More carefully controlled studies where standardized structural properties of different cereals are linked to the postprandial response are needed to further elucidate the underlying mechanisms and determinants for the effect of specific cereals and product traits on postprandial glycemic control.Consumption of whole grain has been associated with lower incidence of type-2 diabetes, cardiovascular disease and their risk factors including improved glycemic control. In comparison with other whole grain products, rye bread has been shown to induce lower insulin response in the postprandial phase, without affecting the glucose response. This phenomenon has been referred to as the “rye factor” and is being explored in this review where we summarize the findings from meal and extended meal studies including rye-based foods. Overall, results from intervention studies showed that rye-based foods vs. (wheat) control foods had positive effect on both insulin and glucose responses in the postprandial phase, rather than on insulin alone. Mechanistic studies have shown that the rye factor phenomenon might be due to slowing of the glucose uptake in the intestine. However, this has also been shown for wheat-based bread and is likely an effect of structural properties of the investigated foods rather than the rye  The link between cereal consumption, health and disease has been widely studied and whole grain intake has been consistently associated with lower risk of developing or dying from several major non-communicable diseases such as cardiovascular disease, type-2 diabetes, colorectal cancer, and their main risk factors –5. On thAcute or extended meal studies investigating the effect of rye-based meals on postprandial glycemic response have repeatedly shown a pattern of reduced insulin following rye-based meals, despite similar glucose response. This phenomenon has been described and discussed as the “rye factor,” both within academia and in the industry , and it The purpose of this review was to gather studies that have investigated the acute effect of rye products on postprandial insulin and glucose and evaluate the occurrence of the rye factor phenomenon. Furthermore, we aimed to evaluate characteristics of investigated products to identify features that could help us to improve the understanding of the mechanisms behind the rye factor phenomenon. Lastly, we intended to evaluate the effect of habitual consumption of rye products on postprandial glucose and insulin response.A search was conducted in PubMed, Scopus, and Web of Science to identify studies investigating postprandial glucose and postprandial insulin response following at least one rye product and a non-rye control product. Reference lists of known and identified articles were inspected to identify additional relevant studies. In addition to studies investigating acute postprandial effects, studies investigating effects of regular rye consumption on insulin, glucose and other known risk markers for diabetes was included. Studies on extracts or isolated fiber fractions, as well as studies including insulin dependent diabetics, were excluded. Data on identified studies were extracted into tables. If studies included several different test products, only products directly compared to the rye products were included in the tables. Products with added extracts or isolated fiber fractions were not considered, as were products designed to test the effect of adding acids to a test product. Only outcomes related to glucose and insulin metabolism were considered.Additionally, a dataset was made containing detailed information on the pairwise testing of a rye product to a non-rye product in the Postprandial phase. As several of the included studies included more than one pair of products, the same study could appear several times in this table. Similarly, a test product could appear several times, if compared to more than one other product in the original study. Since the studies evaluated the Effect on glucose and insulin in various ways, focus was put on the area under the curve (AUC) for a time period of 3–4.5 h or 2 h for studies of shorter duration and the peak values, as these measures were available for the majority of the studies. As neither AUC nor peak were reported in all studies, it was decided to use both methods in the evaluation. It was evaluated whether the rye products resulted in lower/same/higher response than the wheat product in at least one of the mentioned evaluation methods (AUC or peak). In case rye product showed higher/lower response in one the methods and no effect in the other method it was classified as lower/higher according to the method that showed effect. None of the included studies reported conflicting results  for any pairwise comparisons. The tested pairs were categorized as follows: “no effect” (no effect on glucose or insulin) “glucose reduction” , “insulin reduction” , “reducing both” (lower glucose and lower insulin), and “increase” (higher glucose and/or insulin).In total, 24 studies investigating the effects of rye products in the postprandial or extended postprandial phase were found . Most ofFrom the 24 studies included in Generally, it should be noted that the majority of the pairs (64%) fall into categories showing a positive effect of rye in the postprandial phase (lower glucose and/or insulin response), whereas 32% show no effect and only 4% show a negative effect in the form of higher insulin or glucose following consumption of a rye product, compared to a control product . Interesper se, due to confounding by differences in structural properties or through difference in volume  have been shown to induce insulin secretion  and it hin vitro and animal studies to improve insulin sensitivity (Rye contains several different bioactive compounds that have been suggested to have positive effects on various health outcomes, such as glycemic control and insulin sensitivity . Lignanssitivity , 65. An sitivity , 66, butsitivity . Human ssitivity . The fewsitivity  and as wsitivity .If the mechanism behind the rye factor is mainly related to fiber content and structure, a rye factor phenomenon could likely be obtained with other cereals than rye. Eelderink et al. used a similar methodology as Östman et al. to examine the postprandial response to two wheat based breads with similar ingredients, but different structure (a standard sliced loaf bread and a flat bread; In summary, limited evidence for the underlying mechanism behind the rye factor exist, but it appears that structural properties, such as particle size, viscosity, and fiber matrix, are likely the major determinants for the postprandial response to consumption of cereal products.Amongst the studies included in this review there is a large variation in the methodology used to evaluate the postprandial response to the tested products. Some studies report the results of repeated measures models, some report AUC or iAUC over time periods varying between 2 and 5 h and some used other measures, such as peak values, glycemic index and insulin disposition index. This makes it impossible to directly compare the effect size between different studies and give an overall estimate on the magnitude of the effect across studies. While postprandial glucose response has been shown to correlate with glycated hemoglobin, which is a stronger predictor of diabetes risk, little is known about the long term implications of postprandial insulin response . Some stOur understanding of the mechanism of action behind the effect of different cereals on postprandial glucose and insulin response remains suggestive, as only few studies include more mechanistic outcome measures such as measures of glucose kinetics using tracer techniques. Studies by Eelderink et al. and Östman et al. shed some light on a potential underlying mechanism by incorporating tracer-techniques, but more studies are needed to draw general conclusions , 71, 72.The degree of characterization and the reporting of compositional information on products vary between studies and makes it hard to make comparisons across studies. Generally, more detailed characterization beyond nutritional values, is needed to further elucidate the effects of rye products on glycemic control as well as the underlying mechanisms. Furthermore, many studies compare rye products with a relatively high fiber content to wheat-based products with a relatively low fiber content, which makes it difficult to distinguish between the effect of fiber content and other factors, such as cereal source. However, it is important to keep in mind that the different cereals have a different fiber content and composition, even in their native form , why theMethod of fermentation has been shown to influence the structure of bread, which could in turn influence the physiological response to consumption of the breads. However, this is often clouded by the fact that sourdough fermented rye breads are often compared to yeast fermented wheat breads, making it difficult to disentangle the effect of cereal source from the method of fermentation. From an applicational point of view it is sensible to test a yeast fermented wheat bread with a sourdough fermented rye bread, as this is the typical types of bread available on the market and consumed by consumers. However, from a mechanistic point of view studies investigating different combinations of cereal sources and methods of fermentation are needed in order to understand the underlying mechanisms and determinates for postprandial response.per se. However, the rye factor phenomenon might not be a unique property of rye-based cereal products, as similar effects have been observed from other types of cereal products with similar fiber content and structural properties. Some studies indicate a role of sourdough fermentation, potentially through its effect on structure, but due to lack of studies properly designed to address this research question, effects of fermentation from other factors cannot be disentangled. There is a need for carefully controlled studies investigating the postprandial effects of products based on different cereals, as well as the structural properties standardized across cereal species to understand the link between structural properties and postprandial response.In conclusion, rye-based products have consistently been shown to lower insulin response in the postprandial phase, either alone or in combination with reductions in glucose response, compared to wheat-based products. Recent mechanistic studies using tracer-techniques have suggested that this may be attributed to slower glucose uptake in the intestine, which in turn may be linked to structural properties of rye products, rather than fiber content RL conceived the idea for the review. KI and KJ conducted the literature search and extracted the data. KI analyzed the data and wrote the article under supervision of RL. All authors read the manuscript, provided valuable inputs, and approved the final manuscript.RL is the founder of the Nordic Rye Forum, which is a research and dissemination platform for research related to rye and health that includes academic institutions as well as institutes and food industry with interest in rye across the Nordic region. The forum and its activities are funded by the industrial partners. RL is the PI of several projects funded by several cereal industrial companies. Such funding is used to carry out scientific studies. RL receives no salary, honorary, or by any other means have any personal economic benefits from industrial collaborations. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


