Wednesday, February 19, 2025

AI in Science Publication: The Good, the Bad and the Questionable





The journey from research generation to manuscript publication presents many opportunities where AI could be used – for better or for worse.

AI in scientific publishing – new opportunities and new dilemmas

When AI-assisted technologies became increasingly mainstream early last year, they were met with both excitement and concern over their potential to reduce the burden of mundane tasks as well as their possible misuse. Particularly in academic settings, and especially in academic publishing.


The global sharing of scientific research progress is integral to the existence of science and its ability to improve our lives and our planet. Through the current publishing model, the journey from research data generation to manuscript publication presents many opportunities where AI could, hypothetically, be used – for better or for worse.

Dmytro Shevchenko, Aimprosoft's lead data scientist, and PhD student in computer science at Kharkiv National University in Ukraine, has five years’ worth of experience working with commercial large language models (LLMs). He believes that there are many beneficial applications of generative AI (GAI) in publishing: “Creating abstracts and summaries is one example. LLMs can generate summaries of research papers, which can help readers quickly understand the main findings and implications of the research.”

Shevchenko also sees LLMs as having a positive impact on the accessibility and reach of research findings, given that they could facilitate the translation of research articles into different languages. “Text checking and correction is another benefit. LLMs are trained on large datasets and can generate coherent and grammatically correct text. This can help improve the overall quality of research papers by making articles more readable and understandable,” he adds.

“I think AI is a fantastic tool to streamline and speed up the publishing process,” echoes Dr. Andrew (Andy) Stapleton, a former research chemist. Stapleton now works as a content creator developing resources, training and products that are helpful for academics. “So much of the boring and procedural can be written faster (abstracts, literature reviews, summaries and keywords etc.).”

In early 2023, it seemed as though many scientific publishers did not share Shevchenko and Stapleton’s enthusiasm for the practical applications of AI. Some limited how the tools could be adopted during manuscript preparation, while others, like Science, took an even more restrictive stance, banning their use entirely.

“The scientific record is ultimately one of the human endeavor of struggling with important questions. Machines play an important role, but as tools for the people posing the hypotheses, designing the experiments and making sense of the results. Ultimately the product must come from – and be expressed by – the wonderful computer in our heads,” Herbert Holden Thorp, the Science journals editor-in-chief, said in January 2023.


In Stapleton’s opinion, this decision was underpinned by a fear of change. He thinks that the technology moved faster than journals were able to assess best practices. Perhaps this was a motivating factor for the outright ban – but there are very real hazards posed by the use of AI in scientific research and publication.


The possibility that AI tools could “supercharge” paper mill systems is explored in Gianluca Grimaldi and Bruno Ehrler’s AI et al.: Machines Are About To Change Scientific Publishing Forever. Paper mill systems, where organizations produce and sell poor or fake journal papers, are just one of the unfortunate consequences of the publish or perish paradigm.

“A text-generation system combining speed of implementation with eloquent and structured language could enable a leap forward for the serialized production of scientific-looking papers devoid of scientific content, increasing the throughput of paper factories and making detection of fake research more time-consuming,” Grimaldi and Ehrler say. Paper mills are already abundant across the globe, and the authors fear that the situation will only worsen with the influx of AI-assisted tools.

Another concern is that, while LLMs can generate text, they can’t always produce accurate or scientifically valid content. “In most cases, LLMs may lack a proper understanding of scientific concepts and context. While they may generate text based on statistical patterns in the training data, they do not understand the meaning of the words or scientific concepts about which they are generating a particular text,” Shevchenko explains, emphasizing that researchers must carefully review and verify the text generated by LLMs to ensure its accuracy and validity.

Fabrication of data is also a potential problem. A recent Nature study used ChatGPT-3.5 and ChatGPT-4 to create short literature reviews on 42 different topics using 84 papers. The researchers found that 18–55% of references generated using ChatGPT-4 and ChatGPT-3.5 were fabricated, respectively. Discussing the work in a BMJ editorial piece, Drs. Nazrul Islam, associate professor of epidemiology and medical statistics, and Mihaela van der Schaar, the John

Humphrey Plummer Professor of machine learning, artificial intelligence and medicine at the University of Cambridge, said, “This issue is particularly pressing with the proliferation in conspiracy theories, misinformation, disinformation and skepticism towards scientific consensus, such as the antivax movement.”

“There are also ethical issues associated with using LLMs in scientific publications, including issues of plagiarism, attribution and intellectual property rights,” Shevchenko says. “Researchers must ensure that appropriate information is provided to sources and collaborators and that ethical principles of scholarly publishing are adhered to.

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Tuesday, February 18, 2025

Improving ultrasound cancer treatment by tricking the cells at the nanoscale





One of the latest developments in killing cancer cells involves using ultrasound waves, typically used in medical imaging. Ultrasound therapy for cancer uses sound waves to disrupt cancer cell membranes. Unlike normal cells, cancer cells lack some of the repair mechanisms that protect a normal cell against damage. The lack of repairability makes them more vulnerable to specific treatments, such as low-frequency ultrasound waves, which can potentially cause cell death. The method is appealing due to its noninvasive nature and cost-effectiveness.


However, the effectiveness of ultrasound therapy can vary depending on the type of cancer and its location in the body. This variability and how different cancer cells respond to mechanical forces may require tailoring treatments to individual patients.


