Canarieae of the Burseraceae family, composed of trees and shrubs supplied with resin channels. Its uses in folk medicine are related to aromatic properties, which have numerous medicinal applications and are present in reports from traditional peoples, sometimes as the only therapeutic resource. Despite its economic and pharmacological importance in the region, and although the family is distributed in all tropical and subtropical regions of the world, most of the scientific information available is limited to Asian and African species. Therefore, the present work aimed to review the secondary metabolites with possible pharmacological potential of the species Trattinnickia rhoifolia Willd, popularly known as “Breu sucuruba”. To this end, an identification key was created for chemical compounds with greater occurrence in the literature of the genus Trattinnickia. The most evident therapeutic activities in the consulted studies were antimicrobial, antioxidant, anti-inflammatory, antiviral, antifungal, anesthetic and antiparasitic. An expressive chemical and pharmacological relevance of the species was identified, although its potential is insufficiently explored, mainly in the face of the NTDs present in the Brazilian Amazon.Plant-derived products may represent promising strategies in the treatment of Neglected Tropical Diseases (NTDs). From this perspective, it is observed that the Amazon phytogeographic region contains the tribe  Over the years, natural products have been used as raw material sources in the synthesis of chemical compounds that result in new drugs, a good part of which are used in the treatment of Neglected Tropical Diseases (NTDs) . That isIn parallel to the biological variety found in the Amazon Forest, there are NTDs that encompass a group of 17 common infectious diseases in the region, including dengue, rabies, trachoma, buruli ulcer, endemic treponematosis, Hansen’s disease (leprosy), American trypanosomiasis, African trypanosomiasis, cysticercosis, dracunculiasis, echinococcosis, foodborne trematode infection, lymphatic filariasis, onchocerciasis, schistosomiasis and soil-borne helminth infection, as well as leishmaniasis. Public health problems are also included, such as the human immunodeficiency virus (HIV)—which causes the acquired immunodeficiency syndrome (AIDS)—tuberculosis, malaria and other neglected infections. Thus, it is a heterogeneous group of diseases with serious social consequences, due to their high capacity for morbidity.NTDs affect more than one billion people worldwide, with greater severity in individuals submitted to socioeconomic vulnerability, generally belonging to underdeveloped or emerging countries. As a result, social, public health, productivity and life quality problems are intensified, particularly among marginalized populations. Amid the secondary factors related to the persistence of NTDs, the following stand out: (a) gaps in science and research, for presenting insufficient knowledge, non-related to these diseases, (b) market factors, such as high-cost drugs, in existing or developing vaccines, and (c) gaps in public health, represented by poor access to medicines and treatments as a consequence of failures in administrative planning, even when such services are offered for free .From this perspective, NTDs represent an enormous challenge for Brazil and other nations, since they are considered the infections with the highest levels of occurrence—such as cutaneous or visceral leishmaniases, whether endemic or not. These diseases are heightened by their multiple forms of clinical manifestations, which depend on the pathogenicity of the infecting species. Its characteristics modalize leishmaniasis among its subclinical infections, with localized or disseminated microlesions, whether asymptomatic or not. In addition, wounds can spontaneously heal or progress from milder to more severe forms, which is why the WHO recommends priority treatment for this disease .Leishmaniasis is considered an important public health problem in the world and is one of the six most important infectious and parasitic diseases of NTDs, with an annual incidence of 2 million cases of different clinical forms, representing a risk to 350 million people in developing countries ,2.Sarcomastigophara, order Kinetoplastida and family Trypanosomatidae, which are responsible for morbidity and mortality in several countries in tropical zones. Seven species that cause tegumentary leishmaniasis have already been identified in Brazil, six from the subgenus Viannia and one from the subgenus Leishmania. The three main species are: L. (V.) braziliensis, L. (V.) guyanensis and L. (L.) amazonensis, and more recently, the species L. (V.) lainsoni, L. (V.) naiffi, L. (V.) lindenberg and L. (V.) shawi, identified in states in the North and Northeast regions [Leishmaniases are diseases caused by the protozoan of the genus Leishmania that are marked by great clinical pleomorphism. The parasites that cause them are included in the subkingdom Protozoan, phylum  regions .Leishmaniases have factors that are increased by the virulence and dissemination of the protozoan, which depend on the host–parasite relationship. This is because the manifestation of the disease is not only correlated with the species of parasite involved, but also with the susceptibility of the host, assessed by its immune response . FurtherDue to the incipience of first-line medicines and considering the potential of the Amazon, research in the areas of phytochemistry and ethnopharmacology are increasingly important to expand knowledge in strategic areas related to Research, Development and Innovation (RD and I) about traditional medicines. Hence, it is possible to create prototypes of promising new chemotherapeutic agents with anti-leishmanial activity, with minimized or non-existent side effects.Trattinnickia rhoifolia (T. rhoifolia), an angiosperm tree present in the biogeographic region that comprises Central America that belongs to the Burceraceae family, of the Canarieae tribe [Amid the promising Amazonian plants for such objectives, we highlight the species ae tribe ,8.Trattinnickia rhoifolia is used by traditional peoples to cure sore throats and skin lacerations, as well as to treat and prevent tumors and leukemia. To this end, the most used parts of the plant are the trunk bark, resin and leaves [The species d leaves .Trattinnickia, studies have already been carried out on photochemical mapping in the bark of the species Trattinnickia peruviana, which indicated the presence of lichen xanthone and triterpenes. Furthermore, triterpenes and sesquiterpene lactones were isolated in the resin of the species Trattinnickia aspera [Trattinnickia glaziovii [For the genus a aspera ,8,9. Addlaziovii ,8,9.T. rhoifolia, the focus of this study, triterpenes, monoterpenes, amentoflavones, sterols and sesquiterpene lactones have already been identified in different parts of the plant, such as resin, leaves and in the bark of its trunk [Regarding the species ts trunk ,11.Trattinnickia rhoifolia Willd and consequently of the genus Trattinnickia, which is a promising source for obtaining biopharmaceuticals from the production of secondary plant metabolites and, as a result, represents an opportunity in the field of drug innovation. For this reason, it is essential to know the research that addresses its main characteristics, such as taxonomic, ethnopharmacological and phytochemical studies, in order to direct future biological tests based on the bioactive action of the species Trattinnickia rhoifolia Willd.It is important to present the phytochemical mapping of the species Trattinnickia and the studies on their pharmacological potential. Data collection was carried out from September 2020 to May 2021, using the following databases: CAPES journals, PubMed, Science Direct from Elsevier, Wiley Online Library, Springer-Nature, Taylor and Francis, BMC, Hindawi, Scielo, ACS—American Chemical Society, and Google Scholar, as well as the scientific article and patent databases “The LENS” and “ORBIT Intelligence”.In this sense, this study constitutes, methodologically, an analytical bibliographical review related to the mapping of secondary metabolites found in the genus The inclusion criteria for this work were: original articles and exclusive dissertations of the genus and species studied, with full text available in Portuguese, English or other languages. Exclusion criteria were: abstracts, online sites without scientific sources, incomplete texts, unrelated and repeated articles.Burseraceae, genus Trattinnickia and species Trattinnickia rhoifolia Willd, correlated with secondary metabolites and their pharmacological potential. The articles were selected by reading the titles and abstracts of publications, associated with the Boolean descriptor “AND”, in order to refine the samples.As for the search strategy, the descriptive words used in this work were: family Trattinnickia rhoifolia Willd, mainly due to reports of the use of the resin, bark and leaves of the plant by traditional peoples of the Amazon Region and, in this sense, assisting future studies that seek to understand and perform the chemical mapping of that species, highlighting its high pharmacological potential.Therefore, the innovation present in this study consists in elucidating the potential use of the species Trattinnickia rhoifolia and address the scarcity of studies on the classes of metabolites present in the studied species, which comes from the Burseraceae family.Hence, the review contributes to direct future studies that also prove the importance of evaluating the biological activities of the species Burseraceae family has 19 genera and more than 700 species [Boraginales, Dilleniales, Icacinales, Metteniusiales and Vahliales. Besides, this system suggests the inclusion of Burseraceae in the order Sapindales, class Dicotiledoneae and subclass Rosidae (APG IV 2016) [The  species , composeBurseraceae distributed in South America, only 6 are native . In their turn, the other two (Dacriodes and Protium) were introduced and are representative in the Amazon Region [Burseraceae is the natural production of aromatic oleoresins, which are used regionally in alternative medicinal treatments and in the ethnopharmacology of Amazonian traditional peoples. The plant genera Dacryodes and Protium are popularly known as: “almescla”, “breu-branco”, “breu-preto”, “breu-vermelho”, “breu-terra”, “breu-limão”, “ breu-manga”, “caraña”, “copal”, “copal-ouro”, “copal-negro”, “elemi”, “manila-elemi”, “frankincenso”, “gugul”, “maaliol”, “mirra” and “okume” [Of the 19 genera of  “okume” ,11,12.Burseraceae family is concentrated in