Key Evidence Research Articles

The contribution of household fruit and vegetable growing to fruit and vegetable self‐sufficiency and consumption

Societal Impact StatementHousehold fruit and vegetable (F&V) production in allotments and gardens can provide sustainable access to nutritious food. The present study demonstrates that UK household F&V production supplies more than half of the vegetables and potatoes and 20% of the fruit that growers consume annually. Importantly, study participants ate 6.3 portions of their recommended 5‐a‐day F&V (70% higher than the UK national average), and their wasted F&V was 95% lower than the national average. This provides key evidence to demonstrate the role household F&V production could play in providing access to fresh F&V, which is key to a healthy, food‐secure population.Summary Improving access to and consumption of fruits and vegetables (F&V) is crucial to a healthy and food‐secure population, as current low intakes are linked to high rates of non‐communicable diseases, premature death and increased healthcare costs. Household F&V production could improve diet quality and food system resilience, however, quantitative evidence for its potential is limited. We studied year‐long F&V production, purchases, donations and waste in UK food‐grower households (N = 85) using a food diary approach. Median year‐round household self‐sufficiency was 51% in vegetables, 20% in fruits and 50% in potatoes. The median daily per capita F&V intake was 507 g, which is the equivalent of 6.3 portions of F&V and 70% higher than the UK national average. On average, own production accounted for half of each household's annual 5‐a‐day F&V requirements. F&V waste was negligible, equivalent to 0.12 portions per day and 95% lower than the UK average F&V waste. We demonstrate that promoting household F&V production could improve food system resilience, diet‐related public health and sustainability.

How Do Young Adult Drinkers React to Varied Alcohol Warning Formats and Contents? An Exploratory Study in France.

Research on alcohol warnings has increased in the last decade, providing key evidence to governments on warning format and contents. The bulk of this research, however, has been conducted in Anglosphere countries, whereas fewer studies have focused on other countries which have high per capita alcohol consumption, and where the high social acceptability of drinking is liable to affect how people accept and react to prevention measures. Since France has one of the highest per capita alcohol consumption rates in the world according to the World Health Organization (WHO), we therefore explore how young adults in France react to warnings on alcoholic beverage advertisements. We conducted 25 in-depth interviews, in 2017, with 18-25-year-old drinkers in France. Respondents were asked open-ended questions on the perceived impact of various warning contents (i.e., on health risk, social-cost risk, and on short- vs. long-term risk) and formats (text only vs. larger text combined with colored pictograms). Warnings that targeted youth-relevant risks (i.e., road accidents or sexual assault) were considered to be the most meaningful and credible, although warnings communicating longer term risks (i.e., brain, cancer) were also thought to be influential. Less familiar risks, such as marketing manipulation and calorie intake, elicited the most negative reactions. Larger text-and-pictogram warnings were considered to be the most effective format in capturing attention and increasing awareness. Regardless of format and content, however, these warnings were not perceived as effective for decreasing alcohol consumption.

Unveiling 2,000years of differentiation among Tungusic-speaking populations: a revised phylogeny of the paternal founder lineage C2a-M48-SK1061.

Previous studies demonstrated Y chromosome haplogroup C2a-M48-SK1061 is the only founding paternal lineage of all Tungusic-speaking populations. To infer the differentiation history of these populations, we studied more sequences and constructed downstream structure of haplogroup C2a-M48-SK1061 with better resolution. In this study, we generated 100 new sequences and co-analyzed 140 sequences of C2a-M48-SK1061 to reconstruct a highly revised phylogenetic tree with age estimates. We also performed the analysis of the geographical distribution and spatial autocorrelation of sub-branches. Dozens of new sub-branches were discovered, many sub-branches were nearly unique for Ewenki, Evens, Oroqen, Xibe, Manchu, Daur, and Mongolian. The topology of these unique sub-branches is the key evidence for understanding the complex evolutionary relationship between different Tungusic-speaking populations. The revised phylogeny provided a clear pattern for the differentiation history of haplogroup C2a-M48-SK1061 in the past 2,000years. This study showed that the divergence pattern of founder lineage is essential to understanding the differentiation history of populations.