Researchers from the Indian Institute of Science IISc) and the National University of Singapore have been trying to improve the effectiveness of ultrasound therapy. A new study shows how subtle nanoscale changes can enhance ultrasound treatments' effectiveness in killing cancer cells.


Their work focuses on subtly changing the Extracellular matrix (ECM), a 3D network of proteins and other molecules that surrounds and supports cells and tissues. The ECM is like a web that surrounds cells, providing physical support. The surface of the ECM also provides binding spots for cell receptors known as integrins. Integrins are proteins that help cells attach to each other and the ECM.


In healthy tissues, the spaces between the binding points on the ECM are around 50 to 70 nanometers (nm) apart. However, in cancerous environments, things get a little more crowded. Excess ECM causes these spaces to shrink below 50 nm. This increased density affects how the cancer cells interact with the ECM, influencing how they respond to treatments.


“We found more cancer cells being killed when the binding spacing is increased to around 50-70 nm,” remarks Ajay Tijore, Assistant Professor at IISc and corresponding author of the study.
vThe study found that when cancer cells were grown on arrays with 50 nm and 70 nm spacings, their cell membranes stretched under the influence of a protein called myosin, leading to an influx of calcium into the cells. This calcium influx disrupted the mitochondria, eventually causing the cells to die. However, at 35 nm spacing, the cells couldn't bind as effectively. They failed to generate the necessary myosin forces, leading to a reduced response to the ultrasound waves. All they had to do was increase the spacing between the cancerous cells so that the ultrasound waves could destroy the cells effectively.


“While doing these experiments, we stumbled upon literature on a drug called Cilengitide. It was one of the most widely studied drugs and went to Phase III clinical trials, but it failed," explains S Manasa Veena, PhD student at IISc and first author of the study.
vv“Oral cancer is a major problem in the Indian subcontinent. There is a lot of ECM deposition, leading to swelling, inflammation … and extreme choking of the tumour microenvironment. This is what we are currently working on.” remarks Prof. Tijore.




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Saturday, February 15, 2025

Budget for agri research needs to be doubled to widen impact: Paper



Just days before the Budget, the quarterly bulletin by Indian Council for Research on International Economic Relations (ICRIER) arm Agriculture Policy, Sustainability, and Innovations (APSI) has underscored the dire need to double the current budgetary allocation for agriculture research and development (R&D) in order to broaden its impact.

The bulletin was released recently and said despite numerous initiatives and increased expenditures on agricultural R&D, there is a pressing need to scale up these efforts for broader impacts. This calls for higher allocations of funds.
Eminent agriculture economist Ashok Gulati is the chief editor of the bulletin, which comprises chapters written by various experts.
“Achieving this would require nearly doubling the current budgetary allocation for agriculture research and development expenditure (ARDE) from the current Rs 9,941 crore allocated to the Department of Agricultural Research and Education (DARE) within the next 2-3 years,” a chapter in the bulletin said.

It said previous studies have shown that each rupee invested in agriculture research yields a much higher return (11.2) compared to investments in fertiliser subsidies (0.88), power subsidies (0.79), education (0.97), or roads (1.10).
“Therefore, reallocating funds from fertiliser and power subsidies to agricultural R&D could significantly enhance food and nutritional security amid climate change challenges,” the chapter said.
Underscoring the need to push research from the lab to the field, the report said that since 2014, the National Agricultural Research System under — the aegis of the Indian Council of Agricultural Research (ICAR) — released 2,380 varieties of various field crops, but El Nino in 2013 brought down agri-GDP growth to 1.4 per cent in FY24 compared to 4.7 per cent in FY23.
Among these ICAR-released varieties, 1,971 are climate-resilient, including cereals (913), oilseeds (335), pulses (364), forage crops (106), fibre crops (189), sugarcane (54), and potential (underutilised) crops (10).
“We need some satisfactory answers to this. One plausible answer is that whatever has been done so far is not enough to protect Indian agriculture from extreme weather events. Or, there is a serious lack of extension-related activities that may have aided in research moving from lab to land,” it added.


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Friday, February 14, 2025

Multi- and transgenerational effects of environmental chemicals on mollusks: An underexplored experimental design in aquatic (eco)toxicological studies





(Eco)toxicological studies frequently evaluate the effects of chemicals in one life stage of organisms, but the use of these outcomes can only partially estimate populational effects. In this regard, multi- and/or transgenerational studies should be performed in order to provide information on contaminant effects in a populational functioning context. The present review aimed to summarize and critically evaluate the current knowledge regarding multi- and/or transgenerational effects of traditional and emerging environmental chemicals on mollusks. Results showed that these kinds of studies were performed in aquatic mollusks (bivalve and gastropod), being Gastropoda the mollusk Class most frequently studied. Additionally, freshwater species and multigenerational studies were more common for this class. For the Bivalvia class, only marine species were evaluated, and transgenerational exposure was more commonly assessed. The effects were reported for 15 species, highlighting the marine bivalves Crassostrea gigas and Saccostrea glomerata, and the freshwater gastropod Lymnaea stagnalis. Multi- and transgenerational effects were described for 8 environmental chemical groups, mainly metals, pesticides, and pharmaceuticals. In general, multi- and transgenerational exposure induced biometric, developmental, and reproductive impairments in mollusks, indicating that environmental chemicals might lead to generational impairments, reduced population growth and reproductive capacity, and decreased fitness. The current study indicated that bivalves and gastropods are suitable organism models to assess the multi- and transgenerational adverse effects induced by traditional and emerging environmental chemicals.

