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We investigated destination memory, defined as the ability to remember to whom a piece of information was previously transmitted, for emotional destinations (i.e., a happy or sad person) in Korsakoff's syndrome (KS). We asked patients with KS and control participants to tell facts to neutral, positive, or negative faces. On a subsequent recognition task, participants had to decide to whom they told each fact. Compared with control participants, patients with KS demonstrated lower recognition of neutral, emotionally positive, and emotionally negative destinations. Patients with KS demonstrated lower recognition of emotionally negative than for emotionally positive or neutral destinations, but there were no significant differences between recognition of neutral and emotionally positive destinations. Our study demonstrates a compromised ability to process negative destinations in KS. Our study highlights the relationship between memory decline and impaired emotional processing in KS.

Background: This study examined the psychometric properties (factor structure, measurement invariance, convergent and criterion validity, inter-correlations, and reliabilities) of an Arabic version of the modified-Abbreviated Math Anxiety Scale (m-AMAS) and gender differences in math anxiety in an Arabic speaking Middle Eastern country, Qatar., Methods: A large sample of students in grade 7 to 10 ( N  = 731) completed the m-AMAS, three different scales to measure science anxiety, test anxiety, and general anxiety, as well as a scholastic math achievement test., Results: The two-factor structure of the m-AMAS was confirmed, with good to adequate reliabilities, and its compositional measurement invariance was established across girls and boys in the four grades. In addition, math anxiety correlated positively with science anxiety, test anxiety, and general anxiety. Regression analyses showed that math anxiety was negatively associated with math achievement, even when test anxiety, science anxiety, and general anxiety were considered. Furthermore, girls showed higher math anxiety than boys., Conclusion: These adequate psychometric properties of the Arabic m-AMAS suggest that the construct of math anxiety has a cross-cultural similarity., 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 © 2023 Megreya, Al-Emadi and Moustafa.)

We propose that neural damage in Parkinson's disease (PD) is due to dysregulation of iron utilization rather than to high iron levels per se. Iron deposits are associated with neuronal cell death in substantia nigra (SN) resulting in PD where high levels of iron in SNs are due to dysregulation of iron utilization. Cytosolic aconitase (ACO1) upon losing an iron-sulfur cluster becomes iron regulatory protein 1 (IRP1). Rotenone increases levels of IRP1 and induces PD in rats. An increase in iron leads to inactivation of IRP1. We propose a novel treatment strategy to prevent PD. Specifically in rats given rotenone by subcutaneous injections, iron, from iron carbonyl from which iron is slowly absorbed, given three times a day by gavage will keep iron levels constant in the gut whereby iron levels and iron utilization systematically can be tightly regulated. Rotenone adversely affects complex 1 iron-sulfur proteins. Iron supplementation will increase iron-sulfur cluster formation switching IRP1 to ACO1. With IRP1 levels kept constantly low, iron utilization will systematically be tightly regulated stopping dysregulation of complex 1 and the neural damage done by rotenone preventing PD.

The Alzheimer's disease (AD) continuum is a unique spectrum of cognitive impairment that typically involves the stages of subjective memory complaints (SMC), mild cognitive impairment (MCI), and AD dementia. Neuropsychiatric symptoms (NPS), such as apathy, anxiety, stress, and depression, are highly common throughout the AD continuum. However, there is a dearth of research on how these NPS vary across the AD continuum, especially SMC. There is also disagreement on the effects of specific NPS on each stage of the AD continuum due to their collinearity with other NPS, cognitive decline, and environmental factors (e.g., stress). In this article, we conduct a novel perspective review of the scientific literature to understand the presence of NPS across the AD continuum. Specifically, we review the effects of apathy, depression, anxiety, and stress in AD, MCI, and SMC. We then build on this knowledge by proposing two theories of NPS' occurrence across the AD continuum. Consequently, we highlight the current landscape, limitations (e.g., differing operationalization), and contentions surrounding the NPS literature. We also outline theories that could clear up contention and inspire future NPS research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Self-imagination refers to a mnemonic strategy of imagining oneself at a scene related to a cue., Objective: We tested the effect of self-imagination on memory recall in Alzheimer's disease (AD) Methods: Individuals with AD and healthy controls were invited to perform two conditions. In the control (i.e., semantic elaboration) condition, participants were asked to define to which semantic category (e.g., dance) words (e.g., waltz) belong. However, in a self-imagining condition, participants were asked to imagine themselves in a scene related to the stimuli (e.g., dancing waltz). Both conditions were followed by two free memory tests with two different intervals (20 seconds vs. 20 minutes)., Results: Analysis showed a beneficial effect of self-imagination for the 20-second but not for the 20- minute recall in AD participants and controls., Conclusion: Clinicians can incorporate our findings when assessing, especially when trying to rehabilitate, episodic memory in AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease (AD) is currently diagnosed using a mixture of psychological tests and clinical observations. However, these diagnoses are not perfect, and additional diagnostic tools (e.g., MRI) can help improve our understanding of AD as well as our ability to detect the disease. Accordingly, a large amount of research has been invested into innovative diagnostic methods for AD. Functional MRI (fMRI) is a form of neuroimaging technology that has been used to diagnose AD; however, fMRI is incredibly noisy, complex, and thus lacks clinical use. Nonetheless, recent innovations in deep learning technology could enable the simplified and streamlined analysis of fMRI. Deep learning is a form of artificial intelligence that uses computer algorithms based on human neural networks to solve complex problems. For example, in fMRI research, deep learning models can automatically denoise images and classify AD by detecting patterns in participants' brain scans. In this systematic review, we investigate how fMRI (specifically resting-state fMRI) and deep learning methods are used to diagnose AD. In turn, we outline the common deep neural network, preprocessing, and classification methods used in the literature. We also discuss the accuracy, strengths, limitations, and future direction of fMRI deep learning methods. In turn, we aim to summarize the current field for new researchers, suggest specific areas for future research, and highlight the potential of fMRI to aid AD diagnoses., (© 2022 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Background: Within the concept of the self, a distinction can be made between ideal self (i.e., what would like to become) and feared self (i.e., what would not like to become in the future)., Objective: We investigated ideal self and feared self in patients with mild Alzheimer's disease (AD). We have also measured these self-related processes in relation to depression and anxiety., Methods: We invited 31 patients with mild AD and 35 control participants to decide whether they would consider the statement (e.g., I will be healthy) as a representation that they would like to acquire (i.e., ideal self) or to avoid (i.e., feared self)., Results: Analysis demonstrated that more participants assigned the "I will be healthy" statement to ideal self than to feared self, and this tendency was observed in both AD participants and controls. Less depression and anxiety were observed in participants who have assigned the "I will be healthy" statement to their ideal self compared to those who assigned this statement to their feared self, and this was observed in both AD participant and control groups., Conclusion: Our study demonstrates that AD patients tend to endorse positive health traits and to integrate these traits into their ideal self. AD patients tend to endorse health-related images that are associated with hopes when projecting into their future self. This positive projection into the self may create a motivational force (e.g., aspirations and hopes) to embody the "healthy" self that AD patients desire to be., Competing Interests: The authors declare no conflict of interest., (© 2022 – The authors. Published by IOS Press.)

