OsGLP8-2 gene or ten OsGLP genes (OsGLP8-2 to OsGLP8-11) resulted in a similar sensitivity to Cd and Cu toxicity. When subjected to Cu and Cd stress, the glp8-2 and glp8-(2-11) mutants displayed a more sensitive phenotype based on the plant height, root length, and dry biomass of the rice seedlings. Correspondingly, Cu and Cd concentrations in the glp8-2 and glp8-(2-11) mutants were significantly higher than those in the wild-type (WT) and OsGLP8-2-overexpressing line. However, Cu and Cd accumulation in the cell wall was the opposite. Furthermore, we determined lignin accumulation. The overexpressing-OsGLP8-2 line had a higher lignin accumulation in the shoot and root cell walls than those of the WT, glp8-2, and glp8-(2-11). The expression of lignin synthesis genes in the OsGLP8-2-overexpressing line was significantly higher than that in the WT, glp8-2, and glp8-(2-11). The SOD activity of OsGLP8-2, Diaminobe-nzidine (DAB), propidium iodide (PI) staining, and Malondialdehyde (MDA) content determination suggested that OsGLP8-2 is involved in heavy metal-induced antioxidant defense in rice. Our findings clearly suggest that OsGLPs participate in responses to heavy metal stress by lignin deposition and antioxidant defense capacity in rice, and OsGLP8-2 may play a major role in the tandem repeat gene clusters of chromosome 8 under heavy metal stress conditions.Copper (Cu) and cadmium (Cd) are common heavy metal pollutants. When Cd and excessive Cu accumulate in plants, plant growth is reduced. Our previous study showed that Germin-like proteins (GLPs), which exist in tandem on chromosomes, are a class of soluble glycoproteins that respond to Cu stress. In this study, hydroponic cultures were carried out to investigate the effect of GLP on Cd and Cu tolerance and accumulation in rice. The results showed that knockout of a single  OsGLPs involved in Cd and Cu detoxification and tolerance in rice.OsGLPs regulate lignin deposition in cell wall by altering expression of lignin synthesis genes.OsGLP8-2 may play a major role in the tandem repeat gene clusters of rice chromosome 8 when Cd and Cu exposure.Copper (Cu) is an essential micronutrient element for the normal growth and development of plants . HoweverO-methyltransferase (CCR), and other enzymes related to lignin synthesis increase  are a class of soluble glycoproteins that are highly homologous to the germin sequence of wheat . GLP gen species . GLPs, m species . GLPs sh species . These p species . Earlieresponses . It has h blight . Transgenfection . In addinfection , droughtnfection , UV-B ranfection , and varn levels . Similarn levels . Zhou etGLP family  and overexpressing OsGLP8-2 transgenic rice, were constructed using Crispr/Cas-9 technology and the method of homologous recombination  showed that heavy metal treatment significantly upregulated the abundance of OsGLP proteins  and the P family . Our curgenetics . In thisbination . Further−1 CaCl2 nutrient solution in the dark for two days to induce rooting. After CaCl2 culture, rice seedlings were cultured with kimura B nutrient solution containing 0.18 mmoL−1 KH2PO4, 0.36 mmoL−1 (NH4)2SO4, 0.54 mmoL−1 MgSO4·7H2O, 0.18 mmoL−1 KNO3, 0.36 mmoL−1 Ca(NO3)2·4H2O, 46.25 μmoL−1 H3BO3, 0.32 μmoL−1 CuSO4·5H2O, 0.76 μmoL−1 ZnSO4·7H2O, 9.15 μmoL−1 MnCl2·4H2O, 0.11μmoL−1 H2MoO4·H2O, 20 μmoL−1 EDTA−FeSO4 .The nutrient solution was replaced every 2 days.Rice seeds were soaked in 10% sodium hypochlorite for 5 min under dark conditions. The seeds were then washed thoroughly, soaked in deionised water, and placed in an incubator at 37°C for germination. Uniformly emerging rice seedlings were evenly placed on a floating net and cultured in 0.5 mol L−1 CuSO4 treatment, or 25 μmol L−1 CdCl2 treatment. A normal kimura B nutrient solution was used as the control. Four replicates were set, and each replicate was comprised of 5 rice seedlings. All rice seedlings were grown in a greenhouse under long-day conditions (14 h light/10 h dark) at 28°C/24°C. Oryza sativa cv ‘Dongjin’ was used as the wild type (WT) in this study.Two-week-old rice plants were cultured for 5 days under normal conditions, 10 μmol LGLP8-2 were selected as gRNAs. Primers were designed based on these sequences, and the annealed product was fused with the pRGEB31 vector. The coding sequences of OsGLP8-2 were amplified from the cDNA of the WT . Two specific primers (CriOsGLP8-2F and CriOsGLP8-11R) were used to identify mutants, with 10 genes (OsGLP8-2 to OsGLP8-11) knocked out. If a clear band was observed after 1% agarose gel electrophoresis (OsGLP8-2 was fused with the pOx vector to form a recombinant plasmid (GLP8-2OE) driven by the 35S promoter. The primers used for vector construction are listed in The CRISPR/Cas9 system was used to construct the rice mutants. Two sequences of 20 bp in exons of Agrobacterium tumefaciens EHA105. The A. tumefaciens-mediated genetic transformation system was used to construct transgenic rice.The recombinant plasmids were sequenced and introduced into −1 CuSO4 for 12 h. About 50 mg of root tips were collected and snap-frozen in liquid nitrogen to extract total RNA for transcriptome sequencing . Bioinformatic analysis of the data was performed using the Omicsmart online real-time interactive platform. Each material was repeated three times. Fold change ≥ 2, and FDR ≤ 0.05.Four-day-old WT rice seedlings were treated with 3 μmol L−1 Na2EDTA for 30 min to remove heavy metal ions attached to the surface of the roots. They were then placed in an oven at 80°C until a constant weight, and the dry weight was recorded. Dry plant samples or cell wall materials (0.2 g) were digested with 5.0 mL of guaranteed HNO3:HClO4 = 87:13 (v:v) mixed acid. Cd and Cu concentrations were determined using an inductively coupled plasma optical emission spectrometer . A plant standard [GBW10043 (GSB-21)] was purchased from the National Research Centre for Standards of China and used to ensure reliable results during the digestion and analysis processes.The roots of the rice were washed with 20 mmol Lg for 5 min, and the supernatant was discarded. The pellet was washed 3 times with 95% ethanol. Finally, the pellet was washed twice with ethanol-hexane solution (v:v=1:2) and dried at room temperature to obtain the crude cell wall. The determination of heavy metals in the cell wall was performed as previously described in Determination of Cu and Cd concentrations section.Extraction of crude cell walls was according to the methods of The stems of the rice plants were stained with Safranin O-Fast Green staining and paraffin sectioned by embedding technology to determine lignin deposition in the cell walls . The roo−1 NaOH solution was added, and the reaction mixture was diluted to 25 mL with glacial acetic acid. The mixture was centrifuged at 1000×g for 5 min. The absorbance of the supernatant was measured at 280 nm, with the reaction solution containing no sample as a blank control.Six milligrams of cell wall residue were transferred to a glass test tube, and 2.5 mL of 25% bromoacetyl-acetic acid solution (v/v=1:3) and 0.1 mL of 70% perchloric acid were added. The tube was covered, sealed, and placed in a water bath at 70°C for 30 min. The test tube was shaken every 10 min. After cooling, 10 mL of 2 mol L-ΔΔCt method (ACTIN1 (LOC_Os03g50885) was used as the internal control. Three biological replicates were used for qRT-PCR, and three technical replicates were set for each biological replicate. The primers used are listed in Total RNA from rice seedlings was extracted using an RNA Extraction Kit . The cDNA was then obtained after inversion was used as a template, and the SYBR Green fluorescence quantitative kit  was used for fluorescence quantitative PCR amplification. The expression of the target gene was calculated using the 2t method . The hou2O2. DAB powder was dissolved in 50 mmol L−1 Tris-HCl (pH 6.0) to prepare a 1 mg mL−1 dye solution. Rice leaves (3–4 cm) were immersed in DAB dye solution, vacuumed for 2 hours until the leaves sank to the bottom of the tube, and placed in the dark for 12 hours. The dyed rice leaves were boiled in 95% ethanol for decolourisation. After bleaching was complete, the leaves were immersed in 70% ethanol, and pictures were taken using a stereo microscope .The Diaminobenzidine (DAB) staining method was used for the quantitative detection of Hg for 15 min at 4°C. Then, 500 μL of the supernatant was transferred to a clean 2 mL centrifuge tube, and 1.5 mL of 0.5% thiobarbituric acid (TBA) was added and mixed well. The tubes were placed in a water bath at 90°C for 20 min. After cooling, the mixture was centrifuged at 10,000 rpm for 5 min. The absorbance of the supernatant was determined at 450, 532, and 600 nm. C (μmol L-1)=6.45×(A532-A600)-0.56×A450Leaf samples (0.1 g) were ground with 1.5 mL of trichloroacetic acid (TCA) on ice and centrifuged at 12,000×−1 propidium iodide (PI) solution and soaked in the dark for 15 min. The root tips were removed from the dye solution and rinsed repeatedly with deionised water. Staining was observed with a fluorescence microscope .Rice root tips (1 cm) were placed in 3 μg LP ≤ 0.05). GraphPad Prism 6 was used to graph the data after processing. The values in the graph are the mean ± SD (n = 3). Different letters indicate the differences between several rice lines.The data were analysed using Excel and SPSS25.0 for analysis of variance and LSD multiple comparison testing   . Four-dareatment Figure 1OsGLPs to heavy metal tolerance, we designed the primers for OsGLP8-2 and OsGLP8-11 to knock out multiple genes at the same time, and obtained the glp8-2 and glp8-(2-11) mutants, respectively (OsGLP8-2 for subsequent experiments (To understand the contribution of glp8-2 and glp8-(2-11), and GLP8-2OE seedlings were treated with 10 μmol L−1 