bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDAC2 in Primary Sensory Neurons Constitutively Restrains Chronic Pain by Repressing α2δ-1 Expression and Associated NMDA Receptor Activity
Authors: Zhang Jixiang , Chen Shao-Rui , Zhou Meng-Hua , Jin Daozhong , Chen Hong , Wang Li , DePinho Ronald A. , Pan Hui-Lin 
Published: October 2022

α2δ-1 (encoded by theCacna2d1gene) is a newly discovered NMDA receptor-interacting protein and is the therapeutic target of gabapentinoids (e.g., gabapentin and pregabalin) frequently used for treating patients with neuropathic pain. Nerve injury causes sustained α2δ-1 upregulation in the dorsal root ganglion (DRG), which promotes NMDA receptor synaptic trafficking and activation in the spinal dorsal horn, a hallmark of chronic neuropathic pain. However, little is known about how nerve injury initiates and maintains the high expression level of α2δ-1 to sustain chronic pain. Here, we show that nerve injury caused histone hyperacetylation and diminished enrichment of histone deacetylase-2 (HDAC2), but not HDAC3, at theCacna2d1promoter in the DRG. Strikingly,Hdac2knockdown or conditional knockout in DRG neurons in male and female mice consistently induced long-lasting mechanical pain hypersensitivity, which was readily reversed by blocking NMDA receptors, inhibiting α2δ-1 with gabapentin or disrupting the α2δ-1–NMDA receptor interaction at the spinal cord level.Hdac2deletion in DRG neurons increased histone acetylation levels at theCacna2d1promoter, upregulated α2δ-1 in the DRG, and potentiated α2δ-1–dependent NMDA receptor activity at primary afferent central terminals in the spinal dorsal horn. Correspondingly,Hdac2knockdown-induced pain hypersensitivity was blunted inCacna2d1knockout mice. Thus, our findings reveal that HDAC2 functions as a pivotal transcriptional repressor of neuropathic pain via constitutively suppressing α2δ-1 expression and ensuing presynaptic NMDA receptor activity in the spinal cord. HDAC2 enrichment levels at theCacna2d1promoter in DRG neurons constitute a unique epigenetic mechanism that governs acute-to-chronic pain transition.SIGNIFICANCE STATEMENTExcess α2δ-1 proteins produced after nerve injury directly interact with glutamate NMDA receptors to potentiate synaptic NMDA receptor activity in the spinal cord, a prominent mechanism of nerve pain. Because α2δ-1 upregulation after nerve injury is long lasting, gabapentinoids relieve pain symptoms only temporarily. Our study demonstrates for the first time the unexpected role of intrinsic HDAC2 activity at the α2δ-1 gene promoter in limiting α2δ-1 gene transcription, NMDA receptor-dependent synaptic plasticity, and chronic pain development after nerve injury. These findings challenge the prevailing view about the role of general HDAC activity in promoting chronic pain. Restoring the repressive HDAC2 function and/or reducing histone acetylation at the α2δ-1 gene promoter in primary sensory neurons could lead to long-lasting relief of nerve pain.
Maladaptive Laterality in Cortical Networks Related to Social Communication in Autism Spectrum Disorder
Authors: Persichetti Andrew S. , Shao Jiayu , Gotts Stephen J. , Martin Alex 
Published: October 2022

