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Drilling for the International Continental Scientific Drilling Program (ICDP) Early Jurassic Earth System and Timescale project (JET) was undertaken between October 2020 and January 2021. The drill site is situated in a small-scale synformal basin of the latest Triassic to Early Jurassic age that formed above the major Permian–Triassic half-graben system of the Cheshire Basin. The borehole is located to recover an expanded and complete succession to complement the legacy core from the Llanbedr (Mochras Farm) borehole drilled through 1967–1969 on the edge of the Cardigan Bay Basin, North Wales. The overall aim of the project is to construct an astronomically calibrated integrated timescale for the Early Jurassic and to provide insights into the operation of the Early Jurassic Earth system. Core of Quaternary age cover and Early Jurassic mudstone was obtained from two shallow partially cored geotechnical holes (Prees 2A to 32.2 m below surface (m b.s.) and Prees 2B to 37.0 m b.s.) together with Early Jurassic and Late Triassic mudstone from the principal hole, Prees 2C, which was cored from 32.92 to 651.32 m (corrected core depth scale). Core recovery was 99.7 % for Prees 2C. The ages of the recovered stratigraphy range from the Late Triassic (probably Rhaetian) to the Early Jurassic, Early Pliensbachian (Ibex Ammonoid Chronozone). All ammonoid chronozones have been identified for the drilled Early Jurassic strata. The full lithological succession comprises the Branscombe Mudstone and Blue Anchor formations of the Mercia Mudstone Group, the Westbury and Lilstock formations of the Penarth Group, and the Redcar Mudstone Formation of the Lias Group. A distinct interval of siltstone is recognized within the Late Sinemurian of the Redcar Mudstone Formation, and the name “Prees Siltstone Member” is proposed. Depositional environments range from playa lake in the Late Triassic to distal offshore marine in the Early Jurassic. Initial datasets compiled from the core include radiography, natural gamma ray, density, magnetic susceptibility, and X-ray fluorescence (XRF). A full suite of downhole logs was also run. Intervals of organic carbon enrichment occur in the Rhaetian (Late Triassic) Westbury Formation and in the earliest Hettangian and earliest Pliensbachian strata of the Redcar Mudstone Formation, where up to 4 % total organic carbon (TOC) is recorded. Other parts of the succession are generally organic-lean, containing less than 1 % TOC. Carbon-isotope values from bulk organic matter have also been determined, initially at a resolution of ∼ 1 m, and these provide the basis for detailed correlation between the Prees 2 succession and adjacent boreholes and Global Stratotype Section and Point (GSSP) outcrops. Multiple complementary studies are currently underway and preliminary results promise an astronomically calibrated biostratigraphy, magnetostratigraphy, and chemostratigraphy for the combined Prees and Mochras successions as well as insights into the dynamics of background processes and major palaeo-environmental changes.

In this research, our aim was to assess the occurrence of Staphylococcus aureus in a Hungarian large-scale dairy farm during the S. aureus control program conducted in the course of our studies. Furthermore, the phenotypic and genotypic properties of the isolates (type of haemolysis, antibiotic susceptibility, staphylococcal enterotoxin (SE) gene carrying ability and spa type) were determined. S. aureus was detected in all bulk tank milk samples collected during this study. Two different spa types were identified among the 17 strains isolated in the farm. A total of 14 of the 17 studied strains (82%) showed β-haemolysis on blood agar, 2/17 strains (12%) expressed double zone and 1/17 strains (6%) showed weak β-haemolysis. All strains were susceptible to most antibiotics tested (cefoxitin, chloramphenicol, clindamycin, erythromycin, gentamicin, tetracycline and trimethoprim/sulphamethoxazole), but all strains were resistant to penicillin G. A total of 11 of the 17 strains (65%) were found to harbour seg, sei, selm, seln, selo genes; 4/17 strains (24%) harboured sei, selm, seln, selo genes and 2/17 strains (11%) harboured sei gene. Since the new SEs/SEls can also cause foodborne outbreaks potentially and all strains were found to be resistant to penicillin G, it is essential to decrease and keep the prevalence of S. aureus low in the dairy farm and the implementation of the S. aureus control program is also highly justified. The results showed that the S. aureus count decreased by the end of our studies, so the control program was proved to be effective.

Math anxiety (MA) is a prevalent academic anxiety that can affect student mental health and academic performance worldwide. Using a very large sample of students in grades 7 to 10 (N = 7172) in Qatar, the present study examined the associations among gender, math anxiety, and attitudes towards Science, Technology, Engineering, and Mathematics (STEM). In addition, the factorial structure of the "Student Attitudes towards STEM Survey" (STEM-S) was examined. The results confirmed the three-factor structure of the STEM-S, with good-to-excellent reliabilities. Females exhibited higher levels of math anxiety and more negative attitudes towards the STEM domains than males across all grade groups. In addition, strong negative correlations were found between math anxiety and STEM-related attitudes. Multiple linear regression analysis revealed negative associations between math anxiety and attitudes towards STEM when gender was partialized out. In stark contrast, there were close to zero associations between gender and STEM-related attitudes when math anxiety was partialized out. Consistently, structure equation modelling reported that math anxiety mediated the associations between gender and STEM-related attitudes. Therefore, providing psychological interventions for high math-anxious female students may improve their representation in STEM-related education and occupations., Competing Interests: Declaration of competing interest None of the authors have any competing interests in the manuscript., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Drug resistance is a significant challenge in pancreatic ductal adenocarcinoma (PDAC), where stromal elements such as adipose-derived mesenchymal stem cells (ASCs) contribute to a chemoresistant tumor microenvironment (TME). This study explored the effects of oxaliplatin (OXP) and 5-fluorouracil (5-FU) on PDAC cells (Capan-1) and ASCs to investigate the mechanisms of chemoresistance. While OXP and 5-FU reduced Capan-1 viability in a dose- and time-dependent manner, ASCs demonstrated high resistance, maintaining > 90% viability even at cytotoxic doses. Transcriptomic analyses revealed OXP-induced transcriptional reprogramming in ASCs, with over 7000 differentially expressed genes, highlighting the pathways related to DNA damage response, cell cycle regulation, and stress-related signaling. In contrast, 5-FU elicited limited transcriptional changes, affecting only 192 genes. Cytokine proteome profiling revealed that OXP-treated ASCs significantly influenced the tumor microenvironment by promoting immune evasion (via IL-4, GM-CSF, IP-10, and GROα) and driving extracellular matrix remodeling (through EMMPRIN and DPPIV). In contrast, 5-FU induced comparatively weaker effects, primarily limited to hypoxia-related pathways. Although OXP reduced angiogenic factors, it paradoxically activated pro-survival pathways, thereby enhancing ASC-mediated tumor support. These findings underscore ASCs as modulators of chemoresistance via secretome alterations and stress adaptation. Therefore, future strategies should prioritize the precise targeting of tumor cells while also focusing on the development of personalized treatments to achieve durable therapeutic responses in PDAC.

