bluuebunny/crossref_metadata_2025 huggingface dataset:
Les problèmes, leurs expériences et leurs publics
Authors: Cefaï Daniel
Published: February 2021

La question de l’expérience est centrale pour comprendre la façon dont des problèmes publics émergent, impulsent de nouvelles politiques, conduisent à la transformation de milieux de vie, façonnent en retour des histoires de vie. Elle est ici resituée en relation à l’histoire du mouvement réformateur aux États-Unis, à la naissance de l’enquête sociologique et à la pensée pragmatiste de la démocratie au début du 20e siècle (ici représentée par John Dewey, mais aussi George H. Mead, Jane Addams, Mary P. Follett et Robert E. Park). Mais qu’est-ce que cette expérience ? L’objectif est de réactiver des catégories et des hypothèses pragmatistes pour décrire les troubles de l’expérience, leur conversion en situations problématiques, la part de l’émotion et de l’évaluation dans la canalisation de l’attention publique, et sa réorientation par l’attribution de causes et l’imputation de responsabilités. Dans la perspective d’une écologie de l’expérience publique, on rappelle enfin la place centrale de l’enquête et de l’expérimentation, avec leur dimension esthétique, dans la formation des problèmes publics.
La Segunda Celestina de Feliciano de Silva a la luz de nuevos datos sobre su biografía
Authors: Cáseda Teresa Jesús Fernando
Published: February 2021

Este estudio aporta un buen número de documentos desconocidos que dan luz sobre la biografía de Feliciano de Silva, localizados en el Archivo Histórico de la Nobleza. Da noticia de su fecha de nacimiento (1479), asunto que tanto debate ha suscitado a lo largo de los años, y desvela muchos aspectos relativos a su familia, a su situación económica, etc. Establece el origen de diversos personajes de su continuación de La Celestina a partir de su biografía: su primo el «arcediano» o el «arcediano el viejo», Polandria —su esposa Gracia Fe—, Celestina —probable-mente Catalina Maldonado—, etc. Estudia algunas curiosas relaciones onomásticas de la obra con los nombres que aparecen en otras obras de sus amigos judeo-conversos portugueses o de Núñez de Reinoso. Y sitúa el origen de otros muchos personajes de su comedia: por ejemplo el juego onomástico con su propio nombre en el caso de Félides o Filínides, que ocultan en ambos casos a Feliciano de Silva.
Materialización del dolor de Celestina en la Tercera parte de la Tragicomedia de Celestina
Authors: García Álvarez Juan Pablo Mauricio
Published: February 2021

En este artículo se analiza el dolor de Celestina como un elemento configurador del personaje en el texto escrito por Gómez de Toledo. Las heridas físicas y emocionales se convierten en una materialización de los valores morales y sociales de la vieja, mostrando con ello un tratamiento original. El análisis del dolor nos permite construir una cultura emocional representada en la celestinesca.
Los territorios del cuerpo en disputa: aborto, estigma y ciberfeminismo
Authors: Cevallos Castells María Rosa
Published: February 2021

En países como Kenia y Ecuador el aborto es un tema de vida o muerte para muchas mujeres que atraviesan embarazos no deseados. Kenia tiene la tasa más alta de África de mortalidad por aborto inseguro; alrededor de 6.000 mujeres mueren cada año por causas relacionadas con el aborto. Así mismo, en Ecuador el aborto inseguro es una de las principales causas de muerte materna; en 2018 al menos 18 mujeres murieron por causas relacionadas con abortos inseguros (FLACSO, 2019).
Deģenerēti ZnO nanokristāli: sintēze, īpašības un pielietojums
Authors:   , Zukuls Anzelms
Published: February 2021

Promocijas darbs veltīts Ga3+ dopētu deģenerētu ZnO pusvadītāju nanokristālu solvotermālajai sintēzei un iegūto materiālu kristāliskās struktūras, elektronu stāvokļu struktūras un morfoloģijas, kā arī optisko un magnētisko īpašību izpētei. Eksperimentālajā daļā pētīti veidi, kā panākt augstāku dopējuma pakāpi un brīvo lādiņnesēju koncentrāciju, kā arī to ietekme uz lokalizētu virsmas plazmonu rezonanses izsauktu gaismas absorbciju infrasarkanā spektra daļā vai pārejas metālu (Fe3+, Ni2+, Mn2+) dopēta ZnO magnetizācijas raksturu. Literatūras apskatā apkopota informācija par laika posmu no 1954. līdz 2020. gadam, izmantojot jaunāko literatūru, kas atrodama dažādās interneta datubāzēs. Literatūras apskatā apkopota informācija par dažādām nanokristālu sintēzes metodēm, kas tiek izmantotas cinka oksīdu saturošu nanokristālu izveidei, deģenerēti pusvadītāju metālu oksīdi, to optiskās īpašības, kā arī atšķaidīti magnētiski oksīdu pusvadītāju nanokristāli. Rezultātu izvērtējumā aprakstīti ar solvotermālo sintēzes metodi iegūtie un dažādi dopētie ZnO nanokristāli, to optiskās, morfoloģiskās un fizikālās īpašības. Pētījumu rezultāti liecina par iespēju pielāgot ZnO nanokristālos ievadītā gallija daudzumu, kontrolējot šķīdinātājus un piedevas. Ar pārejas metāliem un galliju kodopēto ZnO nanokristālu magnētiskās īpašības mainās atkarībā no ievadītā gallija daudzuma, kā arī, veicot fotodopēšanu Ga dopētiem ZnO nanokristāliem, iespējams mainīt to brīvo lādiņnesēju koncentrāciju.
complexFuzzy: A novel clustering method for selecting training instances of cross-project defect prediction
Authors: Ozturk Muhammed Maruf
Published: February 2021