WRKY and nucleotide-binding site (NBS) resistance-related genes may help to clarify their variation patterns and lead to crop improvements. In this study, the weedy rice line LM8 was examined at the whole-genome level. To identify the Oryza sativa japonica subpopulation that LM8 belongs to, the single nucleotide polymorphisms (SNPs) of 180 cultivated and 23 weedy rice varieties were used to construct a phylogenetic tree and a principal component analysis and STRUCTURE analysis were performed. The results indicated that LM8 with admixture components from japonica (GJ) and indica (XI) belonged to GJ-admixture (GJ-adm), with more than 60% of its genetic background derived from XI-2 (22.98%), GJ-tropical (22.86%), and GJ-subtropical (17.76%). Less than 9% of its genetic background was introgressed from weedy rice. Our results also suggested LM8 may have originated in a subtropical or tropical geographic region. Moreover, the comparisons with Nipponbare (NIP) and Shuhui498 (R498) revealed many specific structure variations (SVs) in the LM8 genome and fewer SVs between LM8 and NIP than between LM8 and R498. Next, 96 WRKY and 464 NBS genes were identified and mapped on LM8 chromosomes to eliminate redundancies. Three WRKY genes  in group III and one RNL  type NBS gene (ORUFILM12g000772) were detected in LM8. Among the NBS genes, the RPW8 domain was detected only in ORUFILM12g000772. This gene may improve plant resistance to pathogens as previously reported. Its classification and potential utility imply LM8 should be considered as a germplasm resource relevant for rice breeding programs.Common weedy rice plants are important genetic resources for modern breeding programs because they are the closest relatives to rice cultivars and their genomes contain elite genes. Determining the utility and copy numbers of  Weedy rice (Oryza sativa f. spontanea), which is a conspecific relative of cultivated rice that commonly grows in close proximity to cultivated rice, has certain wild rice characteristics that combine to form diverse features  , are involved in regulating plant responses to multiple stresses, including pathogen or bacterial infections, drought, cold, freezing, and wounding . They us2-23HXH) . Both th2-23HXH) . The WRKectively . The WRKectively .R) and avirulence genes that protect against infections. Similar to other crops, rice has evolved two defense strategies, namely pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI)  domain and C-terminal leucine rich repeats (LRRs) along with a Toll/interleukin-1 receptor/resistance (TIR) domain in the N-terminal region . The prety (ETI) . Of the I system . The WRK studied .japonica and indica strains. Moreover, a comparative analysis was performed using NIP and R498 reference genomes. In addition, the weedy rice WRKY and NBS gene family members were identified and collated for a comprehensive genome-wide analysis and comparison with diverse species. Phylogenetic relationships and the conserved motifs among families were investigated to provide useful insights into the conserved regulator. On the basis of our study findings, LM8 may be used to clarify the rice de-domestication process, while also serving as a resource for plant biotechnologists and breeders interested in enhancing rice traits through genetic modifications.The LM8 weedy rice line was named because its pericarp is green until maturity. There is increasing interest in this weedy rice line among breeders because of its green pericarp and small grains, which may be preferred by consumers. In this study, LM8 was used for a whole-genome analysis after a high-quality genome was assembled. The subpopulation classification of LM8 was completed using cultivated 22.1Oryza species used for the subgroup classification of LM8 included 180 cultivated varieties and 23 weedy rice varieties. The O. sativa groups japonica and indica were designated as GJ and XI, respectively. Using the 3K database (https://registry.opendata.aws/3kricegenome/), 20 cultivated varieties were randomly selected from the GJ-adm (admixture components within japonica and indica), GJ-trp , GJ-sbtrp , GJ-tmp (primarily East Asian temperate), XI-1A (East Asia), XI-1B (modern varieties of diverse origins), XI-2 (South Asia), XI-3 (Southeast Asia), and XI-adm groups. The NIP and R498 genomes were selected as the representative japonica and indica reference genomes for the whole-genome comparison with LM8.The 203 2.2http://snp-seek.irri.org). Information for 10 straw hull (SH) and 10 black hull awned (BHA) US weedy rice lines and 3 Chinese weedy rice lines was downloaded from the National Center for Biotechnology Information (NCBI) database (SRR4334499). The NIP, R498, and Arabidopsis genome data at the chromosome level were obtained from online databases . Details regarding the LM8 genome are available in the NCBI BioProject database (accession number PRJNA754271).The SNP databases for the 180 cultivated varieties are available online  were detected using the GATK (4.2.2.0) software, which was followed by (1) identification of active regions; (2) assembly of plausible haplotypes; (3) estimation of the per read likelihoods using the PairHMM algorithm; and (4) determination of the sample genotype. First, the GATK-HaplotypeCaller tool (versions 4.2.2.0) was used to analyze the bam files to obtain the sample GVCFs, after GATK-GenotypeGVCFs were used to genotype the variants with CombineGVCFs. Second, raw variants generated from the calling steps were filtered to identify the high-quality variants using the following parameters of GATK VariantFiltration: QD <2.0, MQ <40.0, FS >60.0, MQRankSum <−12.5, ReadPosRankSum <−8.0, and SOR >4.0. After combining the 3K-SNP data, the 5.12 Mb raw variants were filtered again (mis <10% and maf >5%) to generate the 4.03 Mb variant files  software, with 1,000 bootstrap replicates. As previously described . The K value for which the cross-entropy curve reflected a sensible model was chosen .On the basis of the whole-genome SNPs among the 201 escribed , a typic2.4versus NIP and LM8 versus R498) using the MUMmer (4.0.0rc1) software with the following parameters: nucmer -l 50 -c 100 -mum; delta-filter -i 90 -l 100 -1. According to the results of the collinearity analysis, presence-absence variations (PAVs) and structural variations (SVs) were identified using the SVUM and SYRI programs, respectively. In the final sequence variation files, variant sequences longer than 50 kb were retained, whereas variant sequences in the gap region were eliminated during the original variation test. Each SV was calculated for 1 Mb windows to generate the final Circos results.Two comparisons were completed . The Molecular Evolutionary Genetics Analysis  program was used to construct a maximum-likelihood gene family phylogenetic tree, with 1,000 bootstrap replicates. Next, the WRKY and NB-LRR genes were mapped to 12 chromosomes using MapChart (2.3).To identify the 33.1japonica-type weedy rice line. To further classify LM8 within the japonica group, its SNPs as well as those in other weedy rice lines and accessions from the 3K database selected on the basis of the 3K classifications were downloaded to construct a neighbor-joining phylogenetic tree. The indica group (XI) served as the control. The phylogenetic tree constructed according to pairwise Nei’s genetic distances showed that the 10 subpopulations could be clustered into two groups (japonica and indica) (japonica and indica). Moreover, LM8 was also classified in the japonica group. To verify the classification of LM8 in GJ-adm, a PCA was performed using the genome-wide SNPs in domesticated and weedy rice varieties  and indica  subgroups (japonica and indica groups) or weedy rice varieties  value (2 to 10) were used to assign individuals to population structures and to explain the PC1-based clustering of LM8. The final population subgroups were determined according to (1) the likelihood value of these models and (2) the previously reported classification of accessions on the basis of the 3K database. When K was set to 2, the likelihood value was highest (0.570) and most of the rice accessions were clearly divided into the indica and japonica groups  was optimal for grouping samples and was selected for assigning the posterior membership coefficients to each accession , R498 , and LM8 were detected and examined. Next, the deletion (DELs), insertion (INSs), inversion (INVs), translocations (TRANS) and duplication (DUPs) were identified between LM8 and NIP (as reference) and between LM8 and R498 . It is unclear whether the abundant SVs in LM8 affect WRKY gene sequences in LM8, NIP, and Arabidopsis and MEGA (v11) , ORUFILM05g002725 , and ORUFILM05g001757   . The groGA (v11) . An earlGA (v11) . In anot3.4NBS genes (496), followed by the genomes of LM8 (464) and Arabidopsis (165)  in LM8, the NBS genes in the LM8 and NIP genomes were mainly CN, CNL, NBS, NL, and TN types   formed distinct clusters, unlike the WRKY genes  . In the 4Oryza sativa has been divided into two major groups (indica and japonica). Advances in biotechnology-based research have clarified the differences among these two groups and other varietal types at the isozyme, DNA, and genome levels. The diverse 3K-RG accessions of Asian rice cultivars were classified into the XI-1A, XI-1B, XI-2, XI-3, XI-adm, GJ-adm, GJ-trp, GJ-sbtrp, and GJ-tmp subpopulations following a neighbor-joining method-based phylogenetic analysis of genomic SNPs. The results of the current study are consistent with previously reported findings regarding japonica rice . Additionally, there were more specific SVs than common SVs, reflecting the clear difference between the evolution of LM8 and the evolution of NIP and R498. Besides, considering of yield-related traits in rice, the small grain is another representative characterize to LM8. As a results, the quantitative trait loci for grain length were localized to chromosome 3  bind to plant-specific cis-regulatory elements and activate gene expression. Furthermore, diverse plant processes may be responsive to various WRKY TF family members during exposures to a variety of stresses  and 97 WRKY genes in the Oryza nivara genome have been identified and mapped to the corresponding chromosomes. WRKY genes in the rice genome and compared them with Arabidopsis genes. Future research on WRKY genes may further elucidate their genetic diversity and contributions to stress resistance. In this study, 96 WRKY genes were identified in the weedy rice line LM8 and then clustered into nine groups. The distribution of the WRKY genes on 12 chromosomes resulted from a long de-domestication process and the evolution of Oryza species. Our findings suggest that the group III rice WRKY gene family expanded more quickly than the other gene families. This phenomenon likely contributed to the adaptive responses of rice to complex environmental conditions. By using an online resource (https://www.arabidopsis.org/), three genes in LM8  were predicted to affect the flowering stage, embryo cotyledonary stage, and vascular leaf senescence stage.Many WRKY TF-encoding genes have been identified in the genomes of NBS genes encode proteins responsible for plant immune responses to pathogens. Most of these genes in rice were identified in earlier genome-wide re-sequencing analyses. In 2004, Zhou et al. identified 535 NB domain-encoding sequences in the NIP genome, but genes encoding TIR-NB-LRR proteins were not reported. The NB-LRR genes in the genomes of O. rufipogon Griff. wild rice lines Huaye 1 and Huaye 2 reportedly differ from the corresponding genes in two reference genomes. More than 108 of these genes were revealed by different comparisons . Furthermore, these NB-LRR genes were mainly localized to chromosomes 2 and 11. In an earlier investigation, 2,688 NB-LRR genes served as queries for a BLAST search; these genes were anchored to 12 chromosomes in three rice cultivars and eight wild rice accessions (ORUFILM12g000772). This gene includes sequences for the CC, NB-ARC, and LRR domains. The ORUFILM12g000772 protein sequence was downloaded and aligned with LOC_Os12g39620, At5g66900, At5g66910, and AtRWP8.1  can be found in the article/ZYH performed the research, analyzed the sequencing data, and wrote the first draft of the manuscript. QWY designed the study and edited the manuscript. WHQ and XMZ supervised the project and provided experimental advice. FL, YLC and LFZ prepared the supplementary materials. JFH, YYW, DJL, MX, WYF, YMN, WLG, SZW and ZRL retrieved and reviewed the relevant literature and downloaded publicly available data. All authors contributed to and approved the final manuscript.