Background : Monomicrobial Enterobacterales necrotizing fasciitis is associated with exceedingly high mortality rates. Although effective antimicrobial therapy is an important part of treatment, the traditional microbiological diagnostic methods are not fast enough to meaningfully influence early therapeutic decisions. Methods : Here, we report the application of the BioMérieux Biofire Filmarray Joint Infection Panel (BFJIP) for the rapid detection of the causative agent and susceptibility prediction in such a case. Aside from the BFJIP-based rapid diagnostic approach and culturing, the whole genome sequencing (WGS) of the causative agent was performed using Illumina MiSeq and Oxford Nanopore MinION platforms. Results : The BFJIP indicated the presence of K. pneumoniae , without KPC, VIM, IMP, NDM, OXA-48 carbapenemase genes, and CTX-M-type extended-spectrum beta-lactamases. Based on the WGS data, the isolate belonged to the K1-capsule-type ST23, harboured a pNTUH-2044-like plasmid, and was positive for all the virulence factors associated with this lineage. The conventional susceptibility results were also in accordance with the BFJIP results; the isolate lacked any of these acquired resistance mechanisms. Conclusions : Despite this being the first case of the successful identification of pathogenic bacteria in necrotising fasciitis using this assay, the BFJIP may become a useful tool for rapid identification of pathogens in necrotising fasciitis cases and guiding antimicrobial therapy for better clinical outcomes.

Cells have evolved various DNA repair mechanisms to prevent DNA damage from building up. Malfunctions during DNA repair can influence cellular homeostasis because they can bring on genomic instability through the improper recognition of DNA damage or dysregulation of the repair process. Maintaining proper DNA repair is also essential for stem cells (SCs), as they provide a differentiated cell population to the living organism. SCs are regularly used in personalized stem cell therapy. Patients must be treated with specific activators to produce these SCs effectively. This report investigated the impact of treating mesenchymal stem cells (MSC) with lipopolysaccharide, tumor necrosis factor, interferon-gamma, polyinosinic acid, interleukin 1 beta, while monitoring their transcription-related response using next-generation sequencing. RNA sequencing revealed robust gene expression changes, including those of specific genes encoding proteins implicated in DNA damage response. Stem cells can effectively repair specific DNA damages; moreover, they fail to undergo senescence or cell death when genetic lesions accumulate. Here, we draw attention to an elevated DNA repair activation following MSC induction, which may be the main reason for the ineffective stem cell transplantation and may also contribute to the genetic drift that can initiate tumor formation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Math anxiety (MA) is a worldwide appearing academic anxiety that can affect student mental health and deter students from math and science-related career choices., Method: Using the Arabic version of the Modified-Abbreviated Math Anxiety Scale (m-AMAS), the prevalence of MA was investigated in a very large sample of students (N = 10093) from grades 7 to 12 in Qatar., Results: The results showed a better fit to the original two-factor model of the m-AMAS (learning MA and Evaluation MA) than to a single-factor solution. This two-factor model was also confirmed in each grade. Notably, the distribution of MA scores was right-skewed, especially for learning MA. Using the inter-quartiles ranges, norms for MA were provided: A score of ≤16 indicates low MA whereas a score of ≥30 identifies high MA. Previous studies conducted in Western countries defined high math-anxious students as those who score above the 90th percentile corresponding to a score of 30 on the m-AMAS. Using this cut-off criterion, the current study found that one-fifth of students in Qatar were highly math-anxious, with a higher proportion of females than males. We also calculated the percentage of participants selecting each response category for each questionnaire item. Results showed that attending a long math class was the context that elicited the highest levels of learning MA. In contrast, having an unexpected math test was the situation that triggered the highest levels of evaluation MA., Conclusion: The prevalence of MA might vary across different cultures., (© 2024 British Psychological Society.)

Introduction: Adipose tissue-derived mesenchymal stem cells are promising contributors to regenerative medicine, exhibiting the ability to regenerate tissues and modulate the immune system, which is particularly beneficial for addressing chronic inflammatory ulcers and wounds. Despite their inherent capabilities, research suggests that pretreatment amplifies therapeutic effectiveness. Methods: Our experimental design exposed adipose-derived mesenchymal stem cells to six inflammatory factors for 24 h. We subsequently evaluated gene expression and proteome profile alterations and observed the wound closure rate post-treatment. Results: Specific pretreatments, such as IL-1β, notably demonstrated an accelerated wound-healing process. Analysis of gene and protein expression profiles revealed alterations in pathways associated with tissue regeneration. Discussion: This suggests that licensed cells exhibit potentially higher therapeutic efficiency than untreated cells, shedding light on optimizing regenerative strategies using adipose tissue-derived stem cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Szűcs, Monostori, Miklós, Páhi, Póliska, Kemény and Veréb.)

Adipose-derived mesenchymal stem cells are increasingly being used in regenerative medicine as cell therapy targets, including in the treatment of burns and ulcers. The regenerative potential of AD-MSCs and some of their immunological properties are known from in vitro studies; however, in clinical applications, cells are used in non-ideal conditions and can behave differently in inflammatory environments, affecting the efficacy and outcome of therapy. Our aim was to investigate and map the pathways that the inflammatory microenvironment can induce in these cells. High-throughput gene expression assays were performed on AD-MSCs activated with LPS and TNFα. Analysis of RNA-Seq data showed that control, LPS-treated and TNFα-treated samples exhibited distinct gene expression patterns. LPS treatment increased the expression of 926 genes and decreased the expression of 770 genes involved in cell division, DNA repair, the cell cycle, and several metabolic processes. TNFα treatment increased the expression of 174 genes and decreased the expression of 383 genes, which are related to cell division, the immune response, cell proliferation, and differentiation. We also map the biological pathways by further investigating the most altered genes using the Gene Ontology and KEGG databases. Secreted cytokines, which are important in the immunological response, were also examined at the protein level, and a functional assay was performed to assess wound healing. Activated AD-MSC increased the secretion of IL-6, IL-8 and CXCL-10, and also the closure of wounds. AD-MSCs presented accelerated wound healing under inflammation conditions, suggesting that we could use this cell in clinical application.

The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes simplex viruses 1 and 2 (HSV1 and HSV2), well-known human pathogens that can cause lifelong infections, can induce changes in MSCs. In non-healing ulcers, HSV infection is known to affect deeper tissue layers. In addition, HSV infection can recur after initially successful cell therapies. Our aim was to study the response of adipose-derived MSCs (ADMSCs) to HSV infection in vitro. After confirming the phenotype and differentiation capacity of the isolated cells, we infected the cells in vitro with HSV1-KOS, HSV1-532 and HSV2 virus strains. Twenty-four hours after infection, we examined the gene expression of the cells via RNA-seq and RT-PCR; detected secreted cytokines via protein array; and determined autophagy via Western blot, transmission electron microscopy (TEM) and fluorescence microscopy. Infection with different HSV strains resulted in different gene-expression patterns. In addition to the activation of pathways characteristic of viral infections, distinct non-immunological pathways (autophagy, tissue regeneration and differentiation) were also activated according to analyses with QIAGEN Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genome and Genome Ontology Enrichment. Viral infections increased autophagy, as confirmed via TEM image analysis, and also increased levels of the microtubule-associated protein light chain 3 (LC3B) II protein. We identified significantly altered accumulation for 16 cytokines involved in tissue regeneration and inflammation. Our studies demonstrated that HSV infection can alter the viability and immunological status of ADMSCs, which may have implications for ADMSC-based cell therapies. Alterations in autophagy can affect numerous processes in MSCs, including the inhibition of tissue regeneration as well as pathological differentiation.

The importance of three-dimensional (3D) models in pharmacological tests and personalized therapies is significant. These models allow us to gain insight into the cell response during drug absorption, distribution, metabolism, and elimination in an organ-like system and are suitable for toxicological testing. In personalized and regenerative medicine, the precise characterization of artificial tissues or drug metabolism processes is more than crucial to gain the safest and the most effective treatment for the patients. Using these 3D cell cultures derived directly from patient, such as spheroids, organoids, and bioprinted structures, allows for testing drugs before administration to the patient. These methods allow us to select the most appropriate drug for the patient. Moreover, they provide chance for better recovery of patients, since time is not wasted during therapy switching. These models could be used in applied and basic research as well, because their response to treatments is quite similar to that of the native tissue. Furthermore, they may replace animal models in the future because these methods are cheaper and can avoid interspecies differences. This review puts a spotlight on this dynamically evolving area and its application in toxicological testing., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Author(s).)