Over the last decade, researchers have investigated to what extent cross-project defect prediction (CPDP) shows advantages over traditional defect prediction settings. These works do not take training and testing data of defect prediction from the same project. Instead, dissimilar projects are employed. Selecting proper training data plays an important role in terms of the success of CPDP. In this study, a novel clustering method named complexFuzzy is presented for selecting training data of CPDP. The method is developed by determining membership values with the help of some metrics which can be considered as indicators of complexity. First, CPDP combinations are created on 29 different data sets. Subsequently, complexFuzzy is evaluated by considering cluster centers of data sets and comparing some performance measures including area under the curve (AUC) and F-measure. The method is superior to other five comparison algorithms in terms of the distance of cluster centers and prediction performance.
Circle formation by asynchronous opaque robots on infinite grid
Authors: Adhikary Ranendu , Kundu Manash Kumar , Sau Buddhadeb
Published: February 2021

This paper presents a distributed algorithm for circle formation problem under the infinite grid environment by asynchronous mobile opaque robots. Initially all the robots are acquiring distinct positions and they have to form a circle over the grid. Movements of the robots are restricted only along the grid lines. They do not share any global co-ordinate system. Robots are controlled by an asynchronous adversarial scheduler that operates in Look-Compute-Move cycles. The robots are indistinguishable by their nature, do not have any memory of their past configurations and previous actions. We consider the problem under luminous model, where robots communicate via lights, other than that they do not have any external communication system. Our protocol solves the  circle formation problem using seven colors. A subroutine of our algorithm also solves the line formation problem using three colors.
Intuitionistic fuzzy index matrix representation of color images
Authors:   Department of Mathematics, Vellalar College for Women, Nivendhaa R. K. , Parvathi R. ,   Department of Mathematics, Vellalar College for Women
Published: February 2021

It is usual in image processing that binary (black & white) and gray images are represented by crisp sets and fuzzy sets respectively. In this paper, an attempt has been made to represent a color image (RGB) using intuitionistic fuzzy index matrices. The objective of this representation is to apply mathematical operators on intuitionistic fuzzy index matrices in processing RGB images.
Generalized net model of a biometric authentication system based on palm geometry and palm vein matching using intuitionistic fuzzy evaluations
Authors:   Prof. Dr. Assen Zlatarov” University, Ivanova Zhelyana , Bureva Veselina ,   Prof. Dr. Assen Zlatarov” University
Published: February 2021

In the current research work a multimodal biometric system is investigated. It combines the palm vein authentication and palm geometry recognition methods. The system will be used to manage the access control. The apparatus of generalized nets is applied to model the biometric authentication processes. The constructed generalized net model of biometric authentication system based on palm geometry and palm vein matching using intuitionistic fuzzy evaluations can be used for simulation of the real processes. The intuitionistic fuzzy evaluations are used to compare the user traits with the templates stored in database.
Generalized nets and intuitionistic fuzziness as tools for modelling of data mining processes and tools
Authors:   Department of Bioinformatics and Mathematical Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Atanassov Krassimir ,   Prof. Asen Zlatarov University
Published: February 2021

The possibilities for using the apparatuses of generalized nets and intuitionistic fuzzy sets as means for modelling and evaluation of Data Mining processes and tools are discussed and illustrated by examples.
Unexpected mitochondrial lineage diversity within the genusAlonellaSars, 1862 (Crustacea: Cladocera) across the Northern Hemisphere
Authors: Neretina Anna N. , Karabanov Dmitry P. , Sacherova Veronika , Kotov Alexey A.
Published: February 2021

Representatives of the genusAlonellaSars (Crustacea: Cladocera: Chydorinae) belong to the smallest known water fleas. Although species ofAlonellaare widely distributed and often abundant in acidic and mountain water bodies, their diversity is poorly studied. Morphological and genetic approaches have been complicated by the minute size of these microcrustaceans. As a result, taxonomists have avoided revising these species. Here, we present genetic data onAlonellaspecies diversity across the Northern Hemisphere with particular attention to theA. excisaspecies complex. We analyzed 82 16S rRNA sequences (all newly obtained), and 78 COI sequences (39 were newly obtained). The results revealed at least twelve divergent phylogenetic lineages, possible cryptic species, ofAlonella, with different distribution patterns. As expected, the potential species diversity of this genus is significantly higher than traditionally accepted. TheA. excisacomplex is represented by nine divergent clades in the Northern Hemisphere, some of them have relatively broad distribution ranges and others are more locally distributed. Our results provide a genetic background for subsequent morphological analyses, formal descriptions ofAlonellaspecies and detailed phylogeographical studies.
Coronavirus Disease (COVID-19) Outbreak and Adaptive Immune System of the Body: A Review
Authors: Deep Amar , Swaroop Suchit , Kumar Ajay , Rungta Sumit
Published: February 2021

