bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic cancer: Assessment of neoadjuvant chemotherapy outcome based on radiomics of pretreatment computed tomography.
Authors: Li Xiang , Tang Tianyu , Liang Tingbo , Bai Xueli
Published: October 2019

56

Background: To evaluate contrast enhanced-computed tomography (CE-CT) features to predicting treatment response and survival after neoadjuvant chemotherapy (NAC) for patients with borderline resectable and locally advanced pancreatic cancer. Methods: Sixty-one patients with pancreatic cancer receiving NAC were enrolled and underwent pre-treatment abdominal CE-CT. The patients were divided into groups according to post-treatment tumor size changes. Based on the pretreatment CE-CT images, 396 radiomic features were extracted from three-dimensional regions of interest. The optimal features were selected and three supervised machine learning classifiers were developed. Finally, univariate and multivariate analyses were performed to evaluate the ability of the selected features to predict the histopathological response and outcome. Results: Nine, seven, and five radiomic features, respectively, were selected as optimal features in three experiments. Two features, Haralick Entropy and Histogram Entropy, were consistent among the experiments and both were higher in patients with enlarged tumors. Moreover, a lower Histogram Entropy score was significantly associated with a better histopathological response (p = 0.008) and smaller tumor size (p = 0.041) in patients after tumor resection. In univariate Cox regression analysis, lower Histogram Entropy (p = 0.006) and lower Haralick Entropy (p = 0.001) predicted a better prognosis. Meanwhile, lower Haralick Entropy (p = 0.048) was an independent predictor of longer survival time in multivariate Cox regression analysis. Conclusions: Radiomic features are strongly correlated with NAC treatment response and prognosis in pancreatic cancer, suggesting the potential of imaging radiomics to help tailor the treatment of pancreatic cancer in the era of personalized medicine.
Analysis of serum by Raman spectroscopy finds changes in blood metabolites of cancer patients in 45 seconds.
Authors: Ito Hiroaki , Miyazaki Tomokazu , Uragami Naoyuki , Yokoyama Noboru , Inoue Haruhiro
Published: October 2019

57

Background: Cancer is an important disease that accounts for many of the causes of death worldwide, and early diagnosis is important for improving treatment results. In medical care, blood test is a simple and excellent test method, but there is still no cancer blood diagnosis method with high accuracy that can be performed in general hospitals. We are trying to detect cancer patients by analyzing serum using Raman spectroscopy. Methods: Among the outpatients who underwent upper gastrointestinal endoscopy or colonoscopy, 236 subjects who agreed to participate in the study were included. Raman scattering spectra were measured by irradiating a 1064 nm wavelength laser for 15 seconds with serum collected from the subject before endoscopic examination. The average value measured a total of three times was taken as the measured value, and the three measured values were averaged to obtain the value of each examinee. In the obtained Raman scattering spectra, the scattering spectral intensities of the wavelength originating in the specific molecules were analyzed. Results: We were able to obtain clear Raman scattering spectra of all serum samples. When comparing the Raman scattering spectral intensities of the wavelength originating in specific molecules, a large number of serum measurement values were gathered at the center, and the measurement values of the cancer patients' serum were over low or high. By setting the appropriate cutoff line, cancer patients (gastric cancer or colon cancer) and non-cancerous persons could be relatively clearly distinguished (sensitivity, 100%; Specificity, 75%). Conclusions: Our micro Raman system is able to acquire Raman scattering spectra of serum samples. Furthermore, it has been suggested that cancer diagnosis using serum could be possible by comparing the scattering spectral intensities caused by specific molecules. Clinical trial information: UMIN000034306.
Plasma circulating tumor DNA-based genetic profiling of lung cancer patients in Vietnam using ultra-deep massive parallel sequencing with unique identifier tagging.
Authors: Do Huy Phuoc , Nguyen Thao Thanh Tran , Tran Uyen Vu , Tran Thanh-Truong , Dang Anh-Thu Huynh , Nguyen Vu Trieu , Nguyen Chu Van , Do Han Ngoc , Phan Minh-Duy , Tran Le Son , Nguyen Hoai-Nghia , Giang Hoa
Published: October 2019

58

Background: Lung cancer is by far the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Genotype-directed therapy becomes a promising method for cancer treatment beside surgery and chemo-radiotherapy. Liquid biopsy using massive parallel sequencing has emerged as a non-invasive alternative procedure in profiling cancer driver mutations. In this study, we report the spectrum of clinically actionable mutations in plasma circulating tumor DNA of 299 non-small cell lung cancer patients using ultra-deep massive parallel sequencing with unique identifier tagging. Methods: Plasma circulating tumor DNA was extracted, ligated with unique identifier (Swift Bioscience), enriched of the target coding regions of EGFR, KRAS, NRAS, BRAF and the breakpoints of ALK, ROS1 (IDT) and sequenced using NextSeq 550 (Illumina) at mean coverage depth of 20,000X. Results: Out of 299 patients tested, 128 (42,8%) carried driver mutations. Genetic alterations were identified in EGFR (79 samples, 26,4%), KRAS (30 samples, 10%), ALK (7 samples, 2,34%), ROS1 (6 samples, 2%), BRAF (3 samples, 1%). There was no sample with NRAS mutation. In 79 EGFR-cases, there were 23 carry two pathogenic variants. 28 mutation types of EGFR were found including 19 indels and 9 missense variants L858R and T790M were the major ones. One case was found with concomitant EGFR and BRAF. Our study showed the spectrum and frequency of the cancer driver mutations detected in liquid biopsy was correlated to those detected in tissue biopsy samples. Conclusions: For the first time the spectrum of mutation types in liquid biopsy of Vietnamese NSCLC patients were investigated and showed the correlation with those detected in tissue biopsy samples.
Body mass index in non-small cell lung cancer patients treated with anti-PD-1 immune checkpoint inhibitors.
Authors: Tateishi Akiko , Horinouchi Hidehito , Masuda Ken , Jo Hitomi , Shinno Yuki , Okuma Yusuke , Yoshida Tatsuya , Goto Yasushi , Yamamoto Noboru , Ohe Yuichiro
Published: October 2019