Recent years have seen a rapid increase in the number of studies using evidence-accumulation models (such as the drift diffusion model, DDM) in the fields of psychology and neuroscience. These models go beyond observed behavior to extract descriptions of latent cognitive processes that have been linked to different brain substrates. Accordingly, it is important for psychology and neuroscience researchers to be able to understand published findings based on these models. However, many articles using (and explaining) these models assume that the reader already has a fairly deep understanding of (and interest in) the computational and mathematical underpinnings, which may limit many readers' ability to understand the results and appreciate the implications. The goal of this article is therefore to provide a practical introduction to the DDM and its application to behavioral data - without requiring a deep background in mathematics or computational modeling. The article discusses the basic ideas underpinning the DDM, and explains the way that DDM results are normally presented and evaluated. It also provides a step-by-step example of how the DDM is implemented and used on an example dataset, and discusses methods for model validation and for presenting (and evaluating) model results. Supplementary material provides R code for all examples, along with the sample dataset described in the text, to allow interested readers to replicate the examples themselves. The article is primarily targeted at psychologists, neuroscientists, and health professionals with a background in experimental cognitive psychology and/or cognitive neuroscience, who are interested in understanding how DDMs are used in the literature, as well as some who may to go on to apply these approaches in their own work., 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 Myers, Interian and Moustafa.)

Background: Verbal fluency tasks are widely used to assess cognitive and linguistic abilities in older adults. In this study, we investigated whether pupillometry can be used to measure verbal fluency in healthy older adults., Methods: We invited 45 older adults (Mean age = 66.55 years, SD = 4.32) to perform a verbal fluency task, which involves generating as many words as possible beginning with the letter "P" for a duration of one minute. We also invited participants to perform a control task, which involves counting aloud for one minute. In both tasks, we recorded pupil activity with eye-tracking glasses., Results: Analysis demonstrated a larger pupil size during the verbal fluency condition than in the counting condition. Significant positive correlations were observed between pupil size and correct responses on the verbal fluency task., Conclusion: The larger pupil size during the verbal fluency condition can be attributed to the cognitive load inherent in the verbal fluency task and/or to the ability of older adults to produce correct answers on this task. Our study demonstrates how pupillometry can be used as an ecological physiological assessment of not only verbal fluency, but also linguistic ability in general, in normal aging., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Dementia with Lewy bodies (DLB) is an insidious neurodegenerative disease characterised by a precipitous decline in cognition, sleep disturbances, motor impairment and psychiatric features. Recently, criteria for prodromal DLB (pDLB) including clinical features and biomarkers have been put forward to aid the classification and research of this ambiguous cohort of patients. Researchers can use these criteria to classify patients with mild cognitive impairment (MCI) with Lewy bodies (MCI-LB) as either possible (either one core clinical feature or one biomarker are present) or probable pDLB (at least two core clinical features, or one core clinical feature and at least one biomarker present). However, as isolated REM sleep behaviour disorder (iRBD) confirmed with polysomnography (PSG) can be included as both a clinical and a biomarker feature, potentially reducing the specificity of these diagnostic criteria. To address this issue, the current study classified a cohort of 47 PSG-confirmed iRBD patients as probable prodromal DLB only in the presence of an additional core feature or if there was an additional non-PSG biomarker. Thirteen iRBD patients demonstrated MCI (iRBD-MCI). In the iRBD-MCI group, one presented with parkinsonism and was thus classified as probable pDLB, whilst the remaining 12 were classified as only possible pDLB. All patients performed three tasks designed to measure attentional deficits, visual hallucinations and visuospatial impairment. Patients also attended clinical follow-ups to monitor for transition to DLB or another synucleinopathy. Findings indicated that the only patient categorised by virtue of having two core clinical features as probable pDLB transitioned over 28 months to a diagnosis of DLB. The performance of this probable pDLB patient was also ranked second-highest for their hallucinatory behaviours and had comparatively lower visuospatial accuracy. These findings highlight the need for more stringent diagnostic research criteria for pDLB, given that only one of the 13 patients who would have satisfied the current guidelines for probable pDLB transitioned to DLB after two years and was indeed the patient with two orthogonal core clinical features.

Background: There is a recent interest in pupil dilation during the retrieval of autobiographical memory. We pursued this line of research by measuring pupil diameter during the retrieval of self-defining memories, that is, memories that are highly vivid, emotionally intense, and are retrieved to reflect enduring concerns in a person's life., Methods: We invited 40 participants to retrieve self-defining memories while their pupil activity was recorder with eye-tracking glasses. We analyzed memories regarding specificity (i.e., specific or general) and emotional valence (neutral, positive, negative, or mixed)., Results: Analysis demonstrated larger pupil diameter during the retrieval of specific than general self-defining memories. However, no significant differences in pupil diameter were observed across the four emotional categories of self-defining memories., Discussion: The increased pupil size during retrieval of specific self-defining memories can be attributed to the autonoetic experience during retrieval of these memories and/or to the cognitive load as required to construct these memoires. By investigating pupil dilation during the retrieval of self-defining memories, our study provides an original, ecological, and reliable physiological assessment of these memories., (© 2022. Fondazione Società Italiana di Neurologia.)

Recent studies have shown that alpha oscillations (8-13 Hz) enable the decoding of auditory spatial attention. Inspired by sparse coding in cortical neurons, we propose a spiking neural network model for auditory spatial attention detection. The proposed model can extract the patterns of recorded EEG of leftward and rightward attention, independently, and uses them to train the network to detect auditory spatial attention. Specifically, our model is composed of three layers, two of which are Integrate and Fire spiking neurons. We formulate a new learning rule that is based on the firing rate of pre- and post-synaptic neurons in the first and second layers of spiking neurons. The third layer has 10 spiking neurons and the pattern of their firing rate is used in the test phase to decode the auditory spatial attention of a given test sample. Moreover, the effects of using low connectivity rates of the layers and specific range of learning parameters of the learning rule are investigated. The proposed model achieves an average accuracy of 90% with only 10% of EEG signals as training data. This study also provides new insights into the role of sparse coding in both cortical networks subserving cognitive tasks and brain-inspired machine learning., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Prospective memory, which is the ability to remember to perform an intended action in the future, has been found to be diminished in cognitively impaired non-demented individuals (CIND). This study investigated whether providing CIND with a social motive would improve their prospective memory performance. Accordingly, CIND and controls were asked to perform a prospective memory task which includes one of the following three conditions: a reward (i.e., a candy bar), no feedback, or a social motive (i.e., that performing the prospective memory task would be a favor for the experimenter). The participants also rated their commitment to achieve the three prospective conditions. Results showed lower prospective memory in CIND than in controls. Unlike controls, CIND did not benefit from the social motive; however, both populations demonstrated commitment toward this condition relative to the "reward" or "control" conditions. Although social motivation did not ameliorate prospective memory, CIND seem to demonstrate commitment to perform prospective memory tasks that involve social benefits for others.

