Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

It is broadly acknowledged that children with Developmental Language Disorder (DLD) show verb-related limitations. While most previous studies in Spanish have focused on tense, the mastery of lexical aspect—particularly telicity—has not been the primary focus of much research. Lexical aspect refers to whether an action has a defined endpoint (telic verbs) or not (atelic verbs). This study investigates the effect of telicity on verb recognition in Chilean children with DLD compared to their typically developing (TD) peers using the Event-Related Potential (ERP) technique. The research design is a mixed factorial design with between-group factors of 2 (DLD/TD) and within-group factors of 2 (telic/atelic verbs) and 2 (coherent/incoherent sentences). Participants included 36 school-aged children (18 DLD, 18 TD) aged 7 to 7 years and 11 months. The task required subjects to listen to sentences that either matched or did not match an action in a video, with sentences including telic or atelic verbs. The study found notable differences between groups in how they processed verbs (N400 and post-N400 components) and direct objects (N400 and P600 components). DLD children struggled to differentiate telic and atelic verbs, potentially because they employed overgeneralization strategies consistent with the Event Structural Bootstrapping model.

Recent research has suggested that working memory training interventions may benefit children with Developmental Language Disorder (DLD). The current study investigated a short and engaging adaptive working memory intervention that targeted executive skills and aimed to improve both language comprehension and working memory abilities in children with DLD. Forty-seven 6- to 10-year-old children with DLD were randomly allocated to an executive working memory training intervention (n=24) or an active control group (n=23). A pre-test/intervention/post-test/9-month-follow-up design was used. Outcome measures included assessments of language (to evaluate far transfer of the training) and working memory (to evaluate near transfer of the training). Hierarchical multiple regression analyses controlling for pre-intervention performance and age found group to be a significant predictor of sentence comprehension and of performance on six untrained working memory measures at post-intervention and 9-month follow-up. Children in the intervention group showed significantly higher language comprehension and working memory scores at both time points than children in the active control group. The intervention programme showed potential to improve working memory and language comprehension in children with DLD and demonstrated several advantages: it involved short sessions over a short period; caused little disruption in the school day; and was enjoyed by children.

This study aimed to compare procedural learning skills between Spanish-speaking preschool children (ages 4 years to 4 years, 11 months) with Developmental Language Disorder (DLD) and their typically developing (TD) peers. Using the Serial Reaction Time task, participants (30 DLD and 30 TD children) respond to visual stimuli in a sequenced manner over four blocks, followed by a random order block. The task assessed reaction time (RT) and accuracy. Results showed a significant interaction between group and block for reaction time (RT) and accuracy, with children with DLD exhibiting longer RTs and accuracy deficits across blocks. In contrast, the TD group showed higher RT efficiency and accuracy in the sequential blocks and as expected, decreased performance in the random block according to the experimental manipulation. Overall, the results of this investigation suggest that there was no implicit learning in the DLD group, as indicated by the SRT task paradigms of procedural memory. These findings align with the Procedural Deficit Hypothesis (PDH), suggesting that linguistic deficits in the TD population may derive from a general dysfunction of the procedural memory system domain in the Spanish context.

In the field of Natural Language Processing (NLP), Large Language Models (LLMs) have shown great potential in document-level event extraction tasks, but existing methods face challenges in the design of prompts. To address this issue, we propose an optimization strategy called "Definition-driven Document-level Event Extraction (DDEE)." By adjusting the length of the prompt and enhancing the clarity of heuristics, we have significantly improved the event extraction performance of LLMs. We used data balancing techniques to solve the long-tail effect problem, enhancing the model's generalization ability for event types. At the same time, we refined the prompt to ensure it is both concise and comprehensive, adapting to the sensitivity of LLMs to the style of prompts. In addition, the introduction of structured heuristic methods and strict limiting conditions has improved the precision of event and argument role extraction. These strategies not only solve the prompt engineering problems of LLMs in document-level event extraction but also promote the development of event extraction technology, providing new research perspectives for other tasks in the NLP field.

Musyakalah is one of the Arabic linguistic styles included under the category of majaz. This style is commonly used in Al-Quran. The Indonesian translation of Al-Quran is a case where many of the figures of speech are translated literally, thereby causing serious semantic problems. Thus, the research problem of this is formulated with the following questions: 1) How many musyakalah ayahs are there in Al-Quran?; 2) How are the musyakalah ayahs translated, literally (harfiyya) or interpretatively (tafsiriyya)?; 3) How many ayahs are translated literally and how many are translated interpretatively?; and 4) Which translated musyakalah ayahs have the potential to raise semantic and theological problems? The corpus in this research consists of all musyakalah ayahs in Al-Quran and their translation to Indonesian published by the Department of Religious Affairs of Indonesia. The research adopted a descriptive-semantic method. The findings of this research are: 1) There are only eleven ayahs in Al-Quran using musyakalah style, namely: Alhasyr ayah 19, Ali Imran ayah 54, Annaml ayah 50, Alanfal ayah 30, Asysyura ayah 40, Albaqarah ayah 15, Almaidah 116, Aljatsiah ayah 34, Attaubah ayah 79, Annisa ayah 142, and Albaqarah 194; 2) The musyakalah ayahs translated literally are: Aljatsiah 34, Almaidah 116, Asysura 40, Annaml 50, and Alhasyr 19, whereas the musyakalah ayahs translated interpretatively are Albaqarah 194, Annisa 142, Attaubah 79, Albaqarah 15, Alanfal 30, and Ali Imran 54; 3) Of the eleven musyakalah ayahs, only Alhasyr ayah 19 that is translated correctly and does not have the potential of creating misinterpretation. Meanwhile, the interpretation of the other four ayahs can potentially cause misinterpretation or are against the basic principles of Islam. The six remaining ayahs are translated interpretatively and thus do not have the potential to be misinterpreted; 4) The findings suggest that musyakalah ayahs are more appropriately translated interpretatively. Therefore, the following is recommended: 1) Considering the different characteristics of Arabic and Indonesian languages, studies on Al-Quran translation into Indonesian should continuously be carried out; 2) In order to avoid misinterpretation, it is better that the translation of musyakalah ayahs uses tafsiriyya (interpretative) approach; 3) The harfiyya (literal) and tafsiriyya (interpretative) approaches should be developed for other styles beside musyakalah..

To address the problems of insufficient semantic fusion between text and questions and the lack of consideration of global semantic information encountered in machine reading comprehension models, we proposed a machine reading comprehension model called BERT_hybrid based on BERT and hybrid attention mechanism. In this model, BERT is utilized to separately map the text and questions into the feature space. Through the integration of Bi-LSTM, attention mechanism, and self-attention mechanism, the proposed model achieves comprehensive semantic fusion between text and questions. The probabilities distribution of answers is computed using Softmax. Experimental results on the public dataset DuReader demonstrate that the proposed model achieves improvements in BLEU-4 and ROUGE-L scores compared to existing models. Furthermore, to validate the effectiveness of the proposed model design, we analyze the factors influencing the model’s performance.

Bio-molecular reagents like antibodies required in experimental biology are expensive and their effectiveness, among other things, is critical to the success of the experiment. Although such resources are sometimes donated by one investigator to another through personal communication between the two, there is no previous study to our knowledge on the extent of such donations, nor a central platform that directs resource seekers to donors. In this paper, we describe, to our knowledge, a first attempt at building a web-portal titled Bio-Resource Exchange that attempts to bridge this gap between resource seekers and donors in the domain of experimental biology. Users on this portal can request for or donate antibodies, cell-lines and DNA Constructs. This resource could also serve as a crowd-sourced database of resources for experimental biology. Further, in order to index donations outside of our portal, we mined scientific articles to find instances of donations of antibodies and attempted to extract information about these donations at the finest granularity. Specifically, we extracted the name of the donor, his/her affiliation and the name of the antibody for every donation by parsing the acknowledgements sections of articles. To extract annotations at this level, we propose two approaches – a rule based algorithm and a bootstrapped relation learning algorithm. The algorithms extracted donor names, affiliations and antibody names with average accuracies of 57% and 62% respectively. We also created a dataset of 50 expert-annotated acknowledgements sections that will serve as a gold standard dataset to evaluate extraction algorithms in the future. Contact: [email protected], [email protected] Database URL: http://tonks.dbmi.pitt.edu/brx Supplementary information: Supplementary data are available at Database online.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition, characterized by persistent deficits in communication/social interaction and restricted and repetitive patterns of behavior, interests or activities. It is usually identified in childhood, despite late diagnoses in cases of greater functionality. Havighurst proposes a set of fundamental tasks throughout the life cycle, whose achievement is probably compromised in the ASD, even though it lacks scientific evidence. This study innovates, as it is based on Havighurst's theoretical model for understanding the development process of three adults and one young person, diagnosed with ASD level I, at different life stages. Through the methodology of life histories, interviews were subject to content analysis. Results pointed out the early detection and interventions importance, minimizing adversities, above all by those who had late diagnoses. Self-perceived success, not expected, was found in some development tasks (e.g. conscience and morality development). Also were noticed expected limitations related to ASD (e.g. difficulties in relationships with peers and in the labor market inclusion). Probably, in cases of greater severity and less functionality/autonomy, there would be greater failure in development tasks. It is crucial to improve research on this developmental model and on the factors that delay the diagnosis, including cases of different levels of severity.

Transmission of values and religious concepts to children is one of the most important issues in the third millennium and it has drawn varied and different views among experts and scholars in the world. Research specialized in religious literature for children and adolescents create new capacities in the presentation of religious concepts to the group. Plans have been considered to transfer values and religious concepts in the curricula of primary school children in the group in Iran. It is one of the topics that the authors note to the introduction of the minutiae of religion in the first three elementary grades. In this study, the collection and analysis methods providing content related to the minutiae of religion in reading books the first till third sections of the years 2013-2015. In addition, the plan includes aspects of other branches of religion in these books on information collected from text books that collected and classified. The result is that "definitely good and forbidding the evil" and "prayer" have the highest frequency of applications in the selected books. Further branches made of branches of religion in these books, represents the values of religious, moral and social as well.

Sustainable development and education in sustainable development (ESD) are crucial and interconnected topics under wide discussion today. Young adults need to be educated in how to help bring about change. Thus, the dynamic relationship between school and home is important. In education, use could be made of English language classes, especially since English is a global language that enables access to the sustainability literature and facilitates discussion in global conferences and meetings. Consequently, English as a foreign language (EFL) students could gain confidence from being able to understand and use the terminology of, for example, sustainability. In this paper, the use of competence-based language teaching (CBLT) is proposed as a means of introducing sustainability topics into EFL writing classes at a university in Saudi Arabia. Students’ competence in sustainable development is therefore considered based on their ability to write about suggested sustainable development topics, measured on a scale for five dimensions of ESD proposed by Michelsen and Fischer (2017). The results demonstrate that the students possessed competence in sustainable development and intended to participate in its implementation. Thus, recommendations are made for the stakeholders in the education sector to include sustainable development topics as an initial offering in the curricula of various specialties using the CBLT approach.