The distribution of effect sizes may offer insights about the research done and reported in a scientific field. We have evaluated 12 412 manually collected correlation effect sizes (Sample 1) and 31 157 computer-extracted correlation effect sizes (Sample 2) published in journals focused on social or developmental psychology. Sample 1 consisted of 243 studies from six journals published in 2010 and 2019. Sample 2 consisted of 5012 papers published in 10 journals between 2010 and 2019. The 25th, 50th and 75th effect size percentiles were 0.08, 0.17 and 0.33, and 0.17, 0.31 and 0.52 in Samples 1 and 2, respectively. Sample 2 percentiles were probably larger because Sample 2 only included effect sizes from the text but not from tables. In text authors may have emphasized larger correlations. Large sample sizes were associated with smaller reported correlations. In Sample 1 about 70% of studies specified a directional hypothesis. In 2010 no papers had power calculations, while in 2019 14% of papers had power calculations. These data offer empirical insights into the distribution of reported correlations and may inform the interpretation of effect sizes. They also demonstrate the importance of computation of statistical power and highlight potential reporting bias., (© 2022 The Authors.)

Background and Aims: From 2019 till the present, infections induced by the novel coronavirus and its mutations have posed a new challenge for healthcare. However, comparative studies on pediatric infections throughout waves are few. During four different pandemic waves, we intended to investigate the clinical and epidemiological characteristic of the pediatric population hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection., Methods: Between March 2020 and December 2021, we performed our retrospective research on children infected with the SARS-CoV-2 virus at the University of Szeged. We analyzed the data of all patients who required hospitalization due to positive results of SARS-CoV-2 tests (Nucleic Acid Amplification Test or rapid antigen test). Data analysis included demographic data, medical history, clinical findings, length of hospitalization, and complications, using medical records., Results: In this study, data from 358 coronavirus-infected children were analyzed. The most affected age group was children over 1 month and under 1 year (30.2%). The highest number of cases was recorded in the fourth wave (53.6%). Fever (65.6%), cough (51.4%), nasal discharge (35.3%), nausea and vomiting (31.3%), and decreased oral intake (28.9%) were the most common symptoms. The most common complications were dehydration (50.5%), pneumonia (14.9%), and bronchitis/bronchiolitis (14.5%). Based on RR values, there are considerable differences in the prevalence of the symptoms and complications between the different age groups and waves. Cox proportional hazard model analyzes showed that fever and tachypnoea had a relevant effect on days to recovery., Conclusions: We found trends similar to those previously published, overall statistics. The proportion of children requiring hospitalization varied from wave to wave, with the fourth wave affecting the Hungarian child population the most. Our findings suggest that hospitalization time is unrelated to age, but that certain symptoms (fever and tachypnoea) are associated with longer hospitalization. The onset of certain symptoms may differ by age group., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Ubiquitylation is critical for preventing aberrant DNA repair and for efficient maintenance of genome stability. As deubiquitylases (DUBs) counteract ubiquitylation, they must have a great influence on many biological processes, including DNA damage response. To elucidate the role of DUBs in DNA repair in Drosophila melanogaster, systematic siRNA screening was applied to identify DUBs with a reduced survival rate following exposure to ultraviolet and X-ray radiations. As a secondary validation, we applied the direct repeat (DR)-white reporter system with which we induced site-specific DSBs and affirmed the importance of the DUBs Ovarian tumor domain-containing deubiquitinating enzyme 1 (Otu1), Ubiquitin carboxyl-terminal hydrolase 5 (Usp5), and Ubiquitin carboxyl-terminal hydrolase 34 (Usp34) in DSB repair pathways using Drosophila. Our results indicate that the loss of Otu1 and Usp5 induces strong position effect variegation in Drosophila eye following I-SceI-induced DSB deployment. Otu1 and Usp5 are essential in DNA damage-induced cellular response, and both DUBs are required for the fine-tuned regulation of the non-homologous end joining pathway. Furthermore, the Drosophila DR-white assay demonstrated that homologous recombination does not occur in the absence of Usp34, indicating an indispensable role of Usp34 in this process., (© 2022. The Author(s).)

We report on children with cancer in Hungary suffering from COVID-19, surveying a 13-months-long period of time. We performed a retrospective clinical trial studying the medical documentation of children treated in seven centers of the Hungarian Pediatric Oncology-Hematology Group. About 10% of children admitted to tertiary hemato-oncological centers for anti-neoplastic treatment or diagnosis for de novo malignancies were positive for SARS-CoV-2 infection. Nearly two-thirds of the infected patients were asymptomatic or had only mild symptoms but showed seropositivity by 1-4.5 months after positive PCR. One third of the SARS-CoV-2-positive children were hospitalized due to symptomatic COVID-19. Five children required antiviral treatment with remdesivir. One child was referred to the intensive care unit, requiring intubation and mechanical ventilation. Delay in the scheduled anti-cancer treatment did not exceed 2 weeks in the majority (89%) of cases. There was only one patient requiring treatment deferral longer than a month. There was no COVID-19-related death in patients under 18 years of age, and nor was multisystem inflammatory syndrome diagnosed. In conclusion, SARS-CoV-2 infection did not represent an untoward risk factor among children with cancer in Hungary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Müller, Szűcs-Farkas, Szegedi, Csóka, Garami, Tiszlavicz, Hauser, Kriván, Csanádi, Ottóffy, Nagy, Kiss and Kovács.)

Összefoglaló. A bőrpótlóknak mind a klinikumban, mind a gyógyszerkutatásokban kiemelt szerepük van. Ezek a kezdetleges mesterséges bőrszövetek segíthetik a bőr regenerálódását, modellezhetik a főbb funkciókat, de megvannak a korlátaik is, mechanikailag sérülékenyek, és nem tartósak. A legtöbb bőrpótló vagy acelluláris, vagy csak egy-két sejttípust tartalmaz. Az eredeti bőrrel megegyező szerkezetű, teljesen funkcionális mesterséges bőrszövet a mai napig nem létezik. A háromdimenziós szövetnyomtatás megoldást kínálhat erre a problémára is, hiszen a bőrszövet minden sejtes eleme felhasználható, megfelelő hidrogélek és biotinták segítségével pedig olyan komplex struktúrák hozhatók létre, amelyek képesek a bőr teljes funkcionális repertoárját biztosítani. Ez nemcsak klinikai szempontból kiemelt jelentőségű, hanem a preklinikai kísérletek esetében kiválthatja az állatmodelleket és számos toxikológiai vizsgálatot is. Orv Hetil. 2022; 163(10): 375-385. Summary. Skin substitutes have a prominent role in therapeutic applications and drug research. These simple artificial skin tissues can support skin regeneration, in vitro they can model the main functions of the skin but they also have limitations such as being mechanically vulnerable and not durable enough. Most skin substitutes are either acellular or contain only one or two cell types. Fully functional artificial skin substitute with the same structure as the original skin has not been produced to this day. Three-dimensional tissue bioprinting can also offer a solution to this problem, as all cellular elements of skin tissue can be used, and with the help of appropriate hydrogels and bioinks, complex structures can be created that can provide a complete functional repertoire of the skin. It is important not just in the clinical therapeutic use, but it can also trigger the replacement of animal models and a number of toxicological studies in preclinical trials. Orv Hetil. 2022; 163(10): 375-385.