Despite the relevance of multi- and transgenerational evaluations, these kinds of studies are not part of standard ecotoxicity tests with mollusks (Bouly et al., 2022; ReƔtegui-Zirena et al., 2017; Salice et al., 2010). This most likely occurs due to characteristics that are required to conduct such experiments. For example, freshwater gastropods are suitable model systems to be used in multi- and transgenerational exposures due to the fact that they are easy to culture, have a small size, reach reproductive age early, reproduce continuously under laboratory conditions, have high egg production, and have a short embryonic development period (Ubrihien et al., 2022). Taking these desired characteristics into consideration, a limitation in the number of species that are suitable candidates for this type of study appears. Nevertheless, both multi- and transgenerational studies should be considered by policymakers in their decisions, as they highlight effects on the population level, which is more ecologically relevant. In fact, the Organization for Economic Co-operation and Development (OECD) recently published a new guideline that considered multiple generations of the fish Japanese Medaka (Oryzias latipes; OECD, 2023), evidencing the progress of assessments for fish, but not for mollusks.

Despite the growing number of review articles on the use of mollusks (i.e., bivalves and gastropods) as model systems in ecotoxicological studies, environmental risk assessments, and biomonitoring programs (Beyer et al., 2017; Caixeta et al., 2022, 2020; Curpan et al., 2022; Rocha et al., 2015; Rodrigues et al., 2023), the knowledge concerning multi- and/or transgenerational effects of chemicals on this group remains scarce. Therefore, the current review aimed to evaluate the current state of knowledge regarding multi- and/or transgenerational effects on mollusks exposed to different environmental chemicals. A scientometric and systematic review was performed, and data were then summarized and critically discussed. Additionally, gaps in knowledge and recommendations for future studies were identified herein.


Numerous synthetic chemicals are produced annually and, eventually, released into the aquatic environment (Naidu et al., 2021). Due to their different purposes and properties, both fauna and flora might be affected by the presence of these chemicals in their habitat. In order to prevent irreversible environmental damage and impacts on human health, guidelines were created to lead policymakers in their decisions (Villa and McLeod, 2002). Besides tests from guidelines, different (eco)toxicological studies are conducted to understand the effects of environmental chemicals and their mechanisms of action and toxicity. Among aquatic organisms, mollusks are frequently used in (eco)toxicological studies with traditional and emerging pollutants and environmental monitoring programs due to their ecological, medical, and economic value (Caixeta et al., 2022; Harayashiki et al., 2020; Rocha et al., 2015).

Regardless of the importance of mollusks in (eco)toxicological studies, most experiments only considered one life stage of these organisms, disregarding the possible effects on the whole life cycle and population (Bouly et al., 2022; ReƔtegui-Zirena et al., 2017). In this regard, multi- and transgenerational studies might answer the questions regarding this subject. In multigenerational studies, several generations are exposed to the same pollutant and, most of the time, to the same concentrations. This allows the observation of possible adaptive mechanisms to that particular pollutant, that would increase the survival success of that population in an environmental pollution scenario, or it might reveal aggravated or delayed effects of pollutants, which could endanger the local population (Salice et al., 2009; Ubrihien et al., 2022). While transgenerational studies allow the understanding of how the following generations might be affected by parental exposures (Po and Chiu, 2018; ReƔtegui-Zirena et al., 2017; Yingprasertchai et al., 2017). As the observed effects cannot be ascribed to the direct contact of these organisms to the pollutant (Perez and Lehner, 2019). In addition, it is possible to evaluate if these effects in the offspring are temporary or permanent, and if there is an increase in the pollutant tolerance in this type of study (ReƔtegui-Zirena et al., 2017; Yingprasertchai et al., 2017).


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Thursday, February 13, 2025

Effects of air pollution on natural ecosystems







As well as having effects on human health, air pollution can also be harmful to our natural environment. Pollutants in the air can be toxic to sensitive plants and trees, while pollutants in rainfall damage habitats by depositing acid or excess nutrients. Water bodies such as rivers and lakes are also susceptible to the effects of air pollution.



The most significant air pollution for our natural environment occurs when reactive nitrogen compounds, such as ammonia and nitrogen oxides, are deposited to sensitive sites. Deposition can be through direct contact between polluted air and plants. This type of deposition is called ‘dry deposition’ and it mostly happens close to pollution sources.

Deposition also occurs when pollution is dissolved in precipitation (rain and snow), which falls onto sensitive sites. We call this ‘wet deposition’ and it can happen at long distances away from the pollution source.

Ammonia is by far the biggest contributor to nitrogen deposition and comes from agricultural activities such as livestock housing, slurry/manure storage and spreading and fertiliser use. More information on ammonia emissions in Northern Ireland can be found here.

Another source of nitrogen deposition is from nitrogen oxides, which are produced from road transport (petrol and diesel engines) and some types of industry.

Sulphur dioxide is another air pollutant that has harmful effects on vegetation and it is produced from burning fuels, in particular coal.


Northern Ireland has 294 Areas of Special Scientific Interest, 54 Special areas of Conservation and 16 Special Protection Areas that have been designated as needing protection because of the importance of the species and habitats that they support. Sites include peatlands, native woodlands, species-rich grasslands and freshwater & coastal habitats. For more information on protected sites, see here.