Background: Dementia with Lewy bodies (DLB) is a common cause of dementia with poor prognosis and high hospitalization rates. DLB is frequently misdiagnosed, with clinical features that overlap significantly with other diseases including Parkinson's disease (PD). Clinical instruments that discriminate and track the progression of cognitive impairment in DLB are needed., Objectives: The current study was designed to assess the utility of a mental rotation (MR) task for assessing visuospatial impairments in early DLB., Methods: Accuracy of 22 DLB patients, 22 PD patients and 22 age-matched healthy controls in the MR task were compared at comparing shapes with 0°, 45° and 90° rotations., Results: Healthy controls and PD patients performed at similar levels while the DLB group were significantly impaired. Further, impairment in the visuospatial and executive function measures correlated with MR poor outcomes., Conclusion: These findings support the MR task as an objective measure of visuospatial impairment with the ability to adjust difficulty to suit impairments in a DLB population. This would be a useful tool within clinical trials., (© 2022 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Anger and aggression have large impact on people's safety and the society at large. In order to provide an intervention to minimise aggressive behaviours, it is important to understand the neural and cognitive aspects of anger and aggression. In this systematic review, we investigate the cognitive and neural aspects of anger-related processes, including anger-related behaviours and anger reduction. Using this information, we then review prior existing methods on the treatment of anger-related disorders as well as anger management, including mindfulness and cognitive behavioural therapy. At the cognitive level, our review that anger is associated with excessive attention to anger-related stimuli and impulsivity. At the neural level, anger is associated with abnormal functioning of the amygdala and ventromedial prefrontal cortex. In conclusions, based on cognitive and neural studies, we here argue that mindfulness based cognitive behavioural therapy may be better at reducing anger and aggression than other behavioural treatments, such as cognitive behavioural therapy or mindfulness alone. We provide key information on future research work and best ways to manage anger and reduce aggression. Importantly, future research should investigate how anger related behaviours is acquired and how stress impacts the development of anger., Competing Interests: Conflict of InterestThe authors declared not having any conflict of interest., (© The Author(s) 2022.)

Creativity is associated with finding novel, surprising, and useful solutions. We argue that creative cognitive processes, divergent thinking, abstraction, and improvisation are constructed on different novelty-based processes. The prefrontal cortex plays a role in creative ideation by providing a control mechanism. Moreover, thinking about novel solutions activates the distant or loosely connected neurons of a semantic network that involves the hippocampus. Novelty can also be interpreted as different combinations of earlier learned processes, such as the motor sequencing mechanism of the basal ganglia. In addition, the cerebellum is responsible for the precise control of movements, which is particularly important in improvisation. Our neurocomputational perspective is based on three creative processes centered on novelty seeking, subserved by the prefrontal cortex, hippocampus, cerebellum, basal ganglia, and dopamine. The algorithmic implementation of our model would enable us to describe commonalities and differences between these creative processes based on the proposed neural circuitry. Given that most previous studies have mainly provided theoretical and conceptual models of creativity, this article presents the first brain-inspired neural network model of creative cognition., (Copyright © 2022. Published by Elsevier Ltd.)

The COVID-19 pandemic has contributed to an increase in psychological distress. However, protective factors such as social support, psychological flexibility, and coping mechanisms can help individuals cope with the effects of psychological distress. This study aimed to test a recent hypothesis suggesting that psychological flexibility is not necessarily a coping strategy but a mechanism that can influence the coping strategies an individual employs during stressful events. We tested a mediation model that COVID-19 concerns would contribute to higher levels of perceived social support, which would directly increase psychological flexibility, and finally test if the effect of psychological flexibility on distress was mediated by approach and avoidant coping strategies. The results show that social support facilitates higher levels of psychological flexibility. Further, that psychological flexibility indirectly reduces psychological distress by reducing avoidant coping and increasing approach coping strategies. Within the context of COVID-19, we have shown the importance of social support and psychological flexibility for reducing distress. We have provided further evidence that psychological flexibility might not be a coping mechanism but a strategy that leads individuals to engage in more approach coping strategies and fewer avoidant coping strategies., (© 2022. The Author(s).)

Background: While event-based prospective memory refers to enacting intending action in response to a specific event or cue ("e.g., When I tell you there are 10 minutes left, please give me this stopwatch"), time-based prospective memory refers to enacting intending action in relation to a specific time ("In 10 minutes time, please ask me for a pencil"). Relative to event-based prospective memory, little is known about time-based prospective memory in Korsakoff's syndrome (KS)., Method: We used behavioral tasks to investigate event- and time-based prospective memory as well as episodic memory and executive function in patients with KS and control participants., Results: Analysis demonstrated lower event- and time-based prospective memory in patients with KS than in control participants. Interestingly, we found lower time-based than event-based prospective memory in patients with KS. Further, significant correlations were observed between prospective memory and episodic memory and executive function in the patients., Conclusions: Prospective memory is important for everyday life tasks, and failures of prospective memory can endanger patients' safety. One clinical implication of our findings is the importance of including an evaluation of prospective memory in cognitive evaluation of KS.

MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene expression, cell differentiation, and immunity against viral infections. In this study, we have used the computational tools, RNA22, RNAhybrid, and miRanda, to predict the microRNA-mRNA binding sites to find the putative microRNAs playing role in the host response to influenza C virus infection. This computational research screened the following four miRNAs: hsa-mir-3155a, hsa-mir-6796-5p, hsa-mir-3194-3p and hsa-mir-4673, which were further investigated for binding site prediction to the influenza C genome. Moreover, multiple sites in protein-coding region (HEF, CM2, M1-M2, NP, NS1- NS2, NSF, P3, PB1 and PB2) were predicted by RNA22, RNAhybrid and miRanda. Furthermore, 3D structures of all miRNAs and HEF were predicted and checked for their binding potential through molecular docking analysis. The comparative results showed that among all proteins, HEF is higher in prevalence throughout the analysis as a potential (human-derived) microRNAs target. The target-site conservation results showed that core nucleotide sequence in three different strains is responsible for potential miRNA binding to different viral strains. Further steps to use these microRNAs may lead to new therapeutic insights on fighting influenza virus infection., 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 Hassan, Iqbal, Naqvi, Alashwal, Moustafa and Kloczkowski.)

A spiking neural network model inspired by synaptic pruning is developed and trained to extract features of hand-written digits. The network is composed of three spiking neural layers and one output neuron whose firing rate is used for classification. The model detects and collects the geometric features of the images from the Modified National Institute of Standards and Technology database (MNIST). In this work, a novel learning rule is developed to train the network to detect features of different digit classes. For this purpose, randomly initialized synaptic weights between the first and second layers are updated using average firing rates of pre- and postsynaptic neurons. Then, using a neuroscience-inspired mechanism named, "synaptic pruning" and its predefined threshold values, some of the synapses are deleted. Hence, these sparse matrices named, "information channels" are constructed so that they show highly specific patterns for each digit class as connection matrices between the first and second layers. The "information channels" are used in the test phase to assign a digit class to each test image. In addition, the role of feed-back inhibition as well as the connectivity rates of the second and third neural layers are studied. Similar to the abilities of the humans to learn from small training trials, the developed spiking neural network needs a very small dataset for training, compared to the conventional deep learning methods that have shown a very good performance on the MNIST dataset. This work introduces a new class of brain-inspired spiking neural networks to extract the features of complex data images., 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 Faghihi, Alashwal and Moustafa.)

