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Nature Medicine

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• Biochemistry, Genetics and Molecular Biology (miscellaneous)
• Medicine (miscellaneous)

Nature Research

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10788956, 1546170X

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• Biomolecules

Treating Cancers Using Nature’s Medicine: Significance and Challenges

Samson mathews samuel.

1 Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar; ude.llenroc.dem-rataq@6102sms

Peter Kubatka

2 Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia; [email protected]

Dietrich Büsselberg

There was a time when plant-derived natural formulations were the cornerstone of ancient therapeutic approaches for treating many illnesses [ 1 ]. With the advent of science-based ‘modern’ medicine, plant-based natural remedies for treating ailments came under intense scrutiny for their lack of scientific basis [ 1 ]. However, researchers kept seeking to identify the scientific basis of herbal remedies, medicinal plants, and functional foods. In recent decades, the emphasis on identifying therapeutic plant-based active principles led to significant advancements in the identification and use of natural compounds to treat various diseases ( Figure 1 ) [ 2 , 3 ]. Much of the current knowledge of medicinal plants and their therapeutic properties derives from traditional Chinese or Indian medicine [ 3 ]. It is notable that an estimated 25–28% of modern medicines used by humanity, including those applied for the treatment of cancers, are directly or indirectly derivatives/compounds obtained from plants or other natural sources [ 3 , 4 ].

Pharmacological effects of natural compounds in various diseases. Naturally derived compounds have been used for their anti-oxidant, anti-diabetic, anti-cancer, anti-microbial, anti-inflammatory, immuno-modulatory, cardio-/vasculo-/hepato-/nephro-, and neuro-protective effects. Created with http://biorender.com/ .

Cancers remain a major cause of death worldwide and significantly contribute to the social and economic burden. There remains an unmet need to develop cancer prevention strategies for those at risk and improve treatment strategies for the benefit of those already affected. Only a minor proportion of cancers are caused by hereditary or genetic predisposition. Cancers often develop over years or even decades, triggered by different processes involving DNA damage, epigenetic modifications, metabolic alterations, chronic inflammation, interactions between aberrant molecular pathways, inhibition of apoptosis, and cellular cross-talk with neighboring tissues. Interestingly, plant-based natural compounds can target one or more of these neoplasticity-triggering mechanisms and thus suppress the initiation, progression, metastatic spread, and relapse of cancers.

The Content of this Special Issue. This Special Issue in Biomolecules , entitled “Plant-Derived Natural Compounds in the Management of Cancer: Significance and Challenges”, provides a broad and up-to-date overview of the significant aspects encompassing the research and developments in the use of plant-derived natural compounds in the treatment of various cancers.

Eighteen manuscripts are published in this Special Issue, including one feature paper from among eight published original research articles and one feature paper, as well as two editor’s choice articles, from among ten published review articles.

In their featured original article, Woo et al. [ 5 ] identified the ability of honokiol, a traditional Chinese-medicine-based natural biphenolic compound (extracted from Magnolia species), to target and sensitize cancer cells to undergo TRAIL-mediated apoptosis. Honokiol treatment in cancer cells correlated with the degradation and downregulation of anti-apoptotic survivin and c-FLIP. Interestingly, honokiol exposure led to the inhibition of STAMBPL1 (deubiquitinase), which, in turn, facilitated the ubiquitin–proteasome system-linked degradation of survivin and c-FLIP.

Takac et al. [ 6 ] investigated the effect of acridine chalcone 1C (AC1C) in human colorectal cancer cells. They observed that pro-oxidant properties of AC1C support the production of ROS and RNS, promoting mitochondrial dysfunction, DNA damage, and the activation of apoptosis in these cells via the activation of the MAPK-signaling mechanism. Using the anti-oxidant N-acetyl cysteine, the authors reversed the effect of AC1C, which further supported the anti-proliferative/pro-apoptotic effects of AC1C-induced oxidative stress in the colorectal cancer cells.

In most cancers, post-chemotherapy-induced leukopenia (CIL) significantly contributes to the higher mortality rates among patients. In their retrospective pilot study, Varughese et al. [ 7 ] indicated that a diet inclusive of green jackfruit flour, ‘Jackfruit365 (JF365)’, significantly reduced CIL in cancer patients who were also treated with pegfilgrastim. This study should pave the way for further in-depth investigations to identify the active component for this CIL-suppressing effect of JF365.

Abhinand et al. [ 8 ] studied the multiple anti-angiogenic targets of an herbal formulation, triphala churna (THL), prepared from dried fruits from three medicinal plants used in ancient Indian ayurvedic medicine. THL contains over a dozen different phytochemicals, each of which can pharmacologically inhibit tumor progression. However, with their approach of combining in silico (docking) and in vitro techniques, the team identified that punicalagin and chebulagic acid, among other components of THL, were key contributors inhibiting angiogenesis by targeting multiple components of the VEGF/VEGFR2 axis.

