Rule-based systems to automatically count bites from meal videos.

Eating behavior is a key factor for nutritional intake and plays a significant role in the development of eating disorders and obesity. The standard methods to detect eating behavior events (i.e., bites and chews) from video recordings rely on manual annotation, which lacks objective assessment and standardization. Yet, video recordings of eating episodes provide a non-invasive and scalable source for automation. Here, we present a rule-based system to count bites automatically from video recordings with 468 3D facial key points. We tested the performance against manual annotation in 164 videos from 15 participants. The system can count bites with 79% accuracy when annotation is available, and 71.4% when annotation is unavailable. The system showed consistent performance across varying food textures. Eating behavior researchers can use this automated and objective system to replace manual bite count annotation, provided the system's error is acceptable for the purpose of their study. Utilizing our approach enables real-time bite counting, thereby promoting interventions for healthy eating behaviors. Future studies in this area should explore rule-based systems and machine learning methods with 3D facial key points to extend the automated analysis to other eating events while providing accuracy, interpretability, generalizability, and low computational requirements.

Oxidative Metabolism in Brain Ischemia and Preconditioning: Two Sides of the Same Coin.

Brain ischemia is one of the major causes of chronic disability and death worldwide. It is related to insufficient blood supply to cerebral tissue, which induces irreversible or reversible intracellular effects depending on the time and intensity of the ischemic event. Indeed, neuronal function may be restored in some conditions, such as transient ischemic attack (TIA), which may be responsible for protecting against a subsequent lethal ischemic insult. It is well known that the brain requires high levels of oxygen and glucose to ensure cellular metabolism and energy production and that damage caused by oxygen impairment is tightly related to the brain's low antioxidant capacity. Oxygen is a key player in mitochondrial oxidative phosphorylation (OXPHOS), during which reactive oxygen species (ROS) synthesis can occur as a physiological side-product of the process. Indeed, besides producing adenosine triphosphate (ATP) under normal physiological conditions, mitochondria are the primary source of ROS within the cell. This is because, in 0.2-2% of cases, the escape of electrons from complex I (NADPH-dehydrogenase) and III of the electron transport chain occurring in mitochondria during ATP synthesis leads to the production of the superoxide radical anion (O2•-), which exerts detrimental intracellular effects owing to its high molecular instability. Along with ROS, reactive nitrosative species (RNS) also contribute to the production of free radicals. When the accumulation of ROS and RNS occurs, it can cause membrane lipid peroxidation and DNA damage. Here, we describe the intracellular pathways activated in brain tissue after a lethal/sub lethal ischemic event like stroke or ischemic tolerance, respectively, highlighting the important role played by oxidative stress and mitochondrial dysfunction in the onset of the two different ischemic conditions.

Sensed Presence, Attenuated Psychosis, and Transliminality: At the Threshold of Consciousness.

INTRODUCTION: The experience of "sensed presence" or "felt presence" in the absence of "other" has been described as a complex multimodal experience to which meaning is given. Sensed presence (SenP) is a transdiagnostic experience that exists along a continuum that can appear during isolation, spirit quests, exposure to extreme elements, bereavement, anxiety, and psychosis. Given the prevalence and vast heterogeneity of SenP, in addition to a surprising lack of targeted research into this phenomenon, this research examined the interrelationship of SenP, attenuated psychosis symptoms (APS), and transliminality. Transliminality is composed of absorption, fantasy proneness, paranormal belief, mystical experiences, increased creativity, and hyperaesthesia. METHODS: A completely anonymous online survey of unusual experiences and mental health was distributed via social media (i.e., Twitter, Facebook, Reddit, and mass emailing lists) to recruit participants. Demographic data were analyzed using χ2 tests and one-way ANOVAs. A two-step cluster analysis was conducted to identify distinct sub-categories of transliminality followed by ANOVAs with bootstrapping at 1,000 iterations to compare SenP, increased APS, and transliminality. Pearson's bivariate correlations were conducted to determine the association between SenP, APS, and transliminality. RESULTS: Together with descriptive findings, we show distinct characteristics between clusters. T1 cluster consisted of individuals with few SenP experiences, low APS, and low transliminality. T2 consisted of individuals with a moderate prevalence of SenP, low APS, moderate transliminality, and increased overall feeling of closeness to G-d. There was no significant difference in APS between T1 and T2 or in the level of distress associated with APS. T3 individuals showed a significantly higher prevalence of SenP in all domains (frequency, distress, vividness, and total score), higher APS, and higher transliminality, compared to T1 and T2. The T3 cluster met criteria for high risk to develop psychosis. CONCLUSION: Thus, our findings demonstrate a strong association and entanglement of these experiences which suggests that the interrelatedness of transliminality/absorption and APS may serve as a potentially provocative underlying structure in the phenomenology of SenP.