Cyberaggression including the most wide-spread variants of flaming  and trolling  is affecting mental health of adolescents and youth although it could be .The aim was to study prevalence of flaming and trolling experience in Russian youth and adolescents and its relationship to general aggression and tolerance.525 adolescents 12-13 years old, 1029 adolescents 14-17 years old, 736 youth 18-30 years from 8 Federal regions in Russia appraised their experience of flaming or trolling online  using vignettes. 1105 parents of adolescents appraised whether their children experienced flaming or trolling online. Then they filled Aggression Questionnaire  and Tolerance Index .More than one-half of adolescents (51-58% in 12-13 years old and 64% in 14-17 years old) and youth (45-69%) reported experience of flaming and trolling online, mostly as observers (32-65%). Parents accurately appraised flaming experience in their children but underestimated trolling experience (p<.05). Adolescents and youth observing flaming online report higher hostility, anger and physical aggression  while lower social tolerance . In adolescents observing trolling online these effects are stronger than in youth observing trolling online .Observing trolling and flaming online is related to higher aggression and low tolerance in adolescents and youth and for adolescents the relationship is stronger. The reported study was funded by RFBR, project 20-013-00857.The reported study was funded by RFBR, project 20-013-00857.


Neuropsychological assessments of attention are valuable sources of information in the clinical evaluation of adults with attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether the attention performance of adults with ADHD is stable or fluctuates over time, which is of great importance in the interpretation of clinical assessments. This study aimed to explore the stability of attention performance of adults with ADHD in repeated assessments at one-month intervals. Twenty-one adults diagnosed with ADHD took part in this study by completing selective attention and vigilance tests three times, each one month apart. Test scores of participants were compared with and interpreted based on test norms. A considerable proportion of ‘below average’ performance scores were observed in most of the variables of selective attention and vigilance in all three assessments. Further, selective attention and vigilance performance scores did not differ significantly between the three repeated assessments. Finally, the majority of participants received consistent test score interpretations across the three repeated assessments. This study confirms previous research and highlights abnormal selective attention and vigilance performance in adults with ADHD. Further, this study preliminarily demonstrates relatively stable attention performance across repeated assessments, which has the potential to support clinical assessment, treatment planning, and evaluation. Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder that lasts into adulthood in the majority of cases and affects about 6% of adults worldwide ,2. DeficThe close relationship between attention and higher-order cognitive functions has been observed in both clinical samples ,24,25,26Considering the fundamental and central role of attention in the clinical neuropsychology of adults with ADHD, an accurate assessment of attention is of great importance for clinical practice, as it may contribute to developing individualized treatment plans and improving the accuracy of treatment evaluation. Neuropsychological performance tests are the mainstay in the assessment of attention functions within the clinical evaluation of adult ADHD. A broad variety of neuropsychological tests are available for neuropsychological practice and research, which have been shown to be sensitive in assessing abnormal attention in both children and adults with ADHD ,35,36,37One possible explanation for the consistently inconsistent findings of attention performance in adults with ADHD may be the instability of individuals’ attention performance over time. Intra-individual variability in attention task performance over a period of seconds or milliseconds has been observed repeatedly in individuals with ADHD within the course of a single, one-time assessment ,44,45,46Considering that neuropsychological evaluations in clinical practice are usually based on a single, one-time assessment and assume the stability of their findings without repeated assessment, an examination of intra-individual neuropsychological performance fluctuations in adults with ADHD appears relevant and of clinical importance. Thus, the present study aimed to explore the stability of attention performance in adults with ADHD over time through three repeated assessments in one-month intervals. More specifically, a sample of adults diagnosed with ADHD completed a neuropsychological assessment of selective attention and vigilance three times under stable conditions within a time interval of about one month on average. We expected, first, that a substantial number of adults with ADHD perform in the below-average range  of the n = 6), addiction disorders (n = 1), anxiety disorders (n = 1), and post-traumatic stress disorder (n = 1). Twelve of the 21 individuals were currently treated with stimulant medication under stable conditions on all three assessment days. The remaining 9 participants did not take stimulant medication on any of the assessment days. Descriptive information and ADHD symptom scores are presented in A total of 21 adults diagnosed with ADHD took part in the present study. All participants were recruited from the Department of Psychiatry and Psychotherapy of the SRH Clinic Karlsbad-Langensteinbach, Germany. Participants were self-referred or referred by local psychiatrists or neurologists to the clinic for a comprehensive ADHD diagnostic because of suspected ADHD in adulthood. The diagnosis of adult ADHD was made jointly by at least two experienced clinicians after a thorough diagnostic assessment. Both clinicians were clinical (neuro)psychologists of the Department of Psychiatry and Psychotherapy of the SRH Clinic Karlsbad-Langensteinbach and mutually agreed upon the diagnostic decision. The diagnostic assessment procedure followed the guidelines for a first-time adult ADHD diagnosis . SpecifiThis study is part of a larger project which comprises an extensive battery of measures for the assessment of symptoms, impairments, and cognitive functioning of adults with ADHD. In the following sections, only the measures relevant to this study are described.The German short version of the WURS-K was administered to assess ADHD symptoms in childhood . This scThe German version of CAARS-S:L was applied to assess the severity of current ADHD symptoms . The CAASelective attention and vigilance were assessed with two computerized tests of the Vienna Test System  that may get lighter or darker or stay the same were presented on the screen. Participants were asked to respond as quickly as possible to changes in circles and squares  by pressing the response button. No response is needed when a triangle gets lighter or darker. Each stimulus was presented for 1500 ms, and a change may take place after 500 ms. The interstimulus interval was 1000 ms. A total of 144 stimuli were presented, 30 of which were targets. The test duration is about 8 min. The mean reaction time (RT), the logarithmic standard deviation of the reaction times (SDRT), and the number of missed reactions (omission errors) were recorded. Adult norms are accessible consisting of 295 individuals representing the general population  aged between 16 and 77 . All individuals in the normative group performed tests in the German language. The internal consistency (Cronbach’s α) of this test is excellent, with 0.95 in the normative sample.The test WAFV was administered to assess vigilance. In this test, squares that may get darker or stay the same were presented one by one on the screen. Participants were asked to press the response button as quickly as possible whenever a square got darker. The frequency of targets (squares getting darker) is 5%. Each stimulus was presented for 1500 ms, and a change may take place after 500 ms. The interstimulus interval was 500 ms. A total of 900 stimuli were presented, 50 of which were targets. The test duration is 30 min. The mean RT, the logarithmic SDRT, and the number of omission errors were recorded. The WAFV and the WAFS are evaluated based on the same normative group, consisting of 295 individuals representing the general population  aged between 16 and 77 . All individuals in the normative group performed tests in the German language. The internal consistency (Cronbach’s α) of this test is excellent, with 0.96 in the normative sample.All participants were invited to take part in the study on a voluntary basis. It was stressed to all participants that the study was for research purposes only and will not affect their clinical evaluation and treatment. All participants signed the written informed consent before taking part in the study. The neuropsychological assessment of selective attention and vigilance was performed three times on three different assessment days. The time interval between the different assessments was, on average, 1 month from each other, ranging from 21 to 49 days, and in 90% of the cases ranging from 21 to 35 days. The assessments per person took place, as much as possible, on the same day of the week and at the same time of the day. All assessments were performed in a quiet environment at the Department of Psychiatry and Psychotherapy of the SRH Clinic Karlsbad-Langensteinbach, Germany. The order of the administration of all tests (including measures of selective attention and vigilance) was randomized across participants but kept constant for each individual across all three assessment days. Self-report symptom scales were completed only once, i.e., prior to the first attention assessment. Participants were rewarded with 60 euros upon completion of all three assessments. Participants who were included in the present study were assessed between January 2019 and June 2021. The study was approved by the ethical review board of the medical faculty of the University of Heidelberg, Germany .p < 0.017 (p = 0.05/3) was applied. The magnitude of pairwise differences is indicated using effect size Cohen’s r, with r = 0.1 indicating a small effect, r = 0.3 indicating a medium effect, and r = 0.5 indicating a large effect [Missing values occurred in 2.7%, 4.7%, and 13.8% of the data for the first, second, and third assessments, respectively, and the missing values were not replaced. Descriptive statistics of attention performance scores are presented for all participants. Moreover, T-scores based on representative normative data as provided by the test publisher are computed . T-scoree effect .p < 0.017 (p = 0.05/3) was applied.Moreover, the absolute values of individual T-score differences between any two of the three assessments are calculated for each test variable. Further, to examine whether