In Northern Ireland, ammonia is the air pollutant of primary concern for its effects on designated sites.


Ammonia can have a directly toxic effect on sensitive vegetation, like lichen and mosses. Ammonia and nitrogen deposition reduce plant species richness and diversity, favouring species that are tolerant to excess nutrients. This leads to changes in plant and animal communities within our habitats and can also alter their ecosystem function. For example, peatlands sequester carbon and are therefore crucial in the fight against climate change. If peatlands are being damaged by ammonia and nitrogen deposition, they will not be able to store carbon as effectively.


DAERA monitors the condition of designated sites, and assessments can help to identify where damage from air pollution is a contributing factor to habitat damage and species loss.

Monitoring Air Pollution at Designated Sites


In collaboration with partners UK Centre for Ecology and Hydrology, Ulster Wildlife and the National Trust, NIEA’s Air Quality and Biodiversity Unit delivers a programme of monitoring and evidence work. The work aims to identify and quantify sources of atmospheric nitrogen input to the NI designated site network, to inform mitigation strategies and to evaluate how these naturally N-poor ecosystems are affected by the addition of nitrogen.


Concentrations of ammonia have been monitored at Ballynahone Bog since September 2014. Ammonia monitoring has been ongoing since June 2020 on an additional seven SACs (Curran Bog, Garry Bog, Moneygal, Peatlands Park, Sliabh Beagh, Cuilcagh Mountain and Turmennan). At Cuilcagh SAC and Ballynahone Bog, ammonia monitoring is accompanied by wet deposition monitoring. As of July 2022, ammonia monitoring has also been initiated at Murlough SAC.


Most ammonia air pollution samplers are exchanged at monthly intervals. This monitoring aligns with the UK National Ammonia Monitoring Network (ongoing since the 1990s) in addition to a network of 25 rural location sites run by AFBI.


Modelling provides estimates of annual mean concentrations for NH3 and NOx right across NI, as well the amount of nitrogen deposited in rainfall. These estimates are used to make comparisons with the Critical Levels that have been calculated for NH3 and NOx and the Critical Loads for nitrogen deposition.


Image right shows a wet deposition monitor at Ballynahone Bog: rainfall is collected and then samples taken each month to be analysed for the presence of nitrogen pollution.


Biomonitoring is also carried out at a number of sites to determine the effect of nitrogen on vegetation. Samples for foliar analysis are collected in winter or spring, before temperatures rise and growing commences.


Local prevailing wind patterns play a key role in atmospheric nitrogen pollution input to designated sites, in terms of local ammonia concentrations and N deposition originating from local, regional and transboundary sources. To investigate local wind patterns and their temporal variability with locally measured weather data, and to analyse these data in conjunction with NH3 measurements, meteorological data is collected at Ballynahone Bog and Peatlands Park.


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Wednesday, February 12, 2025

NRT research and innovation: Quantum information science and technology








Drawing insight from physical science, mathematics, computer science and engineering, the emerging field of quantum information science and engineering (QISE) holds extraordinary promise in creating next-generation technologies for processing and communicating information. Many researchers, policymakers and industry leaders believe that quantum technology could transform the nation's most vital societal and economic systems, from strengthening healthcare delivery to ensuring national security. But to harness the power of QIS and build national competitiveness in the field, the United States must invest in a new generation of researchers equipped with the skills and knowledge to drive new discoveries in quantum mechanics.

As part of its commitment to advancing quantum information science and technology, the U.S. National Science Foundation Research Traineeship (NRT) Program is supporting a range of cutting-edge projects focused on expanding our country's quantum workforce. These innovative NRTs are preparing a new wave of scientists to unearth the promise of the quantum revolution.

Quantum Engineering NRT at Colorado School of Mines, in partnership with San José State University


After founding one of the country's first graduate programs in quantum engineering, the Colorado School of Mines (Mines) is leveraging their NRT to take quantum technology graduate-level education to the next level. In partnership with San José State University, Mines is providing diverse STEM graduate students with innovative interdisciplinary research opportunities to become leaders in the QISE workforce. Trainees engage with a comprehensive curriculum in quantum computing and take part in hands-on research at key national labs with industry partners like Google and IBM. Through this work, Mines is pioneering a model for QISE graduate education that will ultimately be accessible to a wide range of institutions and students across the country.

Accelerating Quantum-Enabled Technologies, University of Washington


Accelerating Quantum-Enabled Technologies (AQET) at the University of Washington brings together faculty expertise in physics to chemistry, computer science and engineering to provide graduate students with cutting-edge training. Following a "learn, practice, apply" approach, trainees take part in foundational and interdisciplinary courses followed by a team capstone project focusing on real-world applications. Working with partners like IBM and Pacific Northwest National Laboratory, AQET is one of the first programs to connect hardware and software scientists and engineers to explore the power of quantum technologies.

