The aim of this systematic review was to evaluate existing literature on inflammatory markers in CSF from patients with hydrocephalus and identify potential markers capable of promoting hydrocephalus development and progression. rd 2020 were identified from PubMed, Embase, and reference lists. Studies were screened for eligibility using the predefined inclusion and exclusion criteria. Data from eligible studies were extracted, and sources of bias were evaluated. We included articles written in English investigating inflammatory markers in CSF from patients with hydrocephalus and control subjects. The review was conducted according to the PRISMA guidelines by three independent reviewers.  Relevant studies published before December 3β, and LRG compared with control subjects, whereas the CSF of PHH patients had increased levels of IL-6, IL-18, and VEGF. CSF from patients with “other hydrocephalus diagnoses” had elevated IFN-γ compared to control subjects, and VEGF was increased in congenital hydrocephalus, spina bifida, and hydrocephalus associated with tuberculous meningitis compared with controls.  Twenty-two studies analyzed CSF from 311 patients with idiopathic normal pressure hydrocephalus (iNPH), 178 with posthemorrhagic hydrocephalus (PHH), 151 with other hydrocephalus diagnoses, and 394 control subjects. Fifty-eight inflammatory markers were investigated. The CSF of iNPH patients had increased CSF levels of IL-6, IL-1β, LRG, IL-18, VEGF, and IFN-γ are elevated in CSF from patients with hydrocephalus and may be involved in promotion of hydrocephalus development and progression. They may serve as novel disease biomarkers, and their signaling pathways may represent targets for pharmacological management of hydrocephalus. IL-6, IL-1 Hydrocephalus is characterized by excessive amounts of cerebrospinal fluid (CSF) accumulating within the brain ventricles resulting in an increased intracranial pressure . The CSFThe systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement , but is Studies were included in the review if they were (1) original research, (2) written in English, and (3) available in full text. Studies were excluded from the review if they (1) were reviews, meta-analyses, conference abstracts, comments, notes (i.e. gray literature), case reports, duplicates, or not published in English; (2) were not available in full text; (3) were animal or postmortem studies; (4) did not focus on patients with hydrocephalus; (5) did not analyze CSF for presence of inflammatory markers; (6) did not include a control group; (7) did not separate patients with hydrocephalus of different etiologies into separate groups; or (8) did not make a statistical comparison between patients with hydrocephalus and control subjects .rd 2020. The following search terms were applied in all four searches: “hydrocephalus” AND “cerebrospinal fluid” OR “CSF” OR “cerebrospinal fluid” AND “inflammation” OR “inflammatory” OR “inflammatory marker” OR “biomarker” OR “marker” OR “cytokine.” A unique search term was, in addition, applied to each of the four searches.PubMed and Embase were searched for relevant studies published before December 3Search 1 “normal pressure hydrocephalus” OR “NPH” OR “idiopathic normal pressure hydrocephalus” OR “iNPH.” The search was limited to studies published after January 1st 2005 where the international iNPH guidelines were first presented and later published [Search 2 “hemorrhage” OR “bleeding” OR “posthemorrhagic” OR “post-hemorrhagic” OR “post hemorrhagic.”Search 3 “trauma” OR “traumatic” OR “post-traumatic” OR “posttraumatic” OR “post traumatic” OR “post head injury.”Search 4 “meningitis” OR “infection” OR “infectious” OR “bacterial” OR “viral” OR “encephalitis.” Additional relevant studies were identified and manually curated from reference lists.The following data were extracted from each study: first author's name, publication year, study design, patient groups, number of patients in each group, diagnostic criteria including inclusion and exclusion criteria, age, sex, type of medication given, type of surgery performed, CSF source, preanalytical CSF handling, analytical method, CSF marker(s) analyzed, and result of CSF analysis.Authors SDL, NR, MJ, AS, and NM designed the protocol and search strategy.Initially, authors SDL and NR independently screened the studies by title and abstract. Studies that clearly violated the eligibility criteria were excluded. Afterwards, SDL and NR independently assessed the studies for eligibility by full-text review. After the independent assessment, SDL and NR collectively selected the studies for the final analysis. Authors SDL and EKO extracted data from relevant studies independently. After independent data collection, SDL and EKO collectively screened the extracted data, discussed any disagreements, and corrected any inconsistencies.most evidence when two or more studies reported consistent results, and a maximum of one study reported a contradictory result. Inflammatory markers were categorized as having limited evidence when results were reported from a single study.Inflammatory markers were separated into two categories based on the degree of consistency in results among studies. Inflammatory markers were categorized as having The potential risk of bias was assessed by the evaluation of the following data from each study: study design, sample size, age and sex, diagnostic criteria, inclusion and exclusion criteria, medication, circumstances of CSF sampling, pre-analytical CSF handling, selection of inflammatory markers for CSF analysis, and analytical methods.The PubMed and Embase search identified 1198 potential studies for the review, and 3 additional studies were identified from relevant reference lists. The initial search thus revealed 1201 potential studies for the review. Screening by title and abstract resulted in an exclusion of 1002 studies. Full-text review for eligibility of the remaining 199 studies led to the exclusion of 177 further studies. Hence, 22 studies were included in the final analysis .N = 311), PHH patients (N = 178), and patients with other hydrocephalus diagnoses (N = 151). The latter patient group included hydrocephalus associated with tuberculous meningitis (N = 44), spina bifida (N = 28), aqueduct stenosis (N = 25), acute hydrocephalus of unknown origin (N = 12), congenital hydrocephalus (N = 9), hydrocephalus following embolization of unruptured intracranial aneurysms (N = 8), fetal onset hydrocephalus (N = 7), late onset hydrocephalus (N = 7), arrested hydrocephalus (N = 6), and hydrocephalus with brain atrophy (N = 5). The CSF from patients with hydrocephalus was compared to CSF from control subjects (N = 394). The 22 studies investigated the presence of 58 inflammatory markers in total.The 22 studies included in the review were cross-sectional, case-control studies. Five studies were prospective –25, whilThe 22 studies applied different analytical methods to detect presence of inflammatory markers in the CSF samples. The analytical methods included enzyme-linked immunosorbent assays (ELISAs) , 23–35, CSF from iNPH patients was screened for presence of 36 inflammatory markers spread across 11 studies , 42. Detβ , and LRG showed most evidence of increased levels in CSF from iNPH patients compared to control subjects  iNPH Patients. In 2005, English international guidelines for the clinical diagnosis of iNPH were published [ublished , 39. Twoublished , 33 refeublished , 46. Fivublished –38, 42. ublished , 34.(2) PHH Patients. Patients diagnosed with PHH are heterogeneous in relation to age of onset, underlying pathological event, and clinical presentation. The internationally accepted diagnostic criteria for PHH are yet to be established [ablished . Howeverablished , 40, 41.ablished . Of the ablished , 29, 31,ablished , 28.(3) Patients with Other Hydrocephalus Diagnoses. Seven studies investigated patients with other hydrocephalus diagnoses [iagnoses , 40, 42.(1) All Patients with Hydrocephalus. The majority of the studies enrolled patients with hydrocephalus according to a certain diagnostic criteria. Only two studies specified the inclusion criteria that extended beyond the diagnostic criteria [criteria , 42. Onecriteria . Four stcriteria , 27, 28.criteria , 28, precriteria , 24, devcriteria , 42.(2) Control Subjects. The ideal control group should be the representative of the population from which patients arise [ts arise . Of the ts arise , 40–42. ts arise , 27, 38.ts arise , 33, 37.ts arise , 36. Onets arise . Of the ts arise , 38–42. ts arise , 42. Addts arise , 28, 39.Ideally, patients should not receive medication that is expected to influence the levels of the investigated inflammatory markers . However(1) CSF Sampling. It remains controversial whether a protein concentration gradient exists from the ventricular to the lumbar space [ar space –53. To rar space . Ten stuar space –39, 42, ar space , 40, 41.ar space , whereasar space . A thirdar space . Two stuar space , 34. Twoar space , 36.(2) Preanalytical CSF Handling. Preanalytical factors such as centrifugation, time from sampling to storage, storage material, and storage temperature are known to influence CSF analyses [g for 10 min at 4°C or room temperature prior to storage at -80°C [g/2500-3000 rpm for 6-10 min) [analyses –58. CSF at -80°C . Fourteeat -80°C , 33, 39 at -80°C , 37, 38.-10 min) , 37, 38.-10 min) . Eight s-10 min) –30, 32, -10 min) . The rem-10 min) –58. Howe-10 min) , 37–39. -10 min) .(3) Selection of Inflammatory Markers for CSF Analysis. The majority of the studies provided information in the introduction of their publication explaining why the inflammatory markers, or at least why some of them, were selected for analysis. Eight studies stated that some of the selected inflammatory markers had been detected previously in CSF from patients with hydrocephalus [cephalus –38, 41. cephalus . The stucephalus . Biased cephalus .