Since the outbreak of COVID-19, its effects on different aspects of life have been subject to much research, including food security, a domain that has been of special concern in many low-income countries. Ethiopia has been facing many challenges related to food security for decades via drought, famine, and conflict. Within this context, this case study assessed the impact of the COVID-19 pandemic on food security in Ethiopia. Results show that the ongoing pandemic has negatively impacted different regions and at-risk groups in a heterogeneous manner. This has been mainly through disruptions in the Ethiopian food value chain and the relative failure of social security programmes to address the losses generated by COVID-19. The population in the capital city, Addis Ababa, was able to maintain the same level of food security despite income losses caused by the COVID-19 pandemic. However, at-risk groups such as refugees, internally displaced persons (IDPs), and conflict affected regions were seen to suffer significantly from food insecurity exacerbated by COVID-19. Furthermore, this paper particularly emphasizes the importance of considering contextual factors other than COVID-19, such as conflicts or climate change, when discussing the state of food security in Ethiopia. A novel Coronavirus infection COVID-19), first identified in late December 2019, was declared a pandemic by the World Health Organisation (WHO) on 11 March 2020. The virus quickly spread, with approximately 456.9 million reported cases and 6.04 million reported deaths worldwide as of mid-March 2022. The impact of this disease is manifold at both national and individual levels, but one of the most important consequences induced by this pandemic is its disruptive effect on food security, especially for the most deprived individuals ..36].In terms of sex distribution, most of the cases were seen to occur in men (60.69%), within the ages of 20 to 30 . Early iThe COVID-19 vaccine campaign, in Ethiopia, started on the 13 March 2021. This was following the delivery of the first 2.2 million doses of the AstraZeneca vaccine to the country on the 4 March 2021, through the COVAX initiative . The AstSince Ethiopia’s first COVID-19 case on 13 March 2020, multi-sectoral measures have been taken by authorities, including closing public transport, banning public gatherings and other social activities, and school closures for several months. Oxford COVID-19 Government Response Tracker collects data daily to track government’s response to COVID-19 . The scoThe Protocol for Screening and Quarantine of Cross-Country Truck Drivers and Other Crews was issued on 8 May 2020, to enhance the health screening, testing, case management for truck drivers, and decontamination of trucks at the point of entry and final destinations.Movement restrictions were implemented for a time after the first case, including mandatory 14-day quarantine for travellers coming from outside of Ethiopia, land border closures, and prohibition of all non-essential inbound and outbound traffic. Tigray, Oromia, Amhara, and several other regional authorities also banned public transportation and put restrictions on other vehicle movements between urban and rural areas . The ProContact tracing was also adopted to interrupt chains of transmission by listing, tracing, and following-up persons who had contact with confirmed COVID-19 cases. According to data from the Ministry of Health of Ethiopia, as of 11 July 2021, a total of 374,083 contacts of confirmed cases had been identified, and 87.95% of the contacts had completed 14 days of follow-up. 11.27% of the contacts had tested positive, and this contributed to 15.22% of the total cases . Health Since Ethiopia had already established a social protection system, namely, the Productive Safety Net Program (PSNP), before the pandemic, after the outbreak of COVID-19 , the EthPositive results have been observed among PSNP participants compared to non-PSNP participants . HoweverCOVID-19 has disrupted the food value chain through factor market, production, transportation, and buying behaviours, further influencing food price and availability negatively. Prices reflecting supply and demand of different commodities further impact households from urban, rural, and different regions in Ethiopia.The price of agricultural inputs has surged, and accessibility has deteriorated amid the pandemic due to the currency  depreciation and a surge in inflation. From August 2020 to August 2021, the exchange rate of Birr to the US dollar fell sharply in both the official and parallel markets. The decline in the parallel market was even greater than the official market, leading to a large differential between the two markets  46]. Th. Th46]. Studies have shown that the impact of COVID-19 restriction measures on the food value chain varies depending on the characteristics of a commodity, including the resource needed for production and its intensity . AgriculAs local and migratory laborers are disrupted by border closure, movement, and gathering restrictions, productions of different food are below average. Large commercial farms along the Awash River in Afar; Humera areas of Tigray; Metama in Amhara; and parts of Oromia and Southern Nations, Nationalities, and Peoples’ Region (SNNPR) that depend on migratory laborers are notably impacted . DespiteEven though livestock price has increased despite the declined body condition across many pastoral areas due to pasture and water shortage, as staple food prices increase more significantly, the terms of trade (TOT) disfavours pastoral and agro-pastoral households. According to the Somali Disaster Prevention and Preparedness Office, the goat to maize TOT in the Jigjiga market in July 2021 was over 30% lower than the five-year average . The unsProtocol for Screening and Quarantine of Cross-Country Truck Drivers and Other Crews on 8 May 2020. Measures such as thermal and clinical health screening at point of entry, decontamination of trucks at point of entry, and destination prolonged transportation time, producing further delays in the supply chain. Travel bans have also reduced the volume and frequency of trucks running between areas. Farmers’ access to input and output markets are limited by reduced food commodity movement due to transportation impacted by travel bans, border testing requirements, and high transportation cost. The authority issued the Surveys taken by the International Food Policy Research Institute (IFPRI) on the vegetable and dairy value chains in Ethiopia in 2020 show that fear of disease risk and the slowdown of restaurant businesses resulted in falling consumption of vegetable and dairy products. Consumers linked raw milk, vegetables, and their downstream products with a higher risk of contracting the virus and perceived those traders who had contacted many people and travelled to different places in the distribution process having high COVID-19 risk. Some farmers interviewed said that they had to leave some vegetables to rot in the field due to the lack of buyers ,52.As a country with high sensitivity and vulnerability, the food value chain in Ethiopia has been hit harder by COVID-19 than countries with a robust food system . SensitiThis chapter aims to examine the added effects of the COVID-19 pandemic on food security in Ethiopia. This will be accomplished by reporting the degree to which the domestic public programmes related to food security have managed to mitigate the adverse effects of COVID-19 on Ethiopian households. As introduced in the case presentation, the PSNP is widely seen as the flagship of the safety net in Ethiopia. Therefore, assessing the performance of this programme is of primary importance regarding the purpose of this section and this article.To this end, an evaluation of the PSNP from March to June 2020 found that households targeted by the PSNP were less prone to being food-insecure during the beginning of the COVID-19 pandemic than the ones who did not benefit from the PSNP . By relyHowever, other studies present less optimistic results. Study conducted by Deshpande et al. found that although the government managed to provide relatively more assistance to the poorest share of its population compared to the richest  and the poorest one  ), only 1Furthermore, it must also be noted that the government has not managed to maintain some of its social protection programmes after COVID-19 pandemic struck the country. For instance, the school feeding programme running in Addis Ababa has been interrupted following the closure of schools . As schoWhat should be retained from this section is that, overall, Ethiopia has struggled to ensure the adequate functioning of its food social security programmes in a time where food insecurity has increased throughout the country. Indeed, while the PSNP has managed to provide help to the individuals it already covered before the COVID-19 pandemic hit the country, it has mostly failed to compensate for the increased number of individuals at risk of being food insecure following the COVID-19 aftermath. Moreover, the government has not managed to maintain the running of other food related social security programmes, such as the school feeding programmes in Addis Ababa. Suggestions explaining this rather complicated situation will be provided in the discussion section.The COVID-19 pandemic has disproportionately affected the urban parts of Ethiopia, due to their high population density. Those employed in informal sectors; retail; hospitality; and micro, small, and medium-sized enterprises were the hardest hit by the economic shutdown caused by the COVID-19 pandemic . HoweverAddis Ababa, the capital city of Ethiopia, and the city with the heaviest burden of COVID-19 cases, is an interesting example. Due to the large variations in wealth status found in this city, both cases of overnutrition and undernutrition were observed even before the pandemic. Undernourishment was mainly seen in children, affecting 15% of children under five within the city .However, a study assessing a representative sample of households in Addis Ababa, through the conduct of telephone surveys, found that food insecurity had not changed significantly from what was reported before the pandemic, in September 2019. Despite reported