Impurity profiling has a rising importance nowadays due to the increased health problems associated with impurities and degradation products found in several drug substances and formulations. Three advanced, accurate and precise chemometric methods were developed as impurity profiling methods for a mixture of bisoprolol fumarate (BIS) and perindopril arginine (PER) with their degradation products which represent drug impurity or a precursor to such impurity. The methods applied were Partial Least Squares (PLS-1), Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and Artificial Neural Networks (ANN). Genetic Algorithm (GA) was used as a variable selection tool to select the most significant wavelengths for the three chemometric models. For proper analysis, a 5-factor 5-level experimental design was used to establish a calibration set of 25 mixtures containing different ratios of the drugs and their degradation products (impurities). The validity of the proposed methods was assessed using an independent validation set. The designed models were able to predict the concentrations of the drugs and the degradation products/impurities in the validation set and pharmaceutical formulation. The proposed methods presented a powerful alternative to traditional and expensive chromatographic methods as impurity profiling tools., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2021. Published by Elsevier B.V.)

Background: Tyrosine kinase inhibitors (TKI) were initially demonstrated as an efficacious treatment for renal cell carcinoma (RCC). However, after a median treatment length of 14 months, a vast majority of patients develop resistance. This study analyzed a combination therapy of tipifarnib (Tipi) + sunitinib that targeted exosome-conferred drug resistance., Methods: 786-O, 786-O-SR (sunitinib resistant), A498, A498-SR, Caki-2, Caki-2-SR, and 293T cells were cultured. Exosomes were collected using differential ultracentrifugation. Cell proliferation, Jurkat T cell immune assay, and immunoblot analysis were used for downstream analysis., Results: SR exosomes treatment displayed a cytotoxic effect on immune cells. This cytotoxic effect was associated with increased expression of PD-L1 on SR exosomes when compared to sunitinib-sensitive (SS) exosomes. Additionally, Tipi treatment downregulated PD-L1 expression on exosomes derived from SR cell lines. Tipi's ability to downregulate PD-L1 in exosomes has a significant application within patients. Exosomes collected from patients with RCC showed increased PD-L1 expression over subjects without RCC. Next, exosome concentrations were then compared after Tipi treatment, with all SS cell lines displaying an even greater reduction. On immunoblot assay, 293T cells showed a dose-dependent increase in Alix with no change in either nSMase or Rab27a. Conversely, all the SS and SR cell lines displayed a decrease in all three markers. After a cell proliferation employed a 48-h treatment on all SS and SR cell lines, the drug combination displayed synergistic ability to decrease tumor growth., Conclusions: Tipifarnib attenuates both the exosome endosomal sorting complex required for endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways, thereby blocking exosome biogenesis and secretion as well as downregulating PD-L1 on SS and SR cells.

To help address the increasing challenges related to the provision of dementia care, dementia registries have emerged around the world as important tools to gain insights and a better understanding of the disease process. Dementia registries provide a valuable source of standardized data collected from a large number of patients. This review explores the published research relating to different dementia registries around the world and discusses how these registries have improved our knowledge and understanding of the incidence, prevalence, risk factors, mortality, diagnosis, and management of dementia. A number of the best-known dementia registries with high research output including SveDem, NACC, ReDeGi, CREDOS and PRODEM were selected to study the publication output based on their data, investigate the key findings of these registry-based studies. Registries data contributed to understanding many aspects of the disease including disease prevalence in specific areas, patient characteristics and how they differ in populations, mortality risks, as well as the disease risk factors. Registries data impacted the quality of patients' lives through determining the best treatment strategy for a patient based on previous patient outcomes. In conclusion, registries have significantly advanced scientific knowledge and understanding of dementia and impacted policy, clinical practice care delivery., 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 Heikal, Salama, Richard, Moustafa and Lawlor.)

It is well established that pupil activity indexes cognitive processing. For instance, research has consistently demonstrated that the pupil reacts to working memory span task performance. However, little is known about pupil reaction to cognitive processing in Alzheimer's Disease (AD). We thus investigated whether span tasks can modulate pupil size in patients with AD. We invited 24 patients with AD and 24 healthy older adults to perform backward and forward spans, as well as to count aloud in a control condition, while their pupil activity was recorded with eye tracking glasses. In patients with AD, analysis demonstrated larger pupil size during backward spans ( M = 2.12, SD = .39) than during forward spans ( M = 1.98, SD = .36) [ t (23) = 3.22, p = .004], larger pupil size during forward spans than during counting ( M = 1.67, SD = .33) [ t (23) = 4.75, p < .001], as well as larger pupil size during backward spans than during counting [ t (23) = 10.60, p < .001]. In control participants, analysis demonstrated larger pupil size during backward spans ( M = 3.36, SD = .49) than during forward spans ( M = 2.85, SD = .68) [ t (23) = 5.82, p < .001], larger pupil size during forward spans than during counting ( M = 2.09, SD = .62) [ t (23) = 5.42, < .001], as well as larger pupil size during backward spans than during counting [ t (23) = 9.70, p < .001]. Results also demonstrated a significant interaction effect between groups and conditions [ F (2,92) = 16.63, p < .001]; in other words, patients with AD have shown fewer variations on the pupil size across the conditions compared to the control participants. The larger pupil size during backward spans, compared with forward spans or counting, can be attributed to the high cognitive load of backward spans. The modulation of pupil size, as observed across backward/forward spans and counting, can possibly be attributed to sympathetic/adrenergic and parasympathetic/cholinergic activities. Our study demonstrates the value of pupillometry as a potential biomarker of cognitive processing in AD., (Copyright © 2022 El Haj et al.)

A large body of research attributes learning deficits in schizophrenia (SZ) to the systems involved in value representation (prefrontal cortex, PFC) and reinforcement learning (basal ganglia, BG) as well as to the compromised connectivity of these regions. In this study, we employed learning tasks hypothesized to probe the function and interaction of the PFC and BG in patients with SZ-spectrum disorders in comparison to healthy control (HC) subjects. In the Instructed Probabilistic Selection task (IPST), participants received false instruction about one of the stimuli used in the course of probabilistic learning which creates confirmation bias, whereby the instructed stimulus is overvalued in comparison to its real experienced value. The IPST was administered to 102 patients with SZ and 120 HC subjects. We have shown that SZ patients and HC subjects were equally influenced by false instruction in reinforcement learning (RL) probabilistic task (IPST) ( p -value = 0.441); however, HC subjects had significantly higher learning rates associated with the process of overcoming cognitive bias in comparison to SZ patients ( p -value = 0.018). The behavioral results of our study could be hypothesized to provide further evidence for impairments in the SZ-BG circuitry; however, this should be verified by neurofunctional imaging studies.