A diagnosis of drowning is not always possible based on the traditional autopsy findings. The most widely used ancillary methods are based on the detection of diatoms and other waterborne organisms in the organs of the systemic circulation by light microscope or polymerase chain reaction (PCR). One of the greatest concerns is sample contamination. Bone marrow is a favourable source because the compact bone protects the sample from water ingress in the case of advanced decay. In our pilot study, we aimed to adopt sternal bone marrow aspiration - which is a widely used technique in haematology - for postmortem sampling. Control experiments of non-drowning victims showed that cleaning the skin over the sternum can prevent external contamination. Sternal aspirate samples were taken from seven suspected drowning victims along with lung, spleen, and femoral bone marrow samples. All specimens were examined for the presence of diatoms by light microscope and Cyanobacteria-specific DNA by PCR. We were able to obtain bone marrow aspirates from all cases without complications. In four of the sternal samples both diatoms and cyanobacterial DNA were detected, while one additional sternum sample was tested positive with PCR, but no diatom shells were detectable. Sternal bone marrow aspiration is simple and quick, which can be performed at the beginning of an autopsy, minimizing the chance of contamination. We have shown that this sampling method can be adopted for postmortem diatom testing. This minimally invasive technique might be used in virtual autopsy (postmortem computed tomography, PMCT) settings without opening body cavities., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Poor response to treatment is a defining characteristic of reading disorder. In the present systematic review and meta-analysis, we found that the overall average effect size for treatment efficacy was modest, with a mean standardized difference of 0.38. Small true effects, combined with the difficulty to recruit large samples, seriously challenge researchers planning to test treatment efficacy in dyslexia and potentially in other learning disorders. Nonetheless, most published studies claim effectiveness, generally based on liberal use of multiple testing. This inflates the risk that most statistically significant results are associated with overestimated effect sizes. To enhance power, we propose the strategic use of repeated measurements with mixed-effects modelling. This novel approach would enable us to estimate both individual parameters and population-level effects more reliably. We suggest assessing a reading outcome not once, but three times, at pre-treatment and three times at post-treatment. Such design would require only modest additional efforts compared to current practices. Based on this, we performed ad hoc a priori design analyses via simulation studies. Results showed that using the novel design may allow one to reach adequate power even with low sample sizes of 30-40 participants (i.e., 15-20 participants per group) for a typical effect size of d = 0.38. Nonetheless, more conservative assumptions are warranted for various reasons, including a high risk of publication bias in the extant literature. Our considerations can be extended to intervention studies of other types of neurodevelopmental disorders., (© 2021. The Author(s).)

Objectives: According to the Porto criteria, upper endoscopy and ileocolonoscopy with histology for patients with pediatric inflammatory bowel disease (pIBD) are recommended with small bowel imaging (SBI). We aimed to evaluate the adherence to the Porto criteria and biopsy sampling practice and to evaluate the diagnostic yield of magnetic resonance enterography (MRE) first time in a nationwide pIBD inception cohort. Methods: Newly diagnosed pIBD cases (ages 0-18 years) are registered in the prospective, nationwide Hungarian Paediatric IBD Registry (HUPIR). We analyzed the diagnostic workup of patients recorded between the 1st of January 2007 and the 31st of December 2016. Results: Data for diagnostic workup was available in 1,523 cases. Forty percent of the cases had complied with the Porto criteria. Adherence to the Porto criteria increased significantly from 20 to 57% ( p < 0.0001) between 2007 and 2016. The most frequent reason for the incomplete diagnostic work-up was the lack of small bowel imaging (59%). In 2007, 8% of cases had a biopsy from all segments, and this rate reached 51% by 2016 ( p < 0.0001). We analyzed the diagnostic yield of MRE in 113 patients (10.1%), who did not have any characteristic lesion for Crohn's disease. The MRE was positive for the small bowel in 44 cases (39%). Conclusions: Adherence to the Porto criteria increased significantly during the 10-year period. This is the first study that reports multiple biopsy sampling as the less accepted recommendation. The diagnostic yield of MRE in patients without characteristic lesion for Crohn's disease is 39%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Müller, Dezsőfi, Cseh, Szűcs, Vass, Nemes, Kadenczki, Tárnok, Szakos, Guthy, Kovács, Karoliny, Czelecz, Tokodi, Tomsits and Veres.)

Background: Two hypotheses were tested regarding the characteristics of children with mathematical learning disabilities (MLD): (a) that children with MLD would have a 'core deficit' in basic number processing skills; and (b) that children with MLD would be at the end of a developmental continuum and have impairments in many cognitive skills., Methods: From a large sample (N = 1,303) of typically developing children, we selected a group definable as having MLD. The children were given measures of basic number processing and domain-general constructs. Differences between the observed sample and a simulated population were estimated using Cohen's d and Bayes factors. Receiver operating characteristic curves were plotted, and the area under the curve was computed to ascertain the diagnostic power of measures., Results: Results suggest that the differences between the MLD and control group can be defined along with general characteristics of the population rather than assuming single or multiple 'core deficits'. None of the measures of interest exceeded the diagnostic power that could be derived via simulation from the dimensional characteristics of the general population., Conclusions: There is no evidence for core deficit(s) in MLD. We suggest that future research should focus on representative samples of typical populations and on carefully tested clinical samples confirming to the criteria of international diagnostic manuals. Clinical diagnoses require that MLD is persistent and resistant to intervention, so studies would deliver results less exposed to measurement fluctuations. Uniform diagnostic criteria would also allow for the easy cross-study comparison of samples overcoming a serious limitation of the current literature., (© 2021 Association for Child and Adolescent Mental Health.)

Purpose: Percutaneous endoscopic gastrostomy (PEG) is a safe method to feed patients with feeding difficulty. This study aimed to compare the outcomes of conventional PEG and laparoscopic-assisted PEG (L-PEG) placement in high-risk pediatric patients., Methods: In our tertiary pediatric department, 90 PEG insertions were performed between 2014 and 2019. Children with severe thoracoabdominal deformity (TAD), previous abdominal surgery, ventriculoperitoneal (VP) shunt, and abdominal tumors were considered as high-risk patients. Age, sex, diagnosis, operative time, complications, and mortality were compared among patients who underwent conventional PEG placement (first group) and those who underwent L-PEG placement (second group)., Results: We analyzed the outcomes of conventional PEG placement (first group, n=15; patients with severe TAD [n=7], abdominal tumor [n=6], and VP shunts [n=2]) and L-PEG placement (second group, n=10; patients with VP shunts [n=5], previous abdominal surgery [n=4], and severe TAD [n=1]). Regarding minor complications, 1 (6.6%) patient in the first group underwent unplanned PEG removal and 1 (10%) patient in the second group had peristomal granuloma. We observed three major complications: colon perforation (6.6%) in a patient with VP shunt, gastrocolic fistula (6.6%) in a patient with Fallot-tetralogy and severe TAD, and pneumoperitoneum (6.6%) caused by early tube dislodgement in an autistic patient with severe TAD. All the three complications occurred in the first group (20%). No major complications occurred in the second group., Conclusion: In high-risk patients, L-PEG may be safer than conventional PEG. Thus, L-PEG is recommended for high-risk patients., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2021 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Science anxiety refers to students' negative emotions about learning science. Across two studies, we investigated the psychometric properties of the newly developed Abbreviated Science Anxiety Scale (ASAS), which was adapted from the modified Abbreviated Math Anxiety Scale (m-AMAS) (Carey E., 2017). Using a sample of students in grades 7 to 10 (N = 710), Study 1 reported a two-factor structure of the ASAS (learning science anxiety and science evaluation anxiety) and negative associations between the ASAS factors and science achievement. Study 2 replicated this two-factor model in students in grades 11 and 12 (N = 362) and found that students in the "Arts" track were more anxious about science than those in "Sciences" track. Both studies consistently reported positive inter-correlations between the ASAS factors, with good internal reliabilities and modest meaningful associations with test anxiety and general anxiety, suggesting that science anxiety might be a distinct construct. Further, female students had higher science anxiety (especially science evaluation anxiety) than male students, even when test anxiety and general anxiety were considered in models. In summary, the ASAS is a brief, valid, and reliable instrument that can be used to guide and improve science education., Competing Interests: The authors have declared that no competing interests exist.