Neonatal outcomes of preterm neonates and its predictors in Ethiopian public hospitals: Multicenter prospective follow-up study

IntroductionPreterm birth remains the most significant clinical and public health encounter. Preterm infant outcomes pose key evidence for clinicians and policymakers and are extensively used to set clinical and policy verdicts to improve services. It is necessary to conduct the outcomes of neonates frequently, as it varies from place to place and even from time to time in a similar place. There is limited literature in Ethiopia about preterm neonates’ outcomes and their predictors. ObjectiveThis study aimed to assess the neonatal outcomes of preterm neonates and their predictors in South Gondar zone public hospitals, Northwest Ethiopia, 2021. MethodsA prospective observational study was employed on 462 preterm neonates in South Gondar Zone Public Hospitals. The data were entered into Epidata 4.6 and analyzed using STATA version 16/MP software. A parametric log-normal survival model was used to identify possible predictors for preterm neonate death. Statistical significance was declared at a P-value less than 0.05. ResultThe overall preterm survival rate was 71.1% (95% CI: 66.7, 75.1). Thirty-six percent of preterm neonates were diagnosed with sepsis. One-fourth of the neonates had respiratory distress syndrome. Gestational age greater than 34 weeks (β = 1.04; 95% CI: 0.53, 1.56), respiratory distress syndrome (β = 0.85; 95% CI: 0.49, 1.22), body mass index (β = −1.34; 95% CI: −1.87, −0.80), non-union marital status (β = −0.71; 95% CI: −1.34, −0.09), multiple pregnancies (β = −0.66; 95% CI: −0.99–0.32), multiparous (β = 0.35; 95% CI: 0.01, 0.69), hypothermia (β = −1.19; 95% CI: −1.76, −0.62), Kangaroo Mother Care (β = −1.9; 95% CI: −2.34, −1.41) and non-cephalic presentation (β = −1.23; 95% CI: −1.99,-0.46) were significant predictors. ConclusionIn this study, the preterm survival rate was low. Gestational age greater than 34 weeks, no respiratory distress syndrome, and multiparous mothers were positively associated with the survival of preterm neonates. Though, high pre-pregnancy maternal body mass index, non-union marital status of mothers, multiple pregnancies, hypothermia, Kangaroo mother care is not given, and non-cephalic presentation were negatively associated. A significant focus should be given to implementing WHO recommendations on preventing and caring for preterm births.

Protocol for a Prospective, Observational Cost-effectiveness Analysis of Returning Secondary Findings of Genome Sequencing for Unexplained Suspected Genetic Conditions

PurposeAlthough costly, genome-wide sequencing (GWS) detects an extensive range of variants, enhancing our ability to diagnose and assess risk for an increasing number of diseases. In addition to detecting variants related to the indication for testing, GWS can detect secondary variants in BRCA1, BRCA2, and other genes for which early intervention may improve health. As the list of secondary findings grows, there is increased demand for surveillance and management by multiple specialists, adding pressure to constrained health care budgets. Secondary finding testing is actively debated because some consider it opportunistic screening for future health risks that may not manifest. Given the economic implications of secondary finding testing and follow-up and its unproven clinical utility, the objective is to assess the incremental cost-effectiveness of secondary finding ascertainment per case detected and per unit of improved clinical utility in families of children with unexplained suspected genetic conditions undergoing clinical GWS. MethodsThose undergoing trio genome or exome sequencing are eligible for the study. Positive secondary finding index cases will be matched to negative controls (1:2) based on age group, primary result(s) type, and clinical indication. During the 2-year study, 71 cases and 142 matched controls are expected. Health service use will be collected in patients and 1 adult family member every 6 months. The per-child and per-dyad total cost will be determined by multiplying use of each resource by a corresponding unit price and summing all cost items. Costs will be estimated from the public and societal payer perspectives. The mean cost per child and per dyad for secondary finding–positive and secondary finding–negative groups will be compared statistically. If important demographic differences are observed between groups, ordinary least-squares regression, log transformation, or other nonparametric technique will be used to compare adjusted mean costs. The ratio of the difference in mean cost to the secondary finding yield will be used to estimate incremental cost-effectiveness. In secondary analyses, effectiveness will be estimated using the number of clinical management changes due to secondary findings or the Clinician-Reported Genetic Testing Utility Index (C-GUIDE) score, a validated measure of clinical utility. Sensitivity analysis will be undertaken to assess the robustness of the findings to variation in key parameters. ImplicationsThis study generates key evidence to inform clinical practice and funding allocation related to secondary finding testing. The inclusion of family members and a new measure of clinical utility represent important advancements in economic evaluation in genomics.