Capturing Eating Behavior from Video Analysis: A Systematic Review.

Current methods to detect eating behavior events (i.e., bites, chews, and swallows) lack objective measurements, standard procedures, and automation. The video recordings of eating episodes provide a non-invasive and scalable source for automation. Here, we reviewed the current methods to automatically detect eating behavior events from video recordings. According to PRISMA guidelines, publications from 2010-2021 in PubMed, Scopus, ScienceDirect, and Google Scholar were screened through title and abstract, leading to the identification of 277 publications. We screened the full text of 52 publications and included 13 for analysis. We classified the methods in five distinct categories based on their similarities and analyzed their accuracy. Facial landmarks can count bites, chews, and food liking automatically (accuracy: 90%, 60%, 25%). Deep neural networks can detect bites and gesture intake (accuracy: 91%, 86%). The active appearance model can detect chewing (accuracy: 93%), and optical flow can count chews (accuracy: 88%). Video fluoroscopy can track swallows but is currently not suitable beyond clinical settings. The optimal method for automated counts of bites and chews is facial landmarks, although further improvements are required. Future methods should accurately predict bites, chews, and swallows using inexpensive hardware and limited computational capacity. Automatic eating behavior analysis will allow the study of eating behavior and real-time interventions to promote healthy eating behaviors.

Machine Learning in Nutrition Research.

Data currently generated in the field of nutrition are becoming increasingly complex and high-dimensional, bringing with them new methods of data analysis. The characteristics of machine learning (ML) make it suitable for such analysis and thus lend itself as an alternative tool to deal with data of this nature. ML has already been applied in important problem areas in nutrition, such as obesity, metabolic health, and malnutrition. Despite this, experts in nutrition are often without an understanding of ML, which limits its application and therefore potential to solve currently open questions. The current article aims to bridge this knowledge gap by supplying nutrition researchers with a resource to facilitate the use of ML in their research. ML is first explained and distinguished from existing solutions, with key examples of applications in the nutrition literature provided. Two case studies of domains in which ML is particularly applicable, precision nutrition and metabolomics, are then presented. Finally, a framework is outlined to guide interested researchers in integrating ML into their work. By acting as a resource to which researchers can refer, we hope to support the integration of ML in the field of nutrition to facilitate modern research.

'Are these my thoughts?': A 20-year prospective study of thought insertion, thought withdrawal, thought broadcasting, and their relationship to auditory verbal hallucinations.