Many studies on the drift-diffusion model (DDM) explain decision-making based on a unified analysis of both accuracy and response times. This review provides an in-depth account of the recent advances in DDM research which ground different DDM parameters on several brain areas, including the cortex and basal ganglia. Furthermore, we discuss the changes in DDM parameters due to structural and functional impairments in several clinical disorders, including Parkinson's disease, Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorders, Obsessive-Compulsive Disorder (OCD), and schizophrenia. This review thus uses DDM to provide a theoretical understanding of different brain disorders., 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 Gupta, Bansal, Alashwal, Kacar, Balci and Moustafa.)

Schizophrenia spectrum disorders (SZ) are characterized by impairments in probabilistic reinforcement learning (RL), which is associated with dopaminergic circuitry encompassing the prefrontal cortex and basal ganglia. However, there are no studies examining dopaminergic genes with respect to probabilistic RL in SZ. Thus, the aim of our study was to examine the impact of dopaminergic genes on performance assessed by the Probabilistic Selection Task (PST) in patients with SZ in comparison to healthy control (HC) subjects. In our study, we included 138 SZ patients and 188 HC participants. Genetic analysis was performed with respect to the following genetic polymorphisms: rs4680 in COMT , rs907094 in DARP-32 , rs2734839, rs936461, rs1800497, and rs6277 in DRD2 , rs747302 and rs1800955 in DRD4 and rs28363170 and rs2975226 in DAT1 genes. The probabilistic RL task was completed by 59 SZ patients and 95 HC subjects. SZ patients performed significantly worse in acquiring reinforcement contingencies during the task in comparison to HCs. We found no significant association between genetic polymorphisms and RL among SZ patients; however, among HC participants with respect to the DAT1 rs28363170 polymorphism, individuals with 10-allele repeat genotypes performed better in comparison to 9-allele repeat carriers. The present study indicates the relevance of the DAT1 rs28363170 polymorphism in RL in HC participants.

While there are many studies on pareidolia in healthy individuals and patients with schizophrenia, to our knowledge, there are no prior studies on pareidolia in patients with bipolar disorder. Accordingly, in this study, we, for the first time, measured pareidolia in patients with bipolar disorder ( N = 50), and compared that to patients with schizophrenia ( N = 50) and healthy controls ( N = 50). We have used (a) the scene test, which consists of 10 blurred images of natural scenes that was previously found to produce illusory face responses and (b) the noise test which had 32 black and white images consisting of visual noise and 8 images depicting human faces; participants indicated whether a face was present on these images and to point to the location where they saw the face. Illusory responses were defined as answers when observers falsely identified objects that were not on the images in the scene task (maximum illusory score: 10), and the number of noise images in which they reported the presence of a face (maximum illusory score: 32). Further, we also calculated the total pareidolia score for each task (the sum number of images with illusory responses in the scene and noise tests). The responses were scored by two independent raters with an excellent congruence (kappa > 0.9). Our results show that schizophrenia patients scored higher on pareidolia measures than both healthy controls and patients with bipolar disorder. Our findings are agreement with prior findings on more impaired cognitive processes in schizophrenia than in bipolar patients., 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 Abo Hamza, Kéri, Csigó, Bedewy and Moustafa.)

Background: Among all types of tobacco consumption, Water-Pipe Smoking (WPS) is the most widely used in the Middle East and second-most in several other countries. The effect of WPS on normal development is not yet fully understood, thus the aim of this study is to explore the acute toxicity effects of WPS extract on zebrafish larvae., Methods: In this study, we compared the effects of WPS smoke condensates at concentrations varying from 50 to 200 µg/mL on developmental, cardiac, and behavioural (neurotoxicity) functions. Gene expression patterns of cardiac biomarkers were also evaluated by RT-qPCR., Results: Exposing zebrafish embryos to 50, 100, 150 and 200 µg/mL WPS for three days did not affect the normal morphology of Zebrafish embryos, as the tail flicking, behavioural and locomotion assays did not show any change. However, WPS deregulated cardiac markers including atrial natriuretic peptide (ANP/NPPA) and brain natriuretic peptide (BNP/NPPB). Furthermore, it induced apoptosis in a dose-dependent manner., Conclusion: Our data demonstrate that WPS can significantly affect specific cardiac parameters during the normal development of zebrafish. Further investigations are necessary to elucidate the pathogenic outcome of WPS on different aspects of human life, including pregnancy.

The present study was performed to evaluate the influence of low crude protein (CP) levels, zinc sources (organic as zinc methionine-Zn-Met and inorganic as zinc oxide-ZnO) and their interactions on growth performance, carcass traits, and blood components of growing Japanese quail. A total of 450 one-wk-old Japanese quail with the same body weights were randomly distributed into 9 groups of 50 birds. The 9-diet treatments comprised 3 levels of CP (20, 22, and 24%) and 3 Zn source (0 g of Zn/kg diet, 0.1 g ZnO/kg diet, and 0.1 g Zn-Met/kg diet). The results obtained from this study showed that there were no significant differences among the groups, except for differences in body weight (BW) and body weight gain (BWG) at 3 to 5 - and 1 to 5 wk of age for quail supplemented with 24% and 20% CP. All the studied biochemical parameters were significantly influenced by different levels of CP and Zn, except urea and creatinine, which were affected by CP levels only. In conclusion, dietary protein level for growing Japanese quails could be reduced to 20% without negative effects on their performance, carcass traits, and blood metabolites., Competing Interests: DISCLOSURES The authors have no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

A 60-day experiment was performed to assess the efficacy of dietary Astragalus membranaceus polysaccharides (ASP) in attenuation of sub-lethal thallium (Tl) toxicity in Nile tilapia. Six experimental groups (in triplicates) were designed where a fish group was raised in clean water and fed basal diet and served as control (CONT), two groups were fed the basal diet supplemented with 0.15% and 0.30% ASP (ASPL and ASPH), Tl-intoxicated group exposed to 1/10 of 96-h LC50 (= 41.9 μg/L), and two other groups were fed 0.15% and 0.30% ASP and concomitantly exposed to 41.9 μg Tl/L (ASPL-Tl and ASPH-Tl). At the end of the experiment, fish behavioral responses, clinical signs, survivability, growth, whole-body composition, intestinal digestive enzymes, serum biochemical parameters, hepatic antioxidative biomarkers, and transcription of stress and apoptosis genes were assessed. Results showed that the whole-body composition, intestinal α-amylase and protease enzymes, serum AST and blood urea levels, and hepatic GSH were not significantly different among groups (P > 0.05). The Tl-intoxicated fish group was off food, had darkened skin, showed restlessness and hyperexcitability, and high mortalities. FBW, WG, SGR and FI were significantly decreased alongside increase FCR in the Tl-exposed group. Tl exposure caused significant increases (P < 0.05) in intestinal lipase enzyme and serum indices such as ALT, creatinine, total cholesterol, triglycerides, glucose, and cortisol levels. Moreover, a significant decreases in hepatic CAT and SOD enzyme activities and significant increases in hepatic MDA contents were also noticed (P < 0.05). Furthermore, Tl exposure induced significant upregulation of hepatic HSP70 and apoptosis-related genes (p53 and caspase 3). Interestingly, dietary supplementation with ASP in ASPL-Tl and ASPH-Tl groups modulated the parameters mentioned above but still not reached the CONT values. Altogether, this study suggests that ASP could be beneficial in the modulation of sub-lethal Tl toxicity effects in Nile tilapia. Additionally, we can conclude that using natural feed supplements such as ASP in aquafeed might be necessary for maintaining the overall health performances of Nile tilapia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Insecticides are widely employed in agriculture to control pests and as major factors for enhancing crop productivity. Thiacloprid (TH) is one of the most-used insecticides worldwide. In this study, the negative impact of TH on the brain tissue of developing chicken embryo models and the modulatory effect of chicoric (CA) and rosmarinic (RA) acids were investigated. The eggs were injected in ovo with different doses of TH (0.1, 1, 10, and 100 μg/egg). TH significantly increased the oxidative damage in the brain of exposed embryos in a dose-dependent manner ( p < 0.05). TH significantly elevated the oxidative stress markers; protein carbonyl, malondialdehyde content, and DNA damage ( p < 0.05). Myeloperoxidase activity and nitric oxide significantly increased with overexpression of the pro-inflammatory cytokines (interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta) and stress-related and apoptotic genes (NF-KB, Caspase-3) in the brain tissue on both biochemical and molecular levels ( p < 0.05), while downregulating the expression of antiapoptotic Bcl-2. Co-treatment of CA and RA with TH markedly decreased the insecticide-induced toxicity with a prominent synergistic effect ( p < 0.05). In conclusion, TH is suggested to be a possible neurotoxic to embryos of vertebrates including human. The study also revealed the antioxidant, anti-inflammatory, genoprotective, and antiapoptotic property of CA and RA against TH toxicity.

