The war in Ukraine has caused severe disruption to national and worldwide food supplies. Ukraine is a major exporter of wheat, maize, and oilseeds, staples that are now suffering a war-triggered supply risk. This paper describes the background of the problem and illustrates current trends by outlining some of the measures that may be deployed to mitigate the conflict’s impacts on achieving SDG 2 (Zero hunger), especially focusing on ending hunger, achieving food security, improving nutrition, and promoting sustainable agriculture. In order to understand the main research strands in the literature that are related to food security in the context of wars, the authors adopted a bibliometric literature review based on the co-occurrence of terms technique, conducted with 631 peer-reviewed documents extracted from the Scopus database. To complement the bibliometric assessment, ten case studies were selected to narrow down the food insecurity aspects caused by the war in Ukraine. The co-occurrence analysis indicated four different thematic clusters. In the next stage, an assessment of the current situation on how war affects food security was carried out for each one of the clusters, and the reasons and possible solutions to food security were identified. Policy recommendations and theoretical implications for food security in the conflict context in Ukraine were also addressed. A situation that exists when all people, at all times, have physical, social and economic access to sufficient, safe and nutritious food that meets their dietary needs and food preferences for an active and healthy life”.The armed conflict in Ukraine poses a considerable challenge to food markets worldwide. On 17 July 2023, the UN Secretary-General, Antonio Guterres, noted the following: “The production and availability of food is being disrupted by conflict, climate change, energy prices and more”. These words show that addressing food security is complicated by conflicts, including active military operations in the territory of Ukraine, climate change, and energy prices [Before 2014, humanity was successfully overcoming the problem of food security in small steps; there has been a continuous decline in food security indicators since then. The impact of the COVID-19 pandemic on food security has also been devastating, with an estimated increase in the number of people suffering from hunger in 2020 equal to the previous five years combined. This means that almost one in three people in the world 2.37 billion) did not have access to adequate food in 2020 [7 billionSince February 2022, the war in Ukraine has caused numerous consequences, including severe stress in food security, with impacts on the national and global levels. The reasons for this severe stress are rising prices and supply chain disruptions . Most imUkraine is among the largest exporting countries of sunflower seeds, oilseeds, rapeseed, corn, and wheat . For exaIn 2021, Ukrainian farmers grew the largest harvest in agri-production history; as a result, the exports to the EU increased by 50%, leaving behind the trade with China and Russia .According to the results from There was a decrease in harvesting for all presented agricultural holdings in 2020 ; howeverThe largest importers of wheat from Ukraine are Egypt, Indonesia, Turkey, Pakistan, Bangladesh, Tunisia, Morocco, Yemen, Lebanon, Philippines .In the first 8 months of 2021, Ukraine exported products of the oil and fat industry that were worth USD 4.1 billion, which is 11% more than in the same period in 2020. This information was provided by the Deputy Minister of Economy of Ukraine, Taras Kachka, in an official announcement on the ministry’s website .Before the war, Ukraine provided 46% of the sunflower oil exports, 9% of wheat exports, 17% of barley exports, and 12% of corn exports to the world markets, according to data from the US Department of Agriculture . DespiteAs of 30 June 2022, the Agricultural Price Index was 34% higher in comparison to January 2021. Maize and wheat prices were 47% and 42% higher, respectively, when compared to January 2021, while rice prices are about 8% lower. According to the World Bank’s April 2022 Commodity Markets Outlook, the war in Ukraine has altered global patterns of trade, production, and consumption of commodities in ways that will keep prices at historically high levels through the end of 2024, exacerbating food insecurity and inflation .Food prices were already high before, and the war is driving food prices even higher . CommodiInternational wheat prices had a steep increase in May 2022 in response to the announcement of a wheat export ban by India. As exports from Ukraine remain hindered by war disruptions, and after India’s larger wheat shipments in recent months played an important role in partially offsetting lost exports from Ukraine, the country’s export restriction exacerbated global availability uncertainty. According to the UN FAO, the disruptions caused by war in Ukraine have raised the average food price index to its highest level ever . Thus, tThe war has significantly disrupted the transport of commodities. Almost all of Ukraine’s grain exports went through Black Sea ports, which were not operational before the “Initiative on the Safe Transportation of Grain and Foodstuffs from Ukrainian ports” was signed in Istanbul, Turkey, on the 22nd of July 2022. It was expected that Ukraine would export up to 20 million tonnes of wheat during the season (summer 2022), which corresponds to about 10% of global wheat exports.However, in 2023, the situation remains critical. According to information from the Ministry of Foreign Affairs of Ukraine, in the first 10 days after the breakdown of the Grain Deal, shelling launched towards Ukrainian territory destroyed 180,000 tonnes of grain and damaged 26 port infrastructure facilities and five civilian vessels [The war will also disrupt agricultural production in Ukraine in the coming seasons. Spring planting for crops such as maize, barley, and sunflowers typically occurs from April to May, while winter wheat is planted from September to mid-November. Shortages of labor and inputs (such as fuel and fertilizers), destruction of farming equipment, and safety concerns of growers will have a severe impact on Ukraine’s agricultural  production. Estimates on how much Ukraine’s agricultural production will decline in the upcoming season vary from 25 to 50 percent .In May 2022, it was estimated that one-third of Ukrainians suffered from food insecurity . AdditioDue to the war in Ukraine, ripple effects have led to record levels of food insecurity. The number of people experiencing acute food insecurity or at high risk as of June 2022 (million) increased by 7.3 in Asia and the Pacific, 6.3 in the Middle East, North Africa, and Eastern Europe, 9.7 in West Africa, 9.6 in Southern Africa, 10.5 in Eastern Africa, and 3.6 in Latin America and the Caribbean [However, in order to meet the current demand for wheat, 25 million tonnes need to be replaced by alternative sources . At COP The FAO’s 2023 report predicts that nearly 600 million people will be chronically undernourished in 2030, indicating a huge gap before the SDG goal of eradicating hunger is met. By comparison, this figure is about 119 million more than in a scenario where there was neither a pandemic nor war in Ukraine, and about 23 million more than if there had been no war in Ukraine .The ongoing fighting in Ukraine could trigger a global food crisis, as 36 of the 55 countries already experiencing a food crisis depend on exports from Ukraine and Russia. Before 2022, both countries produced about 30% of the world’s supply of wheat and barley, a fifth of corn, and more than half of sunflower oil . RoughlyDue to this reliance on exports from both countries, the war in Ukraine is affecting food security globally. The concept of food security encompasses four dimensions: food availability, access, stability, and utilization. The addition of a further dimension to the concept, like sustainability or agency, has been discussed among scholars  and has To conclude, the war in Ukraine has led to severe disruptions in terms of agricultural production . The BlaBased on previous experiences and studies, the war itself can have long-term influences on the physical, chemical, and biological characteristics of soil, and using this land for growing food might potentially lead to health problems . In thisIn order to achieve these goals, the authors opted for a bibliometric analysis of the literature, where a search string was created to understand what scholars have been covering in the field. After a screening process, a total of 635 peer-reviewed papers were selected and used to proceed with the co-occurrence technique. In the second stage, the authors judiciously selected nine case studies to illustrate how the impact of war in Ukraine puts food security in danger on local and global scales. This also allowed us to indicate measures that may be deployed to mitigate the conflict’s impacts on achieving SDG 2 (Zero hunger), with a focus on ending hunger, achieving food security, improving nutrition, and promoting sustainable agriculture.The present research considers a bibliometric analysis and the case study research approach developed from a literature review ,31, as iIn this context, the bibliometric analysis was conducted for specific terms related to war and food security on Scopus, a widely known scientific database of peer-reviewed academic documents containing more than 5000 journals and 24,000 publications. The bibliometric analysis is considered a quantitative computer-assisted review methodology commonly used to identify the main studies, authors, and journals or to understand the bibliometric networks evidencing, for example, the major discussions of a research field ,33.The data collection took place in August 2022, where the documents used to compose the sample were collected through a search string containing terms connected to ‘war’ and food security, such as ‘food’ OR ‘grain’ OR ‘cereal’ OR ‘agriculture’ OR ‘crop*’ OR ‘agricultural’. The search string initially returned 732 documents and, after applying the exclusion criteria, as stated in The investigation was performed using the VOSviewer software , and theIn this sense, the bibliometric analysis becomes relevant for this study for several reasons. For example, the bibliometric analyses based on the co-occurrence of terms could help scientists to identify research trends in a specific field, evidencing its big picture, as well as helping the researcher to map the knowledge of each one of the clusters found in order to delve into a specific area of the studied field. Therefore, the co-occurrence technique could help scientists to reduce the complexity of a field, supporting the conduct of discussions based on how different concepts converge and relate to each other  were identified and used in order to assess the current situation on how war affects food security .C1: The red cluster focuses on the social dimensions of the interlinkage between food security and war. War, as one of the main causes of food insecurity, causes destruction, displacement, control of food, and starvation, which makes governments often unable or reluctant to address food shortages, and instead they try to prevent the exacerbation of the situation . During Moreover, trade wars or international food trade barriers due to political conflicts lead to food insecurity . As a reInternal factors such as economic recession, environmental deterioration, political instability, and inter-ethnic conflicts are other reasons for food insecurity . Famine Suggestions made by authors in this cluster to address food insecurity at a global level include respecting food as a basic human right, merging local