Neuroimaging studies of individuals with autism spectrum disorders (ASDs) consistently find an aberrant pattern of reduced laterality in brain networks that support functions related to social communication and language. However, it is unclear how the underlying functional organization of these brain networks is altered in ASD individuals. We tested four models of reduced laterality in a social communication network in 70 ASD individuals (14 females) and a control group of the same number of tightly matched typically developing (TD) individuals (19 females) using high-quality resting-state fMRI data and a method of measuring patterns of functional laterality across the brain. We found that a functionally defined social communication network exhibited the typical pattern of left laterality in both groups, whereas there was a significant increase in within- relative to across-hemisphere connectivity of homotopic regions in the right hemisphere in ASD individuals. Furthermore, greater within- relative to across-hemisphere connectivity in the left hemisphere was positively correlated with a measure of verbal ability in both groups, whereas greater within- relative to across-hemisphere connectivity in the right hemisphere in ASD, but not TD, individuals was negatively correlated with the same verbal measure. Crucially, these differences in patterns of laterality were not found in two other functional networks and were specifically correlated to a measure of verbal ability but not metrics of other core components of the ASD phenotype. These results suggest that previous reports of reduced laterality in social communication regions in ASD is because of the two hemispheres functioning more independently than seen in TD individuals, with the atypical right-hemisphere network component being maladaptive.SIGNIFICANCE STATEMENTA consistent neuroimaging finding in individuals with ASD is an aberrant pattern of reduced laterality of the brain networks that support functions related to social communication and language. We tested four models of reduced laterality in a social communication network in ASD individuals and a TD control group using high-quality resting-state fMRI data. Our results suggest that reduced laterality of social communication regions in ASD may be because of the two hemispheres functioning more independently than seen in TD individuals, with atypically greater within- than across-hemisphere connectivity in the right hemisphere being maladaptive.
Status of a Child Born as a Result of IVF Procedure
Authors: Bączyk-Rozwadowska Kinga 
Published: October 2022

Abstract
Due to the constant development of medicine and biotechnology, including the in vitro procedure, more and more infertile couples can fulfil their desire to have a child. Traditional rules of family law concerning the determination of status familiae of such children have then turned out to be insufficient. The situation is even more complicated when IVF procedure assumes the use of donated genetic material or the involvement of a surrogate mother. Therefore in the field of family law the intention to “create” a child starts to play quite an important role. Family law is then undergoing far-reaching transformations, especially in those countries where same-sex couples are eligible to start IVF procedures (Great Britain, USA, Germany, Austria).
Limits of Parental Interference in a Child’s Personal Rights – Selected Issues
Authors: Michałowska Kinga 
Published: October 2022

Abstract
The article discusses the issues of the limits of parental interference in children’s personal rights. The conducted research covers the subject broadly. It starts with the general issues of legal capacity as the basis for the protection of subjective rights and then proceeds to demonstrating the lack of limitations in the protection of a child’s personal rights. A child growing up in a family remains under parental authority, which gives rise to certain obligations and rights of parents towards the child. Parents look after, educate and guide the child, carrying out their duties in the best interests of the child and guided by their good. It happens, however, that by caring for children, parents violate their personal rights. Therefore, the determinants of exercising parental authority were examined. Particular attention was paid to the scope of rights resulting from parental authority, the assessment of the manner of exercising it, the right of the child to express his or her own position and the principle of the best interests of the child. These determinants made it possible to indicate the limit of parental interference in the child’s personal rights. The practical side of the implementation of the right to the protection of a child’s personal rights was also indicated, as well as a proposal to amend the content of the family and guardianship code.
Private Autonomy and Family Public Policy in Italy
Authors: Buccianti Giovanni Liberati 
Published: October 2022

Abstract
The article deals with the general clause of public policy in Italian family law. It analyses the recent case-law application of both international and internal public policy in the Italian legal system. Nowadays, public policy is used for protecting and developing the fundamental rights of individuals in the EU space. However, the content of this general clause is debated, and there are several theses (e.g. constitutional, discretionary, globalized public policy). Adhering to one concept rather than another has different consequences. Think, for example, of the recognition of double paternity acquired abroad through a surrogacy contract. Moreover, family public policy can be viewed both as public policy of the family (a general clause that protects the family rather than its members) and public policy in the family (a general clause that protects the fundamental rights of the individuals rather than the family). Subsequently, the article analyses prenuptial and postnuptial agreements in Italy. Italian jurisprudence considers both agreements invalid because they are in contradiction to public policy. The article suggests that families can use the contractual instrument. However, personal and patrimonial clauses in domestic family agreements need to be compatible both with the public policy of the family and public policy in the family. Ultimately, public policy becomes a tool attributed to ordinary judges for guaranteeing widespread constitutional legality.
Identification of factors affecting outcomes in patients with Guillain Barre syndrome
Authors: Bhatia Vaidehi Dipesh , Khant Poonam Batuk , Vyshnavee Inguva , Shiyaf Mohammed , Thunga Girish , Gorthi Sankar Prasad , Kunhikatta Vijayanarayana 
Published: October 2022