Clove is a well-recognized spice used in many cuisines all over the globe. Cloves are utilized to treat an upset stomach and as an expectorant. Clove oil is well known for its anesthetic effect, which helps to quickly relieve a toothache. Clove bud extracts (CBE) were used by Kello et al. [ 9 ] to showcase their ability to induce oxidative stress and DNA damage and activate apoptosis in human breast cancer cells. CBE treatment increased ROS- and RNS-related stress and activated the caspase-dependent apoptotic pathways while significantly modulating these cells’ Akt, p38MAPK, JNK, and ERK ½ pathways.

Isothiocyanates, which are abundant in cruciferous vegetables (Brassicaceae family such as broccoli, brussels sprouts, cabbage, and cauliflower), have been well studied for their chemopreventive chemotherapeutic effects in cancers. Treatment with Benzyl isothiocyanate (BITC), a degradation product of glucosinolates, found in edible plants of the Brassicaceae family, caused cell shrinkage and suppressed cell viability in gastric adenocarcinoma cells [ 10 ]. Han et al. [ 10 ] found that the BITC treatment-induced ROS production, and subsequent mitochondrial dysfunction, led to the mitochondria-mediated cytochrome-c release and caspase-dependent apoptosis. In another study, 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), a wasabi compound, inhibited the growth and viability of human leukemia cells by the concurrent induction of autophagy and mitotic arrest [ 11 ].

Nineteen different stilbenoids (phenolic compounds found in berries) were investigated by Treml et al. [ 12 ] to study their pro-/anti-oxidant properties in a cellular model of THP-1 macrophage-like cells. Their results show that the different stilbenoids can act as either pro-oxidants or anti-oxidants, and an in-depth study on how these characteristics can be used to combat various cancers is warranted.

Breast cancer remains the leading cause of cancer-related morbidity and mortality worldwide. Three of the review articles have focused on the potential anti-cancer effects of phytochemicals in breast cancers. In their featured review article, Varghese et al. [ 13 ] focused on the mechanism of tumor angiogenesis in light of the altered metabolism of tumor endothelial cells and how miRNAs influence this process in breast cancers. The authors looked through several miRNAs that modulated angiogenesis in breast cancer. They outlined several plant-derived natural compounds (cardamonin, resveratrol, silibinin, curcumin, metformin, genistein, triptolide luteolin, among others) that can alter several miRNA-dependent targets to block tumor angiogenesis and thus repress breast cancer growth and proliferation. In an editor’s choice review article from the same group, Samuel et al. [ 14 ] focused on the widely used anti-diabetic drug metformin as a cancer-preventive and chemotherapeutic agent in treating breast cancer. The article outlines the molecular mechanism of metformin action. It provides an in-depth discussion of the available cellular, pre-clinical, and clinical studies that have tested the anti-tumor potential of metformin as a potential anti-cancer/anti-tumor agent in breast cancer therapy. Abu Samaan et al. [ 15 ] reviewed the clinical effects of paclitaxel (PTX, a taxane compound first isolated from the Pacific yew tree), a commonly used chemotherapeutic drug, and provided mechanistic insights into its anti-cancer effect in different types of breast cancers. While discussing the novel advances in the application of PTX in breast cancers and the use of PTX in neoadjuvant therapy in combination with other anti-cancer drugs, the review also highlights its side effects, the development of resistance to PTX in breast tumors, and possible ways to overcome this treatment-induced resistance to PTX.

In a second editor’s choice article, Samec et al. [ 16 ] discuss the epigenetic post-translational histone modifications as the basis of antineoplastic effects of several phytochemicals in breast, prostate, and colorectal cancers. The authors provide the basis of histone modifications as molecular regulators of chromatin structure. They reviewed the effects of monotherapy and combination therapy using natural compounds on curbing breast, prostate, and colorectal cancers. Along the same theme of epigenetic modifications, Jasek et al. [ 17 ] reviewed the aberrant modifications in the function of DNA methyltransferases (DNMTs) as crucial triggers in the pathogenesis of human cancers. They looked at several pre-clinical and clinical studies that showcase the ability of phytochemicals and plant-based diets to target the epigenetic regulators and modulators of gene transcription and the activity of DNMTs and DNA methylation status in curbing tumor growth and progression.

Gastrointestinal (GI) cancer and its increasing incidence and rapid progression is the theme of Al-Ishaq et al.’s [ 18 ] article. The authors focus on several modifiable and non-modifiable risk factors for the increase in GI cancers and how several bioactive plant-derived secondary metabolites and diets rich in such phytochemicals reduce the incidence (chemopreventive effect) and progression (therapeutic effect) in cancers of the GI tract. They summarize several key molecular mechanisms/pathways (such as the PI3K/Akt, AMPK, mTOR, MAPK, NF- κB, Wnt/β-catenin pathways) that are modulated by natural compounds such as carotenoids, proanthocyanidins, isothiocyanates, and several other plant-metabolites to curb tumor growth and progression.