Increasing research has indicated a strong association between identity functioning and eating disorder (ED) symptomatology. However, a detailed investigation of identity throughout ED treatment is lacking. The present longitudinal study examined identity in inpatients with an ED and explored its co-development with ED symptomatology throughout treatment. At admission (Wave 1), 110 women with an ED (Mage=21, SD=6.08, range:14-45) participated, of whom 83.64% participated during treatment (Wave 2) and 55.45% at discharge (Wave 3). Questionnaires on identity synthesis, identity confusion, identity processes, and ED symptomatology were completed. Latent growth curve modeling was used to address the research questions. Throughout treatment, a decrease in identity confusion and an increase in identity synthesis and adaptive identity processes were found. Accordingly, increases in identity synthesis and identification with commitment were related to general decreases in drive for thinness and body dis-satisfaction. Similarly, such decreases in ED symptoms were related to general decreases in identity confusion and ruminative exploration. The present study points to an increase in identity functioning throughout treatment, and longitudinal associations between identity functioning and ED symptomatology were found. Helping the patient to decrease ruminative exploration and to increase identification with previously made life commitments seem important in ED treatment.

Developmental Coordination Disorder (DCD) is a neurodevelopmental condition characterized by non-progressive central motor impairments. Mild movement disorder features have been observed in DCD. Until now, the etiology of DCD remains unclear. Recent studies suggested a genetic substrate in some patients with DCD, but comprehensive knowledge about associated genes and underlying pathogenetic mechanisms is still lacking. In this study, we first identified genes described in literature in patients with a diagnosis of DCD according to the official diagnostic criteria. Second, we exposed the underlying pathogenetic mechanisms of DCD, by investigating tissue- and temporal gene expression patterns and brain-specific biological mech-anisms. Third, we explored putative shared pathogenetic mechanisms between DCD and frequent movement disorders with a known genetic component, including ataxia, chorea, dystonia, and myoclonus. We identified 12 genes associated with DCD in literature, which are ubiquitously expressed in the central nervous system throughout brain development. These genes are involved in cellular processes, neural signaling and nervous system development. There was a remarkable overlap (62%) in pathogenetic mechanisms between DCD-associated genes and genes linked with movement disorders. Our findings suggest that some patients might have a genetic etiology of DCD, which could be considered part of a pathogenetic movement disorder spectrum.

(1) Background: Attention Deficit Hyperactivity Disorder (ADHD) and Developmental Language Disorder (DLD) are neurodevelopmental disorders that affect various areas of chil-dren’s development, such as language. There is an emerging idea that ADHD is characterised by the presence of language difficulties, which could be explained by the high comorbidity between ADHD and DLD. The purpose of this study is to analyse the empirical evidence of language com-petence in children aged 6–17 years old, diagnosed with ADHD and/or DLD. (2) Method: Fifteen studies with experimental designs were identified from Scopus, PsycINFO and WoS databases, reporting on language skills in children diagnosed with ADHD and/or DLD. Studies relating ex-ecutive functioning to language skills in this target population were also included. (3) Results: The literature is heterogeneous and different components of language are also examined. Even though the results are contradictory they convincingly demonstrate that there are overlapping symptoms between ADHD and DLD, such as language skills and executive functions. (4) Conclusions: the differences in the samples limit the generalisability of the results. Therefore, this review highlights the importance of considering language skills when designing individualised interventions for the population with ADHD and DLD, both in comorbidity and in isolation.

POGZ (Pogo transposable element derived with ZNF domain) is known to function as a regulator of gene expression. While variations in the POGZ gene have been associated with intellectual disabilities and developmental delays in humans, the exact pathophysiological mechanisms re-main unclear. To shed light on this, we created two lines of conditional knockout mice for Pogz, one specific to excitatory neurons (Emx1-Pogz mice) and the other to inhibitory neurons (Gad2-Pogz mice) in the brain. Emx1-Pogz mice showed a decrease in body weight, similar to total Pogz knockout mice. Although the two lines did not display significant morphological ab-normalities in the telencephalon, impaired POGZ function affected the electrophysiological prop-erties of both excitatory and inhibitory neurons differently. These findings suggest that these mouse lines could be useful tools for clarifying the precise pathophysiological mechanisms of neurodevelopmental disorders associated with POGZ gene abnormalities.

Considering that emotional events diversify as one ages, this study formulates the Salient Episodic Memory Aggregation Hypothesis, which claims that aging induces homogenization of episodic memory and consequently increases the salience of emotional episodes. To test this hypothesis, the study focused on sadness episodic memory and conducted a web-based survey and a combined analysis consisting of natural language processing, machine learning, and network graph analysis. A sample of 2,954 adults aged between their 20s and over 70s participated in this study. They were asked to describe a sad event they had experienced and assess the psychological properties of the recalled episodes. After isolating and lemmatizing episodic words using natural language processing, vocabulary frequency was counted for each generation, and network graph analysis based on machine learning was performed to compare the structures of sadness episodes between generations. As a result, there were mainly two types of episodic words for which frequencies either declined or increased with age. The network structures of episodic words for the older generations possessed higher proximity (shortest path length) to higher concentrations of episodic words. These findings support the current hypothesis, indicating that the nature of sadness episodes differ between generations, and that older people have more aggregated episodic memory structures.

This Special Issue of Humanities comes at a time when the viability of the humanities are challenged on numerous fronts. On the one hand, the humanities face material threats as the politics of austerity continues throughout Europe and the United States, diminishing public support and making profit margin and “job creation” the primary measure of value or the basis of state university funding decisions. On the other, the humanities face conceptual, theoretical and ethical challenges, as the emergence of post-racial and post-humanist discourses signal what Foucault called “a change in the fundamental arrangements of knowledge.” The defining boundaries of constructs such as “race” and “human” have been radically called into question, challenging us to rethink the classificatory systems that found hierarchical relationships between, for example, the “fully human” and sub-human or non-human others. Despite dominant nations’ professed commitment to a universal human rights paradigm, racialized identities are still often the targets of disenfranchisement and dehumanization, while the exploitation and destruction of the natural world continues in the name of “progress” and profits.

This paper addresses the grammatical challenges associated with the development of clause complexity, focusing on the performance of a group of monolingual Spanish-speaking schoolchildren with Specific Language Impairment/Developmental Language Disorder (SLI/DLD) in a longitudinal corpus of oral narrative samples. The study examines the presence of interclause relations of subordination and equivalence (hypotaxis and parataxis) in language samples of two groups: an experimental group made up of 24 schoolchildren with SLI/DLD and a control group made up of 24 schoolchildren with typical development (TD). The results show that while both groups use parataxis as the most common relation between clauses in all school grades, there is a significant decrease in paratactic relations and a significant increase in hypotactic relations from first to fourth grade of primary education. Although the development patterns are highly similar, the SLI/DLD group shows greater difficulties in mastering more complex (hypotactic) relations in fourth grade compared to the control group, indicating that they are less sophisticated in the use of these types of complex relations. These findings suggest that focused support on the most complex structures is needed towards the fourth grade of primary education, given the demands of the school academic register from 6 and 7 years of age, and the potential problems that the development of clause complexity can cause in school-age children.

Obsessive-Compulsive Disorder (OCD) is a mental health condition marked by recurrent intrusive thoughts or sensations that compel individuals to perform repetitive behaviors or mental acts. Obsessions and compulsions significantly disrupt daily life and cause considerable distress. Early identification and intervention improve long-term outcomes. This study aimed to evaluate the ability of four advanced artificial intelligence models (ChatGPT-3.5, ChatGPT-4, Claude, and Bard) to accurately recognize OCD compared to human professionals and to assess recommended therapies and stigma attributions. This study was conducted during March 2024 utilizing 12 vi-gnettes. Each vignette depicted a client, either a young adult or a middle-aged male or female, attending an initial therapy session. Each vignette was evaluated ten times, resulting in 480 evaluations. The results were compared with those of a human sample of 514 psychotherapists, as reported by Canavan. Significant differences were found. AI models demonstrated higher OCD recognition rates and confidence levels than human professionals and showed 100% confidence in recognition, compared to 87% among psychotherapists. AI models also recommended evi-dence-based interventions more frequently, with ChatGPT-3.5 and Claude at 100%, ChatGPT-4 at 90%, and Bard at 60%, compared to 61.9% among psychotherapists. Additionally, AI models ex-hibited significantly lower stigma and danger estimations, though both AI and psychotherapists demonstrated high willingness to treat the described cases. The findings suggest that AI models surpass human professionals in recognizing OCD and recommending evidence-based treatments while also demonstrating lower stigma. These results highlight the potential of AI tools to enhance OCD diagnosis and treatment in clinical settings.

Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutation in Fd59a caused swelling in the apical region of the testis. More importantly, only a few mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted, and apoptosis of sperm bundles was increased. Furthermore, results from RNA-sequencing and qRT-PCR suggest that Fd59a can regulate expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

Global warming and the associated increasing frequency of heatwaves are on the rise leading to numerous health complications. Diabetic patients are more vulnerable to heat exposure than healthy individuals, owing to their impaired sweating ability, however, little is known about how heat exposure may impact the function of skin cells, commonly keratinocytes. Our recent report provided the first proof-of-concept revealing that the metabolic composition of sweat EVs is associated with metabolic changes in healthy individuals and type 2 diabetes patients. Given this and the shared cellular proprieties of eccrine sweat glands with keratinocytes, we questioned whether the metabolic changes in sweat EVs may mirror the responses of keratinocytes upon heat exposure. To this, we exposed HaCat, which were maintained in low (mimicking healthy condition) and high glucose (mimicking diabetes condition) to acute (90 min), chronic (48 h), and repetitive heat exposure at 40 ⁰C. Through conducting a set of experiments including a targeted metabolomics approach, Greiss assay, western blotting analysis, and electron microscopy studies. The data demonstrate that heat exposure results in substantial changes of metabolite levels belonging to amino acids, pyrimidine metabolism, and glycolysis pathways in high glucose maintained HaCat cells when compared to those noted in low glucose condition. Exploring the molecular mechanisms through which heat exposure may impact the metabolic composition in keratinocytes, our discoveries highlight nitric oxide (NO) as a novel biomarker that the level is correlated with heat duration and frequency. Furthermore, data reveal that the HSP-70 protein levels and mitochondrial morphology are consequently altered. This study provides evidence of shared metabolic alterations in keratinocytes and sweat EVs collected from clinical study and proposes, for the first time, NO as a novel biomarker for monitoring changes in health and diabetes upon heat exposure.

Human development encompasses the integration of neuromotor, psychological, social-emotional, and cognitive processes across time. However, a better understanding of the interconnectedness of motor and cognitive development throughout the lifespan is needed. The integrative and dynamic nature of short-term motor skill acquisition and long-term developmental processes may foster executive functions. Unfortunately, assessments of motor competence have traditionally focused on skillfulness from a movement perspective, using restrictive task protocols that decontextualize performance and limit cognitive involvement. Additionally, traditional motor-cognitive dual-task assessments centered on cognitive involvement during specific movement protocols, have minimized impacts of task complexity and motor competence on cognitive performance. To gain a more ecologically valid understanding of the relation between motor and cognitive development, a novel assessment paradigm using an integrative approach to motor-cognitive dual-tasking is needed. The purpose of the present paper is to: 1) provide a conceptual bridge, based on multidisciplinary evidence, to effectively link the concurrent development of motor competence and executive functions via learning-related and exercise-related neurotrophic mechanisms, and 2) use this conceptual bridge to inform the development of novel motor-cognitive dual-task assessments that account for the role of task complexity, current levels of motor competence, and the continuous decision-making inherent in “real world” performance environments.