Background. Guillain Barre syndrome (GBS) is a rare autoimmune neurological disorder resulting in variable clinical course and outcome. Various factors such as age, symptoms and disease form that influence the outcome of GBS have been previously studied.
Aim. This study aimed at identifying factors affecting the outcomes in patients with GBS.
Methods. A retrospective observational study was conducted on GBS (ICD-G61.0) patients admitted to the hospital between 2014 and 2019. Patient information on demographics, medical and medication history, laboratory parameters, electrophysiological data, type of GBS and therapy received were retrieved from medical records. Univariate and multivariate analysis were conducted to identify factors associated with outcome (improved and not improved) and calculate odds ratio (OR).
Results. A total of 212 GBS patients were included in the study, of which 67% were males and the mean age was 39.9±20.1 years. 168 (79%) patients showed improvement whereas the remaining 44(21%) did not show improvement. Patients with hypertension (OR=4.512; CI=1.309-15.556, p=0.017), alcoholics (OR=5.148; CI=1.234-21.472, p=0.025), sepsis (OR= 9.139; CI=1.102-75.760, p=0.040) and cardiac arrest (OR=17.495; CI=1.249-245.027, p=0.034) were associated with risk of no improvement. Whereas those treated with IVIgG plus Physiotherapy/Occupational therapy (OR=0.062; CI=0.016-0.242, p=0.001) and Plasmapheresis plus Physiotherapy/Occupational therapy (OR=0.007; CI=0.000- 0.147, p=0.001) were associated with improvement.
Conclusion. Understanding these factors help to further give a more directed and focused management to improve the condition in patients who are at risk of poor outcome. Further follow-up studies could be done to determine and manage the residual disabilities associated with GBS to improve patient’s quality of life.
Proton pump inhibitors use and risk of inflammatory bowel diseases: a meta-analysis of observational studies
Authors: Shastri Sanjana Aditya , Kantamneni Raveena , Rashid Muhammed , Chandran Viji Pulikkel , Suhita Ramadugula , Begum Izwath , Nair Sreedharan , Thunga Girish 
Published: October 2022

Background and objective. Proton Pump Inhibitors (PPIs) reduce gastric acid production and they are indicated for myriad gastrointestinal conditions. Prolonged use of PPI has been linked to the risk of inflammatory bowel disease (IBD) though this fact is not well established. We aimed to conduct a systematic review and meta-analysis to estimate the risk of IBD occurrence with PPI use.
Methodology. The databases such as PubMed, Scopus, and Cochrane Library were accessed from inception to December 2020. Additionally, the bibliographic search and a random search in Google, Google Scholar, and ResearchGate were performed to find additional sources. The observational studies estimating the risk of IBD following the use of PPI, published in the English language were considered for this review. The methodological quality of included studies was assessed using the Modified Downs and Black checklist.
Results. Eight out of 2038 studies with 157,758 participants were included in this meta-analysis. A significantly higher risk of IBD (adjusted odds ratio [aOR] 2.43; 95% Confidence Interval [CI] 1.18-5.02; P=0.02; n=6) was observed in participants taking PPIs for any indication. Moreover, a significant association was observed between PPI exposure on the different types of IBD such as ulcerative colitis and Crohn’s disease together (aOR: 3.60; 95% CI: 1.10-11.74), collagenous colitis (OR: 4.73; 95% CI: 1.99-11.22) and lymphocytic Colitis (OR: 3.77; 95% CI: 2.91- 4.87), but not with ulcerative colitis (P=0.47) and microscopic colitis (P=0.07) alone. Similarly, a significant association was observed among Europeans (aOR: 3.98; 95% CI: 2.36-6.71), but not with North American (aOR: 0.48; 95% CI: 0.01- 26.71) studies. Overall the study quality was good.
Conclusion. The current evidence indicates that exposure to PPI is significantly associated with increased risk of IBD. Further, adequately powered studies from various parts of the world are needed for better quantification and generalizability of our findings.
PROSPERO Protocol Registration Number: CRD42020209674
Koncepcióváltás a belvízgazdálkodásban: talajtani és vízminőségi kérdések
Authors: Pálffy Benjámin , Fekete István , Barta Károly 
Published: October 2022