capacities , creatinC2: The green cluster emphasizes the nutritional dimension of food security and war, showcasing historical examples.The analysis presented in the paper is closely connected to the historical context and empirical evidence provided in these excerpts, which underscores the critical importance of addressing food security in conflict contexts . These hMoreover, the information regarding the direct and indirect impacts of war on agricultural crop production offers valuable insights into the complexities of the issue . The desFurthermore, the focus on the nutritional deficiency and health consequences of food insecurity during and after wars aligns perfectly with the broader discussion on achieving Sustainable Development Goal 2 (Zero Hunger)  and inteLastly, these insightful excerpts are highly relevant to the paper’s policy recommendations. By highlighting both historical precedents and contemporary evidence of the wide-ranging impacts of food insecurity during conflicts, the paper can make a compelling case for specific policy actions. For instance, it may recommend strategies to protect agricultural infrastructure, mitigate the environmental impact of war, and address nutritional deficiencies among affected populations . In esseC3: The blue cluster represents the complex relationship between agriculture and food production with food availability, and, consequently, their impacts on human health and well-being. Other factors addressed in this cluster are the industrialized world and the impacts of climate change, along with wars, displacement of people, and agricultural land abandonment.Generally, developing countries depend on agriculture as a primary driver of the economy as well as the main provider of nutrition for people. However, when a military conflict takes place in a country, it usually leads to disruption in agricultural production, primarily in lands closest to the war areas . FarmersThere are also the issue that various kinds of weapons used in war zones leave behind the harmful waste of heavy metals or even nuclear waste. This leads to damage such as irreversible pollution. As far as it results in the contamination of food, there is a clear connection to C2 . Moreover, it leads to the destruction of the ecosystem and animal life such as insects, which are important for pollination and crop production in those areas ,59. AlonThe cluster also shows efforts and solutions to agricultural and ecological crises during and after war and emphasizes the importance of thorough research regarding all aspects related to the targeted area, including the geographical, ecological, and ideological factors to provide the ultimate, long-lasting solutions . This coC4: The yellow cluster illustrates the impact of war and political conflict on various aspects of the economy and vice versa and how this shapes the public policies in politics, health, education, and other domains.For instance, it was observed that poverty and low wages in developing countries push farmers and workers in the agricultural field to join the armed conflict due to their constant economic struggle . In addiAnother phenomenon is that the economy and international trade, especially food trade, have been a growing cause of political dispute . A good When a military conflict takes place in the country, multiple factors have to be considered. Therefore, the impact of war on food security in the Ukrainian context would be different compared to other conflict situations in the world. In order to understand the situation of food insecurity aspects caused by the war in Ukraine, an analysis of 10 case studies was conducted. These case studies were selected based on the expert-driven literature review. The results of this study are presented below.CASE STUDY 1: “Impacts of the conflict in Ukraine on global food security” .Short descriptionIn particular, the study examines the possible impact of the war in Ukraine on Ukraine’s production and export of agricultural commodities, especially grains and oilseeds. It also outlines the impact of trade sanctions against Russia on the export of cereals and oilseeds. At the same time, this research investigates the possible impact of higher energy prices on global agricultural production and trade.Implications for Food SecurityThe study concludes that from a food security perspective, there is enough food on the global level. However, higher food prices could become a problem and put food availability under some pressure for a part of the population that has a low income, spends a large part of their income on cereals, and is highly dependent on imports of Ukrainian and Russian cereals . For the EU, food prices rose by 5% for crops and 2% for food; however, given the relatively low proportion of income spent on food, this should not be a problem for the average citizen.CASE STUDY 2: “Implications of the Russia–Ukraine war for global food security” Short descriptionThis research investigates how conflicts can affect the capacity of food systems and supply chains to function appropriately due to production declines , destroyed agricultural yields and water infrastructure, or disruptions in agricultural inputs in the foreign markets, as well as how these can affect the capacity of consumers to access sufficient food because of their declining purchasing power. At the same time, the paper outlines what happens with the capacity of international food aid when trying to meet growing food needs in times of crisis.This study suggests solutions to listed problems, such as establishing an international community strategic food reserve or including new rules in international humanitarian law that provide sufficient protection to food systems-related infrastructures and activities.Implications for Food SecurityAfter a decline during the past decade, global hunger is rising again, and the ongoing war in Ukraine is expected to increase this trend (experts estimate that 7.6 to 13.1 million people are threatened).The reason for this is the volatility of major food commodities and fertilizers, which may affect production decisions and spur speculative behavior. It will affect international society, but countries most dependent on imports of Ukrainian and Russian cereals, such as Egypt, Lebanon, and Tunisia , will be the most impacted by war-related disruptions.This war is also affecting the ability of international agencies to provide food aid to countries that are suffering from famine or other armed conflicts because of rising costs, with the risk of excluding millions of people from current food aid programs.CASE STUDY 3: “Potential medium-term impacts of the Russia-Ukrainian war on the Dutch agriculture and food system: An assessment” Short descriptionThis research assesses the potential impacts of the war in Ukraine on different agricultural sectors in the Netherlands, both with and without taking into account the European Union or national policy response. The focus is on the medium-term impacts (period 2021–2025), considering 2021 as a pre-Ukraine war reference point. In this study, the authors also explore potential impacts on employment. The assessment addresses the impacts on primary production, as well as on upstream and downstream industries. The results show the impact on the Netherlands’ use (including consumption) and on the Dutch agricultural net trade position.Implications for Food SecurityThe impacts found as a result of this research for the different scenarios suggest that the medium-term impact of the Ukraine war on Dutch agriculture is relatively limited . Moreover, energy prices and agricultural commodity prices were already increasing because of other factors .At the same time, the uncertainty with respect to energy prices and energy-related inputs  is likely to be one of the most pronounced impacts of the Ukrainian war on Dutch agriculture in the short to medium term. An energy price increase is likely to have worldwide impacts on agricultural production and consumption and will create a passing on effect on agricultural product prices.CASE STUDY 4: “Quantifying War-Induced Crop Losses in Ukraine in Near Real Time to Strengthen Local and Global Food Security” Short descriptionIn order to estimate the direct and indirect effects of the war and the expected yield of winter crops in Ukraine, a 4-year panel (2019–2022) of 10,125 village councils in Ukraine was used. Satellite imagery  was used to provide information on direct damage to agricultural fields  to classify crop cover using machine learning, and to compute the Normalized Difference Vegetation Index (NDVI) (by sensors Landsat and MODIS) for winter cereal fields as a proxy for yield. This research focuses on the supply side in order to investigate the effects of the war in Ukraine on food security, unlike the other studies that focus rather on the demand.Implications for Food SecurityThe result of this study shows that food production can be analyzed using satellite imagery to generate measures of agricultural production as outcome variables as well as indicators of conflict, considering that causality runs from conflict to food security . Particularly in Ukraine, taking area and yield reduction together suggests a war-induced loss of winter crop output of up to 25% if the current winter crop can be harvested fully. Having this information can help to improve decision making by policymakers and private parties to minimize war-induced losses.CASE STUDY 5: “The conceptual principles of state policy of Ukraine in the field of food security in terms of European integration” Short descriptionThe article (1) examines organizational and economic features (problems) of insufficient food supply in Ukraine; (2) substantiates the structural components of the program of balanced production of food and food raw materials; (3) determines measures of state policy on the food security of the population of Ukraine; (4) develops a methodological approach to substantiation and implementation of state policy on the implementation of the principles of ensuring food safety and quality in Ukraine; (5) substantiates the strategy of ensuring the physical and economic accessibility of food.Implications for Food SecurityAs a result of this research, the structural components of the program of balanced production of food and raw materials were formed . The mechanism of the methodological approach construction is formed on the principle of problems–directions–measures. The proposed strategic tools  enable solutions for the tasks of improving nutrition at the local level and gaining additional positive impact on the formation of a model of sustainable agricultural development, which can influence global food security.CASE STUDY 6: “The reinvasion of Ukraine threatens global food supplies” Short descriptionThis study outlines that the reduction in the vast quantities of edible food that are wasted in rich countries every day, as well as the replacement of animal-based foods with plant-based options, could feed an additional number of people and mitigate climate change. It also questions the existing model of global trade and systems of agricultural production, which is dependent on oil for fertilizers, transport, and agrichemicals; this model encourages the consumption of energy-dense ultra-processed foods.Implications for Food SecurityAccording to this research, the war in Ukraine, together with pre-war factors , caused the already rising global food prices to reach an all-time high. The consequences will be felt by everyone, but some populations are especially vulnerable . There are also many poor people in rich countries who will suffer. Several actions are required in order to combat food insecurity, such as replacing all animal-based foods with plant-based ones, which could feed an