β, and LRG were associated with the most evidence of significantly increased CSF levels. For PHH patients, IL-6, IL-18, and VEGF were associated with the most evidence of significantly increased CSF levels. For patients with other hydrocephalus diagnoses, IFN-γ and VEGF were significantly increased in several types of hydrocephalus compared to controls.In the current review, we systematically evaluated the existing literature on inflammatory markers in CSF from patients with hydrocephalus. We sought to identify promising inflammatory markers for future experimental research that aims to elucidate whether inflammatory markers can alter CSF dynamics and contribute to hydrocephalus development and progression. If neuroinflammation is involved in the pathogenesis of hydrocephalus, inflammatory markers may serve as novel disease biomarkers. Modulation of inflammatory pathways affects a range of systemic illnesses , 60 and κB pathway was recently demonstrated to cause CSF hypersecretion and subsequent hydrocephalus in rats [κB pathway [κB pathway. IL-1β is secreted primarily by immune cells in situations of infection, cell injury, and inflammation [κB pathway can be initiated by IL-1β [β also appears to have the prerequisites to promote choroidal CSF hypersecretion and cause hydrocephalus development.Activation of the NF- in rats . IL-6 dr in rats , 62, whe in rats . IL-6 ha pathway . IL-6 maammation . Similarby IL-1β . Hence, α2-glycoprotein) is produced by various cell types including hepatocytes, astrocytes, neutrophils, and epithelial cells in the inflamed tissue. LRG levels rise in inflammatory conditions such as meningitis, tuberculosis, and rheumatoid arthritis and are therefore suggested to be a marker of inflammation similar to acute-phase proteins [β [β levels. LRG signals by binding to endoglin (ENG), a component of the receptor complex for TGF-β, and LRG is therefore proposed to modulate TGF-β signaling [β signaling pathway has been reported to crosstalk with the NF-κB pathway [β, would initiate such crosstalk and hence potentially promote choroidal CSF hypersecretion and hydrocephalus development. IL-18 is secreted by immune cells such as macrophages and nonimmune cells such as epithelial cells, keratinocytes, and osteoblasts [β and therefore shares properties related to the receptor structure and signaling pathways, including activation of the NF-κB pathway [β, VEGF is capable of activating the NF-κB pathway [γ is secreted primarily by immune cells [γ intensifies the inflammatory response. The elevated IFN-γ levels in patients with other hydrocephalus diagnoses suggest presence of an ongoing inflammatory condition. Although IFN-γ primarily activates the JAK/STAT pathway [γ is also capable of activating the NF-κB pathway [γ has the prerequisites to promote choroidal CSF hypersecretion similarly to IL-6, IL-1β, IL-18, and VEGF.LRG . However, as some studies failed to report an age distribution or compared CSF from a mix of children and adults, results separated according to age would likewise have been associated with certain limitations.Another limitation of this review is the heterogeneity in sampling and handling of CSF across the included studies. Several studies directly compare lumbar CSF with ventricular CSF which may have influenced the results due to differences in the protein content from the ventricles to the lumbar space. The influence of sample time on CSF protein concentration remains debatable . HoweverThe review included inflammatory markers both directly and indirectly linked to inflammation. The definition of an indirect inflammatory marker falls within a grey area. Hence, some of the indirect inflammatory markers might be more relevant than others. The current review included indirect inflammatory markers that appeared relevant based on the identified studies in the original search. Regarding medication, it is surprising that only one study comment on the use of medication in relation to the investigated outcome . It can β, LRG, IL-18, VEGF, and IFN- γ, which were associated with the most evidence of increased levels in CSF from patients with hydrocephalus compared to control subjects. Future research should investigate whether these markers directly contribute to hydrocephalus development and progression. Such research will elucidate whether inflammatory markers may serve as novel disease biomarkers and whether their signaling pathways represent potential targets for pharmacological management of hydrocephalus. Future studies investigating the presence of inflammatory markers in CSF from patients with hydrocephalus should strive to eliminate the potential sources of bias presented in the current review. Efforts should be made to minimize patient heterogeneity. Patient diagnosis should occur in accordance with published international guidelines, and the inclusion and exclusion criteria should be clearly stated. Control subjects should, if possible, resemble healthy individuals. Studies should avoid small sample sizes, and patients should be matched on age and sex. CSF samples should preferably originate from the same space, be handled in the same manner, and if possible, be analyzed with the same analytical method. Furthermore, inflammatory markers should preferably be selected for analysis in an unbiased manner. The efforts done to eliminate the sources of bias may result in the identification of additional inflammatory markers, which are potentially involved in hydrocephalus development and progression.Despite the limitations, this systematic review presents a currently needed overview of the relevant literature and enables identification of promising inflammatory markers for future experimental research. In the current systematic review, we evaluated the existing literature on inflammatory markers in CSF from patients with hydrocephalus. We identified six inflammatory markers, IL-6, IL-1


Thousands of research articles on neuroblastoma have been published over the past few decades; however, the heterogeneity and variable quality of scholarly data may challenge scientists or clinicians to survey all of the available information. Hence, holistic measurement and analyzation of neuroblastoma-related literature with the help of sophisticated mathematical tools could provide deep insights into global research performance and the collaborative architectonical structure within the neuroblastoma scientific community. In this scientometric study, we aim to determine the extent of the scientific output related to neuroblastoma research between 1980 and 2018.We applied novel scientometric tools, including Bibliometrix R package, biblioshiny, VOSviewer, and CiteSpace IV for comprehensive science mapping analysis of extensive bibliographic metadata, which was retrieved from the Web of ScienceTM Core Collection database.We demonstrate the enormous proliferation of neuroblastoma research during last the 38 years, including 12,435 documents published in 1828 academic journals by 36,908 authors from 86 different countries. These documents received a total of 316,017 citations with an average citation per document of 28.35 ± 7.7. We determine the proportion of highly cited and never cited papers, “occasional” and prolific authors and journals. Further, we show 12 (13.9%) of 86 countries were responsible for 80.4% of neuroblastoma-related research output.These findings are crucial for researchers, clinicians, journal editors, and others working in neuroblastoma research to understand the strengths and potential gaps in the current literature and to plan future investments in data collection and science policy. This first scientometric study of global neuroblastoma research performance provides valuable insight into the scientific landscape, co-authorship network architecture, international collaboration, and interaction within the neuroblastoma community. Neuroblastoma (NB) is the most common extracranial malignant pediatric tumor that typically arises in the adrenal medulla or paraspinal sympathetic ganglia . The hisIn addition to tumor histology, many molecular genetic markers of NB have been identified, including amplification of the N-myc proto-oncogene protein (MYCN), mutations of the anaplastic lymphoma kinase (ALK) receptor, allelic deletions in the 1p, 3p and 11q chromosomal regions, chromosomal gain of 17 or tumor cell ploidy . AmplifiTreatment regimens for patients with NB differ accordingly and depend on tumor behavior as predicted by tumor histology and molecular features . ChildreOver the past decades, national and international collaborative research efforts have led to increased knowledge of biological and clinical tumor features, thereby refining patient’s risk stratification and treatment strategies, leading to significant increases in survival rates. Currently, patients with low- and intermediate-risk NB have an overall survival rate of about 90% , 17. HowGiven the enormous volume, heterogeneity and variable quality of NB-related publications, an assessment of the scientific literature on this topic is essential for both clinicians and researchers. Hence, we employed scientometric methodologies and innovative visualization tools to analyze extensive bibliographic metadata related to NB research.The study objectives are: 1) to assess the publication output as proxy for productivity of a researcher (quantity indicator); 2) to gauge the impact of the research on the scientific community by analysis of citation dynamics in NB research during 1980–2018 ; 3) to identify and characterize the most prolific authors; 4) to examine the academic journals publishing papers related to NB; 5) to examine geographical distribution of the research performance on NB; 6) to analyze the co-authorship network architecture; 7) to identify the most cited NB papers; 8) to perform a keyword analysis.h-index.All peer-reviewed scientific publications relating to NB research were retrieved from the Web of Science™ Core Collection Database . The search terms {“neuroblastoma(s)”} OR {“ganglioneuroblastoma(s)”} OR {“ganglioneuroma(s)”} OR {“peripheral neuroblastic tumor(s)”} were used in the title field and results were filtered by publication year from 1980 through 2018. No language restrictions were imposed. The complete metadata for each original publication and review article was compiled and manually exported on November 12, 2019. The “citation report” function from Web of Science was applied to assess citation rates and h-, m-, and g indices. The h-index, a common proxy measure for individual scientific output, is defined as the number of papers with citation number ≥ h (at least one citation) [h-index depends on both the number of a scientist’s publications and their impact on peers (number of citations). Since the h -index does not account for the career span of the author, the m-index or m-quotient  was applied. Further, to account for the citation evolution of the most cited papers of the given author over time, the g-index, which gives credit for the most highly cited papers in a data set, was used. The annual growth rate of scientific publications was assessed applying a calculator available at www.investopedia.com/calculator/cagr.aspx.Bibliometrix (version 1.7), an R-Tool of R-Studio (Version 3.6.1) for comprehensive science mapping analysis, and biblioshiny, the shiny interface providing a web-interface for bibliometrix, were used to import and manage the metadata from Web of Science™ . Baselinitation) . ConsequCollaboration measures included the number of documents per author (documents/author), number of authors per document (authors/document), and number of co-authors per document (author’s appearance/documents).In addition, using the word co-occurrence in our bibliographic data collection, we mapped the conceptual structure of an entire word’s framework with a dimensionality reduction technique and Multiple Correspondence Analysis (MCA)  We identhttp://www.vosviewer.com), a network analysis software tool, was used to construct a keyword co-occurrence network [VOSviewer  was applied to determine the keywords with strong citation bursts, which serves as an indicator of the most active area of research attracting a special degree of attention from the scientific community. Relationships between author’s keywords, references used, and the top authors were summarized by a Sankey plot (three-fields plot).P-values of < 0.05 were considered