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Background: Previous retrospective analyses have revealed higher response rates and a trend towards longer progression-free survival (PFS) and overall survival (OS) in response to immune checkpoint inhibitors (ICIs) in overweight patients. There are few reports concerning the association between the overweight state and the efficacy of ICIs specifically in non-small cell lung cancer (NSCLC) patients. We investigated the association between the body mass index (BMI) and the efficacy of ICIs in patients with NSCLC. Methods: Patients with advanced NSCLC who received ICI therapy (nivolumab or pembrolizumab) at the National Cancer Center Hospital from January 2016 to December 2018 were included in this retrospective cohort study. Based on their BMI, the patients were categorized into the overweight (A) group (BMI ≥25) and the non-overweight (B) group (BMI < 25). The PFS was compared between the two groups as the primary outcome. Results: Data of a total of 323 patients (median age, 63 years) were analyzed; 87 (26.9%)/43 (13.3%)/193 (59.8%) patients received pembrolizumab as 1st line therapy, pembrolizumab as 2nd line therapy, and nivolumab, respectively. Tumor proportion score was ≥50% in 58.4% (139/238) patients. The ECOG-PS was ≥2 in 37 patients (11.5%). The median body weight was 58.1, and the median BMI was 21.4. Of the 323 patients, 46 (14.2%) were categorized into group A (overweight) and 277 (85.8%) into group B (non-overweight). The median PFS and OS in two groups were as follows: A, 6.9 m/B, 5.6 m (HR 0.84, 95% CI [0.57-1.25], p = 0.38), and A, 22.3 m/B, 15.4 m (HR 0.90, 95% CI [0.56-1.43], p = 0.64), respectively. In accordance with the ICI regimen that the patients received, the PFS was A, 7.9 m/B, 7.8 m (HR 0.86, 95%CI [0.37-2.04], p = 0.74) in the patients who received pembrolizumab as 1st line therapy, A, 7.5 m/B, 5.3 m (HR 0.60, 95% CI [0.18-2.00], p = 0.40) in the patients who received pembrolizumab as 2nd line therapy, and A, 6.5 m/B, 4.4 m (HR 0.84, 95% CI [0.52-1.36], p = 0.48) in the patients who received nivolumab. Conclusions: Overweight NSCLC patients treated with ICIs showed a trend (non-statistically significant) towards a longer PFS as compared to non-overweight patients.
High throughput proteomic analysis and machine learning algorithm identifies DUOX2 (dual oxidase 2) as a novel biomarker for response prediction of concurrent chemoradiotherapy for locally advanced rectal cancer.
Authors: Lee Hyebin
Published: October 2019

71

Background: Although many efforts to predict treatment response of concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer (LARC) have been made, no molecular has proved to be a robust biomarker. Methods: We performed mass spectrometry-based quantitative proteomic analysis of pretreatment Formalin-fixed, Paraffin-embedded (FFPE) biopsy samples of 13 patients with LARC, who were treated with CCRT followed by curative surgery. Based on pathologic report of surgical specimens, we divided thirteen patients as two response groups: complete response (CR) and non-complete response (nCR) groups. Results: A total of 3,637 proteins were identified and 498 proteins were confirmed as expressed at significantly different levels (DEPs; differently expressed proteins) between these two groups. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were also performed: the result showed that up-regulated DEPs enriched in biological processes (BP) were significantly different between two groups; immune response, cell migration & motility, protein transport in CR group; amide/peptide biosynthetic process, translation, posttranscriptional regulation of gene expression and detoxification in nCR group. To identify the best classifier to evaluate predictive power of signatures, we employed for different machine learning algorithms to classify samples between CR and nCR groups. As a result, we identified the predictive relevance of dual oxidase 2 (DUOX2) as the strongest predictive biomarker. Conclusions: This study identified a new biomarker, DUOX2, applicable to discrimination between CR and nCR after NACRT for LARC. To our knowledge, the present study provides the first identification of a clinical biomarker for response prediction based on in-depth proteomics and machine learning algorithms.
PDL-1 expression in oral squamous cell carcinoma and implications for treatment.
Authors: Srinivasalu Vijay Kumar , Subramaniam Narayana , Iyer Subramania , Nambiar Ajit , Koyakutty Manzoor , Thankappan Krishnakumar , Das Manjula , Dhar sujan Kumar , Balasubramanian Deepak
Published: October 2019