Quantum Networks Training and Research Alliance, University of Georgia and University of Tennessee, Knoxville


Collaboration and innovation are driving a unique partnership between the University of Georgia and the University of Tennessee, Knoxville focused on harnessing the quantum revolution. Together these two prominent research institutions are building the Quantum Networks Training and Research Alliance in the Southeast (QuaNTRASE), offering cutting-edge, transdisciplinary training to a new generation of scientists with deep knowledge of quantum technologies. As part of its efforts to support a quantum-ready workforce, QuaNTRASE prepares trainees to explore complex research questions while creating powerful opportunities for historically marginalized student populations. In addition to foundational courses, training includes cross-institutional and interdisciplinary advising and mentoring focusing not only on academic research but on creating community, particularly among first-generation STEM graduate students and minority and female students. As UT STEM Education Professor Mehmet Aydeniz shared, "Preparing future generations for jobs in the quantum and AI fields is a national priority. We aim to prepare the scientists and engineers of the future who will be instrumental to the nation's leadership in science and quantum computing specifically."


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Monday, February 10, 2025

How Ncl & SUMOylation Boost HIF-1α & Pyroptosis in Ischemic Hindlimb!




 

Liquid-liquid phase separation (LLPS) has emerged as a flexible intracellular compartment that modulates various pathological processes. Hypoxia-inducible factor-1α (HIF-1α) has been shown to play an essential role in inflammation after ischemic injury. However, the mechanisms underlying HIF-1α-induced inflammation in ischemic diseases have not been defined. This study found that HIF-1α mediated the progression of ischemia-induced muscle injury. After ischemic injury, SUMO1 is upregulated and rapidly activates NLRP3 inflammasome through the upregulation of HIF-1α, leading to enhanced inflammation and pyroptosis. Co-IP revealed an interaction between SUMO1 and HIF-1α and SUMOylation of HIF-1α at K477. Moreover, we demonstrated the important role of dynamic phase separation of Nucleolin (Ncl) in regulating HIF-1α mRNA stability through fluorescence recovery after photobleach (FRAP) analysis. The stability of HIF-1α is regulated by Ncl liquid-liquid phase separation and SUMOylation in ischemia-induced hindlimb injury. HIF-1α can promote the expression of NLRP3 and other inflammation-related molecules, leading to pyroptosis, suggesting that Ncl/LLPS/HIF-1α or SUMO1/HIF-1α pathway may be a new target for the treatment of inflammation in ischemic diseases. Although previous studies have found that HIF-1α is able to promote the expression of target genes after hypoxia, and these genes are used to maintain the stability of the intracellular environment to adapt to hypoxia. We found that HIF-1α is involved in the activation process of NLRP3 inflammasomes after hind limb ischemia, which enriches our understanding of the biological role of HIF-1α.



1. Introduction
Limb ischemia is a serious clinical condition affecting many patients worldwide and there is no effective therapy . Ischemia activates the NOD-like receptor protein 3 (NLRP3) inflammasome, which induces tissue damage by releasing inflammatory cytokines including interleukin-1β (IL-1β) and IL-18 or Gasdermin-D (GSDMD) . However, the molecular mechanisms underlying activation of the NLRP3 inflammasome remain largely unknown.
Previous studies have shown that many inflammatory factors are released from damaged tissues after ischemic injury . Our prior research found that the increased expression of NLRP3 inflammasomes led to the activation of Caspase-1 (Casp-1), IL-1β and IL-18 and pyroptosis . However, the specific regulatory mechanism of NLRP3 activation in limb ischemic disease is unclear.
Hypoxia-inducible factor-1α (HIF-1α) is an essential hypoxic response molecule in the body . Under hypoxic conditions, HIF-1α and HIF-1β form a dimer, which promotes the transcription of hypoxia stress-related genes . Therefore, HIF-1α is vital in inflammation and pyroptosis in ischemic diseases .
Specifically, during the initial phases of atherosclerosis, HIF-1α has been shown to stimulate the production of reactive oxygen species (ROS) and activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, both of which are instrumental in triggering endothelial cell dysfunction . This dysfunction is a key event in the pathogenesis of atherosclerosis, which can ultimately cause myocardial infarction. In this context, HIF-1α further exerts its influence on the inflammatory cascade by regulating the NLRP3 inflammasome, a process that can result in the pyroptotic death of cardiomyocytes . Despite these insights, the specific contribution of HIF-1α to the pathophysiology of lower limb ischemic diseases remains understudied. Our study aims to address this gap by investigating the potential regulatory mechanisms of HIF-1α in these conditions, which could provide novel therapeutic targets for the treatment of peripheral arterial disease.

2. Results
2.1. Ischemia triggers the activation of NLRP3 inflammasome in vivo
To explore whether ischemia can cause the activation of NLRP3 in muscle tissue, we constructed a mouse hindlimb ischemia model and examined the gastrocnemius muscles three days after the ischemic surgery. We found that the mRNA levels of NLRP3, Casp-1, GSDMD, IL-18, and IL-1β were increased in the ischemic left limb compared with the non-ischemic right limb . Western blot analysis further showed that the protein expression of NLRP3, Casp-1, and GSDMD was increased in the ischemic tissues compared to the non-ischemic tissues. The release of IL-18 and IL-1β in the serum of ischemic mice was significantly higher than that of non-ischemic mice measured by ELISA.


(E-H) Western blot analysis showed increased NLRP3, Pro-Casp-1, Cleaved-Casp-1 and GSDMD protein expression in muscle after ischemic surgery (n = 4 or 3). (I) ELISA of serum IL-1β and IL-18 levels from control and ischemia groups (n = 3). Data are presented as Mean ± SEM and analyzed using a two-tailed t-test. Expression of mRNA and protein is expressed as fold changes relative to the CTRL, which is set to 1.