Munkánk során igyekeztünk a belvízminőséggel, annak időbeli változásaival kapcsolatos kérdéseket megválaszolni.Az eddig vizsgált nehéz agyag talajtextúrájú algyői mintaterületről származó eredmények rávilágítanak arra, hogy tápanyagok tekintetében számottevő terhelés érheti az elvezetés során a belvizet befogadó felszíni víztestet különösen a belvízelöntés kezdeti időszakában. A terhelést kiemelten a lebegőanyaghoz kötött tápanyagformák adják, míg emellett a felszíni vízborítás kialakulását követő első napokban és hetekben jelentős, környezetvédelmi határértéket is átlépő mineralizált nitrogéntartalomra is kell számítani.A belvizes környezet reduktív jellemzőinek erősödésével a nitrát – külső utánpótlás nélkül – hamar átalakul, míg a hőmérséklet és a biológiai aktivitás emelkedésével a lebegőanyagtartalom koagulációja és flokkulációja is jelentősen csökkenti a tápanyagterhelést.Ezen a mintaterületen képződött belvíz öntözővízként való hasznosítását az öntözőrendszer eltömődéséhez vezető magas lebegőanyagtartalom, illetve esetenként magas vas- és mangántartalom nehezítheti jellemzően szintén a tavaszi időszakban, amikor pl. kelesztő öntözéshez használhatjuk fel a vizet a magasabb térszíneken.Általános érvényű következtetések levonásához a kutatás későbbi szakaszában két új, eltérő talajtani és hidrológiai adottságú mintaterületre is kiterjesztjük vizsgálatunkat. A helyszíni mérésekkel párhuzamosan összeállítunk egy laboratóriumi kísérletet kiemelten a talajtényező hatásának megfigyeléséhez. Ez lehetőséget fog nyújtani arra is, hogy a tápanyagformák időbeli átalakulásáról is pontosabb képet kapjunk.
Generative Methods for Guard and Camera Placement in Stealth Games
Authors: Xu Qihan , Tremblay Jonathan , Verbrugge Clark 
Published: October 2022

Enemy observers, such as cameras and guards, are common elements that provide challenge to many stealth and combat games. Defining the exact placement and movement of such entities, however, is a non-trivial process, requiring a designer balance level-difficulty, coverage, and representation of realistic behaviours. In this work we explore systems for procedurally generating both camera and guard placement in a stealth game context. For the former we use an approach based on weakening theoretical results for optimal camera placement, while for the latter we perform automatic roadmap construction, generating more specific patrol behaviours through a grammar-based technique. We evaluate both approaches with a non-trivial implementation in Unity3D, and apply quantitative metrics to demonstrate how different parametrizations can be used to control level difficulty without sacrificing believability.
Intelligent Content Generation via Abstraction, Evolution and Reinforcement
Authors: LeBaron Dean , Mitchell Logan , Ventura Dan 
Published: October 2022

We present a system for autonomously generating puzzles in the form of a 2D, tile-based world. Puzzle design is entirely dependent on tile characteristics, which are implemented as abstract classes that can be modified by the system. Thus, the system controls not only the base-level puzzle design but also (to some extent) the meta-level component design. The result is a rich space of possible puzzles that the system explores with a combination of evolutionary computation and Q-learning. The system autonomously produces a variety of puzzles of varying difficulty to create a game called Loki's Castle. The system is almost completely autonomous, requiring only a minimal description of what a puzzle should include, and the abstraction allows extensibility so that future versions can invent entirely new classes of tiles. Several puzzle examples are presented to demonstrate the system's capability.
Implementing Injunctive Social Norms Using Defeasible Reasoning
Authors: Blass Joseph , Horswill Ian 
Published: October 2022

Believability requires video game characters to consider their actions within the context of social norms. Social norms involve a broad range of behavioral defaults, obligations, and injunctions unrelated to strictly causal reasoning. Defeasible reasoning involves rationally compelling but deductively invalid arguments, such as reasoning with rules that allow exceptions. This paper investigates having video game characters use defeasible reasoning to consider injunctive social norms when selecting and planning actions.
Toward an Automated Measure of Narrative Complexity
Authors: Harmon Sarah , Jhala Arnav 
Published: October 2022