We determined the relative importance of the so-called approximate number system (ANS), symbolic number comparison (SNC) and verbal and spatial short-term and working memory (WM) capacity for mathematics achievement in 1,254 Grade 2, 4 and 6 children. The large sample size assured high power and low false report probability and allowed us to determine effect sizes precisely. We used reading decoding as a control outcome measure to test whether findings were specific to mathematics. Bayesian analysis allowed us to provide support for both null and alternative hypotheses. We found very weak zero-order correlations between ANS measures and math achievement. These correlations were not specific to mathematics, became non-significant once intelligence was considered and ANS measures were not selected as predictors of math by regression models. In contrast, overall SNC accuracy and spatial WM measures were reliable and mostly specific predictors of math achievement. Verbal short-term and WM and SNC reaction time were predictors of both reading and math achievement. We conclude that ANS tasks are not suitable as measures of math development in school-age populations. In contrast, all other cognitive functions we studied are promising markers of mathematics development., (© 2020 John Wiley & Sons Ltd.)

Gut microbial composition alters in some special situations, such as in ulcerative colits (UC) after total proctocolectomy and ileal pouch-anal anastomosis (IPAA) surgery. The aim of our study was to determine the composition of the intestinal microbiome in UC patients after IPAA surgery, compared with UC patients, familial adenomatous polyposis (FAP) patients after IPAA surgery and healthy controls. Clinical data of patients, blood and faecal samples were collected. Faecal microbiota structure was determined by sequencing the V4 hypervariable region of the 16S rRNA gene. Overall, 56 patients were enrolled. Compared to the Healthy group, both the Pouch active and UC active groups had higher Enterobacteriaceae , Enterococcaceae and Pasteurellaceae abundance. The Pouch and UC groups showed distinct separation based on their alpha and beta bacterial diversities. The UC group had higher Prevotellaceae , Rikenellaceae , Ruminococcaceae abundance compared to the Pouch active group. Pouch and FAP participants showed similar bacterial community composition. There was no significant difference in the bacterial abundance between the active and inactive subgroups of the Pouch or UC groups. Gut microbiome and anatomical status together construct a functional unit that has influence on diversity, in addition to intestinal inflammation that is a part of the pathomechanism in UC.

Introduction: Exudative tonsillitis is a common clinical picture during childhood. The majority of these cases are caused by viruses (Epstein-Barr virus [EBV], cytomegalovirus [CMV], influenza virus, parainfluenza virus, and adenovirus), and only some infections are caused by bacteria, mainly group A streptococci (GAS). On the basis of international guidelines, routine use of early antibiotic treatment is not recommended in these cases, because it seems not to prevent GAS-associated complications. Aim: Our aim was to determine those laboratory results which are useful to distinguish between bacterial and viral infections in children with exudative tonsillitis to reduce antibiotic overuse. Method: In our study, we evaluated 135 clinical data from 133 children with exudative tonsillitis. Patients were grouped according to the following criteria: the first group contained patients with acute CMV or EBV infections, while in the second group, CMV or EBV infections were not confirmed using serology. Results: On the basis of our results, EBV or CMV infections (66/135, 48.8%) were serologically confirmed in the majority of cases with exudative tonsillitis between 2016 and 2017, while the causative role of GAS was minimal in this patient group (3/65, 4.61%). In spite of this finding, the majority of patients (92%) were treated with antibiotics. Conclusion: Our retrospective findings confirmed that it is not possible to determine the causative agent of this clinical picture on the basis of symptoms, and physical findings, moreover laboratory results, such as high white blood cell count could not confirm bacterial infection. At the same time, elevated transaminase levels may refer to viral origin of infection, especially EBV or CMV with high predictive value; the use of extended laboratory tests may reduce the unnecessary antibiotic consumption. Orv Hetil. 2020; 161(2): 50-55.

Nickel(ii) complexes of peptides CSSACS-NH2, ACSSACS-NH2, SSCSSACS-NH2 and GACAAH-NH2 have been studied by potentiometric and various spectroscopic (UV-vis, CD, NMR, and ESI-MS) techniques. All peptides have high nickel(ii) binding ability in the form of square planar complexes and the stability order of the peptides is: CSSACS-NH2 > ACSSACS-NH2 > SSCSSACS-NH2 ∼ GACAAH-NH2. The different metal binding affinities of these peptides are related to the differences in the speciation and in the binding modes of the major species. An almost exclusive formation of bis(ligand) complexes via an (NH2,S-) 5-membered chelate from the amino terminus is characteristic of CSSACS-NH2. The (NH2,N-,S-) tridentate chelate is the major coordination mode of ACSSACS-NH2 but the distant cysteine can also contribute to metal binding. The higher nickel(ii) binding ability of AC[combining low line]SSAC[combining low line]S-NH2 relative to the peptides containing an N-terminal XY-Cys motif may have important biological consequences. For example, the occurrence of the (NH2,N-,S-,S-) donor set is a common feature of both the ACSSACS-NH2 ligand and the nickel(ii) binding loop of the NiSOD enzyme (HC[combining low line]DLPC[combining low line]G…..,). In the case of SSCSSACS-NH2 and GACAAH-NH2 the amino terminus of one peptide can completely saturate the coordination sphere of the nickel(ii) ion via the formation of the (NH2,N-,N-,S-) binding mode. This rules out the formation of bis(ligand) complexes and any contribution of the distant cysteine or histidine to nickel(ii) binding in the 1 : 1 complexes. On the other hand the distant cysteine of SSCSSACS-NH2 and histidine of GACAAH-NH2 can behave as independent metal binding sites for the formation of dinuclear complexes in the presence of excess metal ions.

Introduction: Transfer is a planned movement of patients and their medical records from one provider to another. Only a few data are available from real life in inflammatory bowel disease patients in this topic., Aim: Our aim was to retrospectively evaluate the results of the transfer of our patients without longitudinal transition., Method: Data of the transferred patients at the University of Szeged were analysed. Patients were diagnosed in paediatric care. Transfer strategy at our departments was detailed medical summary., Results: 59 patients were enrolled in this study. 28.8% of the patients had mild to moderate disease activity and 71.2% was in remission at the time of transfer. Steroid therapy was initiated in 58% of the patients within an average of 9.1 months after the transfer. Anti-tumor necrosis factor therapy was given to 24% of the patients during the paediatric care and to an additional 23% in the adult care within an average of 28 months. Almost 70% of the patients received immunosuppressive therapy during paediatric and adult care. Surgery was required in 17% of the patients within an average 10.7 months after the transfer., Conclusion: Our results revealed that one-third of the paediatric patients have been transferred to adult care in active stage of disease. Shortly after the transfer 58% of the patients required corticosteroids and 17% surgery. Every fifth patient needed biological therapy to be initiated after the transfer. Longitudinal transition may have a potential to decrease the need for therapeutic change and the relatively high rate of surgery. Orv Hetil. 2018; 159(44): 1789-1793.