income losses in 64% of interviewed household, as a result of COVID-19 restrictive measures, these households still managed to maintain a similar level of food consumption. While a significant impact on food consumption was not observed, the composition of the types of food consumed did change. The surveyed households in Addis Ababa were seen to move more towards staple foods while avoiding vegetables and raw meat, reducing their nutritional diversity. However, this move away from raw meat and vegetables may be a result of beliefs that they carry COVID-19 risks rather than the unavailability of these food items .These unexpected results suggest that food security and consumption has remained resilient despite the financial challenges posed by the COVID-19 pandemic in Addis Ababa. Although there is a lack of literature explaining this resilience, potential reasons could be that expenditures on non-food items may have now been redirected to food items with the closure of bars or cinemas early in the pandemic . MoreoveDespite the resilience of Addis Ababa’s food security, households with a lower wealth status, and households in urban areas outside of Addis Ababa, faced a greater risk of food insecurity resulting from COVID-19. This risk is reflected in a study assessing vulnerable households in nine different urban areas of Ethiopia since the start of the pandemic. Within these vulnerable groups, 27% of beneficiaries of the UPSNP, despite receiving assistance, reported having experienced food shortages. Increased food prices, devaluation of the Ethiopian Birr, and an already low income following the pandemic were cited as factors leading to food insecurity. Workers in the informal sector, daily wage earners, daytime laborers, street vendors, and women were amongst the most vulnerable to income loss and hence food insecurity . In addiWhile Ethiopia’s urban areas had the heaviest share of COVID-19 cases, the economic shutdown caused by COVID-19 restrictions still had a significant impact on food security in rural areas. Eighty percent of the Ethiopian population resides in rural areas, with agriculture as the main source of income and economic activity. In a study by the world bank, loss of income was reported in 25% of farming households at the beginning of the pandemic. Moreover, some households reported that they were unable to maintain their normal level of farming activities since the start of the pandemic, citing the inability to hire labor, stay-at-home advice, and mobility restrictions as the main reasons. As most Ethiopian farmers are subsistence farmers, this reduction in farming activity can also result in food insecurity . While most urban households relied on savings to cope with income losses related to COVID-19, the same was not true for rural households. In the rural households studied by the world bank, 60% could not cope with the loss of income at all . Being lWhile the impacts of COVID-19 were apparent at the beginning of the pandemic, these effects were seen to taper off as the pandemic progressed and households seemed to adapt. In addition, while movement restrictions did affect economic activity in rural households by reducing daily laborers, for the most part, the households themselves were able to maintain farming activity. It is also important to note that in 2020, the locust invasion affected food security and farming outcomes beyond COVID-19 .As mentioned above, households already vulnerable to food insecurity are more prone to face further challenges as a result of COVID-19. Refugees and internally displaced people (IDP) are amongst the most vulnerable groups to food insecurity, usually forced to rely on aid and food assistance . AccordiEthiopia is currently the third largest refugee-hosting country in Africa. Most of the registered refugees in Ethiopia come from its neighbouring countries: South Sudan, Somalia, Eritrea, and Sudan . In addiAccording to the ninth Ethiopian national displacement report, IDPs and returnee IDPs were found to be amongst the most affected groups, in Ethiopia, by the COVID-19 pandemic. The supply of products, including food, decreased while the price of food was rising. Shortage of food, as assessed by this report, was present in 81% of the villages housing returning IDPs. In addition, 85% of the assessed villages reported that food prices had increased, affecting their ability to purchase food items . SimilarMoreover, a mixed method panel study on IDPs and refugees sheds light on the impact of COVID-19 in these groups. The devaluation of the Ethiopian Birr, reduction of income, and an increase in prices of food following the start of the COVID-19 pandemic were identified as exacerbators of food insecurity. Eating less frequently and avoiding the purchase of expensive foods were reported as coping methods by IDPs and refugees. While staples such as white flour were the highest in their diets, eggs, meat, and dairy products were reduced or completely avoided by these households. Moreover, a study by Harris et al. (2021) reported food shortages were much higher in the IDP and refugee households than in the other low-income households assessed .IDPs and refugees, already at risk to food insecurity, are currently facing greater challenges due to the COVID-19 pandemic . HoweverThe northern Tigray, Amhara, and Afar regions, where the current conflict is mainly concentrated, face the highest level of food insecurity within Ethiopia . Food seTo summarize, Ethiopia’s food security has been threatened and exacerbated by the COVID-19 pandemic in different ways and has had a varied impact across the country. Ethiopia’s sensitive food value chain was hit hard by COVID-19, with its impacts reflected in increased food prices and shortage of food availability. While social protection programmes such as the PNSP exist to counter these impacts, the Ethiopian government was unable to keep up with the increased level food insecurity that followed COVID-19. As a result, high risk populations such as beneficiaries of PNSP, refugees, and IDPs reported increased food insecurity. Additionally, the recent conflict Ethiopia’s northern region has added an additional strain to Ethiopia’s food security that had already been impacted by COVID-19.Food insecurity in Ethiopia is already exacerbated by many different factors. Recurring droughts, though often not national events, cause severe damage to regional access to agriculture in the east and Northeast. Desert locusts, recently propagated by extraordinary rains due to climate change, can cause damage to enormous portions of crop fields. Conflict and ensuing displacement leave hundreds of thousands of people vulnerable to food insecurity by way of loss of homes and domestic animals, lack of access to clean water, and interrupted access to markets and trading. It is important for these factors to be considered when examining the impact of COVID-19 on food security in Ethiopia.Food value chain has two implications for the food security of a country, namely, the food supply, and a source of income that determines households’ purchasing power. A resilient food system involves not only food but also the robustness of a country’s currency and market, its dependence on imports and exports, and the social security system. In the case of Ethiopia, due to its dependency on imports and exports, the price surge in imported staple foods, fuel, and agricultural input caused by the depreciation of ETB has put greater pressure on both producers and consumers. As the agricultural field is labor-intensive, food production activities are disrupted by the lack of labor when travel restrictions are implemented, resulting in a shortage of food supplies, rising food prices, and severe economic hardship for poor families who count on labor as a source of income. Compared with other regions, the pastoral regions of Ethiopia  have been hit harder. The poor infrastructure condition, droughts, rising temperatures, and desert locust situation, which were particularly pronounced in these regions before COVID-19, have already put these areas in a vulnerable position, making regions highly dependent on food imports. The inconsistency in price growth of staple and animal products, and greater currency depreciation in the parallel market after COVID-19, have produced greater food security challenges to pastoralist households and caused further imbalances among poor pastoral regions and other parts of Ethiopia. Regarding ongoing and disrupted domestic social security programmes, we have reported above that the PSNP and other programmes have struggled to support many individuals who became more prone to food insecurity amid the COVID-19 pandemic. This problem might be partly explained by the fact that the pandemic is not the only concern for Ethiopian authorities. For instance, as the ongoing conflicts in Oromia and Tigray have intensified since mid-2020, it seems that the Ethiopian authorities have been more actively working on dealing with this conflict rather than with the COVID-19 pandemic and its impact on food security and nutrition. This idea has been suggested by different authors, who have claimed that most of the government and public’s attention has been centred on the war in Tigray . WithoutFinally, while the COVID-19 pandemic has negatively impacted Ethiopia’s food security, further research needs to be conducted to identify these impacts in specific households. Currently, most studies are based on surveys and self-reported answers concerning food security. These answers could potentially be affected by a social desirability bias. Moreover, due to the social distancing measures resulting from the pandemic, many of the studies collected their data through phone surveys. This poses a problem since phones are generally only accessible to wealthier households, particularly in rural households. As a result, some of the households most vulnerable to food insecurity may be getting overlooked. Furthermore, due to the conflict in the northern region of Ethiopia, data from the most affected regions, particularly Tigray, are scarce. Therefore, it is currently difficult to get a holistic image of COVID-19′s impact on food security and nutrition in the whole country as some regions remain inaccessible and excluded.