CuSO4 or 25 μmol L−1 CdCl2 for 5 days. Both the glp8-2 and glp8-(2-11) mutants showed hypersensitivity to Cu and Cd toxicity compared with the WT seedlings (glp8-2 and glp8-(2-11) mutants, while OsGLP8-2 overexpression increased heavy metal tolerance in rice (glp8-2 and glp8-(2-11) seedlings were significantly lower than those of WT and GLP8-2OE seedlings  seedlings had higher Cu concentrations than the WT, while that in GLP8-2OE was lower. This was especially obvious when the rice seedlings were treated with 10 μmol L−1 CuSO4 (−1) displayed a trend similar to Cu toxicity  mutants accumulated less Cu in the cell wall than those of the WT and GLP8-2OE when exposed to 3 and 10 μmol L−1 CuSO4  (glp8-2 and glp8-(2-11) rice seedlings.Cell walls are the main compartments that accumulate heavy metals . We deteOsGLPs, lignin synthesis, and heavy metal accumulation, we comparatively analysed lignin synthesis in different rice seedlings treated with elevated Cd and Cu levels. The Safranin O-Fast Green staining and phloroglucinol-HCl staining in stems and roots showed that the lignin content in the glp8-2 and glp8-(2-11) mutants was lower than that of the WT and GLP8-2OE rice (glp8-2 and glp8-(2-11) mutants under Cu and Cd stress, and the lignin content was about 4.6% lower than the WT   mutants, especially in the OsGLP8-(2-11) mutants, but elevated significantly in the OsGLP8-2OE seedlings. The expression pattern of five lignin-related genes under Cu and Cd toxicity showed the same trend as lignin content in the roots and heavy metal accumulation in the cell wall.To determine whether the alteration of OsGLPs expression levels affects the lignin synthesis pathway, we tested the changes in the expression levels of lignin-related genes, including phenylalanine ammonia-lyase (PAL), 4-coumarate CoA ligase (4CL), caffeoyl-CoA-O-methyltransferase (CCoAoMT), cinnamate-4-hydroxylase (C4H), and cinnamoyl-CoA reductase (CCR). Cu and Cd treatments significantly induced the expression of five lignin biosynthetic enzyme genes  Figure 6OsGLPs in oxidative stress caused by heavy metal stress, we compared DAB staining in WT and transgenic rice lines. There was no significant difference in the leaf colour of the four lines in the absence of excess Cu and Cd. When exposed to Cu and Cd, the leaf colour was darker than that of the control and GLP8-2OE. Compared with the WT, the glp8-2 and glp8-(2-11) mutants were darker, especially the OsGLP8-(2-11) mutant  content indicates the degree of peroxidation of the cell membrane and is an important indicator of plant stress resistance . As showglp8-2 and glp8-(2-11) mutants were higher than that of the WT and OsGLP8-2OE  is a nuclear fluorescent dye that indicates the integrity of the plasma membrane . When thglp8-(2-11)) and the mutant of OsGLP8-2 (glp8-2) showed the same phenotypes, such as heavy metal tolerance and accumulation, lignin deposition and gene expression levels, and antioxidant defence abilities. We speculated that OsGLP8-2 may display the main contribution in the tandem repeat gene clusters on chromosome 8 in responding to heavy metal stress. The time course for expression levels of OsGLP8-2, OsGLP8-3, OsGLP8-5, OsGLP8-7, and OsGLP8-11 genes on chromosome 8 were detected under Cu and Cd treatment. The expression of these five genes was significantly upregulated and reached a peak under Cu exposure for 3 h and Cd exposure for 12 h. Among these genes, Cd and Cu treatments upregulated the expression of OsGLP8-2, with the highest fold change. Its highest level was 71 times higher than that of the control under Cu stress and 11.3 times higher under Cd stress  of the OsGLP family was identified, and its protein level was significantly upregulated under Cu stress , which were the mutants of the OsGLP8-2 gene and ten genes (OsGLP8-2 to OsGLP8-11), respectively, were obtained. When treated with heavy metals, the loss of function of OsGLPs aggravated growth inhibition in rice  seedlings, causing more serious toxicity and ultimately leading to a sensitive phenotype. The main components of the cell wall include cellulose, hemicellulose, lignin, and cell wall proteins (glp8-2 and glp8-(2-11) seedlings was lower than that of the WT and OsGLP8-2OE lines  resulted in a sharp decrease in extracellular lignin content in Picea abies suspension cells   . These fpolymers . When Osglp8-2 and glp8-(2-11) mutants did not show significant differences. qRT-PCR of 5 randomly selected genes on chromosome 8 showed that OsGLP8-2 was more easily induced by Cu and Cd, and its upregulation was much greater than other tandem genes (glp8-2 and glp8-(2-11) mutants under heavy metal stress conditions.In addition, the em genes Figure 8via lignin deposition in the cell wall and antioxidant defence capacity. OsGLP8-2 may play a main role in tandem repeat gene clusters on chromosome 8 in rice under heavy metal stress. Further studies on the physiological role of other OsGLP members, except for OsGLP8-2, in this tandem repeat gene cluster should be investigated to explain the diversity of GLP functions.Our findings suggest that OsGLPs play a critical role in heavy metal resistance for rice The data presented in the study are deposited in the NCBI SRA repository, accession number PRJNA910469.XS: Investigation, writing-original draft. YQ and AW: Investigation and methodology. YW and YR: Investigation. TX: Methodology. ZS: Funding acquisition. QW and YX: Supervision, project administration, writing - review & editing. All authors contributed to the article and approved the submitted version.


Correction to: European Journal of Nuclear Medicine and Molecular Imaging (2022) 49:427–435https://doi.org/10.1007/s00259-021-05241-2The article Coronavirus (COVID-19) pandemic mediated changing trends in nuclear medicine education and training: time to change and scintillate, written by Gopinath Gnanasegaran, Diana Paez, Mike Sathekge, Francesco Giammarile, Stefano Fanti, Arturo Chiti, Henry Bom, Sobhan Vinjamuri, Thomas NB Pascual, and Jamshed Bomanji, was originally published online on March 4, 2021 with Open Access under a Creative Commons Attribution 4.0 International License. After publication in volume 49, issue 2, page 427–435 the author(s) decided to cancel the Open Access. Therefore, the copyright of the article has been changed on September 6, 2022 to © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022 with all rights reserved.


Radiologia Brasileira (RB), the official publication of theColégio Brasileiro de Radiologia e Diagnóstico por Imagem , initially in partnership with Prof.Giovanni Guido Cerri and then on my own since 2011. It is now time for change andrenewal. As of January, Prof. Valdair Muglia, the current president of the CBR, willbecome the new Editor-in-Chief of RB.For 21 years, I have had the honor of being Editor-in-Chief of the journal.Over the years, the journal has undergone several changes, in attempts to improve it andadapt it to international standards. Initially, we instituted the online review system,which allowed greater agility in the processing of articles under evaluation, precludingthe need to use traditional mail (which carries the risk of loss or misplacement), aswell as allowing the articles to be evaluated by two reviewers and, occasionally, evenby three. In addition, the journal now has an online version with full-text articles inEnglish, allowing researchers from all over the world to access its content. AfterRB came to be indexed in the Scopus/Scimago database, it began to beclassified according to its impact.PubMed Central subsequently approved the journal on the basis of scientific merit,paving the way for its final indexing in PubMed.The next goal was to get the journal indexed in international databases. That is theobjective of practically all major national and international medicaljournals.Researchers in the field of radiology, especially those who participate in graduate programs evaluated by the Brazilian Office for the Advancement ofHigher Education, have benefited greatly from these advances in the qualification of thejournal, not only in the evaluation of the programs to which they belong but also intheir personal evaluations, such as when they apply for research grants from fundingagencies,6.The current goal, which has been sought with the indispensable participation of Prof.Muglia, is indexing in the Web of Science database ,from which the Journal Citation Reports (JCR) is sourced annually. The JCR is thecitation reference most widely used for calculating the impact factor of ajournalAt this moment of farewell, some acknowledgments need to be made. Initially, I would liketo thank the successive boards and presidents of the CBR for the trust placed in ourwork over all these years, during which they have supported and sponsored all of ourinitiatives. I would also like to thank Dr. Alexandre Moroz, the editorial coordinatorof the journal, our right and left arm, who, with simplicity and competence, has been offundamental importance in maintaining the quality of the journal. Without him, my taskwould have been impossible. The roles played by the editorial board and reviewers, whohave been of enormous importance in the process, cannot be forgotten. Despite beingextremely busy professionals, they have made part of their scarce free time available,working anonymously to review articles, evaluate them, edit them, accept them, or rejectthem, thus ensuring what is most important in a scientific journal: the quality andscientific rigor of the material published.Although I am stepping away, I remain at the disposal of the CBR and the newEditor-in-Chief, Prof. Muglia, who has collaborated so much with the journal and with mepersonally in recent years, which undoubtedly makes him highly qualified to assume thisimportant role.