2.2. Hypoxia induces the activation of NLRP3 inflammasome and promotes cell pyroptosis in vitro
The C2C12 cell line, a commonly used murine myoblast model in biomedical research, serves as a valuable in vitro system for investigating various physiological and pathological aspects of muscle. Its widespread application stems from its exceptional ability to simulate muscle injury and repair processes. To verify whether hypoxia could promote inflammatory response in C2C12 cells, we divided C2C12 cells into normoxic and hypoxic groups. To induce hypoxia, the cells were treated at 37 °C, 5 % CO2 and 1 % O2 for 24 h, and we found that the mRNA levels of NLRP3, Casp-1, GSDMD, IL-18, and IL-1β were increased in hypoxic cells compared with control cells by qPCR . Western Blot also showed that the protein levels of NLRP3 and GSDMD were upregulated in the hypoxic group, and the levels of Pro-Casp-1 and Cleaved-Casp-1 were increased compared with the control group . These findings indicate that hypoxia induces Casp-1 activation by promoting NLRP3 expression. Subsequently, we found that IL-1β and IL-18 in the hypoxic cells were significantly increased by ELISA . We detected pyroptosis by PI staining. The results showed that the positive PI staining rate in hypoxic cells was significantly higher than that in control cells, proving that hypoxia caused cell membrane rupture and induced pyroptosis. All these results indicate that hypoxia can promote NLRP3-mediated inflammatory response and pyroptosis.




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Friday, February 7, 2025

Keysight Technologies and University of Malaga Launch 6G Research Lab








Keysight Technologies, Inc. and the University of Malaga have inaugurated a new 6G research and innovation laboratory aimed at advancing next-generation connectivity technologies. This facility is part of Keysight’s European infrastructure, promoting collaboration with industry, research communities, and academic institutions.


The lab features three main workspaces: Monitor, Measurement, and Experience. The Monitor workspace allows for real-time mobile network experimentation using the Victoria Network platform. The Measurement area will utilize Keysight’s latest testing hardware and software, while the Experience section will demonstrate 6G use cases to provide hands-on engagement.


Research will target multiple areas including new spectrum and components for improved data throughput, AI and machine learning integrations to enhance network performance, and networked sensing for innovative applications. Additionally, the lab will focus on creating digital twins for testing, developing scalable network architectures, and ensuring robust security measures.



Giampaolo Tardioli, Vice President of 6G and Next Generation Technology at Keysight, expressed that the lab will be critical for fostering innovation in the 6G sector, allowing researchers to develop transformative technologies that enhance connectivity. Similarly, Pedro Merino from the University of Malaga highlighted the lab’s potential to establish the institution as a key player in international 6G collaborations, facilitating advancements in research and innovation.


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Thursday, February 6, 2025

Medical research depends on government money – even a day’s delay in the intricate funding process throws science off-kilter








In the early days of the second Trump administration, a directive to pause all public communication from the Department of Health and Human Services created uncertainty and anxiety among biomedical researchers in the U.S. This directive halted key operations of numerous federal agencies like the National Institutes of Health, including those critical to advancing science and medicine.


These operations included a hiring freeze, travel bans and a pause on publishing regulations, guidance documents and other communications. The directive also suspended the grant review panels that determine which research projects receive funding.


As a result of these disruptions, NIH staff has reported being unable to meet with study participants or recruit patients into clinical trials, delays submitting research findings to science journals, and rescinded job offers.


Shorter communication freezes in the first few days of a new administration aren’t uncommon. But the consequences of a freeze lasting weeks or potentially longer underscore the critical role the federal government plays in supporting biomedical research. It also brings the intricate processes through which federal research grants are evaluated and awarded into the spotlight.


I am a member of a federal research grant review panel, as well as a scientist whose own projects have undergone this review process. My experience with the NIH has shown me that these panels come to a decision on the best science to fund through rigorous review and careful vetting.

How NIH study sections work


At the heart of the NIH’s mission to advance biomedical research is a careful and transparent peer review process. Key to this process are study sections – panels of scientists and subject matter experts tasked with evaluating grant applications for scientific and technical merit. Study sections are overseen by the Center for Scientific Review, the NIH’s portal for all incoming grant proposals.


A typical study section consists of dozens of reviewers selected based on their expertise in relevant fields and with careful screening for any conflicts of interest. These scientists are a mix of permanent members and temporary participants.


I have had the privilege of serving as a permanent chartered member of an NIH study section for several years. This role requires a commitment of four to six years and provides an in-depth understanding of the peer review process. Despite media reports and social media posts indicating that many other panels have been canceled, a section meeting I have scheduled in February 2025 is currently proceeding as planned.


Reviewers analyze applications using key criteria, including the significance and innovation of the research, the qualifications and training of the investigators, the feasibility and rigor of the study design, and the environment the work will be conducted in. Each criterion is scored and combined into an overall impact score. Applications with the highest scores are sent to the next stage, where reviewers meet to discuss and assign final rankings.


Because no system is perfect, the NIH is constantly reevaluating its review process for potential improvements. For example, in a change that was proposed in 2024, new submissions from Jan. 25, 2025, onward will be reviewed using an updated scoring system that does not rate the investigator and environment but takes these criteria into account in the overall impact score. This change improves the process by increasing the focus of the review on the quality and impact of the science.