The focus of this article is the evaluation of the quality and the degree of community engagement in an expert-based, public-health communicative intervention for Alcohol Use Disorder (AUD). In 2023 the Canadian Alcohol Use Disorder Society collaborated with a grass-roots community health group, a regional health authority, and an academic participatory researcher to organize a working group to mount a social-marketing campaign to increase community support for AUD medical treatment in family-practice settings in a rural community in British Columbia. The partnership working group conducted a series of activities in the school system, the town council, and the community. This article covers the formative evaluation and the summative evaluation of the working group's effectiveness. The formative evaluation ("lessons learned" and "recommendations") consists of consensus evaluations of the quality of each activity using a variety of data sources. The formative evaluation followed improvement science methods and used consensus meetings to provide and reflect on formal and informal feedback. Formative results reflect the consensus of the participants in the working group and they record the reactions in the community. The summative evaluation measures evidence of community engagement found in transcribed text from meeting minutes. The summative evaluation used theory-based frameworks and text data visualization to assess the engagement dynamics of the working group. The summative evaluation helps to put the formative evaluation into perspective as communicative action. The summative evaluation validates the formative evaluation by revealing the communicative dynamics of engagement which resulted in the community’s increased capacity to understand and support Alcohol Use Disorder Treatment options. The working group and the entire intervention was seen by the participants and the public as a success and capable of replication. In a small community, it instilled new understandings and attitudes, bringing an emerging awareness of medication as an optional health mitigation strategy for Alcohol Use Disorder. Our study furthers this overall assessment by using theoretical constructs and analysis of communicative records to trace engagement characteristics of interest to researchers, societies, and community groups contemplating similar interventions in the future. The study also validates the effectiveness of communicative analysis as a measure of social-marketing for expert-based public health interventions.

The accurate diagnosis and effective treatment of mental health disorders such as depression remain challenging owing to the complex underlying causes and varied symptomatology. Traditional information extraction methods struggle to adapt to evolving diagnostic criteria such as the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) and to contextualize rich patient data effectively. This study proposes a novel approach for enhancing information extraction from mental health data by integrating medical knowledge graphs and large language models (LLMs). Our method leverages the structured organization of knowledge graphs specifically designed for the rich domain of mental health combined with the powerful predictive capabilities and zero-shot learning abilities of LLMs. This research enhances the quality of knowledge graphs through entity linking and demonstrates superiority over traditional information extraction techniques, making a significant contribution to the field of mental health. It enables a more fine-grained analysis of the data and the development of new applications. Our approach redefines the manner in which mental health data are extracted and utilized. By integrating these insights with existing healthcare applications, the groundwork is laid for the development of real-time patient monitoring systems. The performance evaluation of this knowledge graph highlights its effectiveness and reliability, indicating significant advancements in automating medical data processing and depression management.

Equipped with an early social predisposition immediately post-birth, humans typically form associations with mothers and other family members through exposure learning, canalized by a spontaneous predisposition to biological motion, face configuration, and other cues of animacy. If impaired, reduced social preferences can lead to social interaction impairments such as autism spectrum disorder (ASD) via misguided canalization. Despite being taxonomically distant, domestic chicks also follow a homologous developmental trajectory toward adaptive socialization through imprinting, which is guided via predisposed preferences that are homologous to those of humans, thereby suggesting that chicks are valid animal models of ASD. In addition to the convergent similarities in predisposition with human newborns, accumulating evidence suggests the construct validity of the chick model. Considering the recent progress in the evolutionary neurobiology of vertebrates, we reviewed the advantages and limitations of the chick model of developmental mental diseases in humans.

The present study aimed to investigate the effect of a motor skills training program in children with DCD considering their gender. The Movement Assessment Battery for Children (MABC-2) classified the children and assessed skill changes over time. The study was implemented at four kindergartens in the Khorezm region of Uzbekistan. In the study, all children had DCD (5.17 ± 0.70 years; 10 girls), and all indicators on MABC-2 were less than 16 percent. Participants were divided into an experimental group (n=17) receiving ten weeks of motor skills training program for 45 min twice per week, the control group (n=7) proceeded with exercises of everyday living. All children in the experimental group had a significant increase in total percentile rank of MABC-2 and concerning each domain (manual dexterity; throwing and catching; balance). In the control group, a significant decrease in the total percentile rank of MABC-2 and each domain of MABC-2 was observed. The effectiveness of the intervention program was similar across both genders. The study supports that a period of 10 weeks of a motor skills training program can increase the quality of children's motor coordination and represent a valuable procedure for physical education specialists to enhance motor skills for children with DCD.

Sex/gender (S/G) differences in ASD language profiles have been poorly investigated. The present study aims to explore whether male (M) and female (F) children with ASD and with normal non-verbal cognitive abilities differ in their linguistic profiles. A sample of 76 Italian children with ASD (range: 4.9 – 8 years), including 50 M and 26 F, was retrospectively recruited. Language profiles were analyzed using standardized tests for the evaluation of receptive and expressive vocabulary as well as grammar. Grammatical comprehension was the most impaired domain compared to the other language measures in both M and F children. Comparing language profiles between S/G, F showed significantly better scores than M in grammatical production (p=.002), and M showed better active negative sentences comprehension (p=.035). Moreover, comparing the language profiles between M and F with receptive disorder, F had significantly worse grammatical comprehension and better grammatical production than M. Even among children without receptive disorder, F had significantly higher grammatical production scores. The S/G differences in language profile, particularly better expressive language in F than M, can partially contribute to the delayed ASD diagnosis or underdiagnosis of F without intellectual disability. Finally, our results document the importance of accurately investigating both expressive and receptive abilities in children with ASD.

Radio-dynamic therapy (RDT), as an emerging cancer treatment method, has attracted attention due to its remarkable therapeutic efficacy using low-dose, high-energy radiation (such as X-rays), and has shown significant potential in cancer treatment. The RDT system typically consists of scintillators and photosensitizers. Scintillators absorb X-rays and convert them to visible light, activating nearby photosensitizers to generate cytotoxic reactive oxygen species (ROS). Challenges faced by the two-component strategy, including low loading capacity and inefficient energy transfer, hinder its final effectiveness. In addition, the tumor microenvironment (TME) with hypoxia and immunosuppression limits the efficacy of RDTs. Recent advances introduce one-component RDT systems based on nanomaterials with high-Z metal elements, which effectively inhibit deep-seated tumors. These novel RDT systems exhibit immune enhancement and immune memory, potentially eliminating both primary and metastatic tumors. This review comprehensively analyzes recent advances in the rational construction of RDTs, exploring their mechanisms and its application in the treatment of deep-seated tumors. Aimed at providing a practical resource for oncology researchers and practitioners, the review offers new perspectives for potential future directions in RDT research.

Perceived peer support is a critical factor in the academic adjustment of higher vocational college students. While previous studies have explored this relationship, few studies have delved into the underlying mechanisms. This study surveyed 9782 students from 35 higher vocational colleges in 13 provinces and cities in China to explore the relationship and mechanisms between perceived peer support and academic adjustment. Drawing on Conservation of Resources theory and Social Support Resource theory, the findings revealed that perceived peer support not only directly predicted the academic adjustment of higher vocational college students, but also indirectly through the independent mediating effect of academic hope and professional identity, as well as the chain-mediating effect of academic hope to professional identity. Additionally, students from vocational high schools showed a more significant increase in academic hope due to perceived peer support compared to those from general high schools, highlighting the moderating effect of educational background. The study provided a new theoretical perspective for understanding the complex mechanisms of academic adjustment in students and offers valuable guidance for educational practice, emphasizing the importance of fostering perceived peer support, academic hope, and professional identity in higher vocational education.

Background: Anxiety disorders can be both an independent risk factor of many somatic conditions and the cause of complications of various organic disorders leading to poor prognosis. Objectives: The purpose of this study is to compare the heart rate variability (HRV) recorded both during the day and at night in patients with anxiety disorders and healthy individuals. Methods: The study was conducted on fifty consecutive outpatients with anxiety disorders who participated in intensive group psychotherapy. The diagnosis was made according to DSM-IV-TR criteria using the PSE-10 questionnaire. Out of 50 patients under study, 17 were diagnosed with panic disorder (PD) and 21 with generalized anxiety disorder (GAD). The control group consisted of 40 healthy people. The resulting three groups were compared in terms of circadian HRV using the Oxford Medilog Suprima Holter System. Results: The HRV analysis showed the nocturnal falls in the time and frequency parameters related to parasympathetic activity (rMSSD, pNN50, HF). The most unfavourable alterations were observed in the PD group, which comprised the disappearance of day vs. night amplitude of the majority of HRV parameters. Hence, the PD group was particularly susceptible to the arrhythmic events. It was noticeable that nocturnal vagotonia in the PD group was significantly lower as compared with the GAD and control group. Conclusions: The innovative aspect of the present study was to find a distinct profile of HRV with regard to the types of anxiety disorders because of the existing considerable differences between the nature of PD and GAD.

The question of what generates conscious experience has mesmerized thinkers since the dawn of humanity, yet its origins remain a mystery. The topic of consciousness has gained traction in recent years, thanks to the development of large language models that now arguably pass the Turing test, an operational test for intelligence. However, intelligence and consciousness are not related in obvious ways, as anyone who suffers from a bad toothache can attest - pain generates intense feelings and absorbs all our conscious awareness yet nothing particularly intelligent is going on. Still, in the hard sciences, this topic is frequently met with skepticism because to date no protocol to measure the content or intensity of conscious experiences in an observer-independent manner has been agreed upon. Here we present a novel proposal: Conscious experience arises whenever a quantum mechanical superposition forms. Our proposal has several implications: First, it suggests that the structure of the superposition determines the qualia of the experience. Second, quantum entanglement naturally solves the binding problem, ensuring the unity of phenomenal experience. Finally, a moment of agency may coincide with the formation of a superposition state. We outline a research program to experimentally test our conjecture via a sequence of quantum biology experiments. Applying these ideas opens up the possibility of expanding human experience through brain-quantum computer interfaces.

This study aimed to identify miRNA editing sites during adipose tissue development in Ningxiang pigs and analyze their characteristics and functions. Based on the small RNA-seq data from subcutaneous adipose tissue samples of Ningxiang pigs at four stages (30, 90, 150 and 210 days), we constructed a developmental atlas of the miRNA editome in adipose tissue of Ningxiang pigs. The characteristics and functions of this editome were further explored through bioinformatics analysis. The findings revealed that a total of 505 miRNA editing sites were identified with C-to-U editing types being the most prevalent, followed by U-to-C, A-to-G and G-to-U. Importantly, these four types of miRNA editing exhibited a base preference. The number of editing sites showed obvious differences among age groups, with the highest occurrence of miRNA editing events observed at 90 days of age and the lowest at 150 days of age. In the miRNA seed region, a total of 9 miRNA editing sites were identified with significant differences in editing levels (P < 0.05), and located in ssc-miR-23a, ssc-miR-27a, ssc-miR-30b-5p, ssc-miR-15a, ssc-miR-497, ssc-miR-15b, and ssc-miR-425-5p, respectively. Target gene prediction and enrichment analysis revealed that the editing of miR-497 may potentially regulate fat deposition by inhibiting adipose synthesis via influencing target binding. These results provide new insights into the regulatory mechanism of pig fat deposition.

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

Species of the genus Drosophila have served as favorite models in speciation studies; however, genetic factors of interspecific reproductive incompatibility are underinvestigated. Here we performed the analysis of hybrid female sterility by crossing Drosophila melanogaster females and Drosophila simulans males. Using transcriptomic data analysis, molecular, cellular, and genetic approaches, we analyzed differential gene expression, transposable element (TE) activity, piRNA biogenesis, and functional defects of oogenesis in hybrids. Premature germline stem cell loss was the most prominent defect of oogenesis in hybrid ovaries. Due to the differential expression of genes encoding piRNA pathway components, rhino and deadlock, the functional RDCmel complex in hybrid ovaries was not assembled. However, the activity of the RDCsim complex was maintained in hybrids, independent of the genomic origin of piRNA clusters. Despite the identification of a cohort of overexpressed TEs in hybrid ovaries, we found no evidence that their activity can be considered the main cause of hybrid sterility. We revealed a complicated pattern of Vasa protein expression in the hybrid germline, including partial AT-chX piRNA targeting of the vasasim allele and a significant zygotic delay in vasamel expression. We arrived at the conclusion that the hybrid sterility phenotype was caused by intricate multi-locus differences between the species.