Development and validation of Medical Device Key Evidence Tool ('MeDKET'): An evidence-based framework to explain success in selected European and US companies.

Innovating in Medical Device (MD) industry is challenging. This study aims to develop and validate an evidence-based framework that helps innovators of small and large enterprises (SEs and LEs) assess their readiness for successful MD development and deployment. We conducted a key-informant process (stage 1) where 25 international experts identified a list of emergent Health Technology Assessment (HTA) themes they believed were essential to company success. A sample of 22 European and US selected companies (13 SEs and 9 LEs) then reached a consensus on a list of key themes through a robust Delphi process (stage 2). Finally, we constructed (stage 3) and validated (stage 4) the checklist for SEs and LEs. The checklist for SEs and LEs included 21 and 15 items (i.e., fundamental Yes/No questions) with nine overlapping criteria for both SEs and LEs. In both groups, MD success was driven by three major item categories: (i) R&D assessment strategy; (ii) device-outcome measures; (iii) company profiling. Alongside the retrospective validation study, we collected 40 case studies on MDs (23 successes and 17 failures) across the selected enterprises. The retrospective validation provided the proportion of successful and failed case studies that met the 'MeDKET' criteria. We discovered that early HTA plays a pivotal role in MD industry success with different implications based on enterprise size. This study is the first of its kind to provide a holistic picture of the perceived role of early-stage HTA in MD industry success.

Climatology of Tropical Cyclone Rainfall Magnitude at Different Landfalling Stages: An Emphasis on After-Landfall Rain

Abstract Estimating the magnitude of tropical cyclone (TC) rainfall at different landfalling stages is an important aspect of the TC forecast that directly affects the level of response from emergency managers. In this study, a climatology of the TC rainfall magnitude as a function of the location of the TC centers within distance intervals from the coast and the percentage of the raining area over the land is presented on a global scale. A total of 1834 TCs in the period from 2000 until 2019 are analyzed using satellite information to characterize the precipitation magnitude, volumetric rain, rainfall area, and axial-symmetric properties within the proposed landfalling categories, with an emphasis on the postlandfall stages. We found that TCs experience rainfall maxima in regions adjacent to the coast when more than 50% of their rainfall area is over the water. TC rainfall is also analyzed over the entire TC extent and the portion over land. When the total extent is considered, rainfall intensity, volumetric rain, and rainfall area increase with wind speed intensity. However, once it is quantified over the land only, we found that rainfall intensity exhibits a nearly perfect inversely proportional relation with the increase in TC rainfall area. In addition, when a TC with life maximum intensity of a major hurricane makes landfall as a tropical depression or tropical storm, it usually produces the largest spatial extent and the highest volumetric rain. Significant Statement This study aims to describe the cycle of tropical cyclone (TC) precipitation magnitude through a new approach that defines the landfall categories as a function of the percentage of the TC precipitating area over the land and ocean, along with the location of the TC centers within distance intervals from the coast. Our central hypothesis is that TC rainfall should exhibit distinct features in the long-term satellite time series for each of the proposed stages. We particularly focused on the overland events due to their effects on human activities, finding that the TCs that at some point of their life cycle reached major hurricane strength and made landfall as a tropical storm or tropical depression produced the highest volumetric rain over the land surface. This research also presents key observational evidence of the relationship between the rain rate, raining area, and volumetric rain for landfalling TCs.