This study examined visual, spatial-sequential, and spatial-simultaneous working memory (WM) performance in children with mathematical learning disability (MLD) and low mathematics achievement (LMA) compared with typically developing (TD) children. Groups were matched on reading decoding performance and verbal intelligence. Besides statistical significance testing, we used bootstrap confidence interval estimation and computed effect sizes. Children were individually tested with six computerized tasks, two for each visuospatial WM subcomponent. We found that both MLD and LMA children had low visuospatial WM function in both spatial-simultaneous and spatial-sequential WM tasks. The WM deficit was most expressed in MLD children and less in LMA children. This suggests that WM scores are distributed along a continuum with TD children achieving top scores and MLD children achieving low scores. The theoretical and practical significance of findings is discussed. Statement of Contribution What is already known on this subject? Working memory plays an important role in mathematical achievement. Children with mathematical learning disability (MLD) usually have low working memory resources. Conflicting results have been reported concerning the role of VSWM in individuals with MLD. What the present study adds? Children with different degree of impairment in math achievement and typically developing children were tested. Visual, spatial-sequential, and spatial-simultaneous working memory tasks were examined. Only spatial-sequential and spatial-simultaneous working memory tasks discriminated the two impairments groups., (© 2017 The British Psychological Society.)

Recent studies have highlighted the fact that some tasks used to study symbolic number representations are confounded by judgments about physical similarity. Here, we investigated whether the contribution of physical similarity and numerical representation differed in the often-used symbolic same-different, numerical comparison, physical comparison, and priming tasks. Experiment 1 showed that subjective physical similarity was the best predictor of participants' performance in the same-different task, regardless of simultaneous or sequential presentation. Furthermore, the contribution of subjective physical similarity was larger in a simultaneous presentation than in a sequential presentation. Experiment 2 showed that only numerical representation was involved in numerical comparison. Experiment 3 showed that both subjective physical similarity and numerical representation contributed to participants' physical comparison performance. Finally, only numerical representation contributed to participants' performance in a priming task as revealed by Experiment 4. Taken together, the contribution of physical similarity and numerical representation depends on task demands. Performance primarily seems to rely on numerical properties in tasks that require explicit quantitative comparison judgments (physical or numerical), while physical stimulus properties exert an effect in the same-different task.

Most mathematical cognition research has focused on understanding normal adult function and child development as well as mildly and moderately impaired mathematical skill, often labeled developmental dyscalculia and/or mathematical learning disability. In contrast, much less research is available on cognitive and neural correlates of gifted/excellent mathematical knowledge in adults and children. In order to facilitate further inquiry into this area, here we review 40 available studies, which examine the cognitive and neural basis of gifted mathematics. Studies associated a large number of cognitive factors with gifted mathematics, with spatial processing and working memory being the most frequently identified contributors. However, the current literature suffers from low statistical power, which most probably contributes to variability across findings. Other major shortcomings include failing to establish domain and stimulus specificity of findings, suggesting causation without sufficient evidence and the frequent use of invalid backward inference in neuro-imaging studies. Future studies must increase statistical power and neuro-imaging studies must rely on supporting behavioral data when interpreting findings. Studies should investigate the factors shown to correlate with math giftedness in a more specific manner and determine exactly how individual factors may contribute to gifted math ability.

Working memory allows complex information to be remembered and manipulated over short periods of time. Correlations between working memory and mathematics achievement have been shown across the lifespan. However, only a few studies have examined the potentially distinct contributions of domain-specific visuospatial and verbal working memory resources in mental arithmetic computation. Here we aimed to fill this gap in a series of six experiments pairing addition and subtraction tasks with verbal and visuospatial working memory and interference tasks. In general, we found higher levels of interference between mental arithmetic and visuospatial working memory tasks than between mental arithmetic and verbal working memory tasks. Additionally, we found that interference that matched the working memory domain of the task (e.g., verbal task with verbal interference) lowered working memory performance more than mismatched interference (verbal task with visuospatial interference). Findings suggest that mental arithmetic relies on domain-specific working memory resources.

Introduction: Individuals with high levels of mathematics anxiety are more likely to have other forms of anxiety, such as general anxiety and test anxiety, and tend to have some math performance decrement compared to those with low math anxiety. However, it is unclear how the anxiety forms cluster in individuals, or how the presence of other anxiety forms influences the relationship between math anxiety and math performance., Method: We measured math anxiety, test anxiety, general anxiety and mathematics and reading performance in 1720 UK students (year 4, aged 8-9, and years 7 and 8, aged 11-13). We conducted latent profile analysis of students' anxiety scores in order to examine the developmental change in anxiety profiles, the demographics of each anxiety profile and the relationship between profiles and academic performance., Results: Anxiety profiles appeared to change in specificity between the two age groups studied. Only in the older students did clusters emerge with specifically elevated general anxiety or academic anxiety (test and math anxiety). Our findings suggest that boys are slightly more likely than girls to have elevated academic anxieties relative to their general anxiety. Year 7/8 students with specifically academic anxiety show lower academic performance than those who also have elevated general anxiety., Conclusions: There may be a developmental change in the specificity of anxiety and gender seems to play a strong role in determining one's anxiety profile. The anxiety profiles present in our year 7/8 sample, and their relationships with math performance, suggest a bidirectional relationship between math anxiety and math performance.

Mathematics anxiety (MA) can be observed in children from primary school age into the teenage years and adulthood, but many MA rating scales are only suitable for use with adults or older adolescents. We have adapted one such rating scale, the Abbreviated Math Anxiety Scale (AMAS), to be used with British children aged 8-13. In this study, we assess the scale's reliability, factor structure, and divergent validity. The modified AMAS (mAMAS) was administered to a very large ( n = 1746) cohort of British children and adolescents. This large sample size meant that as well as conducting confirmatory factor analysis on the scale itself, we were also able to split the sample to conduct exploratory and confirmatory factor analysis of items from the mAMAS alongside items from child test anxiety and general anxiety rating scales. Factor analysis of the mAMAS confirmed that it has the same underlying factor structure as the original AMAS, with subscales measuring anxiety about Learning and Evaluation in math. Furthermore, both exploratory and confirmatory factor analysis of the mAMAS alongside scales measuring test anxiety and general anxiety showed that mAMAS items cluster onto one factor (perceived to represent MA). The mAMAS provides a valid and reliable scale for measuring MA in children and adolescents, from a younger age than is possible with the original AMAS. Results from this study also suggest that MA is truly a unique construct, separate from both test anxiety and general anxiety, even in childhood.