Brain tumors (high-grade malignant gliomas, including glioblastoma and anaplastic astrocytoma) are among the most devastating and rapidly growing cancers. The chemotherapeutic effect of resveratrol (a polyphenolic component found in berries, nuts, grapes, and red wine) on malignant brain tumors is the focus of the review from Kiskova et al. [ 19 ]. The authors discuss in vitro and in vivo studies that pave the way for advanced clinical research in this area to test resveratrol and its efficacy in treating brain tumors.

Lichens are fascinating symbiotic organisms found in nature and capable of producing different phenolic compounds, including anthraquinones, xanthones, dibenzofurans, depsides, and depsidones. In their review article, Solárová et al. [ 20 ] discuss the molecular mechanisms responsible for the anti-neoplastic potential of several lichen-derived secondary metabolites. While Abotaleb et al. [ 21 ] reviewed the therapeutic potential of different plant-derived phenolic compounds in the treatment of cancer, Satheesh et al. [ 22 ] discuss the possibility that using vitamin C in combination with other conventional anti-cancer treatments can eradicate cancer stem cells (key contributors to therapeutic resistance, metastasis, and relapse).

Are “Natural Substances” the Answer to More Efficient Anti-Cancer Therapy? The articles published in this Special Issue prove that plant-based natural formulations are a vital source of chemopreventive and chemotherapeutic agents. Phytochemicals have a plethora of biological anti-cancer activities and could thus be a rational and practical approach to the effective treatment of cancers. While science and pharmaceutics have made significant advancements in chemically synthesized pharmacological anti-cancer agents and the early diagnosis and identification of cancers, the unfortunate truth is that modern medicine is desperately short of new and targeted therapeutic approaches. It takes years for a new drug to get through research and development and into clinical use, and this is accompanied by high costs [ 3 ]. The once sidelined, natural/plant-based remedies offer ways of relieving this crisis of drug development and harnessing naturally available active compounds to make cancer therapeutics more efficient, as well as more cost-effective and attainable to less privileged patients.

Standard cancer treatment strategies (surgery and radiation) and routinely used chemotherapeutic drugs, in combination with natural bioactive compounds ( Figure 2 ), could prove to be more efficient in treating cancers in terms of (1) a reduction in drug dosage, (2) alleviating side-effects, (3) overcoming drug resistance by re-sensitizing cancers to respond to drugs, (4) targeting cancer stem cells, and (5) curbing metastases and relapses in cancers [ 23 , 24 ].

Benefits of combination therapy (using natural compounds in anti-cancer treatment). The conventional cancer treatments include surgical removal of the tumor, chemotherapy, and radiation therapy, in addition to the standard therapeutic procedures, depending on the type/sub-type of cancer. In a heterogeneous population of cancer patients, while conventional/standard treatment practices benefit some patients, in others, the treatment strategy may have little to no effect. In such a scenario, using a natural compound in combination with the conventional/standard treatment procedures may prove to be beneficial in several ways. Created with http://biorender.com/ .

With the advancements in genomics and understanding regarding the existence of genetic diversity between different patient populations, and even among individual patients, the world of modern medicine is fast embracing the concept of and need for preventive, personalized, precision medicine (3P medicine). In this scenario, when drugs tailored to treat patients on a case-by-case basis become important, turning to ‘natural sources’ of reliable drugs may help to ease the challenges. A serious clinical problem in cytotoxic anti-cancer therapies is the acquired resistance or insensitivity of cancer cells to conventional chemotherapeutics. The current research highlights the potential importance of phytochemicals in increasing chemotherapeutic agents’ sensitivity and/or efficacy against cancer [ 25 ]. Targeting specific molecular pathways by the use of plant nutraceuticals can improve therapeutic outcomes by increasing the sensitivity of cancer cells and reversing their resistance towards the currently applied therapeutic modalities, and thus represents an essential clinical approach to improving the clinical management of cancer. In this regard, testing conventional chemotherapies, in combination with phytopharmaceuticals, on patient-derived cancer cells, using progressive methods, can predict the patient responses and provide outputs for a personalized approach in an individual.

Although this Special Issue focuses on ‘plant-derived natural compounds in cancers’, we acknowledge that ‘natural sources’ for bioactive compounds with medicinal properties are found not just in terrestrial plants but throughout nature, and can help treat various other diseases, as well as cancer [ 26 ]. The marine environment, microbes (bacteria and fungi), slime molds, lichens, and unexpected sources of medicinal remedy, such as the saliva of the Gila monster (the compound found in the saliva, which turned out to be the basis for exenatide, a synthetic anti-diabetic drug), have yielded remarkable therapeutic agents for the treatment of numerous diseases [ 26 ]. Analgesics (painkillers), anti-biotics/anti-microbials, anti-malarials, drugs to treat metabolic and cardiovascular diseases as well as diseases of the nervous and digestive systems, and potential drugs to treat COVID-19, are just few examples of the many therapeutic benefits that humanity has received from from nature [ 27 , 28 , 29 , 30 , 31 ].