In this special issue, we aimed to expand the horizon of the interested reader and give a stage to recent advances in DBS for neuropsychiatric disorders.For over two decades, the value of deep brain stimulation (DBS) in the treatment of different neuropsychiatric diseases has been studied. Over the years, the field has made substantial progress and a number of effective or promising clinical applications have been introduced, e.g., for treatment-refractory obsessive-compulsive disorder  and others. Despite this effort, DBS must still be considered a niche topic for both clinicians and the broader field of neuroscience, even in indications with convincing evidence for effectiveness (This Research Topic consists of 8 articles reviewing the current status and perspectives of Deep Brain Stimulation (DBS) for Neuropsychiatric Disorders. Fifty authors from 6 different countries contributed to this topic, leading to almost 15,000 online views and circa 3,000 article downloads at the time of this writing. The majority of the papers were Reviews, but also Opinion, Perspective and Original Research papers were published. The topic theme “DBS for Neuropsychiatric Disorders” was deliberately broadly formulated to cover different diseases and different anatomical targets. Although much effort has been done in recent years regarding the whole of DBS for neuropsychiatric indications, data are still sparse and derived from small open-label studies and therefore this collection can help the reader to have a broader impression of the current status of the DBS therapy also for non-stablished indications. The articles published in this Research Topic covered the treatment of aggression and self-destructive behavior, obsessive-compulsive disorder (OCD), resistant depression (MDD), Tourette syndrome (TS) and drug addiction with DBS.Treating Agression and Self-destructive Behaviors by Stimulating the Nucleus Accumbens: A Case Series , reports the results of nucleus accumbens stimulation in 6 patients with self-destructive aggressive behavior, from various etiologies. The authors report substantial reduction in self-destructive and aggressive behavior  evaluated whether DBS is effective in reducing TS symptoms and target-specific differences. In this comprehensive review (65 studies and 376 patients included), the four most commonly used targets for Tourette syndrome (TS) were studied . When the GPi was targeted, there were increased score reductions compared to the thalamic targets, but the authors conclude that DBS is a clinically effective treatment option for treatment-refractory TS. Some questions remain unanswered such as: is there a best target for TS? Are there specific clinical features that would improve in different targets? If so, what are the best candidates for each one (The systematic review Neuromodulation of Obsessive-Compulsive Disorder (OCD): A review of invasive and non-invasive methods , discussed the rationale and theory behind neuromodulation in OCD. The authors provided an extensive overview of the cortico-striato-thalamo cortical loops involved in OCD, pointing the role of the latero orbitofrontal-ventromedial caudate pathway, limbic network, default mode network, and salience network in the development of the symptoms. This theoretical basis was then translated to provide anatomical and physiological basis for Transcranial Magnetic stimulation (TMS), Transcranial direct and alternate current stimulation , vagus nerve stimulation (VNS) and DBS of various targets. An important message of this interesting review is that mechanistic studies aiming to understand the functional networks implicated in OCD are key to identifying optimal targets. Planning DBS based in connectomic analysis might improve our results in the next years not only for motor diseases, but also for complex psychiatric conditions, such as OCD , reviewed and summarized current targets for Major Depressive Disorder (MDD) and relevant diffusion tensor imaging (DTI) studies. Ninety-five studies were included, showing 7 different DBS targets for MDD and 9 white matter tracts with microstructural abnormalities reported. The authors show that each DBS target corresponds to dysfunctional brain regions and circuits associated with different MDD subtypes. They present a taxonomy of DBS targets based on their associated white matter tract and modulated dysfunctional brain circuits and propose DTI-based personalized targeting strategy. Also it would be very interesting to further explore this idea, trying to correlate such imaging subtypes with clinical features. It is possible that, within the wide range of MDD symptoms, some are more or less correlated with the microstructural changes in white matter and would respond better to a chosen target stimulation.In line with this concept, the paper Sobstyl et al. included in this collection a systematic review entitled Subcallosal Cingulate Cortex Deep Brain Stimulation for Treatment-Resistant Depression: A Systematic Review. Fourteen studies were identified with a total of 230 patients with treatment-resistant depression who underwent SCC DBS. The results showed that DBS response and remission rates are not significantly higher than the rate of non-responders and patients without remission. As the authors state, these conclusions should be viewed with caution, since it could be due to small sample size and lack of control groups. The ideas for improving the accuracy and results are in line with the idea of personalizing targets with neuroimaging and individual features.Exploring the subcallosal cingulate cortex (SCC) target for MDD, Marquez-Franco et al. also analyzed the characteristics of the cortico-subcortical connections to explain DBS results in OCD and MDD. The study Deep Brain Stimulation Neuromodulation for the Treatment of Mood Disorders: Obsessive Compulsive Disorder and Treatment Resistant Depression reviewed the anatomical background, neurochemical substrates of MDD and OCD, imaging studies and DBS target size, location and stimulation parameters for those conditions.Deep Brain Stimulation in Drug Addiction Treatment: Research Progress and Perspective . The authors review the neurobiology of drug addiction, and the postulated mechanism of action of DBS in such conditions. The nucleus accumbens was considered the most promising target for drug abuse, but positive effects were also described in other brain regions. Different substances were subject of study , but the data is still preliminary, due to lack of double-blinded studies and clinical trials in larger cohorts.Drug addiction treatment is also an interesting and important topic, addressed by the paper Why Has Deep Brain Stimulation Had So Little Impact in Psychiatry?Mocking et al. debate in this interesting paper, that it is not the lack of patients, knowledge, technology or efficacy of DBS that hinders its development and applications in psychiatry. The reasons behind this issue are discussed in the article, and for the sake of the thrill, no spoilers should now be disclosed! What we, however, can presently disclose, is that the motivation for this Research Topic was the will and the need to change this scenario for the years to come.Finally, one might ask, after over two decades of DBS for psychiatric indications, All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.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.


Maltreatment in sports is an epidemic and occurs in many relational forms such as physical, sexual, and emotional abuse or neglect. Maltreatment in sports also exists in forms of non-relational abuse and focuses on mezzo and macro forms of maltreatment such as systematic abuse, organizational abuse, and physiological abuse or neglect . It is imperative to study the effects of maltreatment in sports as athletes can be the victims (survivors) as well as perpetrators of abuse. Recent research in the field of social work points to the benefits of Trauma-Informed Sports and Short Focused Brief Therapy (SFBT) as possible interventions. It is imperative for transferability in the field of maltreatment in sports, that practitioners define each form of abuse in the context of maltreatment and trauma. This commentary aims to discuss the different forms of maltreatment in sports that could affect athletes and provide discussion and insights into the void of research surrounding certain forms of non-relational abuse and the role trauma-informed therapies serve in promoting athlete wellbeing from a social work lens. Maltreatment in sports is an undeniable problem. Athletes might experience sexual maltreatment, physical maltreatment, psychological maltreatment, neglect, and exploitation in practicing their sport , 2. MounThis conceptual analysis aims to discuss the current void of research in sports maltreatment from a social work and trauma-informed perspective. The analysis defines and discusses examples of relational and non-relational forms of maltreatment in sports. The piece also discusses athlete health and wellbeing, a culture of safety in sport, and trauma-informed interventions from a social work perspective. The authors provide future recommendations for advancing the assessment and intervention process of athletes experiencing maltreatment. This conceptual analysis provides a timely review of risk and safety concerns in the world of youth, collegiate, and professional athletics. Many of these risk factors could impact athletes to a greater degree given the post-pandemic challenges faced in social and emotional development . This isAthlete vulnerability concerns arise when the sport puts individuals at risk for abuse and exploitation. Researchers categorize maltreatment as relational and non-relational in nature. Since most forms of maltreatment exist within the context of relationships, it is imperative to understand the nature of relationships that exists within an athletic setting. Additionally, athletes may experience multiple forms of abuse and maltreatment due to these complex relationships , 2.Relational maltreatment typically includes four types of abuse: physical, sexual, emotional, and neglect , 8 see . These fNon-relational abuse occurs in non-critical relationships. These types of abuse include systematic abuse, organizational abuse, and physiological abuse see . While tExamining the impact of athlete maltreatment through a biopsychosocial perspective can deepen our understanding of the complexities of sport-related maltreatment and how it affects an athlete. The biopsychosocial model emphasizes a holistic health perspective in which biological, psychological, and social health symptoms and conditions