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.

The methacholine challenge test is considered to be the gold standard bronchoprovocation test used to diagnose asthma, and this test is always performed in pulmonary function labs or doctors' offices. Methacholine (MCH) acts by inducing airway tightening/bronchoconstriction, and more importantly, MCH is hydrolyzed by cholinesterase enzyme (ChE). Recently, the American Thoracic Society raised concerns about pulmonary function testing during the COVID-19 pandemic due to recently reported correlation between cholinesterase and COVID-19 pneumonia severity/mortality, and it was shown that cholinesterase levels are reduced in the acute phase of severe COVID-19 pneumonia. This work describes the microfabrication of potentiometric sensors using copper as the substrate and chemically polymerized graphene nanocomposites as the transducing layer for tracking the kinetics of MCH enzymatic degradation in real blood samples. The in-vitro estimation of the characteristic parameters of the MCH metabolism [Michaelis-Menten constant (K m ) and reaction velocity (V max )] were found to be 241.041 μM and 56.8 μM/min, respectively. The proposed sensor is designed to be used as a companion diagnostic device that can (i) answer questions about patient eligibility to perform methacholine challenge tests, (ii) individualize/personalize medical dosing of methacholine, (iii) provide portable and inexpensive devices allowing automated readouts without the need for operator intervention (iv) recommend therapeutic interventions including intensive care during early stages and reflecting the disease state of COVID-19 pneumonia. We hope that this methacholine electrochemical sensor will help in assaying ChE activity in a "timely" manner and predict the severity and prognosis of COVID-19 to improve treatment outcomes and decrease mortality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

There is a lack of predictive markers for early and rapid identification of disease progression in COVID-19 patients. Our study aims at identifying microRNAs (miRNAs)/small nucleolar RNAs (snoRNAs) as potential biomarkers of COVID-19 severity. Using differential expression analysis of microarray data (n = 29), we identified hsa-miR-1246, ACA40, hsa-miR-4532, hsa-miR-145-5p, and ACA18 as the top five differentially expressed transcripts in severe versus asymptomatic, and ACA40, hsa-miR-3609, ENSG00000212378 (SNORD78), hsa-miR-1231, hsa-miR-885-3p as the most significant five in severe versus mild cases. Moreover, we found that white blood cell (WBC) count, absolute neutrophil count (ANC), neutrophil (%), lymphocyte (%), red blood cell (RBC) count, hemoglobin, hematocrit, D-Dimer, and albumin are significantly correlated with the identified differentially expressed miRNAs and snoRNAs. We report a unique miRNA and snoRNA profile that is associated with a higher risk of severity in a cohort of SARS-CoV-2 infected patients. Altogether, we present a differential expression analysis of COVID-19-associated microRNA (miRNA)/small nucleolar RNA (snoRNA) signature, highlighting their importance in SARS-CoV-2 infection.

Natural chalcones possess antitumor properties and play a role as inducers of apoptosis, antioxidants and cytotoxic compounds. We recently reported that novel nitrogen chalcone-based compounds, which were generated in our lab, have specific effects on triple-negative breast cancer cells. However, the outcome of these two new compounds on human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains nascent. Thus, we herein investigated the effects of these compounds (DK-13 and DK-14) on two HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data revealed that these compounds inhibit cell proliferation, deregulate cell-cycle progression and significantly induce cell apoptosis in both cell lines. Furthermore, the two chalcone compounds cause a significant reduction in the cell invasion ability of SKBR3 and ZR75 cancer cells. In parallel, we found that DK-13 and DK-14 inhibit colony formation of both cell lines in comparison to their matched controls. On the other hand, we noticed that these two compounds can inhibit angiogenesis in the chorioallantoic membrane model. The molecular pathway analysis of chalcone compounds exposed cells revealed that these compounds inhibit the expression of both JNK1/2/3 and ERK1/2, the major plausible molecular pathways behind these events. Our findings implicate that DK-13 and DK-14 possess effective chemotherapeutic outcomes against HER2-positive breast cancer via the ERK1/2 and JNK1/2/3 signaling pathways.

Platelet-rich plasma (PRP) provides a treatment option for female pattern hair loss (FPHL). However, the most suitable preparation method is not yet clear. The primary aim is to compare between the efficacy of single- versus double-spin PRP preparation injection in the treatment of FPHL, while the secondary aim is to assess the relationship between vascular endothelial growth factor (VEGF) concentrations in different prepared PRP preparations (pre- and post-activation) and the obtained treatment results. 15 female patients with FPHL were subjected to intradermal injection of double-spin prepared PRP into the right (Rt) half of the scalp and single-spin prepared PRP into the left (Lt) half of the scalp, three sessions, 3 weeks apart. Evaluation of treatment response was done through comparing patients' photographs, patients' satisfaction and trichoscopic assessment (measurement of terminal hair density) before and after treatment. In addition, VEGF concentration was measured in different PRP samples before and after activation with calcium gluconate. Results showed clinical improvement in both sides of scalp 6 weeks after last PRP session. Meanwhile, Rt median terminal hair density measured by trichoscan following treatment was significantly higher compared to Lt median terminal hair density. Furthermore, VEGF concentration did not differ significantly in single- versus double-spin prepared PRP, or upon calcium activation. PRP is effective in treatment of FPHL. Double-spin method could yield better results than single-spin method. Adding calcium gluconate prior to PRP injection is of no value., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