test score interpretations differed from one assessment to another, the percentage of consistent test score interpretations is indicated for each comparison. Consistent test score interpretation is considered if both test scores indicate below-average performance (T ≤ 36) or both test scores indicate no below-average performance (T > 36). The percentage of consistent test score interpretation is calculated by the number of participants who received consistent test score interpretation divided by the total number of participants. The percentage of consistent test score interpretations across three assessments is also calculated for each variable. Finally, Spearman correlation coefficients are calculated to indicate the association between test scores at any two of the three assessments and a Bonferroni adjusted significance level of Descriptive statistics of attention performance for the three assessments and the percentages of participants who scored below average (T ≤ 36) are presented in p < 0.01). However, for SDRT, a significant correlation is observed only between the first and the third assessment of selective attention . For omission errors, significant correlations are observed between any two of the three assessments of selective attention (medium to large effect size) but only between the first and the second assessment in the vigilance task (medium effect size).Further, individual changes are indicated by absolute T-score differences from one time point to another. Descriptive statistics of absolute T-score differences between assessments are presented in This study aimed to explore the stability of attention performance over time in adults diagnosed with ADHD by repeatedly assessing selective attention and vigilance three times with a one-month time interval between each assessment. Results confirmed previous research showing that a considerable proportion of individuals with ADHD score in the below-average range in both selective attention and vigilance. Furthermore, both performance scores and test score interpretations (below average or not) remained relatively stable over time.Inspecting the attention performance of adults with ADHD revealed that the percentage of participants who scored in the below-average range was higher than expected from a representative norm group  in mostDifferent from our expectations, the comparisons of attention performance between the three assessments revealed relatively stable scores with nonsignificant group differences of negligible to small size. Moreover, most individuals deviated only slightly in the performance scores, as shown by individual T-score differences of about 5 points (ranging from 3.2 to 8.9) from one assessment to another, which further supports the notion of stable selective attention and vigilance dysfunction over time. Prior to data analysis, we expected selective attention and vigilance performance to fluctuate from one assessment to another based on research showing cognitive performance fluctuations in tasks over seconds and milliseconds in individuals with ADHD ,48,50,51More importantly for clinical practice, test score interpretations were consistent across the three assessments for the majority of participants. Specifically, more than 74% of participants received consistent test score interpretations (below or no below-average performance) across all three assessments, and more than 80% of participants received consistent test score interpretations between any two assessments for most variables. Consistent test score interpretations are encouraging for clinicians by providing an evidence base that the results of a one-time neuropsychological attention assessment may be well suited as a basis for clinical evaluation, treatment planning, and treatment evaluation. Of note, there are still about 20-25% of participants who received inconsistent test score interpretations across the different assessments, which may indicate unstable attention performance over time. For these cases, a one-time attention assessment may bias or distort the interpretation of cognitive performance scores, and it is advisable to integrate results from neuropsychological performance assessment with other clinical measures (of attention) in order to receive a comprehensive and valid understanding of the individual’s functioning ,72,73. HOf note, the data of this study need to be interpreted in the context of several limitations. Most importantly, the sample size of this study is relatively small and may lead to low statistical power. Thus, the conclusions of this study should be taken as preliminary and require replication on larger and more homogenous samples. Larger samples would yield more robust findings and may allow the investigation of moderating factors, such as symptom presentation, comorbidities, or medication status. Support for the robustness of our results is given by the good psychometric properties of our instruments and a similar distribution of scores in one-time assessments on independent and large clinical samples ,33. SecoThis study confirms previous research that a considerable proportion of adults with ADHD show below-average selective attention and vigilance performance. Moreover, this study highlights that selective attention and vigilance performance did not differ significantly between three repeated assessments in one-month intervals. In this context, the majority of individuals showed only minor T-score differences between the three assessments and received consistent test score interpretations. Pending future replication on larger samples, this study forms an empirical evidence base relevant for clinical practice as it suggests that the results of a one-time attention assessment may be sensitive in revealing attention deficits and may be stable over time for the majority of individuals, thus being useful to guide individual treatment planning and evaluation.


In particular, in the last decade, HMF has been considered as a starting material for designing biobased surfactants, not only because of its renewability and carbon footprint, but also because of its enhanced biodegradability. This Review presents recent examples of the different approaches to link the hydrophilic and lipophilic moieties into the hydrophobic furan (and tetrahydrofuran) ring, giving a variety of biobased surfactants that have been classified here according to the charge of the head polar group. Moreover, strategies for the synthesis of different non‐furanic structures surfactant molecules  derived from HMF are described. The new HMF‐based amphiphilic molecules presented here cover a wide range of hydrophilic‐lipophilic balance values and have suitable surfactant properties such as surface tension activity and critical micelle concentration, to be an important alternative for the replacement of non‐sustainable surfactants. Amphiphiles: In the last decade, 5‐hydroxymethylfurfural (HMF) has been considered as a starting material for designing biobased surfactants, not only because of its renewability and carbon footprint, but also because of its enhanced biodegradability. This Review summarizes recent examples of different approaches to provide new highly biodegradable biobased amphiphiles starting from HMF and its derivatives, which have been classified according to the charge of the head polar group. A classification of surfactants is based on the charge of the head group when the amphiphile is dissolved in water, and they are cationic, anionic, amphoteric (or zwitterionic) compounds. Another classification is based on the ratio of the hydrophilic and hydrophobic portions of the molecule, which are determined by the hydrophilic‐lipophilic balance (HLB) value  and derivatives for the synthesis of surfactants constitutes an alternative for obtaining potentially biodegradable surfactants.Particularly, 5‐hydroxymethylfurfural (HMF), produced by dehydration of hexoses (mainly fructose), is one of the top biobased chemicals from carbohydrate biomass. HMF is a key platform molecule that enables the construction of a plethora of high value‐added furanic compounds for the production of bulk materials, fine chemicals, polymers, and also biofuels.34, 3522.1n‐C12H25(OCH2CH2)nOSO3Na) is the most important AES, and also the main component of soil conditioning products used in the excavation industry and fracking.Anionic surfactants are widely used in the manufacture of industrial and household cleaning products due to their foaming capacity, ability to stabilize water‐in‐oil emulsions, and their ability to bind and remove positively charged particles, such as clay, dirt, and stains, by ionization. Linear alkylbenzene sulfonates (LAS) Scheme  are the In the last years, the need to prepare chemicals from renewable materials to face environmental concerns over fossil fuels consumption has motived the preparation of new oleofuran sulfonates from renewables with strong surfactant performance in minimal concentrations.38, 393(CO)12, supported metal catalysts  on carbon, metal oxides, and mixed metal oxides, the olefins undergo carbonyl‐ene reaction with DFF to produce dialkyl furan compounds with two alcohol groups in α‐position of the furan ring. Therefore, one or more hydrophilic functional groups can be added by sulfonation to provide new amphiphilic molecules with new potential activity as anionic oleofuran surfactants furan (BHMF) and bis(hydroxymethyl)‐tetrahydrofuran (BHMTHF), produced by HMF hydrogenation, was claimed as possible replacements of LAS and AES.42, 4312–C14) allowed lowering CMC (0.02–0.05 g L−1) and interfacial tension (2.3–4 m Nm−1) towards isopropyl myristate, similarly to LAS, with CMC around 0.08 g L−1 and surface tension around 0.9 m Nm−1, and AES, with CMC around 0.05 g L−1 and surface tension around 3.9 m Nm−1, showing high potential for use in detergents, dispersants, and plasticizers.The evaluation of the surfactant properties of these compounds with different chain lengths revealed that longer hydrophobic chains ‐2‐furoate surfactants. The high performances of the process using stable and reusable solid acid catalyst, along with the fact that solvents or additives are not required, represent a promising sustainable route to produce these cleavable surfactants that should then show good biodegradability.in situ by cyclodehydration of n‐butyl glycoside uronate intermediates, under aqueous acid media in presence of butanol. The butyl 5‐(dibutoxymethyl)‐2‐furoate intermediate is transacetalized with a fatty alcohol and subsequently saponified, yielding the target product. This one‐pot cascade procedure yielded acetal‐based furanic carboxylate surfactants with 15–20 % molar yield with respect to oligomannuronates. The evaluation of surfactant properties of sodium 5‐dioctylacetal‐2‐furoates such as CMC, surface tension activity towards water, and foaming capacity, revealed that this compound presents a CMC and surface tension of 0.31 g L−1 and 31.7 m Nm−1, respectively, exhibiting promising properties as anionic surfactants able to replace the conventional fossil‐based SLES with CMC and surface tension around 0.33 g L−1 