are causally influenced by each other .Biological effects of maltreatment impact individuals throughout their life span. Repeated stress and trauma impact brain development and functioning, which control regulatory responses and processes of the autonomic nervous system leading to increased degeneration of neural processing known as the allostatic load . The allScientific research shows adults who experience maltreatment have lessened gray matter volume in their hippocampus and increased gray matter volume in the dorsomedial prefrontal cortex and the orbitofrontal cortex, which are emotional and mental regulator systems and increase their risk of developing major depressive disorder . This maDetrimental effects on the autonomic nervous system due to maltreatment include decreased restricted cardiac output activity and dysregulated patterns of physiological reactivity . In sporDysregulated cortisol levels and dehydroepiandrosterone (DHEA-S), or androgen, correlate with multiple health issues like high blood pressure, mood changes, weight gain, and overactive adrenal gland responses . AndrogeMaltreatment can also cause severe negative impacts on the psychological wellbeing of athletes. Various forms of maltreatment may impair performance, increase willingness to cheat, and lead to athletes dropping out or other psychosomatic disorders, including depression, anxiety, post-traumatic stress disorder (PTSD), disordered eating, substance abuse, self-harm, and suicide , 25, 26.Female athletes are more vulnerable to adverse effects of maltreatment. Elite female athletes who experience emotional abuse often experience social withdrawal by the end of their careers . TraumatAthlete victims (survivors) of maltreatment may conceal their distress to maintain their team position or preserve anonymity . Their cSocial relationships significantly protect individuals from several causes of morbidity and mortality, including depression and social relationships . IndividSports maltreatment occurs as a broader societal and social problem, with societal risk factors based on entrenched prejudices expressed through power differences and through range of interpersonal mechanisms. Athletic identity refers to the degree of strength and exclusivity to which a person identifies with the athlete role or the degree to which one devotes special attention to sport relative to other engagements or activities in life . Brewer'Evidence on the early impacts of maltreatment supports the importance of the interaction of the parent-child relationship quality and shows that maltreatment can impact the frontal lobe volume in adulthood . This isPrevention of maltreatment in sports requires a multifaceted approach relative to sport-specific factors of risk and the implementation of prevention initiatives over time . Sport sSport social workers are individuals who athletes perceive as neutral and unaffected by the power structures in sport. They protect and enhance the wellbeing of athletes and assist athletes with their negotiations in relationships with others , 13, 36.Sport social workers promote the health and wellbeing of athletes through direct practice, community organizing, advocacy, policy development, education, and research on micro, mezzo, and macro levels . Sport sCentral concepts within social work education and practice include perspectives on biopsychosocial wellbeing, person-in-environment, and ecological systems. Sport social workers understand the importance of a holistic, rather than singular, perspective when working with athletes and that athletes develop within social environments. Holistic approaches in athlete development focuses on the athlete's physical, psychological, and social development through sports participation , 13, 39.Sport social workers also recognize the critical nature of interacting with other environments and social systems. Within an ecological theoretical foundation, sport social workers consider how the athlete's past leads to various levels of vulnerability. Sport social workers seek to understand the root of the issue and how it affects the athlete's vulnerability on micro, mezzo, and macro levels , 41. FurSport social workers also have unique training in person-centered, strength-based approaches. The ability to meet an athlete where they are allows social workers to demonstrate competence within sports and foster rapport within the settings of the sport . StrengtSport social workers also understand the difference between professional collaboration and professional competition . There iIn all categories of maltreatment, research shows the higher level of sport competition increases the prevalence rate of harm compared to athletes in lower levels of competition . AthleteSports acceptance is part of the cultural fabric. Integrating cultural competence in working with athletes is essential, as managing trauma and grief varies by culture –46. AddiAthletes may present symptoms of abuse differently than non-athletes due to sports cultures encouragement of obedience and the suppression of emotions . ResearcIn addition to CBT and EMDR previously mentioned in this commentary, other therapeutic modalities guided by trauma-informed principles may be considered, such as Dialectical Behavioral Therapy , ARC [ASkills- and strengths-based focuses are crucial elements in working with trauma-exposed individuals who are often overwhelmed with feelings of guilt, blame, fear, and anxiety –58. DepeSafe sport is defined as an athletic environment that is respectful, equitable, and free from all forms of non-accidental violence to athletes  of abuse in education initiatives to prevent maltreatment in sports has proven beneficial due to their lived experiences and intricate understanding of abuse within the sports culture , 11, 18.Ignoring the epidemic of maltreatment in sports could be detrimental to what sports can positively do for an athlete's wellbeing and the development of healthy coping skills. Successful prevention and eradication of maltreatment in sports must be a multiagency, systematic approach involving athletes, entourage members, coaches, sport managers, team physicians, trainers, educators, and fans. Athletes should also be empowered to use their voice and provided avenues to speak up and advocate for positive changes for future generations of athletes.While there has been significantly more research on relational forms of maltreatment in sports over the last decade, minimal research is available on non-relational forms of maltreatment, including athlete exploitation, athlete trafficking, and organizational abuse rooted in systematic maltreatment. Additional research should focus on developing holistic approaches to combat maltreatment, such as athlete-centered coaching models and education for all stakeholders on the signs and symptoms of abuse .Although several laws exist to prevent sexual abuse in sports and on school campuses, minimal interventions and policies for other forms of non-relational maltreatment in sports have been explored. International mandates on prohibiting the sexual relationships between athletic staff members, stakeholders, and athletes; reporting and investigating requirements of suspected or reported abuse; and the use of third-party entities to promote athlete autonomy and hold organizations accountable for potential maltreatments, whether relational or non-relational, should all be further explored for the advocation of athletes and the prevention of maltreatment in sports.The importance of a trauma-informed perspective in advocating for athletes and promoting a culture of safety in sports cannot be understated, as seen by the documented biopsychosocial impacts of maltreatment on long-term health and wellbeing . In realAll authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.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.


The analysis demonstrates significant superiority of MECC in reducing the composite incidence of postoperative mortality, stroke, renal failure, and myocardial infarction over CECC.418.See Article page 2-carrying capacity, increased transfusion requirements, and multiorgan dysfunction, leading to increased risks of morbidity and mortality.Cardiopulmonary bypass (CPB), a prerequisite for major cardiac surgery, inevitably accompanies hemodilution and systemic inflammatory response syndrome that may contribute to impairments in the O,Miniaturized extracorporeal circulation (MECC) has been developed to minimize the drawbacks of CPB by attenuating systemic inflammatory response syndrome via limiting the blood–air interface and reducing the artificial tubing length with the renunciation of cardiotomy suction and a venous reservoir.Journal, Cheng and colleaguesIn this issue of the Despite its potential superiority over CECC, MECC has not received general acceptance in clinical practices because of several lingering concerns. First, the closed-circuit nature of MECC may jeopardizes the safety buffer in the event of massive bleeding. Second, there is concern about its limited capacity of removing air bubbles from the circulating blood. Third, the use of cell savers instead of CPB suction systems may also lead to hemodilution and the need for heparinization of the recruited blood may result in more hemorrhagic conditions. Fourth, as the authors stated, the high cost of the MECC circuit may hamper its application to get general acceptance. Lastly, we believe insufficient comparative outcome data—demonstrating superiority of MECC—might have prevented its widespread applications.The issue of MECC is of growing interest, and the present study well handled this issue through a large-scale meta-analysis. In light of the findings of this current study, there seems to be no reason not to use MECC in isolated valve surgeries as well as in coronary arterial bypass graft, provided that the aforementioned concerns are adequately addressed further. One limitation in the paper by Cheng and colleagues noticed is that although the analysis demonstrates significant superiority of MECC in reducing the composite incidence of postoperative mortality, stroke, renal failure, and myocardial infarction over CECC, the data could not confirm the results on each of the primary end points due to the limited numbers of each event. Despite these limitations, this comparative collective data on MECC and CECC will broaden our perspective in the area of CPB and contribute to the accumulation of evidence in this field. A further collection of clinical experiences and data analysis from the larger, well-designed randomized trials are warranted for a deeper understanding of this issue.