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Background: PDL-1 expression has been shown in multiple tumours to be a key factor in treatment response and immunogenicity. In oral squamous cell carcinoma (OSCC), its role is controversial; the expression levels, prognostic significance and therapeutic relevance are unclear. This study was performed to determine the incidence of PDL-1 expression in OSCC, and to determine its correlation with demographic, clinical and pathological features, recurrence and survival. Methods: PDL1 expression levels were determined by immunohistochemistry (DAKO kit) on 64 samples of OSCC obtained during resection on tumour (T) and tumour infiltrating lymphocytes (TILs). Statistical analysis was performed for corelation with clinicopathological features and survival. We also analysed PD1/PDL1 expression on the mRNA-seq data from The Cancer Genome Atlas (TCGA) (n = 527) and Gene Expression Omnibus (GEO) (n = 61) for validation. Results: PDL1 expression of < 1% was the most common for T (92%) and TILs (56%). Tumour PDL-1 expression < 1% had higher lymphovascular invasion (LVI) (p = 0.044) and bone invasion (p = 0.010). TIL PDL-1 expression < 1% was more common in patients < 45 years (p = 0.023) with more local recurrences (p = 0.020). For TCGA data, overall survival (OS) in the young ( < 45 years) was reduced in patients with low ( < 1%) PD1 expression (p = 0.010) while GEO data showed that older patients ( > 45 years) had a significantly higher PD1 expression level (p = 0.044). Conclusions: PDL1 expression in OSCC was low. Low TIL PDL1 expression was more common in patients with age < 45 years, with a higher chance of local recurrence. Genomic data also validated a potential link between PD1 expression and age. On the tumour, PD1 expression may be an important prognosticator, while on TILs, PDL1 is likely more relevant. Moreover PDL1 expression on the tumour is likely to be heterogeneous, so TIL PDL1 expression may be more representative of the tumour microenvironment and a better prognostic marker.
Glucocorticoid Receptor Polymorphisms Influence Muscle Strength in Cushing’s Syndrome
Authors: Müller Lisa Marie , Kienitz Tina , Deutschbein Timo , Riester Anna , Hahner Stefanie , Burger-Stritt Stephanie , Berr Christina M , Oßwald Andrea , Braun Leah , Rubinstein German , Reincke Martin , Quinkler Marcus
Published: October 2019

Context

An important clinical feature of Cushing’s syndrome (CS) is proximal muscle myopathy caused by glucocorticoid induced protein metabolism. However, interindividual differences cannot be explained solely by the pure extent of hypercortisolemia.

Objective

To evaluate the effects of glucocorticoid receptor (GR) polymorphisms (BclI, N363S, ER22/23EK and A3669G), which influence peripheral glucocorticoid sensitivity on muscular function in endogenous CS.

Methods

205 patients with proven endogenous CS (128 central, 77 adrenal) from 3 centers of the German Cushing’s Registry and 125 subjects, in whom CS was ruled out, were included. All subjects were assessed for grip strength (via hand grip dynamometer) and performed a chair-rising test (CRT). DNA samples were obtained from peripheral blood leukocytes for GR genotyping.

Results

In patients with active CS, normalized handgrip strength of the dominant and nondominant hand was higher in A3669G minor allele than in wildtype carriers (P = .006 and P = .021, respectively). CS patients in remission and ruled-out CS showed no differences in handgrip strength regarding A3669G minor allele and wildtype carriers. Male CS patients harboring the ER22/23EK wildtype presented lower hand grip strength than minor allele carriers (P = .049 dominant hand; P = .027 nondominant hand). The other polymorphisms did not influence handgrip strength. CRT showed no differences regarding GR polymorphisms carrier status.

Conclusion

Handgrip strength seems to be more susceptible to hypercortisolism in A3669G wildtype than in A3669G minor allele carriers. This might partially explain the inter-individual differences of glucocorticoid-induced myopathy in patients with endogenous CS. ER22/23EK polymorphism seems to exert sex-specific differences.
Impaired Respiratory Function in Women With PCOS Compared With Matched Controls From a Population-Based Study
Authors: Underdal Maria Othelie , Salvesen Øyvind , Henriksen Anne Hildur , Andersen Marianne , Vanky Eszter
Published: October 2019

Context

Increased prevalence of asthma has been reported from epidemiological studies in women with polycystic ovary syndrome (PCOS).

Objective

To investigate respiratory function in women with PCOS compared with controls in a clinical setting.

Design

An 8-year clinical follow-up study including self-reported asthma diagnoses and spirometry of women with PCOS randomized to metformin or placebo during pregnancy in the original studies (the Pilot and the PregMet-study), compared with matched controls from a population-based cohort study (The HUNT Study).

Setting

Secondary and tertiary care centers.

Participants

A total of 145 women with PCOS (54% of original cohort) were matched 1:3 to controls, on gender, age, and smoking-status.

Main outcomes and measures

Self-reported doctor-diagnosed asthma (DDA), percentage of predicted forced expiratory volume in the first second of expiration (FEV1 % predicted), percentage of predicted forced vital capacity (FVC % predicted).