A rapid increase in the number of patients with Alzheimer's disease (AD) is expected over the next decades. Accordingly, there is a critical need for early-stage AD detection methods that can enable effective treatment strategies. In this study, we consider the ability of episodic-memory measures to predict mild cognitive impairment (MCI) to AD conversion and thus, detect early-stage AD. For our analysis, we studied 307 participants with MCI across four years using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Using a binary logistic regression, we compared episodic-memory tests to each other and to prominent neuroimaging methods in MCI converter (MCI participants who developed AD) and MCI non-converter groups (MCI participants who did not develop AD). We also combined variables to test the accuracy of mixed-predictor models. Our results indicated that the best predictors of MCI to AD conversion were the following: a combined episodic-memory and neuroimaging model in year one (59.8%), the Rey Auditory Verbal Learning Test in year two (71.7%), a mixed episodic-memory predictor model in year three (77.7%) and the Logical Memory Test in year four (77.2%) of ADNI. Overall, we found that individual episodic-memory measure and mixed models performed similarly when predicting MCI to AD conversion. Comparatively, individual neuroimaging measures predicted MCI conversion worse than chance. Accordingly, our results indicate that episodic-memory tests could be instrumental in detecting early-stage AD and enabling effective treatment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Anxiety spectrum disorders are characterized by excessive and uncontrollable worrying about potential negative events in the short- and long-term future. Various reports linked anxiety spectrum disorders with working memory (WM) deficits despite conflicting results stemming from different study approaches. It remains unclear, however, how different anxiety spectrum disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD), differ in WM function. In this study, we utilized verbal, numerical, and sequential evaluations of WM to cover most possible facets of the WM data space. We used principal component analysis to extract the uncorrelated/whitened components of WM based on these measures. We evaluated medication-free patients with GAD, SAD, and PD patients as well as matched healthy individuals using a battery that measures WM duration and load. We found that patients with GAD and SAD, but not PD, exhibited poor performance only in the WM principal component that represents maintenance. There were no other significant differences between the four groups. Further, different WM components significantly predicted the severity of anxiety symptoms in the groups. We explored the clinical utility of WM components for differentiating patients with anxiety spectrum disorders from healthy individuals. By only using the WM components that represent maintenance and encoding, we managed to differentiate patients from controls in 84% of cases. For the first time, we present multiple novel approaches to examine cognitive function and design cognitive screening, and potentially diagnostics, for psychiatric disorders., Competing Interests: This study received funding from Arab Palestinian Investment Company (APIC), Hikma Pharmaceuticals LLC., and GMS Holdings. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. 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 Abushalbaq, Khdour, Abo Hamza, Moustafa and Herzallah.)

Future thinking, which is the ability to project oneself forward in time to pre-experience an event, is intimately associated with emotions. We investigated whether emotional future thinking can activate emotional facial expressions. We invited 43 participants to imagine future scenarios, cued by the words "happy," "sad," and "city." Future thinking was video recorded and analysed with a facial analysis software to classify whether facial expressions (i.e., happy, sad, angry, surprised, scared, disgusted, and neutral facial expression) of participants were neutral or emotional. Analysis demonstrated higher levels of happy facial expressions during future thinking cued by the word "happy" than "sad" or "city." In contrast, higher levels of sad facial expressions were observed during future thinking cued by the word "sad" than "happy" or "city." Higher levels of neutral facial expressions were observed during future thinking cued by the word "city" than "happy" or "sad." In the three conditions, the neutral facial expressions were high compared with happy and sad facial expressions. Together, emotional future thinking, at least for future scenarios cued by "happy" and "sad," seems to trigger the corresponding facial expression. Our study provides an original physiological window into the subjective emotional experience during future thinking.

Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide. Human papillomaviruses (HPVs) and Epstein-Barr virus (EBV) have been reported to be present in different types of human cancers, including CRCs, where they can play a key role in the onset and/or progression of these cancers. Thus, we herein explored the prevalence of high-risk HPVs and EBV in a cohort of 94 CRC tissue samples and 13 colorectal normal tissues from the Lebanese population using polymerase chain reaction, immunohistochemistry, and tissue microarray methodologies. We found that high-risk HPVs are present in 64%, while EBV is present in 29% of our CRC samples. Additionally, our data showed that high-risk HPV types (16, 18, 35, 58, 51, 45, 52, 31, and 33) are the most frequent in CRC in the Lebanese cohort, respectively. Our data point out that HPVs and EBV are copresent in 28% of the samples. Thus, this study clearly suggests that high-risk HPVs and EBV are present/copresent in CRCs, where they could play an important role in colorectal carcinogenesis. Nevertheless, further investigations using a larger cohort are needed to elucidate the possible cooperation between these oncoviruses in the development of CRC.

Information security has for long time been a field of study in computer science, software engineering, and information communications technology. The term 'information security' has recently been replaced with the more generic term cybersecurity. The goal of this paper is to show that, in addition to computer science studies, behavioural sciences focused on user behaviour can provide key techniques to help increase cyber security and mitigate the impact of attackers' social engineering and cognitive hacking methods (i.e., spreading false information). Accordingly, in this paper, we identify current research on psychological traits and individual differences among computer system users that explain vulnerabilities to cyber security attacks and crimes. Our review shows that computer system users possess different cognitive capabilities which determine their ability to counter information security threats. We identify gaps in the existing research and provide possible psychological methods to help computer system users comply with security policies and thus increase network and information security., 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 Moustafa, Bello and Maurushat.)

Serial evaluation of blood lactate, including lactate clearance, may have greater value over single measurement at the time of presentation. The rationale of the current study was to evaluate the use of lactate clearance after 6 hours of admission to pediatric intensive care unit (PICU) as a predictor of mortality in critically ill children. A prospective observational study was conducted in a nine-bed PICU of a tertiary care teaching hospital over a period of 6 months. Lactate levels were measured in arterial blood samples of 76 patients at the time of admission and 6 hours later. According to calculated lactate clearance, patients were divided into group A (lactate clearance more than 0) which included 71% of patients and group B (lactate clearance ≤0) which included 29% of patients. Lactate level at admission was a poor predictor of mortality (area under receiver operating characteristic curve [AUC] = 0.519, p  = 0.789). Lactate clearance after 6 hours of admission was a significant predictor of mortality (AUC = 0.766, p  < 0.001). Using Kaplan-Meier survival curve, overall survival was significantly better among group A ( p  < 0.001). Using multivariate logistic regression model, lactate clearance after 6 hours (odds ratio = 0.98, 95% confidence interval [CI]: 0.96-0.99) and The Pediatric Index of Mortality 2 (PIM2) score (odds ratio = 4.7, 95% CI: 1.85-12.28) had independent prognostic significance with regard to mortality ( p  = 0.030, 0.001 respectively). We conclude that lactate clearance after 6 hours of admission can predict mortality in critically ill children., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Proteins are tiny players involved in the activation and deactivation of multiple signaling cascades through interactions in cells. The TNFR1 and MADD interact with each other and mediate downstream protein signaling pathways which cause neuronal cell death and Alzheimer's disease. In the current study, a molecular docking approach was employed to explore the interactive behavior of TNFR1 and MADD proteins and their role in the activation of downstream signaling pathways. The computational sequential and structural conformational results revealed that Asp400, Arg58, Arg59 were common residues of TNFR1 and MADD which are involved in the activation of downstream signaling pathways. Aspartic acid in negatively charged residues is involved in the biosynthesis of protein. However, arginine is a positively charged residue with the potential to interact with oppositely charged amino acids. Furthermore, our molecular dynamic simulation results also ensured the stability of the backbone of TNFR1 and MADD death domains (DDs) in binding interactions. This DDs interaction mediates some conformational changes in TNFR1 which leads to the activation of mediators proteins in the cellular signaling pathways. Taken together, a better understanding of TNFR1 and MADD receptors and their activated signaling cascade may help treat Alzheimer's disease. The death domains of TNFR1 and MADD could be used as a novel pharmacological target for the treatment of Alzheimer's disease by inhibiting the MAPK pathway.