and 31.8 m Nm−1, respectively. Moreover, a study of biodegradability showed that sodium 5‐(dioctyloxymethyl)‐2‐furoate exhibited ready biodegradability and absence of aquatic ecotoxicity.Recently, an alternative route towards the anionic sodium 5‐‐2‐furoates starting directly from alginate or oligo‐alginates Scheme  through 3 into 2,5‐furandicarboyxlic acid (FDCA) was carried out, which was converted into 2,5‐furandicarbonyl dichloride by reaction with SOCl2. Selective mono‐esterification of the dichloride derivative with n‐decanol gives the decyl‐FDA monoester (Scheme The preparation of decyl furan dicarboxylic acid monoester (decyl‐FDCA ester) bearing a hydrophilic carboxylate head group and fatty ester as lipophilic tail as biodegradable surfactant was recently described starting from HMF.r Scheme . The bio8–C18) were obtained at 100 °C in a few hours. Then, the 5‐alkoxymethylfurfural compounds were selectively oxidized into the corresponding sodium furoic salts with excellent yield over Au/CeO2 using air as oxidant, in a basic aqueous solution at 65 °C. It was shown that both catalysts (H‐Beta zeolite and Au/CeO2 samples) were stable and could be reused several times. The overall yield and selectivity of the two combined steps for the production of biodegradable and renewable anionic surfactants with the different fatty alcohols (C8–C18) were very high (Table −1) as the commercial dodecylbenzene sulfonic acid sodium salt (SDBS) (33 m Nm−1) for 1 wt% concentration in water, although the CMC for SODF was 0.9 g g−1 while reported CMC−1.Another interesting type of surfactants based on furoic acid salts was produced by introducing an ether moiety (instead of an ester) as lipophilic part. The process involves the selective etherification of the hydroxymethyl group of HMF with fatty alcohols in the presence of solid acid catalyst, followed by the oxidation of the formyl group into carboxylate sodium salt Scheme .[48] T2.216–22), sometimes branched, usually used as ingredients in softeners, haircare products, anti‐corrosion products and as dispersants and emulsifiers. If anionic surfactants are the most important ingredients in detergents due to their cleaning efficiency, cationic surfactant are the main components in softeners being distearyldimethylammonium chloride (C18 chain), the first worldwide cationic softener produced.Cationic surfactants are usually quaternary ammonium salts bearing long‐chain alkyl groups  can be directly achieved by reductive amination of the formyl group of HMF (or derivatives) with ammonia or primary amines Scheme . The rea2 in the presence of homogeneous and heterogeneous metal‐based catalysts or in the presence of sodium borohydride as reductant.2 pressure, in ethanol, by direct reductive amination of HMF with primary and secondary amines to produce N‐substituted aminomethyl‐hydroxymethylfurans with good yields up to 95 %.N‐alkyl‐5‐(hydroxymethyl)‐2‐furfuryl amine surfactant precursors were obtained in excellent yields by reductive amination of HMF with fatty amines in a one‐pot two‐step process using hydrogen and Pd supported catalyst.N‐substituted furfurylamine precursors of surfactants based on furan‐quaternary ammonium salts.A recent Review compiled the latest advances for the reductive amination of HMF focused on the use of H2.3Nonionic surfactants are the second class of surfactants more used for industrial and household cleaning products, cosmetics, and disinfectants. They contain as hydrophilic moiety non‐water ionizable groups such as polyoxyethylene, ether, polyhydroxyl, amide, and so on, giving neutral dissolutions. They exhibit higher emulsifying capacity for oils than anionic surfactants for removal of organic soils/grease, and thus combinations of nonionic and anionic surfactants are frequent. The water solubility of the head group is due to hydrogen bonding, which decreases with increasing temperature, and consequently the water solubility of nonionic surfactants decreases with increasing temperature. The decrease in solubility leads to the formation of a cloudy emulsion called the cloud point. This property is unique to nonionic surfactants and is determining for their optimum use in formulations at high temperature. The cloud point depends on the ratio of hydrophilic/hydrophobic moieties and varies from room temperature to very high temperature; for instance, in the case of a very high hydrophilic/hydrophobic ratio, there is no cloud point.Recently, we have reported the preparation of new nonionic biobased amphiphilic molecules starting from three renewable chemicals  trough a one‐pot cascade process, leading to a family of interesting cleavable surfactants with high sensitivity to acidic conditions Scheme .[55] T−1 while in the GMF‐esters compounds the CMC was in the range 0.06–0.08 mol L−1, supporting their potential as new nonionic surfactants.Cleavable acetal linkages have been also used in the preparation of glucosilated HMF derivatives Scheme .[56] D8–C26). The further reductive amination of the HMF monoester with suitable amine using NaBH4 allowed obtaining new amphiphilic molecules bearing a functional group having sufficient hydrogen bonding capacity to provide hydrophilic properties to the furan moiety  emulsions while SMF derivatives were able to stabilize water‐in‐oil (W/O) emulsions (H16S). This new series of biobased surfactants constitutes alternatives to the use of conventional polyethoxylated surfactants for applications in detergents and cosmetics.Very recently, the preparation of a series of new anionic surfactants by green Morita–Baylis–Hillman reaction via addition of hydrophobic α,β‐unsaturated carbonyl compounds (acrylates or acrylamides) to furanic aldehydes catalyzed by a tertiary amine was reported Scheme . Ts Scheme . The tot−1, which was considerably lower than that of gemini imidazoline amphoteric surfactants (2.25 mmol L−1), while the decrease of the surface tension (up to 30 m Nm−1) was similar to that gemini imidazoline amphoteric surfactant (30.42 m Nm−1)The evaluation of surfactant properties such as the CMC and surface tension reduction of aqueous solution (pH=4–9) Scheme  revealed3The high reactivity of HMF molecule allows converting it into several building blocks of non‐furanic structures that can be used as starting materials for the synthesis of biobased surfactants. These transformations include ring‐opening of HMF by hydration into levulinic acid, hydrogenative ring‐opening giving 3‐hydroxymetylcyclopentanol, and Diels–Alder reaction of HMF with dienophiles into aromatic compounds. In this section, we discuss different approaches to transform these derivatives into amphiphilic molecules.3.1Levulinic acid has been classified by the US Department of Energy as one of the twelve promising platform molecules for the synthesis of several chemicals with multiple applications.−1 (1 % in water), similar to that of the commercial sodium dodecyl sulfate surfactant (35.2 m Nm−1). These results showed that the new ketal‐type biobased surfactant prepared from renewable sources constitutes a possible replacement of commercial sodium dodecyl sulfate surfactant. Moreover, the ketal nature of the 4‐decyl‐2‐methyl‐1,3‐dioxolane‐2‐propanoic acid sodium salt converts this amphiphilic molecule into a cleavable surfactant under acidic conditions, which is of great interest from handling and biodegradation standpoints.For instance, anionic renewable surfactants were prepared by ketalization between ethyl levulinate and long‐chain vicinal diols and subsequent saponification Scheme .[75] KAnother different route for the preparation of cleavable amphiphilic molecules involving ketals of levulinic acid was reported by Doll et al.76, 77−1) determined in aqueous solution (2.5 mm) was lower than that of commercial sodium myristate (59 m Nm−1), whereas the CMC was one order of magnitude lower than that of the commercial sample, (5.10−3 vs. 2.10−2 m). In addition, the methyl 4‐alkoxypentanoates should give access to new family of nonionic surfactants through the transesterification of the methyl ester with polyalcohols or polyoxyethylene glycol. They can be potential substitutes of commercial fossil‐based polyoxyethylene alkyl ethers widely used in industrial and household products and cosmetics formulations.[We have seen that reductive etherification of methyl levulinate with fatty alcohols to produce methyl 4‐alkoxypentanoates has been recently described as a new route for the preparation of precursors of new anionic or nonionic biobased surfactants Scheme .[78] TN‐alkyl‐5‐methyl‐2‐pyrrolidones that constitute important intermediates in the synthesis of pharmaceuticals, agrochemicals, and surfactants.[N‐substituted‐5‐methyl‐2‐pyrrolidones involves as the first step the acid‐catalyzed formation of an imine intermediate by reaction of a primary amine with the ketone group of the levulinic acid (or ester) followed by hydrogenation of the imine intermediate and subsequent cyclization  is an important synthesis route for the preparation of factants.84, 85n Scheme .N‐alkyl‐5‐methyl‐2‐pyrrolidones combine the hydrophilic head formed by dipolar pyrrolidone ring and the hydrophobic alkyl group conferring a unique combination of solvency and surface activity. Hence, pyrrolidones have been reported to improve the properties of surfactants such as water solubility, compatibility, and solvency.N‐alkyl chain with approximately C8 induces significant surface activity, reaches a maximum for C12–C14, and then for longer chains drops due to low water solubility. For instance, Surfadone LP‐100 and LP‐300 with C8 and C12 alkyl chain, respectively, are commercialized by Ashland owing to their great performance due to their high surface activity at low concentration, rapid wetting, synergism with anionic surfactants  to reduce surface tension  from industrial, economic, and environmental perspectives.Various strategies including the use of H2, using robust and recyclable heterogeneous bifunctional catalysts  are presented in this section.Taking into account the goals of sustainable development, the production of alkyl‐pyrrolidones as nonionic surfactants should be based on efficient and recyclable solid catalysts. Therefore, some relevant examples on reductive amination of levulinic (or esters) with primary amines and Hx, CrOx, MoOx, WOx, and ReOx) over the activity of Pt/TiO2 catalysts was explored. Results showed that Pt‐MoOx over TiO2 was the most active catalyst. This was attributed to the stronger Lewis acidity of Pt‐MoOx/TiO2, generated by the combination of Pt and Mo metal species, compared with the other transition metal oxide‐based catalysts. Later, Vidal et al.2 catalyst, where the Pt crystal faces are decorated with TiOx species,[2 by hydrogen dissociation on the metal and spillover migration to Lewis acid sites of the support,N‐substituted 5‐methyl‐2‐pyrrolidones starting from ethyl levulinate and nitro compounds in the presence of Pt supported on TiO2 nanotubes catalyst (Pt/TiO2‐NT). Owing to suitable acidity of the surface catalyst and controlled adsorption of the nitro compounds, the cascade process was successfully