Phase entrainment of neuronal oscillations is thought to play a central role in encoding speech. Children with developmental dyslexia show impaired phonological processing of speech, proposed theoretically to be related to atypical phase entrainment to slower temporal modulations in speech (<10Hz). While studies of children with dyslexia have found atypical phase entrainment in the delta band (~2Hz), some studies of adults with developmental dyslexia have shown impaired entrainment in the low gamma band (~35-50Hz). Meanwhile, studies of neurotypical adults suggest asymmetric temporal sensitivity in auditory cortex, with preferential processing of slower modulations by right auditory cortex, and faster modulations processed bilaterally. Here we compared neural entrainment to slow (2Hz) versus faster (40Hz) amplitude-modulated noise using fNIRS to study possible hemispheric asymmetry effects in children with developmental dyslexia. We predicted atypical right hemisphere responding to 2Hz modulations for the children with dyslexia in comparison to control children, but equivalent responding to 40Hz modulations in both hemispheres. Analyses of HbO concentration revealed a right-lateralised region focused on the supra-marginal gyrus that was more active in children with dyslexia than in control children for 2Hz stimulation. We discuss possible links to linguistic prosodic processing, and interpret the data with respect to a neural 'temporal sampling' framework for conceptualizing the phonological deficits that characterise children with developmental dyslexia across languages., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Our ability to allocate attention at different moments in time can sometimes fail to select stimuli occurring in close succession, preventing visual information from reaching awareness. This so-called attentional blink (AB) occurs when the second of two targets (T2) is presented closely after the first (T1) in a rapid serial visual presentation (RSVP). We hypothesized that entrainment to a rhythmic stream of stimuli-before visual targets appear-would reduce the AB. Experiment 1 tested the effect of auditory entrainment by presenting sounds with a regular or irregular interstimulus interval prior to a RSVP where T1 and T2 were separated by three possible lags (1, 3 and 8). Experiment 2 examined visual entrainment by presenting visual stimuli in place of auditory stimuli. Results revealed that irrespective of sensory modality, arrhythmic stimuli preceding the RSVP triggered an alerting effect that improved the T2 identification at lag 1, but impaired the recovery from the AB at lag 8. Importantly, only auditory rhythmic entrainment was effective in reducing the AB at lag 3. Our findings demonstrate that manipulating the pre-stimulus condition can reduce deficits in temporal attention characterizing the human cognitive architecture, suggesting innovative trainings for acquired and neurodevelopmental disorders.

Aim: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn's disease (CD) and the effect of transforming growth factor-β (TGF-β) on these miRs in duodenal epithelial and fibroblast cells., Methods: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-β (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well., Results: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, P ≤ 0.01) and to the control group (CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P ≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 ± 1.02 vs, Control: 1.00 ± 0.40, P ≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs, Control: 1 ± 0.09, P ≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs, Control: 1 ± 0.15, P ≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs, Control: 1 ± 0.06, P ≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-β treatment did not influence the expression of miR-122., Conclusion: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-β plays an important role in the regulation of the expression of these miRs.

Human attention fluctuates across time, and even when stimuli have identical physical characteristics and the task demands are the same, relevant information is sometimes consciously perceived and at other times not. A typical example of this phenomenon is the attentional blink, where participants show a robust deficit in reporting the second of two targets (T2) in a rapid serial visual presentation (RSVP) stream. Previous electroencephalographical (EEG) studies showed that neural correlates of correct T2 report are not limited to the RSVP period, but extend before visual stimulation begins. In particular, reduced oscillatory neural activity in the alpha band (8-12 Hz) before the onset of the RSVP has been linked to lower T2 accuracy. We therefore examined whether auditory rhythmic stimuli presented at a rate of 10 Hz (within the alpha band) could increase oscillatory alpha-band activity and improve T2 performance in the attentional blink time window. Behaviourally, the auditory rhythmic stimulation worked to enhance T2 accuracy. This enhanced perception was associated with increases in the posterior T2-evoked N2 component of the event-related potentials and this effect was observed selectively at lag 3. Frontal and posterior oscillatory alpha-band activity was also enhanced during auditory stimulation in the pre-RSVP period and positively correlated with T2 accuracy. These findings suggest that ongoing fluctuations can be shaped by sensorial events to improve the allocation of attention in time.

Background: Evidence suggests the central role of tumor necrosis factor (TNF)-α in the pathomechanism of inflammatory bowel disease (IBD); however, its effect on epigenetic factors, including small non-coding microRNAs (miRs), is less known. Our present aim was the comparative investigation of the expression of TNF-α and immune response-related miRs in children with Crohn's disease (CD) and ulcerative colitis (UC)., Methods: Fresh-frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) biopsies were used to analyze the expression of miR-146a, -155, -122, and TNF-α by real-time reverse transcription polymerase chain reaction in macroscopically inflamed (CD: 12 FFPE and 24 FF; UC: 10 FF) and intact (CD: 12 FFPE; 14 FF) colonic biopsies of children with IBD and controls (16 FFPE; 23 FF). The expression of miR-146a, -155, and -122 was also determined in TNF-α-treated HT-29 colonic epithelial cells., Results: Increased expression of TNF-α was observed in the colonic mucosa of children with CD and UC in comparison with controls. Expression of miR-146a and -155 was higher in the inflamed mucosa of children with CD and UC than in the intact mucosa. Expression of miR-122 elevated in the macroscopically intact colonic regions of CD compared with controls and patients with UC. In HT-29 cells, TNF-α treatment increased the expression of miR-146a and -155, but not that of miR-122., Conclusions: Our results showed altered expression of miR-146a, -155, and -122 in the colonic mucosa of children with IBD and in TNF-α-treated colonic epithelial cells. Our data suggest the TNF-α-related involvement of these miRs in the pathogenesis of IBD.

A large body of research suggests that mathematical learning disability (MLD) is related to working memory impairment. Here, I organize part of this literature through a meta-analysis of 36 studies with 665 MLD and 1049 control participants. I demonstrate that one subtype of MLD is associated with reading problems and weak verbal short-term and working memory. Another subtype of MLD does not have associated reading problems and is linked to weak visuospatial short-term and working memory. In order to better understand MLD we need to precisely define potentially modality-specific memory subprocesses and supporting executive functions, relevant for mathematical learning. This can be achieved by taking a multidimensional parametric approach systematically probing an extended network of cognitive functions. Rather than creating arbitrary subgroups and/or focus on a single factor, highly powered studies need to position individuals in a multidimensional parametric space. This will allow us to understand the multidimensional structure of cognitive functions and their relationship to mathematical performance., (© 2016 Elsevier B.V. All rights reserved.)

Although several studies have compared the representation of fractions and decimals, no study has investigated whether fractions and decimals, as two types of rational numbers, share a common representation of magnitude. The current study aimed to answer the question of whether fractions and decimals share a common representation of magnitude and whether the answer is influenced by task paradigms. We included two different number pairs, which were presented sequentially: fraction-decimal mixed pairs and decimal-fraction mixed pairs in all four experiments. Results showed that when the mixed pairs were very close numerically with the distance 0.1 or 0.3, there was a significant distance effect in the comparison task but not in the matching task. However, when the mixed pairs were further apart numerically with the distance 0.3 or 1.3, the distance effect appeared in the matching task regardless of the specific stimuli. We conclude that magnitudes of fractions and decimals can be represented in a common manner, but how they are represented is dependent on the given task. Fractions and decimals could be translated into a common representation of magnitude in the numerical comparison task. In the numerical matching task, fractions and decimals also shared a common representation. However, both of them were represented coarsely, leading to a weak distance effect. Specifically, fractions and decimals produced a significant distance effect only when the numerical distance was larger.