Lessons to be Learned and Taught. It is time that differences in opinions regarding the ‘better’ treatment option between practitioners of traditional and modern medicine be set aside, and the different groups work together for the greater good of humanity. On the one hand, practitioners of traditional natural medicine must be willing to share their knowledge. On the other hand, scientists, researchers, and clinicians must support and protect those who practice traditional/natural medicine and be willing to learn from them and their experiences. The knowledge gained from traditional medicine should go hand-in-hand with the pharmaceutical industry’s expertise in drug development [ 3 ]. The lack of international standardization when evaluating the composition, efficacy, safety, and quality of natural medicinal compounds in therapeutics must be overcome [ 3 ]. Coordination and collaboration is necessary between local, regional, national, and international drug regulatory agencies and the pharmaceutical industry to provide clear guidelines regarding the scientific data on the therapeutic effects of compounds derived from natural sources and the regulation/approval processes and manufacturing practices for new drugs [ 3 ].

While there is so much to thank nature for, there is so much more to gain from it. It is likely that we have barely scratched the surface of the medicines that nature has to offer us. Hence, there remains an imminent need to protect our planet from the threats of drastic climate change and unnecessary human interventions that erode and destroy natural resources and their molecular diversity, ultimately depriving humanity of potential sources of natural medicines. Let us play a part in protecting nature and, in turn, let nature protect us!

This work was supported by a National Priorities Research Program grant (NPRP11S-1214-170101; awarded to Professor Dr. Dietrich Büsselberg, June 2019–present) from the Qatar National Research Fund (QNRF, a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.

Conflicts of Interest

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Study connects enjoyment of nature to lower inflammation levels

by Tom Fleischman, Cornell University

Plenty of studies link exposure to the natural world and improved mental and physical health, but a new Cornell study connects enjoyment of nature to a specific biological process—inflammation.

Led by Anthony Ong, professor in the Department of Psychology and director of the Center for Integrative Developmental Science (CIDS) in the College of Human Ecology, the study showed that more frequent positive contact with nature was independently associated with lower circulating levels of three different indicators of inflammation.

"By focusing on these inflammation markers, the study provides a biological explanation for why nature might improve health," Ong said, "particularly showing how it might prevent or manage diseases linked to chronic inflammation , like heart disease and diabetes."

Postdoctoral researcher Dakota Cintron and Gabriel Fuligni are co-authors of "Engagement With Nature and Proinflammatory Biology," which published March 29 in Brain, Behavior, and Immunity .

Ong said pursuing this line of research was as much out of curiosity as anything else.

"Part of it has been inspired by place, being here in Ithaca and being surrounded by nature," he said. "I grew up in Los Angeles—people live in their cars and in traffic. So for me, the study was really trying to answer the question, 'What are the health benefits of nature?'"

Cintron is a current member of CIDS; Fuligni joined the group as an undergraduate after writing a paper on the topic while in one of Ong's classes.

The team used for their study the second wave of the Midlife in the U.S. (MIDUS) survey, a longitudinal study of health and aging in the United States. The first wave of the survey was conducted in 1994-95, the second 10 years later.

Ong's analyses focused on a subset of individuals—1,244 participants, 57% women, with a mean age of 54.5—who participated in a biomarker sub-study during the second wave, during which they were assessed for physical health and provided comprehensive biological assessments via a physical exam , urine sample and fasting morning blood draw.

The participants were asked how often they experienced being out in nature, as well as how much enjoyment they got from it.

"It's not just about how often people spend time outdoors, but also the quality of their experiences," said Ong, admitting that he himself is sometimes guilty of not being fully present in nature. He recalled a recent warm day when he was strolling around Beebe Lake while scrolling on his phone, which detracted from the pleasantness of the experience.

"I realized I was physically in a beautiful natural setting, but mentally I was elsewhere," Ong said. "It was a reminder to myself to be more mindful and engaged when I'm in nature, to really soak in the benefits."

Concentrations of three biomarkers for inflammation—interleukin-6 (IL-6), a cytokine closely involved in the regulation of systemic inflammatory processes; C-reactive protein, which is synthesized in response to stimulation by IL-6 and other cytokines; and fibrinogen, a soluble protein present in blood plasma —were measured, and structural equation modeling was conducted to detect the association between nature engagement and the three biomarkers.

Even when controlling for other variables such as demographics, health behaviors, medication and general well-being, Ong said his team found that reduced levels of inflammation were consistently associated with more frequent positive contact with nature.

"We tried to get rid of this finding by controlling for a host of factors, but we couldn't get rid of it," he said. "So it's a pretty robust finding. And it's this sort of nexus of exposure and experience: It's only when you have both, when you are engaging and taking the enjoyment out of it, that you see these benefits."

Mindfulness while enjoying the natural world is the key, Ong said.

"It's good to remind ourselves that it's not just the quantity of nature," he said, "it's also the quality."

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Stanford Medicine-led study identifies novel target for epilepsy treatment

Researchers find that a little-understood part of the brain appears to be involved in starting seizures and keeping them going.

April 17, 2024 - By Kimberlee D'Ardenne

Stanford Medicine researchers and their colleagues found that removing or inhibiting the fasciola cinereum may help epilepsy patients who aren't helped by surgery. Tom - stock.adobe.com

Removing part of the brain’s temporal lobe is the only treatment available to the millions of people with a form of epilepsy that medications often don’t alleviate. But even that approach fails a third of the time.