Small and medium-sized enterprises (SMEs) play an important role in supporting Indonesia’s economic growth and provide employment for people. Nevertheless, SMEs are most vulnerable when there is a flood. Small and medium sized enterprises are worse off especially after the flood, because they are relatively limited in resources and less resilient. The study aimed at identifying the vulnerability level to floods and analysing the economic valuation of flood mitigation. The population in this study were SMEs located in flood-prone areas in Klaten Regency, Central Java province, Indonesia. This research used a purposive sampling technique with 152 respondents. Data collection was carried out using a direct interview method to business actors with the help of a questionnaire. There were two analytical tools used in this research, including vulnerability index and economic valuation. The results showed that Klaten Regency is located in the upper area vulnerability category of moderate flood. The economic valuation of flood mitigation is IDR 100 000 (USD6.99) to IDR 149 999 (USD10.49). Most SMEs perceive that flood mitigation is the responsibility of the government. Small and medium enterprises (SMEs) have a vital role in supporting Indonesia’s economic growth, in which their number has reached 62.92 million units or approximately 99.99% of the total existing business actors. They contribute about 57.08% of GDP and provide around 117 million jobs for the people of Indonesia BPS . NeverthIndonesia ranks sixth amongst the world’s most vulnerable countries to the risk of flooding Isa . Based oFlood is a hazard with a large number of potential damages and losses. Nevertheless, in case there is a threat of flooding in a low vulnerability area, the SMEs tend to have the capacity to overcome it so that the risks can be minimised. Meanwhile, in a moderate or high vulnerability level area, the risk of flooding will be higher. It means that vulnerability is the main factor that causes the risk of flooding Isa . TherefoFloods definitely have adverse impact on the short-run regional economic development; hence, mitigation activities must be promoted to reduce the impact Isa . NeverthAn approach often employed in the economic valuation is the WTP or willingness to accept compensation  exposed to certain risks after a flood. Vulnerability is expressed on a scale from 0 to 1. Vulnerability can be temporary or permanent, depending on the difficulty of the problem that must be addressed, namely internal and external organisation, according to the factors that determine vulnerability.According to Auzzira, Haigh and Amaratunga , the BolA] firm is regarded as small if it meets the following three criteria, such as, it has relatively small share of the market place, it is managed by owners in a personalized way management structure, and it doesn’t form part of a large enterprise. (p. 1131–1138)[Small and medium enterprises are defined differently from one country to another. Each definition of SMEs uses different criteria and indicators. This study uses a definition supported by the Indonesian Central Statistics Agency (BPS). BPS provides a definition of SMEs based on labour force. Small businesses are business entities that have a workforce of 5–19 people, whilst medium businesses are business entities that have a workforce of 20–99 people.Many SMEs prefer to operate in urban areas because of high growth of urban markets  the individual data of respondents, such as age, gender and educational background; (2) the characteristics of SMEs, namely type of business, legal entity, number of workers, distance to river, production costs and products; (3) the knowledge level of SMEs about floods and their risks; and (4) the WTP of SMEs for flood mitigation activities.Data collection was carried out through in-depth interviews on SMEs and supported by questionnaires and focus group discussions (FGDs) to gain information on the aspects related to vulnerability to floods and mitigation activities. There were two analytical tools used in the present study, namely flood vulnerability index  and econThe flood vulnerability index is determined through compilation of all indices of the aspects of flood vulnerability  101 020 000 (USD 7064.34), IDR 59 550 000 (USD 4164.34) and IDR 38 700 000, respectively (USD 2706.29). Meanwhile, the fields with the highest loss are livestock and fisheries, agriculture and the loss of productivity, with the values of, respectively, IDR 140 700 000 (9839.16), IDR 57 400 000 (USD 4013.99) and IDR 15 920 000 (USD 1113.29).The WTP for flood mitigation is an alternative for flood risk reduction from the aspect of individual SMEs’ owners Kim . Public Most respondents prefer to use their energy for flood mitigation activities, instead of giving a sum of money. Most of them perceive that flood mitigation should be the government’s responsibility. Therefore, if they are required to contribute in the form of money, they will prefer the minimum amount.Based on the flood vulnerability index generated from the perception of SMEs, it can be concluded that Klaten Regency is in the category of moderate flood vulnerability. The sensitive aspect is the most influential aspect of the vulnerability of Klaten regency, followed by the aspects of adaptive ability and exposure.Furthermore, the economic valuation analysis reveals that the WTP of the SME owners to reduce the flood risks is in the range of IDR 100 000–149 999 . As indiBased on the conclusion, several suggestions can be proposed relating to this issue. The suggestions include the following:Collaboration is required between the government, the SME owners and stakeholders related to sustainable flood mitigation, both structural and non-structural.It is suggested for the SME owners to have insurance and improve individual resilience to flood hazards, because these are natural hazards with high risks that can occur anytime. Thus, the SME owners in flood-prone areas have to face a high risk of uncertainty.The National Agency for Disaster Countermeasure (BNPB) should conduct socialisation and trainings to reduce flood risks.


At present, the research and innovation of packaging materials are in a period of rapid development. Starch, a sustainable, low-cost, and abundant polymer, can develop environmentally friendly packaging alternatives, and it possesses outstanding degradability and reproducibility in terms of improving environmental issues and reducing oil resources. However, performance limitations, such as less mechanical strength and lower barrier properties, limit the application of starch in the packaging industry. The properties of starch-based films can be improved by modifying starch, adding reinforcing groups, or blending with other polymers. It is of significance to study starch as an active and intelligent packaging option for prolonging shelf life and monitoring the extent of food deterioration. This paper reviews the development of starch-based films, the current methods to enhance the mechanical and barrier properties of starch-based films, and the latest progress in starch-based activity, intelligent packaging, and food applications. The potential challenges and future development directions of starch-based films in the food industry are also discussed. From farm to table, food ingredients or products are susceptible to external damage or contamination, predominantly by pathogenic bacteria and oxidation, resulting in deterioration quality . TherefoIn recent years, degradable food packaging has developed rapidly. Diverse degradation technologies emerged with endless successions, such as photodegradable and biodegradable . HoweverStarch is the primary carbohydrate storage form in plant tubers and seed endosperm, generally found in maize, potato, cassava, and cereals . Starch Starch modification or blending with different materials is primarily used to resolve the above problems ,24. WithIn recent years, most of the studies on starch-based biodegradable films have focused on the sources of starch films , their p2, CH4, or H2O) [Biodegradable plastics refer to those that can be degraded by indigenous micro-organisms under natural or unique conditions and eventually convert into environment-friendly biomass or small nontoxic molecule (such as CO or H2O)   ,37. Star or H2O) . The raw or H2O) . At pres or H2O) ,41,42. S or H2O) ,44.Starch-based degradable packaging research and development began in the 1980s, and it experienced rapid growth during this period. After approximately 10 years of development, it demonstrated that only the starch component in those so-called degradable films could be degraded, while other film materials were just broken into fragments, which continued to exist in soil and water, still causing harm to the environment . Hence, Starch-filled plastics are made by mixing a small amount of original starch or modified starch with polyethylene or other thermoplastics and adding other applicable additives. Its purpose is to enhance the biodegradability of traditional petroleum-based starch materials. Nonetheless, its degradation still needs several years and cannot be thoroughly degraded ;Blended starch plastics are made of starch mixed with synthetic resin or other natural polymer materials. They are generally blends of starch/modified starch (30–60%) and synthetic biodegradable materials, which can be completely biodegradable and do not pollute the environment . CompareAll starch plastics, also known as thermoplastic starch plastic, are a natural polymer biodegradable material. They are prepared by adding degradable plasticizers and other additives  through The increasing use of starch-based biodegradable materials in food packaging has many advantages. These include reduced use of petroleum products, environmental friendliness and safety and reliability of food packaging . DespiteGood mechanical properties are essential for the actual use of food packaging materials . HoweverStudies have shown that the elongation of the starch film is negatively correlated with amylopectin content when starch is 6.3% to 25.0%. In contrast, the tensile strength of starch films was positively correlated with the amylose content, which was increased to 40% ,63. HoanAlthough the pure starch-based film has mechanical properties that can be selected by researching the properties of various starches, it does not meet food packaging requirements. Currently, chemical and physical modification of starch is predominantly used to enhance the mechanical properties of the starch film ,67. Dai In addition, starch can be acidified and hydrolyzed into starch nanocrystals to prepare enhanced mechanical properties of the material . It has One of the main functions of food packaging is to maintain food’s stability and extend its storage period. In contrast, the barrier performance of packaging materials is a decisive factor affecting the shelf life of food . Starch-Spoilage of food is closely related to environmental humidity, and the water vapor barrier is critical for retaining or extending food shelf life . DiffereIn contrast, synergistic composite modification can increase the effectiveness of starch modification, thereby increasing the water resistance of starch-based materials. Cheng and Cui  research2 NPs, SiO2 NPs, and nano-clay, have been demonstrated to be potent in enhancing water repellency. Zhang and Wang [2 NPs with different particle sizes on the properties of potato starch film. The results showed that the addition of SiO2 NPs improved the water resistance of the film. Ni and Zhang [In addition to directly modifying starch, it can be blended with some hydrophobic materials to improve the water-resistance of starch-based materials. Hydrophobic substances, such as lipids, hydrophobic nanoparticles, biomass materials, and their derivatives, are often added to starch films to strengthen their hydrophobicity. On the one hand lipids in the films can form a double layer by stacking hydrophobic lipids on a preformed starch-based film. On the other hand, lipid substances can also be added to starch film solutions in the form of