In December 2019, a severe disease with an unknown aetiology has appeared in a Wuhan City, Hubei province, China. Immediately, it was identified as novel Coronavirus Disease (COVID-19) that has spread globally and also called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and was characterised in China. As we know the presence of viruses with new genetic diversity in nature, it is unclear from where this virus has evolved and transmitted to humans at the first place. As the outbreak of COVID-19 progresses, epidemiological data is essential to guide situational awareness, and intervention strategies and also immune response in COVID-19. That’s why treatments dealing with the immune-pathology of SARS-CoV-2 infection is a major issue for focus now-a-days, while a rapid and well-coordinated immune response represent the first line of defence against the viral infection. Presently, limited data and information is available on the host innate and adaptive immune status of SARS-CoV-2 infected patients. Here, authors described that how the immune system plays the first line of defence against viral infection, and attempt to compile, accumulate and disseminate the immune response information on COVID-19 from the World Health Organisation (WHO), MEDLINE, Embase, Cochrane Library, Centers for Disease Control and Prevention COVID-19 Research Database and trials registries for the recognition in progress and finished studies, cohort, and from Randomised Controlled Trials (RCTs).
Celebrity Advertisement and Young Voters’ Choice of Political Candidates in Ghana: Looking Through the Lens of Tertiary Students
Authors: Asomaning Rudolph , Ababio Evans
Published: February 2021

The drive to win elections by political candidates has resulted in the employment of marketing tools such as celebrity advertising. Celebrities have been engaged in endorsing various political candidates. The current study sought to investigate the influence of celebrity advertisement on young voters’ choice of political candidates in Ghana. The study employed the quantitative technique through regression statistics to establish the influence. A sample of about 400 students (respondents) was drawn for the study. The results showed that there was weak positive but significant influence of celebrity advertisement on young voters’ choice of political candidates. This indicates that political parties that engage celebrities in advertising for their candidates and brands stand the chance of winning over young voters to vote for their candidates. It is recommended that celebrity advertising should be designed in such a way that it could improve the capacity of creating long lasting impact in the minds of young voters, influencing young voters to better recognize political candidates at voting points as well as influencing recalling of political candidates during national elections. Policies makers should put measures in place to regulate the contents and type of adverts that can be run by celebrities for political parties since most of these adverts are directed to and consumed by young voters.
Effects of Feeding Frequency on Growth Performance and Production of Labeo rohita (Hamilton, 1822) Reared in Cage
Authors: Sarker Md. Al-Amin , Jasmine Saleha , Okela Mst. Sultanan
Published: February 2021

Optimum feeding schedule is one of the main things for the proper growth of fish and other animals. A study was conducted to optimize the effects of different feeding frequencies on growth performance and production of Rui (Labeo rohita) under pond cage culture system in Rajshahi, Bangladesh. Labeo rohita with an average weight of 302.23±4.07g (mean ± SD) were randomly stocked in 9 cages at 30 fish/cage in all the treatment. Fish were fed (4% of body weight) a commercial floating feed with three different feeding schedules: feeding of fish thrice daily in T1treatment; twice in T2 treatment and once in T3 treatment. Water quality parameters were measured during the study period. The physico-chemical parameters of pond water were within suitable ranges for fish culture in cages. The obtained values of the water quality parameters were temperature 28.26 to 28.46°C, pH 6.91 to 6.94, DO 5.04 to 5.33 mg/l, CO2 2.95 to 3.02 mg/L. The mean final weight gain was significantly highest in T1 (345.05 g) a followed by T2 (324.66 g) and T3 (257.82 g). The Specific growth rate (SGR) value were significantly higher in T1 treatment (0.91% bwd-1; Body weight per day) than T2 (0.87% bwd-1) and T3 treatment (0.73% bwd-1). The feed conversion ratio (FCR) value was significantly lower in T1 fish group (2.72) than other two T2 (2.84) and T3 (3.44) treatments. The fish productions were 18.13, 17.55 and 15.67 kg/cage/cycle in T1, T2 and T3 respectively. The highest net profit was found (Bangladeshi Taka, BDT 1445.38) in T1 compared to T2 (BDT 1329.24) and T3 treatment (BDT 937.99). The cost benefit ratio (CBR) was significantly higher in T1 (0.57) than T2 (0.53) and T3 (0.37). The feeding schedule three times in a day was most suitable than other two schedules.
Assessment of Some Heavy Metals and Iron Parameters amongst Dumpsite Scavengers in Port Harcourt, Nigeria
Authors: Godwin A. S. , Brown H. , Nwachuku E. O.
Published: February 2021

Aim: The aim of the study was to determine the levels of some heavy metals, namely Cadmium (Cd), Lead (Pd), and Iron (Fe) in waste scavengers in port-Harcourt, Nigeria

Study Design:  This study is a cross-sectional observational study.

Place and Duration of Study: This study was conducted in Port Harcourt, Rivers State, Nigeria, between March, 2019 and October, 2019.

Methodology: A total of 170 subjects of ages between 16 to 43 years. Of this, 100 were dumpsite scavengers while 70 were apparently healthy control subjects. The subjects involved in this study gave their informed consent and had no history of diabetes mellitus, hypertension, and renal and hepatic disorders, and have been in scavenging activity for at least one year. Three milliliters (3ml) of blood was taken from each subject and put in plain bottles. The serum obtained was put in plain bottles and stored at -200C prior to analysis. The heavy metals were assayed using the Atomic Absorption Spectrophotometry (AAS) while the hepatic parameters were assayed using Mindray Biochemistry auto analyzer (Model BS120, Shenzhen, China). Serum ferritin was assayed using enzyme immunoassay while serum transferrin was done using colorimetric method. Data obtained were analyzed using Student’s t test and Pearson’s correlation.

