Self‐rating scales are frequently used to screen for anxiety and depression in patients with irritable bowel syndrome (IBS). Different cutoff values are recommended in literature, and guidelines have suggested the use of other screening instruments over time. The aim of this study was to assess the correlation between the most commonly used psychological screening instruments for anxiety and depression in IBS and to compare custom cutoff scores for these instruments.

Introduction: Rapid-onset obesity, hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) is a rare syndrome beginning at 3-6 years of age with approximately 150 cases described. Additional features include eye abnormalities, neurobehavioral dysfunction and paraneoplastic tumors. The etiology of the complex phenotype remains unknown. Methods: This study aims to investigate the genetic landscape of this complex phenotype by whole exome sequencing (WES) and copy number variation (CNV) analysis. We recruited 33 families (27 trios, 1 duo and 5 singletons) with a proband with ROHHAD syndrome (Ize-Ludlow 2007, Pediatrics). WES of 89 individuals was performed at the Center for Mendelian Genomics, Broad Institute. The Illumina platform with a mean coverage of ~100X (> 90% targets 20x) and Infinium Global Screening Array BeadChip 24v1.0 were used. Results: This report includes 28 probands (female = 18, 64%) with rapid onset obesity (100%), hypoventilation (88%), hypothalamic dysfunction (69%), eye disorders (62%) and neurobehavioral abnormalities (76%). Neuroendocrine tumor, ganglioneuroblastoma, was present in 38% (n=13). No unifying causative single gene or CNV was identified, but a number of sequence variants are prioritized. ARNT2, which encodes for a helix-loop-helix transcription factor, plays a role in the development of the hypothalamic-pituitary axis, postnatal brain growth, and visual and renal function. The de novo monoallelic missense variant was found in a 14-year old white girl (BMIz +3.25) with extreme obesity and a neurobehavioral phenotype. OCRL1, a multi-domain protein involved in cytoskeleton-plasma membrane adhesion, endosomal trafficking and in primary cilium assembly. Mutations in this gene have also been known to cause Lowe syndrome. A hemizygous X-linked frameshift variant in a 5-year old white boy with extreme obesity (BMIz +5.48), central hypoventilation neurobehavioral dysfunction and ganglioneuroblastoma. A monoallelic missense variant in NSD1, a transcriptional intermediary factor acting as a histone methyltransferase, was identified in a 8-year old Hispanic girl with severe obesity (BMIz +2.91), neurobehavioral disorder, pituitary and eye dysfunction and ganglioneuroblastoma. NSD1 is known to cause Sotos and Beckwith-Wiedemann. Compound heterozygous variants in KIF7, a key component of the Hedgehog signaling pathway, were identified in a 14-year old white girl with severe obesity (BMIz +3.00), autistic behavior, pituitary dysfunction and central hypoventilation. This gene is known to cause autosomal recessive hydrolethalis and acroscallosal syndromes with mutations also noted in Bardet-Biedl, Meckel and Joubert syndromes. Conclusion: While no unifying genetic cause has been identified in ROHHAD syndrome, it is possible that the phenotype represents a collection of complex genetic syndromes.

By successfully solving the problem of forecasting, the processes in the work of various companies are optimized and savings are achieved. In this process, the analysis of time series data is of particular importance. Since the creation of Facebook’s Prophet, and Amazon’s DeepAR+ and CNN-QR forecasting models, algorithms have attracted a great deal of attention. The paper presents the application and comparison of the above algorithms for sales forecasting in distribution companies. A detailed comparison of the performance of algorithms over real data with different lengths of sales history was made. The results show that Prophet gives better results for items with a longer history and frequent sales, while Amazon’s algorithms show superiority for items without a long history and items that are rarely sold.

Replication is an important tool used to test and develop scientific theories. Areas of biomedical and psychological research have experienced a replication crisis, in which many published findings failed to replicate. Following this, many other scientific disciplines have been interested in the robustness of their own findings. This chapter examines replication in primate cognitive studies. First, it discusses the frequency and success of replication studies in primate cognition and explores the challenges researchers face when designing and interpreting replication studies across the wide range of research designs used across the field. Next, it discusses the type of research that can probe the robustness of published findings, especially when replication studies are difficult to perform. The chapter concludes with a discussion of different roles that replication can have in primate cognition research.