As the COVID-19 pandemic became a global emergency, social distancing, quarantine, and limitations in outdoor activities have resulted in an environment of enforced physical inactivity (EPI). A prolonged period of EPI in older individuals accelerates the deterioration of skeletal muscle health, including loss of muscle mass and function, commonly referred to as sarcopenia. Sarcopenia is associated with an increased likelihood of the progression of diabetes, obesity, and/or depression. Well-known approaches to mitigate the symptoms of sarcopenia include participation in resistance exercise training and/or intake of balanced essential amino acids (EAAs) and high-quality  protein. As the pandemic situation discourages physical exercise, nutritional approaches, especially dietary EAA intake, could be a good alternative for counteracting against EPI-promoted loss of muscle mass and function. Therefore, in the present review, we cover (1) the impact of EPI-induced muscle loss and function on health, (2) the therapeutic potential of dietary EAAs for muscle health  in the EPI condition in comparison with protein sources, and finally (3) practical guidelines of dietary EAA intake for optimal anabolic response in EPI. As the coronavirus SARS-CoV-2  outbreak has spread around the world, extended periods of time restricted to home have become routine. The associated enforced physical inactivity is significant, which inevitably leads to muscle atrophy [Despite significant research endeavors, no effective therapeutics to prevent loss of muscle mass in aging has been discovered. Resistance exercise and consumption of increased dietary protein and/or essential amino acids (EAAs) are the two most potent and safe anabolic stimuli to counteract the loss of muscle mass and strength in sarcopenia. However, given the pandemic situation of staying at home or in quarantine, it is likely to be difficult for older adults to perform sufficient exercise to reverse the adverse effects of EPI, particularly with concurrent clinical conditions. The most practical and effective means of slowing the loss of muscle mass and function in EPI is by optimal nutrition, particularly including adequate intake of free dietary EAAs, which can be formulated with the optimal composition ,3. An apIn this review, we discuss the potential role and underlying mechanisms of dietary EAAs in counteracting the deterioration of muscle mass and function in older adults in the EPI environment.Physical inactivity, defined as not meeting the minimum of physical activity to preserve physical fitness and health as recommended by health organizations such as the American College of Sports Medicine (ACSM), American Heart Association (AHA), and the World Health Organization (WHO), is considered to be a leading risk factor for chronic diseases such as obesity, type 2 diabetes, or dyslipidemia . Loss ofIndividual isolation has become common due to the global impact of COVID-19. Governments have recommended social distancing to prevent further infection from spreading via social gatherings and any group activities, which in turn leads to the inevitable reduction of outdoor activities as well as workouts in a gym. Pinto and her colleagues reported that COVID-19 promotes the global decline of habitual physical activity, which contributes to the progression of chronic diseases such as obesity, sarcopenia, and diabetes . People Physical inactivity can become a life-threatening problem in older adults with clinical conditions . For exaDecreased muscle mass in older adults is associated with increased mortality and reduced quality of life . Muscle For the reasons discussed above, there is a growing need for an effective countermeasure to EPI to prevent older people from further loss of muscle mass and strength ,24. AlthIn general, muscle growth occurs when the rate of protein synthesis is greater than the rate of protein breakdown , whereas muscle loss occurs when the rate of breakdown exceeds the rate of synthesis . AlthougSynthesis of new proteins typically requires all 20 amino acids, which consist of 9 EAAs and 11 non-essential amino acids (NEAAs). Unlike NEAAs, EAAs need to be provided exogenously, typically in the context of a food source, since our body cannot produce EAAs. Over the past few decades, clinical studies have shown that EAAs, but not NEAAs, simulate MPS ,29. EAAsMuscle is composed of specific ratios of 20 AAs, indicating that a particular amount of each EAA is required to produce new muscle protein. It was therefore thought that mimicking the EAA profile in muscle protein would be the most effective composition to stimulate muscle protein synthesis. However, clinical research discovered that the optimal composition of EAAs is different from the EAA profile of muscle protein for several reasons ,31,36,37The stimulation of MPS depends largely on the rate of EAA appearance in the circulation following intake of dietary EAA sources such as mixed meals, protein food sources, or EAA supplements ,38. ContGiven sufficient availability of all the EAAs, dietary leucine can activate intracellular signaling responsible for the stimulation of MPS, i.e., the mTOR signaling pathway. Leucine may also act as an insulin secretagogue, leading to further stimulation of MPS through the insulin receptor . StudiesIt has been repeatedly demonstrated in clinical studies that dietary EAAs are effective in enhancing MPS and thus lean body mass (reflecting muscle mass) in older adults in various circumstances. For example, a small amount of dietary EAA intake  for 12 weeks significantly increased lean body mass in healthy older women . In addiMetabolic dysfunction in aging can be ameliorated by free EAAs, likely through improvements in muscle mass. Eleven g of EAA + arginine supplementation twice a day for 16 weeks in older adults with insulin resistance increases lean body mass . In addiTaken together, these data indicate that the optimal stimulation of MPS and thus better preservation of muscle mass in the EPI situation can be best accomplished by the provision of a sufficient amount of a balanced composition containing all the EAAs in free form.Dietary EAA intake, particularly when combined with resistance exercise training, increases muscle mass, strength, and function as well as muscle quality (defined as muscle strength or function per unit of muscle mass) ,6,27. OlThe decline of strength and function with advanced age is only partially explained by loss of muscle mass. This observation implies a loss of muscle quality, which is likely due in part to a progressive accumulation of non-functional proteins in the muscle through suppressed muscle protein turnover ,36. StimMitochondrial function declines progressively with aging . Recent To summarize, supplemental EEA consumption can improve muscle quality via (1) increased functionally active protein, (2) mitochondrial biogenesis, and (3) efficacy in energy-generating machinery in mitochondria. All of these processes are likely to be mediated by all stimulation of protein turnover.EAAs can serve as a promising nutraceutical to attenuate the accelerated progression of sarcopenia in the COVID-19 era. Here, we provide conceptual guidelines for dietary EAA intake to maximize muscle health in terms of dosage, composition, timing, and frequency of dietary EAA intake.The first key to optimal EAA supplementation is determining the preferred dosage. The optimal amount of EAAs per intake for boosting MPS in older adults is approximately 15 g, as it was shown that the stimulation of MPS is linearly increased from a dose of 3 g up to 15 g of dietary EAA intake, which stimulates MPS to the same extent as 40 g of whey protein . HoweverThe second key to dietary EAAs in preserving muscle mass and function is to consume an optimal composition of all nine EAAs . The maximal synthesis of new muscle protein requires the provision of all the EAAs, and a specific proportion of individual EAAs determined by clinical studies. For better results, it is recommended to enrich leucine in the balanced EAA composition for older adults to maximize net gain in muscle protein via MPS stimulation . KatsanoThe third key to dietary EAAs in preserving muscle mass is the optimal timing of consumption. EAA intake between meals will help to preserve the postprandial rate of MPS in conditions in which age-related anorexia and weakened masticatory activities in older adults ,62 inducIt is recommended for older adults to consume up to 15 g of balanced dietary EAAs before breakfast, between meals, and immediately before bedtime to maximize the anabolic response  . In addiMaintaining muscle mass and function with aging has become increasingly challenging for older individuals in the current circumstance of COVID-19 owing to the EPI-mediated acceleration of loss of muscle mass and function, particularly in older individuals. COVID-19-based EPI induces loss of muscle mass and function similar to other catabolic circumstances, including restriction to an intensive care unit or serious trauma. While there exist no safe and effective drugs to reverse sarcopenia, dietary EAAs are a promising nutraceutical to effectively prevent loss of muscle mass and quality in EPI or in various disease conditions such as cancer cachexia, heart failure, and chronic kidney disease. It is important to consume balanced EAAs with optimal dosage, composition, timing, and frequency in order to achieve superior effects as compared to other potentially anabolic nutrients, including high-quality protein. EAAs can better preserve muscle mass and also improve muscle quality than any intact dietary protein. Further, supplementation of the diet with an appropriate composition of free EAAs, when combined with exercise, could enhance gains in muscle mass and physical performance in older adults, with associated health and social benefits. Due to the fact that previous studies were largely conducted in normal conditions, more clinical evidence with respect to the effect of EAA supplementation needs to be accumulated in the condition of EPI.


MicroRNAs (miRNAs) are a group of endogenous small non-coding RNAs that regulate gene expression. In general, miRNAs can guide their effector partners in the cytoplasm, Argonaute proteins, to silence transcripts with sequence complementarity by mRNA cleavage or translation resting. They can also control gene expression by targeting promoters or enhancers in the nucleus. In plants, miRNAs regulate plant development and response to environmental stresses by controlling expression levels and activities of a variety of downstream genes. Even though a large number of plant miRNAs have been identified and linked to various cellular processes, our understanding of the precise roles and mechanisms of miRNAs in plant development, evolution, and adaptation is still limited. This Research Topic presents new and important findings on three fronts: the roles of miRNAs in plant morphology and environmental stresses, the regulatory network based on multi-omics data, and reviews and applications of two classic methods in miRNA study.Ren et al., further confirmed this phenomenon in sweet potato by examining the miRNA circuit between miR319 and its target TCPs. Intriguingly, they revealed that the significance of IbmiR319-targeted IbTCPs in leaf anatomical morphology is accredited to photosynthetic rate caused by the change in leaf submicroscopic structure. Branching is another critical morphologic trait in many plants. Mallet et al., first reviewed and highlighted the regulatory contribution and the action of evolutionarily conserved miRNA factors in different species, and then identified seven miRNAs and their nine corresponding target genes potentially involved in branching in Rosebush.Several classical miRNAs are proven to play an important role in plant morphological development. Li et al., expanded this line of investigation by examining the mechanism of miRNA-mediated root growth and development in response to nutrient deficiency in peanut (Arachis hypogaea L.). Under both nitrogen and potassium deficiency, the dry weight of both shoot and root tissues was significantly reduced. Li et al., identified the down- and up-regulated miRNAs  that were potentially associated with these changes by screening expression patterns of the miRNA target genes under these stress treatments. Villalba-Bermell et al., performed experiments that mimicked the climate change by inducing combined adverse environmental conditions to scan how the core miRNA network reacts. Under the various combinations of four stresses , they found that a high proportion of the miRNA families showed a non-additive response to multiple stresses in comparison to that observed under each one of the stresses individually.From the early days of studying miRNAs, scientists have found several miRNAs that were involved in the response to environmental stresses in model plants. Zhang et al., revealed a novel scenario in which MIR157d became the target of Verticillium dahlia. They showed that a trans-kingdom fungal sRNA, VdrsR-1, could be secreted into host cells and target miR157d and further modulate plant floral transition by affecting the miR157d/SPL13A/B regulatory module, resulting in prolonged host vegetative growth that would benefit fungal propagation. On the other hand, our knowledge on the highly conserved miRNAs is expanding due to more inquiries into the functions of their target genes. Taken miR160 and their target ARFs (Auxin response factors) as an example, in addition to the classical role in auxin response, functions of the circuits in many aspects of development such as flowering time, fiber length, germination, tillering, leaf morphology, etc., were also reported in different plants. In addition, they were shown to take part in a series of biotic and abiotic stresses, including responses to stress caused by bacteria, fungi and pest, and induced by heat, cold, and drought .A recent hotspot of small RNA (sRNA) studies is to examine their roles in responding to diseases caused by bacteria or fungi. Lactuca sativa, Deng, Qin et al.) and foxtail millet , respectively. By integrating multiple omics datasets including genome, transcriptome, miRNAome, degradome, and the correlation among them, much noise has been removed from the gene regulatory network centered on miRNAs. Consequently, clearer network motifs such as feed-forward loops were identified, and many regulations were discovered and found to be conserved in other species. Therefore, many previously unknown regulations uncovered by these studies are thought to be legitimate for follow-up studies.As multi-omics has become a powerful tool to uncover gene functions, the high noise often hinders its application, especially in non-model plants. This Research Topic features the reporting of two genome scaled miRNA regulatory networks involving upstream transcription factors and downstream targets constructed in lettuce . Li and Ren creatively applied this method by using publicly available PARE datasets to systematically explore the miRNA processing modes. Their effort revealed a conserved processing mode existing in four examined plants.Molecular biological and high-throughput sequencing methods for miRNA research have greatly accelerated the understanding of miRNA functions. For instance, the short tandem target mimic (STTM) approach could capture the endogenous miRNAs as a sponge and reveal the effect of miRNA loss-of-functions. via CRISPR-based genome editing as an emerging technology will also greatly value our knowledge of plant miRNAs. miR-CRISPR approach allows us to concurrently knock out miRNA family loci or selectively knock out individual members. Similar approaches can be applied to the target genes of miRNAs. A sophisticated combination of the strategies will provide clearer pictures of the roles of corresponding plant miRNAs in near future.The regulatory roles and mechanisms of miRNAs in plant development, evolution, and adaptation are constantly being discovered and expanded, including new functions of those known and conserved miRNAs, even miRNA themselves have become the target of plant-fungus interaction. At the same time, the methods on miRNA research are also continuously evolving. Expanded use of STTM and PARE-seq are providing strong support for functional studies of miRNAs in non-model plants. It has become very promising that the full mining of multi-omics data centered on miRNAs will greatly improve the existing understanding of miRNA function, evolution, etc., in the future. Functional analysis of miRNAs XY prepared the first draft of this Editorial. LL, TU, and XZ revised it. All authors approved the Editorial for publication.This work was supported by the National Natural Science Foundation of China (32070248) and Beijing Academy of Agriculture and Forestry Sciences .Author TU was employed by Ficus Biotechnology. The remaining 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.