additional 350 million people, and changing the existing model of global trade in order to increase food stocks in countries that have disinvested in domestic production in favor of cheaper imports. At the same time, the systems of agricultural production need to be less energy-dense.CASE STUDY 7: “The War in Ukraine, Agricultural Trade and Risks to Global Food Security” .Short descriptionThis research investigates global food supply chains. The war in Ukraine, together with rising prices in late 2021, have affected import-dependent countries in the Middle East and North Africa (MENA) region and sub-Saharan Africa, which rely heavily on Russian and Ukrainian wheat. However, global demand for wheat is expected to be met in the current marketing year (2022/23), since countries such as Australia, Brazil, and the USA will increase exports to fill the gap left by Russia and Ukraine.Implications for Food SecurityAccording to this research, the war in Ukraine increases the risk of food insecurity for import-dependent countries with low per capita incomes. The key to dealing with crises and mitigating the risks of food shortages could be a reduction in bureaucratic and tariff barriers to trade by global supply chain structures. Also, targeted political efforts are needed to ensure that Ukraine and Russia remain integral parts of the world agricultural trading system. On the other hand, transitions to (more) closed food economies are not advisable, as this would remove players from international markets, could lead to food shortages in many countries, and might take focus away from environmental and health-related issues.CASE STUDY 8: “We need a food system transformation—In the face of the Russia-Ukraine war, now more than ever” .Short descriptionThis paper discusses moving towards changes in global food consumption habits and the food supply chain. The research shows how transformation towards a healthy, fair, and environmentally friendly food system reinforcement can bring short-term relief and avert the existential threat our food system poses to the health of people and the planet. It confirms that the need for sustainable solutions is still present while facing the Russia–Ukraine war.Implications for Food SecurityThe authors of this study suggest that global food insecurity has its origin not in a shortage of supply but in high economic inequalities and maldistribution. Even though global food production is more than sufficient to feed an even higher world population, it is not supplied to those with limited financial means. This paper proposes three levers for solving short-term problems and long-term sustainable development: 1. Accelerate the shift toward healthier diets with fewer animal products in Europe. 2. Increase the production of legumes and strengthen Farm2Fork. 3. Reduce the amount of food waste. “Farm to Fork” is, namely a scheme led by the European Union, to promote the sustainability of farming processes, i.e., from production (the farm) until it reaches the plate of the end-consumer (the fork).CASE STUDY 9: “What the war in Ukraine means for energy, climate and food” .Short descriptionThis paper shows how war in Ukraine influenced the markets and geopolitics of energy, oil, and gas prices and the reconsideration of countries’ energy supplies. Particularly, it outlines the possibility of rising energy prices and the potential loss of grain supplies from Ukraine and Russia to reinforce inflationary effects and drive up prices for food and other commodities.Implications for Food SecurityAccording to Christopher Barrett, in the short term, the prices of wheat and other grains have increased due to hoarding and bidding wars. But global food stocks are sufficient to cover the loss. Even though there could be disruptions to fertilizer markets because fossil fuels are a major feedstock, the effect should be mitigated by substitutes. However, the cost of rising petrol and electricity prices to the larger food supply system could be substantial. As a result, some of the greatest casualties of the war in Ukraine will be people who are already severely struggling in other places .CASE STUDY 10: “Caught off guard and beaten: The Ukraine war and food security in the Middle East” .Short descriptionThe study provides a detailed analysis of the food-related vulnerability of the Middle East  in the wake of the Ukraine war. It shows the varying impacts of it, including a deepened food sector crisis, worsened by political–economic instabilities, limited domestic agriculture, and the lack of reliable grain reserves. At the same time, the paper highlights country-level response strategies related to regional aid and cooperation that have emerged in the Gulf countries.Implications for Food SecurityThe author of this study outlined that the war in Ukraine is hitting the Middle East very hard due to the relatively high dependence levels and the baseline political, economic, and environmental vulnerabilities. For example, around 80% of the 30 million Yemeni population is dependent on aid. At the same time, countries having significant storage capacity and available reserves were better able to avoid or delay shortfalls or price hikes despite high dependence . As a short-term solution, food subsidy systems for the most vulnerable have softened some of the impacts of the price hikes. In oil- and/or gas-exporting countries, the increase in carbon fuel prices after the war in Ukraine meant that additional revenues could be used in the mitigation of the food crisis . At the same time, environmental vulnerabilities can weaken the ability of local agriculture to provide food. As a result, many Middle East countries, especially with political–economic instability , will be relying on international cooperation in the short and medium term, including shipments under the Black Sea Grain Initiative.It should be noted that the case studies illustrate a variety of situations and contexts where food security is endangered because of the ongoing war in Ukraine or is avoided due to various means used to achieve it. These are summarized in According to the results obtained by the analyses of a set of 10 case studies, the war in Ukraine can affect food security due to many reasons. Among them are production declines , destroyed agricultural yields and water infrastructure, and agricultural inputs disrupted in foreign markets. The conflict is also affecting the ability of international agencies to provide food aid to countries that are suffering from famine or other armed conflicts . An enerDespite the assumption that there is enough food on the global level, higher food prices could become a problem and put food availability under some pressure for the part of the population that has a low income, spends a large part of their food on cereals, and is highly dependent on imports of Ukrainian and Russian cereals  ,70,74,77Based on the research, solutions to the listed problems can be suggested. One such solution is an improvement in decision making by policymakers and private parties to minimize war-induced losses by forecasting food production using satellite imagery . CarefulThe author of  argued tThe case studies’ results complement the findings from the bibliometric analysis, evidencing that those aspects such as food security and government, nutrition and war, food safety and health, and economics and public policies can also be found in the context of the war in Ukraine.At the same time, the results provide a better understanding of the fact that the war in Ukraine also unleashed a new type of complex global food crisis with supply interruptions and rising costs of key agricultural inputs such as fuel, transport, and fertilizers. The results indicate that this war is not only generating food insecurity in Ukraine, but also globally, due to the shortage in grain production and supply and the higher prices.This study aimed to explore the extent of the food insecurity problem due to the war in Ukraine by unveiling the research streams in which scholars have been conducting research related to the impact of war on food security aspects. Ten case studies that directly tackle the food security problem in the context of the war in Ukraine helped to reveal relevant secondary data that could support the bibliometric exploration, which could further contribute to policymaking.The results from the bibliometric analysis indicate the existence of at least four main thematic clusters that scholars are covering on the food security aspects in the general war context (not only in Ukraine): food security and government aspects (C1), human history, nutrition, and war (C2), agriculture, food safety, and health (C3), and economics and public policies (C4). The case studies complement the findings in these clusters, evidencing that these aspects can also be found in the context of the war in Ukraine, which is further evidenced by the secondary data gathered.This study also has implications that the authors agree upon for their relevance for policy making. Firstly, the results indicate that the war is not solely generating food insecurity in Ukraine, but also globally, due to the shortage in grain production and the higher prices. Secondly, it has been evidenced that the war could compromise the capacity of food systems and supply chains. This could reduce the capacity of consumers to have access to sufficient amounts of food and important micronutrients, which could lead to malnutrition. Moreover, the shortage of food production can also be a consequence of the reduced import or production of fertilizers and agrichemicals. Finally, the situation unveiled the necessity of consistent food policies to tackle the situation on a local and global scale, especially related to the necessity of sustainable food systems in order to guarantee the health of people and the planet.This study has limitations which could be related to the methods deployed. The bibliometric analysis based on the co-occurrence analysis operates under the assumption that the mere frequency of term co-occurrence signifies strong conceptual relationships, disregarding potential nuances in contextual meaning. Additionally, the quality and comprehensiveness of the data sources can impact the accuracy of results, potentially introducing biases or incomplete insights. The subjectivity involved in term selection and the dynamic nature of language further add complexities to the interpretation. Also, reliance on 10 expert-selected case studies may limit the generalizability of findings and introduce selection bias, potentially impacting the broader applicability and representativeness of conclusions. The authors believe, however, that these limitations could bring relevant ideas for future studies.Firstly, the authors believe that gathering qualitative data through interviews with relevant stakeholders could contribute to elaborating the policymaking aspects previously suggested. In addition, a deep understanding of the reality of farmers in Ukraine and an exploration of their necessities could help the Ukrainian government to formulate specific policies to alleviate the problems related to food production and the food supply chain. Thirdly, an assessment conducted by the Ukrainian government to understand the health conditions of the Ukrainian citizens can help find those who need urgent support in terms of malnutrition, whether it involves the daily amount of food consumed or the important micronutrients. Fourthly, the authors believe that future research could seek to understand the current policies in place and find relevant gaps that have not been tracked by Ukrainian and European Union authorities in order to guarantee the proper functioning of food systems and the health of the planet and population at the same time.