Results

Women with PCOS reported more DDA compared with controls (19% vs 9%; P < 0.01). Spirometry indicated a combined obstructive (FEV1 % predicted, 93.7 vs 102.0; P < 0.01) and restrictive (FVC % predicted, 94.5 vs 103.7; P < 0.01) respiratory impairment in PCOS compared with controls. Metformin in pregnancy did not affect respiratory function at follow-up.

Conclusion

Women with PCOS reported higher prevalence of DDA compared with controls matched for age and smoking status. In addition, respiratory function was decreased, with both obstructive and restrictive components. Further insight to the underlying pathogenesis of these observations is needed.

Clinical trial registration

ClinicalTrials.gov: The PregMet study: NCT00159536. The Pilot study: NCT03259919.
Effects of Pegvisomant and Pasireotide LAR on Vertebral Fractures in Acromegaly Resistant to First-generation SRLs
Authors: Chiloiro Sabrina , Giampietro Antonella , Frara Stefano , Bima Chiara , Donfrancesco Federico , Fleseriu Cara Maya , Pontecorvi Alfredo , Giustina Andrea , Fleseriu Maria , De Marinis Laura , Bianchi Antonio
Published: October 2019

Purpose

Osteopathy is an emerging complication of acromegaly. In somatostatin receptor ligands (SRL)-resistant patients, pegvisomant (PegV) and pasireotide LAR (Pasi) are used for acromegaly treatment, but their effect on skeletal health is still not defined.

Methods

In a longitudinal retrospective international study, we evaluated incidence of radiological vertebral fractures (VFs) in 55 patients with acromegaly resistant to first-generation SRL.

Results

At study entry, prevalent VFs occurred in 23 patients (41.8%). Biochemical acromegaly control was reached in 66.7% of patients on PegV and in 66.7% of patients on Pasi. During the follow-up, incident VFs (iVFs) were detected in 16 patients (29.1%). Occurrence of iVFs was associated with prevalent VFs (P = .002), persistence of active acromegaly (P = .01) and higher value of insulin-like growth factor 1 (IGF-1) during follow-up (P = .03). Among patients with active disease at last visit, iVFs occurred less frequently in patients on treatment with Pasi (25%) compared to PegV (77.8% P = .04), independently of the IGF-1 values (P = .90). In patients who reached biochemical control, 22.7% on PegV and 12.5% on Pasi had iVFs (P = .40). Among both treatment groups, the presence of pre-existent VFs was the main determinant for iVFs.

Conclusion

Our data show for the first time that patients with biochemically active disease treated with Pasi had lower risk of iVFs versus those treated with PegV. It also confirms that the presence of pre-existent VFs was the main determinant for iVFs. Additional studies on larger populations and with longer follow-up are needed to confirm our data and disclose the mechanisms underlying our findings.
Long-Term Outcomes of 125 Patients With Metastatic Pheochromocytoma or Paraganglioma Treated With 131-I MIBG
Authors: Thorpe Matthew P , Kane Ari , Zhu Jason , Morse Michael A , Wong Terence , Borges-Neto Salvador
Published: October 2019

Context

Prognosis of metastatic pheochromocytoma/paraganglioma following 131-Iodine metaiodobenzylguanidine (MIBG) is incompletely characterized due to small samples and shorter follow-up in these rare, often indolent tumors.

Objective

To describe long-term survival, frequency, and prognostic impact of imaging, biochemical, and symptomatic response to 131-I MIBG.

Design

Retrospective chart and imaging review at a tertiary referral center.

Patients

Six hundred sixty-eight person-years of follow-up in 125 patients with metastatic pheochromocytoma/paraganglioma with progression through prior multimodal treatment.

Intervention

Median 18 800 MBq 131-I MIBG.

Main Outcome Measures

Overall survival, Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) imaging response, symptomatic response per chart review, and biochemical response (20% change over 2 consecutive assays of catecholamines, vanillylmandelic acid, metanephrines, or chromogranin A).

Results

Median survival standard deviation [SD] from diagnosis was 11.5 years [2.4]; following metastasis, 6.5 years [0.8]; post treatment, 4.3 years [0.7]. Among 88 participants with follow-up imaging, 1% experienced complete response, 33% partial response, 53% stability, and 13% progression. Fifty-one percent showed subsequent progression, median progression-free survival [SD] of 2.0 years [0.6]. Stability/response vs progression at first imaging follow-up (3–6 months) predicted improved survival, 6.3 vs 2.4 years (P = 0.021). Fifty-nine percent of 54 patients demonstrated biochemical response. Fifty percent of these relapsed, with median time to laboratory progression [SD] of 2.8 years [0.7]. Biochemical response did not predict extended survival. Seventy-five percent of 83 patients reported improvement in pretreatment symptoms, consisting primarily of pain (42%), fatigue (27%), and hypertension (14%). Sixty-one percent of these patients experienced subsequent symptomatic progression at median [SD] 1.8 years [0.4]. Symptomatic response did not predict extended survival.