The seed habit is the most complex and successful method of sexual reproduction in vascular plants. It represents a remarkable moment in the evolution of plants that afterwards spread on land. In particular, seed size had a pivotal role as for evolutionary success and agronomic trait, especially in the field of crop domestication. Given that crop seeds constitute one of the primary products for consumption, it follows that seed size represents a fundamental determinant of crop yield. This adaptative feature is strictly controlled by genetic traits from both maternal and zygotic tissues, although seed development and growth are also affected by environmental cues. Despite being a highly exploited topic for both basic and applied research, there are still many issues to be elucidated as for developmental biology as well as for agronomic science. This review addresses a number of open questions related to cues that influence seed growth and size, and how developmental processes are influenced by them. Besides, new insights on the genetic-molecular control of this adaptive trait are presented.

Self-sustained learning (SSL) is considered a crucial factor in promoting students’ long-term learning and development in a sustainable society. To deepen the understanding of SSL, especially in the context of learning English as a second language, the current study examined the influence of intercultural communicative skills, language mindset, and positive L2 self on SSL in English learning among 1,238 college students in China. The results showed that students not only had a strong language mindset, positive L2 self, and intercultural communicative skills but also scored higher in long-term self-sustained English learning. Findings from the Structural Equation Modeling indicated that both language mindset and intercultural communicative skills positively predicted positive L2 self and self-sustained English learning. Furthermore, language mindset and intercultural communicative skills had an indirect impact on self-sustained English learning through positive L2 self. These findings suggest that to promote English learners’ SSL, instructors should help facilitate students’ intercultural communicative skills and foster a growth language mindset, as well as positive language learning beliefs.

Tryptophan, an essential amino acid in mammals obtained from the diet, is influenced by maternal diet, which impacts early life and development of offspring. This is studied under the Developmental Origins of Diseases and Health (DOHaD) concept, so factors from conception to early childhood affect health and disease susceptibility. Tryptophan is metabolized mainly through two pathways: serotonin (5-HT) and kynurenine. The kynurenine pathway, active in the brain, gut, liver, and placenta, breaks down over 95% of tryptophan and plays roles in inflammation, neurotransmission, immune responses, and immune modulation during pregnancy. The serotonin pathway uses up to 5% of Tryptophan, mainly in the gut, adipose tissues, pancreatic cells, and central nervous system, and regulates responses to environmental changes, including sleep, cognition, and feeding behavior. Key enzymes in these pathways include Trp-2,3-dioxygenase (TDO), indoleamine-2,3-dioxygenase (IDO) type1 (IDO1), and type 2 (IDO2) (kynurenine pathway), and tryptophan hydroxylase type 1 (TPH1) and type 2 (TPH2), serotonin pathway. The fetus-placental unit manages tryptophan metabolism. Serotonin and kynurenine are crucial for placental health and fetal development. Serotonin adjusts placental blood volume and aids neurodevelopment. Kynurenine metabolites protect the fetus from maternal immunity and offer initial neuroprotection. At birth, infants switch from placental nutrients to breast milk, rich in tryptophan and protective bioactive molecules. Tryptophan, solely from breast milk, is crucial for infants. Its levels are high in newborns (first three weeks, 2-4 times higher than in adults), gradually declining to adult levels by the fourth week. The highlights the importance of tryptophan for the serotonin and kynurenine pathways in fetuses, newborns and babies applied to the DOHaD concept.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and restricted interest for specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD and identifying potential therapeutic strategies. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 hours post-fertilization. After the exposure, embryos were transferred to fish water and the effects on behavior and neurotransmitters profile were analyzed at both larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. Neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the interest of this model in the study of ASD.

Recommender Systems (RecSys) are crucial in managing information overload and enhancing user satisfaction across various digital platforms, including e-commerce and entertainment. Evolving from traditional models to Deep Neural Networks (DNNs) and, more recently, Large Language Models (LLMs), these systems leverage sophisticated algorithms to analyze user behaviors and preferences. LLMs, such as GPT-4, are trained on extensive datasets to comprehend and generate natural language, significantly advancing their ability to deliver personalized recommendations. This tutorial explores the transformative impact of LLMs on RecSys, discussing their development, application in handling complex datasets, and the integration of contextual insights. Real-world examples illustrate how LLMs enhance recommendation accuracy and user experience, highlighting challenges and future directions in the field.

Despite the growing capabilities of large language models, concerns exist about the biases they develop. In this paper, we propose a novel, automated mechanism for debiasing through specified dataset augmentation in the lens of bias producers that can be useful in a variety of industries, especially ones that are “restricted” and have limited data. We consider that bias can occur due to intrinsic model architecture and dataset quality. The two aspects are evaluated using two different metrics we created. We show that our dataset augmentation algorithm reduces bias as measured by our metrics.

The rapid advancement of large language models (LLMs), such as ChatGPT, has revolutionized natural language processing, enabling these models to generate coherent and contextually relevant text. These capabilities hold significant potential for various applications, particularly in the medical field. LLMs can assist healthcare professionals by providing accurate information, supporting diagnostic processes, and enhancing medical education. However, the implementation of LLMs in clinical settings faces several barriers, including technical limitations, ethical concerns, regulatory constraints, and practical challenges. Ensuring accuracy, reliability, and interpretability is crucial, along with addressing biases, ensuring data privacy, and establishing ethical guidelines. Future research should focus on improving training techniques, developing explainable AI methods, and creating efficient, resource-saving models. Expanding applications through domain-specific models and multi-modal integration can further unlock the potential of LLMs. By addressing these challenges and prioritizing responsible development, LLM technology can be safely and effectively integrated into various domains, driving innovation and improving outcomes. This paper explores the current state of LLM technology, its medical applications, barriers to implementation, and directions for future research and development

Until the 1950s, developmental dyslexia was defined as a hereditary visual disability, selectively affecting reading without compromising oral or non-verbal reasoning skills. This changed radically after the development of the phonological theory of dyslexia; this not only ruled out any role for visual processing in its aetiology, but also cast doubt on the use of discrepancy between reading and reasoning skills as a criterion for diagnosing it. Here I argue that this theory is set at too high a cognitive level to be explanatory; we need to understand the pathophysiological visual and auditory mechanisms that cause children’s phonological problems. I discuss how the ‘magnocellular theory’ attempts to do this in terms of slowed and error prone temporal processing which leads to dyslexics’ defective visual and auditory sequencing when attempting to read. I attempt to deal with the criticisms of this theory and show how it leads to a number of successful ways of helping dyslexic children to overcome their reading difficulties.

Sentiment analysis has become an important tool for understanding public opinion across languages and domains. Recently, there has been an increase in the number of studies on sentiment analysis in low-resource languages such as Kazakh. This is important to ensure that modern text analysis technologies are accessible to all users, regardless of their language background. The aim of the study is to create a sentiment analysis model for analyzing texts in Kazakh. As part of this work, we aim to use fine-tuning techniques on our own dataset for already existing models, thus improving their accuracy and efficiency for analyzing Kazakh language texts. This paper presents a manually collected dataset "KazIntTelCom" from the city information service 2GIS, consisting of user reviews, manually annotated by the authors taking into account the polarity of sentiment (i.e. negative positive or neutral). This dataset was used to fine-tune two pre-trained multi-lingual Transformer-based sentiment analysis models taken from the HuggingFace platform. The distillBERT and XLM-RoBERTa models were used for tuning. Also, the models were tested on the dataset "KazSAnDRA". The results show that accurate tuning even on a relatively small dataset gives a significant increase in performance, which is confirmed by an increase in the accuracy index by 20%-30%. In addition, false misses and false detections are analyzed, which allows us to identify directions for further improvement of the models. The contribution of this work, in addition to the dataset, is the analysis of model errors, which will help future developers to make more accurate settings of hyperparameters of training for sentiment analysis in Kazakh. These results are important for natural language processing and their adaptation to low-resource languages, promoting more inclusive and equitable access to modern analytical tools. Thus, this study demonstrates the effectiveness of the Transformers architecture for sentiment analysis in Kazakh and opens new opportunities for further model improvement.

European strategic policy directions towards a sustainable blue economy have strengthened interest in maritime investments, thus increasing sectoral competition for marine space. Emerging repercussions out of such a rising interest need to be handled by Marine Spatial Planning (MSP) as a means for: properly allocating marine space to diverse uses; managing conflicts and promoting synergies among them; and pursuing a multi-use perspective of this space. A critical stage of each MSP exercise is the exploration of land-based spatial/developmental directions and their current or potential repercussions in the marine environment in order for constraints but also perspectives in policy choices/maritime uses in the MSP context to be featured; and attainment of a successful coherence or coordination between land and marine spatial/developmental policies to be ensured, by analyzing Land-Sea-Interaction (LSI) and embedding it in the MSP. The latter is the focus of this paper aiming to illuminate critical issues emerging from land-based (terrestrial) policy frameworks for feeding MSP endeavors; and is accomplished in the Northern Aegean Sea, Greece. Towards this end, a multilevel approach is adopted, delving into diverse policy contexts at the local, regional and national/European level and aiming to attain more informed MSP decisions in the specific study region.

This research presents the Cross-Cultural Intelligent Language Learning System (CILS), a novel approach integrating Artificial Intelligence (AI) into language education to enhance cross-cultural communication. CILS utilizes advanced AI technologies to provide adaptive, personalized learning experiences that cater to the unique linguistic and cultural backgrounds of each learner. By dynamically adjusting content and methodology, CILS significantly improves linguistic proficiency and cultural understanding, essential for effective global interactions. The implementation of CILS in platforms such as Busuu and HelloTalk has demonstrated marked improvements in engagement and communication skills among learners. Empirical studies validate the system's effectiveness in real-world settings, showing enhanced learner performance and increased intercultural competence. Additionally, the Technology Acceptance Model (TAM) applied confirms that the usability and perceived usefulness of AI-driven systems strongly influence learner acceptance and sustained use. This study not only underscores the potential of AI in transforming language education but also highlights the critical role of cultural sensitivity in designing educational technologies.

Background: Virtual Reality (VR) is an emerging tool in the management of anxiety, one of the most disturbing symptoms of Alcohol Use Disorder (AUD), which often leads to relapse. Still, patients with Alcohol Use Disorder frequently have a history of Acute Symptomatic Seizures, and they are subsequently excluded from studies using VR because of the hypothesized fear of inducing photosensitive seizures. The first part of this narrative review explores the pathophysiological mechanisms of seizures associated with AUD, specifically acute symptomatic seizures. In contrast, the second part explores virtual reality’s safe use in seizure-prone individuals, highlighting that the current state-of-the-art is based on a biased per-ception and old epidemiological data from studies conducted on photosensitive seizures in the late 90s. VR exposure has yet to be reported as triggering seizures within known pharmacovigilance databases. Significance: The implications weigh heavily on VR research currently associated with this significant adverse event. Further studies are necessary to address the risk of seizures triggered by VR in patients predisposed to developing seizures, like alcohol use disorder patients with a history of acute symptomatic seizures. Such research is essential to ensure that the potential benefits of Virtual Reality as a tool for managing anxiety in individuals with alcohol use disorder and acute symptomatic seizures are not unduly restricted. Furthermore, AUD can also serve as an intervention model feasible to de-bias attitudes toward the current lack of evidence base concerning the significant adverse events of VR-induced seizures, therefore facilitating the clinical implementation of this unharnessed digital treatment interface.