ПРАДАВНІСТЬ УКРАЇНСЬКОЇ МОВИ, ВІДДЗЕРКАЛЕНА В МОВАХ СУСІДІВ. 2

The essay organizes a picture of homologous series of correspondences in the phenomena of Ukrainian and neighboring languages discovered over several centuries and collected in the author’s research in 2002–2021. Two groups of correspondences — inter-Slavic (1–6) and peri-Slavic (7–10) — became the cornerstones of the topic. These correspondences are found: (1) in the Upper Lusatian language (1st–2nd centuries) — discovered by H. Schuster-Ševc, the common compensatory lengthening of е, о > i in a closed syllable, which, according to the priority assessment of O. Stryzhák (1991), legalizes the concept of the Proto-Ukrainian language; in addition, there are common prothetic wand massive separate lexical and grammatical matches; (2) in Polabian — according to K. Polański, common systematic replacement of length with the result o > ü (still preserved in the Ukrainian dialects of Siverian Region: cf. Ukr. Siver. p[ü]dkladý, p[ǘ]ydem, v[ǘ] z’mem, k[ǘ]stka), and also ě («yat’») > i; prothetic w-, vocalization l̥ > åł > åŭ (as in Slovenian); (3) in the Oskol relic area of Polissia dialects of the Ukrainian language, also in manifestations of the rule of peripheral archaisms and the rule of G. Ascoli; (4) in Belarusian — along with massive lexical and grammatical matches (H. Pivtorák), the key evidence is, according to Yu. Shevelyóv, the contrast of the linguistic landscape on both sides of the Lida-Loiv isogloss strand; (5) in the Novgorod charters (XI-XII centuries) — according to H. Pivtorák as well as to the data provided by V. Yanin and A. Zaliznyak, in some of these charters the systematicity of proto-Ukrainian features indicates the separate influences of Kyiv speech; the lexicographer V. Dahl points to the same; (6) in Proto-Slavic (II century) — there are 18 (Proto-)Ukrainian innovations in the Proto-Slavic dictionary according to the list of M. Swadesh, from this group one innovation is shared with the group of 14 Russian innovations (khoróshyi); (7) in Gothic (III-IV centuries) — Gothic influence was widespread among the Slavs (V. Toporov, V. Martynov); it is followed by common-, East-Slavic and exclusively Ukrainian Gothicisms — both lexical (stráva, vára, tsiámryna, skýba, lýkhva, mýto, shéliah etc.) and grammatical — noun suffix -ar, verb prefix us-; the systematicity of Gothic influences in the toponymy of Ukraine is also proven (Piskáva r. IF, Tanyskáva r. Pl, Frumýliv stream IF, villages Trakhtemýriv Kv, Hovýliv Tr etc.); (8) in Celtic languages (II century) — noun suffix of the singulativ -yna, which arose in the Celtic world (L. Bednarczuk), lexical Celticisms (smeréka, bevz’, oboríh, cheliadýn), onomastics data (Kamúla mt., Rádorobel r.; Dazhdboh, Viy); counterparts in archaeological finds (Potýssia, Ólbia, Kániv, Chornóbyl, Súbotiv); (9) in the vernacular Latin language (II century) — an exclusive Ukrainian analogy with the grammar of Western Romance languages (I. Sharovólskyi) is the simple future imperfect tense (yístymu, znáty-mesh, bráty-mete... /manger-ò, sapr-ai, prender-ete/); contact (rather than book) lexical Latinisms are also here (tsybúlia, chynsh, tsiátka... /cepola, census, centus/); (10) in Scythian (-V / +II centuries) — according to 38 examples attested by Aristophanes, the Scythian pronunciation of Greek words had the same sound substitutions as the current Ukrainian («θ > t»: Téklia, Tanasiychúk; «χ > k»: Kryshtópivka; «φ > p»: Stepán, Panás, Pylýp, Suprún); according to V. Abaev, the Ukrainian phoneme г [ɦ] is a Scythian heritage; Iranian names of Kyiv residents are known from the annals (Прастѣнъ, Истръ, Съфандръ), Ukrainian has lexical Scythisms (potvóra, pochvára, sharováry), surnames (Perederíy, Peredríy), numerous toponyms; historical theonyms (Khors, Symárgl). The final picture can be seen from the features of Ukrainian itself — the all-Slavic character of its material; among its 82 defining features (40 phonetic and 42 lexicalgrammatical), 34 features are unique, and 48 are common to the languages of other Slavs, including: 31 with Upper Lusatian, 29 with Belarusian, 27 with Lower Lusatian, 19 with Polabian, 11 with Russian, from 23 to 20 with each of other 8 Slavic languages. The unique combination of these diagnostic facts from different epoques constitutes the specific essence of Ukrainian. Most of them are self-sufficient.