Conclusions

Imaging, symptomatic, and laboratory response to multimodal treatment including high-dose 131-I MIBG were achieved on long-term follow-up in metastatic pheochromocytoma or paraganglioma. Imaging response at 3 to 6 months was prognostic.
Scaffold-Free Endometrial Organoids Respond to Excess Androgens Associated With Polycystic Ovarian Syndrome
Authors: Wiwatpanit Teerawat , Murphy Alina R , Lu Zhenxiao , Urbanek Margrit , Burdette Joanna E , Woodruff Teresa K , Kim J Julie
Published: October 2019

Context

Polycystic ovary syndrome (PCOS) is a prevalent disorder in reproductive aged women associated with a number of endocrine and metabolic complications, including increased risk of endometrial cancer.

Objective

To study the effect of the characteristic increased androgen levels in PCOS on the endometrium, a novel scaffold-free multicellular endometrial organoid was established.

Design

Human endometrial organoids were constructed using primary endometrial epithelial and stromal cells from endometrial tissues. Organoids were treated for 14 days with physiologic levels of estradiol and testosterone to mimic a normal follicular phase or PCOS hormone profiles. Organoids were harvested for immunostaining and ribonucleic acid sequencing.

Setting

Academic institution.

Patients

Endometrial tissues from 10 premenopausal women undergoing hysterectomy for benign pathologies were obtained following written consent.

Main Outcome Measures

Organoid architecture, cell specific markers, functional markers, proliferation, and gene expression were measured.

Results

A method to generate scaffold-free endometrial organoids containing epithelial and stromal cells was established. These organoids exhibited distinct organization with epithelial cells lining the outer surface and stromal cells in the center of the organoids. Epithelial cells were polarized, organoids expressed cell type specific and functional markers, as well as androgen, estrogen, and progesterone receptors. Treatment with PCOS hormones increased cell proliferation and dysregulated genes in endometrial organoids.

Conclusions

A new multicellular, scaffold-free endometrial organoid system was established that resembled physiology of the native endometrium. Excess androgens in PCOS promoted cell proliferation in endometrial organoids, revealing new mechanisms of PCOS-associated with risk of endometrial neoplasia.
MICAL-L1 coordinates ciliogenesis by recruiting EHD1 to the primary cilium
Authors: Xie Shuwei , Farmer Trey , Naslavsky Naava , Caplan Steve
Published: October 2019

The endocytic protein EHD1 plays an important role in ciliogenesis by facilitating fusion of the ciliary vesicle and removal of CP110 (also known as CCP110) from the mother centriole, as well as removal of Cep215 (also known as CDK5RAP2) from centrioles to permit disengagement and duplication. However, the mechanism of its centrosomal recruitment remains unknown. Here, we address the role of the EHD1 interaction partner MICAL-L1 in ciliogenesis. MICAL-L1 knockdown impairs ciliogenesis in a similar manner to EHD1 knockdown, and MICAL-L1 localizes to cilia and centrosomes in both ciliated and non-ciliated cells. Consistent with EHD1 function, MICAL-L1-depletion prevents CP110 removal from the mother centriole. Moreover, upon MICAL-L1-depletion, EHD1 fails to localize to basal bodies. Since MICAL-L1 localizes to the centrosome even in non-ciliated cells, we hypothesized that it might be anchored to the centrosome via an interaction with centrosomal proteins. By performing mass spectrometry, we identified several tubulins as potential MICAL-L1 interaction partners, and found a direct interaction between MICAL-L1 and both α-tubulin–β-tubulin heterodimers and γ-tubulin. Our data support the notion that a pool of centriolar γ-tubulin and/or α-tubulin–β-tubulin heterodimers anchor MICAL-L1 to the centriole, where it might recruit EHD1 to promote ciliogenesis.
Tumor-derived extracellular vesicles: molecular parcels that enable regulation of the immune response in cancer
Authors: Sheehan Colin , D'Souza-Schorey Crislyn
Published: October 2019

Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound vesicles released by cells that contain bioactive cargoes including proteins, lipids and nucleic acids. Multiple subpopulations of EVs have now been recognized and these include exosomes and microvesicles. EVs have been thought to facilitate intercellular and distal communication to bring about various processes that enable tumor progression and metastases. Here, we describe the current knowledge of the functional cargo contained within EVs, with a focus on tumor microvesicles, and review the emerging theory of how EVs support immune suppression in cancer.
Expanding our horizons: central pattern generation in the context of complex activity sequences
Authors: Berkowitz Ari
Published: October 2019

Central pattern generators (CPGs) are central nervous system (CNS) networks that can generate coordinated output in the absence of patterned sensory input. For decades, this concept was applied almost exclusively to simple, innate, rhythmic movements with essentially identical cycles that repeat continually (e.g. respiration) or episodically (e.g. locomotion). But many natural movement sequences are not simple rhythms, as they include different elements in a complex order, and some involve learning. The concepts and experimental approaches of CPG research have also been applied to the neural control of complex movement sequences, such as birdsong, though this is not widely appreciated. Experimental approaches to the investigation of CPG networks, both for simple rhythms and for complex activity sequences, have shown that: (1) brief activation of the CPG elicits a long-lasting naturalistic activity sequence; (2) electrical stimulation of CPG elements alters the timing of subsequent cycles or sequence elements; and (3) warming or cooling CPG elements respectively speeds up or slows down the rhythm or sequence rate. The CPG concept has also been applied to the activity rhythms of populations of mammalian cortical neurons. CPG concepts and methods might further be applied to a variety of fixed action patterns typically used in courtship, rivalry, nest building and prey capture. These complex movements could be generated by CPGs within CPGs (‘nested’ CPGs). Stereotypical, non-motor, non-rhythmic neuronal activity sequences may also be generated by CPGs. My goal here is to highlight previous applications of the CPG concept to complex but stereotypical activity sequences and to suggest additional possible applications, which might provoke new hypotheses and experiments.
NORDIC LEGAL SYSTEM: ROOTS, STRENGTH, TRENDS
Authors: Хассельбальк Оле , Khasselbalk Ole
Published: October 2019