Preschoolers with disabilities and their caregivers have been neglected in health and social service provision in most low-income countries and arguably too in low resourced areas of more affluent nations. Yet as this rapid review of published literature identifies, there are low-cost, evidence-based strategies to address their needs that can be implemented in communities by local people. Five key features of the necessary supports are examined. First the leadership functions required to create and implement the support services. Second, the family-centred, home-based support provided to caregivers and the personnel undertaking this form of support. Third, providing opportunities for peer support to flourish and encouraging the formation of advocacy groups across families. Fourth, mobilizing the support of significant groups within the community; notably traditional healers and leaders; health services and poverty alleviation initiatives. Fifth, devising ways in which preschool educational opportunities can be offered to children as a prelude to their inclusion in primary schools. The review serves a further purpose. It provides an example of how public health researchers and academics could achieve more rapid implementation of evidence-based knowledge into existing and new support services through dissemination to community practitioners.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Abstract: Remarkably, the p53 transcription factor, referred to as “the guardian of the genome”, is not essential for mammalian development. Moreover, efforts to identify p53‑dependent developmental events have produced contradictory conclusions. Given the importance of pluripotent stem cells as models of mammalian development, and their applications in regenerative medicine and disease, resolving these conflicts is essential. Here we attempt to reconcile disparate data into justifiable conclusions predicated on reports that p53‑dependent transcription is first detected in late mouse blastocysts, that p53 activity first becomes potentially lethal during gastrulation, and that apoptosis does not depend on p53. Furthermore, p53 does not regulate expression of genes required for pluripotency in embryonic stem cells (ESCs); it contributes to ESC genomic stability and differentiation. Depending on conditions, p53 accelerates initiation of apoptosis in ESCs in response to DNA damage, but cell cycle arrest as well as the rate and extent of apoptosis in ESCs are p53-independent. In embryonic fibroblasts, p53 induces cell cycle arrest to allow repair of DNA damage, and cell senescence to prevent proliferation of cells with extensive damage.

Large Language Models (LLMs) have demonstrated promising capabilities to solve complex tasks in critical sectors such as healthcare. However, LLMs are limited by their training data which is often outdated, the tendency to generate inaccurate ("hallucinated") content and a lack of transparency in the content they generate. To address these limitations, retrieval augmented generation (RAG) grounds the responses of LLMs by exposing them to external knowledge sources. However, in the healthcare domain there is currently a lack of systematic understanding of which datasets, RAG methodologies and evaluation frameworks are available. This review aims to bridge this gap by assessing RAG-based approaches employed by LLMs in healthcare, focusing on the different steps of retrieval, augmentation and generation. Additionally, we identify the limitations, strengths and gaps in the existing literature. Our synthesis shows that proprietary models such as GPT-3.5/4 are the most used for RAG applications in healthcare. Also, there is a lack of standardized evaluation frameworks for RAG-based applications. In addition, the majority of the studies do not assess or address ethical considerations related to RAG in healthcare. It is important to account for ethical challenges that are inherent when AI systems are implemented in the clinical setting. Lastly, we highlight the need for further research and development to ensure responsible and effective adoption of RAG in the medical domain.

This research ventures into the critical public health challenge of childhood obesity by exploring the dynamic interplay between psychological well-being and Body Mass Index (BMI) throughout various developmental stages of childhood. It delves into how emotional regulation, attachment dynamics, and social relationships correlate with obesity from early childhood to adolescence. Highlighting key findings, such as the negative correlation between psychological resilience and higher BMI in young children, the impact of social relationships on obesity risk during pre-adolescence, and the link between adaptive emotional strategies and higher BMI in adolescents, this study brings to the fore the nuanced relationship between psychological factors and obesity. Utilizing the interdisciplinary process of bioinformatics, this research synergizes psychometric and biomedical data to unearth psychological markers critical for crafting targeted, age-appropriate interventions. This study advocates for a holistic healthcare approach, emphasizing the integration of psychological support within obesity prevention and management strategies, thereby underscoring the indispensable role of psychological factors in the fight against childhood obesity. The application of bioinformatics methods to analyze complex datasets demonstrates how collaboration across medical specialties can enrich our understanding and response to childhood obesity, contributing significantly to the development of comprehensive, bioinformatics-enhanced healthcare solutions.

The pursuit of Artificial Intelligence (AI) that emulates human cognitive processes is a cornerstone of ethical AI development, ensuring that emerging technologies can integrate seamlessly into societal frameworks requiring nuanced understanding and decision-making. Zero-Shot Instance Retrieval (ZSIR) stands at the forefront of this endeavour, potentially providing a robust platform for AI systems, particularly large visual language models, to demonstrate and refine cognition-aligned learning without the need for direct experience. In this paper, we critically evaluate current cognition alignment methodologies within traditional zero-shot learning paradigms, using visual attributes and word embedding generated by large AI models. We propose a unified similarity function that quantifies the cognitive alignment level, bridging the gap between AI processes and human-like understanding. Through extensive experimentation, our findings illustrate that this similarity function can effectively mirror the visual-semantic gap, steering the model towards enhanced performance in zero-shot instance retrieval. This work not only benchmarks the cognition alignment of AI, but also sets a new precedent for the development of visual language models attuned to the complexities of human cognition.}

Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

Tao and Ming (name) or Tao and Yan (language or speech) is an inseparable pair of important concepts in traditional Chinese language philosophy. In LaoTze’s opinion, Tao could not be spoken out, and language or speech could not reach Tao’s essence. Yan and Tao are separated from each other, and they are paradoxical. All the confusion derives from Yan regardless of how delicate they are. Tao can be expressed in words, but it will never be expressed through common languages. In this article, Tao is regarded as a human being’s thoughts or intentions and is even considered to be the origin of the real world. Language can express people’s thought, although it has some limitations. There exist some contradictions between the real word and the world expressed in words. To enable people to better understand the existence of the real world from multiple perspectives at the language or linguistic level without being constrained by words, this article studies LaoTze’s linguistic philosophy reflected in his opinion on the relationship between Tao and Yan and makes a comparative analysis of modern Western language philosophers’ stand on language (or speech) and existence.

RNA sequencing techniques, like bulk RNA-seq and Single Cell (sc) RNA-seq, are critical tools for the biologist looking to analyze the genetic activity/transcriptome of a tissue or cell during an experimental procedure. Platforms like Illumina's next-generation sequencing (NGS) are used to produce the raw data for this experimental procedure. This raw FASTQ data must then be prepared via a complex series of data manipulations by bioinformaticians. This process currently takes place on an unwieldy textual user interface like a terminal/command line that requires the user to install and import multiple program packages, preventing the untrained biologist from initiating data analysis. Open-source platforms like Galaxy have produced a more user-friendly pipeline, yet the visual interface remains cluttered and highly technical, remaining uninviting for the natural scientist. To address this, SeqMate is a user-friendly tool that allows for one-click analytics by utilizing the power of a large language model (LLM) to automate both data preparation and analysis (differential expression, trajectory analysis, etc). Furthermore, by utilizing the power of generative AI, SeqMate is also capable of analyzing such findings and producing written reports of upregulated/downregulated/user-prompted genes with sources cited from known repositories like PubMed, PDB, and Uniprot.

Since the beginning of the internet era, there has been an explosion of growth in structured data (such as numbers, symbols, and labels) as well as unstructured data (including images, videos, and text). Efficient and accurate mixed query of these two types of data is a key technology to achieve high-quality information retrieval, and it is also a major challenge that needs to be solved urgently in the industry. In this study, we employ an advanced Transformer model that combines strategies and fine-tuning techniques for multi-task learning. Specifically, the model is first pre-trained on a large-scale, general-purpose dataset to learn different types of data representations and basic language comprehension skills. After that, we fine-tuned the parameters of the model to better suit these specific data processing tasks for specific application scenarios, such as image annotation, video content analysis, and structured data query. At the heart of the model is the self-attention mechanism, which allows the model to automatically emphasize the important parts and ignore irrelevant information when processing the input data. In addition, we have introduced task-specific adaptation layers that are designed to add additional processing power to the original Transformer architecture, such as a semantic analysis layer for unstructured text data and a relational extraction layer for structured data. This combination of general pre-training and task-specific fine-tuning allows the model to flexibly process and integrate information from different data sources, improving processing efficiency and accuracy. Experimental results show that the model performs well in a variety of data processing tasks, significantly improves the accuracy and efficiency of information retrieval, and verifies the strong potential and adaptability of large language models in processing mixed data types.

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of myosin heavy chains (MyHCs) they express and changes in MyHC expression during phylogeny. Myogenic progenitors from mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB. They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC, cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of their food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift towards slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs they express. Thyroid hormone shifts 2A MyHC towards 2B in jaw, laryngeal muscles and possibly extraocular muscles.

In an era marked by rapid technological progress and global dynamics, the Neo-Language Acquisition and Learning Theory challenges conventional language acquisition paradigms through its conceptualization of 'Grit: The Unyielding Will to Connect,' emphasizing determination, motivation, and adaptability as the primary drivers of language learning, transcending age-related constraints and critical periods. This theory also underscores 'Self-Preservation: Language as the Canvas of Reality,' as language plays a pivotal role in preserving and conveying our individual and collective experiences. Recent global events have underscored the theory's relevance, prompting a reevaluation of language education in response to changing circumstances. Moreover, 'Techno-Training: Language Acquisition and Learning in the Digital Age' is integral to the theory, as it recognizes the influence of technology on modern language education. Beyond traditional methods, these three reshape our fundamental understanding of said theory. Drawing from historical evidence, psychological principles, and contemporary applications, they supported the conceptualization of the theory itself. Overall, the Neo-Language Acquisition and Learning Theory revolutionizes language education, spotlighting the power of motivation, determination, and adaptability to navigate the evolving landscape of language learning and acquisition.

Large language models (LLMs) have recently garnered significant attention due to their remarkable ability to assimilate vast amounts of information and effectively process natural language. In healthcare, natural language constitutes a substantial portion of medical data, rendering LLMs highly promising for various healthcare applications. This study seeks to explore the potential of LLMs in healthcare and clinical decision support (CDS), following PRISMA guidelines for reviews. The analysis encompasses 44 LLMs, each influenced by several factors impacting their performance. Notably, the datasets utilized for pretraining and finetuning processes play a crucial role in determining the model’s domain specificity. Furthermore, distinct model architectures are tailored for specific tasks, while prompting strategies are frequently employed to refine and enhance the model’s performance. LLMs exhibit considerable promise for a wide array of healthcare applications. For instance, LLMs possess the potential to handle and analyze medical information efficiently, facilitate contextual understanding among clinicians and patients, as well as automate the documentation of clinical notes and reports. Presently, however, their implementation within the field remains limited. Notable improvements have been witnessed in the performance of current healthcare-oriented LLMs, with some achieving expert-level competence in medical question-answering (MQA). However, these LLMs face prominent challenges, encompassing ethical concerns, issues related to accountability, and a lack of appropriate regulations. Nevertheless, this study reveals numerous promising applications in healthcare where LLMs could significantly augment the efficiency, accessibility, and manageability of healthcare delivery. Addressing the challenges LLMs encounter is essential for their seamless integration into practical healthcare applications. As a relatively new technology, the development of LLMs is still in its early stages, but their potential is evident through this study. Consequently, fostering collaboration among healthcare professionals, developers, regulators, and other stakeholders is imperative to cultivate dependable LLMs that align with the demands of the healthcare sector.