emulsions to obtain starch-lipid composite films . Bedroomand Wang  studied nd Zhang  studied Due to the growth of aerobic microorganisms and the chemical deterioration of food ingredients, the infiltration of oxygen dramatically affects the quality of packaged food . To imprThe combination of nanoparticles and starch has been proven to be an effective method to improve the oxygen barrier properties of starch-based materials. For example, Wattinee and Phatthtanit  used theOxidation and microbial contamination are the leading causes of food spoilage. Starch packaging is similar to traditional packaging based on the problem of how to prolong the shelf life of products. It does not delay food spoilage by itself . Food pr2 to prevent food oxidation rancidity, packaging through the diffusion of antioxidants to the food surface or released into the packaging environment can inhibit its oxidation rancidity, so that the food is in a safer state. The fixed type can only keep the parts directly in contact with the package.The antioxidant active film can achieve an antioxidant effect by adding antioxidants to the packaging materials that can delay or prohibit food oxidation. When food is packaged in this packaging material, antioxidants are released into the interior of the packaging to extend the shelf life of the food and, to some extent, maintain the quality of the food . VariousOxidative degradation of foods is one of the significant non-microbial causes of food spoilage. Prevention of oxidation is most important for maintaining nutritional quality in foods, such as fresh produce, processed foods, and fresh meat . The useSynthetic antioxidants, such as butyl-hydroxytoluene and butyl-hydroxyanisole (BHA) starch substrates to prevent lipid oxidation, have been commonly used in food packaging . NonetheDue to their apparent volatility, volatile antioxidants in packaging materials delay food oxidation more effectively than non-volatile compounds. Essential oil, as a volatile antioxidant, is widely used in starch-based films to enhance their antioxidant properties. Elham and Majid  analyzedThe growth of microorganisms in food can lead to food spoilage, which reduces food’s nutritional value and safety . As withNatural antibacterial materials mainly come from animals and plants, as well as microorganisms and their derivatives . Common Organic antimicrobial with some application are quaternary ammonium salts, polyphenols, pyridine, etc. They kill bacteria by electrostatic adsorption, have a powerful antibacterial effect, and are inexpensive . However2 and ZnO, which have a solid binding ability with the active enzyme center of bacteria. Metal ions released by inorganic antibacterial materials in specific environments will either compound with nitrogen and oxygen in proteins after entering bacteria, or destroy the spatial conformation of protein molecules, inhibit DNA replication of cells, hinder the normal physiological functions of bacteria, and lead to bacterial death [Staphylococcus aureus was stronger than Gram-negative Escherichia coli. Chen and Li [S. aureus and E. coli. With the increase of AgNO3 solution concentration, the inhibitory effect of ACS film was greatly amplified.Inorganic antimicrobial agents generally refer to nano-metallic materials, such as Ag and Cu, or photocatalytic antimicrobial agents, such as TiOal death . Hu and al death  preparedn and Li  preparedCommonly used antioxidant and antibacterial materials have good antioxidant and antibacterial effects . HoweverControlled release packaging (CRP) extends product shelf life by controlling the release of active substances in food storage . There aZhang and Zhao  preparedIn addition to extending the shelf life of food through active substances, a new type of intelligent food packaging can be developed by giving new functions to starch-based packaging materials . IntelliCompared with other degradable polymers, the most significant advantage of starch-based film is that it is colorless and transparent, and the color change of food packaging film will not be affected by the sample matrix. Starch-based intelligent food packaging mainly combines indicators and provides intuitive, quantitative, or semi-quantitative information about packaged food through visual changes, such as color . It inclThe film-forming ability of starch makes the biopolymer an ideal proppant for preparing intelligent colorimetric films. Recently, interest in developing intelligent pH-sensitive films using starch has increased. pH changes are the primary food freshness and standard conditions. As food rots under the action of microorganisms, the pH value around food changes, so the relationship between food freshness or quality and pH value can be verified . OrganicStarch as a film matrix, mixed with indicators, can respond by sensing changes in food. When food rots, ammonia, dimethylamine, triathlon, and other gases will be produced. These gases will change the pH value around the food, and the natural pigment in the packaging film will change the color through its mechanism. For example, bok choy anthocyanins generally increase with pH, ranging from mauve to blue-purple to blue-green. This distinct color change allows the consumer to clearly identify whether the food is at the fresh, medium fresh, or spoiled stage and bring reference to consumers’ consumption. Choi and Lee  designedElectrochemical methods in pH sensors are used to convert chemical information into electrical signals for analytical experiments. The sensor receives chemical information and converts it into usable energy, which it converts into electrical signals . In foodPerishable food is sensitive to temperature, and low-temperature storage can effectively prolong its shelf life. High temperatures accelerate the deterioration of food quality and lead to food reaching the end of shelf life in advance. Time and temperature are key factors affecting the quality of most foods. The time–temperature indicator (TTIs) can record and indicate the temperature change of the remaining shelf life of food during its circulation . ThroughCompared to other areas, research on time and temperature indicators began late, and there is little relevant research. For example, Carolina and Pricila  added myStarch films have made great progress in mechanical and barrier properties, and a large amount of research work on this subject shows the promise of starch films as an alternative to petroleum-based polymers as food packaging materials. Starch modification and additives have proved successful in producing films with similar properties to conventional packaging materials. In addition, starch-based films are used as carriers of functional ingredients to prepare active and smart packaging by combining antibacterial, antioxidant, and indicator agents to improve shelf life and quality, while facilitating the observation of food spoilage levels.In response to consumer demand, there is a need to extend the shelf life of food products in the food industry. In the overall food circulation link, it is essential to maintain the high level of food quality. Certain starch-based biodegradable films have been used in food packaging. E. coli was superior to that of Listeria monocytogenes and S. aureus. The antibacterial activity of YDE3 film was better, which could prolong the shelf life of pork by more than 50%  were prepared by controlling the pH value of the film-forming solution and applied to real-time monitoring of shrimp freshness (In addition to applied research on active packaging, scholars have also developed intelligent packaging film materials based on starch. At present, they are primarily focus on indicator intelligent packaging materials. Indicative intelligent packaging combines intelligent functions with standard packaging technology and provides consumers information through external color changes. Chen and Zhang  preparedreshness B. The reBased on the existing studies, intelligent packaging materials are mainly prepared using the color principle of CR and ATH, which has a good indicator effect on food with a significant change in pH value during food spoilage. Still, the precise relationship between pH value change and quality change remains to be further studied. In addition, the film material with antibacterial function has been prepared based on intelligent packaging, so developing intelligent, active packaging material is a research direction in the future.Starch-based biodegradable materials may play an important role in the future development of sustainable food packaging materials, reducing the energy and environmental stress of petroleum-based packaging materials. The current limitation is mainly due to the poor mechanical properties and barrier properties of starch-based packaging materials due to the properties of starch itself. Researchers can solve this problem by physically or chemically modifying starch or mixing it with other biopolymers and functional additives. After meeting the basic conditions of food packaging, starch-based active packaging can be prepared by adding antioxidant or anti-bacterial substances, which can extend the shelf life of food and reduce food waste. Starch time and temperature indicator films can detect food freshness in real-time by the color reaction. Starch-based films are widely used in food packaging and have a good protective effect on fresh food. In the future, it will be possible to prepare active or smart packaging using starch-based materials.Although some of these methods have improved the properties of starch-based films, more research is still needed to create starch-based films with similar mechanical and barrier properties to traditional plastic packaging. Starch-based biodegradable materials can be affected by starch type, preparation techniques, storage conditions and other factors during preparation, resulting in a lack of homogeneity and stability of the product. Currently, most research on food packaging applications is completed at the laboratory level. Industrial manufacturing, safety regulations, environmental issues, and consumer acceptance have also limited the commercialization of starch-based films. In addition, the combination of starch and other materials needs further study to meet practical needs. Many additives have great potential in developing antibacterial and antioxidant films. There is still quite a lot of interesting work to be done in terms of developing antimicrobial agents that can be used in starch matrices. There is a lack of appropriate criteria for assessing and quantifying antimicrobial and antioxidant activity. For example, in “food mimics” solutions, the mimics corresponding to different foods should be expanded rather than limited to water. The field of starch-based smart films has great potential, although so far its functionality has been relatively limited. At present, pH indicators are mostly used in intelligent packaging. While changing the environment around the food in package, active substances will also change the pH change of the system, which may lead to the irreversibility or timeliness of indicators in packaging film and cause consumers to make a wrong judgment on product quality. Further studies are needed to investigate the combination of functional food components with multireactive starch membranes. By mixing with heat-sensitive, moisture-sensitive, gas-sensitive, and other multifunctional packaging materials to prepare new intelligent packaging, the film can have a variety of different functions, can prepare the corresponding stimulus response packaging according to the food needs, and have a slow/controlled release effect on the active substances in the film.In summary, although starch-based active and intelligent packaging still has shortcomings in terms of material selection, preparation, and its role, there is no doubt that starch has become the most likely substrate to replace petroleum-based traditional packaging due to its structural properties and other advantages, and it has the possibility of substrates leading the development of intelligent food packaging in the future.