the oil–gum–resin, from which fractions considered volatile are usually obtained [The mapping of the chemical compounds of the obtained ,12. In pobtained .The manipulation of the resin is historically common among the traditional peoples of the Amazon, who use it in the manufacture of varnishes and paints, along with boat-caulking. The aromatic constituents that are present in the resin, bark and branches of the plant are widely used through combustion, as well as for lighting the homes of traditional Amazonian peoples, as repellents for undesirable insects and also in religious rituals ,11,12,13Burseraceae family focus on the constituents present in its leaves, of which the monoterpenes represent the dominant class of compounds, distributed in limonene, α-phellandrene, p-cimene and their monocyclic derivatives. Aldehydes, ketones and acids are also present, though less frequently [Cryptococcus neoformans var. Neoformans—a systemic human fungus of high prevalence in immunosuppressive patients [The chemical characterization studies of the equently ,15. In pequently ,13. Therpatients .Burseraceae family. The most common and complex are in the genera Canarium and Commiphora, except in the species Boswellia carterii. In those cases, cadinene is isolated in essential oils obtained from the leaves, as the substance is found in lower concentrations in other parts of some species of this family [Canarium, the elemol group was also isolated, which constitutes the synthesis of germacra (10), 4 diene, widely used to combat Phlebotomus—the genus to which the agents that transmit malaria and leishmaniasis belong [There are similar chemical profiles that identify over 30 sesquiterpenes in the s family ,16. Froms belong ,17,18. TProtium leaves are rich in cariophilia, which is generally ubiquitous, and in sesquiterpenes, described as bactericides for the etiological agents that cause acquired respiratory infections, such as otitis, sinusitis and pneumonia [Burseraceae [Canarieae, isolations of furanosesquiterpenes are described, which are furanogermacrane skeletons, forming 2-acetyl-8-12-epoxygermacra-1, (10), 4,7,11 tetraene and 2-methyl-8-12-epoxygermacra-1, (10) 4,7,11-tetraene. It is noteworthy that the active ingredients of these molecules are sources used in the composition of antimalarials [On the other hand, essential oils from neumonia ,18,19. Sseraceae . In studalarials ,18,19, walarials ,18,20.Burseraceae resins, the existence of tetracyclic and pentacyclic triterpenes is identified. These compounds are responsible for important characteristics, such as oxidation, due to the presence of tetracyclic tirucallane in the C-17 side chain, which is found as elemolic acid. In the scientific literature, the anti-inflammatory activity and the inhibition of the production of nitric oxide are also reported, in addition to in vitro antitumor activity [Canarium schweinfurthii and Dacriodes eludis, species of the tribe Canarieae, in which the study related to the respective compounds proved the existence of anti-inflammatory, antimicrobial, antiplasmodic, antiulcerogenic, anticariogenic, antiviral, anti-HIV, hepatoprotective, cardioprotective and analgesic activities [In activity ,19,20. Ttivities ,21,22,23Burseraceae. Kaempferol, quercetin and their respective derivatives were identified in Protium and Commiphora [Burseraceae. However, coumarinolignoids and propacin have already been identified and isolated from Protium opacum—compounds that have hepatoprotective, immunomodulatory and anticancer activities [Protium helio and P. icicariba stand out [In their turn, flavonoids are essential in plant systematics, but there were few technical-scientific reports found about these compounds in mmiphora ,22,23,24tivities ,25,26. Atand out .Burseraceae focuses mainly on pentacyclic triterpenes. The most abundant are the α-amyrin and β-amyrin isomers [Chemical research on the stem of the botanical family  isomers , which h isomers ,13,20, w isomers .P. robustum, P. trifoliatum, P. nitidifolium and P. subserratum, collected in the Amazon region, identified sesquiterpenes in a higher percentage, as well as the following compounds: spatulenol, caryophyllene oxide, Khusimone, α-copaen-4-ol, and in smaller amounts, α-cubeben, α-copaene, trans-caryophyllene, α-trans-bergamothene, γ-muurolene, α-muurolene, γ-cadinene [trans-caryophyllene, α-elemene, α-gurjunene, germacrene D, α- and β-selinene, cis-calamenene, trans-calamenene and cadalene [The studies carried out using stems, branches and bark of the species cadinene ,20, α-cacadalene ,20,28,29Burseraceae, but coumarinolignoid and propacin have already been identified and isolated from the species Protium opacum [The literature also describes the presence of aromatic compounds such as coumarins, phenylpropanoids, flavonoids and, to a greater extent, lignans, which demonstrates the biological potential of the family ,18. TherTrattinnickia rhoifolia Willd is popularly known in the Amazon region as “Breu sucuruba”. Its native origin is not endemic to Brazil, but T. rhoifolia Willd has an Amazon phytogeographic occurrence [Plantae, phylum Tracheophyta, class Magnoliopsida, order Sapindales, family Burseraceae, genus Trattinnickia and species Trattinnickia rhoifolia, which has wide ethnopharmacological use by indigenous peoples , digitized base and cylindrical shaft. In addition, it has a grayish rhytidome with depressions and detachment in small woody plaques, which leave light streaks, lenticels are present, 2 mm thick dead brown skin and 1 cm thick bright orange skin. Orange sapwood has transparent exudation with a “breu” smell [The species u” smell ,12,18.Trattinnickia rhoifolia Willd is more predominant in the upper parts of the species, so that only the aromas attributed to the presence of terpenes are uniform. Due to this characteristic, the resin is used to combat some species of insects from the Psicodidae and Culicidae families. As a result of this practice, there is a reduction in the prevalence of malaria and leishmaniasis in indigenous villages and riverside communities [Trattinnickia are widely known in the Amazon region by popular medicine as repellent, analgesic, anti-inflammatory, expectorant and healing plants [The distribution of the aromatic resin present in the species munities ,30,32,33g plants ,13,20,34Trattinnickia in parasitic diseases such as leishmaniasis [Nonetheless, scientific research that demonstrates its performance is incipient or almost non-existent, as illustrated by the scarcity of studies on the action mechanisms of species of the genus maniasis .Burseraceae family has extensive chemical mapping and demonstration of its pharmacological properties, proven by its anti-inflammatory, antimicrobial, antiparasitic and antifungal activities. However, there are few studies regarding the identification of compounds for the genus Trattinnickia  [Studies involving eicosane and nonacosane produced important antiparasitic effects against strains of or cells ,39. In tnthrene) .Trattinnickia rhoifolia, the existence of amentoflavan was identified, also found in oil-resins, 5α, 6α epoxy-β-sitosterol (IV) and 5β, 6β-epoxy-β-sitosterol (V) [In studies on extracts from the leaves of erol (V) ,46. Besierol (V) .From this perspective, the authors have reported that amentoflavone acts in favor of the inhibitory activity of cAMP phosphodiesterase, among other enzymes. The process of inhibiting these mechanisms results in tissue regeneration ,45. FurtTrattinnickia, which belongs to the Burseraceae family, represents an important ethnopharmacological source widely used by traditional peoples in the Brazilian Amazon due to its cultural and cosmological attributes in the treatment of Neglected Tropical Diseases, related to anti-inflammatory processes and antiparasitic and repellent functions.The extensive bibliographical research revealed that the genus Trattinnickia rhoifolia are similar to the traditional use of the species, which associates the following properties to the “breu scuruba”: anticancer, anti-inflammatory, antimicrobial, neurological and antiparasitic, all attributed to the phytochemistry of the genus.The reviewed scientific literature indicates that the biological activities of The main classes of secondary metabolites, already characterized both in number of compounds and in pharmacological and environmental importance, are: alkaloids, terpenoids, sesquiterpenes, flavonoids, biflavonoids, oxyphytosterols and volatile oils. However, scientific support is restricted to mappings available for Asian and African genera, and studies on the subject are limited to these continents, even though the family is distributed in several tropical and subtropical regions of the world.Trattinnickia as a multipurpose drug related to its pharmacological groups, there are several limitations in the current literature, especially with regard to studies for the species Trattinnickia rhoifolia Willd. On the other hand, popular knowledge bases are important to recognize that traditionally used extracts of the species Trattinnickia rhoifolia Willd can be effective not only when isolated or in direct use, but can also represent new and promising alternatives, with modulating effects when used in combination with other herbs or drugs.Although the results of this review are very promising for the use of the genus Trattinnickia rhoifolia Willd is essential for further work because of the importance of the results raised here, especially given the pharmacological potential of the group, which should be better explored—especially concerning the use of the species for its anti-inflammatory and analgesic activities, as reported by traditional communities in the Amazon region and presented in this article.Therefore, studying the species


The article, Indications for fertility preservation not included in the 2017 Japan Society of Clinical Oncology Guideline for Fertility Preservation in Pediatric, Adolescent, and Young Adult Patients treated with gonadal toxicity, including benign diseases written by Masanori Ono, Kimikazu Matsumoto, Narikazu Boku, Nobuharu Fujii, Yumi Tsuchida, Tatsuro Furui, Miyuki Harada, Yoshinobu Kanda, Akira Kawai, Mitsuru Miyachi, Atsuko Murashima, Robert Nakayama, Hiroyuki Nishiyama, Chikako Shimizu, Kazuhiko Sugiyama, Yasushi Takai, Keishi Fujio, Ken‑Ichirou Morishige, Yutaka Osuga, and Nao Suzuki was originally published Online First without Open Access.http://creativecommons.org/licenses/by/4.0.With the author(s)’ decision to opt for Open Choice the copyright of the article changed on February 16, 2022 to © Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The original article has been corrected.