The co-occurrence of delusions and other symptoms at the onset of psychosis is a challenge for theories about the aetiology of psychosis. This paper explores the relatedness of delusions about the experience of thinking (thought insertion, thought withdrawal, and thought broadcasting) and auditory verbal hallucinations by describing their trajectories over a 20-year period in individuals diagnosed with schizophrenia, affective and other psychosis, and unipolar depression nonpsychosis. The sample consisted of 407 participants who were recruited at index hospitalization and evaluated over six follow-ups over 20 years. The symptom structure associated with thought insertion included auditory verbal hallucinations, somatic hallucinations, other hallucinations, delusions of thought-dissemination, delusions of control, delusion of self-depreciation, depersonalization and anxiety. The symptom constellation of thought withdrawal included somatic hallucinations, other hallucinations, delusions of thought dissemination, delusions of control, sexual delusions, depersonalization, negative symptoms, depression, and anxiety. The symptom constellation of thought broadcasting included auditory verbal hallucinations, somatic hallucinations, delusions of thought-dissemination, delusion of self-depreciation, fantastic delusions, sexual delusions, and depersonalization. Auditory verbal hallucinations and delusions of self-depreciation were significantly associated with both thought insertion and thought broadcasting. Thought insertion and thought withdrawal were significantly associated with other hallucinations, delusions of control, and anxiety; thought withdrawal and thought broadcasting were significantly related to sexual delusions. We hypothesize that specific symptom constellations over time might be explained as the product of pseudo-coherent realities created to give meaning to the experience of the world and the self of individuals in psychosis based on both prior top-down and ongoing bottom-up elements.

Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target.

BACKGROUND & AIMS: The landscape and function of the immune infiltrate of intrahepatic cholangiocarcinoma (iCCA), a rare, yet aggressive tumor of the biliary tract, remains poorly characterized, limiting development of successful immunotherapies. Herein, we aimed to define the molecular characteristics of tumor-infiltrating leukocytes with a special focus on CD4+ regulatory T cells (Tregs). METHODS: We used high-dimensional single-cell technologies to characterize the T-cell and myeloid compartments of iCCA tissues, comparing these with their tumor-free peritumoral and circulating counterparts. We further used genomics and cellular assays to define the iCCA-specific role of a novel transcription factor, mesenchyme homeobox 1 (MEOX1), in Treg biology. RESULTS: We found poor infiltration of putative tumor-specific CD39+ CD8+ T cells accompanied by abundant infiltration of hyperactivated CD4+ Tregs. Single-cell RNA-sequencing identified an altered network of transcription factors in iCCA-infiltrating compared to peritumoral T cells, suggesting reduced effector functions by tumor-infiltrating CD8+ T cells and enhanced immunosuppression by CD4+ Tregs. Specifically, we found that expression of MEOX1 was highly enriched in tumor-infiltrating Tregs, and demonstrated that MEOX1 overexpression is sufficient to reprogram circulating Tregs to acquire the transcriptional and epigenetic landscape of tumor-infiltrating Tregs. Accordingly, enrichment of the MEOX1-dependent gene program in Tregs was strongly associated with poor prognosis in a large cohort of patients with iCCA. CONCLUSIONS: We observed abundant infiltration of hyperactivated CD4+ Tregs in iCCA tumors along with reduced CD8+ T-cell effector functions. Interfering with hyperactivated Tregs should be explored as an approach to enhance antitumor immunity in iCCA. LAY SUMMARY: Immune cells have the potential to slow or halt the progression of tumors. However, some tumors, such as intrahepatic cholangiocarcinoma, are associated with very limited immune responses (and infiltration of cancer-targeting immune cells). Herein, we show that a specific population of regulatory T cells (a type of immune cell that actually suppresses the immune response) are hyperactivated in intrahepatic cholangiocarcinoma. Targeting these cells could enable cancer-targeting immune cells to act more effectively and should be looked at as a potential therapeutic approach to this aggressive cancer type.

Altered heparan sulfate metabolism during development triggers dopamine-dependent autistic-behaviours in models of lysosomal storage disorders.

Lysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause. Using mouse and cellular models of MPS-IIIA, we discovered that autistic-like behaviours are due to increased proliferation of mesencephalic dopamine neurons originating during embryogenesis, which is not due to lysosomal dysfunction, but to altered HS function. Hyperdopaminergia and autistic-like behaviours are corrected by the dopamine D1-like receptor antagonist SCH-23390, providing a potential alternative strategy to the D2-like antagonist haloperidol that has only minimal therapeutic effects in MPS-IIIA. These findings identify embryonic dopaminergic neurodevelopmental defects due to altered function of HS leading to autistic-like behaviours in MPS-II and MPS-IIIA and support evidence showing that altered HS-related gene function is causative of autism.