statistically significant. This study did not require approval of an ethics committee.Categorical variables were expressed as frequency and percentage, continuous variables were represented as medians with maximum and minimum or as means with standard deviation. The Spearman correlation coefficient was used to test correlations between selected continuous variables. Statistical analyses were performed with SPSS v. 23  and GraphPad Prism v. 6.01 . All tests were two-sided. n = 626, 5.0%) and began to increase extensively after 1991, reaching a peak in 2015 . Linear fitting of the data revealed an increase in the number of publications written between 1980 and 2018 . The average annual percentage growth rate indicating increasing annual scientific production was 11.8%. The highest annual growth rates were noted in 1986 (711%) and in 1990 (519.5%) while the lowest was recorded in 1998 (− 91.1%). After 1991, the growth rates were stable, ranging from − 20.3 to + 31.5%  articles and 465 (9.8%) reviews, were published by 36,908 authors from 86 countries. The total publications output was very low prior to 1990 , the number of multi-authored documents increased significantly   was 28.35 ± 7.7. There was a consistent citation dynamic ranging from 29.5 CPI in 1980 to 30.8 CPI in 2010. After 2011, the CPI was 12.7, which was lower compared to the period 1980–2010, because most newly published articles had not been cited much at the time of data extraction for our study. While the number of single-authored documents remains stable over time (r03) Fig. .Fig. 2Dn = 169), Matthay KK  had the highest h- and m-indices  while Seeger RC  had the highest average citation per item count (100.2)  published a single paper related to neuroblastoma and were considered “occasional” authors; 5178 (14.0%) published two papers; 2076 (5.6%) published three papers; 3781 (10.2%) published four or more papers. Authors who published more than one paper were considered to be “core” authors. Of the top ten contributing authors, Berthold F  was ranked first in the number of published articles , followed by Cancer Research , Journal of Pediatric Surgery , and Pediatric Blood and Cancer . The most cited journals were Cancer Research , Journal of Clinical Oncology , Journal of Neurochemistry , Oncogene (n = 9223), and Journal of Biological Chemistry (n = 9197). Cancer Research (80) had the highest h index, following by Journal of Clinical Oncology (75), and Journal of Biological Chemistry (56). Table In the time frame analyzed, there were 1828 academic journals publishing papers related to neuroblastoma research. n = 4328), had the highest h-index (141), and ranked first in terms of single country publications (n = 2284). Other high prolific countries were Japan (n = 1364), Italy (n = 1336), and Germany (n = 1128). The Netherlands had the highest rate of average article citations (n = 39.12), followed by the USA (n = 35.45), France (n = 33.24), Sweden (n = 33.16), and China (n = 32.61).Eighty-six countries were involved in NB total research output. Among them, 9999 (80.4%) of publications were contributed by the top twelve most productive countries, putting out more than 300 publications , France , Germany , and the USA . The international collaboration network is presented in Figure n = 160), the USA and Italy (n = 156), the USA and the UK (n = 137), and the UK and Italy (n = 131).Researchers from the USA showed the highest collaboration performance with a total link strength (TLS) of 1438, followed by Germany (TLS = 852), the United Kingdom (TLS = 829), Italy (TLS = 801), and France (TLS = 707). International collaboration analysis showed that 136 articles (30.0%) produced by Sweden had international authors, followed by authors from the UK .Of 12,435 publications related to NB, 12,136 (94.8%) were cited at least one time and 299 (2.4%) publications remain uncited after their publication. Table n = 4505), “apoptosis” (n = 821), “differentiation” (n = 371), “mycn” (n = 262), “ganglioneuroma” (n = 222), “oxidative stress” (n = 218), “neuroblastoma cells” (n = 214), “retinoic acid” (n = 195), “chemotherapy” (n = 153), “SH-SY5Y” (n = 153). The overall keyword network visualization is presented in Fig. The most frequent author’s keywords were “neuroblastoma”  and global pediatric cancer research, (4.3%) indicating high scientific interest in NB research , 26. We n = 4,136,224 citations) [Performance indicators measured by the number of received citations are used to identify the quality of the scientific publication and gauge its impact on the scientific community . In our tations) .h-index, total citations, and average article citations. As a high-income country, the USA allocates a large budget to research and has a vast number of research centers [We showed that 12 (11.6%) of 86 countries were responsible for 80% of NB-related research output. Of these, the USA was the leading country regarding total number of publications,  centers –36.There is a global trend in science towards national and international collaborations to improve patient care –39. Espen = 1), “Neurosciences” (n = 3), “Biochemistry Molecular Biology” (n = 2), “Multidisciplinary Sciences” (n = 1). The frequent publishing of NB-related papers indicates that the interest of readers and journal editors in Journal of Neurochemistry, Journal of Pediatric Surgery, PLOS One and Neuroscience Letters was also very high. Moreover, the Journal of Neurochemistry published the highest number of NB related articles, indicating the high significance of the molecular, cellular and biochemical aspects of NB research.Among the top 20 journals publishing articles on NB, 13 (65%) were listed in the category “Oncology” while the remaining 7 (35%) constituted distinct categories such as “Surgery”  and International Neuroblastoma Response Criteria (INRC). An additional three out of the ten most-cited articles were directly linked with the molecular and genetic factors involved in NB tumorigenesis. The identification of these tumor features and consequent discovery of druggable targets, such as ganglioside GD2 antibodies, has led to improvement of clinical outcomes . AnotherThe keywords employed most often by authors reflect the dynamics of research hotspots during the study period. We found that the keywords “neuroblastoma” and “apoptosis” were the most common and showed the greatest increase over time. Additionally, all of the top keywords with the strongest citation burst were related to the molecular-biological topics in NB research, suggesting the high significance of this NB sub-field. However, the examination of the field’s conceptual structure through a co-word analysis revealed other thematic network clusters, indicating diversity within research sub-fields.h-index and impact factor of the author, article, journal and country. Nevertheless, we believe that our study provides a detailed scientometric analysis and improves insights into international research on NB.Some limitations of our study should be addressed in future scientometric research. First, we used only the Web of Science™ database to search for publications, neglecting other search engines such as Scopus, Google Scholar or Index Medicus. Thus, other sources may yield different numbers of research items or citation counts. Second, due to constantly changing citation volumes over time, the results of our study are of temporary nature and valid for the time point of the present study’s data extraction . Third, the share of non-cited papers should also be considered when determining the This scientometric study provides an in-depth analysis of global neuroblastoma research, highlighting the multidisciplinary nature of the NB community. Over the past four decades, NB research has progressed enormously, resulting in a better understanding of underlying tumor biology and leading to the development of new molecular therapies. Collaborative research has led to substantial progress in patient stratification and implementation of standardized treatment protocols. Studies like this one are useful for researchers, clinicians, journal editors, and others working on NB in order to understand the strengths and potential gaps in the research and to plan future investments in data collection and science policy. Given the disease burden, especially associated with high-risk NB, a specific analysis of research publications and collaboration networks in this area is warranted to build on the more general scientometric studies.Additional file 1 Figure S1 Individual profiling of the top ten authors with regard to the number of published articles and total citations (TC) received per year. The size of the circles indicate the number of publications per year.Additional file 2 Figure S2 A choropleth map detailing the geographic distribution of collaborating countries. The color intensity (from light-blue to dark-blue) is proportional to the number of publications. The number of links (presented as red lines) between any two countries represents the strength of collaboration.Additional file 3 Figure S3 Top 10 keywords with the strongest citation bursts during last 38 yearsAdditional file 4 Figure S4 Common conceptual frames associated with neuroblastoma studies. Clustering of the 12,435 retrieved articles, including 7 different concepts of clusters of sizes 8, 5, 5, 11, 6, and 2 reflecting concepts frequently linked to neuroblastoma research.Additional file 5 Figure S5 The three-fields plot shows the relationship between the author’s keywords (research contents = right field), references authors use , and the top authors (middle field).Additional file 6 Table S1: Total number of publications with corresponding average citations per item, h-index, and annual growth rateAdditional file 7 Table S2: Citation rate and dynamics