Artificial Intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use ChatGPT holds a prom-inent position using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for gen-erating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT in-tegration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex data sets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.

The oocyte is the major determinant of embryo developmental competence in all mammalian species. Although fundamental advances have been generated in the field of reproductive medicine and assisted reproductive technologies in the past three decades, researchers and clinicians are still trying to elucidate molecular factors and pathways which could be pivotal for the oocyte’s developmental competence. The cell-to-cell and cell-to-matrix communications are crucial not only for oocytes but also for multicellular organisms in general. This latter mentioned communication is among others possible due to the Connexin and Pannexin families of large-pore forming channels. Pannexins belong to a protein group of ATP-release channels, therefore of high importance for the oocyte due to its requirements of high energy supply. An increasing body of studies on Pannexins provided evidence that these channels not only play a role during physiological processes of an oocyte but also during pathological circumstances which could lead to the development of diseases or infertility. Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore playing a fundamental role in the communication between the oocyte and accompanying cells. Herein, the role of Pannexins and Connexins for the processes of oogenesis, folliculogenesis, oocyte maturation and fertilization will be discussed, and at the end of this review, Pannexin and Connexin related pathologies and their impact on the developmental competence of oocytes will be provided.

The voice contains elementary social communication cues, conveying speech, as well as paralinguistic information pertaining to the emotional state and the identity of the speaker. In contrast to vocal-speech and vocal-emotion processing, voice-identity processing has been less explored. This seems surprising, given the day-to-day significance of person recognition by voice. A valuable approach to unravel how voice-identity processing is accomplished is to investigate people who have a selective deficit in recognising voices. Such a deficit has been termed phonagnosia. In the present chapter, we provide a systematic overview of studies on phonagnosia and how they relate to current neurocognitive models of person recognition. We review studies that have characterised people who suffer from phonagnosia following brain damage (i.e. acquired phonagnosia) and also studies, which have examined phonagnosia cases without apparent brain lesion (i.e. developmental phonagnosia). Based on the reviewed literature, we emphasise the need for a careful behavioural characterisation of phonagnosia cases by taking into consideration the multistage nature of voice-identity processing and the resulting behavioural phonagnosia subtypes.

This article provides a literature review on tubal carcinoma to offer an updated insight into its preventative strategies, diagnosis, treatment, and oncological surveillance. In addition to the search string utilized, the authors' focus extended to key scientific studies, consensus statements, guidelines, and relevant case reports essential for the proper clinical management of the disease, providing a methodologically well-structured literature review combined with the practical expertise in the oncological field. The article also includes two emblematic clinical cases that emphasize the importance of understanding the physiopathology and the current state of the art in the anatomopathological advancements of tubal/ovarian/peritoneal carcinoma, often assimilated into a single clinical entity.

The article presents the potential of liposomal cannabidiol in the treatment of Panic Disorder, when used in integration with Complex Cognitive Psychotherapy. The advantages of the integrated treatment, developed by the Author, and based on the use of liposomal cannabidiol combined with cognitive psychotherapy, are discussed. A new and original tool is presented and described, developed, and tested for the first time by the Author and called NegEnt Panic Blocker.

Preschoolers with disabilities and their family caregivers are missed out in many public health initiatives especially in low-income countries. Yet they can benefit from early intervention to promote their development from soon after birth and to provide a better quality of life for their families. In this paper, we describe how a community-based approach has been implemented with minimal funding in two areas in Zimbabwe: a township in Harare and in rural areas of Manicaland Province. Our aim in sharing this information – allied with references to research studies recently undertaken in Africa – is that it will enable similar supports to be replicated in other communities by local personnel. A logic model is used to describe the situation in which the two projects work, the various inputs they have provided to their community and the different forms of support they have offered to the children and their caregivers. The project outputs are listed in terms of the number of beneficiaries helped and activities undertaken. The outcomes achieved for the children, the family and communities are reported. The sustainability and extensions of community-based projects to address unmet needs are discussed. The main conclusion is that disadvantaged communities can be energized to address the needs of their most marginalized residents.

Decision-making is a complex process of selecting an option from the given choices by analyzing the background information like risk, loss, and gain within the alternative options presented. It has been observed in earlier studies that people are prompt to make less rational decisions when choices are given in a language less known to them. Therefore, to understand the effect of languages on decision-making, we have questioned native Hindi speakers in French and English. French being the foreign language, and English as their second language. Thus, this effect of a non-native language brings to light the important role that the native language plays routinely in judgment and decision-making. In this paper, we developed a Neuropsychological assessment to decipher the effects on decision-making between choices when given in foreign language and second language in comparison with the native language of an individual, which is termed as foreign language effect(Fle). We have explored various possible situations to understand the foreign language effect(Fle) in decision-making and does this change translates when the decision is to be made in the second language. Our study concludes that the Foreign language is least affected by the intuitive biases, followed by the second language, and the native language is most affected by it.

Naturally fermented dairy products are an important component of the human diet. They are a valuable source of nutrients as well as vitamins and minerals. Their importance as a source of probiotic bacterial strains should not be overlooked. A number of studies highlights the positive effects of species of the Lactobacillacea on the intestinal microbiota, the overall homeostasis of the body, as well as a complementary treatment for some diseases. However, data on the effects on intestinal epithelial cells of postmetabolites released by bacteria are incomplete. This is likely due to the fact that these effects are species and strain specific. In the present study, we investigated the effects of postmetabolites produced by a pre-selected candidate probiotic strain Limosilactobacillus fermentum on HT-29 intestinal epithelial cells. Our data showed a pronounced proliferative effect, evaluated by flow cytometry, quantification of cell population, and determination of mitotic index. This was accompanied by stabilization of the cell monolayer, measured by increase of TEER (trans epithelial electric resistance) and reorganization of actin filaments. The data obtained are a clear indication of the positive effects, that the products secreted by L. fermentum strain 53 have on the intestinal epithelial cells.

Natural language Processing (NLP) has significantly transformed in the last decade, especially in the field of Language Modeling. Large Language Models (LLMs) have achieved SOTA performances on Natural Language Understanding (NLU) and Natural Language Generation (NLG) tasks by learning language representation in self-supervised ways. This paper provides a comprehensive survey to capture the progression of advances in Language Models. In this paper, we examine the different aspects of Language Models, which started with a few million parameters but have reached the size of a trillion in a very short time. We also look at how these LLMs transitioned from task-specific to task-independent to task-and-language-independent architectures. This paper extensively discusses different pre-training objectives, benchmarks, and transfer learning methods used in LLMs. It also examines different fine-tuning and In-Context learning techniques used in downstream tasks. It also explores how LLMs can perform well across many domains and datasets if sufficiently trained on a large and diverse dataset. Next, it discusses how, over time, the availability of cheap computational power and large datasets have improved LLM’s capabilities and raised new challenges. As part of our study, we also inspect LLMs from the lens of scalability to see how their performance is affected by the model’s depth, width, and data size. Lastly, we provide an empirical comparison of existing trends and techniques and a comprehensive analysis of where the field of LLM currently stand.

Psychosis can be defined as a combination of psychopathological symptoms including delusions and/or hallucinations without insight. Psychotic disorders may configure a primary psychiatric illness or represent the result of a functional/structural brain damage induced by substance use, neurological diseases or other medical conditions. They are multifactorial disorders in which genetic, environmental and gene-environment interaction factors contribute to the expressiveness of the symptoms. Among the environmental factors, psychotropic substances represent the most important removable facilitators of psychosis. In our study, we compared the prevalence of substance induced psychosis between a sample of patients affected by cannabis use disorder and a sample of patients affected by cocaine use disorder analyzing retrospectively the data of outpatients with no personal or family history of psychiatric illnesses.

Development encompasses processes that occur at multiple length-scales, includ- ing gene regulatory interactions, cell movements and reorganisation, cell signalling and growth. It is essential that the timing of events in all of these different processes are coordinated to generate well patterned tissues and organs. However, how the timing of intrinsic cell state changes is coordinated with events at the multi-tissue and whole organism level is unknown. Here, we argue that an important mechanism which accounts for integration of timing across levels of organisation is provided by tissue tectonics: i.e. how morphogenetic events driving tissue shape change result in the relative displacement of signalling and responding tissues and coordinate devel- opmental timing across scales. In doing so, tissue tectonics provides a mechanism by which the cell specification events intrinsic to cells can be modulated by the temporal exposure to extracellular signals. This exposure is in turn regulated by higher-order properties of the embryo such as their physical properties, rates of growth and the combination of dynamic cell behaviours impacting tissue morphogenesis. Tissue tec- tonics creates a downward flow of information from higher to lower levels of biological organisation, providing an instance of downward causation in development.

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder characterized by difficulty maintaining attention, impulsivity and hyperactivity. Although the cause of this disorder is still unclear, recent studies state that heredity is important in the development of ADHD. This is linked to a few comorbidities: depression, criminal behavior and anxiety. Although genetic factors play a major role in the pathogenesis of ADHD, there are also non-genetic factors, one of which would be oxidative stress (OS) that are associated with ADHD. OS is implicated in the pathogenesis of ADHD, through lower levels of antioxidant enzymes such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), as well as a lower total antioxidant status (TOS) compared to control groups. Moreover, there is a close bidirectional connection between the nervous system and the intestinal microbiota, and the communication between the two systems is carried out through the gut-brain axis (GBA). A thorough review of diet, OS implications, mechanism of action, pharmacokinetics, and drug-drug interactions are reviewed here, with a special focus on treatment in adults with comorbid conditions.

With the rapid growth of large language models (LLMs), there is increasing demand for memory and computation in LLMs. Recent efforts on post-training pruning of LLMs aim to reduce the model size and computation requirements, yet the performance is still sub-optimal. In this paper, we present a plug-and-play solution for post-training pruning of LLMs. The proposed solution has two innovative components: 1) Relative Importance and Activations (RIA), a new pruning metric that jointly considers the weight and activations efficiently on LLMs; and 2) Channel Permutation, a new approach to maximally preserve important weights under N:M sparsity. The two proposed components can be readily combined to further enhance the N:M semi-structured pruning of LLMs. Our empirical experiments show that RIA alone can already surpass all existing post-training pruning methods on prevalent LLMs, e.g., LLaMA ranging from 7B to 65B. Furthermore, N:M semi-structured pruning with channel permutation can even outperform the original LLaMA2-70B on zero-shot tasks, together with practical speed-up on specific hardware. Our code is available at: https://github.com/biomedical-cybernetics/Relative-importance-and-activation-pruning

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore the functional association between protein disorder properties and different mental diseases. To address this gap, we collected disrupted gene sets for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control gene set from normal brains using DisGeNET and GeneCards databases. The state-of-the-art predictor IUPred2A was then utilized to calculate the disorder properties , followed by a thorough comparison between the disordered proteins in mental diseases and healthy controls. Functional enrichment analysis and protein-protein interaction networks were conducted to investigate the IDPs’ functional roles in psychiatric diseases. Additionally, we demonstrated the role of IDPs in protein binding formations through a case study of alpha-synuclein using protein docking. Our findings reveal that differentially expressed proteins in mental disorders, especially in ASD and ADHD, exhibit more IDPs than those in healthy controls. IDPs in psychiatric disorders are significantly enriched in neurodevelopmental pathways and play an important role in in gene expression regulation. Our results indicate distinct functional patterns of disorder proteins among mental diseases and healthy controls. When comparing the IDPs between ASD and ADHD, we observed that IDPs in ADHD are more likely linked to the synaptic signaling and regulation, while IDPs in ASD are more tendentiously related to diverse and complex biological processes. Our work offers valuable insights into the important functions of IDPs in psychiatric disorders, enhancing our understanding of the molecular mechanisms involved in psychiatric disorders.