Housing is one of the major determinants of human health and the current COVID-19 pandemic has highlighted its relevance. The authors summarize the main issues, including dimensional standards, indoor air quality, safety, accessibility, neighborhoods, and area characteristics. The authors propose an operating scheme in order to implement actions to improve residential wellbeing on a local, national, and international level. Our readers might wonder, why another special issue on housing and health? Is it really necessary to study and work on the relationships between housing and human health? Is it still a relevant issue in today’s world? We are quite sure that the answer is yes, because housing was, is, and will remain a central theme for public health worldwide. We must strengthen our knowledge to ensure the best and healthiest living condition for the entire world population. We therefore strongly need new research on this topic, not just to evaluate the current situation in different countries and contexts, but also to be able to validate new solutions aimed at improving the health standards of housing and making them suitable and affordable for a larger portion of the human population.-Dimensional standards-Indoor air quality-Safety-Accessibility-Neighborhoods and area characteristicsHousing represents a core and traditional topic of public health , despiteRelevant classical issues such as thermal and hygrometric comfort, lighting, noise protection, water supply, and waste disposal have a strong impact on both psychological and physical health of inhabitants. Despite being widely recognized as key factors for healthy living environments at both scientific and legislative levels, these factors are not adequately guaranteed in all dwellings worldwide ,17,18,19Sufficient dimensional area is a key determinant for healthy housing . AccordiIndoor air is an historical and widely recognized health determinant ,48,49,50Despite a lack of reliable epidemiological data on a global basis, home accidents are among the leading causes of death, infirmity, and disability worldwide, in both developing and developed countries ,88,89. TAmong emerging safety issues, we would also include structural problems related to extreme natural phenomena, such as floods, tsunamis, earthquakes, landslides, volcanic activities, and heat and cold waves. In the last few years, several catastrophic events have occurred around the globe, causing many victims ,102,103.per se, the elderly are more fragile and susceptible to the harmful effects of their dwellings; therefore healthy ageing is a goal for an economically and socially sustainable future [The aging population faces increasing morbidity, multi-morbidity, functional limitations, and disability ,109. Alte future ,114,115.e future ,117. Thee future ,119,120.e future . AccessiAs is already widely expressed in international literature, the concept of healthy housing also implies a residential setting that can fulfill the expectations of its residents ,122. In -Research, to consolidate evidence on the main health threats in indoor environments and to create strategies to mitigate their effects, as well as elaborating on guidelines and standards;-Education, to spread research-acquired knowledge not only to health sector workers, but to engineers and architects, lawmakers, public administrators, and the general population (directly or via relevant stakeholders);-Lawmaking, to enforce research-based regulation, as it is recognized as key part of health protection in built environments [ronments ,142,143;-Policy, to provide political and financial support to housing in local, national and international programs;-Evaluation and control, to obtain a constant monitoring of implemented housing campaigns in input, output, and process validated indicators, and control of local health authorities on hygienic standards application.As housing is a leading health determinant, improving living conditions in both economically developed and developing countries may reduce mortality and burden of disease, and increase health quality from a physical, psychological, and social point of view ,50,139. To successfully implement these proposals, which we may call RELPE actions, strong commitment and functional coordination and harmonization is needed at a local, regional, national, and international level, providing the involvement of researchers, educators, public health operators, building designers, urban planners, lawmakers, communities, and representative associations.Housing is a key determinant for human health. We have tried to summarize some of the major factors connecting housing and health, citing the most relevant scientific evidence currently available, that shows a strong relation with social and economic conditions; however, it is often very difficult to assess their independent effect . The COV


In the published article, there was an error in the affiliations. Instead of Qilu Hospital, Shandong University, Jinan, China, it should be:1 Department of Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China2 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China3 Department of Emergency, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.YL is affiliated with 1, LW is affiliated with 2, JZ is affiliated with 1, HH is affiliated with 1, HL is affiliated with 1, CL is affiliated with 2, HG is affiliated with 1, YC is affiliated with 3, XC is affiliated with 1.Furthermore, Lin Wang was not included as a co-first author in the published article. This has been corrected, and a new statement has been added to indicate that Yuan Li and Lin Wang contributed equally: “These authors contributed equally to this work.”The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.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.