From review to award


Following peer review, applications are passed to the NIH’s funding institutes and centers, such as the National Institute of Allergy and Infectious Diseases or the National Cancer Institute, where program officials assess the applications’ alignment with the priorities and budgets of institutes’ relevant research programs.


A second tier of review is conducted by advisory councils composed of scientists, clinicians and public representatives. In my experience, study section scores and comments typically carry the greatest weight. Public health needs, policy directives and ensuring that one type of research is not overrepresented relative to other areas are also considered in funding decisions. These factors can change with shifts in administrative priorities.


Grant awards are typically announced several months after the review process, although administrative freezes or budgetary uncertainties can extend this timeline. Last year, approximately US$40 billion was awarded for biomedical research, largely through almost 50,000 competitive grants to more than 300,000 researchers at over 2,500 universities, medical schools and other research institutions across the U.S.


Getting federal funding for research is a highly competitive process. On average, only 1 in 5 grant applications is funded.

Consequences of an administrative freeze


The Trump administration’s initial freeze paused some of the steps in the federal research grant review process. Some study section meetings have been postponed indefinitely, and program officials faced delays in processing applications. Some research groups relying on NIH funding for ongoing projects can face cash flow challenges, potentially resulting in a need to scale back research activities or temporarily reassign staff.


Because my own study section meeting is still scheduled to take place in February, I believe these pauses are temporary. This is consistent with a recent follow-up memo from acting HHS Secretary Dorothy Fink, stating that the directive would be in effect through Feb. 1.


Importantly, the pause underscores the fragility of the research funding pipeline and the cascading effects of administrative uncertainty. Early-career scientists who often rely on timely grant awards to establish their labs are particularly vulnerable, heightening concerns about workforce sustainability in biomedical research.


As the NIH and research community navigate these pauses, this chapter serves as a reminder of the critical importance of stable and predictable funding systems. Biomedical research in the U.S. has historically maintained bipartisan support. Protecting the NIH’s mission of advancing human health from political or administrative turbulence is critical to ensure that the pursuit of scientific innovation and public health remains uncompromised.


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Wednesday, February 5, 2025

eQMS Evolution Drives Improvements in Pharma Data Application in Clinical Trials








Within both the medical technology and pharmaceutical sectors, a significant shift in the clinical trials ecosystem from traditional methods to integrated platforms is enhancing clinical trial management and connecting data within other systems, such as Regulatory Information Management (RIM) systems. Driven by the evolution of electronic quality management systems (eQMS) deployed across a broader range of company functions, the technological advances that allow improved connectivity across company silos are accelerating the collection, management and application of data, leading to tangible improvements in trial efficiency and driving improvements in the timeliness of RIM submissions.


Enhanced Data Management and Real-Time Access


Driven by enhanced data management capabilities, modern eQMS platforms deployed across a company’s technology ecosystem can dramatically improve and streamline the collection and processing of clinical trial information to enable real-time data capture and centralized storage, as well as the passing of critical data and documents into a company’s RIM system. Integration with other critical systems, such as Electronic Data Capture (EDC) and Clinical Trial Management (CTM) systems, creates seamless data exchange and reduces administrative burden.


Collecting data in real-time allows immediate input at the collection point, whether in clinical settings or remote locations. This significantly reduces transcription errors and delays in data availability. Immediate access to trial information enables research teams to promptly make informed decisions and adjust trial parameters as required. These systems’ centralized approach enables smooth data integration from various trial sites and sources, forming a more complete and better organized dataset, which can be analyzed to glean insights about a product’s safety profile and efficacy.


Centralized storage solutions provide a single source of truth for all trial-related data, reducing the challenges of managing multiple databases and reducing data silos. The system maintains comprehensive audit trails, ensuring data provenance and enabling rapid reconstruction of events when needed. Data integrity is further enhanced through automated validation checks that flag inconsistencies or anomalies immediately, allowing prompt investigation and correction. This proactive approach to data quality management significantly reduces the need for retrospective data cleaning.


Streamlining Regulatory Compliance


Regulatory compliance, historically a complex aspect of clinical trials, has been streamlined through sophisticated automation. Contemporary trial platforms incorporate automated compliance checks that validate trial procedures against regulatory requirements in real-time, while maintaining comprehensive audit trails that track all data modifications and access points. This continuous monitoring replaces periodic assessments by immediately flagging potential violations.


Utilizing broad eQMS capabilities in document content systems allows for the connectivity of data and documents in the clinical, quality and regulatory functions. This can help to accelerate regulatory submissions by automatically compiling document content into standardized formats. Built-in templates and workflows ensure complete and properly formatted documentation before submission, reducing review cycles and enabling pharmaceutical companies to bring innovations to market faster.


Advancing Protocol Management


The evolution of protocol management within eQMS represents another significant advance in clinical trials. Version control systems ensure all stakeholders are working with the most current protocol version, ensuring a reduction in human errors. This transparency eliminates confusion and enhances accountability.


Moreover, these systems support adaptive trial designs with flexible tools for managing protocols that can accommodate mid-study changes while ensuring data integrity and compliance. Researchers can modify parameters based on interim results, a capability that was logistically challenging with traditional management systems. This capability is particularly valuable for complex trials that may require protocol adjustments based on interim results.