N-sulfonyl biaryl lactams under mild conditions, developing a general and practical method for atroposelective construction of axially chiral biaryl amino acids. A structurally diverse set of axially chiral biaryl amino acids are obtained in high yields with excellent enantioselectivities. Moreover, a variety of axially chiral unsymmetrical biaryl organocatalysts are efficiently constructed from the resulting axially chiral biaryl amino acids by our present strategy, and show competitive outcomes in asymmetric reactions.Amides are among the most fundamental functional groups and essential structural units, widely used in chemistry, biochemistry and material science. Amide synthesis and transformations is a topic of continuous interest in organic chemistry. However, direct catalytic asymmetric activation of amide C-N bonds still remains a long-standing challenge due to high stability of amide linkages. Herein, we describe an organocatalytic asymmetric amide C-N bonds cleavage of  Asymmetric activation of amide bonds remains a challenge due to the high stability of amide linkages. Here, the authors show an organocatalytic asymmetric C-N bond cleavage of N-sulfonyl biaryl lactams under mild conditions, to access axially chiral biaryl amino acids. Amide synthesis and transformations have been extensively studied in organic chemistry1. However, direct activation of unreactive amide C–N bonds remains challenging owing to the high stability of amide linkages2. A seminal study by Garg, Houk, and coworkers3, described nickel-catalyzed conversion of highly stable amides to esters through insertion of nickel into a typically unreactive amide C–N bond , trifluoromethanesulfonyl (Tf), p-toluenesulfonyl (Ts), and cyclodicarbonyl group32. Despite these advances, direct organocatalytic activation of amide C–N bond, especially in an enantioselective manner, has yet to be achieved.As an important functional group, amides are essential structural units of peptides, proteins, and enzymes, and they have a wide variety of applications in chemistry, biochemistry, and material science34. Unlike well-studied centrally chiral amino acids37, there have been fewer reports on the synthesis and application of axially chiral amino acids , although their derivatives are frequently found in natural products and bioactive compounds42. The lack of efficient synthetic methods and limited number of examples have considerably impeded applications.Among the most important molecules in nature, chiral amino acids have a central role in life and widespread applications in pharmaceutical, chemical, and food industries1a, 1b, and 1c with the twisted structure of naphthyl phenyl scaffolds) is a straightforward and efficient method for atroposelective construction of axially chiral amino acids43. However, organocatalytic ring opening of biaryl lactams for atroposelective construction of axially chiral amino acids remains underexplored. This strategy presents some challenges, including (i) increasing the reactivity of unreactive amide bonds, (ii) choosing a proper organocatalyst to both activate unreactive amide groups and other reactants, and (iii) ensuring excellent enantioselectivity of the desired products. On the basis of Bringmann’s pioneering work42, and the recent advance in constructing axially chiral backbones by ring opening of conformationally labile bridged biaryls48, we envisaged that the N-electron-withdrawing group configurationally labile biaryl lactams with an inherent torsional strain might act as suitable substrates for activation of amide C–N bonds, promoted by a bifunctional organocatalyst. According to our understanding of organocatalysis54, we herein present a strategy for direct organocatalytic asymmetric activation of N-sulfonyl amide C–N bonds promoted by a bifunctional organocatalyst under mild reaction conditions. We developed a straightforward catalytic asymmetric method for the synthesis of a structurally diverse set of axially chiral biaryl amino acids. Moreover, a variety of axially chiral unsymmetrical biaryl organocatalysts are efficiently constructed from the resulting axially chiral biaryl amino acids by our present strategy, and they show good outcomes in asymmetric reactions.Catalytic asymmetric ring opening of biaryl lactams (such as N-Boc 1a or N-Cbz 1b) and benzyl alcohol 2a in the presence of the bifunctional thiourea catalyst60A in dichloromethane (DCM) at room temperature. Unfortunately, no reaction occurred, perhaps because the amide bond resisted breakage, even when activated by Boc or Cbz (entries 1–2). Next, we used a biaryl lactam 1c with a stronger electron-withdrawing substituent (Ts) under the same reaction conditions. Gratifyingly, the desired axially chiral biaryl amino ester 3a was obtained in 92% yield with 75% ee (entry 3). This result confirmed the feasibility of organocatalytic amide C–N activation. Subsequent solvent screening revealed that o-xylene was most effective, providing the desired product 3a in up to 99% yield with 92% ee (entries 4–9). We investigated other bifunctional organocatalysts B, C, and D. Catalyst D was the best catalyst for this reaction, and gave the desired product 3a in up to 99% yield with up to 97% ee (entry 12). Surprisingly, a 2 mol% catalyst loading was sufficient for this transformation (entry 13). When we lowered the catalyst loading to 1 mol%, the product yield decreased considerably (entry 14). In the absence of catalyst, no product was found (entry 15).We initially attempted the synthesis with biaryl lactams containing a naphthyl phenyl scaffold (1c as a model substrate (Table 3a–3f in excellent yields (92–99%) with excellent enantioselectivities (92–96% ee). Both 2-heteroaryls , methanol and tryptophol, also worked efficiently, affording the corresponding products 3g–j in excellent yields and enantioselectivities. Notably, methanol, the simplest alcohol, was also a suitable substrate for this transformation, resulting in the formation of the desired product 3k in 99% yield with 96% ee. Pleasingly, several other groups, such as CF3, a three-membered ring, double and triple bonds, trimethylsilyl (TMS), ether, bromide, acetal group, and even NHBoc groups, were well tolerated, and the corresponding axially chiral biaryl amino esters 3n–3w were generated in excellent yields (93–99%) with good-to-excellent enantioselectivities (91–98% ee). Interestingly, an additional activated keto carbonyl group in the alcohol did not influence the chemical yield, but slightly decreased the enantioselectivity (3x). (S)-1-naphthalen-2-ol ((S)-BINOL)-derived alcohol or l-glycerol–acetonide also were suitable substrates, affording the products 3y & 3z in excellent yields and stereoselectivities. Besides alcohols, other nucleophiles, such as phenol, thiophenol, benzyl mercaptan, diethyl malonate, nitromethane, and amine, did not give satisfying outcomes under the current conditions (see SI for details).With acceptably optimized conditions in hand  with good-to-excellent enantioselectivities (79–96% ee). Notably, Ts was easily replaced with other sulfonyl groups, such as phenylsulfonyl (Bs), methylsulfonyl (Ms), cyclohexyl sulfonyl (Cys), and o-nitrobenzenesulfonyl (Ns). The variety of the resulting axially chiral biaryl amino acids will likely have a range of potential applications.To further demonstrate the generality of this catalytic enantioselective method for the synthesis of axially chiral biaryl amino acids, the scope of biaryl lactam te Table . N-sulfo3a is so stable that it could be stirred at 140 °C in o-xylene for 4 h without any loss in ee. For further investigation on the racemization of compound 3 (3k as an example), see Supplementary Table TS3 for the transformation from PS to PR is 37.4 kcal/mol depicted in Supplementary Fig. Notably, product E, the N,N’-dimethyl analog of catalyst D, was used in this reaction. This result suggested that the H-bond donor motif of the catalyst played a central role in this transformation. When catalysts G & F, which are two moieties of the optimal catalyst D, were investigated separately, a yield of <5% was achieved. When these were used together, product 3a was generated in 69% yield with 12% ee. These results confirmed that the synergistic effects of the bifunctional moieties of the catalyst controlled this transformation.To probe the reaction pathway, control experiments were performed as shown in Fig. 2k attacks the carbonyl carbon of 1c in a nucleophilic manner coupled with a six-membered ring opening and proton transfer from 2k to the catalyst through transition states TS1R & TS1S, and other proton transfer from the catalyst to N– for formation of PR & PS via transition states TS2R & TS2S. According to the energy profiles depicted in Fig. S-configuration product PS should be the main product, which is in agreement with the experimental results. The tunneling effect of the proton in TS1R (with imaginary frequency as −664.05 cm−1) and TS1S (with imaginary frequency as −349.36 cm−1) was computed, and the tiny difference does not affect the energy differences between the two stereoselective transition states. In addition, the MeO···C and N···H–OMe distances are 1.74 Å and 1.32 Å in TS1R, while these are 1.73 Å and 1.39 Å in TS1S, indicating that the attacks of the O atom in methanol should be the dominating process in this step. Moreover, the Gibbs free energies of PR and PS are −11.4 and −12.7 kcal/mol lower than that of reactants 1c + 2k, respectively, demonstrating that the entire reaction should be an exothermic process.To understand the mechanism, we performed DFT calculations. The catalytic reaction contains two processes, namely oxygen of TS1R, and two N–H⋯O (1.77 and 1.92 Å), two C–H⋯π (2.47 and 2.83 Å), and one C–H⋯F (2.57 Å) interaction in TS1S. The strength and number of hydrogen-bond interactions increased in the S-isomer transition state TS1S, which resulted in a lower energy barrier via the more stable transition state TS1S. Further details of these computations can be found in the SI.We performed further non-covalent interaction (NCI) analyses to explore the origin of stereoselectivity. As illustrated in Fig. D, a gram-scale reaction of a biaryl lactam 1c with a benzyl alcohol proceeded smoothly to afford the axially chiral desired product 3a in up to 99% yield with 97% ee.To show the practical utility of our present strategy, a gram-scale reaction was performed Fig. . In the 3 were conducted as shown in Fig. N-Boc axially chiral biaryl amino acid 4 was obtained in excellent yield without loss of enantiopurity through debenzylation and detosylation of axially chiral amino ester 3a. Notably, tripeptide 5, containing both centrally and axially chiral centers, was easily prepared in excellent yield from 4 via an amide formation process  and catalyst D  in o-xylene  were added the appropriate alcohols . The mixture was stirred for 24–48 h at 30 °C. Upon completion of the reaction (monitored by TLC), the reaction mixture was directly purified by column chromatography on silica gel to afford the desired product Supplementary Information