Rothrauff, Lars Engebretsen, Andrew D. Lynch, Olufemi R. Ayeni, Mark V. Paterno, John W. Xerogeanes, Freddie H. Fu, Jon Karlsson, Volker Musahl, Eleonor Svantesson, Eric Hamrin Senorski, Thomas Rauer, Sean J. Meredith, The Panther Symposium ACL Treatment Consensus Group, was originally published Online First without Open Access. After publication in volume 28, issue 8, page 2390–2402 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit


Utricularia includes around 250 species of carnivorous plants, commonly known as bladderworts. The generic name Utricularia was coined by Carolus Linnaeus in reference to the carnivorous organs (Utriculus in Latin) present in all species of the genus. Since the formal proposition by Linnaeus, many species of Utricularia were described, but only scarce information about the biology for most species is known. All Utricularia species are herbs with vegetative organs that do not follow traditional models of morphological classification. Since the formal description of Utricularia in the 18th century, the trap function has intrigued naturalists. Historically, the traps were regarded as floating organs, a common hypothesis that was maintained by different botanists. However, Charles Darwin was most likely the first naturalist to refute this idea, since even with the removal of all traps, the plants continued to float. More recently, due mainly to methodological advances, detailed studies on the trap function and mechanisms could be investigated. This review shows a historical perspective on Utricularia studies which focuses on the traps and body organization.The genus  Utricularia species (bladderworts) are one of the most fascinating carnivorous plants, with tiny traps and seemingly no roots [Utricularia species usually do not follow traditional models of morphological classification. The body organization of Utricularia does not present clearly defined boundaries between ordinary plant organs , or recognizable roots [no roots ,5,6,7,8.no roots ,12,13,14Utricularia were most likely by Conrad Gessner (1516–1565), a Swiss physician and naturalist, in his Historia Plantarum, also called Conradi Gesneri Historia Plantarum [Libri Picturati, , there is one of Utricularia which is accessible at the Jagiellonian Library of the Jagiellonian University in Kraków [Utricularia vulgaris [Hortus Malabaricus in 1689 [Utricularia reticulata as “Nelipu” (Utricularia to be referenced before Carolus Linnaeus (1707–1778), the founder of modern taxonomy, who proposed the genus Utricularia and described seven species in his Species Plantarum [U. vulgaris, U. minor, U. subulata, U. gibba, U. bifida, U. caerulea, and U. foliosa. The U. caerulea treated by Linnaeus was a blend of different taxa [U. caerulea by Linnaeus himself [The earliest illustrations of  Gessner 16–1565, vulgaris , in whic in 1689 , Hendric“Nelipu” A, a Malalantarum : U. vulgent taxa ,20, reprUtricularia was coined by Linnaeus in reference to the traps  which are the carnivorous structures present in all species of the genus from aquatic to terrestrial environments [Utricularia by Linnaeus, many species have been described. In particular, Vahl [Utricularia, mostly by Rafinesque [Utricularia by other authors [The generic name ronments ,22. The ronments . Since tar, Vahl , Brown [ar, Vahl , Smith [ar, Vahl , Saint Har, Vahl ,28,29,30ar, Vahl  contribuar, Vahl . Severalfinesque , who bas authors .Utricularia after dedicating four decades of his life to the bladderworts. Taylor’s [Utricularia species: the Indian U. tayloriana [U. hirta), and the Australian U. petertaylorii [In 1989, Peter Geoffrey Taylor 1926–2011), a British botanist who worked at the Royal Botanic Gardens, Kew, published his magnificent monograph about the genus 11, a Briyloriana , synonymtaylorii . To datetaylorii .Utricularia has been highlighted as unique in many studies  of Lentibulariaceae and s , lithophytic , rheophytic , and some aquatic species  have “rhizoids” [U. aurea, U. breviscapa, U. inflata), a whorl of floats is found at the inflorescence base, resembling swollen shoots filled with aerenchyma cells and lacunae, and with appendages similar to branched shoots. These structures provide stability to the inflorescence, keeping it above the water table and making it more conspicuous to pollinators [All al roots . Some spal roots ,48). Manhizoids” , which chizoids” ,49. In slinators ,35,50.Utricularia shows organs with intermixed morphological traits  of organ categories , and homologous to shoots. This was especially evident to the authors in the dimorphic leaves of U. dusenii , few anatomical characters typical for roots are present in stolons  and root , the ves e.g., ,8). For . For Utrs , of whiu Taylor  postulaton”, cf. ,54. Simistolons  is best known for his The Origin of Species [The Origin of the Species, Darwin wrote: “I care more about Drosera than the origin of all the species in the world”. That sentence became more understandable when, after fifteen years, he published his Insectivorous Plants [Utricularia traps.The bladderwort’s trap is one of the most complex and intriguing structures among living plants D and is  Species , he pass Species  to the Ss Plants , which wUtricularia are similar in general organization and structure, they arise from different parts of the plant in different species: from the petiole and lamina of the leaves, from the base of inflorescences, and/or from stolons and their branches. The traps are foliar structures shaped as globose or ovoid vesicles (bladders) with a length of 0.2 to 12 mm [U. breviscapa, U. foliosa, and U. gibba), the mature traps are even dark violet, most likely due to the presence of bacteria [Although the traps of to 12 mm ,21,59,60bacteria ,62 or anUtricularia and hypothesized the presence of a polarity from stalk to mouth by analyzing the trap glands. Impressively, by controlling the adaxial–abaxial domains of gene activity for growth orientation in proximodistal and orthoplanar polarity in the primordia of U. gibba, simple shifts in the expression of genes homologous to the adaxial expressed PHV/PHB genes and abaxial expressed FIL and KAN genes [Trap development has been the subject of several studies that attempted to anatomically and genetically understand the processes that result in such a complex structure , usi, usiUtria e.g., ,84,85). ,85. Utria nt roots . Furthernt roots . Recent nt roots ,91,92,93nt roots . Moreovent roots . In thisnt roots ,97. Accont roots , the traUtricularia  are needed to better understand the different observed patterns of seedling development, vegetative structures, and possible adaptations, from an evolutionary and phylogenetic perspective.Despite of some studies on post-seminal development ,104,105,Utricularia lineages and thus explain the differences of traps among the taxa .Utricularia and Genlisea and their evolutionary aspects [Utricularia genomes are comparable to those of other higher plants, with the noncoding DNA and transposable elements being the main responsible for genome size discrepancies [U. vulgaris transcriptome, and some of them are also present in the U. gibba genome [U. gibba, with the heterotopic transfer of the function of root genes to other organs [U. gibba genome indicated the absence of homologs of the WOX5 gene [Utricularia were explored, putative domains of WOX genes were identified . The development of genetically transformed Utricularia, as already proposed for U. gibba [Studies showing the minute sizes of chromosomes  and geno aspects ,100 (Figepancies ,102, it epancies  or morphepancies , are prea genome ,120. Accr organs . SimilarOX5 gene ,122, whiOX5 gene , but theU. gibba , could bUtricularia, particularly with the sampling of different life forms, and the inclusion of Genlisea as the other member of the rootless clade in Lentibulariaceae.However, to overcome this gap, and to advance in these important issues related to morphology simplification and loss of roots in Lentibulariaceae, we need a more complete scenario comprising more genomes and transcriptomes for


We aim to conduct a scoping review focused on identifying approaches to documentation burden measurement and their characteristics.Electronic health records (EHRs) are linked with documentation burden resulting in clinician burnout. While clear classifications and validated measures of Based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews (ScR) guidelines, we conducted a scoping review assessing MEDLINE, Embase, Web of Science, and CINAHL from inception to April 2020 for studies investigating documentation burden among physicians and nurses in ambulatory or inpatient settings. Two reviewers evaluated each potentially relevant study for inclusion/exclusion criteria.burnout.Of the 3482 articles retrieved, 35 studies met inclusion criteria. We identified 15 measurement characteristics, including 7 effort constructs: EHR usage and workload, clinical documentation/review, EHR work after hours and remotely, administrative tasks, cognitively cumbersome work, fragmentation of workflow, and patient interaction. We uncovered 4 time constructs: average time, proportion of time, timeliness of completion, activity rate, and 11 units of analysis. Only 45.0% of studies assessed the impact of EHRs on clinicians and/or patients and 40.0% mentioned clinician Standard and validated measures of documentation burden are lacking. While time and effort were the core concepts measured, there appears to be no consensus on the best approach nor degree of rigor to study documentation burden.Further research is needed to reliably operationalize the concept of documentation burden, explore best practices for measurement, and standardize its use. We evaluated all relevant literature identified through in-text references among eligible