performed.2 nanosheets‐supported Pt nanoparticles (Pt/P‐TiO2) catalyst was reported to prepare N‐substituted pyrrolidones by reductive amination of levulinic acid at room temperature and atmospheric H2 pressure (Table 3‐TPD) study showed the stronger acidity of P‐TiO2 sample compared with the conventional TiO2, which is attributed to its nanosheet structure and high surface area that make a greater number of acidic centers available that should be active for condensation and cyclization reactions.For instance, Touchy et al.2, Pd/Al2O3, and Pd/TiO2 catalysts revealed the higher catalytic properties of Pd/ZrO2 for amination attributed to higher Lewis acidity  for reductive amination of ethyl levulinate and levulinic acid reaction was reported  with a primary/secondary ratio of 70 : 30 were obtained. Subsequent sulfatation of the free hydroxy group led to new amphiphilic molecules. It was showed that dodecyl sulfate‐HCPO derivative was not soluble in water, while the evaluation of CMC and interfacial tension towards isopropyl myristate showed that the decyl sulfate‐HCPO derivative exhibited relatively high CMC (≈0.77 g L−1) and interfacial tension (6.1 m Nm−1), which were considerably higher than commercial LAS  and fatty alkyl ether sulfates .When hydrogenation of HMF is performed in water at high temperature (>140 °C), HMF can be converted into 3‐(hydroxymethyl)cyclopentan‐1‐ol (HCPO). The reaction occurs through the hydrogenation of HMF into BHMF as first step, which subsequently undergoes a Piancatelli ring‐rearrangement into 3‐(hydroxymethyl)cyclopentanone that can be subsequently hydrogenated into HCPO.4p‐xylene has been produced by Diels–Alder addition of bio‐ethylene to 2,5‐dimethylfuran (DMF) in the gas phase, at 250–300 °C and high ethylene pressure (up to 62 bar) in the presence of HY or H‐Beta zeolites, achieving 60 and 90 % selectivity to p‐xylene, respectively, at >95 % conversion (Table p‐xylene (at 99 % DMF conversion) under similar reaction conditions  under mild reaction conditions  has been reported , biological, and catalytic processes.107 Howeon Table . Thus, tns Table , entry 7ed Table , entry 8ed Table , entry 9These examples show that the production of biobased aromatics from HMF derivatives can be a feasible alternative to fossil fuels for the preparation of LAS analogues Scheme .52 and solar exposure,2/H2O2 and UV/Fe2+/H2O2 processes.As mentioned in this Review, surfactants find applications in our daily life and in numerous industry sectors, with the global surfactant market size growing steadily. In order to achieve sustainable development, the chemical industry is constantly working on research and development of biobased alternatives to petroleum‐based chemical platforms. Consequently, the interest in producing and using 5‐hydroxymethylfurfural (HMF) as a renewable platform chemical for the production of a wide range of chemicals and materials has grown considerably in recent decades. Therefore, in view of the high demand for surfactants and sustainable development goals, there has been a continuous interest in the last twenty years to design and synthesize new biobased surfactants to limit their environmental impact. In this Review, we have shown the important role of HMF as platform molecule in the synthesis of bio‐based surfactants, not only from the perspective of renewability and carbon footprint, but also by improving biodegradability. The successful synthesis of biobased anionic, nonionic, cationic, and amphoteric oleofuran and tetrahydrofuran surfactants starting from HMF with suitable surfactant properties that cover a wide range of applications has been demonstrated. In the same way, the preparation of advanced amphiphilic molecules, such as gemini surfactants with enhanced and unusual features, or cleavable surfactants with improved biodegradability and elimination, has been thoroughly described. Starting from other HMF derivatives such as levulinic acid (or esters), 3‐(hydroxymethyl)cyclopentan‐1‐ol, or biobased aromatics, new amphiphiles can also be constructed covering different class of surfactants. Nevertheless, many efforts are still needed to improve the synthesis routes avoiding stoichiometric reactions in favor of catalytic routes. In this sense, the design of suitable heterogeneous catalysts and the development of new one‐pot cascade processes (chemo and chemoenzymatic processes) will allow to accomplish efficient, sustainable, and environmentally friendly strategies. Furthermore, since surfactants are major pollutants in the environment, the inclusion of sensitive or labile fragments in the molecule backbone that allow to neutralize (loss of surface tension activity) and/or degrade them quickly should be considered for designing new surfactants molecules.118 In tThe different routes taken to convert HMF into valuable surfactants are summarized in Scheme The authors declare no conflict of interest.Avelino Corma, Professor and founder of the Instituto de Tecnología Química (CSIC‐UPV) in Valencia (Spain), has carried out research in heterogeneous catalysis in academia and in collaboration with companies. He has worked on fundamental aspects of acid‐base and redox catalysis with the aim of understanding the nature of the active sites and reaction mechanisms. With these bases has developed catalysts that are being used commercially in several industrial processes. He is an internationally recognized expert in solid acid and bifunctional catalysts for oil refining, petrochemistry, and chemical processes. He has published more than 1000 research papers and is inventor on more than 130 patents.Sara Iborra is Full Professor at the Chemistry Department of the Technical University of Valencia. She received her Ph.D. in 1987 at the Universidad de Valencia, and in the same year, she joined to the Chemistry Department of the Technical University of Valencia as Assistant professor. She is member of the Institute of Chemical Technology (ITQ) at the Technical University of Valencia since 1991, where she works in the research group of Prof. Avelino Corma. The main focus of her current research involves the application of heterogeneous catalysts (acid‐base and redox) to the synthesis of fine chemicals and biomass transformation.Alexandra Velty graduated in Chemical Engineering at the University of Rennes and received her B.Sc. in Chemistry at the University of Nancy (France). She completed her Ph.D. under the supervision of Prof. Avelino Corma at the Instituto de Tecnología Química  in Valencia (Spain) in 2003 in the field of heterogeneous catalysis and green chemistry for the preparation of fine chemicals. Until now, she is working in Prof. Avelino Corma's group as a permanent member of the Polytechnic University of Valencia. Her research interests focus on heterogeneous catalysis and sustainable chemistry for biomass transformation and fine chemicals preparation.


Substance use disorders (SUDs) continue to be a public health problem. Attention-deficit/hyperactivity disorder (ADHD) is seen as a risk factor for SUD. Prevalence of alcohol and cannabis use amongst adults with SUD and comorbid ADHD impacts both disorders cognitively and behaviourally.Our study aimed to compare alcohol and cannabis use between treatment-seeking SUD patients with ADHD and SUD patients without ADHD symptomatology.Various rehabilitation centres, including the South African National Council on Alcoholism and Drug Dependence (SANCA) Centres, and Private and Provincial Government Substance Abuse Treatment Centres.n = 52) and SUD-ADHD (n = 128) groups were compared on alcohol and cannabis use as a function of gender.A cross-sectional study of adults on drug rehabilitation was conducted. Data on socio-demographic information and alcohol and cannabis use from 185 post-detox inpatients were collected. Diagnoses were based on DSM-IV criteria. Attention-deficit/hyperactivity disorder diagnosis was confirmed by the Diagnostic-Interview for ADHD in Adults (DIVA 2.0). SUD+ADHD (No significant differences in the use of alcohol between the SUD+ADHD and SUD-ADHD groups were found. However, the SUD+ADHD group showed increased cannabis consumption. Especially, the SUD+ADHD females showed an earlier age of onset of cannabis use than the SUD-ADHD females and revealed that they use cannabis for a longer period compared with the SUD-ADHD females and SUD+ADHD and SUD-ADHD males.The results revealed the relationship between ADHD and cannabis use, especially amongst females with ADHD and reinforce the need to consider ADHD in cannabis use SUD in clinical interventions. Similarly, in adults, impulsiveness more often manifests in unsatisfactory occupational performance,8 drug abuse8 and other disadvantageous behaviours.9Whereas hyperactivity symptoms commonly remit over time, impulsiveness and attentional deficits more often persist into adulthood.11 Substance use disorder (SUD) is a frequent comorbidity in adolescents and adults with ADHD.16 ADHD is highly prevalent in individuals seeking treatment for SUD,19 with between 8% and 46% of those diagnosed with ADHD are reported to have comorbid SUD.19It is widely reported that several mental health disorders are overrepresented amongst substance abuse populations.23 Several mechanisms might be involved in the increased risk of SUD in ADHD. Neurobiological models indicate an imbalance in the dopaminergic neurotransmission, in both disorders.25 The mesolimbic dopamine (DA) pathway originally seemed to be crucial for drug reward.26 However, other DA pathways, nigrostriatal and mesocortical, also contribute to drug reward and addiction.27 Wise concluded that both these pathways participated in reward function and addiction. Electrical stimulation of both these pathways is rewarding. Blockade of glutamatergic or cholinergic input to either of the pathways attenuates the habit-forming effects of intravenous cocaine and dopamine in both nigrostriatal and mesocorticolimbic pathways.27Numerous studies have shown an increased risk of developing substance use and SUDs, including alcohol, tobacco and illicit drugs, in patients with ADHD.28 Another aspect of the SMH is that different disorders are associated with specific types of illicit drugs because of pharmacological specificity.29 When individuals with a disorder, experiment with various illicit drugs, they will find that certain drugs relieve emotional or affective states that are causing them problems. The SMH considers that psychiatric disorders precede substance abuse. However, it is not the psychiatric diagnosis that is self-medicated; instead, it is the psychological suffering described by the diagnosis.30The self-medication hypothesis (SMH) has been used to explain substance use because drugs of abuse reduce psychological distress.31 Although alcohol is still frequently used as a substance of abuse in South Africa, the latest data from the South African Community Epidemiology Network on Drug Use (SACENDU) shows that cannabis is currently the most widely used drug in South Africa. Amongst those seeking professional treatment at rehabilitation facilities, there was a significant increase in the