For young children, adults learning English, or individuals with language disorders, complex narratives are difficult to create and understand. While narratives can easily be assessed in terms of their lexical and syntactic difficulty, automatically measuring the level of narrative complexity is a challenging problem. We present and evaluate a preliminary system for assessing narrative complexity, which should help identify suitable texts for readers and assist in narrative skill evaluation.
Building Helpful Virtual Agents Using Plan Recognition and Planning
Authors: Geib Christopher , Weerasinghe Janith , Matskevich Sergey , Kantharaju Pavan , Craenen Bart , Petrick Ronald 
Published: October 2022

This paper presents a new model of cooperative behavior based on the interaction of plan recognition and automated planning. Based on observations of the actions of an "initiator" agent, a "supporter" agent uses plan recognition to hypothesize the plans and goals of the initiator. The supporter agent then proposes and plans for a set of subgoals it will achieve to help the initiator. The approach is demonstrated in an open-source, virtual robot platform.
Dear Leader’s Happy Story Time: A Party Game Based on Automated Story Generation
Authors: Horswill Ian 
Published: October 2022

Players in Dear Leader’s Happy Story Time are placed in the role of contestants in a reality TV show where they are forced to audition for roles in the upcoming film of the host, a deranged billionaire who has inexplicably been elected president. The stories are produced by a story generator that combines stock plots and characters to produce kitsch story outlines. The players then collaborate to improvise a camp performance of the outline. The game design provides a context for experimenting with automatic story generation within a narrative game, as well as an opportunity for experimenting with knowledge representation schemes for expressing the tropes of popular narrative. The story generator uses a higher-order logic for describing tropes, and an HTN planning algorithm based on Nau et al.’s SHOP.
A Declarative PCG Tool for Casual Users
Authors: Horswill Ian 
Published: October 2022

Declarative programming allows designers to create procedural content generators by providing descriptions of desired artifacts rather than bespoke algorithms to generate them. Unfortunately, these systems are notoriously inaccessible, requiring considerable sophistication with formal systems, and detailed understanding of the impact of equivalent formalizations on the system performance. Imaginarium is a declarative PCG system for tabletop role playing games (TTRPGs). Following Compton’s work on casual creators, it trades expressiveness for accessibility. As with Nelson’s Inform 7, its source language is a highly structured subset of English. A single sentence, such as children are parented by at least one adult can be used to simultaneously introduce the predicates child, adult, and parent, along with a cardinality constraint over the parent relation. We describe the system, its knowledge representation language, and the issues in their design. Together, they allow users with minimal STEM background to engage in playful experimentation.
Emotionally Driven Natural Language Generation for Personality Rich Characters in Interactive Games
Authors: Strong Christina , Mehta Manish , Mishra Kinshuk , Jones Alistair , Ram Ashwin 
Published: October 2022

Natural Language Generation for personality rich characters represents one of the important directions for believable agents research. The typical approach to interactive NLG is to hand-author textual responses to different situations. In this paper we address NLG for interactive games. Specifically, we present a novel template-based system that provides two distinct advantages over existing systems. First, our system not only works for dialogue, but enables a character's personality and emotional state to influence the feel of the utterance. Second, our templates are resuable across characters, thus decreasing the burden on the game author. We briefly describe our system and present results of a preliminary evaluation study.
Murder in the Arboretum: Comparing Character Models to Personality Models
Authors: Walker Marilyn , Lin Grace , Sawyer Jennifer , Grant Ricky , Buell Michael , Wardrip-Fruin Noah 
Published: October 2022

Interactive Narrative often involves dialogue with virtual dramatic characters. In this paper we compare two kinds of models of character style: one based on models derived from the Big Five theory personality, and the other derived from a corpus-based method applied to characters and films from the IMSDb archive. We apply these models to character utterances for a pilot narrative-based outdoor augmented reality game called Murder in the Arboretum. We use an objective quantitative metric to estimate the quality of a character model, with the aim of predicting model quality without perceptual experiments. We show that corpus-based character models derived from individual characters are often more detailed and specific than personality based models, but that there is a strong correlation between personality judgments of original character dialogue and personality judgments of utterances generated for Murder in the Arboretum that use the derived character models.