This article investigates the role of local banking development, per se, in European SME debt policies, using a cross-country dataset. Moreover, it assesses whether the debt policies of SMEs are mainly driven by local or national banking development. We find that higher levels of local banking development increase the amount of debt used by SMEs. Results suggest that national banking institutions reduce the influence of local banking sectors on SME financial behavior. Several robustness and further tests validate our results, suggesting that whilst the process of international integration and digitalization of financial markets, local banking development is still relevant despite the moderating role of national banking policies. Consequently, policy makers should first and foremost allow headquarters and central banks to better support local banks in integrating national banking policies in order to reduce the financial constraints on SMEs and spur their economic growth. The influence of financial institutions on firm policies is one of the most important topics in corporate finance. Noteworthy authors found that the development of the financial systemIn this paper, we provide a contribution to this body of literature, studying the effect of LBD on the debt decisions of SMEs, using a unique large dataset composed of SMEs from six different European countries.In addition, our analysis provides another important originality in studying whether SMEs rely more on LBD or national banking development (NBD). NBD refers to the banking development at the country level :Our work aims to provide further investigation in this field of research by focusing on a wide European context of analysis. Based on the main idea that soft information about SMEs is less available to banks in a context of centralized bank industry, where the distance from local firms is higher Stein, , we expeLocal banking development has a positive effect on European SME use of debt.The above arguments that led to the development of the first research hypothesis highlight how firms debt decisions are determined by factors that are related to local banking sectors. Antecedents in literature suggest that institutional factors at the national level also have a key role on corporate debt policies :Moreover, despite the presence of significant differences across provinces . Despite the presence of the European banking union created in 1993 to guarantee the stability of the banking sector in the euro area, each single European country has its own characteristics in terms of banking system. In France, the deregulation process in 1984 had a key role on building the actual banking organization, which is composed on commercial banks that are spread throughout the territory and some of them are among the largest banks in the world  scaled by total assets. We use an accounting-based measure as no information about the market value of small businesses is available. Firms that are more profitable are likely to have a proactive approach versus financial strategies. Size is measured as the logarithm of total assets. Larger firms typically have a bargaining power with their lenders or suppliers. Tangibility is the ratio of tangible fixed assets to total assets. Tangible assets may increase firms’ financial capacity as they are used as collateral. Age is calculated as year minus year of incorporation. Older firms have a long history that reduces information asymmetries and facilitates credit provision. Different Tax Shield is calculated as earnings before interest, taxes, depreciation and amortization minus earnings before interest and taxes (EBITDA—EBIT) scaled by total assets. This variable is particularly important to control for the different tax regimes of the European countries. Firm Growth is measured as sales in year (t) minus sales in year (t−1). Growing SMEs generally require more financial resources  to year (t). Enforcement represents the time required to enforce a right, in terms of number of days necessary to conclude a court case, and takes into account the efficiency of the law courts at the local level  technique, whose advantages have been clearly explained by the extant literature  indicates a large variability of the dependent variables across the SMEs in the sample. Table Descriptive statistics show that our dependent variable play a very important role in the financing of European SMEs. In particular, on average debt represents 20.2% of total assets. Moreover, the standard deviation of Debt for high and low levels of both LBD and NBD based on the median.LBD and NBD increase the use of debt. This demonstrates that different degrees of our key independent variables influence the debt policies of SMEs. Moreover, we sort the whole sample into four sub-samples according to low and high levels of LBD and NBD both based on median values.Additionally, we report descriptive statistics of the variable Debt during the years, observing a mostly stable trend throughout the period examined and suggesting that the influence of the economic cycle should not be very decisive.Furthermore, we show  that is far below the generally accepted cut-off of 10  for regression models  and during the Global Financial Crisis (the period 2008–2010). We observe that the moderating effect of the national banking system on SMEs’ use of debt highlighted in our second hypothesis does not significantly change before and during the crisis. Results are reported in Table As an additional further test, we collected dataAs a first robustness test,LBD and NBD. Although the test suggests the absence of an endogeneity issue, we also checked whether the results were still valid when controlling for this kind of bias by using the 2SLS technique. As previous studies based on Italy have settled endogeneity problems using regressions with instrumental variables (IV), we run 2SLS regressions on Italy using the same IV as in Guiso et al. . Hence, the results of placebo tests confirm the robustness of the findings, which are thus not influenced by chance.As a supplementary robustness test, we run the placebo test. Our sample has a very high number of observations that could affect the statistical significance of the findings . Regressions confirm the validity of the main model results. Moreover, we investigated our hypotheses by using a different proxy of LBD, i.e. Beginning with the milestone contribution of Guiso et al. , the finAssuming that LBD is also relevant in a cross-country environment, this research addresses another important question still unresolved: do European SMEs benefit most from local or NBD? The findings reveal that, notwithstanding the relevance of the local contexts, as indicated by the extant literature, the national dimension of the banking system seems to better drive the debt policies of European SMEs. In particular, our moderation study highlights that the relative importance of LBD decreases with higher levels of NBD. Consequently, in those contexts where the national banking institutions are more developed, local credit markets have a lesser influence on SME debt policies. Hence, although local bank branches are still important, SMEs rely more on the development of the banking macro-system of a country.Our paper is at the crossroads of two lines of literature that in parallel study local (within country) and national (between countries) banking development and their effects on corporate debt policies. At the same time, it advances these strands of research, as it investigates for the first time SME debt strategies considering both local and national banking institutions in a cross-country European setting. The results highlight that the national banking environment moderates the role of the provincial banking system, suggesting that future researchers in this field take into account the macro‐level contingencies in which SMEs are embedded. Thus, the key findings of this article concern the need to joint consider LBD and NBD as crucial determinants of debt decisions of European SMEs. Additionally, further research could explore to which tipping point the level of NBD does not influence the role of LBD. A limitation of this study is the period of analysis that does not consider recent years. Further studies could thus investigate the effect of LBD and NBD for firms during the pre and covid years.Moreover, the work has also implications for policy makers and researchers. Given that national rather than LBD resulted in being more effective in influencing the debt choices of European SMEs, governments should primarily commit to improving the national banking institutions that drive the operations of local banking sectors. Regulations aimed at developing and making more effective national banking sectors are important to ensure SMEs a priority channel to external resources. According to our findings, the banking institutions of a country should act as a fellow traveller that accompanies SMEs towards value creation processes, overcoming obstacles and external frictions for SMEs. This is especially important during the current Covid-19 downturn, where European SMEs are in great need of financial resources to recover from the crisis. In this regard, we recommend that policy makers enhance the effectiveness of the banking systems, especially the national ones, in order to meet the credit need of small European businesses. Decision makers could improve European SME access to outside sources of financing by creating incentive policies and specialized credit patterns for SMEs. The presence of strong national banking institutions should be encouraged. The European Commission and the governments of the individual countries of the European Union should move in this direction, with the final aim to reduce the asymmetric information problems of SMEs and, more generally, all the financial constraints that impede corporate growth. Moreover, governments should upgrade the role of the banking institutions, making them not only credit providers, but also financial advisers that can provide support in understanding appropriate financial strategies. This approach could increase not only the quantity, but also the quality of external funds available for SMEs. In more detail, national banking institutions could establish a program aimed at providing professional financial advice for SMEs. Such a program needs to be applied at the local level in order to bridge the gap of financial skills that SMEs need. Indeed, this is particularly important, as the managers of SMEs are often in need of more financial skills (Van Auken, Our work suggests that the local banking sector is still important, despite the internalization and integration of financial markets, and it can significantly support SME businesses. Local bank branches are directly in charge of collecting and interpreting soft information from their relationship with SMEs in credit provision. Agarwal and Hauswald , p. 2759In conclusion, in the current context where much attention is paid to the financial resources available for SMEs in severe difficulty caused by the coronavirus crisis, it is of importance that European policy makers formulate policies that promote the development of national banking institutions. Indeed, “the state of development of the financial markets does indeed facilitate growth, and is not simply correlated with it” (Rajan & Zingales,