Total hip arthroplasty (THA) is a preferred treatment for primary osteoarthritis (OA) or secondary due to developmental hip dysplasia (DDH). Gait analysis is considered a golden standard for evaluating post-arthroplasty walking patterns. This study compared post-THA spatiotemporal gait parameters (SGPs) between OA and DDH patients and explored correlations with demographic and clinical variables. Thirty patients (15 per group) were recorded during gait, and their SGPs were analyzed. Functionality was evaluated with the Oxford Hip Score (OHS). The OA patients were significantly older than DDH (pr< 0.51, all p< 0.05). The preoperative gait alterations associated with OA or DDH were improved to similar levels in both groups after THA. Post-arthroplasty SGPs and OHS correlations indicate limitations in certain activities. These find-ings must be correlated with kinetic gait analysis data to fully evaluate gait and functionality dif-ferences among patient groups.

Background: Older adults with bipolar disorder (OABD) are individuals aged 50 years and older with bipolar disorder (BD). People with BD may have fewer coping strategies or resilience. A long course of the disease, such as in OABD, could impact the development of resilience strategies, but this remains under-researched in OABD. Therefore, this study aims to assess resilience levels within the OABD and explore associated factors, hypothesizing that resilience could improve psychosocial functioning, wellbeing and quality of life of OABD patients. Methods: This study sampled 33 OABD patients from the OABD cohort at the Bipolar and Depressive Disorders Unit of Hospital Clinic of Barcelona. This was an observational, descriptive and cross-sectional study. Demographic and clinical variables as well as psychosocial functioning, resilience and cognitive reserve were analyzed. Resilience was measured using the CD-RISC-10. Non-parametric tests were used for statistical analysis. Results: The average CD-RISC-10 score was 25.67 points (SD 7.87). Resilience negatively correlated with the total number of episodes (p = 0.034), depressive episodes (p = 0.001), and the FAST (p < 0.001). Participants with normal resilience had a lower FAST (p = 0.046), a higher CRASH (p = 0.026), and more EOBD (p = 0.037) compared to those with low resilience. Conclusions: OABD individuals may exhibit lower resilience levels which correlate with more psychiatric episodes, particularly the number of depressions and worse psychosocial functioning and cognitive reserve. Better understanding and characterization of resilience could aid in early identification of patients requiring additional support to foster resilience and enhance OABD management.

We evaluated the dentofacial characteristics and temporomandibular disorder (TMD) symptomatology of patients with orthopedic instability before and after deprogramming with a stabilization splint. Sixty patients with the signs and symptoms of TMD were assessed using the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and underwent stabilization splint therapy to place the condyles in a more stable musculoskeletal position. The amount of condylar displacement was evaluated using the condylar position indicator (CPI). Six-teen angular and linear hard tissue landmarks were traced and compared from lateral cephalo-grams taken in the maximum intercuspation (MI) position before and in the centric relation (CR) position after the splint therapy. Following the splint therapy, the signs and symptoms of TMD were significantly reduced or completely eliminated in more than 90% of the patients. Compared with the values registered before the splint therapy, a significant reduction in the mean values of condylar displacement was observed on both sides of the vertical, horizontal, and transverse planes of space after the splint therapy. A comparison of pre- and post-splint lateral cephalograms revealed that, following the splint therapy, the mandible moved more posteriorly and rotated more in a clockwise direction. In patients with orthopedic instability and signs and symptoms of TMD, deprogramming of the neuromuscular system with a stabilization splint is highly recommended to provide a correct orthodontic diagnosis and improve the health of temporomandibular joint structures.

The primary objective of this study is to determine the existence of a significant correlation between inflammation levels, as measured by inflammatory markers IL-6, IL-1β, and TNF-α, and the severity of depressive symptoms assessed using HAM-D assessment scale. This could provide additional evidence supporting the hypothesis that inflammation plays a notable role in the pathogenesis of depression. The data analysis supports the hypothesis that the biological mechanisms of inflammation contributes to the clinical manifestations of depression. Elevated levels of inflammatory markers, especially interleukins (IL6, IL1β), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) have been identified in patients with major depressive disorder compared to the findings in healthy controls. Materials and Methods: Inflammatory markers (IL-6, IL-1β, and TNF-α) were measured in a sample of 31 patients hospitalized at the Socola Institute of Psychiatry in Iasi, Romania, and compared to a control group with no psychiatric or inflammatory conditions. One of the main objectives is to determine if there is a significant correlation between inflammation levels, measured by inflammatory markers (IL-6, IL-1β, and TNF-α), and the severity of depressive symptoms assessed using HAM-D scores. Conclusions: The study results suggest a significant correlation between inflammation levels measured by inflammatory markers IL-1β and IL-6 and the severity of depressive symptoms evaluated by HAM-D scores in the study group. These findings support the hypothesis that inflammation may play an important role in the development or exacerbation of depressive symptoms. The relationship between inflammation and depression is also influenced by risk and protective factors that require further research.

Hox genes represent an important gene family that is involved in the segmentation pattern and identity of the segments during the formation of the body plan in metazoans. For many years, several studies have sought to establish a correlation between the evolution of these genes and the evolution of large groups of metazoans. Here, we use publicly available sequences of Hox gene clusters to reconstruct the evolutionary history of anterior Hox genes. We show that information harbored by these genes, in part, reflects the evolution and diversification of most animal archetypes, but in many cases, there were conflicts between the evolutionary history of some genes and the history of large groups, these cases may have occurred due to specific and similar selective pressures in relatively distant groups, which may have led to evolutionary convergences. Our findings also reveal that the evolution of Hox genes (and clusters) as a multigene family is consistent to a birth-and-death model constrained by development, where there is a trade-off between a relatively fast gene turnover and their central developmental roles

As a medical student (Granada University Medical School, Spain), interested in Pediatrics, expended countless hours at the hospital pediatric facilities and got to know many of the children and their medical problems. A particular case, still vivid on my mind, awaken my scientific curiosity. One day, walking and talking with a seven years old child he unexpectedly felt down unconscious with multiple, incontrollable and erratic muscular contractions involving face, body and extremities and salivating. I was overwhelmed thinking it was the child’ last hour. At the time, my knowledge of epilepsy was nil. Following the seizures, the child was up, talking and walking with me as if nothing has happened and without any knowledge of the event. What could have caused the brain motor cortex to suddenly discharge that amount of altered activity causing generalized and erratic muscular contractions remains inexplicable. I migrated to USA, become a Pediatric (Developmental) Pathologist and Director of the Pediatrics Autopsy Service (1962-1999) at the Dartmouth-Hitchcock Medical Center, New Hampshire. I carried out countless postmortem studied of children brains, normal (unaltered) as well as those altered by hemorrhagic, hypoxic-ischemic and/or traumatic damage. With an NIH Fellowship, I spend one year (1967-68) at the Cajal Institute (Madrid, Spain) studying Cajal’ old Golgi preparations and learning about the method. Some of my Golgi studies of children’ brains have been published: The Human Brain. Prenatal Development and Structure, Springer, Heidelberg, Germany, 2012. The present monograph explores the developmental neuropathology of selected perinatal cortical injuries through their acute, subacute and chronic stages. Including: a) how an altered neuronal activity evolves in a damaged cortical region; b) how it moves through the cortex (epileptic auras); and c) how it reaches the motor cortex to be discharged as erratic and incontrollable muscular contractions. Understanding these processes should provide insights into the pathogenesis of epilepsy secondary to perinatal brain damage.

In most Eukaryotes, ubiquitin either exists as free monoubiquitin or as a molecule that is covalently linked to other proteins. These two forms cycle between each other and due to the concerted antagonistic activity of ubiquitylating and deubiquitylating enzymes, an intracellular ubiquitin equilibrium is maintained that is essential for normal biological function. However, measuring the level and ratio of these forms of ubiquitin has been difficult and time consuming. In this paper, we have adapted a simple immunoblotting technique to monitor ubiquitin content and equilibrium dynamics in different developmental stages and tissues of Drosophila. Our data show that the level of total ubiquitin is distinct in different developmental stages, lowest at the larval-pupal transition and in three days old adult males, and highest in first instar larvae. Interestingly, the ratio of free mono-ubiquitin remains within 30-50% range of the total throughout larval development, but peaks to 70-80% at the larval-pupal and the pupal-adult transitions. It stays within the 70-80% range in adults. In developmentally and physiologically active tissues, the ratio of free ubiquitin is similarly high, most likely reflecting a high demand for ubiquitin availability. We also used this method to demonstrate the disruption of the finely tuned ubiquitin equilibrium by the abolition of proteasome function or the housekeeping deubiquitylase, Usp5. Our data support the notion that the ubiquitin equilibrium is regulated by tissue- and developmental stage-specific mechanisms.

In a trip planning service, travelers first set a starting point, a destination, and a sequential list of specific points of interest types (e.g., museums, restaurants, and parks). Based on this information, the service searches the spatial database to customize the best travel itinerary for the tourist. However, in previous studies, planners only considered the time factor when designing the optimal route, and failed to fully consider the quality of each point of interest. In this study, we specifically leveraged the capabilities of large language model to parse and respond to complex travel-related user queries. To apply large language model to route planning, we fine-tuned the model to understand geotagging and user travel preferences. We have introduced a novel graph search algorithm combined with large language model output, which optimizes the route search process to provide optimal travel recommendations by taking into account various factors such as distance length, budget constraints, and popularity of tourist attractions. In addition, we have integrated real-time traffic data and historical travel data to further improve the prediction accuracy and application usefulness of the model. In the experimental validation phase, we designed a series of benchmarks to compare the performance of the system with traditional algorithms and other machine learning-based route planning methods. Experimental results show that our model has a significant improvement compared with traditional methods in improving the speed and accuracy of path selection.

We argue for reconsidering leadership development based on systems design principles. A primary advantage of systems thinking is that it encourages holistic approaches to development and avoids episodic program-based training and piecemeal thinking. The latter approaches are both limited and limiting yet tend to be the preferred approach to leadership development in organizations. Systems approaches to development offer numerous advantages both conceptually and pragmatically, especially through the incorporation of ongoing feedback cycles. Core practices that define a leadership development system are presented and implications are discussed.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, with a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free, and casein-free, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact on children. This review examines the effect of food selectivity, GI problems, and antioxidant deficiencies in ASD and revises the effectiveness of various therapeutic diets, highlighting the need for further research to confirm their long-term benefits.

The rapid advancement of technology has revolutionized language learning, introducing innovative methods that depart from traditional instructional approaches. This study employs a mixed-methods research design to examine the impact of chatbot-based language learning support, adaptive learning algorithms, and virtual reality language immersion on the language learning proficiency and self-regulated learning skills of English as a Foreign Language (EFL) learners. The research design includes quantitative analysis of language proficiency scores and qualitative exploration of learner experiences with the technological interventions. The theoretical implications of this study are rooted in constructivist and socio-cultural learning theories, which underpin the design and implementation of the technological interventions. The triangulation of qualitative and quantitative data revealed that the participants' positive perceptions of the effectiveness of chatbot-based language learning support were supported by the quantitative results, with the variable "chat-bot based support" demonstrating a substantial mean difference compared to other groups. This convergence of findings reinforces the positive influence of chatbot-based support on language learning outcomes and highlights the importance of integrating theoretical perspectives with empirical evidence to gain a comprehensive understanding of the impact of technological interventions on language learning outcomes for EFL learners. The study's findings provide insights into the potential of these technological interventions to optimize language learning outcomes for EFL learners and promote autonomous learning behaviors.