A new study from Stanford Medicine researchers and their colleagues offers an explanation and suggests a more effective approach to treatment. They found that a previously overlooked region of the hippocampus, the fasciola cinereum, appears to be involved in instigating and propagating seizures. Removing or inhibiting the fasciola cinereum may help those patients who don’t find relief after surgery.

“The hippocampus is the best studied part of the brain by far, but there is shockingly little known about the fasciola cinereum,” said Ivan Soltesz , PhD, the James R. Doty Professor in Neurosurgery and Neurosciences and a senior author on the study. “This relatively small region was consistently involved in seizure activity in mice and in people undergoing pre-surgical electrical recordings. Our findings suggest that all patients with drug-resistant temporal lobe epilepsy should have depth electrodes placed in the fasciola cinereum as part of the surgery planning process.”

The work was published April 17 in Nature Medicine . Soltesz and Vivek Buch , MD, the Christina and Hamid Moghadam Faculty Scholar as well as the surgical director of the Stanford Comprehensive Epilepsy Center , are co-senior authors.

A tale of a tail

Worldwide, 65 million people live with epilepsy. Tens of millions have mesial temporal lobe epilepsy, with seizures originating, in part, from the amygdala, an almond-shaped structure involved in processing emotions, and the hippocampus, a region necessary for forming memories. When people with mesial temporal lobe epilepsy of just one hemisphere do not respond to anti-seizure drug therapies, the standard of care is surgery. In these procedures, the amygdala and most of the hippocampus in one hemisphere are either surgically removed or ablated, a technique that involves using a laser to heat up and destroy tissue. Because of the symmetry of the temporal lobe — both hemispheres of the brain have an amygdala and hippocampus — people who have these surgeries usually have minimal side effects, according to the researchers.

Ivan Soltesz

Before performing the surgery, physicians need to identify the brain tissue responsible for seizure activity. They do this by placing electrodes in areas of the brain suspected of starting or propagating seizures and taking recordings from the electrodes. This process, called stereoelectroencephalography, or sEEG, lets them map where in the brain seizure activity happens.

Though the amygdala and its next-door neighbor the hippocampus are common locations for sEEG recordings, the electrodes are typically placed in only the anterior and middle regions of the hippocampus. The human hippocampus, located deep in each hemisphere of the brain near the level of the ear, looks like a sea horse lying on its side, with its head pointing toward the front of the brain. sEEG electrodes are commonly placed in the anterior and medial regions, corresponding to the head, body and the beginnings of the tail of the sea horse.

The idea to record from the fasciola cinereum — the far tip of the sea horse’s tail — in patients with epilepsy undergoing sEEG for surgical planning first formed about three years ago, when Ryan Jamiolkowski , MD, PhD, co-lead author of the study and a resident in neurosurgery, joined the Soltesz lab.

At the time, Quynh-Anh Nguyen, PhD, co-lead author on the study and former postdoctoral scholar in the Soltesz lab who is now at Vanderbilt University, was screening for the hippocampal neurons that were active during seizures in mice. Unexpectedly, Nguyen discovered that neurons in a posterior region of the hippocampus, the fasciola cinereum, were involved in seizures.

Jamiolkowski and the research team used optogenetic techniques to test whether the fasciola cinereum could be a target for epilepsy interventions. The neurons in the fasciola cinereum were made to contain special proteins capable of shutting down neuronal activity when exposed to blue light. When electrical recordings from the hippocampus showed seizure activity, the researchers shined blue light onto the fasciola cinereum, shortening the duration of seizures in mice.

Recording from the human hippocampus tail

To understand the fasciola cinereum’s role in seizure activity in humans, Jamiolkowski and Buch recorded from the small region in six patients. All were undergoing sEEG to identify the source of their seizures in preparation for future surgeries to cure their epilepsy. The fasciola cinereum contributed recorded seizures in all six patients, including some episodes in which the head and body regions of the hippocampus were quiet.

Ryan Jamiolkowski

One of the patients with mesial temporal lobe epilepsy of the left hemisphere had already undergone laser ablation of the amygdala and anterior and middle regions of the hippocampus. The patient continued having seizures, and follow-up sEEG showed that the only part of the hippocampus that remained, the fasciola cinereum, was involved in all recorded seizures. The patient underwent a second surgical ablation that removed almost all of the fasciola cinereum, and the frequency of the seizures decreased by 83%, from one to two each month to once every three months.

The researchers said that patients whose seizures involve the fasciola cinereum may need to undergo two surgeries because of the shape of the hippocampus.

“The hippocampus curves like a banana, and the optical fiber used for laser ablation is a straight line. Reaching anterior and posterior regions requires different trajectories that are not currently feasible to combine into one procedure. The results of our study do not challenge the importance of ablating the amygdala and anterior hippocampus but suggest considering a second ablation targeting the posterior hippocampal tail for the patients whose seizures recur,” Jamiolkowski said.