Painful postsurgical neuropathy is an adverse event inherent to a wide variety of surgical treatments, so its diagnosis and specialized treatment are essential to maintaining the quality of life of the people who suffer from it. We present the case of a 31-year-old male with neuropathy of the genitofemoral nerve diagnosed by electromyography, resulting in intractable left testicular and thigh pain associated with a recent history of ipsilateral inguinal hernioplasty. After assessment by pain medicine and motor and sensory tests, a neurostimulator was placed in T8-T9 with action at the L1-L2 level, as well as a simultaneous electrode in S3, generating optimal pain relief and recovery of functionality. Painful postsurgical neuropathies are an infrequent but potentially devastating complication of a large number of surgical procedures and may be due to direct injury to a peripheral nerve or complex inflammatory processes. The perioperative causes, including anesthesia, traction, compression, and transection, are mechanisms where nerve damage can result in neuropathic pain that can evolve and become chronic, often being refractory to most conservative treatments and promoting excessive and ineffective consumption of painkillers. Considering the opioid epidemic, it is essential that all patients who present with postsurgical pain for more than three months be referred for a specialized evaluation by pain medicine . In obseNeurostimulation modalities arose as a response to modulate the pain impulses provoked in the periphery, which are carried by C fibers and A-delta fibers, interrupting them by stimulating larger A-beta fibers at the common nerve synapse location in the substantia gelatinosa of the dorsal horn . In thisA previously healthy 31-year-old man arrived at the emergency room with a seven-day history of left scrotal and upper ipsilateral thigh pain, arising rapidly and progressively after the surgical approach of a right inguinal hernia. He experienced continuous pain that limited the optimal performance of the activities of daily life, significantly affected his quality of sleep, and diminished the enjoyment of his sexuality due to the exacerbation of pain.Previously, the patient with no significant medical history attended a urological evaluation for experiencing intermittent and oppressive pain in the left testicle for five months; a bilateral direct inguinal hernia was diagnosed through physical examination and ultrasound. An uneventful bilateral laparoscopic hernioplasty was performed, and he was discharged home after the procedure. After a partial improvement in pain with the use of non-steroidal anti-inflammatory drugs, it began to progress rapidly until it became incapacitating, and the patient was taken to the emergency room, where he was evaluated by pain Medicine.After a detailed clinical evaluation by a specialist in algology, the diagnosis of intractable pain associated with L2-L3 radiculopathy and post-surgical neuropathy of the genitofemoral nerve was concluded. The severity of the pain and the response to pharmacological treatments based on pregabalin, opioids, and other analgesics were evaluated, concluding that the pain was refractory to medication. Given this, the placement of differential target multiplexed spinal cord stimulation therapy (Medtronic) was decided for treatment. To determine the effectiveness of the proposed approach, a sensory-motor test with electrostimulation was performed in the fluoroscopy room under sedation and with a sterile technique in a prone position with local anesthesia at the incision sites. An electrode guide was placed at L1-L2 level to be able to position the electrode at the epidural space of T8-T9 level and perform the electrostimulation test, which was positive for groin and anterior thigh pain but not for testis. Subsequently, from a lateral approach, the neurostimulator electrode was inserted to be fixed at the S3 level , like in this neuropathy of the genitofemoral nerve after inguinal hernioplasty. However, the potential for neurological damage to sensory and motor nerves is an inherent risk in any surgical procedure , so it mSurgical adverse events, such as peripheral nerve injury, are an imminent risk due to the nature of this type of treatment, which generally offers greater gains. However, it is essential to have the largest possible arsenal of minimally invasive interventions in algology and pain medicine in order to offer the best possible relief and recovery of function. Neurostimulation has proven to be a customizable tool according to the individual characteristics of each patient and their clinical presentation, so its mastery by specialized pain centers represents a solution for chronic pain, a global public health problem. Additionally, the reincorporation of his sleep and mental health quality, as well as his previous sexual life, confirms the importance of the negative biopsychosocial impact that an inefficient approach to pain has.


Cleft lip and/or palate includes a spectrum of congenital disorders affecting union on the lip, alveolus, hard and/or soft palate. The management of children born with an orofacial cleft requires a complex process from a multidisciplinary team (MDT) to restore form and function. Since the Clinical Standards Advisory Group (CSAG) report in 1998, the UK has reformed and restructured cleft services to improve the outcomes for children born with a cleft.The spectrum of cleft conditions, the members of the MDT and a chronological description of the stages of cleft management from diagnosis to adulthood are described using a clinical example. This paper forms the introduction to a series of more detailed papers which span all major aspects of cleft management. The papers will cover the following topics: dental anomalies; associated medical conditions among children; orthodontic management of patients; speech assessment and intervention; role of the clinical psychologist; challenges for the paediatric dentist; genetics and orofacial clefts; surgery - primary and secondary; restorative dentistry; and global perspectives. Presents an introduction to cleft lip and/or palate.Provides an introduction to the multidisciplinary cleft team.Gives an overview of stages for cleft management from diagnosis to adulthood. A cleft lip can be either unilateral or bilateral with varying degrees of completeness, with some children also having a cleft of the alveolus and palate. An isolated cleft of the palate is distinct from a cleft of the lip and palate and can involve only the soft palate or include the hard and soft palate up to the incisive foramen. The mildest subtype of cleft palate is known as a submucous cleft palate, where the underlying muscular anatomy is deficient in the midline; however, the mucosa remains intact and can be termed a 'hidden cleft'.1,2 The 15-month CSAG study was accepted by the UK government in 1998 and recommended 8-15 multidisciplinary cleft centres nationally, in a process often referred to as 'centralisation'. Three years later, nine cleft services were set up. Within each service, there may be more than one cleft unit (or centre) staffed by the cleft MDTs . Prior to the Clinical Standards Advisory Group (CSAG) report in 1998, there were 57 UK centres treating cleft patients; treatment was inconsistent and clinical outcomes were poor.eft MDTs .Fig. 1 Min utero to adulthood. The majority of interactions with the cleft MDT occur early in the child's life; as the child matures, the routine planned appointments reduce in frequency, unless there are any issues requiring active management and input from any of the MDT members.This series of papers aims to provide a dentally relevant understanding and overview of the management of children born with an orofacial cleft in the UK. This first paper outlines the journey that a child born with a cleft will follow throughout their life, from antenatal diagnosis The papers that follow in this series will focus on various aspects of the MDT and provide an overview of the management focus and input required by each subspeciality to obtain the best outcome for these children.3 Detection of a cleft lip is one of the 11 conditions specifically checked for during the NHS foetal anomaly scan between 18-21 weeks of gestation. As this scan produces a 2D image, it is virtually impossible to determine if the palate is intact, and some centres will offer a magnetic resonance imaging scan to assess the palate in more detail. Following an antenatal diagnosis, the cleft clinical nurse specialist (CNS) will make contact with the parent(s) within 24 hours and will provide much needed support and counselling in preparation for the birth of their baby. They will remain as a key contact for the parent(s) throughout the remainder of the pregnancy and until the birth of the baby and beyond.Approximately 81% of babies with a cleft lip are diagnosed antenatally.4 The presence of a cleft affecting both the lip and palate means the baby is unable to generate sufficient oral pressure to enable suction from either a nipple or the teat of a bottle. Commonly, special feedings bottles are required, including bottles which allow the parent(s) to 'squeeze' and simulate the suction for the baby. This requires training to ensure the 'squeeze' is timed simultaneously with the baby attempting to suck.Following birth, the CNS will visit the family within 24 hours, which may be while they are still in hospital or following discharge home. The CNS has a key role in supporting parents, particularly with feeding in the early days, which is considered to be one of the major concerns for parents.5,6The parent(s) and the baby will meet the cleft surgeon, along with other members of the MDT, during the first outpatient appointment. For a child with a UCLP, the first surgical procedure is the lip repair, which is typically completed at between the age of 3-6 months. The hard palate will also be repaired at this time, but the alveolar cleft is typically left until a later age to preserve facial growth.7The remainder of the palate will be repaired between 9-13 months of age. The aim of the palate repair is to provide an intact palate with normal velopharyngeal function to enable speech development.8These early years following palate repair are critical for speech development and the child will be monitored closely by the cleft team, particularly the cleft specialist speech therapists. At 18 months, and again at three years, the child will have a speech assessment; the exact timing will depend on the number of words the child has developed to ensure an adequate speech sample can be obtained. The aim is to ensure the child has normal speech before starting school. In approximately one-third of patients, a second procedure may be required to improve speech.9 and other abnormalities, including hypodontia (up to 70%)10 and enamel hypoplasia, which may require treatment.11Access to advice from a paediatric dentist is available as the deciduous teeth begin to erupt. The role of the general dentist also begins at this early stage and the importance of dental hygiene cannot be overstated. Patients with a cleft have a higher rate of dental caries At the age of five, the child will attend the cleft unit for the first of up to four audit clinics. At this visit, the child is assessed by dental and orthodontic teams, audiology, psychology, clinical photography, and speech and language therapy. The primary aim of the visit is to identify any arising problems but also to record a series of metrics for the national Cleft Registry and Audit NEtwork (CRANE) database (see CRANE section below).7A