Background & Aims: In this article we connect the dysregulation of the transsulfuration pathway to bone dysregulations and propose a novel treatment for osteoporosis. Current treatments for osteoporosis are very frequently inadequate. In osteoporosis, the risk of fractures increases with increased homocysteine (Hcy)., Methods: Here, we conduct a review on the relationship between osteoporosis and the dysregulation of the transsulfuration pathway., Results: we show that the transsulfuration pathway metabolizes Hcy to L-cysteine. Increased Hcy levels point to the transsulfuration pathway being dysregulated. With the transsulfuration pathway dysregulated, there will be decreased levels of L-cysteine and decreased levels of taurine, which is synthesized from L-cysteine. Taurine levels are decreased in patients with osteoporosis. Taurine regulates intracellular calcium homeostasis. Taurine, also, when conjugated with bile acids assists with absorption of fats and fat-soluble vitamins such as vitamin D and vitamin K. Dysregulated calcium homeostasis, decreased calcium absorption and decreased absorption of vitamin D and vitamin K due to low levels of taurine negatively affect bone mineral density (BMD) leading to osteoporosis and fractures., Conclusions: In this article, we propose that a combination of taurine, calcium, vitamin D and vitamin K, could increase BMD reducing number of years spent in disability and reducing deaths due to fractures in patients with osteoporosis., Competing Interests: Declaration of competing interest TB and AM declares no conflict of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by cardinal motor impairments, including akinesia and tremor, as well as by a host of non-motor symptoms, including both autonomic and cognitive dysfunction. PD is associated with a death of nigral dopaminergic neurons, as well as the pathological spread of Lewy bodies, consisting predominantly of the misfolded protein alpha-synuclein. To date, only symptomatic treatments, such as levodopa, are available, and trials aiming to cure the disease, or at least halt its progression, have not been successful. Wong et al. (2019) suggested that the lack of effective therapy against neurodegeneration in PD might be attributed to the fact that the molecular mechanisms standing behind the dopaminergic neuronal vulnerability are still a major scientific challenge. Understanding these molecular mechanisms is critical for developing effective therapy. Thirty-five years ago, Calne and William Langston (1983) raised the question of whether biological or environmental factors precipitate the development of PD. In spite of great advances in technology and medicine, this question still lacks a clear answer. Only 5-15% of PD cases are attributed to a genetic mutation, with the majority of cases classified as idiopathic, which could be linked to exposure to environmental contaminants. Rodent models play a crucial role in understanding the risk factors and pathogenesis of PD. Additionally, well-validated rodent models are critical for driving the preclinical development of clinically translatable treatment options. In this review, we discuss the mechanisms, similarities and differences, as well as advantages and limitations of different neurotoxin-induced rat models of PD. In the second part of this review, we will discuss the potential future of neurotoxin-induced models of PD. Finally, we will briefly demonstrate the crucial role of gene-environment interactions in PD and discuss fusion or dual PD models. We argue that these models have the potential to significantly further our understanding of PD.

Surface-enhanced infrared absorption spectroscopy offers an alternative to conventional IR spectroscopy and utilizes the signal enhancement exerted by the plasmon resonance of nanostructured metal thin films. Citrate-capped silver nanoparticles were prepared in a single-step method, and their morphology was identified using transmission electron microscopy, scanning electron microscopy, ultraviolet/visible spectrophotometry, and Zetasizer. The nanoparticles generated were deposited on the surface of cheap aluminum slides for different durations aiming for the selection of the best time producing a thin film, suitable to act as a lab-on-a-chip SEIRA substrate. These substrates were coupled to partial least squares regression tools for simultaneous resolving of the quinary mixture in commercial dosage forms of bisoprolol, perindopril, bisoprolol acid degradation product, bisoprolol alkali degradation product, and perindoprilat in concentration ranges of 15-75, 60-300, 15-55, 12-60, and 20-80 μg/mL with limits of detection values of 0.69, 3.43, 0.97, 1.25, and 1.09 μg/mL, respectively. Overall, we could demostrate that the localized surface plasmon resonance sensor coupled to chemometrics provides cheap, simple, selective, multiplex, rapid, and molecular specific procedures for impurity detection, which would be beneficial in many applications for quality control and quality accuracy of active pharmaceutical ingredients.

Renal Cell Carcinoma (RCC) is the most common form of kidney cancer, with clear cell RCC (ccRCC) representing about 85% of all RCC tumors. There are limited curable treatments available for metastatic ccRCC because this disease is unresponsive to conventional targeted systemic pharmacotherapy. Exosomes (Exo) are small extracellular vesicles (EVs) secreted from cancer cells with marked roles in tumoral signaling and pharmacological resistance. Ketoconazole (KTZ) is an FDA approved anti-fungal medication which has been shown to suppress exosome biogenesis and secretion, yet its role in ccRCC has not been identified. A time-course, dose-dependent analysis revealed that KTZ selectively decreased secreted Exo in tumoral cell lines. Augmented Exo secretion was further evident by decreased expression of Exo biogenesis (Alix and nSMase) and secretion (Rab27a) markers. Interestingly, KTZ-mediated inhibition of Exo biogenesis was coupled with inhibition of ERK1/2 activation. Next, selective inhibitors were employed and showed ERK signaling had a direct role in mediating KTZ's inhibition of exosomes. In sunitinib resistant 786-O cells lines, the addition of KTZ potentiates the efficacy of sunitinib by causing Exo inhibition, decreased tumor proliferation, and diminished clonogenic ability of RCC cells. Our findings suggest that KTZ should be explored as an adjunct to current RCC therapies.

Objective: In this study, we, for the first time, evaluated future-oriented repetitive thought in patients with Alzheimer disease (AD), that is, how they think and worry about the future., Methods: We administered the Future-Oriented Repetitive Thought scale to 34 patients with AD and 37 control participants. This scale assessed 3 categories of future-oriented repetitive thought: (1) pessimistic repetitive future thinking (eg, "I think about the possibility of losing people or things that are important to me"), (2) repetitive thinking about future goals (eg, "I make specific plans for how to get things that I want in life"), and (3) positive indulging about the future (eg, "When I picture good things happening in my future, it is as if they were actually happening to me now")., Results: Analysis demonstrated more pessimistic repetitive future thinking, but less repetitive thinking about future goals and positive indulging about the future, in patients with AD than in control participants., Conclusion: Our findings demonstrate a pessimistic view of future in patients with AD, which is possibly attributed to hopelessness and depression.