Three of the patients had bilateral involvement of the mesial temporal lobe, which means the amygdala and hippocampus in both the right and left hemisphere showed seizure activity. Because new memories cannot be formed without at least one intact hippocampus, these patients instead received responsive neurostimulation from a device that detects and interrupts seizure activity. However, most responsive neurostimulation units can be configured to target only the anterior regions of the hippocampus on both sides of the brain. The findings from this study suggest that a more personalized approach that also allows the device to monitor and interrupt seizure activity in the posterior hippocampal tail region might be more beneficial to patients.

“Because one-third of patients — a high percentage — do not get seizure freedom from surgery, we should be putting sEEG electrodes in the fasciola cinereum in all temporal lobe epilepsy patients; seizure activity in this region could be a reason why these surgeries sometimes fail,” Jamiolkowski added. “Knowing which patients have seizures involving the fasciola cinereum would let us target it with either ablation or neurostimulation and help us treat patients better than a one-size-fits all approach.”

A researcher from Cambridge University contributed to the study.

Funding for this study was provided by the Stanford Maternal and Child Health Research Institute, the Tashia and John Morgridge Endowed Fellowship, the Lennox-Gastaut Syndrome Foundation Cure 365, the Stanford Neuroscience Scholars Program, and the National Institutes of Health (grants R25NS065741, K99NS121399, K99NS126725, NS121106 and P30AG066515).

• Kimberlee D'Ardenne Kimberlee D'Ardenne is a freelance writer.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

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• 25 April 2024

NATO is boosting AI and climate research as scientific diplomacy remains on ice

• Natasha Gilbert 0

Natasha Gilbert is a freelance writer in Washington, DC.

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A NATO research vessel conducting studies of marine mammals in the Mediterranean Sea (pictured in 2009). Credit: U.S. Navy Petty Officer 2nd Class Kristen Allen via Mil image/Alamy

Science has been essential to the North Atlantic Treaty Organization (NATO), the political and military alliance founded 75 years ago this month. The 32-country alliance is admitting more members as it faces evolving geopolitical and military threats. The organization’s scientific work focuses largely on defence and civil-security projects that, for instance, investigate how climate change is affecting war, how emerging technologies could enhance soldiers’ performance and how to reduce discrimination and intolerance among military personnel. “The role of science and technology for NATO is likely to grow significantly over the next two decades,” predicts Simona Soare, a defence-technologies researcher at Lancaster University, UK.

How does NATO use science?

“We’re looking to make sure that we can provide scientific advice to the nations of NATO to enable them to maintain a technical and military advantage,” says Bryan Wells, a chemist and the organization’s chief scientist. Wells works at NATO’s Brussels headquarters, where world leaders gathered earlier this month to mark the organization’s 75th anniversary.

NATO has a complex organizational structure including both military and civilian staff. The civilian part of NATO is headed by a senior political figure from a member state and also includes diplomats representing member countries. The military part is headed by senior military personnel.

Much of NATO’s research and development (R&D) takes place through the Science and Technology Organization (STO), a network of more than 6,000 scientists at universities and national laboratories and in industry. They work together on defence research projects. NATO’s member states and non-member countries together contribute around €350 million (US$380 million) annually for the work of this network, says Wells.

The STO also has its own research laboratory, the Centre for Maritime Research and Experimentation (CMRE) in La Spezia, Italy. The laboratory employs around 150 people and is led by Eric Pouliquen, a physicist who has worked on underwater remote sensing.

NATO's civilian arm provides grants for a Science for Peace and Security (SPS) research programme, headed by Claudio Palestini, a researcher in communications engineering.

The programme funds studies in areas such as counterterrorism and cyber defence. Earlier this month , the SPS programme updated its priorities. These now include studies on the impact on defence and security from climate change and from AI; protecting underwater infrastructure, and what it calls "hybrid threats", which includes interference in elections and disinformation. Each of its larger grants is worth between €250,000 and €400,000 and lasts for two to three years.

Wells says the STO publishes research — mostly from the CMRE — in peer-reviewed journals where possible. “We recognize if we can publish openly, it’s very beneficial to do that,” he says.

However, many of its research projects are classified. NATO also does not publish a detailed breakdown of its R&D income and expenditure by country; nor does it release its funding trend data.

What sort of research is NATO doing?

Projects cover a spectrum of fields including using autonomous undersea surveillance to hunt for and identify mines; tracking and identifying submarines; quantum radar; and synthetic biology.

For example, one programme led by CMRE researchers explores how autonomous underwater vehicles can identify submarines using quantum technologies and artificial intelligence. Similarly, another project, 'Military Diversity in Multinational Defence Environments: From Ethnic Intolerance to Inclusion' studied the reasons for intolerance within NATO members’ armed forces as part of an overall strategy to improve diversity and inclusion across the organization..

NATO is examining how AI could affect troops’ ability to conceal themselves and evade detection . Another initiative is investigating how biotechnology could boost soldiers’ performance by enhancing the microbiome or through brain-computer interface technologies.

Why is NATO interested in climate research?