Replications are widely considered an essential tool to evaluate scientific claims. However, many fields have recently reported that replication rates are low and - when they are conducted - many findings do not successfully replicate. These circumstances have led to widespread debates about the value of replications for research quality, credibility of research findings, and factors contributing to current problems with replicability. This special issue brings together researchers from various areas within the field of animal behavior to offer their perspective on the status and value of replications in animal behavior science.

While the COVID-19 pandemic continues to spread globally, with relistic hope that will be solved with adequate vacination, more and more evidences are collected about the presence of psychi-atric and neurological manifestations and symptoms associated with this diseas. Neurological manifestations, are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of centra nervous system symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. The review of the so far published papers shows that although more and more papers are reporting neuro-logical and psyhiatric manifestations associated with COVID-19, many items remain unclear. The long-term psychological implications of this infectious diseases should not be ignored. In this paper, we aim to present a some of psychological consequences and neurological disorders associat-ed with the SARS-CoV-2 infection, and to emphasize the need a global action that requires close coordination and open-data sharing between hospitals, academic and public health institutions and the fast establishment of harmonised research priorities to face acut and long-term the neurological and psychological consequences.

The antidiabetic drug gliclazide is partly metabolized by CYP2C19, the main enzyme involved in omeprazole metabolism. The aim of the study was to explore the interaction between omeprazole and gliclazide in relation to CYP2C19 phenotype using physiologically based pharmacokinetic (PBPK) modeling approach. Developed PBPK models were verified using in vivo pharmacokinetic profiles obtained from a clinical trial on omeprazole-gliclazide interaction in healthy volunteers, CYP2C19 normal/rapid/ultrarapid metabolizers (NM/RM/UM). In addition, the association of omeprazole cotreatment with gliclazide-induced hypoglycemia was explored in 267 patients with type 2 diabetes (T2D) from the GoDARTS cohort, Scotland. The PBPK simulations predicted 1.4–1.6-fold higher gliclazide area under the curve (AUC) after 5-day treatment with 20 mg omeprazole in all CYP2C19 phenotype groups except in poor metabolizers. The predicted gliclazide AUC increased 2.1 and 2.5-fold in intermediate metabolizers, and 2.6- and 3.8-fold in NM/RM/UM group, after simulated 20-day dosing with 40 mg omeprazole once and twice daily, respectively. The predicted results were corroborated by findings in patients with T2D which demonstrated 3.3-fold higher odds of severe gliclazide-induced hypoglycemia in NM/RM/UM patients concomitantly treated with omeprazole. Our results indicate that omeprazole may increase exposure to gliclazide and thus increase the risk of gliclazide-associated hypoglycemia in the majority of patients.

Cytokines and other immune regulatory molecules are critical players in the immune response against cancer. There is growing interest in testing the potential utility of systemic immune biomarkers to track cancer progression and to use them as predictors of effective responses to cancer therapy. The central hypothesis guiding this project is that specific immune biomarkers will serve as predictors of effective vs. ineffective immunotherapy in patients with malignant diseases. The objective of this study was to establish baseline of immune markers in patients already started treatment with immunotherapy (n=10) (T), patients starting, but not yet treated (S) with immunotherapy (n=10) and subjects without diagnosed malignant disease (W) (n=10). Blood was collected and plasma was isolated and used in the biomarker (100 markers) analysis using a protein microarray method (RayBiotech). The biomarkers in the three groups were analyzed by Principal Component Analysis, heat map with clustering, and differential expression based on p value, and Significance Analysis of Microarrays (SAM). Although 15 biomarkers were significantly different between S vs. W groups, based on SAM, only seven were found differentially expressed. Similarly, although 10 biomarkers were significantly different between T vs. W groups, based on SAM, only one biomarker was found differentially expressed. Furthermore, SAM revealed that responders (n=4) vs. stable (n=5) subgroup of patients within the T group exhibited 22 differentially expressed biomarkers. Future larger studies will be needed to evaluate whether immune markers will be able to predict effective vs. ineffective responses to immunotherapy and whether they may have therapeutic potential.