Jews “Holding the Keys to the Church” and the Posthumous Career of Zelman Wolfowicz of Drohobych

At the end of the nineteenth century in the historiography and popular writing of the three nationalities living in what was then Habsburg Galicia—Polish, Jewish, and Ukrainian—there was an ongoing debate about the motif of the alleged leasing of Orthodox churches by Jews in the seventeenth and eighteenth centuries. The motif of the Jews “holding the keys to the church” was intended, in its own way, to justify the anti-Jewish nature of the Khmelnytsky Uprising of 1648, as well as later rebellions in Ukraine. The problem, however, was that most testimonies of such practices came from literary rather than historical sources. Therefore, the discovery in the archival sources of the character of Zelman Wolfowicz (ca. 1680–1757) from Drohobych, a factor of the starostess Dorota Tarłowa and an informal administrator of the estate, who was sentenced to death for all kinds of economic and criminal offences against the population of the demesne, could have held the key evidence confirming the thesis of the oppression of the Ukrainian people by Jewish leaseholders under the authority of the Polish-Lithuanian Commonwealth. In Zelman Wolfowicz’s case, no confirmation was found that he ever “held the keys to the church.” Nevertheless, he was associated with this practice by means of a misread and misunderstood folk song, whose hero happened to bear the same name: Zelman. The power of legend, combined with antisemitic stereotypes, has caused both historiography and ethnography to bolster this image while ignoring the source evidence.

Smart Contract Design in Distributed Energy Systems: A Systematic Review

Blockchain technology and, in particular, smart contracts based on it, offers a new, decentralized mechanism for entering into and fulfilling contracts in diverse markets. Energy markets are no exception, and indeed, the decentralized nature of the blockchain may be particularly important for them as the penetration of residential prosumers offering microgeneration to the grid grows. At this time, however, the literature on smart contracts in energy markets—and particularly their interaction with the technical infrastructure of the smart grid—is limited and scattered. There is a need to consolidate these studies into a comprehensive understanding of the state-of-the-art in smart contract design for the smart grid. However, no existing reviews focus on smart contracts in energy systems. The scope of our study is the role of smart contracts in energy systems and what limitations they encounter. We conduct a systematic review of this topic, focusing on systems that have been implemented as prototypes. These studies provide key evidence on the scalability of smart contracts for energy systems and their interaction with the technical elements of the smart grid. We selected a pool of 76 papers meeting our criteria, with three others excluded for misinterpreting fundamental aspects of blockchains and smart contracts. After reviewing each paper, we found that this literature falls into four categories: market operations, ancillary services, auditing and monitoring, and cybersecurity. We then identify and examine the cross-cutting concerns of data storage in and interoperability between blockchains. We finally discuss the implications of our findings for future research. In particular, there is likely to be a complex interplay between the data generated and stored via the blockchain versus the data required to meet energy system reliability targets and market obligations for participants.

Once Again on Aristotle and the Identity of the Athenian Nomothetai. A Response to Gertrud Dietze-Mager

This article is a short response to a recent contribution by Dietze-Mager in Erga-Logoi 10.2. There, within a larger discussion of the reliability of the Aristotelian Athenaion Politeia as a historical source, Dietze-Mager argues against our proposed identification of the Athenian nomothetai with a special session of the Assembly. In response, we start with a concise summary of our interpretation of the constitutional stages in the Athenaion Politeia in light of the socio-economic methodology of Politics IV, and clarify the role of Aristotle’s political theory in our reconstruction. We then provide a close reading of some key evidence about the identity of the Athenian nomothetai (particularly Aeschin. III 38-40). We demonstrate that Dietze-Mager’s proposed reading of the relevant passage is linguistically and syntactically problematic, arguing that the only possible interpretation of the relevant procedure as described at Aeschin. III 38-40 involves identifying the nomothetai with a special lawmaking session of the Assembly.