proportion of cannabis admissions from less than 1.9% of admissions in 2000 to 8.3% in 2013.32Alcohol is one of the most widespread substances of abuse. Reports showed that South Africa had experienced a remarkable increase in the use of various substances of abuse.33 The use of cannabis is now more accessible to younger and poly-users in the context of modernised, increasingly urbanised societies where old-fashioned controls are collapsing. South Africa is a substantial producer of cannabis (the world’s third largest), most of which is consumed in the southern African region.33 Cannabis is considered by the World Health Organization (WHO) (2015)34 as a drug that is commonly cultivated, trafficked and consumed in the world. This means that its availability to people will continue effortlessly. Therefore, it is reported that this affordability and availability of cannabis is also an important factor influencing substance use by emerging adults, as a strong correlation between the prevalence of cannabis use has been reported throughout life and the feeling of easy availability.35Cannabis, also known as dagga, has been an illegal substance in most parts of the world because of its deleterious nature. Historically, strict rules governed the use of cannabis. However, the change is evolving faster as several countries and nations have or are revising regulations to soften regulated and prohibited laws against its use and production; thereby leaving vulnerable individuals more prone at the receiving end.37 Some data have significantly suggested the role of ‘self-medication’ as a mechanism for the development of SUD. For example, there have been reports of the ‘calming effects’ of alcohol and cannabis amongst individuals with ADHD.38 When not treated sufficiently, individuals with ADHD may use psychoactive substances to self-manage and curtail ADHD symptoms or to express their impulsiveness.39 Literature has shown that early detection of ADHD plays a significant role in the development of SUD in such individuals. Furthermore, past pharmacotherapy protects ADHD individuals from self-medicating and developing SUD and significantly improves ADHD-related impairment across all domains.41 In the past decade, new non-pharmacologic interventions have been developed, such as working memory, intensive school-based interventions for adolescents and neurofeedback and parental training.42 For this study non-pharmacological interventions were not taken into account.The risk of SUD is significantly higher in people with ADHD compared with those who are without ADHD.44In terms of the prevalence of ADHD symptomology in adults and its clinical characteristics, ADHD is more common amongst patients who use cannabis than amongst patients seeking other SUD treatments. In addition, self-medication may not be specific for ADHD symptoms, but rather a way to alleviate co-occurring symptoms related to mood and anxiety, which is common in ADHD patients.The aim of our study, therefore, was to compare alcohol and cannabis use between a group of treatment-seeking SUD patients with and without ADHD.A quantitative, cross-sectional, case-control study of adults seeking treatment for substance abuse was employed.Our study was conducted at various rehabilitation centres, including Private and Provincial Government Substance Abuse Treatment Centres, the South African National Council on Alcoholism and Drug Dependence (SANCA) Help Centres and psychiatric hospitals in South Africa.A convenience sample was used. Altogether, data from 185 post-detox inpatients on drug rehabilitation were collected from seven facilities from April 2018 to November 2019. Facilities were chosen within driving vicinity of researchers involved in our study. Participants were over 18 years of age, seeking treatment as inpatients in the facilities, who had completed primary school to ensure sufficient command of the English language. Exclusion criteria were a history of head injuries and severe neurological disorders, that is, epilepsy, cerebral palsy and severe psychiatric disorders.A questionnaire containing general demographical considerations including ethnicity, home language, education level and employment status.A comprehensive list of a various addictive substances to examine historical or present (active within the month prior to admission) use of substances and start age was completed by the participants.45 It consists of 18 questions based on the criteria diagnosing ADHD according to DSM-IV-Text Revision. The first six questions (ASRS-6) are most predictive of symptoms consistent with a diagnosis of ADHD.46 Participants were expected to rate the frequency of symptoms that they experienced on a five-point Likert-type scale: never (0), rarely (1), sometimes (2), often (3) and very often (4).The ASRS is designed to detect ADHD symptoms in adulthood by relating symptoms to adult situations such as projects, tasks or work. This reliable and valid self-administered instrument was jointly developed in 2005 by the WHO and Kessler and colleagues.Cronbach’s α was computed for the entire sample at 0.85 for inattention and at 0.83 for hypersensitivity-impulsiveness.48 It is divided into two domains to evaluate symptoms applicable to childhood (before age 12) and adulthood, whilst the third part considers functional impairment in five areas of functioning in both age categories.49 To simplify the evaluation of each of the 18 symptom criteria for ADHD, the interview provides a list of specific and realistic examples for both current and retrospective childhood behaviour. The examples are based on conventional descriptions provided by adult patients in clinical practice. Examples are also provided for the types of impairment that are typically associated with the five areas of everyday life: relationships and family life, work and education, social contacts, free time and hobbies, self-confidence and self-image.The DIVA 2.0 is a structured interview for ADHD in adults based on the DSM-IV-TR criteria. The instrument was developed by Kooij and Francken and is the successor of the initial semi-structured interview for ADHD in Adults.The data collection consisted of two stages.Our study was presented and explained to participants in English, and after their written consent, a questionnaire  was distributed. The authors distributed all questionnaires and were available for questions if needed. The response rate for the questionnaires was 99%.All participants who screened positive for ADHD based on their scores on the ASRS-6 (cut-off score for the first six questions of the ASRS was 16) were interviewed making use of the DIVA 2.0 to confirm the presence of ADHD. They formed the SUD+ADHD group. The participants who screened negative on the ASRS-6 formed the SUD-ADHD group.X2 analysis. The level of statistical significance was set at p = 0.05.Data from the Demographic Information and Substance Use questionnaires were entered and analysed using Statistica v. 12 (Dell Software). Multivariate analysis of variance (MANOVA) was employed to establish differences in alcohol and cannabis use, using a 2 × 2 (SUD+ADHD vs. SUD-ADHD x gender) model. Differences in categorical data (demographics) were established by 50 and was approved in agreement with the ethical requirements of the Research Ethics Committee (Human) of Nelson Mandela University (no. H14-HEA-PHA-007).Our study was conducted in accordance with the 1964 Declaration of HelsinkiEach rehabilitation facility’s respective management provided permission to perform our study at the involved centres. The participants were provided with an information document describing the investigation process. Written informed consent was obtained from the participants before the start of completing the questionnaires. The option of withdrawing at any stage of the procedure was given.Of the 185 participants who were screened for ADHD, 57 screened positive for the disorder using the ASRS-6. Subsequent confirmation of ADHD symptomatology using the DIVA established ADHD in 52 participants. The final sample, therefore, consisted of 180 participants, 52 (29%) classified as SUD+ADHD and 128 (71%) as SUD-ADHD see .p = 0.002), with significantly more white people (53.9%) amongst the ADHD group when compared with the non-ADHD group (25.8%). Also, a significant difference in language group representation was found, with a higher prevalence of Afrikaans speakers in the SUD+ADHD group (46.2%) than in the SUD-ADHD group (23.4%). A comparison of the employment status showed no significant difference, but the ADHD group showed a significantly higher level of education than the group without ADHD (p = 0.004).No significant differences in age or distribution between the two groups were found. For both the SUD+ADHD and SUD-ADHD groups, the females were in the minority. Although not statistically significant, there were relatively more females in the ADHD group. For both groups, most participants came from the 18–29 age group. There was a significant difference in ethnic representation  = 0.59, p = 0.62, ƞp2 = 0.02 nor between the genders: F = 0.90, p = 0.44, ƞp2 = 0.04.There were no significant differences for the use of alcohol neither between the SUD+ADHD and SUD-ADHD groups: Therefore, there were no significant differences in the frequency of alcohol use, start age and the duration of use between the SUD+ADHD and SUD-ADHD groups. Gender did not influence the outcome.F = 4.72, p = 0.004, ƞp2 = 0.09. There was no main effect of gender but the analysis showed an interaction effect of gender on the SUD group: F = 4.72, p = 0.004, ƞp2 = 0.14.There was a significant main effect when the two SUD groups were compared. The SUD+ADHD group showed increased use of cannabis when compared with the SUD-ADHD group: Post-hoc analysis (Bonferroni) showed that there was no difference in the frequency of cannabis use between the two groups for both genders but there was a significant difference between the females in the SUD+ADHD and SUD-ADHD groups for the age of onset of cannabis use (p = 0.02) with the ADHD females starting at an earlier age  than the female SUD group without ADHD . There were no significant differences between the SUD+ADHD and the SUD-ADHD males and the ADHD females for the start age of cannabis consumption.p = 0.02) but also than the SUD+ADHD  and SUD-ADHD  males.The SUD+ADHD females also used cannabis for a longer period of time  not only than the SUD-ADHD females . This observation corresponds with previous studies in this field53 The comparison group was not a typical sample of non-ADHD as they were also treated for alcohol use disorder. In addition, the small sample and high alcohol consumption in the South African population31 may have affected the results.Contrary to expectations, we found no evidence of increased alcohol consumption, frequency of consumption, start age and the duration of use and individuals with SUD+ADHD. Neither between male or female nor between SUD+ADHD/SUD-ADHD. Several studies have positively correlated ADHD with increased alcohol abuse.51 The prevalence of ADHD in adults seeking treatment for cannabis