decision is also made at this time if any orthodontic work is required to enable access to the alveolar cleft, for example, arch expansion. The ABG will stabilise the anterior maxilla and provide bony support for the permanent dentition, as well as for future orthodontic appliances. In the UK, the timing of the ABG is based on dental development, with the aim of performing the bone graft before the permanent canine erupts.6As the child's permanent dentition starts to erupt, this period is important for their dentoalveolar development. Children with a complete cleft lip and palate need to be assessed by the cleft surgeon, orthodontist and dentist to start planning their alveolar bone graft (ABG). A panoramic radiograph (orthopantomagram) and an upper occlusal x-ray are both taken to assess the alveolar cleft, as well as the dental development and the presence of any supernumerary teeth (present in to to 35% of cases) that may require removal pre-operatively.9 which allocates a patient-reported score to aspects of appearance, health and quality of life. The results of these PROMs can be compared to means for that cleft phenotype and thus tailor the clinical consultation. An example of a radar plot is shown in The second of the four audit clinics occurs at age 10 and follows the same format as the age five audit clinic. By this stage, the ABG should have been performed. Several cleft centres make use of patient-reported outcome measures (PROMs). One example is the CLEFT-Q questionnaireThe majority of cleft patients will require orthodontics in adolescence, which may include exposing and bonding unerupted canines to assist with their eruption into the ABG site. Specialist restorative dental input may also be required for replacement of missing teeth or reshaping of misshapen teeth, for example, disguising canines as lateral incisors.12The third audit clinic occurs at age 15. It is designed to identify any issues that may need to be managed as the patient is nearing the end of growth. This may include the need for orthognathic surgery, or if there are any functional or aesthetic concerns which necessitate surgical revision of the lip, or a cleft septorhinoplasty.Patients with UCLP may develop a Class III skeletal relationship. This is thought to be due to a combination of maxillary hypoplasia secondary to the cleft itself, as well as the impact of surgical repair and scarring during growth. If this is mild, it may be managed by orthodontics alone; however, some patients with a more severe occlusal abnormality may require orthognathic surgery. This may involve advancement of the maxilla alone, or in those with larger discrepancies, a mandibular setback may also be required to align the top and bottom jaws. As with all major decisions along the pathway, the psychologist will work closely with the patient to assist in the decision-making process.A final audit clinic is conducted around the age of 20 years. If there are no ongoing issues or concerns that require active input from the cleft team, then the patient can be discharged from the cleft service at this point.13 as previous treatments begin to fail, or it may involve genetic counselling as the patient begins to consider having their own family.After being discharged from the cleft pathway, adults may return to any of the cleft MDT teams at any stage if any concerns arise. This may focus on specialist restorative dental careCRANE is a database, set up in 2000, which collects information about children born with a cleft lip and palate in England, Wales and Northern Ireland. Scotland has also recently started submitting data to CRANE. It has two core aims: 1) to collect birth, demographic and epidemiological information on all children born in England, Wales and Northern Ireland with a cleft lip and/or palate; and 2) to collect information on the treatment of children with a cleft lip and/or palate and the outcome of these interventions. The data recorded in the database is collected by the local cleft teams during treatment and from five-yearly audits of each patient. CRANE produces annual reports and is involved in research, commissioning services with the aim of improving the care of patients with cleft.14 Key performance indicators, such as timing of palate repair (by 13 months), are compared against established benchmarks and outcomes, and are compared against the national average. The policy aims to identify situations where centres are between two and three standard deviations below the national average  or more than three standard deviations below the national average . Where outliers are identified, there are robust processes for investigation and quality improvement to ensure services are improved. This remains true for units that are identified as positive outliers where key learning points can be gleaned from their success.The CRANE outlier policy facilitates monitoring of each cleft centre's performance indicators.http://www.bristol.ac.uk/dental/cleft-collective/). Including family members, the study has collected data on over 10,000 participants. Another study, Cleft Care UK, which is closed for recruitment, was a cross-sectional study conducted in 2015, which aimed to investigate the effects of centralisation 15 years after the CSAG report. This study reported its finding across different outcomes,15,16,17,18,19,20showing an overall improvement in surgical, occlusal, speech and language, facial proportions and psychological outcomes, but no improvement in dental and hearing outcomes.The UK hosts the largest prospective longitudinal cohort of cleft patients. The Cleft Collective, which continues to recruit, involves over 3,500 children with orofacial clefts and includes biological samples, and phenotypic, clinical and genetic data (Patients born with cleft lip and palate are managed by an MDT approach that involves a wide range of health care professionals. Each patient journey is unique but there are phases common to many patients with the same cleft phenotype. The burden of care for both patients and their families is high, but the treatment outcomes can be lifechanging. Dentistry is key to many aspects of cleft care, and specialist and general dentists alike will often be involved with the ongoing management of cleft patients throughout their professional career.


One of the strategic goals of the European Medicines Agency (EMA) and the European Medicines Regulatory Network is to support the research and uptake of innovative methods and technologies in the development of medicines. To promote this goal, EMA drew up a list of enabling technologies (ETs), which are novel and fast-growing technologies that have the potential to enable innovation and therefore exert considerable impact on drug development. In this work, enabling technologies identified by the EMA are analysed to measure their impact on drug development by following their journey from publications through early regulatory interactions to clinical trials between 2019 and 2022. This work also reviews the current list of EMA-identified ETs by scrutinising previously unseen innovative technologies identified in EMA submissions data. The analysis shows large variations in the appearance of the various innovative technologies in the different studied data sources, which provided valuable insights into the “Journey of Innovation” that innovative technologies undergo. Several emerging technologies were identified and endorsed for inclusion in the enabling technologies list, whereas some others already on the list were proposed to be excluded due to their low appearance in regulatory interactions as well as clinical trials and publications. Overall, this analysis highlights the relevance and value of continuously scanning and monitoring enabling technologies, supporting Europe’s goal to remain a leader in research and development of innovative technologies, methods, and methodologies relevant to drug development. One of the strategic goals of the European Medicines Agency (EMA) and the European Medicines Regulatory Network is to foster research and the uptake of innovative methods in the development of medicines, as set out in the “Regulatory Science Strategy to 2025”  and the ETs are defined as novel and fast-growing technologies that have the potential to enable innovation and therefore exert considerable impact on drug development , 7. ETs An example of ETs is artificial intelligence (AI), which, in the context of health, can be used to analyse large amounts of data and identify relevant patterns efficiently. AI tools can be utilised in many ways in drug research, discovery and development , 9. For The European Medicines Agency drew up a list of ETs  in 2016,The tracking of ETs in regulatory interactions, clinical trials and publications, and the exploration of the collected data is highly valuable as it supports the continuous future-proofing of the Agency. By analysing the information on ETs, science and technology trends in innovative drug development can be detected early on, allowing the Agency to focus on relevant, most promising developments.Given its relevance, it is critical that the list of ETs is up-to-date. The field of drug development is rapidly changing, and the emergence of novel ETs is continuously ongoing. Additionally, the development and adoption of novel technologies in the pharmaceutical industry in Europe are progressing at different speeds across the various stakeholders in the field  driven by a whole set of changing priorities, challenges, and use cases. For instance, this process has been impacted by the COVID-19 pandemic, resulting in the expedited development and adoption of some innovative technologies, like mRNA-based vaccines and digital technologies . These fThe aim of this work was two-fold: on the one hand, it was aimed to measure the impact of the identified ETs by following and analysing their route  from publications through early interactions with EMA to clinical trials (CTs). On the other hand, this work also aimed to review and suggest an update to the current list of ETs with previously unseen innovative technologies identified during the data analysis to further strengthen the support of EMA for the development of innovative technologies, methods, and methodologies.Scientific publications related to the various ETs were searched in the PubMed databases first without any restrictions, using different search terms for each ET. As these searches resulted in a very large number of hits , the results were limited by using the PubMed Advanced Search Builder applying the following methods:Searches were restricted to publications with a publication date between 2019 and 2022.Searches were restricted to publications in English language.Searches were narrowed down by using a combination of more specific search terms (limiting them to titles and abstracts) and MeSH terms or Major MeSH terms.The aim was to try to capture the widest possible range of publications related to a specific ET, including basic science publications, as eventually the results basic science might also be used in drug development.The accuracy of the searches was evaluated by screening the first approx. 