The formation of functional eggs (oocyte) in ovarian follicles is arguably one of the most important events in early mammalian development since the oocytes provide the bulk genetic and cytoplasmic materials for successful reproduction. While past studies have identified many genes that are critical to normal ovarian development and function, recent studies have highlighted the role of mechanical force in shaping folliculogenesis. In this review, we discuss the underlying mechanobiological principles and the force-generating cellular structures and extracellular matrix that control the various stages of follicle development. We also highlight emerging techniques that allow for the quantification of mechanical interactions and follicular dynamics during development, and propose new directions for future studies in the field. We hope this review will provide a timely and useful framework for future understanding of mechano-signalling pathways in reproductive biology and diseases. In mammals, the ovarian follicles housing the oocytes are the functional units for female reproduction. The maturation of follicles, or folliculogenesis, is not only essential for supporting oogenesis, but also triggers the production of hormones for female sexual characteristics and early pregnancy. The developmental stages of follicles, loosely defined by the follicle size, the number of cells at the follicular envelope and the morphology, can be classified into the primordial, primary, secondary and antral follicle stage  Figure . Follicuex vivo, such as the seminal work by Eppig et al. on 2D systems and organ culture  around the GCs . It takeOne of the most crucial internal components of the follicle is the BM. The basal lamina separating the TCs from the GCs is typically composed of isoforms of collagen IV and laminin , but theBM is common in most tissues in the body and is involved in a variety of diseases . The thiDrosophila, BM stiffness has been shown to determine the shape of developing egg chambers  and the cells in the centre (compression) lead to differential cell shape and division orientation   , therebyr (VEGF) .While the role of TCs in steroid production and hormonal regulation is well documented, the structural and mechanical functions of these cells are less well understood. Recently, cancer-associated fibroblasts have been shown to self-organise to form a capsule around tumour cells and initiate mechanotransduction through active compression . The conDespite growing evidence that mechanical signalling can impact follicle development, questions remain on how these mechanical forces are generated and maintained within the follicles. In particular, it is not known how GC proliferation, which may generate tissue pressure, is coupled to BM remodelling and TC-generated compressive stress during follicle development. Addressing this will require novel methods to quantify cellular dynamics, tissue mechanics and mechanosensing activities in the ovarian follicles see .A key morphological event is the emergence of a fluid-filled cavity (lumen) in the antral follicles . Fluid cin vitro , which is an anionic glycosaminoglycan (GAG) matrix with high molecular weight  . Their aThere has been recent progress in understanding the spatio-temporal dynamics of interstitial ECM in the context of ovarian ageing, fibrosis, and inflammation. During ovarian ageing, the overall collagen deposition increases while the total HA content decreases, with no significant change in the molecular weights . This fivia matrix metalloproteinases, plasminogens, and associated enzymes in ovaries  and activin to maintain primordial or pre-antral follicle dormancy . Here weThe concept of mechanobiology in ovarian biology is relatively new, and biophysical studies to quantify tissue mechanical properties in ovaries remain scarce. To date, AFM remains the primary tool to measure the ovarian biomechanical properties, such as the follicle and stromal stiffness during reproductive ageing and menopause . Here, tThe above-mentioned techniques are mostly confined to measuring the surface mechanics of tissues. To quantify mechanical properties within the tissues, other tools such as magnetic tweezer have been developed. Here, magnetic beads or ferrofluid oil droplets are introduced into tissues, which can be manipulated in the presence of an externally applied magnetic field. If the magnetic properties of the beads or droplets is known, the force-displacement profiles can be used to calculate the local stiffness and viscosity of the tissue . In recein vitro cell aggregates  and in vitro maturation (IVM). Both approaches generate relatively low success rates, potentially due to the removal of the follicle’s mechanical environment that helps to ensure oocyte health. The design of novel biomaterials to provide appropriate mechanical signals may contribute to future improvement of IVF and IVM and even oocyte rejuvenation. Of note, the ovaries are similar to many organs in terms of tissue architecture and functions, and similar biophysical principles may operate in these diverse systems. Indeed, recent work revealed the role of mechanics in lymphocyte infiltration and stromal remodelling during lymph node expansion  that is known to take place during ovarian development? Recent work revealed that cell-cell fluid exchange can lead to collective cell death and the selection of functional eggs in ogenesis , suggest


Selenium (Se) is an important trace element that mainly occurs in the form of selenocysteine in selected proteins. In prokaryotes, Se is also required for the synthesis of selenouridine and Se-containing cofactor. A large number of selenoprotein families have been identified in diverse prokaryotic organisms, most of which are thought to be involved in various redox reactions. In the last decade or two, computational prediction of selenoprotein genes and comparative genomics of Se metabolic pathways and selenoproteomes have arisen, providing new insights into the metabolism and function of Se and their evolutionary trends in bacteria and archaea. This review aims to offer an overview of recent advances in bioinformatics analysis of Se utilization in prokaryotes. We describe current computational strategies for the identification of selenoprotein genes and generate the most comprehensive list of prokaryotic selenoproteins reported to date. Furthermore, we highlight the latest research progress in comparative genomics and metagenomics of Se utilization in prokaryotes, which demonstrates the divergent and dynamic evolutionary patterns of different Se metabolic pathways, selenoprotein families, and selenoproteomes in sequenced organisms and environmental samples. Overall, bioinformatics analyses of Se utilization, function, and evolution may contribute to a systematic understanding of how this micronutrient is used in nature. The essential trace element, selenium (Se), plays a critical role in the growth and development of many organisms from bacteria to humans ,2. Altho5Se2U, or SeU), a tRNA selenonucleoside existing at the wobble position of the anticodons of several tRNAs, and in a Se-containing cofactor (Se-cofactor) used by certain molybdoenzymes [In some prokaryotes, Se is also present in 5-methylaminomethyl-2-selenouridine  have been carried out in various organisms , which could improve our understanding of how this micronutrient is used by different organisms and how the distribution and functions of selenoproteins have been shaped by evolutionary pressures.In this review, we mainly focus on recent advances in bioinformatics and comparative genomic analyses of the metabolism and function of Se, as well as their evolutionary trends in prokaryotes to achieve a more integrated picture of Se utilization in a wide range of organisms. We also discuss recent progress in metagenomic analysis of Se usage in environmental samples, which may provide valuable information for exploring the relationship between environmental factors and the use of this element.Se occurs as inorganic species  and in organic forms in organisms. It appears that Se utilizes the sulfur metabolic pathways, which could be taken up, in the form of selenite/selenate, by the sulfate transport system and reduced to selenide via the assimilatory sulfate reduction system . It was In prokaryotes, the current Se metabolic pathway is comprised of three branches, the Sec, SeU, and Se-cofactor utilization traits. A general scheme of the three Se utilization traits in bacteria is shown in Sec (a specific tRNA whose anticodon matches the UGA codon), and several protein factors dedicated to Sec incorporation. Briefly, the SECIS element binds to the Sec-specific elongation factor (SelB) and forms a complex with Sec-tRNASec. The tRNASec is first charged with serine to yield seryl-tRNASec by canonical seryl-tRNA synthetase (SerRS) and then converted to selenocysteyl-tRNASec by Sec synthase (SelA). SelA utilizes selenophosphate as the active Se donor, which is synthesized from selenide and ATP by SelD.The molecular mechanisms for the biosynthesis and incorporation of Sec into selenoproteins in prokaryotes have been comprehensively summarized in several previous reviews ,24,25,26Sec kinase (PSTK), are needed for the incorporation of Sec into protein [In archaea