studies. Burden is not specifically represented in Medical Subject Headings (MeSH); therefore, we explored both keyword and MeSH terms for 2 burden-related concepts outlined in the HHS report We selected inclusion and exclusion parameters a priori, and iteratively modified them to exclude studies involving niche clinical systems and those strictly comparing to paper-based documentation . We inclThe term “physicians” encompassed attending physicians, fellows, resident physicians, and interns; “nurses” referred to registered nurses. We focused on physicians and nurses given our aim of identifying interprofessional measurements of documentation burden. We excluded studies comparing EHR documentation to paper-based systems if they were not focused on measuring burden, but rather on EHR implementation evaluation.After removing duplicates, 2 reviewers  independently screened article titles and abstracts for relevance using Covidence.One author (AJM) performed data charting for all articles meeting full-text inclusion criteria , Embase (n = 1143), Web of Science (n = 1007), and CINAHL (n = 825). Seven additional manuscripts were identified through in-text references. After eliminating duplicates, 1946 titles/abstracts were screened; of those, 166 were eligible for full-text review. Consensus was achieved for all disagreements concerning the inclusion of full-text articles. Thirty-five studies meeting criteria were summarized in the final analysis .,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Studies were conducted in the United States (n = 31),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Articles were published between 2010 and 2020 with 2018 (n = 8),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Thirty were strictly quantitative studies. While purely qualitative studies were excluded, 5 studies employed mixed methods,,,,,,,,,,,,A diversity of analytical methods was employed. Most studies to which statistical testing were relevant (n = 23) applied parametric (n = 19) as opposed to non-parametric methods (n = 12). Qualitative methods employed in the mixed-methods studies involved informal interviews,effort constructs emerged  gen,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Time spent documenting was assessed in all studies and was measured using 3 key data collection strategies: EHR usage logs (n = 28),,,,,,,,,,,,,,,,,,Less than half the studies assessed the impact of documentation burden on clinicians and/or patients (n = 16). Among those studies, authors referenced the temporal relationship between burden and burnout at a higher proportion (68.8%) compared to those that did not extend beyond measuring time and effort alone (50.0%). Outcomes measured included clinical process measures [n = 8 generalizability due to constraints in sample size (n = 19),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,measurement error including the inability of logs to distinguish between “idle and active” time (n = 6),,,,,,,,,,,,,,,,,,,,,,,,,,Two limitations were ubiquitous across included studies : (a) thr,,,,,,,,,,,,,,,,,,,,,,Six studies cited selection bias derived from both the presence of self-selection and voluntary participation among high-performing subjectsworkflow fragmentation and cognitively cumbersome work —largely align with “proposed core EHR use measures (for practice efficiency)” published by Sinsky and colleagues which indicates burden may be quantified through existing metrics.In this scoping review, we identified 35 studies that explored the measurement of documentation burden among physicians and nurses, underlining the overall paucity of research in the domain. As may be expected, all 35 studies were published post-HITECH Act. Seven effort constructs, 4 time constructs, and 11 units of analysis were uncovered. Our effort constructs—except ,,,,,Historically, TM studies have been considered the gold standard for quantifying the effects of computer systems on task-based clinical workflow and duration.,,,,,burden and a plethora of definitions throughout the literature.,,,,,,,,time and effort, such as workload,,,,burnout is identifiable in controlled vocabularies including, the International Classification of Diseases (ICD), in addition to the Diagnostic and Statistical Manual for Mental Disorders (DSM) and MeSH.,,time.One major finding of this review was the absence of quantitative studies assessing the reliability and validity of time and effort measures. Of the 35 studies included, only 1 study intended to develop a measure of burden ,Strategy on Reducing Burden Relating to the Use of Health IT and EHRs—aims to evaluate the clinical impact of burden  on clinicians and/or patients;The HHS Report—,,,,,In this review, scribes represented 1 of 3 areas of study concerning proposed interventions to mitigate burden (n = 3);effort constructs, 4 time constructs, and 11 units of analysis  our keywords were limited, and/or (b) our queries were not sufficiently broad or narrow.While this study sought to investigate literature on the operationalization of documentation burden and the development and/or validation of quantitative burden measures, research in this domain has not yet matured. Despite employing broad search terms and queries, the majority of the literature retrieved did not detail how to conceptualize and/or measure burden. We extracted manuscripts using keywords, as extant MeSH terms were unable to capture the phenomenon of study interest; in fact, no term for after scheduled duty hours measure described by Cox and colleagues should undergo rigorous testing and validation across settings and specialties.,,Future research should build upon existing burden evidence, focusing on strengthening objectivity and generalizability. Proposed quantitative measures of burden such as the ,,task value, as indicated by task relationship with burden, a high priority area for future research. Such research would allow the identification of tasks that are of high burden but low value so that EHR design and intervention efforts may target the elimination or mitigation of these tasks.However, promisingly, burden measures identified were not strictly unique to individual professions and workflows, supporting the opportunity for defining interprofessional measures of burden in future work. We propose that burden be examined as a global composite measure, indicative of magnitude and directionality, consistent with the characteristics uncovered in this review. This would require: (a) developing a universally agreed-upon inventory for key EHR tasks and activities weighted for relative value according to burden  that could be linked to clinical outcomes such as “quality, financial or professional satisfaction”Documentation burden among interprofessional clinical roles remains understudied and under-measured in both inpatient and ambulatory settings. This review suggests that concrete, validated measures of burden in research are lacking, which pales in comparison to burnout literature.This study was supported by the US National Library of Medicine of the National Institutes of Health (NIH) under the training fellowship award 5T15LM007079 and the National Institute for Nursing Research (NINR) under grant numbers 1R01NR016941 and 5T32NR007969.AJM and SCR conceptualized the scope of this review. AJM, JMS, RC, SS, and EL conducted the initial and full-text screenings. AJM drafted the manuscript with significant revisions and feedback from JMS, RC, KDC, and SCR.Journal of the American Medical Informatics Association online.The data underlying this article are available in the article and in its online None declared.ocaa325_Supplementary_DataClick here for additional data file.


Phthalates are a group of chemicals used in a multitude of important industrial products , mainly as plasticizers to improve mechanical properties such as flexibility, transparency, durability, and longevity of polyvinyl chloride (PVC). The wide occurrence of phthalates in many consumer products, including foods  brings that most people are exposed to phthalates every day, which raises some concerns. Adverse health outcomes from phthalates exposure have been associated with endocrine disruption, deformities in the human reproductive system, increased risk of preterm birth, carcinogen exposure, among others. Apprehension related to the health risks and ubiquitous incidence of phthalates in foods inspires the development of reliable analytical approaches that allow their detection and quantification at trace levels. The purpose of the current review is to provide information related to the presence of phthalates in the food chain, highlighting the health risks associated with their exposure. Moreover, an overview of emerging extraction procedures and high-resolution analytical approaches for a comprehensive quantification of phthalates is presented. Phthalates, generally known as phthalate esters PAEs, , are a fBesides being easily released into the environment, they are rapidly biodegraded and photodegraded, leading to a lower persistence.The most common exposure routes of phthalates are: (i) personal care products ; (ii) food contact plastics  ; (iii) sFrom the described potential routes, food and beverage constitute, undoubtedly, the most important source of human exposure to phthalates ,9. PartiThe phthalates are naturally released into the environment through their production, use, and/or disposal, and therefore can be absorbed by the human body by different routes , as seen in According to Bennett et al. , exposurIn the following sections, we provide descriptive information related to the presence of phthalates in the food chain, highlighting the health risks associated with their exposure. An overview of the emerging extraction procedures and analytical approaches for a comprehensive