P = 4.82 × 10−8), rs754832 (P = 4.83 × 10−8) and rs1873119 (P = 6.39 × 10−8) of ANXA1 gene. Some candidate pathways have been identified related to SIS, including those linked to infection response and hypoxia, “ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN” (P = 0.012) and “MANALO_HYPOXIA_UP” (P = 5.00 × 10−5). Our results provide novel clues for understanding the genetic mechanism of SIS.Shoulder impingement syndrome (SIS) is a common shoulder disorder with unclear genetic mechanism. In this study, Genome-wide Association Study (GWAS) was conducted to identify the candidate loci associated with SIS by using the UK Biobank samples . Based on the GWAS results, gene set enrichment analysis was further performed to detect the candidate gene ontology and pathways associated with SIS. We identified multiple risk loci associated with SIS, such as rs750968 ( Shoulder impingement syndrome (SIS) is a common shoulder disorder which has been considered as the most frequent cause of shoulder pain . It is cFOXP2 gene and rs62053992 in LINC01572 gene , also known as functional enrichment analysis, has been developed to identify functionally related genes that are significantly enriched in concentrations of genes that are signaly associated with complex diseases or traits  were used to define cases based on inpatient Hospital Episode Statistics data. Specific for this study, 3,626 SIS cases were identified according to the ICD10 diagnoses (Data Field: 41202) from the UK Biobank. Among the remaining samples, 3,626 samples were randomly selected as normal controls after excluding osteoarticular disorders according to the ICD 10th. Finally, a total of 7,252 participants from the UK Biobank cohort were included in this study  (rd degree (2 × 1/2(9/2) = 0.088). The subjects who had a self-reported sex inconsistent with the genetic gender, who were genotyped but not imputed or who withdrew their consents were removed. A logistic regression model (implemented in PLINK2) assuming additive genetic effects was used for association analysis, adjusting for age, sex, PC1, PC2 and PC3 as covariates . The quantile-quantile (QQ) plot was made by FUMA , Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database (http://www.genome.ad.jp/kegg/pathway.html), Ambion GeneAssist Pathway Atlas (http://www.ambion.com/tools/pathway), and Gene Ontology (GO) database (http://www.geneontology.org). A total of 2,850 gene ontology terms and pathways were analyzed in this study. 5,000 permutations were conducted to obtain the empirical distribution for the statistical tests. The enrichment scores and the empirical distribution were normalized to account for the different sizes of gene sets for each analyzed pathway databases. For each pathway gene sets, the empirical P value was calculated based on the observed normalized enrichment scores and the empirical distribution  from the UK Biobank in http://biobank.ctsu.ox.ac.uk/crystal/field.cgi?id=41202. Genome-wide significant loci associated with SIS are summarized in Table S1. Significant pathways associated with TWAS of SIS are summarized in Table S2. Quantile-quantile (QQ) plots of observed against expected P values for SIS is shown in Figure S1. All the supplementary materials including the GWAS summary statistics of SIS are available at figshare: https://doi.org/10.25387/g3.12477842.The GWAS data (Category 100314) used in this study are available in P > 0.05). P values; their negative logarithms will be the greatest. Significant associations were detected at the rs750968 (P = 4.82 × 10−8) and rs754832 (P = 4.83 × 10−8) of ANXA1 gene on chromosome nine , rs2130118 (P = 6.46 × 10−8), rs7029105 (P = 6.66 × 10−8), and rs7874184 (P = 4.31 × 10−7). We identified several candidate locus with suggestive association signals, such as the rs9987487 (P = 4.63 × 10−5) of PLGRKT gene on chromosome nine, and rs149598250 (P = 3.15 × 10−5) of PIK3AP1 gene on chromosome ten , TEKT3  and LIN28B .After controlling covariates including age, sex, PC1, PC2 and PC3, no statistical difference associations were observed in age, sex, PC1, PC2 and PC3 between SIS cases and controls . We also found several candidate pathways for SIS, such as “BECKER_TAMOXIFEN_RESISTANCE_DN” , “KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION”  and “IZADPANAH_STEM_CELL_ADIPOSE_VS_BONE_DN” . Among all of the 2,850 pathways analyzed by this study, the “MANALO_HYPOXIA_UP” was the most significant associated signal for SIS in our analysis  gene on chromosome nine. This gene encodes a membrane-localized protein that inhibits phospholipase A2 and has anti-inflammatory activity . Moreover, ANXA1 is essential to regulate bone marrow mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation , alias as hsa-mir-6130, is one of the microRNAs that coordinately regulated in rheumatic heart disease patients with mitral valve stenosis  which involved in regulation of inflammatory response; regulated monocyte chemotactic migration and matrix metalloproteinase activation, such as of MMP2 and MMP9 , which was related to inflammatory response. This gene set up-regulated in macrophages by lipopolysaccharide (LPS) and can lead to an inflammatory condition , another candidate biological gene sets associated with SIS, played a vital role in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA) . For exaThe gene set enrichment researches are receiving increasing attention in genetic study of human complex diseases. Although this is the first molecular mechanism study in SIS combining GWAS and gene set enrichment analysis, there are still several limitations need to be addressed. First, the sample size of SIS GWAS is not large enough. Additionally, our analysis results need to be verified in experimentation via collecting sufficient SIS samples. Consequently, our study results should be interpreted with caution and further studies are needed to confirm the findings and reveal the potential roles of identified locus and pathways in the development of SIS.In conclusion, we conducted GWAS for SIS, and then performed a gene set enrichment analysis based on GWAS results. Finally, a group of significant difference genes and gene sets within SIS were identified, which may provide novel clues for revealing the complex genetic mechanism of SIS.


Cucumis melo L. species, is a local variety of Puglia , which is consumed as a vegetable at the immature stage, like cucumber. In this study, three Barattiere populations  were evaluated for the main quality traits. All genotypes showed a very light green-yellow colour of flesh, without any difference regarding chlorophyll and carotenoid contents. Carovigno’s Barattiere showed the highest values of dry weight (6.8 g 100 g−1 fresh weight - FW), sugars (45 g kg−1 FW), and sweetness index (7.3), while Monopoli’s Barattiere showed the lowest total phenols content (21 mg kg−1 FW). Fasano’s Barattiere showed the highest content of Zn and Cu , while ‘Monopoli’ showed the highest Ba content (0.3 mg kg−1 FW) and the lowest Mg content (94 mg kg−1 FW). No differences between populations were found concerning the content of Ca, K, Na, B, Mn, and Fe. In conclusion, the quality profile of Barattiere makes this local genotype interesting for its traits, and also suggests its consumption by people with specific dietary requirements.Barattiere, belonging to the  Cucumis melo L., which is consumed unripe and is appreciated as an alternative to cucumber (Cucumis sativus L.), due to its better quality profile and the absence of cucurbitacin 1/2; (ii) hue angle, h° = tan−1 (b*/a*). Before the measurements, the colorimeter was calibrated with a standard reference with L, a*, and b* values of 97.01, 0.10 and 1.88, respectively.Barattiere fruits were cut longitudinally and the colour of their external and internal surfaces was measured by using the CIELAB scale , fresh samples  were maintained in a forced draft oven at 105 °C until constant weight was reached.® Freeze Dry System, model 7754030,  equipped with a LABCONCO FreeZone® Stoppering Tray Dryer, model 7,948,030 . The freeze-dried samples were ground at 500 μm by using a Retsch laboratory mill  to obtain a homogeneous powder.For each replication Barattiere fruit samples  were freeze-dried by a LABCONCO FreeZone−1 NaOH. Results were expressed as mg g−1 FW.Glucose and fructose content were determined by ionic chromatography  using a pulsed amperometric detector (PAD) according to protocols used by Renna et al. . Peak se−1 FW) of that sugar in fruits [The sweetness index (SI) was calculated based on the content and sweetness properties of individual carbohydrates by multiplying the sweetness coefficient of each sugar  by the concentration (g 100 gn fruits . The fol2O:CH3COOH 79:20:1% v/v/v). The vials were then placed in a sonicator bath at ambient temperature for 30 min, followed by 1 h in magnetic stirred. The sample was centrifuged at 10,000× g for 10 min at 4 °C and the supernatant was transferred into a volumetric tube. The residue was resuspended in fresh solvent mixture, gently mixed manually and sonicated for 30 min followed stirring (1 h) and centrifugation . The two supernatants were combined, and appropriate aliquots of extracts were filtered (0.45 μm). TPC was determined using gallic acid (R2 = 0.9998) as a calibration standard by using a Perkin-Elmer Lambda 25 spectrophotometer .The TPC was determined by using the Folin Ciocalteu method reported by D’Imperio et al. . BrieflyChlorophylls and carotenoid were determined spectrophotometrically using the extraction procedure reported by Renna et al. . Fresh s3 (10 mL). The microwave digestion protocol was applied in two steps: 15 min up to 200 °C and 10 min at 200 °C stable  by using HNO3 without sample as blanks. After mineralization, the samples, diluted with ultrapure H2O (Milli-Q Millipore 18 M W/cm), were filtered using a 0.45 μm filter. The mineralized samples were analysed with the Agilent 5100 Vertical Dual View ICP-OES  to measure Ca, K, Mg, and Na in radial mode and the minor elements  in axial mode.Macro and microelements  concentrations were determined according to D’Imperio et al. . BrieflyA one-way analysis of variance (ANOVA) was performed using the General Linear Model (GLM) procedure . The separation of means was obtained by the least significant difference (LSD) test. For a visual analysis of data, principal component analysis (PCA)  was performed on mean centred and standardized  data prior to analysis. The data matrix submitted to PCA was made up of 12 observations (three genotypes per four replications) and 28 variables. PCCs  were used to quantify relationships between dependent variables.Cucumis melo L. (unripe melon) used as a vegetable which shows a skin between greenish and slightly yellow and a flesh that is very light green-yellow, with very small differences among populations present locally. The sugar content in this local variety can be considered intermediate within those of cucumber and cantaloupe melon, while TPC appears lower than both cucumber and cantaloupe melon, although this quality trait may vary among populations. Independently of the population, Barattiere fruits showed a Ca content higher than those reported for cucumber and cantaloupe melon, while K content appears intermediate between cucumber and cantaloupe melon. In conclusion, the quality profile of Barattiere makes this local variety interesting for its nutritional traits, suggesting its consumption as an alternative to other vegetables such as cucumber. This example of agro-biodiversity can be considered part of a vegetable heritage worth saving. Moreover, its valorisation may represent a small achievement in pursuit of the diversification of the current food market. Future research activities may be directed toward its comprehensive characterization by using molecular tools.Barattiere is an Italian local variety of