20–50 hits received after a search. The search terms were attempted to be modified in a way thatThe search terms would be broad enough to minimise the risk of losing relevant publicationsThe results would include only a small percentage of irrelevant publications.The list of search terms and the number of hits can be found in In one case (ET: “Mobile/portable manufacturing”), no hits were returned after the search despite using various search terms. To validate this, a more generic search engine (Google) was also used.Requests with associated ETs received by the various EMA procedures [ITF and other EMA procedures ] between 2019 and 2022 were collected from EMA databases (ITF and IRIS databases). The ITF database collects the information submitted in the “ITF meeting request form” by the applicants to the Agency  are associated to enabling technologies by referential terms associations. In both databases, products/developments can have multiple ETs associated to them. The ITF requests and RPIs associated to certain enabling technologies were listed and the occurrence of each enabling technology was counted. Applications without any selected ETs or with “Other innovation aspect / enabling technology” selected were collected and inspected individually to identify the associated –potentially novel –ETs.ClinicalTrials.gov database using the expert search function. Post-marketing surveillance trials (Phase 4) were excluded from the searches. The first 20–30 search results were inspected, and the search terms were modified similarly to the PubMed searches to maximise search accuracy.All clinical trial searches were carried out in the The list of search terms and the number of hits can be found in ClinicalTrials.gov database is to report summary information about clinical study protocols and results. The database was not set up to record information related to technologies and this might lead to underreporting of enabling technology use in clinical trials.The main aim of the Interestingly, search for Mobile/portable manufacturing resulted in 0 hits. To “validate” this result, an additional Google search was carried out. The first 10 results in Google concerned a portable pharmaceutical manufacturing system development at MIT in 2016 and the Portable Continuous Miniature Modular (PCMM) manufacturing platform developed by Pfizer in 2015. Only one of the top 20 results was more recent than these: a small-scale rapid mobile manufacturing platform by Moderna from 2020 .Biodefense/biowarfare, Medicines for tropical diseases, Other smart/advanced material, and Photodynamic product were found to be the least often selected ETs by developers in both ITF and other EMA applications.Some differences were also observed in the data: only 5% of the ITF applications were related to genetically modified organism(s), whereas it was the most frequently referenced category (13% of the requests) in the other EMA datasets. Moreover, digital healthcare and novel biomarkers, omics were amongst the most selected categories (around 8–9%) amongst the ITF applicants. In contrast, only 3–4% of the applicants to other EMA procedures referenced the same categories.in-vitro diagnostics. Other notable themes identified in these 39 requests were artificial intelligence/machine learning, platform technologies, faecal microbiota transplantation (FMT), exosomes, and developments related to special populations, amongst others.As it can be seen in The table below  gives inIt is to be noted that no clinical trials were found to be associated with manufacturing-related ETs , except for 3D printing, which had 9 associated clinical trials.Several ETs had very low appearances across the different data sources. Such ETs included biodefense/biowarfare, Avatar, nude and humanised mice, Bioenhancer, Pharmacological chaperone, Photodynamic product, Printing, and Mobile/portable manufacturing.The European Pharma Strategy highlights that in order to guarantee that high-quality and safe medicines reach patients it is crucial that the European regulatory environment understands and facilitates innovation . SupportThe EMA list of identified enabling technologies has been used by the Innovation Task Force for more than 5 years and more recently, by other EMA procedures, including Scientific Advice, Orphan Designation, Qualification of Novel Methodologies, and Business Pipeline Meetings. In this work, data accumulated over the past 3 years on ETs identified by the EMA was analysed to measure their impact on drug development by following their journey from publications through early regulatory interactions to clinical trials. This study also reviewed the current list of ETs by scrutinising previously unseen innovative technologies identified in EMA submissions data.We identified differences when analysing the appearance of ETs in different data sources over the studied time period . A reasoDigital healthcare has been frequently identified in all studied data sources, including EMA procedures, publications and clinical trials . There iThe lack of clinical trials associated with manufacturing-related ETs could be due to the fact that manufacturing-related ETs are not relevant for clinical trials. In fact, an ET is an attribute of a product, not necessarily of a clinical trial or an EMA submission. An ET associated to a product may be relevant for some but not all CTs carried out with the product.in-vitro diagnostics (IVD)-related requests could be linked to the use of sensors like glucometers or wearable activity trackers or eDiaries, which are decentralised clinical trial enablers. In addition, there are two new EU legislations in this area  and rea (MDR  and IVDRrea (MDR ), which Analysis of EMA procedures without ETs flagged or the category “Other innovation aspect / enabling technology” offered insights into what terms or categories might be missing from the current ETs list. Newly identified technologies/methods/methodologies and treatment mondalities included artificial intelligence and machine learning, manufacturing platform technologies, faecal microbiota transplantation (FMT), developments related to special populations, e.g., pregnant women, a novel environmental monitoring technology, and exosomes. Several of these technologies are described below. It should be noted that applicants may not always choose sufficient or correct ETs when submitting applications, which could be mitigated by adding more detailed instructions to the application forms to help applicants choose the most suitable ET.Artificial Intelligence and Machine Learning were amongst the new ETs, and their appearance is in line with the general trend of increasing application of AI technologies in medicines development . As thesA notable theme identified in the uncategorised requests was related to platform technologies. One of the main characteristics of platform technologies is flexibility, which makes them well suited to fight against novel pathogens or diseases that are sporadic or unpredictable. In 2016, following a public consultation, the World Health Organisation (WHO) presented six promising platforms to increase R&D preparedness for future epidemics . It is eClostridium difficile infections compared to traditional antibiotic therapy. Research and development of FMT-based products have advanced in recent years worldwide. A recent EU-Innovation Network Horizon Scanning report on FMT anticipates further developments in the field, with potential Marketing Authorisation Applications happening in the EU within the next 5–10 years  in Japan, in collaboration with the International Coalition of Medicines Regulatory Authorities (ICMRA), is developing a “regulatory points to consider” document to address the open questions in the field .in-vitro diagnostics and artificial intelligence/machine learning, which were associated with a large number of requests, the other technologies  appeared in a small number of EMA submissions /new ET). Therefore, these terms could be considered weak signals and have to be tracked to evaluate if a new ET should be added to the list.Except for medical devices/In summary, this work explored the presence of ETs in EMA submissions, analysing their relevance with respect to publications and clinical trials. This provided valuable insight into the “Journey of Innovation and Trends” from publications over early interactions with the Regulator to clinical trials. This work also reviewed the current list of EMA ETs and by scrutinising EMA data submissions, previously unseen innovative technologies were identified, resulting in the following recommendations:Analysis of “Other innovation aspect / enabling technology” category in ITF resulted in suggestions for new ET terms, e.g., MDs/IVDs, artificial intelligence/machine learning. Potential future ETs could include platform technologies, FMT, and exosomes.The enabling technologies related to Digital healthcare  could be reviewed and subdivided into more granular terms.Some of the enabling technologies had very low appearances across the studied data sources; therefore, the need for their continued availability in the list should be reassessed .A mechanism for systematically updating the ETs list in a quantitative way .The design of the current analysis is subject to limitations that could be addressed in future research. This cross-sectional study of ETs in EMA submissions, publications and clinical trials looked at a 3-year long time period. A longitudinal review could be carried out, including the interpretation of the time between the identification of the same ET in the different sources, which would allow for the charting of the journey of certain ETs from basic science to their use in regulatory contexts. A more progressive/sensitive methodology could also be considered involving the analysis of patents, venture capital investments, and more dynamic data sources , and social media . Additionally, the examination of the historical events, policies, and regulations that have shaped the development of an ET can provide a deeper understanding of its evolution. The EMA and the members of the EMRN are digital-driven medicines regulators that continuously take advantage of innovations and emerging technologies for the ultimate benefit of public and animal health, and therefore the exploration of machine learning methodologies, e.g., text mining algorithms for the identification of novel ETs in regulatory and public data would also be of high interest.The original contributions presented in the study are included in the article/PV, FE, and AH contributed to the conception and design of the study. PV performed the research and analysed the data. PV and FE wrote the first draft of the manuscript. All authors contributed to the critical revision of the manuscript, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In recent years, great interest has arisen in the study of compounds with antioxidant activity present in agri-food residues. The growing demand from consumers for antioxidants of natural origin, the continuous growth in the world population and the consequent increase in the amount of food residues generated have greatly promoted this field of research. The search for new uses and applications for all this waste has become a mandatory objective within the framework of global environmental management. But, in addition, it offers a promising opportunity to study the great diversity of bioactive compounds that exist in nature and to analyze their biological activity and the associated health benefits. Among agri-food waste, fruit and vegetable by-products constitute a truly abundant and affordable source of natural antioxidants, such as phenolic compounds. These antioxidant phytochemicals are of great interest for different economic sectors, such as food, pharmaceutical and nutraceutical, the latter having seen an exponential development in recent years .However, although antioxidant compounds are widespread in the plant kingdom, their concentrations are usually low. For this reason, it is very important to select those raw materials with the