Artificial Intelligence (AI) has been drawing attention in the field of medical devices. However, due to system complexity, the variability of their architecture, as well as ethical and regulatory concerns there is an ongoing need to analyze its application and performance.This study presents a narrative commentary on the applications of artificial neural networks (ANN) and machine learning (ML) algorithms in medical devices, past, current and future perspectives of application. One research focus of this study was on identifying problems and issues related to the implementation of AI in medical devices. The commentary is based on scientific articles published in PubMed, Scopus ad ScienceDirect databases, official publications of international organizations: European Comission (EC), Food and Drug Administration (FDA), and World Health Organisation (WHO) published in 2009 - 2020 period. AI is revolutionizing healthcare, from medical applications to clinical engineering. However, before grasp-ing the full potential ethical, legal and social concerns need to be resolved and its application needs to be harmonized and regulated regarding equitable access, privacy, appropriate uses and users, liability and bias and inclusiveness.

ABSTRACT Pure hematite nanorods and very long and thin cobalt-doped hematite nanorods (nanoneedles) were prepared by a combined precipitation and annealing method. The influence of the level of cobalt doping on different properties of hematite nanorods was investigated. Incorporation of cobalt in the form of low-spin Co3+ ions into the structure of hematite by substitution for high-spin Fe3+ ions was proved by determination of a significant unit cell contraction by powder X-ray diffraction (PXRD) and characteristic positions of the absorption edge in X-ray absorption near edge structure (XANES) spectra and peaks in X-ray emission (XES) spectra. Cobalt doping caused a gradual elongation and thinning of hematite nanorods – very long and thin 1D nanoparticles (nanoneedles) were formed in the presence of 10 and 12 mol% Co. Magnetic measurements showed a strong increase in low-temperature remanent magnetization and coercivity upon cobalt doping, as well as a disappearance of the Morin transition, which was also confirmed by Mossbauer spectroscopy. Cobalt doping significantly affected optical properties of hematite nanorods – absorption in the visible and NIR ranges increased, which was accompanied by narrowing of the optical band gap. Compared with pure hematite nanorods cobalt-doped hematite nanoneedles showed a significantly better electrocatalytic activity for the oxygen evolution reaction (OER).

A detailed examination of the principle of operation behind the functioning of the full-self-powered humidity sensor is presented. The sensor has been realized as a structure consisting of an interdigitated capacitor with aluminum thin-film digits. In this work, the details of its fabrication and activation are described in detail. The performed XRD, FTIR, SEM, AFM, and EIS analyses, as well as noise measurements, revealed that the dominant process of electricity generation is the electrochemical reaction between the sensor’s aluminum electrodes and the water from humid air in the presence of oxygen, which was the main goal of this work. The response of the sensor to human breath is also presented as a demonstration of its possible practical application.

Focal epilepsy is one of the most frequent specific type of epilepsies, with 30% treatment-resistant patients. There are several directions researchers can follow to improve existing treatment of focal epilepsy: synthesis of new compounds with anticonvulsant activity, repurposing drugs approved for other indications, finding drugs targeted to specific genetic and biochemical defects that underlie focal epilepsy syndromes, development of viral vectors for specific gene therapy, creation of devices and methods for suppression of seizures by electrostimulation and development of methods to increase safety of epilepsy surgery. Improvement of efficacy and safety of current therapies is necessary, as well as developing targeted treatment of genetic epilepsy syndromes that will not only suppress seizures, but stop further epileptogenesis.

Single slit diffraction is part of many high-school physics curricula throughout the world. In this study, we aimed to investigate whether high-school physics teachers from Bosnia and Herzegovina, Serbia and North Macedonia are adequately prepared to discuss with their students about various aspects of the single slit diffraction pattern, particularly about vertical length of diffraction fringes. To that end we conducted a written survey which included 57 high-school physics teachers. Besides asking teachers about students’ difficulties in learning about single slit diffraction, we also asked them to specify their own difficulties with this topic and required them to solve a conceptual task. Almost every second teacher believed that vertical length of diffraction fringes can be increased by changing shape or width of the slit and only 1 out of 57 teachers managed to correctly answer why diffraction fringes become shorter when we move away from the central maximum. We concluded that physics teacher education programmes should be changed to develop understanding of both, horizontal and vertical aspects of the diffraction pattern. To that end it is useful to provide learning opportunities which encourage combining ray and wave model of light.