and eukaryotes, although the biosynthesis of Sec adopts a similar mechanism as in bacteria, additional steps and enzymes, such as the archaeal/eukaryotic Sec synthase (SecS) and O-phosphoseryl-tRNA protein ,27. Howe protein . In addi protein ,29.With regard to the other two Se utilization traits, the 2-selenouridine synthase  has been known to be responsible for the conversion of 2-thiouridine present in some bacterial tRNAs into SeU , while tBacillus selenitireducens and SerV01 from Staphylococcus aureus) have been proposed to be involved in this process in certain organisms [Escherichia coli, and that selenite reduction via Trx system might be an important early step for bacterial selenoprotein biosynthesis [Some other genes have also been reported to participate in Se metabolism in prokaryotes, such as cysteine (Cys) desulfurase/Sec lyase, selenate reductase, and several putative selenite reductases found in different organisms. Cysteine desulfurase/Sec lyase proteins provide sulfur derived from Cys for various processes and/or deliver Se from Sec to SelD for selenoprotein synthesis . On the rganisms ,39,40. Iynthesis ,42.In the past twenty years, a number of selenoprotein genes have been experimentally or computationally identified in various bacteria and archaea. Although several prokaryotic selenoprotein families, such as SelD, glutathione peroxidase (GPX), deiodinase-like (DIO), peroxiredoxin (Prx), and methionine-S-sulfoxide reductase A (MsrA), are also detected in eukaryotes, most of them occur exclusively in bacteria .To date, the majority of bacterial selenoprotein genes were identified using bioinformatics approaches. Both SECIS-dependent and SECIS-independent algorithms have been developed to predict selenoprotein genes in genomic and metagenomic datasets ,44. The In archaea, SECIS elements are mostly located in the 3′-UTR of selenoprotein genes and exhibit quite different structural features to those in bacteria . Both SETo date, more than 80 selenoprotein families and subfamilies are known in prokaryotes. The majority of these selenoproteins contain a Trx-like fold with a redox-active motif. Although more and more selenoprotein genes have been identified in different genomic and metagenomic datasets, a complete collection of prokaryotic selenoproteins is still lacking. Here, we have summarized all the previously reported selenoproteins  from the literature ,66,67,68Sec is a key component for selenoprotein biosynthesis, its efficient identification would be beneficial to the prediction of new selenoprotein families if no known selenoproteins could be detected in genomes with tRNASec. A tRNASec-specific identification tool named Secmarker was recently developed based on conserved structural features of those tRNAs, which revealed new insights into the biology of tRNASec and led to the discovery of novel bacterial selenoprotein families [Since tRNAfamilies .Comparative genomics is an important research field in bioinformatics, which provides a powerful strategy for unraveling the functions and evolutionary dynamics of various genes, pathways, and other characteristics conserved or unique across different species or lineages ,70. By uSyntrophobacter fumaroxidans that has the largest prokaryotic selenoproteome reported so far (39 selenoprotein genes). Although the reasons for such an unusual distribution of Sec utilization are not clear, a dynamic and delicate balance between Sec acquisition and selenoprotein loss events observed in different phyla may partially explain the discrepancy between the catalytic advantages provided by Sec and its restricted use in nature [An early study examined the Sec biosynthetic pathway and known selenoproteins in approximately 600 bacterial and archaeal genomes . Sec wasn nature .Several recent comparative studies have analyzed different Se metabolic pathways, related key genes, and selenoproteomes by using much more sequenced prokaryotic genomes, which not only suggest new functions for several known Se metabolic genes but also imply novel genes involved in Se metabolism and homeostasis. For example, one study reported the presence of a SelD-like protein in certain orders of Crenarchaeota , which has originated from SelD  and might be involved in sulfur metabolism  in hyperthermophilic sulfur-reducing archaea . AnotherA more extensive investigation of the distribution and evolution of Se metabolic pathways and selenoproteins in bacteria have been conducted by analyzing more than 5200 genomes, which demonstrates the largest picture of Se utilization in this kingdom . AlthougHelicobacter pylori strains and related Epsilonproteobacteria, which revealed that Sec incorporation system was lost prior to the split of H. acinonychis and H. pylori, probably due to the adaptation of their progenitor to the host [C. lanienae genomes have completely lost Sec biosynthetic genes and selenoprotein genes, which is a unique feature of this newly defined clade [C. jejuni strains, deletion of the genes encoding Sec insertion machinery and selenoproteins was detected in two C. jejuni strains isolated from guinea pigs, which might be associated with host specialization related to guinea pig diet , anatomy, and physiology [In addition, the complete loss of Sec biosynthesis machinery and selenoproteins was recently found to have occurred in closely related species or even different strains of the same species. Cravedi et al. analyzed the evolution of Sec biosynthesis machinery genes and the selenoproteome of several the host . Miller ed clade . Similarysiology .In archaea, only nine selenoprotein families were previously discovered in a small number of organisms in Methanococcales, Methanopyrales, and Lokiarchaeota ,46,47. ASec is completely encoded inside the C-terminal extended selB gene in diverse species of Alphaproteobacteria  [Sec and for controlling the expression level of selB in bacteria.Very recently, a bioinformatics study examined SelB sequences in certain Alphaproteobacteria and found that the tRNAterales) . This isMetagenomic analysis has become a very popular tool for understanding the microbial diversity and their metabolic potentials in different environments. In the past decade, the rapidly expanding field of metagenomics has produced a vast amount of environmental genomic data, from the world’s oceans to human gut microbiota ,81,82. PThe oceans contain a large number of microbes that cannot be cultivated in vitro. It has been reported that marine biogeochemical cycles and the utilization of Se have co-evolved and could influence each other ,84. By uAn early comparative analysis of Se utilization in the marine microbes was conducted based on 44 diverse aquatic samples from the GOS dataset, which generated the first map demonstrating the distribution and evolution of Sec and SeU utilization traits in a global biogeographical context . ApproxiA much larger comparative metagenomic study was recently performed to examine the biogeographic distribution of both selenoprotein genes and metalloprotein genes in a diverse range of marine, freshwater, and hypersaline environments from the updated GOS dataset . More thIn addition to the GOS project, the Tara Oceans metagenomic dataset was also used to characterize Se utilization in various marine microbial communities . By idenExcept sea water, the use of Sec in marine sediment microbiome was also investigated based on the metagenomic data from the sediments of a deep-ocean industrial waste dump site . By analTo date, metagenomic analyses of Se metabolism and selenoproteins in other environments are very rare. Two recent metagenomic studies examined the abundance of selenate reductase genes in different biosamples from coalmine-impacted aquatic sediments and membrane biofilm reactors, which revealed that nitrate and sulfate could inhibit selenate reduction (a part of the metabolism for synthesis of selenoproteins) and further influence Se status and/or selenoprotein biosynthesis ,89. FutuBioinformatics provides a powerful tool for investigating Se utilization, function, and evolution in different kingdoms of life. Most of these studies have aimed for the identification of selenoprotein genes in different genomic datasets. Compared to other trace elements, such as metals, prediction of selenoprotein genes and the selenoproteome in different organisms is easier and more reliable, due to several highly specific sequence-structural features for Sec insertion machinery. More than 80 selenoprotein families or subfamilies have been reported in the recent decade, most of which are thiol-based oxidoreductases. Recent progress in comparative genomic research of Se metabolism and selenoproteins in prokaryotes has provided important information about the general principles of Se utilization and evolutionary trends in biology. In addition, comparative metagenomics may offer new insights into the use of Se in a much wider range of microbes, as well as its relationship to various environmental conditions. In the future, with the rapid increase in the number of sequenced genomes and improved computational techniques for identifying more selenoprotein genes, bioinformatics and comparative genomics/metagenomics will play a more important role in elucidating Se utilization and function in nature.