highest phytochemical content and those extraction methods that maximize recoveries, with low cost and low environmental impact . In the Focusing on the use of these antioxidant compounds in the food industry, it is necessary to know their behavior when they are added to a food that can undergo further processing or conservation treatments, since these treatments can alter their composition and quantity ,7. It isThis Special Issue includes six original research articles and two review articles that delve into different novel aspects of the extraction, bioaccesibility and use of bioactive phytochemicals present in fruit and vegetable waste. For instance, in the first original article, Ben Abdallah et al.  extracteButyrivibrio, Phascolarctobacterium, Dialister). The results from these researchers suggest that the chemical and structural changes induced by dehydration treatments have an important influence beyond the extraction of bioactives from the raw material, since they also affect the interaction of digestive and microbial enzymes with this material. In the work of Duarte et al. , the potDíaz-Ramírez et al.  contribuRosa canina rosehips was studied at all stages of in vitro digestion, including the fermentative stage in the colon. The phenolic content and the antioxidant capacity of rosehip extracts significantly changed in the different digestion stages, probably due to the transformations that these phytochemicals can undergo and to the release of matrix-bound compounds during in vitro digestion. Flavonols and flavan-3-ols were highly bioaccessible and, therefore, they could easily exert their biological activity in the organism, while most phenolic acids were poorly bioaccessible and, thus, with much more limited biological effects. Finally, this original article pointed out the importance of analyzing the stability and bioaccessibility of phenolic compounds during the digestive process, in addition to their antioxidant capacity. Flavonoid glycosides showed lower antioxidant activity than aglycones, but their higher stability and bioaccessibility during in vitro digestion make them more interesting from a biological point of view.Grape pomace was also used in another article included in this Special Issue. In this case, Milinčić et al.  analyzedMuch of the research focused on the use of agri-food waste to obtain bioactive compound studies on the composition, biological activity and/or the applications of extractable compounds from fruit and vegetable waste, especially phenolic compounds. However, in agri-food by-products, phenolic compounds are generally in free and bound forms. The review article by Zeng et al.  highlighIn the second review article, Sánchez et al.  compiledw/w) exhibits a high sensory acceptance. These results offer a promising opportunity for the food industry: to prepare healthier bakery foods using powder obtained from fruit and vegetable by-products, without the need for a prior extraction process.Finally, Chumroenvidhayakul et al.  added drThere is still a long way to go in research on the potential uses of fruit and vegetable wastes with antioxidant properties. Future research in this field should be driven towards the search for specific applications for each type of plant by-product based on both its physicochemical characteristics and major components. Likewise, since the objective is to obtain a health benefit from the phytochemicals present in fruits and vegetables, it is of vital importance to acquire a complete and in-depth knowledge about the fate of these bioactive compounds, either during food processing or during digestion and gastrointestinal fermentation, as well as all the factors that can influence these aspects of bioactive compounds.Antioxidants journal for giving us the opportunity to be Guest Editors of this Special Issue.Finally, we would like to express our gratitude to all the authors who participated in this Special Issue and to the reviewers for their great work. Many thanks also to the


Childhood cancer affects approximately 600,000 children and adolescents worldwide, and chemotherapy is the main form of treatment. However, chemotherapy treatment causes feelings of fear and anxiety especially in the patient’s caregiver. Thus, strategies that help the health education process directed towards caregivers are essential for strengthening knowledge and reducing anxiety involved with the beginning of treatment.To present a study protocol to evaluate the effect of a multimedia strategy compared to standard guidelines for acquiring knowledge and reducing anxiety among caregivers of children and adolescents with cancer undergoing chemotherapy.A randomized, controlled, single-blind, two-armed clinical trial will be carried out. Fifty-two caregivers of children and adolescents who will start chemotherapy will participate in the study, which will be randomly assigned into Experimental Group, which involves the evaluation of the effect of a multimedia strategy composed of a digital animation film about the chemotherapy process, used as tool for health education or into Control Group, which assesses the effects of standard guidelines, which are verbally provided. Two important moments will be considered to evaluate the results of the intervention . The primary outcome includes reduced anxiety and the secondary outcome refers to the caregivers’ acquisition of knowledge about chemotherapy treatment.The results of this randomized clinical trial will have a positive impact on the participants’ knowledge acquisition, and will also contribute to reduce anxiety observed at the beginning of treatment related to the caregivers’ knowledge deficit. The level of knowledge between groups with anxiety before and after intervention will be compared, highlighting which intervention had the best effect.Registration: RBR-4wdm8q9–Brazilian Registry of Clinical Trials–REBEC (23/03/2022). This study was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte- UFRN, under CAAE—52597121.9.0000.5537. Childhood cancer (from 0 to 19 years of age) represents a public health problem, affecting approximately 300,000 new children worldwide each year, with greater increase in developing countries. Furthermore, the World Health Organization (2022) estimates a prevalence of childhood cancer of approximately 600,000 cases worldwide, with leukemia, central nervous system tumors and non-Hodgkin’s lymphoma being pointed out as the most frequent [It is noteworthy that childhood cancer presents a different behavior if compared to cancer in adults, being marked by uncertain mutations and non-evidenced risk factors, making it a challenge for the scientific community mainly related to early diagnosis and treatment , 3.In this context, in relation to treatment, chemotherapy is the basis for therapy, and can be performed alone or associated with surgery and radiotherapy, considerably contributing to improve the prognosis and survival of patients .However, chemotherapy treatment causes the development of negative feelings such as fear and anxiety among parents or caregivers, mainly related to the stigma of the disease, such as not knowing the therapy, its effects and the purpose of treatment .Furthermore, it is in the impact of the diagnosis and definition of treatment that these feelings emerge, consisting a difficult period for the assimilation of information verbally transmitted by health professionals to caregivers. When information is transmitted in an accumulated way and with the use of technical language, caregivers /parents experience greater tension and lack of understanding about the disease and treatment , 7.It is necessary to take into account that the caregiver may not have sufficient schooling to understand technical terms, and it is necessary to facilitate communication using language accessible to all, which should be enlightening, simple and objective .Thus, the guidelines provided to caregivers / parents of children / adolescents undergoing chemotherapy are part of the activities of health professionals and among them the nurse, who plays an essential role in the health education process. Basic care with food, hygiene, hydration and management of chemotherapy side effects constitute important standard guidelines for caregivers and are provided by health professionals , 10.In this context, the use of educational technologies that allow the insertion of resources that can contribute to the strengthening of health guidelines is highlighted. Therefore, the nurse, as an educator and care coordinator, must be on the developing team and use their knowledge and expertise of care in working with the team that develops these resources , 12.Among tools included in the Educational Technology that can be used for the health education process are multimedia strategies, which represent a set of resources that stimulate all the senses, especially vision and hearing. Digital information can be transmitted through audio, video and animation simultaneously .It is noteworthy that health education using multimedia before invasive procedures has shown significant results , 15, as Thus, it is believed that the use of a multimedia strategy before chemotherapy administration can contribute to reducing the level of anxiety and prepare the caregiver for the management of children and adolescents undergoing chemotherapy. Based on the above, the study is justified due to the need to investigate the effectiveness of strategies aimed at supporting caregivers during cancer treatment. Furthermore, there are still few interventions using educational technologies for caregivers of children undergoing chemotherapy , 17.Thus, the aim of this study was to evaluate the effect of a multimedia strategy compared to standard guidelines for acquiring knowledge and reducing the level of anxiety of caregivers of children and adolescents with cancer undergoing chemotherapy.This protocol will adhere to the Consolidated Standards of Reporting Trials (CONSORT)  and StanThis is a protocol for a randomized, two-arm, controlled, interventional clinical trial with single-blind design that evaluated the effect of the multimedia strategy used as a tool for health education in the experimental group (EG) of caregivers, comparing it with the effects of instructions verbally, here called “standard guidelines”, provided to the control group (CG) of caregivers. Both interventions are related to children and adolescents with cancer undergoing chemotherapy treatment.Recruitment and intervention will be carried out at the largest philanthropic pediatric hospital that is a reference in the care of children and adolescents with cancer, located in the city of Natal, state of Rio Grande do Norte, Brazil.Caregivers of children and adolescents diagnosed with some type of cancer who will start chemotherapy treatment.http://www.gpower.hhu.de/). The calculation was performed considering the study by Bernardi et al. [The sample is probabilistic and simple random. Sample size calculation was performed using the G Power software, version 3.1.9.2  by simple randomness and without the influence of researchers. The site generates a list with the sequence of participants equally divided into the two intervention groups. It is noteworthy that the allocation of participants will be carried out by a researcher who is not involved in the intervention. Additionally, the allocation will be hidden.The randomization of participants will be carried out through the It is noteworthy that randomization will avoid participant selection bias and will allow groups to be compared in terms of their known and unknown risk factors.Participants who accept to participate