All WB with ECF had a more intense color and additive odor. Bread samples with 10% and 15% ECF had more intense overall, additive, acidity, and bitterness flavors. However, all WB had similar overall acceptability (OA) and no correlations were found between OA and VC. The EM “happy” and “sad” were expressed more intensely for WB with 15% ECF, and significant correlations were established between the EM “happy” and separate VC. The main VC in WB were ethanol; 1‐butanol and 3‐methyl; 1‐hexanol; estragole; and hexanoic acid. Finally, 5% ECF could be incorporated into the main WB formula without having a negative impact on bread quality. Also, ECF influences VC formation, and separate VC could be related to emotions induced for consumers.This study evaluated the influence of edible cricket flour (ECF) on the quality parameters and sensory characteristics of wheat bread (WB), including the formation of volatile compounds (VC) and their relationship with emotions (EM) induced for consumers. ECF reduced dough pH, redness, and yellowness. At 5%, ECF increased the porosity of WB (by 7.87%). The quantity of ECF significantly affected WB's specific volume  on the quality parameters and sensory characteristics of wheat bread (WB), including the formation of volatile compounds (VC) and their relationship with emotions (EM) induced for consumers. ECF influences VC formation, and separate VC could be related to emotions induced for consumers. The WB samples were prepared without and with the addition of edible cricket flour . Edible cricket flour was provided by Bugsandus Ltd. . Cricket flour composition is as follows: protein 62.6%, fat 26.5%, ash 3.8%, moisture 2.0%, saturated fatty acids 8.7%, total carbohydrates 5.1%, sugars <0.6%, and salt  at 220°C for 25 min.The WB formula consisted of 1 kg of wheat flour, 1.5% salt, 2% fresh compressed yeast, and 56% water (control bread). Control WB samples were prepared without the addition of edible cricket flour. The dough was mixed for 3 min at a low speed and then for 7 min at a high‐speed regime in a dough mixer . Then, the dough was left at 22 2.3± 2°C, WB samples were subjected to analysis of specific volume, crumb porosity, shape coefficient, mass loss after baking, crust and crumb color coordinates, sensory characteristics and overall acceptability, emotions induced for judges by the bread, and VC profile.After 12 h of cooling at 22 Bread volume was established by the AACC method AACC, , and theThe slices of bread also were tested by applying FaceReader 8.0 software  was used for analysis. The temperature gradient was programmed from the start at 40°C (3 min hold) to 220°C (6°C min−1) up to 250°C . The VC were identified according to mass spectrum libraries .The VC of the bread samples were analyzed by gas chromatography–mass spectrometry (GC–MS) as described by Bartkiene, Mockus, et al. . A solid2.4n = 3; and for bread sensory characteristics, overall acceptability, and emotions induced for trained judges n = 10) ± standard error (SE). In order to evaluate the effects of different quantities of edible cricket flour on WB quality parameters, data were analyzed by one‐way ANOVA and Tukey HSD tests as post hoc tests . Also, Pearson correlations were calculated between various parameters, as well as between the separate VC and overall acceptability of the bread, and between VC and the emotion “happy” induced for judges. The results were recognized as statistically significant at p ≤ .05.The results were expressed as the mean values . The positive correlation between dough acidity parameters (pH and TTA) can be explained by proteolysis, which can lead to the formation of alkaline compounds and the neutralization of dissociated acids in dough. Also, volatilization of small molecular acids during the process is possible. As well as that, the incorporation of proteinaceous ingredients  in the main bread formula can lead to more free amino acids being released into the medium, and this can contribute to more effective yeast growth. In addition, amino acids take part in the Maillard reaction and can lead to a more intense odor, as well as color, of the product.Dough acidity parameters and color characteristics are given in Table Comparing dough color characteristics, the addition of edible cricket flour increased dough redness (a*) and yellowness (b*) coordinates , and the doughs prepared with 10% edible cricket flour had the highest a* and b* . Also, doughs prepared with 10% edible cricket flour had the lowest lightness .r = −.8920, p = .0001; and r = −.8110, p = .001, respectively; and between pH and TTA and b*: r = −.8500, p = .0001; and r = −.8490, p = .0001, respectively). However, the correlations between dough acidity parameters and L* were not significant. The influence of the analyzed factor (different quantities of edible cricket flour) on dough pH, TTA, and a* and b* color characteristics was significant (p = .0001); however, the quantity of edible cricket flour incorporated was not a significant factor in dough L* color coordinate (Table Very strong negative correlations were found between the dough acidity parameters (pH and TTA) and a* and b* color characteristics ; strong and moderate positive correlations were established between bread's specific volume and porosity and bread mass loss after baking . These findings can be explained by more intensive water migration during the baking process from bread that is more porous and has a higher specific volume, which leads to loaves with a lower mass. Bread samples containing edible cricket flour had a higher shape coefficient in comparison with control bread samples, the highest being found in slices of bread with 5% edible cricket flour (2.83). The analyzed factor (different quantities of cricket flour) had a significant influence on WB specific volume (p = .030), porosity (p = .0001), shape coefficient (p = .0001), and mass loss after baking , are given in Table p ≤ .05) on all the analyzed bread crust and crumb color coordinates . Dough TTA showed strong positive correlations with bread crust a* and crumb L* color coordinates , as well as a very strong negative correlation with bread crumb b* color coordinate . Moderate and strong negative correlations were found between bread's specific volume and bread crust L* and b* color coordinates , and a strong positive correlation was established with bread crust a* color coordinate . Very strong correlations were found between bread porosity and all the evaluated crust and crumb color coordinates: negative correlations with crust L* and b*, as well as crumb a* and b* , and positive correlations with crust a*, as well as crumb L* . These correlations could be associated with a higher degree of water migration during the baking process, as well as more intensive Maillard reactions in the bread with higher specific volume and porosity.Comparing bread crust color coordinates, no significant differences in L* and a* color characteristics were established between the control bread samples and slices of bread prepared with 5% edible cricket flour . However, the highest b* coordinate was found in slices of bread prepared with 15% edible cricket flour . Comparing bread crumb color coordinates, the addition of edible cricket flour reduced bread crumb L* . The lowest a* and b* coordinates were found for the crumb of bread samples with 5% edible cricket flour; no significant differences in crumb b* coordinates were found between control bread and bread samples with 5% edible cricket flour. The analyzed factor (different quantities of cricket flour) had a significant influence . Also, a very strong positive correlation was found between valence and overall acceptability . The analyzed factor (different quantities of cricket flour) had a significant influence on the induced emotions “happy” (p = .005), “sad” (p = .014), “surprised” (p = .005), and “disgusted”  profiles of bread prepared with different quantities of edible cricket flour are shown in Figure 3.4The VC profile of WB prepared with different quantities of edible cricket flour and its correlation with overall acceptability and emotions induced for judges are given in Table r = −.664, p = .0185 and r = .6700, p = .0171, respectively). In contrast to the above‐mentioned findings, a strong positive correlation was established between the emotion “happy” and hexanoic acid . Ethanol odor is characterized as vinous; 1‐butanol odor is described as fusel, oily, sweet, balsamic, and whiskey; 3‐methyl odor as fusel, alcoholic, pungent, etherical, cognac, fruity, banana, and molasses; 1‐hexanol odor as pungent, ethereal, fusel oil, fruity and alcoholic, and sweet with a green top note; estragole odor as sweet, phenolic, anise, harsh, spice, green, herbal, and minty; and hexanoic acid odor as cheesy, fruity, phenolic, fatty, and goaty.Similar tendencies were found for 1‐butanol, 3‐methyl‐, and 1‐hexanol: on increasing the percentage of edible cricket flour, the concentration of 1‐butanol, 3‐methyl, and 1‐hexanol was reduced. However, the highest concentration of ethanol was established in slices of bread with 5% edible cricket flour (15.5% of the whole VC). Also, strong negative correlations were found between 1‐butanol and 1‐hexanol and the emotion “happy” induced for judges , pyrazine <2‐ethyl‐> , 2‐nonenal, (E)‐ , 3,5‐octadien‐2‐one , 3‐furanmethanol , and guaiacol <4‐vinyl‐> . The content of most of the above‐mentioned VC was lower in slices of bread prepared with edible cricket flour, in comparison with control bread samples . Hexanal odor is characterized as fresh, green, fatty, aldehydic, grass, leafy, fruity, and sweaty; pyrazine<2‐ethyl‐> odor is described as peanut butter, musty, nutty, woody, and roasted cocoa; 2‐nonenal, (E)‐ odor as fatty, green, cucumber, aldehydic, and citrus; 3,5‐octadien‐2‐one odor as fruity, fatty, and mushroom; 3‐furanmethanol is described as a bready‐type odor; and guaiacol <4‐vinyl‐> odor is associated with dry, woody, fresh, amber, cedar, roasted, and peanut.Despite the fact that some compounds were found in smaller amounts in the bread VC profile, they showed a significant correlation (positive and/or negative) with the emotion “happy” expressed in the faces of judges. Strong negative correlations were found between emotion “happy” and hexanal , pentanoic acid , dec‐(4Z)‐en‐1‐ol , 1H‐pyrrole, 1‐(2‐furanylmethyl) , and heptanoic acid , ethanol, 2‐phenoxy‐ , and nonanoic acid . Comparing the above‐mentioned VC in bread samples, the lowest content of benzaldehyde was found in control bread samples , and on increasing the edible cricket flour content in the main bread formula, benzaldehyde was increased. A similar pentanoic acid content was established in control bread and bread prepared with 5% edible cricket flour ; however, on increasing the edible cricket flour content in the main bread formula, pentanoic acid was increased. The 1H‐pyrrole, 1‐(2‐furanylmethyl) content in control bread and bread samples with 10% and 15% edible cricket flour was similar, and the lowest content of 1H‐pyrrole, 1‐(2‐furanylmethyl) was found in bread samples prepared with 5% edible cricket flour. The highest heptanoic acid content was established in slices of bread with 10% and 15% edible cricket flour , and the highest nonanoic acid content was found in bread samples prepared with 15% edible cricket flour . Benzaldehyde odor is described as strong, sharp, sweet, bitter, almond, and cherry; pentanoic acid odor as acidic and sharp, cheese‐like, sour milky, tobacco, with fruity nuances; dec‐(4Z)‐en‐1‐ol odor as waxy, fatty, and fruity; 1H‐pyrrole, 1‐(2‐furanylmethyl) odor is associated with plastic, green, waxy, fruity, coffee, and vegetable; heptanoic acid odor as cheesy, waxy, sweaty, fermented, pineapple, and fruity; ethanol, 2‐phenoxy odor is described as mild, rose, balsam, and cinnamyl; and nonanoic acid odor as waxy, dirty, and cheesy with a cultured dairy nuance.Positive correlations were found between the emotion “happy” and benzaldehyde (p ≤ .05) on most of the VC identified in bread (except 2[3H]‐furanone and dihydro‐5‐pentyl). Finally, our study is in agreement with previous findings that VC formation is related to many factors, and despite the overall acceptability of the different slices of bread being similar, different VC could be related to the emotions induced for consumers.Bread aroma is one of the first quality parameters perceived by consumers and a most important characteristic of product acceptance. However, sensory analysis methods are limited by human perception (Hansen & Schieberle, 4The influence of edible cricket flour on dough and bread parameters varies and, in most cases, is related to the quantity of additives. Edible cricket flour reduces dough pH, redness, and yellowness. However, 5% edible cricket flour increases the porosity of bread by 7.87%. Sensory analysis showed that the edible cricket flour led to a more intense bread color and additive odor. Also, slices of bread with 10% and 15% edible cricket flour showed a higher intensity of overall, additives, acidity, and bitterness flavors. However, all bread samples showed similar overall acceptability and no correlations were found between bread overall acceptability and VC. However, a higher intensity of the emotions “happy” and “sad” was expressed for bread samples prepared with 15% insect flour, and significant correlations were established between the emotion “happy” and separate VC. Finally, 5% edible cricket flour could be incorporated into the main WB formula without a negative impact on bread quality. Also, edible cricket flour influences the formation of VC, and separate VC could be related to emotions induced for consumers.The authors declare no conflict of interest.