Results: The body mass index (BMI) of the scavengers were significantly lower than that of the control subjects (p=.0001). The activities of the liver enzymes AST, ALT and ALP were significantly higher in the scavengers compared to the control subjects (p=.0001). The levels of total proteins, albumin and globulin of the scavengers were significantly lower than those of the control subjects (p=.0001). The levels of serum iron, transferrin and ferritin were similarly lower in the scavengers compared to the control subjects (p=.0001). However, the levels of cadmium and lead were significantly higher in the scavengers compared to the control subjects (p=.0001).

Conclusion: These findings indicate possible biochemical derangements in the scavengers due to their exposure to the hazards associated with the scavenging activity.
Assessment of Health Related Quality of Life among Chronic Kidney Disease Patients: Challenges for Nephrologists in Pakistan
Authors: Malik Madeeha , Nisha Iter Un , Hussain Azhar
Published: February 2021

Introduction: During the past few decades, health related quality of life has been considered as an important predictor for positive health outcomes. Health-related quality of life assessment helps in determining the impact of disease on the everyday life of patients. Chronic kidney disease severely affects health related quality of life of patient.

Objective: The objective of this study was to assess health related quality of life among patients with chronic kidney diseases in Pakistan.

Methodology: A descriptive cross-sectional study design was used. Study respondents included CKD pre-dialysis and dialysis patients with or without comorbidities visiting tertiary care facilities located in twin cities of Pakistan. Sample size was calculated to be 386 pharmacists to achieve 95% confidence level with 5% margin of error. Convenient sampling technique was used to select respondents. A pre- validated questionnaire Kidney Disease Quality of Life questionnaire (KDQoL-36) was used. Data was coded and analyzed using SPSS 21 after collection. Mann-Whitney and Kruskal-Wallis (p ≥ 0.05) tests were according to different demographic variables.

Results: The results of the current study showed lowest scores for HRQoL in domain of physical health composite (30.77±11.16) followed by domain of symptoms and problems associated with CKD whereas daily life had the highest scores. The results highlighted that females had better HRQoL in all domains mental health (46.30, ± 8.73), burden of kidney disease (69.47, ± 32.35), symptoms (29.79, ± 31.22) and effect of disease on daily activities (40.96, ± 32.11) while lowest score for physical health (30.90, ± 10.34). Married respondents had better HRQoL among all domains than unmarried patients except for physical health (32.26, ± 10.7). A significant difference (p ≥ 0.05) was observed among different domains of HRQoL of CKD patients with respect to different genders, marital status, age groups and qualification levels. Males had relatively better physical health scores but their daily activities were also affected more by their disease. Married respondents had relatively better HRQoL among all domains than unmarried patients except for physical health. No significant difference (p ≥ 0.05) was observed for different stages of disease.

Conclusion: The present study concluded that patients with CKD had poor HRQoL regardless of novel treatments availability. A negative impact was observed across all domains of health related quality of life among chronic kidney disease patients. Necessary programs focusing on health education for patients with low literacy levels should be initiated to increase health awareness and improve mental health among CKD patients.
Does Allergic Rhinitis have any Effect on Choroidal Thickness?
Authors: Kiliç Raşit , Soyaliç Harun
Published: February 2021

Aim: The aim of this study is to compare the choroidal thickness between patients with allergic rhinitis (AR) and healthy controls.

Study Design: Prospective case-control study.

Methodology: This cross sectional case control study consisted of 52 patients with AR and 52 healthy subjects. The choroidal thicknesses were measured horizontally with the digital calipers provided by the Heidelberg Spectralis software. The points of measurements were at the subfovea, 1500 µm nasal and 1500 µm temporal to the center of the fovea. The right eye was assessed in all participants.

Results: There was no statistically significant difference between the groups for age and gender distribution, intraocular pressure and spherical equivalent. Mean subfoveal choroidal thickness, nasal choroidal thickness and temporal choroidal thickness were 382.1±121.7, 328.6±111.8 and 368.1±98.2 in AR patients and 378.5±87, 309±77 and 354.2±94.2 in healthy subjects respectively. These differences were not found statistically significant (P˃0.05).

Conclusion: Choroidal thickness in AR patients was found to be thicker, but not statistically significant.
Assessment of Nocturnal Enuresis Management in Children in the Advanced Diagnostic Center in Khartoum State
Authors: Osman Mhdia Elhadi , Bashar Aaza Ahmed , Khalifa Nasrin E. , Elagib Halima Mustafa
Published: February 2021

Nocturnal enuresis is defined as nighttime bedwetting in children five years of age or older in the absence of neurological or structural problems affecting the bladder. A wide variety of interventions are used to treat nocturnal enuresis include simple behavioral intervention, enuresis alarm, and pharmacological treatment—the aim of the study to assess the management of nocturnal enuresis in children. A prospective cross-sectional study included 150 children attend the advanced diagnostic center. Data collected by direct interview questionnaire was tested –coded and analyzed by SPSS version 20 in tables and graph &excel. The result of this study showed that the highest treatment adopted was simple-cognitive behavioral therapy (87%), with the highest (94.7%) of patient surveyed adopted lifting and awaking technique,(38%) of patient surveyed have taken imipramine, (26%) of patient surveyed have taken 75mg dose of imipramine, (37%)of patients surveyed had a full response from imipramine therapy. The study showed that the first-line treatment that is needed is simple-cognitive behavioral therapy with instruction regarding diet and fluids, and it is very useful. The main drug was used in the treatment of nocturnal enuresis is imipramine with a dose of 75mg.
Efficacy and safety of immune checkpoint inhibitor monotherapy in elderly patients with non‐small cell lung cancer
Authors: Chikaishi Yasuhiro , Inoue Masaaki , Kusanagi Kasumi , Honda Yohei , Yoshida Junichi , Tanaka Masao
Published: January 2021

The efficacy and safety of immune checkpoint inhibitor (ICI) monotherapy in elderly patients with non‐small cell lung cancer (NSCLC) remain unclear, especially in patients older than 80 years. We retrospectively reviewed the records of 10 patients older than 80 years with NSCLCs treated by ICIs. The median age was 85 years (range, 82‐93 years), and 7 patients were men. The median length of follow‐up was 13 months (range, 4.5‐23 months). Eight patients had adenocarcinoma (3 of whom had exon 19 deletions), and two had squamous cell carcinoma. Expression of programmed cell death ligand 1 (PD‐L1) was ≥ 50% in 3 patients, between 1% and 49% in 4 patients, < 1% in 1 patient, and undetected in 2 patients. Patients with undetected PD‐L1 underwent transbronchial lung biopsy. Performance status was graded zero, one, and two in two, seven, and one patients, respectively. First‐, second‐, and third‐line treatments were administered to three, three, and four patients, respectively. The 2‐year overall survival rate was 30.0% (median, 285 days). Time to treatment failure rate on the 2 years was 10.0% (median, 167 days). One patient achieved a partial response, and one achieved a complete response. ICI‐associated adverse events occurred in five patients. In summary, ICIs were effective in some patients older than 80 years; however, some experienced adverse effects. Elderly patients must be selected carefully for ICI treatment.
Correction to: The Seine River Basin
Authors: Flipo Nicolas , Labadie Pierre , Lestel Laurence
Published: January 2021

The below mentioned chapters of this volume were published online first with the copyright year 2019 instead of 2020.
In vitro and in vivo biological activities of azulene derivatives with potential applications in medicine
Authors: Bakun Paweł , Czarczynska-Goslinska Beata , Goslinski Tomasz , Lijewski Sebastian
Published: January 2021

Azulene is an aromatic hydrocarbon that possesses a unique chemical structure and interesting biological properties. Azulene derivatives, including guaiazulene or chamazulene, occur in nature as components of many plants and mushrooms, such as Matricaria chamomilla, Artemisia absinthium, Achillea millefolium, and Lactarius indigo. Due to physicochemical properties, azulene and its derivatives have found many potential applications in technology, especially in optoelectronic devices. In medicine, the ingredients of these plants have been widely used for hundreds of years in antiallergic, antibacterial, and anti-inflammatory therapies. Herein, the applications of azulene, its derivatives and their conjugates with biologically active compounds are presented. The potential use of these compounds concerns various areas of medicine, including anti-inflammatory with peptic ulcers, antineoplastic with leukemia, antidiabetes, antiretroviral with HIV-1, antimicrobial, including antimicrobial photodynamic therapy, and antifungal.
Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial
Authors: Assfalg Robin , Knoop Jan , Hoffman Kristi L. , Pfirrmann Markus , Zapardiel-Gonzalo Jose Maria , Hofelich Anna , Eugster Anne , Weigelt Marc , Matzke Claudia , Reinhardt Julia , Fuchs Yannick , Bunk Melanie , Weiss Andreas , Hippich Markus , Halfter Kathrin , Hauck Stefanie M. , Hasford Jörg , Petrosino Joseph F. , Achenbach Peter , Bonifacio Ezio , Ziegler Anette-Gabriele
Published: January 2021

Aims/hypothesis

Oral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and immune response actions on immunity and the gut microbiome.

Methods

A phase I/II randomised controlled trial was performed in a single clinical study centre in Germany. Participants were 44 islet autoantibody-negative children aged 6 months to 2.99 years who had a first-degree relative with type 1 diabetes and a susceptibleHLA DR4-DQ8-containing genotype. Children were randomised 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months using a web-based computer system. The primary outcome was immune efficacy pre-specified as induction of antibody or T cell responses to insulin and measured in a central treatment-blinded laboratory.

Results

Randomisation was performed in 44 children. One child in the placebo group was withdrawn after the first study visit and data from 22 insulin-treated and 21 placebo-treated children were analysed. Oral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in children who received both insulin (54.5%) and placebo (66.7%), and the trial did not demonstrate an effect on its primary outcome (p = 0.54). In exploratory analyses, there was preliminary evidence that the immune response and gut microbiome were modified by theINSgenotype Among children with the type 1 diabetes-susceptibleINSgenotype (n = 22), antibody responses to insulin were more frequent in insulin-treated (72.7%) as compared with placebo-treated children (18.2%;p = 0.03). T cell responses to insulin were modified by treatment-independent inflammatory episodes.

Conclusions/interpretation

The study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe, but was not associated with an immune response as predefined in the trial primary outcome. Exploratory analyses suggested that antibody responses to oral insulin may occur in children with a susceptibleINSgenotype, and that inflammatory episodes may promote the activation of insulin-responsive T cells.