In studies of arithmetic verification, participants typically encounter two operands and they carry out an operation on these (e.g. adding them). Operands are followed by a proposed answer and participants decide whether this answer is correct or incorrect. However, interpretation of results is difficult because multiple parallel, temporally overlapping numerical and non-numerical processes of the human brain may contribute to task execution. In order to overcome this problem here we used a novel paradigm specifically designed to tease apart the overlapping cognitive processes active during arithmetic verification. Specifically, we aimed to separate effects related to detection of arithmetic correctness, detection of the violation of strategic expectations, detection of physical stimulus properties mismatch and numerical magnitude comparison (numerical distance effects). Arithmetic correctness, physical stimulus properties and magnitude information were not task-relevant properties of the stimuli. We distinguished between a series of temporally highly overlapping cognitive processes which in turn elicited overlapping ERP effects with distinct scalp topographies. We suggest that arithmetic verification relies on two major temporal phases which include parallel running processes. Our paradigm offers a new method for investigating specific arithmetic verification processes in detail., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Paediatric Crohn's disease patients suffer from several complications, including low bone mineral density and inadequate serum levels of 25-hydroxy vitamin D., Aims: The aim of this prospective study was to address the effect of infliximab therapy on bone metabolism, bone mineral density and vitamin D homeostasis. The seasonal variability of serum vitamin D levels in relation to infliximab treatment was also analysed., Methods: Serum osteocalcin and beta-crosslaps (markers of bone metabolism), seasonal variability of vitamin D, and bone mineral density were assessed and followed throughout the yearlong treatment regimen of infliximab in 50 consecutive paediatric patients with moderate to severe Crohn's disease., Results: Bone forming osteocalcin levels were significantly (p<0.001) increased during infliximab therapy. In contrast, no significant changes in beta-crosslaps and vitamin D levels were observed. Vitamin D levels were significantly different when the summer and winter periods were compared at week 0 (p=0.039); however, this difference was not detected after one year of infliximab therapy. Despite the beneficial clinical effect of infliximab, there was no significant change in bone mineral density Z-scores after one year of treatment., Conclusion: Infliximab may beneficially affect bone homeostasis. Moreover, seasonal variability in vitamin D levels observed prior to initiation of infliximab treatment was diminished after one year of treatment., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

This study investigated the role of impaired inhibitory control as a factor underlying attention deficit hyperactivity disorder (ADHD). Children with ADHD and typically developing children completed an animal Stroop task while electroencephalogram (EEG) was recorded. The lateralized readiness potential and event-related brain potentials associated with perceptual and conflict processing were analyzed. Children with ADHD were slower to give correct responses irrespective of congruency, and slower to prepare correct responses in the incongruent condition. This delay could result from enhanced effort allocation at earlier processing stages, indicated by differences in P1, N1, and conflict sustained potential. Results suggest multiple deficits in information processing rather than a specific response inhibition impairment.

Introduction: Although many children encounter difficulties in arithmetic, the underlying cognitive and emotive factors are still not fully understood. This study examined verbal and visuospatial short-term memory (STM) and working memory (WM) performance in children with developmental dyscalculia (DD) and high mathematics anxiety (MA) compared with typically developing (TD) children., Method: Groups were matched on reading comprehension performance and IQ as well as on general anxiety. We aimed to test whether children with DD and MA were differently impaired in verbal and visuospatial STM and WM. Children were individually tested with four computerized tasks: two STM tasks (forward verbal and visuospatial recall) and two WM tasks (backward verbal and visuospatial recall)., Results: Relative to children with TD, those with DD did not show impairments on the forward or backward verbal tasks, but showed specific impairments in the visuospatial WM task. In contrast, children with MA were particularly impaired in the verbal WM task., Conclusions: Knowing the underlying cognitive processes that differentiate why children with DD and MA fail in math could have both educational and clinical implications.

Several studies assumed that the analysis of numerical information happens in a fast and automatic manner in the human brain. Utilizing the high temporal resolution of electroencephalography (EEG) in a passive oddball adaptation paradigm, we compared event-related brain potentials (ERPs) evoked by unattended shape changes and unattended numerosity changes. We controlled visual stimulus properties in a stringent manner. Unattended changes in shape elicited significant, gradual adaptation effects in the range of early visual components, indicating the fast and automatic processing of shapes. Changes in numerosity did not elicit significant changes in these early ERP components. The lack of early number-specific effects was qualified by a significant interaction between Shape and Number conditions. Number change elicited gradual ERP effects only on late ERP components. We conclude that numerosity is a higher-level property assembled from naturally correlating perceptual cues and hence, it is identified later in the cognitive processing stream., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Event-related potential (ERP) studies have detected several characteristic consecutive amplitude modulations in both implicit and explicit mental arithmetic tasks. Implicit tasks typically focused on the arithmetic relatedness effect (in which performance is affected by semantic associations between numbers) while explicit tasks focused on the distance effect (in which performance is affected by the numerical difference of to-be-compared numbers). Both task types elicit morphologically similar ERP waves which were explained in functionally similar terms. However, to date, the relationship between these tasks has not been investigated explicitly and systematically. In order to fill this gap, here we examined whether ERP effects and their underlying cognitive processes in implicit and explicit mental arithmetic tasks differ from each other. The same group of participants performed both an implicit number-matching task (in which arithmetic knowledge is task-irrelevant) and an explicit arithmetic-verification task (in which arithmetic knowledge is task-relevant). 129-channel ERP data differed substantially between tasks. In the number-matching task, the arithmetic relatedness effect appeared as a negativity over left-frontal electrodes whereas the distance effect was more prominent over right centro-parietal electrodes. In the verification task, all probe types elicited similar N2b waves over right fronto-central electrodes and typical centro-parietal N400 effects over central electrodes. The distance effect appeared as an early-rising, long-lasting left parietal negativity. We suggest that ERP effects in the implicit task reflect access to semantic memory networks and to magnitude discrimination, respectively. In contrast, effects of expectation violation are more prominent in explicit tasks and may mask more delicate cognitive processes., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

We examined the representation of two-digit decimals through studying distance and compatibility effects in magnitude comparison tasks in four experiments. Using number pairs with different leftmost digits, we found both the second digit distance effect and compatibility effect with two-digit integers but only the second digit distance effect with two-digit pure decimals. This suggests that both integers and pure decimals are processed in a compositional manner. In contrast, neither the second digit distance effect nor the compatibility effect was observed in two-digit mixed decimals, thereby showing no evidence for compositional processing of two-digit mixed decimals. However, when the relevance of the rightmost digit processing was increased by adding some decimals pairs with the same leftmost digits, both pure and mixed decimals produced the compatibility effect. Overall, results suggest that the processing of decimals is flexible and depends on the relevance of unique digit positions. This processing mode is different from integer analysis in that two-digit mixed decimals demonstrate parallel compositional processing only when the rightmost digit is relevant. Findings suggest that people probably do not represent decimals by simply ignoring the decimal point and converting them to natural numbers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We determined how various cognitive abilities, including several measures of a proposed domain-specific number sense, relate to mathematical competence in nearly 100 9-year-old children with normal reading skill. Results are consistent with an extended number processing network and suggest that important processing nodes of this network are phonological processing, verbal knowledge, visuo-spatial short-term and working memory, spatial ability and general executive functioning. The model was highly specific to predicting arithmetic performance. There were no strong relations between mathematical achievement and verbal short-term and working memory, sustained attention, response inhibition, finger knowledge and symbolic number comparison performance. Non-verbal intelligence measures were also non-significant predictors when added to our model. Number sense variables were non-significant predictors in the model and they were also non-significant predictors when entered into regression analysis with only a single visuo-spatial WM measure. Number sense variables were predicted by sustained attention. Results support a network theory of mathematical competence in primary school children and falsify the importance of a proposed modular 'number sense'. We suggest an 'executive memory function centric' model of mathematical processing. Mapping a complex processing network requires that studies consider the complex predictor space of mathematics rather than just focusing on a single or a few explanatory factors.