Recycling of eroded crust by mélange diapirs evidenced from the Early Cretaceous arc magmatism in southern Tibet

Crustal material recycling in a subduction factory increases the diversity and complexity of arc magma. However, the exact origin and mechanism of its contribution to arc magma are not fully understood. Here, we present new data on the Molang basaltic rocks from the southern Lhasa terrane to gain an in-depth-understanding of the mechanisms of crustal recycling. The zircon UPb ages indicate that these rocks were emplaced at 128 Ma. They display characteristics ranging from forearc basalts to tholeiitic arc basalts with depleted mantle isotope compositions (εNd(t) = +4.58 to +4.86) and zircon ɛHf(t) values (+7.3 to +8.7). The uniform isotopic composition (SrNd) and fractionation of trace elements show that crustal materials could have been added to the magma source in the form of bulk sediment. Therefore, we have proposed an argument supporting the mélange diapirs model. The age spectra of the inherited zircons are consistent with those of the detrital zircons from the subduction hanging wall. This implies that the inherited zircons may be unmolten residues of eroded forearc crust that survived erosion and subduction from the slab in well-mixed mélange diapirs that passed through a comparatively hot mantle wedge and occur as key evidence for crustal recycling in the arc magma. Based on a synthesis of earlier research, we suggest that the Molang basaltic rocks were derived from the partial melting of the mélange diapirs in a steep subduction setting during a new subduction initiation event involving the Neo-Tethyan oceanic slab.

Musculoskeletal Injury in American Football: A Bibliometric Analysis of the Most Cited Articles

Background: Textbook knowledge and clinical dogma are often insufficient for effective evidence-based decision making when treating musculoskeletal injuries in American football players, given the variability in presentation and outcomes across different sports and different levels of competition. Key evidence can be drawn directly from high-quality published articles to make the appropriate decisions and recommendations for each athlete’s unique situation. Purpose: To identify and analyze the 50 most cited articles related to football-related musculoskeletal injury to provide an efficient tool in the arsenal of trainees, researchers, and evidence-based practitioners alike. Study Design: Cross-sectional study. Methods: The ISI Web of Science and SCOPUS databases were queried for articles pertaining to musculoskeletal injury in American football. For each of the top 50 most cited articles, bibliometric elements were evaluated: citation count and density, decade of publication, journal, country, multiple publications by the same first author or senior author, article content (topic, injury area), and level of evidence (LOE). Results: The mean ± SD number of citations was 102.76 ± 37.11; the most cited article, with 227 citations, was “Syndesmotic Ankle Sprains” published in 1991 by Boytim et al. Several authors served as a first or senior author on >1 publication, including J.S. Torg (n = 6), J.P. Bradley (n = 4), and J.W. Powell (n = 4). The American Journal of Sports Medicine published the majority of the 50 most cited articles (n = 31). A total of 29 articles discussed lower extremity injuries, while only 4 discussed upper extremity injuries. The majority of the articles (n = 28) had an LOE of 4, with only 1 article having an LOE of 1. The articles with an LOE of 3 had the highest mean citation number (133.67 ± 55.23; F = 4.02; P = .05). Conclusion: The results of this study highlight the need for more prospective research surrounding the management of football-related injury. The low overall number of articles on upper extremity injury (n = 4) also highlights an area for further research.

MSR84 How Can Explainable Artificial Intelligence Accelerate the Systematic Literature Review Process?

Systematic literature reviews (SLRs) are key evidence requirements for health technology agency decision-making. However, the exponential increase in published articles makes a thorough and practical literature review increasingly challenging. To help researchers conduct an SLR, we developed a machine learning (ML)-based pipeline to accelerate the title and abstract screening (TIABS) step. We assessed this ML-based TIABS using various human-labeled SLRs to ensure its reproducibility.

An Overview of Current Methods for Real-World Applications to Generalize or Transport Clinical Trial Findings to Target Populations of Interest.

It has been well established that randomized clinical trials have poor external validity, resulting in findings that may not apply to relevant - or target - populations. When the trial is sampled from the target population, generalizability methods have been proposed to address the applicability of trial findings to target populations. When the trial sample and target populations are distinct, transportability methods may be applied for this purpose. However, generalizability and transportability studies present challenges, particularly around the strength of their conclusions. We review and summarize state-of-the-art methods for translating trial findings to target populations. We additionally provide a novel step-by-step guide to address these challenges, illustrating principles through a published case study. When conducted with rigor, generalizability and transportability studies can play an integral role in regulatory decisions by providing key real-world evidence.