Trial registration

Clinicaltrials.gov NCT02547519

Funding

The main funding source was the German Center for Diabetes Research (DZD e.V.)

Graphical abstract
Retinal venular tortuosity and fractal dimension predict incident retinopathy in adults with type 2 diabetes: the Edinburgh Type 2 Diabetes Study
Authors:   on behalf of the Edinburgh Type 2 Diabetes Study (ET2DS) investigators, Forster Rachel B. , Garcia Emmanuel Sandoval , Sluiman Anniek J. , Grecian Sheila M. , McLachlan Stela , MacGillivray Tom J. , Strachan Mark W. J. , Price Jackie F.
Published: January 2021

Aims/hypothesis

Our aim was to determine whether a range of prespecified retinal vessel traits were associated with incident diabetic retinopathy in adults with type 2 diabetes.

Methods

In the prospective observational cohort Edinburgh Type 2 Diabetes Study of 1066 adults with type 2 diabetes, aged 60–75 years at recruitment, 718 were free from diabetic retinopathy at baseline. Baseline retinal traits including vessel widths, tortuosity (curvature) and fractal dimensions (network complexity), were quantified using fundus camera images and semiautomated software, and analysed using logistic regression for their association with incident diabetic retinopathy over 10 years.

Results

The incidence of diabetic retinopathy was 11.4% (n = 82) over 10 years. After adjustment for a range of vascular and diabetes-related risk factors, both increased venular tortuosity (OR 1.51; 95% CI 1.15, 1.98; p = 0.003) and decreased fractal dimension (OR 0.75; 95% CI 0.58, 0.96; p = 0.025) were associated with incident retinopathy. There was no evidence of an association with arterial tortuosity, and associations between measurements of vessel widths and retinopathy lost statistical significance after adjustment for diabetes-related factors and vascular disease. Adding venular tortuosity to a model including established risk factors for diabetic retinopathy (HbA1c, BP and kidney function) improved the discriminative ability (C statistic increased from 0.624 to 0.640, p = 0.013), but no such benefit was found with fractal dimension.

Conclusions/interpretation

Increased retinal venular tortuosity and decreased fractal dimension are associated with incident diabetic retinopathy, independent of classical risk factors. There is some evidence that venular tortuosity may be a useful biomarker to improve the predictive ability of models based on established retinopathy risk factors, and its inclusion in further risk prediction modelling is warranted.

Graphical abstract
Identification of potential novel drug resistance mechanisms by genomic and transcriptomic profiling of colon cancer cells with p53 deletion
Authors: Kadioglu Onat , Saeed Mohamed , Mahmoud Nuha , Azawi Shaymaa , Mrasek Kristin , Liehr Thomas , Efferth Thomas
Published: January 2021

TP53 (p53) is a pivotal player in tumor suppression with fifty percent of all invasive tumors displaying mutations in the TP53 gene. In the present study, we characterized colon cancer cells (HCT116 p53 −/−) with TP53 deletion, a sub-line derived from HCT116-p53 +/+ cells. RNA sequencing and network analyses were performed to identify novel drug resistance mechanisms. Chromosomal aberrations were identified by multicolor fluorescence in situ hybridization (mFISH) and array comparative genomic hybridization (aCGH). Numerous genes were overexpressed in HCT116 p53 −/− cells: RND3/RhoE (235.6-fold up-regulated), DCLK1 (60.2-fold up-regulated), LBH (31.9-fold up-regulated), MYB (28.9-fold up-regulated), TACSTD2 (110.1-fold down-regulated), NRIP1 (81.5-fold down-regulated) and HLA-DMB (69.7-fold down-regulated) are among the identified genes with potential influence on multidrug resistance (MDR) and they are associated with cancer progression and tumorigenesis, according to previously published studies. Probably due to TP53 deletion, disturbances in DNA repair and apoptosis are leading to aberrancies in cellular and organismal organization, ultimately increasing tumorigenesis and cancer progression potential. With NFκB, PI3K and HSP70, being at the center of merged protein network, and TH1-2 pathways, being among the influenced pathways, it can be speculated that the inflammatory pathway contributes to a resistance phenotype together with cell cycle regulation and heat-shock response. HCT116-p53 −/− cells have more chromosomal aberrations, gains and losses in copy numbers than HCT116-p53 +/+ cells. In conclusion, numerous genomic aberrations, which might be associated with yet unknown drug resistance mechanisms, were identified. This may have important implications for future treatment strategies.
The Efficacy of Anti-Arrhythmic Drugs in Children With Idiopathic Frequent Symptomatic or Asymptomatic Premature Ventricular Complexes With or Without Asymptomatic Ventricular Tachycardia: a Retrospective Multi-Center Study
Authors: Bertels Robin A. , Kammeraad Janneke A. E. , Zeelenberg Anna M. , Filippini Luc H. , Knobbe Ingmar , Kuipers Irene M. , Blom Nico A.
Published: January 2021