IntroductionGender disparity in academic and organizational settings has been the topic of numerous studies, which have attributed under representation of females within medicine to both individual and institutional reasons. The main objective of our study was to assess gender disparity in leadership positions in committees of professional societies of family medicine (FM).MethodsIn this cross-sectional observational study, we collected publicly available information from 3 major FM societies  and also collected the academic/leadership information for each committee member, including bibliometric parameters of their research productivity.ResultsIn total, our sample size was 960 and composed of 58% men (556) and 42% women (404). There was a significant difference found in all the research productivity variables. Men had a greater number of publications, number of citations, years since first publication, years of active research, and had a larger h-index.ConclusionIn conclusion, gender disparity within FM societies is less significant compared to other professional medical societies and creating an environment that supports women and supports research can aid in achieving gender parity. Gender disparity is a phenomenon that has been studied in varying contexts from high school to post-graduate studies and further into the medical schools and professional careers -2. This Compared to Science, Technology, Engineering, and Math (STEM) careers, medicine is a field in which women have almost attained parity with men in the ratio of matriculation and training . For exaThe increase in female representation is also lacking in higher academic ranks and leadership positions. In the United States, while the number of female graduates has increased, only 43% of Associate Professor, and 31% of Professor positions are occupied by females . DespiteFamily Medicine (FM) associations and societies are professional organizations responsible for establishing training standards, continued education, and professional development for family physicians. The ratio and ranks of male and female committee members can arguably impact the future physicians in terms of mentorship and role models. FM, as a field of medicine, has an almost equal ratio of male to female physicians in many Western countries ,6. FemalSince research productivity is an important factor in the promotion to academic and leadership ranks, several factors which serve as measures of academic achievements, such as the H-index, FM society committee rank, university academic rank, publications, citations and years of active research, were measured and analyzed in our study. The H-index has become a widely used tool to numerically measure the impact of an author’s academic work -11. It iAn Institutional Review Board approval was not needed for our retrospective study since we evaluated data, which is publicly available. Our methodology has been validated in several of our recent manuscripts -11,13. TActive members of each FM Society with, both, a medical degree (MD or DO) and gender information were collected for this study. Gender was confirmed by a combination of publicly available photos and the pronouns used to address each individual in related news articles. Additional resources such as LinkedIn, Google, and institutional websites were subsequently consulted to complement and supplement any missing information. Leadership rank was defined as the position each member held within the FM society, such as President or Vice President. Academic rank was the faculty position the member held at their academic institution. Since universities in different countries may have different faculty titles, all academic ranks were compared and ranks of similar levels were grouped together Table .Data were analyzed using STATA V.14.2 to examine the correlation between gender, research productivity, and academic leadership of FM physicians. Analysis of research productivity was done by using variables such as publications, H-index, number of citations, and years since first publication. These variables were then further analyzed by leadership and academic rank. The research productivity of each society was also compared to one another.Due to the categorical nature of the FM association’s outcome variable, multivariable analysis was performed by using ordinal logistic regression. Each variable was entered into multivariable linear regression. Univariate analysis was performed using χ2 and Wilcoxson rank-sum tests where appropriate. Generalized ordered logistic regression was used to estimate the impact of the primary predictors, including gender, leadership ranks, academic ranks, publications, citations, H-index, years since first publication, years of active research, on becoming a president in CFPC, RACGP, and WONCA.A total of 1726 committee members were identified in our selected FM societies. After excluding non-medical doctors and missing gender information, our sample was 960; of which 556 were male (58%) and 404 were female (42%). Table Variables by leadership and academic ranksp = 0.98); see Table Overall, there were more males in all leadership ranks of FM societies compared to women . When analyzing specific variables across increasing academic ranks, males held higher medians for publications, H-index, and citations for most academic ranks. Females held higher median for publications, H-index, and citations when they were found to have an affiliation, but no formal rank was found .More males within FM societies were affiliated with a University 453 47.19%) compared to 353 (36.77%) females. There were more males within each academic rank except at the Assistant Professor rank; see Table 9% comparOrdinal logistic regressionGeneralized ordered logistic regression was used to estimate the impact of the primary predictors  on becoming a president in CFPC, RACGP, and WONCA. This model was selected instead of binary logistic regression because the outcome (Family Medicine Association category) had 3 ordered categories and the model failed the proportional odds assumption of standard ordered logistic regression. The regression model supports the decision to include the co-variants leadership ranks, academic ranks, publications, and citations. Gender even though was insignificant and was kept in the model, as it was the primary exposure of interest in the preliminary final model. The likelihood test indicated that it is statistically significant. Furthermore, its inclusion caused important changes in the coefficients for other variables in the model.The final step in the model building process was an evaluation of interactions (cut off for interaction was 0.1). Interaction terms were created between each of the main effects in the model, one by one. There was a significant interaction between publications and years of active research  in the models comparing them at all levels. When this interaction term is added to the model, the overall model improved. The log-likelihood increased.Model 1For category 0 (CFPC) as reference, against RACGP & WONCA (g(x) = ln Pr = 1/ Pr = 0g(x) = ˄β01+ ˄ β1 + ˄β21 ( LR2) + ˄β22 (LR3) + ˄β31 (AR2) + ˄β32 (AR3) + ˄β33 ( AR4) + ˄β34 ( AR5) +˄β35 (AR6) + ˄β4 (Publications) + ˄β5 (Citations) +˄β6 (Publications * Years of Active Research)\)Model 2For category CFPC & RACGP as reference, against WONCA g(x) = ln Pr = 2/ Pr = 0g(x) = ˄β01+ ˄ β1 + ˄β21 ( LR2) + ˄β22 (LR3) + ˄β31 (AR2) + ˄β32 (AR3) + ˄β33 ( AR4) + ˄β34 ( AR5) +˄β35 (AR6) + ˄β4 (Publications) + ˄β5 (Citations) +˄β6 (Publications * Years of Active Research)The log odds of working in a first-in-command position within CFPC‘s associations, are 0.45 times for females as compared to male, adjusting for other variables. The log odds of working in a first-in-command position within WONCA’s associations are 1.23 times for females as compared to male, adjusting for other variables.While the ratio of females to males is trending towards equal in medical school matriculants, there is a paucity of published literature on gender disparity within professional medical societies; however, it is reasonable to assume they follow similar trends to other medical specialties since these are closely associated ,13-14.This global perspective of FM societies shows that females comprise about 42% of the society committee workforce which is consistent with the number of females in the FM medical workforce, Canada 45%), Australia (42%), and the USA 38%) %, Austra,10. When8% %, AusIn addition to reasons outlined by other studies that contribute to decreased research productivity seen by females in medical societies, FM is also less research-intensive compared to other specialties; in Australia, there is 1 FM article per 1000 FM doctors, whereas there are 105/1000, 61/1000, and 148/1000 in internal medicine, surgery, and public health respectively . MedicalIn order to influence change, it is necessary to target individual and institutional policies. Despite WONCA being composed of representatives from countries of varying progressive attitudes, as of the writing of this manuscript, they are also the only society to have a “Women and Family Medicine” Working Group; part of this working group’s responsibilities is to advocate for women physicians. This helps create an environment that supports gender equity and is vital in the establishment of gender parity; women in WONCA had more publications and more years of active research compared to other societies and greater odds of holding a “1st in command” position. Similarly, providing support through research training dedicated to FM physicians can help increase research productivity; FM physicians who were provided training reported having increased skills in research methodologies, ability to publish, ability to obtain funding, increased academic promotions, institutional recognition, and improved ability to teach using evidence-based medicine . According to AAMC recommendations, in order for an organization to have long term success, they should (summarized) : 1) EmphLimitationsOur study has its share of limitations including the reliance on publicly available self-reported data via society websites and professional websites such as LinkedIn that may skew against women; an internal survey of members, LinkedIn found that men skewed their profiles to highlight more senior-level experience and had longer profile summaries than women did . It is, This study also used Scopus to determine active years of research, which has certain limitations. First, Scopus does not include citations before 1995, which may skew the results for senior faculty. Second, because years of active research are determined by an author’s year of first publication, it is possible that those who take prolonged breaks during their careers may have their years of active research overestimated, a finding that likely disproportionately affects women, who generally have more familial obligations. Moreover, some individuals may have changed their last names after a change in marital status. In such a scenario, it is not possible to correlate their academic parameters including the number of publications or H-index before and after the change of name. Thus, there is no way to account for and mitigate this limitation in the present study.While FM societies have a greater representation of females compared to other medical societies, the existence of gender disparity parallels the reasons outlined in other studies. The caveat is that FM is not as research-intensive, compared to other medical specialties. In order to reach gender parity within FM societies and improve research productivity in FM, we recommend that societies begin with instituting a working group or committee that focuses on addressing and supporting the needs of women within FM. Greater efforts also need to be given to evaluate which programs have the greatest impact on reducing gender disparity at a multi-institutional level.