use is estimated to be from 34% to 46%.54 Initially factors such as high novelty-seeking traits and self-medication for ADHD symptoms55 were thought to increase the risk of developing SUD in people with ADHD. However, recent findings by Petker et al. provide support for a link between cannabis use with immediate reward preference and symptoms of hyperactive-impulsive ADHD in young adults.56 The evidence for behaviour disinhibition is strengthened by the fact that ADHD shares genetic overlaps with novelty-seeking and substance abuse.16 Although cannabis appears to be a less spontaneous form of self-medication because its pharmacological mechanism has not yet been linked to the forebrain dopaminergic regulation system, animal models and electroencephalogram (EEG) studies have shown that cannabinoids affect impulsiveness and behavioural disinhibition.54 The relationship between cannabis use and ADHD remains unclear and more empirical studies are needed to understand the mechanisms that determine this comorbidity.The current results suggest that also in the South African context, ADHD is highly prevalent in patients seeking treatment for cannabis use. When compared with the SUD-ADHD group, the SUD+ADHD group showed higher levels of cannabis use. Our results are consistent with other studies that describe similarly increased rates of cannabis use in patients with SUD+ADHD.57 Compared to men with ADHD, women with ADHD, portrayed a more complex presentation, more anxiety, more sleep problems and perceived mental health impairment.59 Precocious puberty in girls is associated with increased internalising symptoms, such as depression and anxiety, during adolescence and in young adulthood,60 suggesting the possibility of self-medication to cope with their psychological distress. There appears to be a link between early puberty in females with ADHD and the development of SUD,61 which may explain the significant earlier use of cannabis amongst females within the SUD+ADHD group.Furthermore, our research results show that, although there is no difference in frequency of use, female SUD+ADHD cannabis users show significantly different cannabis use patterns compared to female SUD-ADHD and SUD men with and without ADHD. Our results show that SUD+ADHD females have a significantly earlier age of onset of cannabis use than the SUD-ADHD females. Few previous studies have investigated gender differences in the relationship between ADHD and cannabis use.62 A study by Rucklidge and Tannock showed that adolescent women with ADHD have more psychological distress than men with ADHD.62 Also, compared to women without ADHD, women with ADHD have twice the prevalence of insomnia, anxiety, drug abuse, current smoking and depression.63 Kozak et al. found that the association between anxiety disorders and cannabis use might indicate that mental illness inclusive of ADHD can contribute to the increased likelihood of cannabis use – indicating that to cope with stressors and anxiety, females are more vulnerable to self-medicate with cannabis and are susceptible to developing and maintaining cannabis use.65The results of our study also demonstrate that SUD+ADHD females significantly used cannabis for a longer period when compared not only with the SUD-ADHD females but also with SUD+ADHD and the SUD-ADHD males. Both research and clinical experience have shown that, compared with men, women with ADHD are more likely to experience anxiety and depression concurrently, and these secondary internalising disorders are more likely to be diagnosed rather than underlying ADHD.66 Like other mental health disorders, social and cultural perspectives contribute to understanding adult ADHD and may play a significant role in diagnosing and accepting the condition.67Given the limited data on ADHD from South Africa, our study provides evidence of significant cannabis use, especially in females with ADHD, in treatment-seeking facilities in South Africa. A comparison of the employment status showed no significant difference, but the ADHD group showed a significantly higher level of education than the group without ADHD. There was a significant difference in ethnicity and home language, with the white Afrikaans speaking group being overrepresented in the SUD+ADHD group. We can speculate about the reasons for the observations, but few studies explored cultural factors in an ADHD diagnosis.Treatment facilities are mainly located in Gauteng, North West and East Cape. As a result of insufficient rehabilitation facilities in South Africa, most provinces rely on referrals to areas where treatment centres are available. We did not find a significant link between increased alcohol consumption amongst individuals with SUD+ADHD. In a normal population, the difference might be significant, but in this small comparison treatment-seeking sample, all participants consumed alcohol. Patients were not diagnosed with cannabis use disorder (CUD), but were seeking treatment for SUDs and indicated significant cannabis use.Finally, the data provided is cross-sectional; therefore, no causality can be inferred. It does not provide information on the relationship between ADHD symptoms, ADHD presentations or other comorbidities and the risk of substance use.54 their role in the causal effects of ADHD on lifelong cannabis use deserves further study.Given the specific ADHD symptoms and co-occurring disorders affecting clinical and population samples of ADHD,22 our cross-sectional data indicate increased levels of cannabis consumption amongst SUD+ADHD individuals, especially amongst SUD+ADHD females, highlighting the importance of women-specific treatment programmes to encourage utilisation of substance abuse treatment services.Regardless of the limitations of the research, our research detected significant cannabis use in SUD patients with ADHD when compared with cannabis use in patients without ADHD. Amongst patients seeking treatment in South Africa between 2000 and 2013, an increase in the use of cannabis was observed. Consistent with previous studies,These results strengthen the need to consider cannabis abuse in the context of ADHD in clinical interventions. South Africa needs to strengthen prevention and intervention activities against alcohol and cannabis use, especially in identified risk groups, like ADHD. Our findings, therefore, emphasise the need for early detection, diagnosis and treatment of ADHD to prevent substance use before it escalates to problematic levels.


Bartonella spp. are Gram-negative zoonotic bacteria that are transmitted to humans by several types of animal hosts, including rodents. Several studies have been conducted on the prevalence of Bartonella infections in rodents. However, the risk of rodent-associated Bartonella spp. infection in humans remains unclear. This study aimed to estimate the prevalence and genetic heterogeneity of Bartonella spp. in rodents and shrews from nine provinces of Thailand using culture and molecular techniques.Bartonella spp. were isolated from all samples using conventional culture techniques and polymerase chain reaction. Phylogenetic tree analysis was used to align the Bartonella sequences obtained from this study.A total of 860 blood samples from rodents and shrews across nine provinces of Thailand were collected from January 2013 to June 2016. Bartonella spp. in rodents and shrews was 11.5% . The following nine species of Bartonella were detected: Bartonella tribocorum, Bartonella rattimassiliensis, Bartonella queenslandensis, Bartonella elizabethae, Bartonella chanthaburi spp. nov., Bartonella satun spp. nov., Bartonella coopersplainsensis, Bartonella ranong spp. nov., and Bartonella henselae. The prevalence of Bartonella-positive animals differed significantly among provinces.The prevalence of Bartonella spp. isolated from rodents and shrews across Thailand were detected for the first time in this study. Further studies on the epidemiology of Bartonella infection in rodents and its interaction with human health should be conducted in accordance with the Thai government’s “One Health” approach to humans, animals, and the environment.To the best of our knowledge, the three novel  Bartonella spp. are Gram-negative intraerythrocytic bacteria including more than 40 species and subspecies . These pathogens are associated with various human diseases, such as cat scratch disease (B. henselae), trench fever (Bartonella quintana), Oroya fever (Bartonella bacilliformis), and endocarditis (B. tamiae) [10–12]. In particular, past exposure to rats has been reported in three patients from Thailand with fever, myalgia, and headache . Of these, we did not detect B. tamiae and B. clarridgeae in this study but we found the other two species in addition to B. tribocorum, B. rattimassiliensis, B. coopersplainsensis, B. queenslandensis, and three novel Bartonella spp.The prevalence of rodent-associated reported , 5, 21, reported , 23. Thereported , 9.3–42.reported , 10.1–30reported , and 13.reported , dependireported . In lines rattus , 8; howeB. henselae is a well-known pathogen in wild and domestic cats and causes cat-scratch disease [Bartonella spp. were also found in this province and were isolated from shrews. disease , 29. It  disease , 8 and i disease , 30. ThiB. elizabethae is widely distributed in Asian countries [Bartonella infection in animals (35.1%) among all provinces. Thus, the epidemiology of this infection in febrile patients with rodent exposure should be considered.ountries , 8, 25. ountries  and humaountries . We founB. tribocorum was the most prevalent Bartonella spp. in rodents (27.3%) followed by B. rattimassiliensis (20.2%), both of which had been detected in febrile patients in Thailand in a previous study [Rattus rodents, similar to that reported in the previous studies [In this study, us study . Almost  studies , 30, 33.Bartonella spp.; B. queenslandensis and B. coopersplainsensis were also isolated from Rattus rodents. They have been isolated from rodents and fleas in Taiwan in a previous study [The other two us study .Bartonella spp. in the Chanthaburi, Satun, and Ranong provinces. The public health information concerning Bartonella infections in these three provinces remains unknown. Further collaboration between human and animal sectors can help investigate the possibility of new Bartonella spp. infections in febrile patients with rodent exposure in these three provinces.We found three novel Bartonella spp. isolated from rodents and shrews in Thailand. In this study, nine different Bartonella spp. were detected and most of them were potentially zoonotic, using rodents as reservoir hosts. Further studies on the risk of this infection among humans, rodents, and the environment are needed to advance public health information.To the best of our knowledge, this is the first study that reported the detection of three novel DP, BN, WP, WW, and NC: Collected the samples. DP and WR: Provided technical help during the experiments. PW and MB: Did the statistical analysis. SB: Designed the study and drafted and revised the manuscript. All authors have read and approved the final manuscript.