The aim of the study is to compare the efficacy of flecainide, beta-blockers, sotalol, and verapamil in children with frequent PVCs, with or without asymptomatic VT. Frequent premature ventricular complexes (PVCs) and asymptomatic ventricular tachycardia (VT) in children with structurally normal hearts require anti-arrhythmic drug (AAD) therapy depending on the severity of symptoms or ventricular dysfunction; however, data on efficacy in children are scarce. Both symptomatic and asymptomatic children (≥ 1 year and < 18 years of age) with a PVC burden of 5% or more, with or without asymptomatic runs of VT, who had consecutive Holter recordings, were included in this retrospective multi-center study. The groups of patients receiving AAD therapy were compared to an untreated control group. A medication episode was defined as a timeframe in which the highest dosage at a fixed level of a single drug was used in a patient. A total of 35 children and 46 medication episodes were included, with an overall change in PVC burden on Holter of -4.4 percentage points, compared to -4.2 in the control group of 14 patients. The mean reduction in PVC burden was only significant in patients receiving flecainide (− 13.8 percentage points; N = 10; p = 0.032), compared to the control group and other groups receiving beta-blockers (− 1.7 percentage points; N = 18), sotalol (+ 1.0 percentage points; N = 7), or verapamil (− 3.9 percentage points; N = 11). The efficacy of anti-arrhythmic drug therapy on frequent PVCs or asymptomatic VTs in children is very limited. Only flecainide appears to be effective in lowering the PVC burden.
Frailty predicts outcome of partial nephrectomy and guides treatment decision towards active surveillance and tumor ablation
Authors: Walach M. T. , Wunderle M. F. , Haertel N. , Mühlbauer J. K. , Kowalewski K. F. , Wagener N. , Rathmann N. , Kriegmair M. C.
Published: January 2021

Purpose

To examine frailty and comorbidity as predictors of outcome of nephron sparing surgery (NSS) and as decision tools for identifying candidates for active surveillance (AS) or tumor ablation (TA).

Methods

Frailty and comorbidity were assessed using the modified frailty index of the Canadian Study of Health and Aging (11-CSHA) and the age-adjusted Charlson-Comorbidity Index (aaCCI) as well as albumin and the radiological skeletal-muscle-index (SMI) in a cohort of n = 447 patients with localized renal masses. Renal tumor anatomy was classified according to the RENAL nephrometry system. Regression analyses were performed to assess predictors of surgical outcome of patients undergoing NSS as well as to identify possible influencing factors of patients undergoing alternative therapies (AS/TA).

Results

Overall 409 patient underwent NSS while 38 received AS or TA. Patients undergoing TA/AS were more likely to be frail or comorbid compared to patients undergoing NSS (aaCCI: p < 0.001, 11-CSHA: p < 0.001). Gender and tumor complexity did not vary between patients of different treatment approach. 11-CSHA and aaCCI were identified as independent predictors of major postoperative complications (11-CSHA ≥ 0.27: OR = 3.6, p = 0.001) and hospital re-admission (aaCCI ≥ 6: OR = 4.93, p = 0.003) in the NSS cohort. No impact was found for albumin levels and SMI. An aaCCI > 6 and/or 11-CSHA ≥ 0.27 (OR = 9.19, p < 0.001), a solitary kidney (OR = 5.43, p = 0.005) and hypoalbuminemia (OR = 4.6, p = 0.009), but not tumor complexity, were decisive factors to undergo AS or TA rather than NSS.

Conclusion

In patients with localized renal masses, frailty and comorbidity indices can be useful to predict surgical outcome and support decision-making towards AS or TA.
Flow visualization and skin friction determination in transitional channel flow
Authors: Yimprasert Sattaya , Kvick Mathias , Alfredsson P. Henrik , Matsubara Masaharu
Published: January 2021

The present study experimentally determines the transitional Reynolds number range for plane channel flow and characterizes its transitional state. The pressure along the channel is measured to determine the skin friction coefficient as function of Reynolds number from the laminar state, through the transitional region into the fully turbulent state. The flow structure was studied through flow visualisation which shows that as the Reynolds number increases from the laminar state the transitional region starts showing randomly occurring turbulent spots. With increasing Reynolds number the spots shift into oblique patches and bands of small scale turbulence that form across the channel width, together with large-scale streaky structures found in areas between the turbulent regions. An image analysing technique was used to determine the intermittency factor, i.e. the turbulence fraction in the flow, as function of Reynolds number. It is found that the skin friction coefficient reaches its turbulent value before the flow is fully turbulent (the intermittency factor is still below one). This suggests that the observed streaky structures in non-turbulent regions contribute to the enhancement of the wall-normal transfer of momentum. Also above the Reynolds numbers where the turbulent skin friction coefficient has been established large-scale features consisting of irregular streaky structures are found. They have an oblique shape similar to the non-turbulent and turbulent patches in the transitional flow indicating that the transition process is not fully complete even above the Reynolds number where the skin friction reaches its turbulent level.