Physalis fruit purée drying by the Refractance Window™ (RW™) method. For this, a RW™ dryer layout with a regulated bath at working temperatures of 60, 75, and 90 °C, Mylar™ thicknesses of 0.19, 0.25, 0.30 mm and IR radiation of 250 W for assisting RW™ drying process was used. Experimental curves data were expressed in moisture ratio (MR) in order to obtain moisture effective diffusivities (non-assisted RW™: effD = 2.7–10.1 × 10−10 m2/s and IR-assisted RW™: effD = 4.2–13.4 × 10−10 m2/s) and further drying curves modeling . The Midilli–Kucuk model obtained the best-fit quality on experimental curves regarding statistical tests applied (Coefficient of Determination (R2), Chi-Square (χ2) and Root Mean Square Error (RMSE). Microscopical observations were carried out to study the RW™ drying conditions effect on microstructural changes of Physalis fruit purée. The main findings of this work indicated that the use of IR-assisted RW™ drying effectively accelerates the drying process, which achieved a decrease drying time around 60%. Thus, this combined RW™ process is strongly influenced by the working temperature and IR-power applied, and slightly by Mylar™ thickness.The objective of this work was to study the influence of the drying temperature, infrared (IR) radiation assistance, and the Mylar™ film thickness during  Physalis , goldenberry, or uchuva is a berry that has a high content of vitamin A, B, and C, β-carotene, phosphorus, iron, and bioactive compounds. It also has antioxidant activity, anti-hepatotoxic activity, anti-proliferative effects in hepatoma cells, anti-inflammatory and antidiabetic activity, so that their consumption provides health benefits and reduces the risk of acquiring certain diseases, such as cancer, malaria, asthma, hepatitis, dermatitis, and rheumatism, for which Physalis fruit, it is considered as a promising functional food [nal food .On the other hand, dehydration by the Refractance Window™ (RW™) drying method is a drying technology considered as emerging for the drying of food material that is used to evaporate water from liquid or semi-liquid foods . This drTM drying process of high quality fruit pulps or purées. Hence, when food materials are subjected to an electromagnetic field, the wave penetrates directly into the material, resulting in fast volumetric heating. These electromagnetic waves in IR radiation are displayed under three categories ranges, 0.78–1.4 μm for the near-infrared (NIR), 1.4–3.0 μm for the middle-infrared (MIR), and 3.0–1000 μm for the far-infrared (FIR). Quick energy absorption by water molecules causes rapid evaporation of water, creating an outward flux of rapidly escaping water vapor. In this way, it can reduced drying times, minimize quality losses, and achieve uniform heating, among other advantages [Traditional drying technologies, such as hot-air convective drying, vacuum drying, microwave drying, freeze-drying, among others, aim to ensure that the food quality and stability are preserved during the storage period, being, at the same time, as efficient as possible. However, so as to fulfill efficiently the drying process, shortening operation times and enhancing product quality, as well as using combined drying technologies in which different sources of energy are involved, are becoming more and more current. In this sense, there is the possibility of assisting the different drying processes with several forms of energy that accelerate transfer of matter from the diverse feed sources. Infrared (IR) radiation assistance could be seen as a convenient and alternative method to combine with RWAmong the most important quality properties of dried food, color and texture are widely noteworthy . The fooIn order to successfully transfer knowledge acquired experimentally from studies on food dehydration into industrial applications, drying kinetics modeling is necessary. Besides, a mathematical model is an important tool used to optimize the management of operating parameters and to simulate the drying processes behavior. These simple models, also known as thin-layer models, allow prediction of mass transfer during dehydration and are applied to simulate drying curves under similar conditions . Physalis fruit purée under different drying temperatures, Mylar™ film thickness, and with/without the assistance of IR radiation.In the light of the above considerations, as RW™ drying method is considered an emerging technique based on a thin-layer configuration of the food materials, along with considering that the use of infrared radiation to accelerate/assist drying processes, has proved to be effective and easy to implement. The main advantage of combined drying technologies is being able to dehydrate food materials using high temperatures and short drying time, which allows attaining high-quality retention and/or incorporate a high added-value to food products ,5. TherePhysalis fruits were purchased from local producer Hortifrut Ltd., Santiago, Chile. The samples were selected to provide a homogenous group, based on the date of harvest, color, size, and freshness, according to visual analysis. This visual inspection consisted of discard fruits with mechanical damage, cuts, perforations, and impacts. Then, the fruits were washed in tap water to eliminate any surface contamination of foreign matter, and refrigerated immediately (5.0 ± 0.2 °C). Before drying experiments, the Physalis fruit purée was prepared using a food blender (Minipimer MR-4000) in order to obtain a homogeneous sample containing pulp, seeds, and peel. Afterwards, the Physalis purée samples  were packaged in low density polyethylene bag (10 × 15 cm), vacuum heat-sealed, and kept under freezing conditions (−18.0 ± 0.2 °C), until drying process. The samples frozen were thawed at 5.0 ± 0.2 °C. The moisture content was determined by AOAC  method no. 934.06 , employing a vacuum oven  at 70 °C for 72 h, and an analytical balance accurate to 0.0001 g . Moreover, the total soluble sugar content was calculated with an Abbe refractometer  and the water activity was determined at 25 °C by a Novasina water activity instrument . 2 where Physalis purée was placed and then spread over the Mylar™ film aided by a spatula blade with a 3 mm gap. A water level control device was used to keep a permanent contact between the water and the Mylar™ film. The assistance with IR radiation was obtained by using an infrared lamp  of 250 W , which was placed in a way that ensured covering the greatest surface portion of spread Physalis purée over the Mylar™ film (various previous assays enabled an adequate IR lamp placement), as can be seen in Physalis purée were measured using a digital scale  until reaching an approximate moisture of 10% (w.b.) during each drying experiment under study. The dried samples were stored in polyethylene bags at (5.0 ± 0.2 °C), vacuum heat-sealed, protected from sunlight, until further microstructure and color analysis. All drying experiments were performed in triplicate and the results were expressed as the mean ± standard deviation.A laboratory-scale RW™ drying system was built using a 30 L thermo-regulated bath using temperatures of 60, 75, and 90 °C and a set of Mylar™ film  with different thicknesses of 0.19, 0.25, and 0.30 mm. Three containers were built from Mylar™ film; these have an effective transfer area of 140 cmPhysalis purée drying behavior that takes place during the falling rate period, during which water is transported to the surface material by diffusion transport phenomena being necessary the use of Fick’s second diffusion law (Equation (1)). Thus, moisture ratio (MR) is the dependent variable, which relates the gradient of the sample moisture content in real-time to both initial and equilibrium moisture content. Experimental data were expressed in terms of the MR and were calculated according to Equation (2). Then, the integrated equation of Fick’s second law was also used for long time periods and thin-layer in one dimension, representing the first term in the development of the series, from which the diffusional coefficient is obtained for each temperature. The moisture effective diffusivity (effD) was calculated according to Equation (3).MR is moisture ratio (dimensionless); effD is the moisture effective diffusivity (m2/s); t is drying time (s); x the spatial dimension (m); tX is the moisture content  at any time; oX is initial moisture content (g water/g d.m.); eX is the equilibrium moisture content (g water/g d.m.), and L is the half-thickness (m) of the Physalis purée thin-layer on the Mylar™ film. This value resulted from predicting Diverse mathematical models have been proposed to predict the drying curves behavior of food and agricultural products. The most common drying models are listed in effD was calculated by the Arrhenius equation (Equation (4)) described by [oD is a pre-exponential factor for the Arrhenius equation (m2/s), aE is activation energy (J/mol), R is gas universal constant (8.3145 J/mol K) and T is drying temperature (K).The activation energy was obtained from the Arrhenius equation, where the temperature dependence of ribed by :(4)Deff=Physalis purée samples, from the drying experiments, were fixed with 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer for 2 h, after this period they were washed 3 times × 5 min in double distilled water. Subsequently, the samples were (1) washed with 0.1 M × 5 min sodium cacodylate buffer, (2) dehydrated in ascending alcohols 50, 70, 95, 100 °I and 100 °II for 5 min each, and (3) dried until the critical point, by placing the samples in the Autosamdri-815 Critical Point Dryer for 30 min. This process allowed to remove all water molecules through CO2 blast and ensured the maximum structural preservation for the samples. Finally, the samples were mounted on Aluminum holders and metalized with gold in denton vacuum desk metallizer. Microphotographs were obtained using a scanning electron microscope (Jeol brand JSM IT300LV) operating at 15.0 kV.To perform the scanning electron microscopy (SEM), L* (whiteness/darkness), a* (redness/greenness), and b* (yellowness/blueness), standard illuminant D65, and observer 10°. The above parameters were measured for fresh and dried samples [∆E) using Equation (5), where oL, oa, and ob are the control values for fresh Physalis purée. Ten replicate measurements were performed and results were expressed as the mean ± standard deviation.For the color analysis, a 3nh colorimeter  was used. Color changes were expressed in CIELab system coordinates,  samples . Then, tTM methods (with or without IR radiation). As to mathematical models of drying to be evaluated, a regression analysis was carried out. The determination coefficient ) was the first criterion to select the best model to describe the drying kinetics behavior. Moreover, Chi-square ) and Root Mean Square Error ) were calculated to evaluate the fit quality of the models to experimental data. Where, the R2 > 0.85, χ2 << 0.1 and RMSE << 0.1, were selected as optimal criteria in order to evaluate the fit quality of the proposed models.exp,iMR is the experimental moisture content; pre,iMR is calculated moisture content; i is the number of terms; z is a constant number and N is the number of data.An ANOVA analysis was performed for diffusivities and color parameters values, obtained by StatGraphics Plus v.5.1 , including a MRT (multiple range test) to recognize significant differences between Mylar™ film thicknesses, applied temperatures and difference in RWPhysalis purée were of 4.155 ± 0.012 g water/g d.m, 15.48 ± 1.25 °Brix, 0.975 ± 0.001, respectively. Regarding drying kinetics, all the curves presented an exponential decay behavior and the influence of drying temperature is again remarkable  on Physalis drying, where drying times between 17 and 44 h were reached. Junqueira et al. [Physalis fruit. The authors showed the drying times from 450 to 650 min, for each of the experiments.Finally, the difference between drying temperatures and applied methods shows a significant decrease in drying time, with a difference of up to 100 min, that is the case of non-assisted RW™: 160 min at 60 °C and IR-assisted RW™: 60 min at 90 °C, both using Mylar thickness of 0.19 mm. Therefore, the temperature difference caused a decreasing drying time of around 20% to 30% in non-assisted RW™ and IR-assisted RW™, while the addition of the IR radiation led to a decreased RW™ drying process time of up to 62%, approximately. Against that background, Vega-Gálvez et al.  presentez et al.  evaluateRW™ drying has shown to be a promising drying technology, mainly in time reduction as compared with conventional dehydration methods. Furthermore, when using both combined drying technologies, IR and RW™, for industrial-scale dehydration of fruit and vegetable purée and pulp, as well as other food material, these could be considered as a synergy emerging technology, which allows reducing the drying time and thereby energy consumption.