MS drug beneficial in an underrepresented group
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Flash optimization of drug combinations for Acinetobacter baumannii with IDentif.AI-AMR
Antimicrobial resistance (AMR) is an emerging threat to global public health. Specifically, Acinetobacter baumannii (A. baumannii), one of the main pathogens driving the rise of nosocomial infections, is a Gram-negative bacillus that displays intrinsic resistance mechanisms and can also develop resistance by acquiring AMR genes from other bacteria. More importantly, it is resistant to nearly 90% of standard of care (SOC) antimicrobial treatments, resulting in unsatisfactory clinical outcomes and a high infection-associated mortality rate of over 30%. Currently, there is a growing challenge to sustainably develop novel antimicrobials in this ever-expanding arms race against AMR. Therefore, a sustainable workflow that properly manages healthcare resources to ultra-rapidly design optimal drug combinations for effective treatment is needed. In this study, the IDentif.AI-AMR platform was harnessed to pinpoint effective regimens against four A. baumannii clinical isolates from a pool of nine US FDA-approved drugs. Notably, IDentif.AI-pinpointed ampicillin-sulbactam/cefiderocol and cefiderocol/polymyxin B/rifampicin combinations were able to achieve 93.89 ± 5.95% and 92.23 ± 11.89% inhibition against the bacteria, respectively, and they may diversify the reservoir of treatment options for the indication. In addition, polymyxin B in combination with rifampicin exhibited broadly applicable efficacy and strong synergy across all tested clinical isolates, representing a potential treatment strategy for A. baumannii. IDentif.AI-pinpointed combinations may potentially serve as alternative treatment strategies for A. baumannii.
Free mobility across group boundaries promotes intergroup cooperation
Group cooperation is a cornerstone of human society, enabling achievements that surpass individual capabilities. However, groups also define and restrict who benefits from cooperative actions and who does not, raising the question of how to foster cooperation across group boundaries. This study investigates the impact of voluntary mobility across group boundaries on intergroup cooperation. Participants, organized into two groups, decided whether to create benefits for themselves, group members, or everyone. In each round, they were paired with another participant and could reward the other’s actions during an ‘enforcement stage’, allowing for indirect reciprocity. In line with our preregistered hypothesis, when participants interacted only with in-group members, indirect reciprocity enforced group cooperation, while intergroup cooperation declined. Conversely, higher intergroup cooperation emerged when participants were forced to interact solely with out-group members. Crucially, in the free-mobility treatment – where participants could choose whether to meet an in-group or an out-group member in the enforcement stage – intergroup cooperation was significantly higher than when participants were forced to interact only with in-group members, even though most participants endogenously chose to interact with in-group members. A few ‘mobile individuals’ were sufficient to enforce intergroup cooperation by selectively choosing out-group members, enabling indirect reciprocity to transcend group boundaries. These findings highlight the importance of free intergroup mobility for overcoming the limitations of group cooperation.
Unlocking the potential of experimental evolution to study drug resistance in pathogenic fungi
Exploring the dynamics and molecular mechanisms of antimicrobial drug resistance provides critical insights for developing effective strategies to combat it. This review highlights the potential of experimental evolution methods to study resistance in pathogenic fungi, drawing on insights from bacteriology and innovative approaches in mycology. We emphasize the versatility of experimental evolution in replicating clinical and environmental scenarios and propose that incorporating evolutionary modelling can enhance our understanding of antifungal resistance evolution. We advocate for a broader application of experimental evolution in medical mycology to improve our still limited understanding of drug resistance in fungi.
Paper battery powered iontophoresis microneedles patch for hypertrophic scar treatment
Hypertrophic scar (HS) is a plaque fibrous and indurated dermal lesion that may cause physical, psychological, and cosmetic challenges for patients. Intralesional injection of triamcinolone acetonide (TA) is commonly used in clinical practice, which cause unbearable pain and uneven drug delivery within HS tissue. Herein, we developed a paper battery powered iontophoresis-driven microneedles patch (PBIMNP) for self-management of HS. The high integration of PBIMNP was achieved by incorporating a paper battery as the power source for iontophoresis. The transdermal drug delivery strategy of PBIMNP combined microneedles and iontophoresis techniques, involving “pressing and poking, phase transformation, and diffusion and iontophoresis”, which can actively deliver 90.19% drug into the HS tissue with excellent in vitro drug permeation performance. PBIMNP administration effectively reduced the mRNA and protein levels, leading to a decrease in the expression of TGF-β1 and Col I associated with HS formation, demonstrating its efficacy in HS treatment. The microneedles and wearable design endow the PBIMNP as a highly promising platform for self-administration on HS treatment.
Breaking barriers: we need a multidisciplinary approach to tackle cancer drug resistance
Most cancer-related deaths result from drug-resistant disease(1,2). However, cancer drug resistance is not a primary focus in drug development. Effectively mitigating and treating drug-resistant cancer will require advancements in multiple fields, including early detection, drug discovery, and our fundamental understanding of cancer biology. Therefore, successfully tackling drug resistance requires an increasingly multidisciplinary approach. A recent workshop on cancer drug resistance, jointly organised by Cancer Research UK, the Rosetrees Trust, and the UKRI-funded Physics of Life Network, brought together experts in cell biology, physical sciences, computational biology, drug discovery, and clinicians to focus on these key challenges and devise interdisciplinary approaches to address them. In this perspective, we review the outcomes of the workshop and highlight unanswered research questions. We outline the emerging hallmarks of drug resistance and discuss lessons from the COVID-19 pandemic and antimicrobial resistance that could help accelerate information sharing and timely adoption of research discoveries into the clinic. We envisage that initiatives that drive greater interdisciplinarity will yield rich dividends in developing new ways to better detect, monitor, and treat drug resistance, thereby improving treatment outcomes for cancer patients.
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