The Sensory and Perceptual Scaffolding of Absorption, Inner Speech, and Self in Psychosis.

This study examines the interconnectedness between absorption, inner speech, self, and psychopathology. Absorption involves an intense focus and immersion in mental imagery, sensory/perceptual stimuli, or vivid imagination that involves decreased self-awareness and alterations in consciousness. In psychosis, the dissolution and permeability in the demarcation between self and one's sensory experiences and perceptions, and also between self-other and/or inter-object boundaries alter one's sense of self. Thus, as the individual integrates these changes new "meaning making" or understanding evolves as part of an ongoing inner dialogue and dialogue with others. This study consisted of 117 participants: 81 participants with psychosis and 36 controls. We first conducted a bivariate correlation to elucidate the relationship between absorption and inner speech. We next conducted hierarchical multiple regressions to examine the effect of absorption and inner speech to predict psychopathology. Lastly, we conducted a network analysis and applied extended Bayesian Information Criterion to select the best model. We showed that in both the control and psychosis group dialogic and emotional/motivational types of inner speech were strongly associated with absorption subscales, apart from the aesthetic subscale in the control group which was not significant, while in psychosis, condensed inner speech was uniquely associated with increased imaginative involvement. In psychosis, we also demonstrated that altered consciousness, dialogic, and emotional/motivational inner speech all predicted positive symptoms. In terms of network associations, imaginative involvement was the most central, influential, and most highly predictive node in the model from which all other nodes related to inner speech and psychopathology are connected. This study shows a strong interrelatedness between absorption, inner speech and psychosis thus identifying potentially fertile ground for future research and directions, particularly in the exploration into the underlying construct of imaginative involvement in psychotic symptoms.

Mechanisms by which autophagy regulates memory capacity in ageing.

Autophagy agonists have been proposed to slow down neurodegeneration. Spermidine, a polyamine that acts as an autophagy agonist, is currently under clinical trial for the treatment of age-related memory decline. How Spermidine and other autophagy agonists regulate memory and synaptic plasticity is under investigation. We set up a novel mouse model of mild cognitive impairment (MCI), in which middle-aged (12-month-old) mice exhibit impaired memory capacity, lysosomes engulfed with amyloid fibrils (ß-amyloid and α-synuclein) and impaired task-induced GluA1 hippocampal post-translation modifications. Subchronic treatment with Spermidine as well as the autophagy agonist TAT-Beclin 1 rescued memory capacity and GluA1 post-translational modifications by favouring the autophagy/lysosomal-mediated degradation of amyloid fibrils. These findings provide new mechanistic evidence on the therapeutic relevance of autophagy enhancers which, by improving the degradation of misfolded proteins, slow down age-related memory decline.

Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?

Recently, peroxisome proliferator-activated receptor (PPAR)-α and γ isoforms have been gaining consistent interest in neuropathology and treatment of neuropsychiatric disorders. Several studies have provided evidence that either the receptor expression or the levels of their endogenously-produced modulators are downregulated in several neurological and psychiatric disorders and in their respective animal models. Remarkably, administration of these endogenous or synthetic ligands improves mood and cognition, suggesting that PPARs may offer a significant pharmacological target to improve several neuropathologies. Furthermore, various neurological and psychiatric disorders reflect sustained levels of systemic inflammation. Hence, the strategy of targeting PPARs for their anti-inflammatory role to improve these disorders is attracting attention. Traditionally, classical antidepressants fail to be effective, specifically in patients with inflammation. Non-steroidal anti-inflammatory drugs exert potent antidepressant effects by acting along with PPARs, thereby strongly substantiating the involvement of these receptors in the mechanisms that lead to development of several neuropathologies. We reviewed running findings in support of a role for PPARs in the treatment of neurological diseases, including Alzheimer's disease or psychiatric disorders, such as major depression. We discuss the opportunity of targeting PPARs as a future pharmacological approach to decrease neuropsychiatric symptoms at the same time that PPAR ligands resolve neuroinflammatory processes.