NATO is concerned that c limate change has significant impacts on security . Melting sea ice creates more routes for naval shipping in the Arctic, for example, and NATO and non-NATO countries are increasingly operating in the region.

NATO is also interested in how temperature changes could affect the security of its member and non-member countries as well as of military installations around the world. In a 2024 review paper in the Texas National Security Review , CMRE researchers — along with colleagues from the University of St Andrews, UK, the University of L’Aquila, Italy, and the Swiss Federal Institute of Technology in Zurich — found that submarines could become more difficult to detect using sonar in the North Atlantic Ocean as water temperature rises.

In another study , presented at last week's conference of the European Geosciences Union in Vienna , CMRE researchers working with scientists at the universities of Princeton in New Jersey and Central Florida in Orlando assessed how extreme weather might affect 91 NATO military bases and installations. The researchers found that multiple bases and installations are likely to become susceptible to climate change as emissions continue to rise.

In another project, last year one of NATO’s research vessels moored vertical lines holding oceanographic and acoustic recorders in the Arctic Ocean. The intention was to monitor temperature, salinity and ambient noise throughout the water column. Other research projects are looking at the use of new materials for military clothing in warmer climates, says Wells.

In 2022, NATO also published the first of a series called Climate change and Security Impact Assessment . It is also developing a methodology to map greenhouse-gas emissions from NATO-member military activities and installations.

Personnel from NATO and the Royal Jordanian Navy lower an unmanned undersea vehicle into the Gulf of Aqaba (pictured in 2022). Credit: U.S. Navy photo by Mass Communication Specialist 2nd Class Dawson Roth

How has NATO’s expansion affected science?

NATO’s membership has more than doubled since its founding on 4 April 1949. Finland and Sweden are the latest countries to join. Three more — Bosnia and Herzegovina, Georgia and Ukraine — want to become members.

More members potentially means more funding and support for research and development, as well as access to a bigger pool of scientific expertise. However, Finland and Sweden both participated in NATO’s collaborative research for several years before they joined, says Wells.

Soare says that NATO’s defence science originally focused on aerospace, to help its members catch up after the Soviet Union launched Earth’s first artificial satellites — Sputnik 1 and Sputnik 2 — in 1957. “Throughout the cold war, ensuring air superiority was considered crucial,” she says.

What about a role for science in diplomacy?

In 1958, NATO established research fellowships and projects in what later became its Science for Peace and Security programme, to boost collaboration between nations including the United States and the Soviet Union. “Science provided a path for superpower adversaries to cooperate,” says Paul Arthur Berkman, founder of the Science Diplomacy Center in Falmouth, Massachusetts.

The fellowships and collaborative projects continued to provide a point of contact between NATO and Russia until 2014, when Russia invaded Crimea. That year, Russia, Romania and the United States were jointly developing a system to connect telemedicine capabilities across all three countries to provide medical care in remote and emergency situations. However, the invasion prompted NATO to freeze cooperation with Russia.

Berkman, who in 2010 co-organized and chaired the first dialogue between NATO and Russia regarding environmental security in the Arctic , is concerned at the alliance’s shift away from using science as a “safety valve” in its relations with Russia. He warns that cutting off scientific dialogue with Russia undermines democracy and nations’ ability to tackle global challenges such as climate change.

“Open science is akin to freedom of speech. If we turn off open science, in a sense we’re undermining democracy,” says Berkman.

doi: https://doi.org/10.1038/d41586-024-01052-1

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NYU Named Nature Index “Rising Star” as Research Output Climbs

NYU ranked #8 research institution in North America—up from #25 in 2016—based on increase in articles in top science journals

New York University has been named a Nature Index 2023 Rising Star and is ranked #8 in North America for its growth in research published in the world’s leading science journals.

The Nature Index 2023 Rising Stars list highlights universities, health systems, nonprofits, and other research organizations that have posted the greatest increases—from 2015 to 2022—in authored or co-authored papers appearing in a list of leading journals chosen by an independent group of scientists. NYU was previously named a Nature Index 2016 Rising Star , ranking 25th among institutions in North America at the time.

“Our designation as a Rising Star and top-10 ranking is yet another proof-point  of the growth and momentum of NYU’s research enterprise; the high-caliber and impactful work our researchers undertake each day in their labs; and the University’s increased commitment to science, technology, and the generation of knowledge,” says Stacie Grossman Bloom, NYU’s vice provost for research and chief research officer.  

Examples of research by NYU scientists and NYU Grossman School of Medicine researchers appearing in Nature Index journals in the most recent year measured include:

• A study published in Science revealing the fountain of youth for ants: an insulin-suppressing protein called Imp-L2. The protein blocks the part of the insulin pathway that is responsible for aging in queen ants, providing clues about aging in other species.
• A Nature study demonstrating a new way to self-assemble particles—an advance that offers new promise for building complex and innovative materials at the microscopic level.
• The first-ever rigorous biophysical model of lizard tail autotomy, revealing the mechanism behind how lizards can lose—and later regenerate—their tails to escape predators. The findings are also published in Science .
• A study in Nature Neuroscience showing alternate origins of Alzheimer’s plaques, with neuronal damage taking root inside of cells well before plaques develop, which could explain why drugs to remove amyloid deposits have failed. 
• A discovery published in Nature Communications of the role that specific cells in the nervous system play in migraine pain, providing potential targets for new treatments.
• A study in the Proceedings of the National Academy of Sciences on bias in search engines that finds gender-neutral internet searches yield results that produce male-dominated output, which may promote gender bias and potentially influence hiring decisions.
• Research published in Macromolecules on gel-forming protein molecules, which can inform developing new gel materials for biomedical applications such as tissue engineering and drug delivery.