−10 m2/s, in effD: 5.43–9.33 × 10−10 m2/s); [effD: 2.5–7.14 × 10−10 m2/s); [effD: 1.25–14.3 × 10−10 m2/s), salmon tissue (effD: 1.24–3.09 × 10−10 m2/s) and beef slices (effD: 1.25–3.86 × 10−10 m2/s); [effD: 7.0–11.0 × 10−9 m2/s); [effD: 1.94–2.54 × 10−9 m2/s); [effD: 4.25–7.68 × 10−10 m2/s), and [effD: 1.94–2.54 × 10−9 m2/s). It needs to be mentioned that effD values of previous researches varied because of different drying temperature, sample moisture content, application of pre-treatments and Mylar™ thickness. effD values studied for similar conditions of temperature and thickness (with difference in infrared assistance) indicate significant differences due to the inclusion of the IR radiation that increases the moisture diffusivity values in all the compared experiments, which implies that the addition of the IR radiation directly and significantly influences the migratory capacity of the water that is extracted in the RW™ drying process.Effective diffusivities values were in the range of 2.74 to 13.40 × 100 m2/s);  apple sl0 m2/s);  apple sl0 m2/s);  mango pu9 m2/s);  yam slic9 m2/s);  papaya p/s), and  cucumbereffD values showed a significant influence of drying temperature on this physical parameter . Moreover, a MRT to determine the significant means among the effD was delivered, showing three homogeneous groups for each Mylar™ thickness used. This temperature-dependence effect has been described using Arrhenius-type relationship to get the activation energy (Ea) from the effective diffusivity data. Then, the same ANOVA carried out on effD values presented a significant influence of Mylar™ film thickness on the diffusivity values, keeping constant the RW™ method . MRT analysis didn’t show a greater difference among the Deff values vs Mylar™ thickness, showing two homogeneous groups for each drying temperature used . This showed a clear effect of drying temperature but only a weak effect of Mylar™ film thickness. In this way, it would be possible to select only one appropriate Mylar™ film thickness with respect to the kind of dried food to be developed. Furthermore, this study confirmed again that temperature is one of the main drying operational variables for any drying method, along with IR-assistance also affecting significantly the drying process. Thus, information obtained also can be important for the next hybrid dryer performance taking into account food quality as well as economic costs [In both treatments (non-assisted RW™ and IR-assisted RW™), the effective diffusivity values varies significantly with the used temperature, for it, an ANOVA is necessary to realize. Thus, the ANOVA performed on ic costs .effD values were evaluated considering the same Mylar™ thickness but different RW™ drying method. From this analysis obtained, it was demonstrated a significant influence of assistance of the infrared system on the increased effD , in all cases evaluated . This showed a clear influence of IR radiation as an assistance system for any drying method. Likewise, diverse studies have reported that moisture diffusivities under infrared-assisted drying operations were higher compared to those of non-assisted drying process [Physalis purée, IR radiation impinged on the exposed spread purée and penetrated it. This, radiation energy is readily converted into heat and the purée exposed to IR radiation is intensely heated, reaching a temperature gradient almost to zero within a short period [Furthermore, a third ANOVA assessment was established, in this case, the  process ,22,23. Tt period .k, ok, and k1 values increase as drying temperature increases, this behavior is observed for most of the models and for each RW™ drying process. In addition, it can be seen as the inclusion of the IR radiation on RWTM drying method caused that the parameters k, ok, and k1 were also directly dependent on the heat source (IR radiation), which indicates that the linear increase of parameters k would be related to the physical parameter, effD [n, a–c) did not present significant variations despite increasing the temperature, this could occur due to the food matrix structure that is dried. Furthermore, some authors have found the n parameter not to vary with the temperature, as well as showed an air velocity linear dependence of this parameter n [n, this empirical parameter could be affected in the case of drying fruit slices with or without skin, increasing accordingly the shell thickness. Since this study presented a fruit purée drying by RW™ method, these empirical parameters would not be affected by the presence of the shell, despite the temperature being increased, as well as IR radiation included. On this basis, the Mylar™ film thickness could have been an RW™ drying process operational parameter, which could have affected to empirical parameters, but this behavior did not happen.The kinetic parameters of empirical models can be observed in both RW™ method without IR and IR-assisted RW™ drying method in er, Deff . The othameter n ,26. The ameter n  proposedRMSE ≤ 0.116 and 0.001 ≤ χ2 ≤ 0.024 values were obtained. Furthermore, taking account the criterion of R2 ≥ 0.85, most of the models displayed a good fit quality to all experimental data. However, regarding the statistical values obtained, Midilli–Kucuk  and Page  models showed the best-fit quality on experimental data, for non-assisted RW™ and Infrared-assisted RW™ drying, respectively. Some researchers have attained good outcome when applying both Midilli–Kucuk and Page models on the drying kinetics of different food subjected to different hybrid drying method [Statistical evaluation for each mathematical model showed a good fit because low 0.002 ≤ g method ,29 as weg method . Always effD values for the temperature range 60 to 95 °C, taking account both RW™ method and Mylar™ thickness as independent-factors. The aE values for non-assisted RWTM drying methods were of 41.3, 33.4, and 31.1 kJ/mol for each Mylar™ thickness of 0.19, 0.25, and 0.29 mm, respectively. Whereas aE results for IR-assisted RW™ drying technique were of 34.5, 33.0, and 26.6 kJ/mol for each MylarTM thickness of 0.19, 0.25, and 0.29 mm, respectively. From comparing the Ea results obtained by different RW™ methods for the same Mylar thickness, the non-assisted RW™ drying method obtained Ea values slightly higher than IR-assisted RW™. This may be in part because Ea is the energy barrier to activate water diffusion; hence, the IR-assisted RW™ would need less energy to start the moisture diffusion transport. The results obtained are similar to those obtained in other report [Physalis fruit obtaining 38.78 kJ/mol, other results obtained are similar, 37.27 kJ/mol for figs [The activation energy values calculated based on r report  on the afor figs  for the Physalis purée is conformed of flesh, peel, and seeds. Hence the microstructural observations were accomplished on these different sections of fresh Physalis purée. The microstructure analysis consists of a complex network made of peel and seeds together with the flesh from the fruit, holding water about them. It’s worth recalling that fresh Physalis purée. This microphotography enables exhibiting a skin piece very properly for observation. From the microphotography, a kind of bumps, called “emergencies” by the author [e author  is showne author . These ee author . Beyond Physalis purée samples. Physalis purée deformation and structure.From Physalis purée peel by IR-assisted RW™ drying method, where these drying experiments maintained the tendency to compare it with the fresh Physalis purée peel  and also to the blue color, losing yellow tones (b* coordinate), regarding fresh Physalis samples. Colorimetric coordinates of fresh Physalis purée samples were 83, 99, 34, 62, and 72, 4 to L*, a* and b*, respectively. The colorimetric values showed that all L* coordinate values  and sugars . Thereby, dried Physalis purée would become darker, probably because of an extensive Maillard reaction, as in this particular case of IR-assisted RW™ treated Physalis purées.The e values  decreasea* coordinate . Moreover, although slice Mylar™ thickness  influenced L* and b* values substantially, it failed to affect a* values considerably. Ochoa-Martinez [L*, a*, and b* coordinates for dried mango slices by Refractance Window™ drying. Moreover, a new ANOVA analysis found that RW™ drying method had a significant effect on L*, a*, and b* value  but only at 90° .ANOVA analysis showed that drying temperature  had a significant influence on color indices of Martinez  demonstrΔE as shown in Physalis purée (between 50 ≤ ΔE ≤ 75). An increase in the drying temperature when processing without infrared resulted in an increase in ΔE. In general, the changes of ΔE are mainly due to changes in the chromatic parameters a* and b*, where Abonyi et al. [ΔE values between 20 and 25. Fisher et al. [As to the total color difference or i et al.  found ini et al.  presenter et al.  and Bussr et al.  also fouPhysalis purée, such as β-carotene. Nevertheless, the addition of the IR radiation could suppose a very invasive thermal shock for the Physalis purée drying, obtaining differences of higher color than with respect to the non-assisted RW™ drying process . That is why, since food surface color is one of the quality parameters most evaluated by consumers, and is critical in the acceptance of the product, new strategies should also be considered for developing dried fruit purée, such as pre-treatments with additives that could better protect color compounds. Thus, color changes caused by both RW™ drying process could have occurred, not only by the non-enzymatic browning reaction but also by the destruction of the pigment present in the ΔE values were evaluated considering the diverse factors under study, drying temperature, Mylar™ thickness, and RW™ drying method. This ANOVA analysis found a significant influence of drying temperature as well as RW™ drying method on the ΔE values , in all cases evaluated. Whereas, Mylar™ thickness didn’t show a clear influence on the ΔE values , in the same experiments evaluated.Then, an ANOVA assessment was established, where the Physalis purée samples in relatively shorter time than non-assisted RW™ and other traditional drying methods. The drying kinetics behavior was strongly influenced by the drying temperature and the IR-assistance, whilst slightly by Mylar™ thickness. Both the effD (non-assisted RW™: 2.7 × 10−10 ≤ effD ≤ 10.1 × 10−10 m2/s and IR-assisted RW™: 4.2 × 10−10 ≤ Deff ≤ 13.4 × 10−10 m2/s) and kinetic parameter values showed dependence on the drying temperature (60–90 °C), giving as a result of activation energies between 14.59 and 34.44 kJ/mol. When comparing experimental data to those predicted by the Midilli–Kucuk model, this model could be a useful tool for describing drying kinetics and estimating drying time under different RW™ drying method conditions. Furthermore, the IR-assisted system decreased RW™ drying process time by around 60% to reach an equilibrium moisture content of 10%. Therefore, combined treatments of IR and RW™ would be a good methodology to preserve dried Physalis fruit purée with a minimum impact on its quality properties, as well as reducing energy costs and consumption during the industrial-scale drying process.RW™ drying assisted by infrared heating (IR-assisted RW™) is a method that allows moisture reduction of