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Irritable bowel syndrome (IBS) is the most prevalent disorder of brain-gut interactions that affects between 5 and 10% of the general population worldwide. The current symptom criteria restrict the diagnosis to recurrent abdominal pain associated with altered bowel habits, but the majority of patients also report non-painful abdominal discomfort, associated psychiatric conditions (anxiety and depression), as well as other visceral and somatic pain-related symptoms. For decades, IBS was considered an intestinal motility disorder, and more recently a gut disorder. However, based on an extensive body of reported information about central, peripheral mechanisms and genetic factors involved in the pathophysiology of IBS symptoms, a comprehensive disease model of brain-gut-microbiome interactions has emerged, which can explain altered bowel habits, chronic abdominal pain, and psychiatric comorbidities. In this review, we will first describe novel insights into several key components of brain-gut microbiome interactions, starting with reported alterations in the gut connectome and enteric nervous system, and a list of distinct functional and structural brain signatures, and comparing them to the proposed brain alterations in anxiety disorders. We will then point out the emerging correlations between the brain networks with the genomic, gastrointestinal, immune, and gut microbiome-related parameters. We will incorporate this new information into a systems-based disease model of IBS. Finally, we will discuss the implications of such a model for the improved understanding of the disorder and the development of more effective treatment approaches in the future.

\"The beauty of physics lies in its coherence in terms of a few fundamental concepts and principles. Even physicists have occasion to marvel at the overarching reach of basic principles and their ability to account for features stretching from the microscopic sub-atomic world to the cosmological expanses of the Universe. While mathematics is its natural language, physics is mostly about patterns, connections, and relations between objects and phenomena, and it is this aspect that is emphasized in this book. Since science tries to connect phenomena that at first sight appear widely different, while boiling them down to a small set of essential principles and laws, metaphor and analogy pervade our subject. Consider the pendulum, its swing from one extreme to the other often invoked in social or economic contexts. In molecular vibrations, such as in the CO2 molecule, the quantum motions of electrons and nuclei are metaphorically the pendulums. In electromagnetic radiation, including the visible light we observe, there are not even any concrete material particles, only electric and magnetic fields executing simple harmonic motion. But, to a physicist, they are all \"just a pendulum\". The selection of topics reflects the author's own four-decade career in research physics and his resultant perspective on the subject. While aimed primarily at physicists, including junior students, this book also addresses other readers who are willing to think with symbols and simple algebra in understanding the physical world around us. Each chapter, on themes such as dimensions, transformations, symmetries, or maps, begins with simple examples accessible to all while connecting them later to more sophisticated realizations in more advanced topics of physics.\" -- Publisher's description.

Although online advertising is the lifeline of many internet content platforms, the usage of ad blockers has surged in recent years, presenting a challenge to platforms dependent on ad revenue. Using a simple analytical model with two competing platforms, we show that the presence of ad blockers can actually benefit platforms. In particular, there are conditions under which the optimal equilibrium strategy for the platforms is to allow the use of ad blockers (rather than using an ad-block wall or charging a fee for viewing ad-free content). The key insight is that allowing ad blockers serves to differentiate platform users based on their disutility to viewing ads. This allows platforms to increase their ad intensity on those that do not use the ad blockers and achieve higher returns than in a world without ad blockers. We show robustness of these results when we allow a larger combination of platform strategies, as well as by explaining how ad white-listing schemes offered by modern ad blockers can add value. Our study provides general guidelines for what strategy a platform should follow based on the heterogeneity in the ad sensitivity of their user base. This paper was accepted by Juanjuan Zhang, marketing .

The authors link the rapid and dramatic move from second-price to first-price auction format in the display advertising market, on the one hand, to the move from the waterfalling mechanism employed by publishers for soliciting bids in a preordered cascade over exchanges to an alternate header bidding strategy that broadcasts the request for bid to all exchanges simultaneously, on the other. First, they argue that the move from waterfalling to header bidding was a revenue-improving move for publishers in the old regime when exchanges employed second-price auctions. Given the publisher move to header bidding, the authors show that exchanges move from second-price to first-price auctions to increase their expected clearing prices. Interestingly, when all exchanges move to first-price auctions, each exchange faces stronger competition from other exchanges, and some exchanges may end up with lower revenue than when all exchanges use second-price auctions; yet all exchanges move to first-price auctions in the unique equilibrium of the game. The authors show that the new regime hinders the exchanges' ability to differentiate in equilibrium. Furthermore, it allows the publishers to achieve the revenue of the optimal mechanism despite not having direct access to the advertisers.

Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In this study, a combination of shRNA‐mediated synthetic lethality screening and transcriptomic analysis revealed the transcription factors YAP/TAZ as key drivers of Sorafenib resistance in hepatocellular carcinoma (HCC) by repressing Sorafenib‐induced ferroptosis. Mechanistically, in a TEAD‐dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling HCC cells to overcome Sorafenib‐induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. Our study uncovers a critical role of YAP/TAZ in the repression of ferroptosis and thus in the establishment of Sorafenib resistance in HCC, highlighting YAP/TAZ‐based rewiring strategies as potential approaches to overcome HCC therapy resistance. SYNOPSIS Resistance to therapy occurs in most liver cancer patients treated with Sorafenib, and patients succumb to the disease. A synthetic lethal screen identified a regulatory circuit, which prevents ferroptosis and promotes cancer cell survival, thus promoting resistance to Sorafenib. The transcription factors YAP and TAZ stabilize ATF4 by promoting its nuclear import to cooperatively induce expression of SLC7A11, a cystine importer critical for glutathione synthesis. Glutathione synthesis and homeostasis are required to repress ferroptosis and to maintain Sorafenib resistance in liver cancer cells. Inhibition of Glutathione synthesis re‐sensitizes Sorafenib‐resistant cancer cells to Sorafenib therapy, which then induces ferroptosis and represses tumor growth in murine liver cancer models. Pharmacological repression of the anti‐oxidant pathways regulated by YAP/TAZ and ATF4 could re‐sensitize therapy‐resistant liver cancers to Sorafenib treatment. Graphical Abstract Resistance to therapy occurs in most liver cancer patients treated with Sorafenib, and patients succumb to the disease. A synthetic lethal screen identified a regulatory circuit, which prevents ferroptosis and promotes cancer cell survival, thus promoting resistance to Sorafenib.

Background: Plasma is an ionised gas that is typically generated in high-temperature laboratory conditions. However, recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature. Methods: Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. Results: We show that: (a) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and (b) significantly reduces tumour size in vivo . It is shown that reactive oxygen species metabolism and oxidative stress responsive genes are deregulated. Conclusion: The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by utilisation of another state of matter.

The need for nutritional sources safer than traditional animal products has renewed interest generally in plants and particularly in microalgae. Microalgae have diverse uses in aquaculture, their applications are mainly to provide nutrition and to enhance the colour of the flesh of salmonids. The larvae of molluscs, echinoderms and crustaceans as well as some fish larvae feed on microalgae. Several studies have confirmed that a live multi-specific, low bacterial and microalgal biomass remains essential for shellfish hatcheries. Major advances are expected from new production system, designs and operations from batch run open tanks to more sophisticated continuously-run and closed loop reactors. Currently, studies are underway to examine the cost-effectiveness of the on- and off-site microalgal production systems which can only be achieved by substantial scaling-up and improved quality control. In order to attain sustainability in the usage of microalgae, a systems-based approach is required which integrates different fields such as biotechnology, bioprocess and management procedures.

With the advent of approximation algorithms for NP-hard combinatorial optimization problems, several techniques from exact optimization such as the primal-dual method have proven their staying power and versatility. This book describes a simple and powerful method that is iterative in essence and similarly useful in a variety of settings for exact and approximate optimization. The authors highlight the commonality and uses of this method to prove a variety of classical polyhedral results on matchings, trees, matroids and flows. The presentation style is elementary enough to be accessible to anyone with exposure to basic linear algebra and graph theory, making the book suitable for introductory courses in combinatorial optimization at the upper undergraduate and beginning graduate levels. Discussions of advanced applications illustrate their potential for future application in research in approximation algorithms.

Functional neuroimaging studies in obesity have identified alterations in the connectivity within the reward network leading to decreased homeostatic control of ingestive behavior. However, the neural mechanisms underlying sex differences in the prevalence of food addiction in obesity is unknown. The aim of the study was to identify functional connectivity alterations associated with: (1) Food addiction, (2) Sex- differences in food addiction, (3) Ingestive behaviors. 150 participants (females: N = 103, males: N = 47; food addiction: N = 40, no food addiction: N = 110) with high BMI ≥ 25 kg/m 2 underwent functional resting state MRIs. Participants were administered the Yale Food Addiction Scale (YFAS), to determine diagnostic criteria for food addiction (YFAS Symptom Count ≥ 3 with clinically significant impairment or distress), and completed ingestive behavior questionnaires. Connectivity differences were analyzed using a general linear model in the CONN Toolbox and images were segmented using the Schaefer 400, Harvard–Oxford Subcortical, and Ascending Arousal Network atlases. Significant connectivities and clinical variables were correlated. Statistical significance was corrected for multiple comparisons at q < .05. (1) Individuals with food addiction had greater connectivity between brainstem regions and the orbital frontal gyrus compared to individuals with no food addiction. (2) Females with food addiction had greater connectivity in the salience and emotional regulation networks and lowered connectivity between the default mode network and central executive network compared to males with food addiction. (3) Increased connectivity between regions of the reward network was positively associated with scores on the General Food Cravings Questionnaire-Trait, indicative of greater food cravings in individuals with food addiction. Individuals with food addiction showed greater connectivity between regions of the reward network suggesting dysregulation of the dopaminergic pathway. Additionally, greater connectivity in the locus coeruleus could indicate that the maladaptive food behaviors displayed by individuals with food addiction serve as a coping mechanism in response to pathological anxiety and stress. Sex differences in functional connectivity suggest that females with food addiction engage more in emotional overeating and less cognitive control and homeostatic processing compared to males. These mechanistic pathways may have clinical implications for understanding the sex-dependent variability in response to diet interventions.