The Asian-Australasian Association of Animal Production Societies (AAAP), the only international scientific organization in animal science representing Asia and Pacific region, showed a remarkable development since its inception in 1980. The number of member countries increased from 8 to 19 while 19 congresses were held in 11 different member countries. The AAAP also helped creating the official journal, Asian-Australasian Journal of Animal Sciences in 1988 with the title being changed to Animal Bioscience in 2021. It is an open access journal indexed by most global databases and has become one of the most respected global journals in animal science. Through scientific meetings and journal publication, the AAAP has made a tremendous contribution to the advancement of animal science and industry throughout its member countries over the last 40 years. This paper summarizes the advances in animal science in the Asia–Pacific region, together with the roles of the AAAP scientists and journals in developing animal science. The AAAP region covers diverse environments, religions, cultures, economies, and nature. Asia alone harbors more than 50% of the global population  that is This might be a good opportunity to examine the contributions of AAAP countries to the advancement of science, especially animal science.Reports on scholarly activities over a long period on a global scale are not easy to obtain because of limited availability of realistic data. A recent study showed interesting data illustrating the trend of global scholarly activities. This study used the Scopus database to examine the publication trends of scholarly journal articles, including the science of 12 major countries, during the last 120 years .As depicted in This is clearer if one takes a look at the publication trend in more recent years using different databases . The oveIf one narrows down the scope from all disciplines of science to animal science, the same trend can be seen in which the AAAP scientists in animal science in 2021 show outstanding performance in terms of the output of research articles . Four AAConsiderable improvements have been made in journal publication activities by the AAAP member countries. Currently, 63 journals in the animal science category are indexed by the Science Citation Index Expanded (SCIE) . Of thesThe impact factor (IF) is one way of measuring the citation frequency of journals and is often considered as the degree of quality or reputation of journals. The IF of AAAP journals, similar to that of many other international animal science journals, has continuously improved in recent years. However, the magnitude of improvement within the AAAP varied considerably, as shown in It would be interesting to determine the contribution of AAAP to global research activity in animal science. When the AAAP was founded 40 years ago in 1980, its contribution to global research output in animal science was approximately 15% . PresentWe can see the same picture in journal article quality , althougTherefore, these data show that the R&D capability of the AAAP countries has improved substantially during the last 40 years since the birth of the AAAP. Of course, many factors, such as increased investment in research activity with economic growth, contributed to such results, but the roles of scientific organizations such as the AAAP cannot be ruled out for the development of animal science and the livestock industry.Most scholarly organizations plan to hold conferences, congresses, or various scientific gatherings, and to publish journals to provide a proper platform for their members. It is considered that the AAAP has fully played the role of a scientific organization in both aspects during the last 40 years. In this section, I will summarize the major activities of the AAAP since its foundation in 1980.The descriptions here are mostly based on official records of the AAAP Secretary General’s Office, together with previously published documents –8. PersoThe 1st AAAP congress was held in 1980 under the leadership of the Malaysian Society of Animal Production. After eight years, the official journal AJAS was founded under the leadership of Prof. In K. Han, and later, the journal title was changed to Animal Bioscience (AB) in 2021. The permanent secretary general office was established in Korea in 2000, and different award programs were launched at 10-year intervals: 1990, 2000, and 2010.The AAAP began with eight members and now has a total of 19 members, making it one of the most important international organizations in the world. Charter members were Australia, Indonesia, Japan, Korea, Malaysia, New Zealand, Philippines, and Thailand. Taiwan joined the association in the 2nd Congress held in the Philippines in 1982. Other countries were invited as members in different years, with China and Sri Lanka becoming the most recent AAAP members in 2006. Although the size of membership has more than doubled in the last 40 years, the list is not complete until many other Asian countries join our association. I hope the AAAP council continues to try inviting more nations as members so that other Asia–Pacific animal scientists can participate and benefit from our activities.To date, 19 AAAP animal science congresses have been held in 11 different member countries . MalaysiIt should be emphasized that the AAAP Congress is an important event for not only scientists but also other professionals in the livestock industry. Thus, it is one of the most important scientific gatherings for many scientists to exchange ideas, disseminate animal science, and develop friendships and professionalism. These meetings, especially during the early days, were rare opportunities for scientists from many parts of Asia, especially young scientists, and in that aspect, we must appreciate the great contribution of the AAAP congresses. The participants were not limited to member countries, Asia, or the Pacific region. Most congresses were attended by both member and non-member countries with almost 30 different nationals, except for a few meetings, which shows that the congresses gained international importance and popularity.One of the most important outcomes of the congress may be the proceedings that compile plenaries, symposiums, and scientific presentations, usually in abstract form. International meetings were used to distribute several volumes of heavy thick proceedings in a conference bag in the past, although an increasing number of organizers prefer to put conference contents into handy and easy-to-carry devices, such as disks and USB. Indeed, a few other congresses do not provide hard copies or conference contents in any form of device, but provide participants with access to proceedings only in an online format. Technical development, together with the impact of the pandemic, brought about changes in many gatherings and meetings.Awards are a good stimulus promoting excellence in research and development, and it is fortunate that the AAAP has created several award programs for its members.One of the main award programs is the AAAP Animal Science Award, established in 2000 with a generous donation from the Hans’ Animal Life Science Foundation in Korea. The foundation supported the award program until 2008; thereafter, the award was funded by the country hosting the Congress. Fifteen eminent scientists received awards until 2022.Another award program, the Woogene B&G Award, was initiated in 2010, funded by Woogene B&G (Korea), and all members of the AAAP are thankful to the company for their generous financial support.Our association also has other award programs, especially for young scientists, as follows. One is the travel grant, and young scientists are chosen as awardees to support and encourage their participation. A grant is usually supported by a host country. Another program is the Best Presenter Award, which is given to young scientists  who show excellent performance in oral or poster presentations.It should be recognized that these awards have been supported by the Japanese Society of Animal Science, Korean Society of Animal Science & Technology, and Prof. LC Hsia, Taiwan. The contributions and efforts of the Japanese and Korean Societies and Prof. Hsia are greatly appreciated.The official journal of AAAP, Asian-Australasian Journal of Animal Sciences (AJAS), was founded in 1988 in Korea. According to two previous presidents of the AAAP, Profs. In K. Han and S. Jalaludin, the idea of an official journal publication at the beginning was not well accepted; member countries did not have a real need for such a journal, and people did not have a firm belief in the success of such publication activities in Asia. However, a few dedicated frontier scientists led by Prof. In K. Han, the first editor-in-chief, were able to turn AJAS into one of the most respected global journals in the animal science category.As expected, collecting the manuscripts in the early days proved to be difficult. Less than 50 manuscripts were submitted in the first year; however, this rose to almost 1,000 annually in some years. At present, authors from more than 50 countries have chosen AJAS to report their research work. China and Korea are the major contributing countries. Approximately 70% of submissions are from the AAAP countries, with the remaining 30% originating from the non-AAAP region .Generally, the number of published articles reflects the number of submissions. Papers from the two most submitting countries, China and Korea, account for the highest number of publications. Publications by non-member countries such as the USA, Brazil, and Italy are also gradually increasing.The AJAS has made a tremendous improvement in citation frequency. When AJAS was indexed by the SCIE for the first time in 1997, the IF was lower than 0.1; however, it is now 2.7. The total number of citations in the first year was less than 100, but it was almost 9,000 in 2021, which is an approximately 100-fold increase over the past 20 years . It is eFor successful journal publication, continued and dedicated efforts by many researchers are required. In particular, small society journals such as AB cannot expect enough financial and manpower support from society, which requires dedication from many volunteers. Many volunteers are involved in journal publication. This is definitely a strong asset for AB.Recent outstanding journal quality improvement was, to some extent, due to the recently completed 7-year development program (AJAS 2020 program). Despite recent significant improvements in journal quality, continued innovation is essential to maintain as a leading journal in the ever-changing global publication environment. The AB should be able to provide the best content to become a highly prestigious and respected journal. Continued efforts are required to invite high-quality articles. Furthermore, AB should be able to provide a global standard system to stakeholders such as authors, reviewers, and the general public for efficient and easy access to AB systems.The title of our official journal was changed from Asian-Australasian Journal of Animal Sciences (AJAS) to Animal Bioscience (AB) effective from January 2021. Through this change, it is anticipated that we can enhance journal brand identity, secure international leadership, and perhaps be able to cover the diverse interests of the animal industry and academia in the long run.The AJAS also created an award program in 1990, which has been financially supported by Cargil AgriPurian Inc. (CAPI), Korea. During the early days, awardees were selected solely based on the excellence of research papers published by AAAP member scientists; however, in recent years, authors with the other qualifications such as contribution to journal development through citations and other services have also been chosen as awardees.To date, 42 AAAP scientists have been recognized by this award program. Congratulations to all of these awardees, and their contribution and dedication to the advancement of the journal are greatly acknowledged. We also sincerely appreciate CAPI for their generous support since the inception of the award program.Overall, it is needless to say that the AAAP played a key