Directions and reproduction soil fertility technologies in the post-war period in Ukraine

The article is devoted to the study of the military action's negative consequences on the soil fertility state in Ukraine and directions for their reproduction. The topic actuality is that a third of the arable agricultural lands were affected by military actions, which, taking into account the agrarian direction of production in the eastern and southern regions of Ukraine, threatens a significant decrease in the agricultural products' cultivation. The article aims to substantiate the effectiveness of technologies applied to overcome the affect of military activities on soil fertility reproduction in Ukraine. The study reveals the war negative consequences on the soil structure and properties and argues that it will take hundreds of years to reproduce naturally. The main types of warfare-induced disturbances to soil are defined and described: the soil structure modification (bombs craters, sealing, etc.) and chemical disturbances (pollutants input). Taking into account the existing experience of overcoming the military actions consequences in the agricultural soil reproduction, a certain procedure for reproducing the soil fertility with different degrees and causes of damage is proposed. The options for soil reproduction with a natural integrity of genetic horizons violation and methods of removing contamination with heavy metals (mechanical, physico-chemical, and biological) are considered. For the practical implementation of the proposed measures, an approximate costs' calculation of the soil fertility reproducing from the military actions consequences in Ukraine was made. It has been determined that for the reproduction of soil properties and their suitability for use in agricultural production, the greatest expenses (excluding humanitarian demining) are spent on mechanical melioration (81.8 %). However, the expenses amount depends on the number of shell explosion craters and their caliber, and the methods of reproduction the soil agrochemical properties. The peculiarities of legal regulation in soil conservation and the fertility protection, in determination of damage caused to lands and soils of Ukraine as a result of armed aggression against the country are indicated. The performed calculations will become key evidence in terms of damage amount compensation in lawsuits against the aggressor country. Key words: toxic elements, bombturbation, demining, basalt tuff, bioremediation, phytoremediation.

Inflammatory and interferon gene expression signatures in patients with mitochondrial disease

BackgroundPeople with mitochondrial disease (MtD) are susceptible to metabolic decompensation and neurological symptom progression in response to an infection. Increasing evidence suggests that mitochondrial dysfunction may cause chronic inflammation, which may promote hyper-responsiveness to pathogens and neurodegeneration. We sought to examine transcriptional changes between MtD patients and healthy controls to identify common gene signatures of immune dysregulation in MtD.MethodsWe collected whole blood from a cohort of MtD patients and healthy controls and performed RNAseq to examine transcriptomic differences. We performed GSEA analyses to compare our findings against existing studies to identify commonly dysregulated pathways.ResultsGene sets involved in inflammatory signaling, including type I interferons, interleukin-1β and antiviral responses, are enriched in MtD patients compared to controls. Monocyte and dendritic cell gene clusters are also enriched in MtD patients, while T cell and B cell gene sets are negatively enriched. The enrichment of antiviral response corresponds with an independent set of MELAS patients, and two mouse models of mtDNA dysfunction.ConclusionsThrough the convergence of our results, we demonstrate translational evidence of systemic peripheral inflammation arising from MtD, predominantly through antiviral response gene sets. This provides key evidence linking mitochondrial dysfunction to inflammation, which may contribute to the pathogenesis of primary MtD and other chronic inflammatory disorders associated with mitochondrial dysfunction.

Atherosclerotic renovascular disease: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and the Working Group Hypertension and the Kidney of the European Society of Hypertension (ESH).