Graphic abstract
Fundamental flow measurement capabilities of optical Doppler and time-of-flight principles
Authors: Fischer Andreas
Published: January 2021

In order to understand the fundamental measurement capabilities of different flow velocity measurement principles based on Mie scattering, a fundamental equation of how to calculate the shot noise limit for a respective signal model is derived. The derivation is based on the well-known rules of uncertainty propagation and yields the Cramér–Rao bound without the necessity to calculate the Fisher information. The derived equation is next applied to compare the shot noise limit for Doppler and time-of-flight principles including laser Doppler anemometry (LDA), planar Doppler velocimetry (PDV), laser-two-focus velocimetry (L2F), particle tracking velocimetry (PTV) and particle image velocimetry (PIV). The comparison is performed for an identical mean laser power, while two cases are studied in detail: measuring on a single seeding particle as well as measuring on multiple seeding particles and averaging. LDA, L2F and PTV/PIV obey a similar shot noise limit. For the case of a measurement on multiple seeding particles, the minimal achievable measurement uncertainty is directly proportional to the absolute value of the measured velocity component and inversely proportional to the spatial resolution. The respective shot noise limit for PDV is almost independent of the measured flow velocity component and the spatial resolution. Since PDV is sensitive with respect to a different flow velocity component depending on the observation direction, a comparison with the other principles is only reasonable to a certain extent. However, all shot noise limits in case of measuring on multiple seeding particles show the expected inverse proportionality to the square root of the total number of detected photons and thus also to the square root of the measurement time. Considering a comparable spatiotemporal resolution, an identical mean light power and typical measurement configurations, the PDV shot noise limit is the largest. As a final result, it is derived that each measurement principle obeys an uncertainty principle between position and the respective component of the wave vector, which is in agreement with Heisenberg’s uncertainty principle. Therefore, a common basis is provided to assess the fundamental measurement capabilities of Doppler and time-of-flight measurement systems on the basis of what is possible within the quantum mechanical constraints.

Graphic abstract
First experience with augmented reality neuronavigation in endoscopic assisted midline skull base pathologies in children
Authors: Pennacchietti Valentina , Stoelzel Katharina , Tietze Anna , Lankes Erwin , Schaumann Andreas , Uecker Florian Cornelius , Thomale Ulrich Wilhelm
Published: January 2021

Introduction

Endoscopic skull base approaches are broadly used in modern neurosurgery. The support of neuronavigation can help to effectively target the lesion avoiding complications. In children, endoscopic-assisted skull base surgery in combination with navigation systems becomes even more important because of the morphological variability and rare diseases affecting the sellar and parasellar regions. This paper aims to analyze our first experience on augmented reality navigation in endoscopic skull base surgery in a pediatric case series.

Patients and methods

A retrospective review identified seventeen endoscopic-assisted endonasal or transoral procedures performed in an interdisciplinary setting in a period between October 2011 and May 2020. In all the cases, the surgical target was a lesion in the sellar or parasellar region. Clinical conditions, MRI appearance, intraoperative conditions, postoperative MRI, possible complications, and outcomes were analyzed.

Results

The mean age of our patients was 14.5 ± 2.4 years. The diagnosis varied, but craniopharyngiomas (31.2%) were mostly represented. AR navigation was experienced to be very helpful for effectively targeting the lesion and defining the intraoperative extension of the pathology. In 65% of the oncologic cases, a radical removal was proven in postoperative MRI. The mean follow-up was 89 ± 79 months. There were no deaths in our series. No long-term complications were registered; two cerebrospinal fluid (CSF) fistulas and a secondary abscess required further surgery.

Conclusion

The implementation of augmented reality to endoscopic-assisted neuronavigated procedures within the skull base was feasible and did provide relevant information directly in the endoscopic field of view and was experienced to be useful in the pediatric cases, where anatomical variability and rarity of the pathologies make surgery more challenging.
Ten-year all-cause death following percutaneous or surgical revascularization in patients with prior cerebrovascular disease: insights from the SYNTAX Extended Survival study
Authors: Wang Rutao , Takahashi Kuniaki , Garg Scot , Thuijs Daniel J. F. M. , Kappetein Arie Pieter , Mack Michael J. , Morice Marie-Claude , Mohr Friedrich-Wilhelm , Curzen Nick , Davierwala Piroze , Milojevic Milan , van Geuns Robert Jan , Head Stuart J. , Onuma Yoshinobu , Holmes David R. , Serruys Patrick W.
Published: January 2021

Background

Coronary bypass artery grafting (CABG) has a higher procedural risk of stroke than percutaneous coronary intervention (PCI), but may offer better long-term survival. The optimal revascularization strategy for patients with prior cerebrovascular disease (CEVD) remains unclear.

Methods and results

The SYNTAXES study assessed the vital status out to 10 year of patients with three-vessel disease and/or left main coronary artery disease enrolled in the SYNTAX trial. The relative efficacy of PCI vs. CABG in terms of 10 year all-cause death was assessed according to prior CEVD. The primary endpoint was 10 year all-cause death. The status of prior CEVD was available in 1791 (99.5%) patients, of whom 253 patients had prior CEVD. Patients with prior CEVD were older and had more comorbidities (medically treated diabetes, insulin-dependent diabetes, metabolic syndrome, peripheral vascular disease, chronic obstructive pulmonary disease, impaired renal function, and congestive heart failure), compared with those without prior CEVD. Prior CEVD was an independent predictor of 10 year all-cause death (adjusted HR: 1.35; 95% CI: 1.04–1.73; p = 0.021). Patients with prior CEVD had a significantly higher risk of 10 year all-cause death (41.1 vs. 24.1%; HR: 1.92; 95% CI: 1.54–2.40; p < 0.001). The risk of 10 year all-cause death was similar between patients receiving PCI or CABG irrespective of the presence of prior CEVD (p-interaction = 0.624).

Conclusion

Prior CEVD was associated with a significantly increased risk of 10 year all-cause death which was similar in patients treated with PCI or CABG. These results do not support preferential referral for PCI rather than CABG in patients with prior CEVD.

Trial registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

Graphic abstract