in the research after signing the free and informed consent form will be presented to the study, interventions, instruments used for data collection and any doubts about the research will be cleared before intervention. After this step, participants will assigned one of two groups (CG and EG) according to the randomization list generated prior to the initial assessment.The intervention that will be used in EG is the application of a multimedia strategy associated with the Institution’s standard guidelines. The multimedia strategy is the exhibition of a digital animation film with duration of 12 minutes and 22 seconds addressing the pediatric chemotherapy treatment process.The film is an educational technology developed by Pinheiro et al. , during The digitally animated film will be shown in a quiet room, before starting chemotherapy. The caregiver will be provided with a headset and a tablet to watch the movie.The digital animation film used in the study generally addresses the concept of chemotherapy, chemotherapy administration routes, most frequent side effects and general care during treatment. The film emphasizes health education about chemotherapy for the caregiver.GC will receive instructions verbally. The standard verbal instructions are provided as supplementary material.The intervention period will be carried out in two days consisting of three stages: the first stage is performed on the first day of contact after admission of the child/adolescent to the chemotherapy unit with the caregiver who, after accepting and signing the informed consent form, will be included in the search.The second stage is performed on the second day of contact, which will be on the child’s first day of chemotherapy, and before starting the procedure, the main researcher will apply the instrument to assess the level of anxiety (State Trait Anxiety Inventory—STAI) of caregivers in both groups (CG and EG).Subsequently, the intervention will be carried out according to the groups formed, in which the principal investigator will carry out health education using the multimedia strategy associated with the standard guidelines in the EG and standard guidelines in the CG.The third stage will be carried out on the second day 30 minutes after the end of interventions in which a second researcher, trained to apply the STAI and KAI and who has no understanding of patient allocation, will apply these instruments to participants of both groups, CG and EG.A pilot test will be carried out with the first nine participants, which will serve for research analysis in order to adapt instruments and the methodological approach as necessary to meet the objectives, for better adherence to the intervention protocol.Two instruments will be used for data collection:State Trait Anxiety Inventory (STAI) , an instKnowledge Assessment Instrument (KAI), adapted from the study by Oliveira, Souza and Pellanda , which hThis instrument has a semi-structured questionnaire composed of three stages: the first consists of sociodemographic data of participants; the second contains information about previous guidelines by other professionals and the participant’s opinion about the intervention performed in order to report whether the intervention was able to resolve doubts about the chemotherapy procedure. The third stage consists of nine questions about the chemotherapy process, to quantify the knowledge that participants obtained on the subject after intervention. The STAI and KAI are validated and reliable instruments used in studies with adults and caregivers , 23.The KAI and STAI instruments will be applied as an interview, clarifying the instrument’s questions and marking the alternative chosen by the research participant. It should be noted that STAI was translated and validated into Portuguese by Biaggio, Natalício and Spielberge .The Knowledge Assessment Instrument (IAC) is a form prepared by the main researcher based on the questionnaire used in the study by Oliveira, Souza and Pellanda (2016) in portuguese.The second researcher responsible for the STAI and KAI application after intervention does not know the groups to which participants belong. In addition, data analysts will be blinded to the treatment group to which participants were randomized.Researchers will ensure that the anonymity of participants is protected and data collected will remain confidential so that their identities and any type of identifying information are protected. Two copies of the informed consent form will be provided, both signed by participants, researchers and guardians.After signing the consent form, the patient may terminate his/her participation in the study at any time, if desired, without any consequences related to his/her treatment or follow-up at the institution. The results of this research can be presented at meetings or publications; however, the identity of participants will not be revealed.Losses and dropouts will be carefully recorded, ensuring research reliability. If any participant withdraws from participating in the study, it will be removed from the sample and another participant must be included. A logbook will be used to record information relevant to the study.Data collected in this research will be stored and processed in computerized database using the Microsoft Office Excel 2010 and Statistical Package for the Social Sciences (SPSS) version 20.0 software. Descriptive and inferential statistics of collected variables will be performed, and data will be presented through tables, charts and figures.Statistical analysis of comparison and correlation of data obtained will be performed. The Kolmogorov-Smirnov test will be performed to analyze sample normality. Likewise, Pearson or Spearman tests will be used for correlational analyses. Categorical variables will be analyzed using the chi-square test or Fisher’s exact test. To compare the KAI and STAI assessment with the intervention and control groups, Student’s t-test will be applied. Comparing the IAC and IDATE classification with the group of intervention and control, the chi-square test (χ²) will be applied. Being adopted throughout the study a significance level of 5% at which p = 0.05.The present study was analyzed and approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte–UFRN–CAAE—52597121.9.0000.5537 (03/02/2022)–and CEP 5.176.784 (03/02/2022). This study was also registered in the Brazilian Registry of Clinical Trials–REBEC–RBR-4wdm8q9 as a clinical trial (03/22/2022).The participation of patients will be carried out on a voluntary, non-profit basis and all stages, objectives, risks and benefits of the research will be explained. Participants can drop out the study at any stage without prejudice to treatment, without suffering penalties or judgments of any kind.The primary outcome includes reduction in the level of anxiety of caregivers of children and adolescents undergoing chemotherapy. The before and after STAI anxiety data will provide the levels of anxiety of CG and EG to evaluate which intervention had the best effect.Furthermore, data obtained on participants’ level of anxiety can be used to compare levels before and after intervention of each participant, whether in CG or EG; levels of anxiety between groups before and after intervention, assessing the management of anxiety according to the intervention performed.STAI response possibilities range from 1 to 4, where: 1 = almost never; 2 = sometimes; 3 = often; and 4 = almost always. The final STAI score is directed to the level of anxiety classified as 20 to 40 points–low level; 41 to 60 points–moderate level; 61 to 80 points–high level.Secondary outcomes refer to caregivers’ acquisition of knowledge about chemotherapy treatment. Thus, data will be generated on the level of knowledge of participants after intervention through the KAI, in which participants will have correct answers for questions scoring from zero (no correct answer) to nine points  and the knowledge acquisition can be analyzed in two ways: 1-KAI of verbal guidance participants (CG); 2- KAI of guidelines with educational technology (GE). KAI generates knowledge data on the subject after interventions, which can offer various combinations of analysis that aim to respond the research objectives.In addition, it will provide data for the evaluation of each subject, offering an overview of the health education offered and which themes need greater intervention for a better understanding of caregivers. It is noteworthy that one of the aims of health education is to improve the knowledge of patients and caregivers, thus, knowing which topics are difficult to learn can provide evidence to improve guidelines .Educational technologies are being gradually inserted in the context of pediatric oncology, requiring further discussion of the benefits of their use for caregivers of children with cancer undergoing chemotherapy. Resources that can help in the acquisition of knowledge in a playful way are essential for the effectiveness of cancer treatment .In addition, one of the points that needs to be explored is related to the use of educational technologies that contribute to reducing the level of anxiety of caregivers of children / adolescents with cancer. It is observed in previous studies that videos and games have greater contribution to reduce the level of anxiety when compared with printed materials , 24.A meta-analysis has shown that the prevalence of anxiety and depression in caregivers of cancer patients is approximately 47% and 42%, respectively, affecting their quality of life . CorroboIn this perspective, it was observed that physical symptoms resulting from stress and anxiety can be observed in caregivers of children undergoing chemotherapy, such as hypertension, headache, insomnia, increased body mass index (BMI) and significant immunological changes, such as increased concentration of cytokines and monocytes in the peripheral blood of these individuals .These data are worrying, since increased level of anxiety is harmful to the caregiver’s quality of life as well as to the adaptation of children / adolescents to the chemotherapy treatment. It is necessary to investigate strategies that can contribute to improve caregivers’ quality of life, reducing the condition of mental disorders, anxiety and depression.Thus, the development of studies with the purpose of investigating the benefits of using educational technologies to acquire knowledge and reduce anxiety in the context of pediatric oncology is essential, as both can influence the treatment of children with cancer.Among the possible study limitations, it is highlighted that since it is a specific population, the sample may change due to the number of admissions during the collection period, making it necessary to recalculate the sample or extend collection.The present study is part of an academic master’s degree. The dissertation and its results will be presented to the scientific committee of the Federal University of Rio Grande do Norte–UFRN.Any necessary protocol changes will be effectively communicated and modified in the relevant parts . Any questions about the study will be duly answered by the researchers in the initial evaluation period and during the study period.This study is currently being prepared for the recruitment of participants. It is scheduled to end in April 2023.S1 Checklist(DOC)Click here for additional data file.S1 Fig 2(TIF)Click here for additional data file.S1 File(DOC)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(PDF)Click here for additional data file.S4 File(DOC)Click here for additional data file.S5 File(DOC)Click here for additional data file.