In this article different aspects of rooting, strengthening and trends of the Nordic Legal System (Nordic Law) are discussed. The Nordic Law is considered to be a sum of the legal systems of the countries, which are situated on the Scandinavian Peninsula. Apart of it the concept principles, particularities and advantages of this legal system are analyzed in comparison with the others. The author points the historical background and conditions of this legal system’s appearing and defines the periodization of this legal system strengthening process. He lights out five stages of the mentioned process. Besides this and according to the author’s viewpoint the Nordic Legal System should be characterized as the one of the traditional type and it differs substantially if it is compared to the Roman-Germanic or to the Anglo-Saxon (Anglo-American) legal systems, having the unique legal dimensions. Further in the article the law — making process, the order of parliamentary acts adopting, the laws using practice and handling the custom as a source of law in the Scandinavian countries are described and analyzed. Special attention is paid to the role of courts and judges in the law-making process, their influence on the formation of legal systems and legislation in the Nordic countries. In particular, the article notes the existence of a conflict between judges and parliamentarians. It lies in the fact that judges are not always satisfied with the quality of acts of Parliament, on the basis of which it is not always possible to fairly resolve the case in court. In addition, the author considers the functioning of public and private law institutions in the system of regulation of public relations. At the same time, the author pays the necessary attention to the regulation of social relations in those areas of public life that are not covered by acts of Parliament and in which contractual regulation in interpersonal relations and regulation of the activities of public organizations on the basis of self-regulation are possible. The problem of legal protection of individuals is considered.
Can Busy Organizations Learn to Get Better? Distinguishing Between the Competing Effects of Constrained Capacity on the Organizational Learning Process
Authors: Desai Vinit M.
Published: October 2019

Organizations are getting busier, but can they still learn to get better? This question has urgent practical importance, since competitive pressures in a wide variety of industries have resulted in organizations that increasingly strain their operating limits. This question is deeply connected with organizational learning theory, since organizations operating with constrained capacity may gain experience but lose the ability to digest it—challenging the overall organization’s ability to learn and improve. Some research, though, suggests a seemingly contradictory perspective, with constrained capacity perhaps motivating organizations to adopt more flexible approaches and learn out of necessity. This study integrates the perspectives to examine how constrained capacity impacts organizational learning. To explore this question, the study develops separate theory regarding the amount and timing of capacity crises, suggesting that increasingly constrained capacity tends to detract from learning, but, uniquely, that consistently constrained capacity, rather than periodic spikes, may instead lead to better learning. Hypothesis tests provide support for several of the study’s arguments.
Social media and children: Raising a generation of digital natives
Authors: McDade Niamh
Published: October 2019

Niamh McDade from the Royal Society of Public Health asks how we can maximise the positive effects while mitigating the risks of social media for the mental health and wellbeing of children and young people
Fathers' experiences of the health visiting service: A qualitative study
Authors: Menzies Jennifer
Published: October 2019

Inappropriate and ineffective care of men and fathers is a barrier to positive family care within the health visiting service. This care in relation to fathers needs to be addressed in light of changes to the social climate. The purpose of this study was to investigate the experiences fathers have of the health visiting service, the way the health visiting service is delivered and if it is targeting fathers and families effectively and equitably. The study was of a qualitative interpretive design, using a purposive sample of between five and seven fathers who regularly attended a fathers' group. A semi-structured interview to establish fathers' experiences of the health visiting service and a phenomenological approach and open coding analysis of the experiences of the fathers were used.
Assessment of the Practices for Early Mathematics Thinking in Preschools of Pasaje City, Ecuador
Authors: Reyes-Cedeno Clelia Consuelo , Rivas-Cun Hector Ivan , Espinoza-Cevallos Carmen Elizabeth , Rojas-Garcia Carlos R.
Published: October 2019

Preschool education is fundamental to shape children’s aptitudes and skills in early life. Ecuador is following a global education trend for starting-up mathematical thinking at earlier development ages, but this is only reflected in vehement curricular changes that are not supported properly. As a result, the safeguarding of a good children’s education appears to be lessened. This work aimed to evaluate the mathematics thinking practices in preschools of Pasaje city, Ecuador. The investigation employed a descriptive approach, hence data were collected from 65 teachers and 810 parents from public and private preschools by means of interviews and questionnaire in an attempt define some causes (teacher’s education, children’s socio-economical and family circumstances) that impair the initiation of the numerical, spatial and metric and geometric aptitudes in children. The results showed that not only preschool practices but also the home environment linked to socio-economic status appear to have positive or unfavorable influences on their children’s education.
Cognitive Mechanisms Underlying the Engineering Students’ Desire to Cheat During Online and Onsite Statistics Exams
Authors: Morales-Martinez Guadalupe Elizabeth , Lopez-Ramirez Ernesto Octavio , Mezquita-Hoyos Yanko Norberto , Lopez-Perez Rafael , Resendiz Ana Yolanda Lara
Published: October 2019