In addition to strong growth in the volume of articles published in top journals, NYU recently announced record rankings in annual R&D spending —another key measure of a university’s research performance. NYU reached #15 nationally and #7 among private universities, according to the National Science Foundation’s annual HERD rankings, with $1.29 billion in research expenditures for fiscal year 2022. In moving up eight spots in the ranking, NYU had the greatest climb among the top 50 U.S. research universities.

Founded in 1831, NYU is one of the world’s foremost research universities (with more than $1 billion per year in research expenditures, it is ranked seventh among private research universities) and is a member of the selective Association of American Universities. NYU has degree-granting university campuses in New York, Abu Dhabi, and Shanghai and has 13 other global academic sites, including London, Paris, Florence, Tel Aviv, Buenos Aires, and Accra, and US sites in Washington, DC, Los Angeles, CA, and Tulsa, OK. Through its numerous schools and colleges, NYU is a leader in conducting research and providing education in the arts and sciences, law, medicine, business, dentistry, engineering, education, nursing, the cinematic and performing arts, music and studio arts, public service, social work, public health, and professional studies, among other areas.

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Biodiversity is key to the mental health benefits of nature

New research from King's College London has found that spaces with a diverse range of natural features are associated with stronger improvements in our mental wellbeing compared to spaces with less natural diversity.

Published in Scientific Reports and funded by the National Institute for Health and Care Research (NIHR) and Wellcome, this citizen science study used the smartphone application Urban Mind to collect real-time reports on mental wellbeing and natural diversity from nearly 2000 participants.

Researchers found that environments with a larger number of natural features, such as trees, birds, plants and waterways, were associated with greater mental wellbeing than environments with fewer features, and that these benefits can last for up to eight hours.

Further analysis found that nearly a quarter of the positive impact of nature on mental health could be explained by the diversity of features present. These findings highlight that policies and practices that support richness of nature and species are beneficial both for environment and for public mental health.

Lead author Ryan Hammoud, Research Assistant at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, said:

"To our knowledge, this is the first study examining the mental health impact of everyday encounters with different levels of natural diversity in real-life contexts. Our results highlight that by protecting and promoting natural diversity we can maximise the benefits of nature for mental wellbeing. In practice, this means moving away from heavily curated monocultural pockets and parks of mown grass, which are typically associated with low biodiversity, towards spaces which mirror the biodiversity of natural ecosystems. By showing how natural diversity boosts our mental wellbeing, we provide a compelling basis for how to create greener and healthier urban spaces."

The study took place between April 2018 and September 2023, with 1,998 participants completing over 41,000 assessments. Each participant was asked to complete three assessments per day over a period of 14 days, entering information about their environment and answering a series of questions about their mental health. Natural diversity was defined by how many out of four natural features -trees, plants, birds and water -- were present within the participant's surrounding environment.

Data were collected using the Urban Mind app, developed by King's College London, landscape architects J&L Gibbons and arts foundation Nomad Projects. The Urban Mind project is funded by a Wellcome Climate Impacts Award to Professor Andrea Mechelli, the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre and the NIHR Applied Research Collaboration South London.

Senior author Andrea Mechelli, Professor of Early Intervention in Mental Health at the IoPPN, said:

"In the context of climate change, we are witnessing a rapid decline in biodiversity in the UK as well as globally. Our results suggest that biodiversity is critical not only for the health of our natural environments but also for the mental wellbeing of the people who live in these environments. It is time to recognise that biodiversity brings co-benefits for planetary and human health and needs to be considered vital infrastructure within our cities."

'Smartphone-based ecological momentary assessment reveals an incremental association between natural diversity and mental wellbeing' by Hammoud, R. et al. is published in Scientific Reports. DOI : 10.1038/s41598-024-55940-7

• Mental Health
• Child Psychology
• Evolutionary Biology
• Endangered Plants
• Biodiversity
• Rainforests
• Groundwater
• Chloroplast
• Origin of life
• Conservation ethic
• Natural gas
• Conservation biology

Story Source:

Materials provided by King's College London . Note: Content may be edited for style and length.

Journal Reference :

• Ryan Hammoud, Stefania Tognin, Michael Smythe, Johanna Gibbons, Neil Davidson, Ioannis Bakolis, Andrea Mechelli. Smartphone-based ecological momentary assessment reveals an incremental association between natural diversity and mental wellbeing . Scientific Reports , 2024; 14 (1) DOI: 10.1038/s41598-024-55940-7

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