Opioids have served as a cornerstone in pain management for decades. However, the emergence of increasingly potent synthetic analogs brings forth a range of side effects, including respiratory depression, tolerance, dependence, constipation, and, more importantly, the development of severe and debilitating opioid use disorder (OUD). Search for therapeutics to mitigate OUD has been challenging and this has called for novel approaches that include design of small molecules targeting neuronal circuits involved in addiction (opioid, dopamine, serotonin, norepinephrine, and glutamate receptors, etc.) and development of biologics that target circulating opioids/opiates. In this review, we retrieved and discussed over two dozen of relevant patents filed in the past twelve (12) years that focus on novel approaches to produce therapeutics for OUD. The current review excluded patents on biologics and concentrated on small molecules, which will be discussed separately in a subsequent sequel. The chemical entities disclosed were highlighted and specific examples were provided where necessary. Although the number of patents in the realm of drug discovery for OUD is currently limited, we foresee a continued expansion in the quest for therapeutics for OUD in the years to come.

Functional neurological disorder, or FND, is widely misunderstood, particularly when considering recent research that suggests that the illness has a biological rather than a psychiatric basis. Nonetheless, the long-held view that FND is a purely psychiatric disorder without biological basis, or even a contrived (malingered) illness, remains pervasive both in modern medical care and general society. This is because FND involves an intermittent course of involuntary disability that rapidly alternates with improved neurological control. This has in turn caused shaming, low self-efficacy, and social isolation of the patients. Little research has examined the numerous biomarkers that are shared between FND and canonical neurological disorders and the encouraging outcomes that can follow conventional neurological rehabilitation, modified for this disorder. This review summarizes current research on FND biomarkers and physical rehabilitation results. General healthcare providers would benefit their care for their patients through their improved understanding the illness and recourses for support and treatment that are provided in this review.

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.

This paper offers an in-depth exploration of the complex relationship between seasonality and Autism Spectrum Disorder (ASD). It reviews existing research, providing a comprehensive summary of findings and highlighting the multifaceted dimensions of seasonality as an environmental factor that influences the etiology of ASD. The discussion encompasses various factors, including birth months, maternal health, dietary choices, and vitamin D deficiency, and delves into the intricate interplay of seasonality with environmental influences such as viral infections and solar radiation. The present study raises essential questions regarding the timing of environmental influences and the factors contributing to the rising prevalence of ASD. Ultimately, it underscores the need for future epidemiological research to incorporate more extensive investigations of environmental risk factors and employ advanced statistical analyses. This comprehensive overview contributes to a deeper understanding of how seasonality factors may be linked to the occurrence of ASD and its increasing prevalence, recognizing the multifaceted and diverse nature of these interactions.

The present review aimed to identify through what means neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system (CNS) that, when damaged, lead to distinct PTSD symptoms–namely dissociative reactions or flashbacks. Our review narrowed its focus to three common neurologic injuries including traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the role of noradrenergic neuromodulatory signaling on the HPA axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. This paper also described how damage to the CNS can alter the function of the limbic system and result in characteristic symptoms of PTSD like intrusive memories and acute psychological distress. Further, our review intended to draw attention to a lack of PTSD prognosis in TBI, SAH, and stroke patients who could benefit from early treatment. PTSD symptoms often compound with pre-existing issues further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD such that earlier diagnoses and appropriate treatment are observed in clinic.

Limited understanding exists regarding the intricate dynamics between the levels of social inhi-bition exhibited by both wives and husbands concerning their perceived family support and de-pressive symptoms, particularly within couples who are parents of children diagnosed with au-tism spectrum disorder (ASD). This study used the actor-partner, interdependence mediation model to analyze data collected from 397 pairs of Chinese parents with children diagnosed with ASD. The findings of the study revealed significant indirect actor effects, indicating that the levels of social inhibition exhibited by both wives and husbands were associated with their own de-pressive symptoms through their respective perceptions of family support. In general, the study did not find significant partner effects, except for some indirect effect (IE) of wives on their hus-bands' depressive symptoms through the wives' perceived social support. This observation sug-gests that cultural norms and role expectations within the family context may influence these dy-namics. These results underscore the potential importance of interventions aimed at addressing social inhibition and enhancing perceived family support to alleviate depressive symptoms in this population. Additionally, interventions targeting fathers should emphasize the importance of their involvement in parenting and collaboration with their partners in caring for children with ASD. Such collaborative efforts may contribute to improved outcomes for both parents and chil-dren within families affected by ASD.

Background: Colorectal cancer (CRC) can significantly impact mental health, increasing suicide risk. Variables such as pain and threat perception may be crucial. This study aims to identify predictors of suicide risk in individuals with CRC. Methods: A total of 71 participants (76.06% men) aged 27 to 88 years (M = 65.18, SD = 12.02) were assessed using the SF-36 for pain, the Brief Illness Perception Questionnaire (B-IPQ) for threat perception, the Hospital Anxiety and Depression Scale (HADS) for emotional distress, and the Plutchik suicide risk scale for suicide risk. Descriptive, comparative, and correlational analyses were performed, followed by a linear regression analysis. Results: Nearly 20% of participants exhibited high suicide risk. There was a moderate to high association between suicide risk and the perception of threat, pain, and emotional distress. The linear regression model explained 39% of the variance in suicide risk, with threat perception, pain, and emotional distress as significant predictors. Conclusions: These results indicate the need for multidisciplinary care for individuals with CRC, including emotional support from health psychologists, and holistic, human-centered care from nursing and medical professionals. Future research is necessary to further explore these relationships and improve patient care strategies.

Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modelling of gene expression networks that involve large amounts of data. The integration of data from DNA, RNA, and protein activities has resemblance to pharmacogenomics, which is of utmost importance in the development of cancer drugs. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Expanding the study and application of functional genomics has great promise to advance the process of discovering and repurposing drugs, especially in the field of oncology.

Structured science summaries or research contributions using properties or dimensions beyond traditional keywords enhances science findability. Current methods, such as those used by the Open Research Knowledge Graph (ORKG), involve manually curating properties to describe research papers' contributions in a structured manner, but this is labor-intensive and inconsistent between the domain expert human curators. We propose using Large Language Models (LLMs) to automatically suggest these properties. However, it's essential to assess the readiness of LLMs like GPT-3.5, Llama 2, and Mistral for this task before application. Our study performs a comprehensive comparative analysis between ORKG's manually curated properties and those generated by the aforementioned state-of-the-art LLMs. We evaluate LLM performance through four unique perspectives: semantic alignment and deviation with ORKG properties, fine-grained properties mapping accuracy, SciNCL embeddings-based cosine similarity, and expert surveys comparing manual annotations with LLM outputs. These evaluations occur within a multidisciplinary science setting. Overall, LLMs show potential as recommendation systems for structuring science, but further finetuning is recommended to improve their alignment with scientific tasks and mimicry of human expertise.

(1) Background: Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters with beneficial effects including sedative property. However, despite various clinical trials, scientific evidence regarding the impact of orally ingested GABA, whether natural or synthesized through biological pathways, on sleep is not clear.; (2) Methods: The present study work evaluated GABA-A biding affinity of GABALAGEN(GBL), a low-molecular-weight collagen infused with GABA, through receptor binding assays. The sedative effects of GBL were investigated through electroencephalography (EEG) analysis in the electro foot shock (EFS) stress-induced sleep animal model and then we examined the expression orexin, GABAA receptor in the brain region using immunohistochemistry.; (3) Results: We found that on the binding assay, GBL displayed high affinity to GABAA receptor (IC50 value, 31.5µg/mL)). Also, after treatment of GBL, percent of total time of REM and NREM were significantly and dose-dependently increased compared to the Con group. Consistent with behavioral results, the GBL-treated groups showed that the expression of GABAA receptor immune-positive cells in the VLPO were markedly and dose-dependently increased compared to the Con group. Also, the GBL-treated groups showed that the expression of orexin immune-reactive cells in the LH were significantly decreased compared to the Con group.; (4) Conclusions: In conclusion, GBL showed efficacy and potential to be used as an anti-stress therapy to treat sleep deprivation through antagonism of GABA receptors and consequent inhibition of orexin activity.

Malaria and Typhoid fever are prevalent diseases in tropical regions, exacerbated by unclear protocols, drug resistance, and environmental factors. Prompt and accurate diagnosis is crucial to improve accessibility and reduce mortality rates. Traditional diagnosis methods cannot effectively capture the complexities of these diseases due to the presence of confusable symptoms. Although machine learning (ML) models offer accurate predictions, they operate as "black boxes" with non-interpretable decision-making processes, making it challenging for healthcare providers to comprehend how the conclusions are reached. This study employs explainable AI (XAI) models such as Local Interpretable Model-agnostic Explanations (LIME), and Large Language Models (LLMs) like ChatGPT, Gemini, and Perplexity, to clarify diagnostic results for healthcare workers, building trust and transparency in medical diagnostics. The models were implemented on Google Colab and Visual Studio Code because of their rich libraries and extensions. Results showed that the Random Forest model outperformed Extreme Gradient Boost and Support Vector Machines and important features for predicting Malaria and Typhoid were identified with the LIME plots. Among LLMs, ChatGPT 3.5 demonstrates a comparative advantage over Gemini and Perplexity, hence highlighting how crucial it is to use a hybrid strategy that combines ML, XAI, and LLMs to improve diagnostic performance and reliability in healthcare applications. The study recommends implementing the integrated ML, LIME, and LLM processes because it streamlines the development and maintenance process's workflow overall, makes use of resources more effectively, and improves explainability by allowing the LLM to consider the complete context that LIME provides.

A model for cell proliferation in developmental fields is derived from information theory using a few biological postulates. The model provides an explanation for the success of the Gompertz equation in describing the growth of embryonic, neoplastic, and regenerative systems. Although this equation has been applied to many growth phenomena, its use has been entirely empirical. A theoretical justification for the use of the Gompertz equation in characterizing developmental processes is presented. The model also accounts for a reported relationship among the parameters of the Gompertz equation. A method for quantification and comparison of the determination of developmental fields at different levels of organization is suggested.

Kondo and collaborators recently reported the absence of Hox temporal collinearity in Xenopus tropicalis. They found none in the initiation of accumulation of Hox transcripts (detected via RNA seq). And none in the initial expression sequence of primary unprorocessed transcripts (Identified by using qRT-PCR against introns or intron-exon boundaries). Nor in the initial acquisition by Hox gene DNA of a mark for active chromatin. These findings are in conflict with the idea that temporal collinearity has to do with the initiation of Hox gene transcription or with the opening of and a progression from repressed to active states in Hox chromatin. But collinear acquisition of the same active chromatin mark has been shown by others in murine 5’ Hoxd cluster genes.The reason for this difference is unknown . This careful study thus indicated that the initiation phase of Hox expression shows no temporal collinearity in X. tropicalis. A previous study in X. laevis from the same group also showed that the sequence of times for reaching (normalised) half maximal Hox expression showed no temporal collinearity. These conclusions are likely to be correct. These authors do however also conclude that “experimental evidence for the temporal collinearity hypothesis is not strong” There is however strong evidence that Hox temporal collinearity does occur in early vertebrate embryos. Below. I present and discuss 3 lines of evidence to resolve the present conflict I argue that Hox temporal collinearity actually does exist and that it is part of a central mechanism in early development.