A sample of 327 engineering bachelor students from a public university in Mexico took part in an information integration study to explore systematic thinking underlying propensity for cheating during a course exam. All study participants were provided with written descriptions of 12 scenarios pertaining to the academic evaluation criteria and were asked to rate the likelihood that they would cheat under such circumstances. The 12 scenarios reflected the experimental manipulation of three orthogonal factors: teacher’s teaching style, type of exam, and modality of assessment. Analysis results revealed four distinct attitudes toward cheating among students, two of which were independent of context (low and high desire to cheat) while the remaining two were context-dependent (low and moderate desire to cheat). All groups showed systematic thinking underlying their possible desire to cheat that was typified by the use of a summative cognitive rule for integrating information related to academic cheating. However, evaluation of factor relevance varied across the groups.
The Primary School Moral Education Plan in Slovenia Ten Years after Its Introduction
Authors: Krek Janez , Hodnik Tatjana , Vogrinc Janez
Published: October 2019

Since the 2008/2009 school year, every primary school in Slovenia has had to prepare its own “school moral education plan” and undertake its moral education activities on the basis of this plan. Although the basic content areas of the moral education plan are prescribed by law, the openness of the legal provisions allows schools to exercise professional autonomy. After a decade of the implementation of moral education plans we conducted an empirical quantitative-qualitative study aimed at analysing them in terms of content. The objective was to determine the extent to which the plans include and how they define the prescribed content areas, as well as the extent to which they include and how they define additional content areas that are not prescribed by law but could be included by schools depending on their individual particularities and the specific challenges of their environment. Data were collected through publications on the websites of a representative sample of randomly selected schools and analysed with a specially prepared instrument. The research shows that upgrading moral education activities through the school moral education plan would require (1) reconsideration and upgrading of the concept, (2) continuous state support for the self-evaluation of schools specifically in this area, and (3) support for schools to gain a deeper professional understanding of current moral education challenges and of forming moral education strategies that differ with regard to the content differences in the reasons for individual moral education challenges.
Motion Graphic Animation Videos to Improve the Learning Outcomes of Elementary School Students
Authors: Hapsari Angganingrum Shinta , Hanif Muhammad , Gunarhadi Gunarhadi , Roemintoyo Roemintoyo
Published: October 2019

The purpose of this study was to investigate the effectiveness of the development of motion graphic animation video media in Natural Sciences subjects in Elementary Schools. This study uses a type of Research and Development research with quantitative tests. This study employed the experimental research method involving 27 students in the control group and 27 students in the experimental group. This research was conducted on 5th-grade students in elementary school in 2 different schools. Data collection uses interview methods for preliminary studies, observations and tests to test the effectiveness of animated video media motion graphics. The results of the study showed that there were significant differences between the results of the learning achievement of the experimental group and the control group. As well as motion graphic animation video media, its effectiveness has been tested in improving student achievement, especially the experimental group. Hence, the interactive motion graphic media is effective to be used to improve the students’ knowledge in the science subject of the fifth graders.
Contribution of CLIL Methodology to the Development of Bilingualism and Bilingual Language Competence of Slovak Secondary-School Students
Authors: Hurajova Anna
Published: October 2019

In almost all European countries, many schools offer a form of bilingual education provision according to which content subjects are taught either through two different languages or through one foreign language. This approach is known as Content and Language Integrated Learning (CLIL). The main problem addressed in this research article is the need to examine and describe the contribution of CLIL methodology to the development of bilingual language competence of students of a secondary vocational school. In addition, the study looks at the teaching and learning within a bilingual Slovak-English study program of the school, specifically at the implementation of CLIL methodology in content subjects taught within the program. Specifically, the extent, approaches, materials used in the study program to enhance bilingualism at school in general and the bilingual language competence of the students through CLIL methodology in particular, as well as opinions and perceptions of teachers and students were investigated. Three data collection tools were used – interviews with teachers and students, classroom observations and document review. The results of the study indicate that various factors inside and outside the classroom and school enhance students’ bilingual language competence with CLIL methodology playing an important but not a decisive role.
A Meningeal Syndrome Revealing A Tetanus in A Togolese: Case Report and Review of the Literature
Authors: Léhleng AGBA , Nyinèvi ANAYO K , Lihanimpo DJALOGUE , Mensah GUINHOUYA K , Awissoba AWIDINA-AMA , Kossivi APETSE , Kodzo KUMAKO V. , Damelan KOMBATE , Mofou BELO , Agnon BALOGOU K
Published: October 2019