Revolutionizing Patient Recruitment and Retention


Patient recruitment and retention, often cited as major bottlenecks in clinical trials, have been revolutionized through advanced matching algorithms and enhanced monitoring capabilities. Modern trial platforms identify suitable trial candidates by analyzing eligibility criteria against patient databases, which also ensures better protocol adherence.


The remote monitoring capabilities of these systems reduce the need for in-person visits by providing continuous patient oversight, which is especially beneficial for participants in isolated locations and during epidemics or pandemics. This technological evolution has also led to more diverse patient populations and improved retention rates, which ultimately contributes to more robust trial outcomes.


The Power of Advanced Analytics


The integration of advanced analytics is one of the most transformative aspects of modern eQMS deployed at scale across a company’s organization. Trial platforms process large volumes of data in real-time, enabling both immediate insights and predictive capabilities. Connecting product data that can be generated during trials and through to post-market use gives organizations a greater connected understanding of product performance and safety attributes.


Visualization tools allow researchers to identify trends and potential issues as they emerge, while predictive modeling can forecast outcomes and identify risks before they materialize. This proactive approach to trial management extends to automated report generation and resource allocation, ultimately saving time and resources while improving patient safety.


Enhanced Stakeholder Collaboration


Stakeholder collaboration is enhanced through Cloud-based platforms in eQMS that facilitate immediate information sharing across sites and organizations. Role-based access controls ensure data security while enabling efficient collaboration among sponsors, CROs, investigators and regulatory authorities.


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Tuesday, February 4, 2025

Researchers discover new blood group system - MAL












The discovery of a new blood group, MALhas solved a 50- year-old mystery. Researchers from NHS Blood and Transplant (Bristol), NHSBT’s International Blood Group Reference Laboratory (IBGRL) and the University of Bristol identified the genetic background of the previously known but mysterious AnWj blood group antigen. The findings allow identification and treatment of rare patients lacking this blood group.

Some people can lack this blood group due to the effect of illness, but the rare inherited form of the AnWj-negative phenotype has only been found in a handful of individuals – though due to this discovery it will now be easier to find others in the future.


The two best known blood group systems are ABO and Rh but blood is more complex and matching across the other groups can be lifesaving.


If people who are AnWj-negative receive AnWj-positive blood they could have a transfusion reaction, and this research allows development of new genotyping tests for detecting such rare individuals and reducing the risk of transfusion-associated complications.


The AnWj antigen – an antigen is a surface marker - was discovered in 1972 but its genetic background was unknown until now.(3) The new research, to be published by Blood, the journal of the American Society of Hematology, and now available online in pre-print, establishes a new blood group system (MAL), the 47th ever to be discovered, as home to the AnWj antigen.


The research team established that AnWj is carried on the Mal protein. More than 99.9% of people are AnWj-positive, and such individuals were shown to express full-length Mal protein on their red cells, which was not present on the cells of AnWj-negative individuals. The team identified homozygous deletions in the MAL gene associated with the inherited AnWj-negative phenotype.


The most common reason for being AnWj-negative is due to suffering from a haematological disorder or some types of cancer which suppress antigen expression (4). Only a very small number of people are AnWj-negative due to a genetic cause. There were five genetically AnWj negative individuals in the study including a family of Arab-Israelis.(5) The blood tested included a sample given by a lady in 2015 who was the first AnWj negative person to be discovered in the 1970s.


The research team used whole exome sequencing – the genetic sequencing of all DNA that encodes proteins – to show that these rare inherited cases were caused by homozygous DNA sequence deletions in the MAL gene, which codes for Mal protein.


Proof that Mal is responsible for binding of AnWj antibodies isolated from these rare patients was provided by experiments showing the appearance of specific reactivity with cells in which researchers introduced the normal MAL gene but not the mutant gene.


Louise Tilley, Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, said: “The genetic background of AnWj has been a mystery for more than 50 years, and one which I personally have been trying to resolve for almost 20 years of my career. It represents a huge achievement, and the culmination of a long team effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients.


“The work was difficult because the genetic cases are very rare. We would not have achieved this without exome sequencing, as the gene we identified wasn’t an obvious candidate and little is known about Mal protein in red cells. Proving our findings was challenging, and we appreciate the help of all our collaborators, and the patients, without whom we would not have got to this point.”


Ash Toye, Professor of Cell Biology in the School of Biochemistry and Director of the NIHR Blood and Transplant Research Unit in red cell products at the University of Bristol, said: “It’s really exciting we were able use our ability to manipulate gene expression in the developing blood cells to help confirm the identity of the AnWj blood group, which has been an outstanding puzzle for half a century. This development will help identify these rare donors and help patients in the future.”


Nicole Thornton, Head of IBGRL Red Cell Reference at NHS Blood and Transplant, said: “Resolving the genetic basis for AnWj has been one of our most challenging projects.


“There is so much work that goes into proving that a gene does actually encode a blood group antigen, but it is what we are passionate about, making these discoveries for the benefit of rare patients around the world.


“Now genotyping tests can be designed to identify genetically AnWj-negative patients and donors. Such tests can be added to the existing genotyping platforms.”


Dr Tim Satchwell, Senior Lecturer at UWE Bristol, who contributed to the study whilst a Research Fellow at the University of Bristol, said: “Mal is a very small protein with some interesting properties which made it difficult to identify and meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system. Being able to combine our expertise to finally achieve this has brought the whole team a lot of satisfaction.”


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