reads is currently in development.
Illumina’s new oncology portfolio builds upon the integrated ecosystem of workflows, data and community across genomic, multiomic, and clinical research applications—anchored on the NovaSeq X.
Illumina and Bristol Myers Squibb will jointly present a poster at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting on Sunday, May 31, from 9:00 a.m. to 12:00 p.m. (abstract ID 8591, poster board #381, Lung Cancer: Non–Small Cell Metastatic track).
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