Although it is a vaccine-preventable disease, tetanus is frequently found in sub-Saharan Africa. Because of its rarity, this disease poses two problems for doctors of the 21st century: to make early diagnosis in order to refer patients to appropriate care structures, and to continue to ensure correct prevention of an affection that few current doctors have met. In it generalized form, the diagnosis of tetanus is easy, but when the beginning is localized, tetanus can be change with other diseases leading to a diagnostic wandering and a delay of adequate management. We report a case of tetanus in an 18-year-old male, who was received for neck pain and stiffness of the neck with a positive Kernig sign associated to fever since 48 hours. Initially treated for meningitis, the patient will develop at day 3 of hospitalization, the signs of generalized tetanus which led to evoked the diagnosis of tetanus. This diagnosis was reinforced by the notion of a rusty nail injury to the soles of the right foot 3 weeks before hospitalization and the absence of anti-tetanus vaccination. After using tetanus serum and vaccination with antibiotics (Metronidazole and Penicillin) and Diazepam in association with stripping of the wound under the foot, the patient was improved. This case illustrates that any neurological sign with the first trismus must evoke until proof of the contrary, a tetanus especially in case of association with a wound even if the immunization schedule is up to date.
Splanchnic Aneurysms & Possible Etiology
Authors: Demos Nicholas J. , McGovern Patrick , Smith Peter , Demos Victoria
Published: October 2019

Four cases are reported with splanchnic aneurysms of the branches of the main arteries. Three of the cases presented as emergencies. Possible rupture was present in Case 2 and true rupture in Case 4. The etiology of Cases 1 and 2 may have been a floxacin antibiotics, Table 1. This report is the first clinical chronological association of the antibiotics and arterial and aortic pathology. This association was supported by nationwide research by Pasternak, 11. Detailed experimental work done on mice showed connective tissue fragmentation and arterial cell injury. Apparently, the above antibiotic induced mitochondrial DNA damage and dysfunction, 9.
Adrenal steroids in the blood and urine and the immune status of women with age-associated disorders of glucose tolerance
Authors: Odin V. I. , Poroshina T. E. , Tsyrlina E. V. , Berstein L. M.
Published: October 2019

Dehydroepiandrosterone (DHA), hydrocortisone, and insulin are naturally occurring substances influencing the immune functions. The present paper is devoted to their combined effects on the mitogen-stimulated proliferation of lymphocytes (MSPL) with phytohemagglutinin-M (PHA-M) and Pokeweed mitogen used as stimulants. A positive correlation between blood insulin and urinary DHA levels (r=0.534; p0.05) has been revealed. The level of DHA secretion was in a negative correlation with the values of MSPL stimulated by PHA-M (r=-0.651; p0.01). Hence, age-associated hyperinsulinemia may be regarded as an important regulator of both, adrenal androgen production and the cellular immunity status.
Bioactive compounds in wines produced in a new area for vitiviniculture in Brazil
Authors: Vilas Boas Ana Carolina , Resende Nassur Rita de Cássia Mirela , De Castro Henrique Paôla , Pereira Giuliano Elias , Lima Luiz Carlos Oliveira de
Published: October 2019

Wines are known for its high content of bioactive compounds that can be influenced by the region and climate where the grapes are produced. New regions of production are normally developed using techniques and standards for other traditional regions, but is important to characterize the wine profile, which is different according to the terroir, and can be important for future geographic indications. The aim of this study was to evaluate color, antioxidant activity, anthocyanin content and phenolic compounds profile in wines produced in Minas Gerais State, Brazil. Wines were produced in different wineries of the same region using the varieties Syrah, Merlot, Cabernet Sauvignon, Cabernet Franc (red), Chardonnay and Sauvignon Blanc (white) and Syrah (rose), from municipalities of Cordislândia, Boa Esperança and Três Corações, located in the south of Minas Gerais State, Brazil. Wines produced in Minas Gerais State presented contents of t-resveratrol, total phenolics, anthocyanins, flavonols, flavanols and phenolic acids consistent to the contents observed in wines from traditional regions of production. However, the terroir and the grape variety can result in a differentiation of compounds observed in wines. Syrah red wines produced in Boa Esperança stood out with higher amounts of anthocyanins (24.29 mg L-1), phenolic acids (123,19 mg L-1 ) and flavonols (35.55 mg L-1), when compared to wines from the same variety from other municipalities and other evaluated red wines. Sauvignon Blanc wines from Boa Esperança presented higher contents of phenolic acids and total flavonols, when compared to wines of the same variety produced in Cordislândia. Chardonay wines presented higher total phenolics content, when compared to ohther evaluated white wines.  Rose wine produced in the South of Minas Gerais presented the phenolic acids content of 36,33 mg L-1 and total flavonols content of 29,7 mg L-1. The highest antioxidant activity using the DPPH method, (% of free radicals scavenging - FRS) was observed for Syrah wines from Três Corações, (75.37%), but not different from Cabernet Sauvignon wines from Cordislândia (72.50%), values that can be correlated with the largest content of phenolics observed in wines as phenolic compounds (3009 mg L-1). No differences were observed in the contents of the antioxidant activity of white wines. This results indicate that the studied wines present the necessary nutritional and beneficial characteristics to compete in the supply of bioactive compounds during consumption, when compared to wines produced in traditional and different regions in Brazil and other countries.