This Special Issue on “Adaptive Signal Processing and Machine Learning Using Entropy and Information Theory” was birthed from observations of the recent trend in the literature. Information theoretic learning (ITL) approaches have recently emerged as an effective solution to handle scenarios when we require specific models that fit the data, even in noisy and adverse conditions, and especially when the error distribution is non-Gaussian, such as in supervised learning.The presence of strong disturbances in the error signal can severely deteriorate the convergence behavior of adaptive filters and, in some cases, cause learning algorithms to diverge. Entropy-based cost functions have replaced mean-square-error (MSE)-based ones and have been widely used in adaptive signal processing and machine learning to improve performance by designing and optimizing effective and specific models that fit the data, even in noisy and adverse conditions.Our goal is to publish recent developments in the areas of adaptive signal processing, machine learning, and deep learning using information theory and entropy to improve performance in widespread and popular problems, and also to provide effective solutions to emerging problems.These learning techniques rely on the paradigm of learning from data that have become indispensable tools for extracting information, making decisions, and interacting with our environment.The scope of the Special Issue includes survey, theoretical and applications papers pertaining to all problems involving learning from data. We were able to garner articles submitted on a wide range of topics in this Special Issue. We published 11 papers in our Special Issue. Here, is a synopsis of the eleven papers:In the first paper , titled The second paper , titled The study aims to investigate whether information–entropy measures may provide evidence for guiding discriminative pruning in a neural network for medical data processing, particularly cancer research, by using three cancer databases: breast cancer, cervical cancer, and primary tumor. The authors aimed to investigate the post-training neuronal pruning methodology using dissimilarity measures inspired by the information–entropy theory; the results obtained after pruning the neural network were an improvement over the existing methods.The third paper , titled The authors first revisit the celebrated balance heuristic estimator, a widely used Monte Carlo technique for the approximation of intractable integrals. Then, they establish a generalized framework for the combination of samples simulated from multiple proposals. Their approach is based on considering as free parameters both the sampling rates and the combination coefficients, which are the same in the balance heuristics estimator. Their framework contains the balance heuristic as a particular case. Therefore, their new family of estimators generalizes the balance heuristic. They address five cases of special interest, depending on which parameters are free and the number of samples simulated from each technique. Then, for these five examples, they find the variances for some notable selection of parameters showing that, for the important case of equal count of samples, their estimator with an optimal selection of parameters outperforms the classical balance heuristic. Finally, new heuristics are introduced that exploit the theoretical findings.The authors in the fourth paper , titled The paper also proposes a way to jointly train all the branches of a multi-exit model without hyper-parameters by weighting the predictions from each branch with a trained confidence score. Each confidence score is an approximation to the real one produced by the branch, and it is calculated and regularized while training the rest of the model. They evaluate their proposal on a set of image classification benchmarks, using different neural models and early exit stopping criteria.The authors in the fifth paper , titled The sixth paper , titled A clarity evaluation module is used to adaptively determine whether the input image is a blurred image using improved information entropy. Extensive experiments were performed, the results of which show that the proposed method can detect both blurred and clear images well in poor environments (complex illumination and occlusion). The detector proposed achieves larger gains compared with state-of-the-art detectors. The proposed method can enhance the vehicle feature details in blurred images effectively and improve the detection accuracy of blurred aerial images, which shows good performance with regard to resistance to shake. The paper titled “A Novel Noise Reduction Method of UAV Magnetic Survey Data Based on CEEMDAN, Permutation Entropy, Correlation Coefficient and Wavelet Threshold Denoising” is the seventh paper , and it The least-square twin K-class support vector machine (LST-KSVC) used in leak detection of water pipelines is a novel, simple and fast multi-classification method. However, LST-KSVC has a non-negligible drawback in that it assigns the same classification weights to leak samples, including outliers that affect classification; these outliers are often situated away from the main leak samples. To overcome this shortcoming, the maximum entropy (MaxEnt) version of the LST-KSVC, called the MLT-KSVC algorithm, is proposed in the eighth paper, titled “Leak Detection in Water Pipes Based on Maximum Entropy Version of Least Square Twin K-Class Support Vector Machine” . In thisA major advantage of the use of passive sonar in the tracking of multiple underwater targets is that they can be kept covert, which reduces the risk of being attacked. However, the nonlinearity of the passive Doppler and bearing measurements, the range unobservability problem, and the complexity of data association between measurements and targets make the problem of underwater passive multiple target tracking challenging. To deal with these problems, the cardinalized probability hypothesis density (CPHD) recursion, which is based on Bayesian information theory, is developed to handle the data association uncertainty, and to acquire existing targets’ numbers and states  in the ninth paper  titled “A novel variational autoencoder in the quaternion domain H, namely the QVAE, has recently been proposed, leveraging the augmented second order statics of H-proper signals.The tenth paper , titled In the fault monitoring of rotating machinery, the vibration signal of the bearing and gear in a complex operating environment has poor stationarity and high noise. How to accurately and efficiently identify various fault categories is a major challenge in rotary fault diagnosis.Most of the existing methods only analyze the single channel vibration signal and do not comprehensively consider the multi-channel vibration signal.In the final and eleventh paper , titled Overall, these eleven papers represent an outstanding perspective of current research in the areas covered in our original proposal. They show that the field is thriving and growing. We feature papers on recent developments in the areas of adaptive signal processing, machine learning, and deep learning using information theory and entropy to improve performance in widespread and popular problems, and also to provide effective solutions to emerging problems.We hope you enjoy reading these papers.


Sepsis-associated encephalopathy (SAE) is a common complication caused by sepsis, and is responsible for increased mortality and poor outcomes in septic patients. Neurological dysfunction is one of the main manifestations of SAE patients. Patients may still have long-term cognitive impairment after hospital discharge, and the underlying mechanism is still unclear. Here, we first outline the pathophysiological changes of SAE, including neuroinflammation, glial activation, and blood-brain barrier (BBB) breakdown. Synapse dysfunction is one of the main contributors leading to neurological impairment. Therefore, we summarized SAE-induced synaptic dysfunction, such as synaptic plasticity inhibition, neurotransmitter imbalance, and synapses loss. Finally, we discuss the alterations in the synapse, synapse formation, and mediators associated with synapse formation during SAE. In this review, we focus on the changes in synapse/synapse formation caused by SAE, which can further understand the synaptic dysfunction associated with neurological impairment in SAE and provide important insights for exploring appropriate therapeutic targets of SAE. Sepsis is a severe pathological syndrome that was the most common cause of inpatient death worldwide in 2017, with 48.9 million cases and 11 million deaths  can trigger neurotoxic side effects, such as treating ICU patients with rivastigmine (a cholinesterase inhibitor) can lead to higher mortality rates  and long-term depression (LTD), which represent enhancement and weakening phenomena in the synaptic signal strength between two neurons, respectively. Among them, LTP is generally regarded as one of the main molecular mechanisms constituting the basis of learning and memory. Thus, inhibition of synaptic plasticity can affect learning and memory function. Investigators observed that presynaptic proteins synapsin (SYN), synaptophysin (SYP), postsynaptic density protein 95 (PSD 95), and N-methyl-D-aspartate receptor subunit 2B (NR2B), Amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor subunit (GluR1) were downregulated, and hippocampal LTP inhibition in SAE animals  regulate neuronal excitability and synaptic transmission and maintain the excitatory/inhibitory balance of neural circuits  in the hypothalamus were found to be closely associated with microglia activation and BBB leakage  accumulate at pre- and postsynaptic sites, initiate synapse formation, and play an important role in regulating synaptic transmission and synaptic plasticity  are key regulators of the neuronal morphogenesis . These proteins play different roles in the regulation of synaptic structure and function. SYP, a specific marker of synaptic plasticity, is involved in synaptic vesicle transport and neurotransmitter release, and can specifically reflect the number, distribution and density of synapses  are a family of oligomeric multidomain glycoproteins that are distributed throughout vertebrates and interact with the extracellular matrix, growth factors, cell surface and proteases  in the number of synapses are closely related to many neuropsychiatric diseases. Furthermore, the structural and functional damage of synapses and the abnormalities in the whole process of synapse formation (including synaptic pruning) and synaptic maintenance can lead to synaptic deficits and neurological dysfunction. Therefore, we try to find evidence and relevant clues of abnormal synapse/synapse formation in SAE and explore its molecular mechanism. Taken together, studying the synaptopathy in SAE may bring us a new perspective and direction to understand and explore the pathological mechanism of SAE.CT and YJ collected the literature and wrote the manuscript. HW conceived the topic, wrote and edited the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China (81673417).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.