role in bringing animal scientists together and contributing to the development of livestock production in Asia and the Pacific. The AAAP never missed the regular Animal Science Congress, which served as an important forum for the exchange and dissemination of information and new ideas. Its official journal, AJAS, has become one of the major international journals in the field of animal science. In addition, the association has initiated various award programs to encourage research and other scientific activities of members.Therefore, there is no doubt that the AAAP will continue to thrive, as was the case in the past. However, there are still some challenges and issues ahead of us, and it would be worthwhile to identify some of the key issues and propose possible approaches to dissolve them.As is well known, many local, regional, and international associations and journals are similar in nature to the AAAP and AB. Therefore, the association and journal should be able to provide sufficient motivation to become our member, to attend our congresses, and to publish their work in our journal. Continued efforts to bring innovation to our association and journal will definitely be required to maintain competitiveness.If you look up proceedings and journals, you seldom see abstracts and articles produced from joint projects or collaborations with the AAAP members. More collaboration and interaction among the member countries is required. The AAAP members should seek more opportunities to provide their opinions on regional and global issues.We also need channels to establish more collaboration with other international organizations. This could be a simple exchange program for junior and senior scientists at various meetings. For instance, the mutual invitation of speakers to regular meetings can be attempted at the beginning. It can then be extended to more complicated forms of cooperation, such as co-publication or joint committee activities.In addition to the AAAP, there are a few other international societies in the field of animal science. The best-known organizations are the World Association of Animal Production (WAAP), the European Federation of Animal Science (EAAP), the Latin American Association of Animal Production (ALPA), and the All Africa Society for Animal Production (AASAP). Of these, the EAAP is perhaps the most active association of a true international nature. It is active in expert exchanges, reciprocal session operations, and co-publications. It is also involved in the co-publication of Animal Frontiers, which publishes a type of position papers and is a joint venture between EAAP, American Society of Animal Science (ASAS), Canadian Society of Animal Science (CSAS), and American Meat Science Association (AMSA). The EAAP can be a model for the future development of the AAAP.The member countries that sent the greatest number of delegates to the most recent five congresses have been the same in all five congresses: Japan, Korea, Thailand, Taiwan, and Indonesia . More thThe same member countries presented the most papers in the five congresses, as shown in In fact, those five countries plus China and India, published the most papers in AJAS, with little contribution from other member countries .Therefore, there is severe regional inequality in congress participation, research, and publication activities among our members. Of course, a prompt solution is not evident, but there must be some way to carry it out right away without any extra expenses or prior arrangement. For example, the host country of each congress may prioritize allocating travel grants to delegates from under-represented member countries or set aside at least the minimum number of speaker positions for these countries.Inequality in publications is even more complicated. It not only involves publication cost (APC), but also plays a role in the level of research due to shortage or lack of grants and facilities, which cannot be solved in a short duration. International collaboration with established scientists may provide opportunities for them to upgrade their knowledge and skills necessary for more advanced research and to have a better chance of acceptance by the journal.There are 49 United Nations (UN) member countries in Asia. Of these, 16 Asian countries are AAAP members. Currently, our member countries are mostly located in northeastern and southeastern Asia. It is time to discuss the possibility of inviting Central and Western Asian countries as members. Of course, more efforts need to be made to complete the invitation to all northeastern and southeastern Asian countries.The last, but not the least, limitation is the AAAP constitution. The AAAP statutes are simple and short documents, and yet they describe most of the basic rules necessary for the operation of the association. However, the document was enacted more than 40 years ago, and it surely deserves an in-depth review to determine if any revisions or updates are necessary.I would like to propose the following 5 issues for future discussion.The AAAP membership is granted to only one national society. Although this is probably the best policy, future discussion is needed to determine whether multiple organizations will be allowed. In addition, detailed and formal guidelines to evaluate their applications are required because currently no specific policy is set for this purpose other than submission of a simple letter of intention to the secretary of general.An annual fee of 100 USD per membership was set in 1980. The reasonability of this current annual fees needs to be reviewed.Revenue is one of the key constraints in the efficient operation of the association. The only revenue source is the annual fees, and more stable funding sources should be identified. It is hoped that the AAAP council considers the differential annual fee system and also reviews the possibility of imposing a levy of a certain percentage to congress registration fees, as proposed a few times in the past.The governance structure of AAAP should be reviewed. This can be expanded to perform diverse activities. For example, we may need some standing committees (or ad hoc committees) to deal with the academic contents of congresses, international cooperation, some specific issues, etc.Congress sessions have mostly been directed toward scientific activities. Of course, the main function of our congress is to provide a proper platform for scientists of the member countries, but simultaneously, the congress should be able to provide suitable programs for consumers, policymakers, and the general public. Thus, for instance, reach-out sessions for the layperson, youngsters, or children may be set up, and the sessions can be operated in the local language if necessary. This type of public lecture will become more important in the coming years because providing unbiased scientific information to the general public, especially to the younger generation, is one of the most efficient and secure ways to improve consumer perceptions of the livestock industry.In summary, the AAAP has made splendid achievements during the last 42 years. Various records indicate that the AAAP has made tremendous contributions to the advancement of animal science and the animal industry in the Asia–Pacific region through scientific meetings and journal publications. With the Asia–Pacific region becoming a global leader in science and economy, it is expected that greater responsibility for the AAAP members is required for developing regional and global economies through animal science and the livestock industry. Continued innovations to the association and the journal are necessary to fulfill the aims of the AAAP.


We present the case of a 40-year-old male, who presented to the ophthalmology emergency department with pain and visual loss in his left eye 10 days after an intravitreal injection of a split medication. At the exploration, we found an intense corneal edema in the left eye with endothelial dusting and ciliary hyperemia. LE fundus was impracticable due to anterior chamber opacity. Because of the corneal edema, we performed an anterior segment optical coherence tomography (AS- OCT), visualizing a cyclitic membrane with pupillary block and inflammatory cells in the anterior chamber. There are different treatments to lyse the cyclitic membrane; in this case, we managed the cyclitic membrane with 0,05 ml of intracameral recombinant tissue plasminogen activator (rtPA), a highly potent fibrinolytic protein. We disinfected the eyelids and the conjunctival sac with Povidone Iodine solution, applied topical anesthesia with double anesthetic, and injected 0,05 mL rtPA solution into the anterior chamber using an insulin syringe with a 30-gauge needle. Intracameral rtPA was prepared under sterile conditions using 50 mg vials of rtPA diluted with 50 mL of sterile water to create a 1 mg/ mL solution. Four hours after rtPA treatment, the cyclitic membrane lysed, obtaining pupillary mydriasis. The AS OCT before and after the treatment with intracameral rtPA was of high utility as it allowed the visualization of the cyclitic membrane and its removal.  Fibrinous membrane formation in the anterior chamber may result in reduced visual acuity, photophobia, pupillary block glaucoma, fixed miotic pupil resistant to topical mydriatics, IOL displacement, posterior capsule opacification and loss of ciliary body integrity, which can lead to decreased aqueous production, hypotony, macular edema, and phthisis [3-5].Cyclitic membrane is a fibrous proliferation as a result of severe inflammation and ischemia .There are different treatments to lyse the cyclic membrane. Intracameral injection of recombinant tissue plasminogen activator (rtPA), a highly potent fibrinolytic protein, has been shown to successfully lyse fibrin membranes. Resolution of inflammatory membrane occurred within 24 hours after intracameral rtPA [6].Reported uncommon complications of intracameral rtPA include corneal edema, band keratopathy, anterior chamber turbidity, hyphaema, and IOL opacification [Fig. 1).A 40-year-old male went to the ophthalmology emergency department referring pain and loss of vision in his left eye 10 days after an intravitreal injection of a split medication. Visual acuity (VA) was 1 in the right eye (RE) and hand motion in the left eye (LE). Intraocular pressure was 12 mmHg in RE and 35 mmHg in LE. Biomicroscopic examination highlighted the existence of an intense corneal edema in the left eye with endothelial dusting, ciliary hyperemia, cyclitic membrane with pupillary blockage and inflammatory cells in the anterior chamber (2 +). LE fundus was impracticable due to anterior chamber opacity. Biomicroscopic and ophthalmoscopic examination of the RE was normal. Anterior segment optical coherence tomography (AS- OCT) was carried out, in which the cyclitic membrane together with the inflammation in the anterior chamber was visualized. A secondary pupillary block could also be seen . Intracameral rtPA was prepared under sterile conditions using 50 mg vials of rtPA diluted with 50 mL of sterile water to create a 1 mg/ mL solution. Using an insulin syringe with a 30-gauge needle, 0.05 mL of this solution were injected into the anterior chamber. Four hours after rtPA treatment, a new AS-OCT was performed and lysis of the cyclitic membrane with greater pupillary mydriasis was visualized (Thanks to AS-OCT, we managed to photograph the cyclitic membrane before treatment, and the result after applying rtPA. To our knowledge, it is the first published image of a cyclitic membrane pre and post rtPA treatment in AS-OCT.Conflict of Interest StatementThe authors state no conflict of interest. Informed Consent and Human and Animal Rights statementInformed consent has been obtained from the patient included in the study.Authorization for the use of human subjectsEthical approval: The research related to human use complies with all the relevant national regulations, institutional policies, it is in accordance with the tenets of the Helsinki Declaration and has been approved by the review board of Hospital Universitari i Politecnic La Fe, Valencia, Spain. AcknowledgementsNone. Sources of FundingNone. DisclosuresNone.