quantification of phthalates is also discussed. For this purpose, the keywords “phthalates”, “PAEs”, “environmental”, “food”, “healthy risks”, “extraction technique”, and “analytical platforms” were researched in Pubmed, Scopus, Web of Science, and Google Scholar over the period of 2015 to 2021. It should be pointed out that other references were included outside of the established period due to their relevance to this review.As previously mentioned, PAEs are a class of synthetic chemicals mainly obtained from petroleum and added to an enormous number of everyday products. PAEs, linear and branched, are added to improve the properties of plastic materials  . Lately,Due to the widespread use of these types of compounds and their immense applications, there is a potential risk, for both children and adults, of being exposed to phthalates. Phthalates are relatively released from the products into the environment due to the weak chemical bond between phthalates and other chemicals due to their dipolar interactions .Maternal diet and food preparation practices, such as maternal prenatal high-fat milk consumption was associated with higher benzyl butyl (BBz) and DEHP . The preNon-dietary exposure is another source, where they can be emitted from materials into the air and easily partitioned into the indoor and outdoor environment. Different phthalates have been detected, such as DEHP, diisobutyl phthalate (DiBP), and di-n-butyl phthalate (DnBP) in soil dust . The draThere are numerous studies where it has been shown that phthalates can alter the endocrine system and induce a plethora of effects such as carcinogens, teratogens, and mutagens ,32.Many phthalates, even at a low concentration, are known endocrine disruptors  that havPhthalate exposure in humans has been linked to metabolic changes, such as increasing obesity problems (metabolic syndrome)  and the Some other studies have concluded there is a relationship between phthalate accumulation  and breast cancer . FurtherSeveral mechanisms have been proposed to explain the increase in blood pressure in pregnancy due to exposure to phthalates, namely an increase in oxidative stress, a decrease in serum thyroxin, and an increase in inflammatory cytokines, which could promote gestational hypertension or preeclampsia development ,45,46,47Due to the generalized exposure of phthalates, as mentioned above, in a great diversity of products, both at a domestic and industrial level, the different international health agencies had to regulate the levels of these chemical contaminants.In the United States, the Environmental Protection Agency (EPA) regulated the presence of eight compounds, namely DBP, DiBP, BBP, di-n-pentyl phthalate (DnPP), DEHP, di-n-octyl phthalate (DnOP), DiNP, and diisodecyl phthalate (DiDP) in consumers ,38, restPAEs are a group of chemicals that are widely used as plasticizers ,60,61. IFood contaminants can also occur with the migration of PAEs from packaging to food. In that sense, Arfaeinia et al.  investig2 of DEHP and 0.86 µg/cm2 of DiNP, plastic filter holders releases maximum leaching of 2.49 µg /cm2 of DBP from polytetrafluoroethylene (PTFE) and Parafilm® leached levels up to 0.50 µg/ cm2 of DEHP. To reduce the high levels of PAEs in these materials, a heat or high-temperature process was applied since there is no covalent bond between the PAEs and plastics. Tienpont et al. [2SO4), and DiBP and DEHP were found at trace concentration (ng/g) in alumina and Na2SO4. These authors also measured the PAEs concentration in the commercial solvents , DCM, and acetonitrile (MeCN)), being DEP (0.01 to 0.03 ng/mL), DiBP (0.002 to 0.21 ng/mL), DBP (0.01 to 0.80 ng/mL), di-n-hexyl phthalate , benzylbutyl phthalate , and DEHP (0.28 to 6.39 ng/mL) found in all solvents. The presence of these PAEs in solvents can be reduced by redistillation and/or by SPE [Special attention should be given to the sample preparation step as the sample can certainly be contaminated with laboratory material such as solvents , sorbents , plastic consumables , glassware, laboratory air, fibers, stir bar, among others ,118. Thit et al.  verifiedr by SPE . The phtr by SPE . Neverthr by SPE , all matEfficient pre-concentration and clean-up procedures are necessary to guarantee the quality of the analytical methods, due to the predictable low concentration of these target analytes in samples, as well as the sample complexity . Table 22SO4 [In the LLE procedure, the sample is put in contact with a solvent with a high affinity to PAEs, followed by phase-separation caused by solvent properties, centrifugation, and removal of moisture by treatment with Na2SO4 . In gene2SO4 ,64,66,992SO4 , MeCN [92SO4 ,91,106, 2SO4 ,77,95,962SO4 ,125. DLL2SO4 ,105, as 2SO4 . The dat2SO4 , as a mo2SO4 ,87 used 2SO4  and 150 2SO4  used dee2) [Other extraction techniques used in the determination of PAEs are Soxhlet and SPE. Nevertheless, these extraction techniques are time-consuming, require solvents, and extensive sample handling , which i2)  as adsorIn contrast to LLE, soxhlet, and SPE, SPME comprises sampling, extraction, purification, concentration, and injection into a single procedure. This extraction procedure is solvent-free, does not need previous sample preparation, and consequently, the risk of cross-contamination from solvents, samples, and glassware was reduced . SPME fi3O4) nanoparticles to extract 10 PAEs from milk. The data obtained, with recoveries ranging from 82% to 112%, and LODs and LOQs lower than 19 and 63 ng/L for all target analytes, supported the successful application of this modified QuEChERS-dSPE approach.QuEChERS-dSPE is an extraction technique that comprises two stages, namely extraction and clean-up. The extraction relies on the partitioning via salting-out extraction where an equilibrium between an aqueous and an organic layer  was endorsed, while the clean-up by dSPE used various mixtures of porous sorbents and salts to eliminate matrix interfering compounds . QuEChERThe selection of the most suitable analytical approaches to separate, detect and identify a class of target compounds depends essentially on their physic-chemical properties and the sensitivity requested. As can be observed in 3) or silylation (-COOSiR3) process of the carboxylic acid group [Gas chromatography is the most used analytical approach for PAEs determination since these target analytes present low molecular weight , relatively low polarity, and thermally stable and appropriately volatility . In the id group . Neverthid group . Generalid group ,100,103.id group ,78,87. Cid group ,97, wateid group ,115,117 id group , but FIDid group ,114,125.id group ,100,127,id group , bromoprid group  have alsid group . Furtherid group ,102,127 id group  have alsid group ,100,112,id group ,78 and tid group ,102,127 id group ,69,103, id group ,100,112 id group ,102,127 In summary, the main advantages of GC-MS are high sensitivity (low LODs), especially by splitless injection, high reproducibility of the generated mass spectra by EI, low cost, ease of operation, requires less maintenance, and the identification of compounds is easier due to the available spectra libraries .GC is possibly the most used analytical platform in PAEs analysis. Liquid chromatography (LC) appears as a suitable alternative due to its potentiality in the analysis of thermally unstable and non-volatiles compounds providing a high selectivity . High-peIn summary, LC-MS offers several benefits in comparison to GC-MS, such as being faster, not requiring derivatization, minimal sample preparation, and facilitating the identification and quantification of a greater diversity of compounds . MoreoveThe wide occurrence of phthalates, mainly PAEs, in many products has contributed to the rising concerns about their effects on human health. Nevertheless, the health impacts of PAEs exposure are not completely elucidated. This fact highlights the need for the development of sample preparation and analytical approaches with the purpose of quantifying these target compounds with more accuracy. The evolution of sample preparation has been focused on quickness, simplicity, automatic, low sample handling, low solvent volume, use of green extractant with the aim to reduce the risk of cross-contamination from solvents, samples, and glassware, and also environmentally friendly. The most common extraction techniques used for the measurement of PAEs are LLE and SPME. Regardless, SPME compared to LLE presents several advantages such as being solvent-free, easy to operate, and comprising sampling, extraction, purification, concentration, and injection into a single procedure. Regarding analytical approaches, GC coupled with MS is the most used for the quantification of PAEs, as a result of their well-known volatility. Satisfactory figures of merit in terms of recoveries, accuracy, LODs, and LOQs, was obtained to demonstrate the success of GC-MS in PAEs determination. Despite this fact, a direct UHLC-MS/MS has also been used in PAEs determination with excellent results.The determination of PAEs in samples represents an inspiring task, not only because of the low concentration of these target compounds but also due to the complexity of the sample and the potential risk of cross-contamination during all steps of the analysis. This problem can be minimized by avoiding extraction techniques that require solvents and only using glassware. However, prior to analysis, all glassware should be submitted to washed soaking in an alkaline solution for 48 h, rinsed with purified solvents, and then calcined at 450 °C overnight. After all, as mentioned in this review, it is expected that miniaturized and automated extraction techniques and high-throughput analytical approaches will continue to be developed to improve the accuracy of PAEs determination.


Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high‐quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures – namely translational research, clinical/prevention trials and outcomes research – were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next‐generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health‐related quality‐of‐life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU‐wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost. Key stakeholders from the cancer research continuum met at the European Cancer Research Summit to discuss priorities for the successful implementation of Cancer Mission and Europe's Beating Cancer Plan. The resulting Porto Declaration called for a collective action to develop cancer research infrastructures, foster innovation and decrease inequalities. Here, we present the Summit recommendations for an EU‐wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of cancer patients and survivors. AIartificial intelligenceBECASpecial Committee on Beating Cancer of the European ParliamentBoBBasket of Baskets CCCComprehensive Cancer CentreCCECancer Core EuropeCEEAOCentral–Eastern European Academy of OncologyDARTData Rich Clinical TrialsDKFZGerman Cancer Research CenterDKTKGerman Cancer ConsortiumDRUPDrug Rediscovery ProtocolEACSEuropean Academy of Cancer SciencesEBCPEurope´s Beating Cancer PlanECACEuropean Code Against CancerECPCEuropean Cancer Patient CoalitionEFPIAEuropean Federation of Pharmaceutical Industries and AssociationsEMBLEuropean Molecular Biology LaboratoryEORTCEuropean Organisation for Research and Treatment of CancerERNEuropean Reference NetworkESMOEuropean Society of Medical OncologyIARCInternational Agency for Research on CancerIMIInnovative Medicine InitiativeIQNPath International Quality Network for PathologyJRCJoint Research Centre EUMRImagnetic resonance imagingMTBMolecular Tumour BoardNCTNational Center for Tumor DiseasesNGSnext‐generation sequencingOECIOrganisation of European Cancer InstitutesQoLhealth‐related quality of lifeRCTrandomized clinical trialRTradiation therapyVBHCvalue‐based health careWGSwhole‐genome sequencingWSIwhole‐slide images1The effective implementation of the EU cancer research strategy has been the focus of the European Cancer Research Summit, which took place in Porto in May 2021 and mainly discussed the requirements for distributed and interconnected infrastructures needed to support research on cancer therapeutics, care and prevention . This inAs an integral part of the Horizon Europe Framework Programme for Research and Innovation (2021‐2027), a set of European Research and Innovation Missions aim to deliver solutions to some of the greatest challenges facing Europe, including cancer. As highlighted by one of the Summit speakers, Guy van den Eede, cancer accounts for more deaths than any other disease in the age group of below 65 in the EU. While this geographical area is home to < 10% of the world’s population, it collects 23% of all cancer cases. On average, only one in two cancer patients survive, and one in two of us will face cancer in our lifetimes. In economic terms, cancer costs the EU almost €97 billion in 2018. In futuristic terms, several factors, including the EU’s ageing population, will see that all numbers and costs increase unless serious action is taken, such as doing more on prevention, early detection, quality of care and more .In the context of Horizon Europe, both the Cancer Mission , 6, 7 anIn this landscape, policymakers, academic researchers, patient representatives and pharmaceutical industry members contributed to keynote sessions and panel discussions at the European Cancer Research Summit 2021. Rui Henrique, the main organizer, and Julio E. Celis, the Chair of the Scientific Advisory Committee, welcomed the Summit participants. The Summit started with a brief glimpse over current developments in the European cancer policy landscape. It continued with distilling the view of the cancer research community on the basic requirements that will enable the implementation of an effective European Cancer Mission. Finally, it focused on the specific recommendations by key stakeholders to establish efficient infrastructures for translational research, clinical/prevention trials and outcomes research. Panel discussions complemented the perspectives of key lectures and set the scene for a multivoiced, yet highly collaborative, pan‐European initiative to tackle the challenges of cancer for the individual, the health systems and the society.2Stella Kyriakides, opened the session by thanking the cancer community for supporting EBCP, which in partnership with the European Cancer Mission will address current challenges in cancer research, prevention and care. Ms Kyriakides highlighted the importance of interdisciplinary collaboration and emphasized the need for evidence‐based knowledge and its translation into policy and political decisions. The planned EU initiatives for fostering cancer research, prevention and care will financially be supported partly by EU4Health, but, as Ms Kyriakides noted, the clear commitment of all EU member states would be equally crucial. In addition, European Comprehensive Cancer Centres (CCCs) and the European Parliament Special Committee on Beating Cancer (BECA) will have key parts in these efforts – the concrete contribution of BECA being currently under discussion.The Summit´s first session focused on current and future European cancer policy plans, in which collaboration among policymakers, scientists and patient organizations is deemed indispensable. The EU Commissioner for Health and Food Safety, Marta Temido, Minister for Health, Portugal, recognized that public health authorities alone could not tackle the major societal challenge of cancer. Ms Temido highlighted the need to invest in research and technology using a research‐driven, patient‐centred approach and mentioned that BECA would support efforts across the EU. While clinical research and the national cancer plan are key priorities of the Portuguese government, they should also be prioritized by all other EU member states, indicated Ms Temido, who also encouraged EU member states to sign the ‘Porto Declaration’.Further corroborating the message of Stella Kyriakides on the importance of collaboration, Mariya Gabriel, EU Commissioner for Innovation, Research, Culture, Education & Youth, next informed the audience that the health cluster of Horizon Europe features a Cancer Mission with well‐defined goals as a key priority, aiming at improving prevention, diagnosis and treatment. While the COVID‐19 pandemic caused delays in cancer research and weakened European Research Networks (ERNs), Horizon Europe is expected to restrengthen partnerships in health, such as the partnership on personalized medicine, innovative health initiatives that build on the success of the Innovative Medicine Initiative (IMI), and the European Institute of Innovation and Technology Health. According to the Commissioner, work on the Cancer Mission implementation plan is currently underway; the next is to invigorate EU member states and regional funders. Marie Sklodowska‐Curie actions will also help build scientific excellence and cooperation across countries. The new EC Knowledge Centre on Cancer, launched on 30 June 2021, is expected to coordinate the efforts of EU member states  and similar IP portfolios. MB confirms that, to the best of his knowledge, none of the above funding sources were involved in the preparation of this paper. BB has received research funding from 4D Pharma, Abbvie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi‐Sankyo, Eli Lilly, GSK, Inivata, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche‐Genentech, Sanofi, Takeda, Tolero Pharmaceuticals. FC declares consultancy role for: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi‐Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Medscape, Merck‐Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre‐Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva. SF is a consulting or advisory board member at Bayer, Illumina, Roche; has received honoraria from Amgen, Eli Lilly, PharmaMar, Roche; has received research funding from AstraZeneca, Pfizer, PharmaMar, Roche; has received sponsorship of travel or accommodation expenses by Amgen, Eli Lilly, Illumina, PharmaMar, Roche. SG owns AstraZeneca stock and is a full‐time employee of AstraZeneca. PN has had an advisory role at Bayer, MSD Oncology, has received honoraria from Bayer, Novartis and MSD Oncology, and has had travel expenses paid by Novartis. JO has been an advisory board member at Roche, Novartis, Bayer, Merck, Eisai, Astrazeneca, Pierre Fabre Medicament and Bristol‐Myers Squibb. He has also received research funding by IPO Porto, Astrazeneca, Fundação para a Ciencia e a Tecnologia (FCT) and Liga Portuguesa Contra o Cancro (LPCC). AR is an employee of European Federation of Pharmaceutical Industries and Associations, Brussels, MSD International Business GmbH, Kriens, Switzerland[CvG1], and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA, who may own stock and/or hold stock options in the Company.RS serves as principal investigator of the ASCO TAPUR study. ASCO receives research grants from the following companies in support of the study: Astra‐Zeneca, Bayer, Boehringer‐Ingelheim, Bristol Myers Squibb, Genentech, Lilly, Merck, Pfizer, Seattle Genetics. Dr. Schilsky serves as a member of the managing board of Clariifi and as a consultant to Bryologyx, Cellworks Group, EQRx, and Scandion Oncology. The Netherlands Cancer Institute receives research support via EV from Roche, Astrazeneca, Eisai, Novartis, GSK, Clovis, BMS, MSD, Pfizer, Amgen, Bayer, Lilly, Janssen and Seagen. LZ is founder of everImmune, member of the board of directors of Transgene, member of the scientific advisory board of Transgene, EpiVax, Lytix Biopharma. LZ has also had research contracts with: Merus, Roche, Tusk, Kaleido, GSK, BMS, Incyte, Pileje, Innovate Pharma, and Transgene and has received honoraria by Transgene. All other authors have no conflicts of interest to declare.