Atherosclerotic renovascular disease (ARVD) is the most common type of renal artery stenosis. It represents a common health problem with clinical presentations relevant to many medical specialties and carries a high risk for future cardiovascular and renal events, as well as overall mortality. The available evidence regarding the management of ARVD is conflicting. Randomized controlled trials failed to demonstrate superiority of percutaneous transluminal renal artery angioplasty (PTRA) with or without stenting in addition to standard medical therapy compared with medical therapy alone in lowering blood pressure levels or preventing adverse renal and cardiovascular outcomes in patients with ARVD, but they carried several limitations and met important criticism. Observational studies showed that PTRA is associated with future cardiorenal benefits in patients presenting with high-risk ARVD phenotypes (i.e. flash pulmonary oedema, resistant hypertension or rapid loss of kidney function). This clinical practice document, prepared by experts from the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and from the Working Group on Hypertension and the Kidney of the European Society of Hypertension (ESH), summarizes current knowledge in epidemiology, pathophysiology and diagnostic assessment of ARVD and presents, following a systematic literature review, key evidence relevant to treatment, with an aim to support clinicians in decision making and everyday management of patients with this condition.

Proposal for a Biologic Staging System of Parkinson's Disease.

The Parkinson's disease (PD) research field has seen the advent of several promising biomarkers and a deeper understanding of the clinical features of the disease from the earliest stages of pathology to manifest disease. Despite progress, a biologically based PD staging system does not exist. Such staging would be a useful framework within which to model the disease, develop and validate biomarkers, guide therapeutic development, and inform clinical trials design. We propose that the presence of aggregated neuronal α-synuclein, dopaminergic neuron dysfunction/degeneration, and clinical signs and symptoms identifies a group of individuals that have Lewy body pathology, which in early stages manifests with what is now referred to as prodromal non-motor features and later stages with the manifestations of PD and related Lewy body diseases as defined by clinical diagnostic criteria. Based on the state of the field, we herein propose a definition and staging of PD based on biology. We present the biologic basis for such a staging system and review key assumptions and evidence that support the proposed approach. We identify gaps in knowledge and delineate crucial research priorities that will inform the ultimate integrated biologic staging system for PD.

Abstract 341: Study Of ADAR1 Implicates RNA Editing In Vascular Smooth Muscle Cells As A Mechanism Of Coronary Artery Disease Risk

Adenosine-to-inosine (A-to-I) RNA editing is a common RNA modification catalyzed by ADAR (adenosine deaminase acting on RNA) enzymes. ADAR1 serves a crucial function to edit double stranded RNA (dsRNA) molecules to prevent activation of the dsRNA sensor MDA5 ( IFIH1 ) that stimulates an interferon stimulated gene (ISG) response. Discoveries in human genetics now implicate deficient ADAR1 RNA editing as a causal mechanism in coronary artery disease (CAD). We hypothesize that smooth muscle cell (SMC) specific RNA editing is required to prevent vascular calcification and inflammation. Here, we demonstrate that ADAR1 is the master regulator of RNA editing in primary human coronary artery SMC (HCASMC). ADAR1 KD in HCASMC causes an ISG response characterized by massive upregulation of key ISG genes (e.g. ISG15, IFI6, IFIH1 ). Importantly, ADAR1 KD stimulates the upregulation of genes with known roles in SMC phenotypic transition and CAD risk, including KLF4 , TCF21 , ATF3 , and ZEB2 . This effect is dependent on activation of MDA5. Additionally, we demonstrate ADAR1 and MDA5 regulate SMC phenotypic modulation and calcification in vitro where ADAR1 KD inhibits SMC maturation and dysregulates the calcification gene program in an MDA5 dependent manner. Using scRNAseq data collected from human vascular tissue we show that immunogenic dsRNA are disproportionately expressed in human SMC in atherosclerosis. Similarly, in atherosclerosis prone mice, scRNAseq analysis reveals SMC to have increasing ISG expression as cells transition from mature SMC to a more calcified chondromyocyte phenotype — consistent with MDA5 activation. To further evaluate the role for SMC specific RNA editing in vivo, we generated a conditional SMC specific Adar1 KD mouse ( Adar1 flox/flox , Myh11 CreERT2 , ROSA tdT/+ ). At 2 weeks following SMC- Adar1 KD, mice demonstrate a severe phenotype of elastin degradation and disarray, intravascular hemorrhage, and inflammatory cell infiltration in the aortic wall. This effect was not seen with an endothelial cell specific deletion model ( Adar1 flox/flox , Cx40 CreERT2 ). Here we provide key evidence to support the observations from human genetics that the ADAR1-dsRNA-MDA5 axis is a causal mechanism in vascular disease and warrants further investigation.