Fertilization can significantly affect the quality of crop and soil. To determine the effects of long-term fertilization on crop yield and carbon:nitrogen:phosphorus (C:N:P) stoichiometry in soil, a study was conducted on the terraced fields of the Loess Plateau from 2007 to 2019. Nine fertilization treatments were included: no fertilizer; organic fertilizer (O); organic and nitrogen fertilizers (ON); organic, nitrogen, and phosphorus fertilizers (ONP); organic and phosphorus fertilizers (OP); phosphorus and nitrogen fertilizers; potash and nitrogen fertilizers; potash, nitrogen, and phosphorus fertilizers; and potash and phosphorus fertilizers. Under these treatments except for CK and PK, crop yields initially decreased but later increased. The nutrient content and C:N:P stoichiometry increased in soil depth of 0–20 cm. The soil available nutrients did not change significantly with the duration of fertilization. The O, ON, ONP, and OP had the most evident effect on the enhancement of soil nutrient content, whereas O and ON had the most evident effect on the increase in soil organic carbon (SOC):total phosphorus (TP) and total nitrogen (TN):TP. In soil depth of 0–20 cm, crop yield, SOC:TN, SOC:TN, SOC:TP, and TN:TP significantly correlated with soil nutrients. This study indicated that long-term fertilization can effectively improve crop yield, soil fertility, and soil C:N:P stoichiometry. Meanwhile, the single application of an organic fertilizer or the combination of organic and nitrogen fertilizers can improve the condition of nitrogen limitation in arid and semi-arid areas. Ecological stoichiometry is the science of studying the energy balance of biological systems and multiple nutrient elements , nitrogen (N), and phosphorus (P)) . It provIn agricultural production practices, fertilizers (organic and inorganic) are used to increase the accumulation of C, N, and P in the soil to improve the soil’s ability to supply nutrients to crops . FertiliFertilization is one of the most important methods in agricultural production. Studies have found that soil nutrients and crop growth are affected by frequent fertilization and other factors ,11. FertIn the present study, we chose a typical terraced field plot in the Loess Plateau to conduct a 12-year experiment (from 2007 to 2019) on various fertilization treatments. The objective was to study the changes in characteristics of crop yield, soil nutrient content, and C:N:P stoichiometry with various fertilization methods under different fertilization durations. We hypothesized that (1) long-term fertilization may affect the crop yield and soil nutrient content, (2) the changes in soil nutrient content may alleviate the C:N:P stoichiometry of soil, and (3) the single application of an organic fertilizer or an organic fertilizer combined with an inorganic fertilizer may have an advantage in increasing crop yield and soil nutrients supply.The study site was located at the Ansai Research Station of the Chinese Academy of Sciences , which is a long-term detection sampling site . The ann2 was selected and divided into 36 small plots of 3.5 m × 8.57 m. In total, 9 fertilizer treatments were performed, and each treatment was repeated 4 times  software.Effects of the type of fertilization treatment and duration of fertilization on crop yield, SOC, TN, TP, AN, AP, pH, SOC:TN, SOC:TP, TN:TP, and AN:AP were evaluated using two-way ANOVA. One-way ANOVA was used to evaluate the crop yield, SOC, TN, TP, AN, AP, pH, SOC:TN, SOC:TP, TN:TP, and AN:AP responses to the duration of fertilization. Duncan’s post hoc test at The type of fertilization treatment and duration of fertilization had a considerable impact on crop yield . BetweenAt 0–20 cm soil depths, the duration of fertilization had a significant impact on SOC, TN, TP, AP, and pH . BetweenIn soil depths of 20–40 cm, the duration of fertilization had a significant impact on SOC, TN, TP, AN, AP, and pH . BetweenIn soil depths of 0–20 cm, the duration of fertilization had a significant impact on SOC:TN, SOC:TP, TN:TP, and AN:AP . BetweenIn soil depths of 20–40 cm, the duration of fertilization had a significant impact on SOC:TN, SOC:TP, TN:TP, and AN:AP . BetweenFor the soil depth of 0–20 cm, the correlation matrix showed that crop yield was significantly correlated with SOC, TN, TP, AN, AP, pH, and SOC:TN; SOC:TN with SOC, TN, AN, AP, pH, SOC:TP, and TN:TP; SOC:TP with SOC, TN, TP, AN, AP, TN:TP, and AN:AP; and TN:TP with SOC, TN, TP, AN, AP, pH, and AN:AP a.For the soil depth of 20–40 cm, the correlation matrix showed that crop yield was significantly correlated with SOC and TP; SOC:TN with SOC, TN, AN, AP, pH, and SOC:TP; SOC:TP with SOC, TN, TP, and TN:TP; and TN:TP with SOC, TN, TP, AN, pH, and AN:AP b.Increasing crop production is one of the ways to increase agricultural development in arid and semi-arid regions. Fertilization is an important agronomic measure, and appropriate application of fertilizers can promote the growth and development of farming and improve the quality and yield of crops ,21. ThisThis result can be explained as follows. First, N, P, and potassium (K) are essential nutrients for the growth and development of crops. During the long-term growth of crops, the nutrient elements in the soil are consumed in large quantities. The addition of artificial fertilizers compensates for the deficiency of soil nutrients, thereby increasing the absorption and assimilation of soil N, P, and K by plants; this affects the growth and development of crops, further affecting crop yield . Second,Studies have reported that organic fertilizer is released slowly, and it cannot meet the growth needs of crops in the current season. However, the fertilizer effect is long ,23. ThisSoil nutrients can provide the material basis and energy source for the survival of various microorganisms in the soil and the growth of crops . Soil nuA lack of fertilization long term leads to an increase in the soil nutrient content in the soil layer of 0–20 cm, which is inconsistent with the conclusion that a lack of fertilization long term leads to a decrease in soil organic matter content . It may At a soil depth of 0–20 cm, the application of organic fertilizer or mixed application of organic and inorganic fertilizers had a more enhanced effect on soil nutrient content than the single application of inorganic fertilizer . This isIn this study, it was found that the SOC:TN in 0–20 cm soil layer increased after fertilization with the increase in the number of years of fertilization. Studies have found that the main factors affecting the changes in SOC:TN are changes in SOC and soil TN content after fertilization ,31. SOC:SOC:TP in soil can characterize the potential of soil organic matter mineralization to release or absorb and fix P ,32. AddiIn addition, we found that the overall rate of increase in TN was greater than that in TP under O and ON treatments , resultiIn conclusion, we studied nine fertilization treatments for millet in arid and semi-arid areas and found that crop yield and C:N:P stoichiometric ratio in soil were significantly affected by the duration of fertilization. The long-term use of organic fertilizer, inorganic fertilizer, or a combination of both can effectively increase crop yield, improve soil nutrient environmental conditions, and improve C:N:P stoichiometry in 0–20 cm deep soil layer. The effect of organic fertilizer and combined application of organic and inorganic fertilizers on increasing soil nutrient content is more evident. Fertilization using organic fertilizer or organic fertilizer combined with nitrogen fertilizer can effectively alleviate nitrogen limitation in arid and semi-arid areas. Therefore, this study provided supportive data for changes in soil nutrient content and C:N:P stoichiometric ratio after long-term fertilization in arid and semi-arid regions and provided a theoretical basis for efficient soil fertilization in such areas.


Background: Over the last decades, life expectancy in Latin America and the Caribbean showed a rapid increase, which led to a significant increase in the number of people with dementia. Moreover, 9% of the population in this part of the world are aged 65 or older, and by 2050 this percentage is projected to at least double. For this reason, it is essential to estimate the prevalence of dementia in LAC countries with the aim to determine suitable actions to enhance the quality of life of those affected. Methods: Database searches for articles were conducted September 2020 throughout Pubmed, Web of knowledge, Scopus, Lilacs, and SciELO. The inclusion criteria comprised population- or community-based studies, published in English, Spanish, or Portuguese, reporting data on the prevalence of dementia collected in LAC countries. The complete data search retrieved 1719 non-duplicates. Results: A total of 58 studies met the high-quality inclusion criteria, published 1991-2020, including participants in the following countries: Brazil, Mexico, Argentina, Colombia, Peru, Cuba, Dominican Republic, Venezuela, Ecuador, Trinidad and Tobago, and Jamaica. The most common form of dementia studied was Alzheimer’s disease with prevalence ranging from 5.9% to 23.4%. Estimates differed by age, gender, and education, with oldest, women, and lower-educated adults living in rural areas presenting higher dementia prevalence. Conclusion: This is the first study giving a comprehensive overview of dementia prevalence in LAC countries, which is relevant to estimate care needs and economic costs related to dementia treatment and care.


In “Census Tract Patterns and Contextual Social Determinants of Health Associated With COVID-19 in a Hispanic Population From South Texas: A Spatiotemporal Perspective” :e29205), one error was noted.Due to a system error, the name of one author, Joseph McCormick, was replaced with the name of another author on the paper, Isela de la Cerda. In the originally published paper, the order of authors was listed as follows:Cici Bauer, Kehe Zhang, Miryoung Lee, Susan Fisher-Hoch, Esmeralda Guajardo, Isela de la Cerda, Isela de la Cerda, Maria E Fernandez, Belinda ReiningerThis has been corrected to:Cici Bauer, Kehe Zhang, Miryoung Lee, Susan Fisher-Hoch, Esmeralda Guajardo, Joseph McCormick, Isela de la Cerda, Maria E Fernandez, Belinda ReiningerIn the originally published paper, the ORCID of author Isela de la Cerda was incorrectly published as follows:0000-0002-5844-8102This has been corrected to:0000-0003-3625-8954The correction will appear in the online version of the paper on the JMIR Publications website on August 18, 2021, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories.