Prominent Component Research Articles

Flow of the Game: A Hidden Markov Model of Player Engagement in Online Mobile Games

Practice- and Policy-Oriented Abstract Mobile gaming is a prominent component of the entertainment industry, yet high attrition rates and low engagement are notorious problems faced by most mobile game publishers. This paper investigates the effects of in-game challenge-related factors and reward ads on player engagement in mobile games. Using a Hidden Markov Model, we analyze how perceived challenge, fluctuation of perceived challenge, and reward ads impact players’ engagement states. Our findings indicate that whereas moderate levels of perceived challenge enhance engagement, excessive challenge level has diminishing returns. Furthermore, fluctuations in perceived challenge help sustain engagement by providing a balance between stimulation and cognitive restoration. Third, reward ads provide access to scaffolds, offering temporary support that helps players move to a higher engagement state, especially during challenging phases of the game. For game developers, incorporating dynamic challenge adjustments can improve player experience and keep players engaged. Additionally, reward ads offer a strategic opportunity for game publishers to monetize their games while maintaining engagement, with a stronger impact when players perceive a higher level of challenge. These insights provide valuable practices for designing mobile games that effectively balance user engagement and monetization strategies, ensuring sustained growth in a competitive landscape.

Metabolic pathways, pharmacokinetic, and brain neurochemicals effects of capsaicin: Comprehensively insights from in vivo studies

BackgroundCapsaicin (CAP), a prominent component of chili pepper known for its potent agonistic effects on TRPV1, has attracted significant attention for its diverse physiological effects. Nevertheless, there remains a paucity of data concerning its in vivo distribution, metabolism, pharmacodynamic properties, and influence on the metabolic profile of the brain. MethodsStable isotope tracing, in vitro enzyme incubation, microdialysis coupled with UHPLC-MS/MS techniques were employed to investigate the in vivo metabolic pathways, distribution, and pharmacokinetic properties of CAP, and the potential biases in metabolic pathways was elucidate through molecular docking. Furthermore, the effect of CAP on brain metabolic profiles was assessed using untargeted metabolomics, and spatial visualization analysis was conducted through mass spectrometry imaging. ResultsCAP was distributed predominantly in the kidneys, with lower content in the liver, heart, lungs, brain, and spleen following peripheral administration, and the absorption half-life in the body was about 20 minutes. CAP primarily underwent alkyl terminal dehydrogenation, hydroxylation, and macrocyclization metabolic pathways under the action of CYP2C9, CYP2C19 and CYP2D6, resulting in at least four metabolites. Among them, the hydroxylation products were main metabolites and the dehydrogenation product 16,17-dihydrocapsaicin could interact with the key binding sites Leu515 and Thr550 of TRPV1 like CAP. CAP quickly diffused to various brain regions and the metabolic characteristics in the striatum were relatively different from that in the blood. The distribution of CAP in the brain primarily triggered the release of neurotransmitters in areas associated with reward, cognition, and memory. Both acute and chronic exposure to CAP elevated amino acid levels in cortical regions, while producing contrasting effects on nucleotide metabolites. ConclusionThis study offers an initial in-depth analysis of the distribution patterns, metabolic pathways and pharmacodynamic properties of CAP in the body and brain. These findings established a basis for further studies on CAP's pharmacology properties and its influence on the central nervous system.

Short wavelength infrared (SWIR) spectral and geochemical characteristics of white micas in the Xiaonangou gold deposit, East Qinling: As a hyperspectral tool in exploration

The Xiaoqinling-Xiong’ershan region, a prominent component of the East Qinling Belt, is renowned worldwide for its molybdenum and gold ore fields. Moreover, with gold reserves of at least 1300 tons, it is also China’s major gold mining province, second only to Jiaodong. Seated in eastern center of the Xiong’ershan area, the Xiaonangou gold deposit has an estimated gold reserve of over 60 tons and is characterized by disseminated gold in altered rocks. Based on detailed petrographic investigation, coupled with an analysis of crosscutting relationships, there are three stages of hydrothermal alteration and mineralization: pre-ore K-feldspar + quartz (stage Ⅰ), ore quartz + ankerite + disseminated pyrite + polymetallic sulfide (stage Ⅱ), and post-ore quartz + carbonate (stage Ⅲ). As revealed by a systematic analysis of short wavelength infrared (SWIR) spectroscopy, four main types of alteration minerals exist, including white micas, clay minerals, chlorite, and carbonate minerals. In the ore body, white micas mainly developed in stage Ⅱ, and slightly occurred in stage Ⅰ. The clay minerals and chlorite usually developed in the banded alteration zones outside the orebody. Most of the carbonate minerals, including calcite and dolomite, mainly developed in stage Ⅲ, but the ankerite was associated with disseminated pyrite, quartz and polymetallic sulfides in stage Ⅱ. Of these, white micas were recognized as the most abundant hydrothermal alteration minerals, which were observed to be widely distributed within alteration zones in the Xiaonangou gold deposit. The SWIR parameters and its spatial variation of white mica indicate that the Al-OH absorption positions (Pos2200) exhibit a drifting tendency towards longer (>2205 nm) wavelengths in the ore body vicinity. Additionally, there is a discernible increase in illite crystallinity (IC values) in the same region. The temperature, redox, and pH conditions for associated fluids can be reflected through characterization of these parameters. Furthermore, it demonstrates that the ore-proximal zones are situated in a relatively oxidized, alkaline, and high-temperature environment in the Xiaonangou gold deposit. According to the electron probe microanalysis (EPMA) results, two distinct end members exist in white mica: a Si-poor, Al-rich muscovite and an Al-poor, Si-, Fe-, and Mg-rich phengite. The Si, ivAl, viAl, Mg, Fe, and Ti elements exhibit a linear correlation with the wavelength of Pos2200, demonstrating that the shift in wavelength of white mica is predominantly controlled by Tschermak substitution (ivSivi(Mg，Fe) ↔ivAlviAl). The application of spatial variation in the SWIR spectral parameters along with geochemical properties of white mica facilitates the effective guidance of mineral exploration. In comparison to other deposits, it can be concluded that the longer (>2205 nm) wavelength of the Pos2200 along with the higher IC values (>1.4) of white mica are applicable as valid vectors towards gold mineralization in the Xiaonangou gold deposit.

Abstract C031: Targeting colorectal cancer-associated fibroblasts with all-trans retinoic acid to reprogram the tumor microenvironment

Abstract Cancer-associated fibroblasts (CAFs) are a prominent component of the tumor microenvironment (TME) and are known for their role in supporting tumor growth and progression through interactions with cancer cells and other stromal elements. Liver metastatic CAFs (lmCAFs), in particular, play an important role in establishing the secondary niche that facilitates tumor metastasis. Reprogramming the stroma, particularly targeting the pro-tumorigenic functions of lmCAFs, has emerged as a promising therapeutic intervention to disrupt the supportive environment tumors rely on for progression. An initial drug screen of FDA-approved oncology therapies was conducted on patient-derived colorectal cancer (CRC) CAFs and tumor organoids (PDTOs) to identify compounds that may be re-purposed as stroma targeting agents. All-trans retinoic acid (ATRA) was shown to specifically inhibit the proliferation of CAFs without affecting CRC-PDTOs. ATRA is an active metabolite of Vitamin A that exerts its canonical biological effects by binding to nuclear retinoic acid receptors (RAR). The differential RAR expression in multiple CAFs and PDTOs was confirmed with bulk RNA sequencing, with higher expression found in the CAF lines. Subsequent analysis included the qPCR assessment of glycolysis enzyme levels, CAF activation markers, and ATRA signaling in lmCAFs following treatment with ATRA for 5 days. Protein expression of key components of the TGF-b signaling pathway, including SMAD 2/3, Akt, and b-catenin, were also analyzed. Treatment of lmCAFs with ATRA induced expression of RARb and ALDH1A1, biomarkers associated with ATRA signaling pathways. In one patient-derived CAF line, ATRA treatment exhibited a decrease in CAF activation markers (e.g. aSMA) and glycolytic enzymes (e.g. lactate dehydrogenase). On the other hand, another CAF line showed increased fibroblast activation and a shift away from metabolic dependency on glycolysis upon ATRA treatment. Additionally, ATRA targeted TGF-b signaling through the pSMAD 2/3 and Akt pathways, highlighting the multifaceted impact on CAF function and heterogeneity. ATRA effectively reprograms some CAFs by inhibiting their proliferation and altering key signaling pathways, thereby disrupting the pro-tumorigenic environment of the TME. The results of this study suggest that ATRA holds potential as a therapeutic strategy to target and reprogram the CAFs within the permissive stromal components essential for tumor progression. Citation Format: Brandon Choi, Yuyuan Zhou, Seungil Kim, Shannon M. Mumenthaler. Targeting colorectal cancer-associated fibroblasts with all-trans retinoic acid to reprogram the tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C031.

Evidence that CRISPR-Cas9 Y537S-mutant expressing breast cancer cells activate Yes-associated protein 1 to driving the conversion of normal fibroblasts into cancer-associated fibroblasts

BackgroundEndocrine therapy (ET) has improved the clinical outcomes of Estrogen receptor alpha-positive (ERɑ +) breast cancer (BC) patients, even though resistance to ET remains a clinical issue. Mutations in the hormone-binding domain of ERɑ represent an acquired intrinsic mechanism of ET resistance. However, the latter also depends on the multiple functional interactions between BC cells and the tumor microenvironment (TME). Here, we investigated how the most common Y537S-ERɑ mutation may influence the behavior of fibroblasts, the most prominent component of the TME.MethodsWe conducted coculture experiments with normal human foreskin fibroblasts BJ1-hTERT (NFs), cancer-associated fibroblasts (CAFs), isolated from human BC specimens, and Y537S CRISPR-expressing MCF-7 BC cells (MCF-7YS). Mass spectrometry (MS) and Metacore analyses were performed to investigate how the functional interactions between BC cells/fibroblasts may affect their proteomic profile. The impact of fibroblasts on BC tumor growth and metastatic potential was evaluated in nude mice.ResultsMutant BC conditioned medium (CM) affected the morphology/proliferation/migration of both NFs and CAFs. 198 deregulated proteins signed the proteomic similarity profile of NFs exposed to the YS-CM and CAFs. Among the upregulated proteins, Yes-associated protein 1 (YAP1) was the main central hub in the direct interaction network. Increased YAP1 protein expression and activity were confirmed in NFs treated with MCF-7YS-CM. However, YAP1 activation appears to crosstalk with the insulin growth factor-1 receptor (IGF-1R). Higher amount of IGF-1 were noticed in the MCF-7YS-CM cells compared to the MCF-7P, and IGF-1 immunodepletion reversed the enhanced YAP1 expression and activity. Mutant cells upon exposure to the NF- and CAF-CM exhibited an enhanced proliferation/growth/migration/invasion compared to the MCF-7P. MCF-7YS cells when implanted with CAFs showed an early relative increased tumor volume compared to YS alone. No changes were observed when MCF-7P cells were co-implanted with CAFs. Compared with that in MCF-7P cells, the metastatic burden of MCF-7YS cells was intrinsically greater, and this effect was augmented upon treatment with NF-CM and further increased with CAF-CM.ConclusionsYS mutant BC cells induced the conversion of fibroblasts into CAFs, via YAP, which represent a potential therapeutic target which interrupt the functional interactions between mutant cells/TME and to be implemented in the novel therapeutic strategy of a subset of metastatic BC patients carrying the frequent Y537S mutations.

NGC 7314: X-Ray Study of the Evolving Accretion Properties

We present a comprehensive analysis of the timing and spectral properties of NGC 7314, a Seyfert 1.9 galaxy, using X-ray observations from XMM-Newton, NuSTAR, and RXTE/proportional counter array (PCA). The timing analysis reveals significant variability across different energy bands, with fractional variability values consistent with previous studies. The highly variable soft photons and comparatively less variable high-energy photons imply different origins of these two types. The soft energy photons come from a hot corona near the center, while the high-energy photons are produced by inverse Compton scattering of these primary X-ray photons in a hot plasma away from the central region. The spectral analysis employs various models to characterize the emission components. The results indicate the presence of a soft energy bump, Fe Kα line emission, and a prominent reflection component. The long-term RXTE/PCA data analysis reveals temporal variations in the photon index (Γ) and power-law flux, suggesting evolving emission properties over time. The signature of both broad and narrow Fe Kα emission line features suggested the broad, variable one coming from the accretion disk (∼10−5 pc), while the nonevolving narrow line cannot be well constrained. The absorption feature could originate in a highly ionized region, possibly closer to the broad-line region. The evolution of the inner accretion properties indicates that NGC 7314 could be a potential changing-state active galactic nucleus.

Vertical distribution of intracellular protoporphyrin IX in coastal sediment cores: Implications for sedimentology and microbial community composition

Protoporphyrin IX (PPIX), a basic porphyrin system found in nature, all “porphyrin-type” tetrapyrroles with a biological function are biosynthetically derived thereof. PPIX is a metalloprosthetic group of numerous proteins involved in diverse metabolic and respiratory processes across all domains of life, and is thus considered essential for respiring organisms. Determining the biotic and abiotic factors that influence marine microbial growth and community structure is critical for understanding global biogeochemical cycles. Here, we present vertical profiles of intracellular PPIX and four derivative products (Chlorophyll-a/b and Pheophytin-a/b) from two coastal sediment cores, alongside ancillary geochemical and 16S rRNA microbial community data. Our findings indicated that PPIX is present in the natural sediment environment and displays a decreasing trend with depth, revealing a significant positive correlation with both organic matter and microbial abundance. Co-occurrence networks revealed that the environmental distribution of PPIX was positively correlated with the microbial porphyrin producer (high genetic completeness), but negatively correlated with auxotrophs (absence or low genetic completeness). It emphasized the critical role of PPIX as a biological molecule involved in key physiological processes. These results suggest that PPIX is a prominent component of the shared extracellular metabolite pool, especially in anoxic marine sediments where it exists at physiologically relevant concentrations for microbial metabolism. This study highlighted the significance of PPIX in microbial ecology and its potential impact on biogeochemical cycles in marine sedimentary environments.

Chemical Synthesis and Enzymatic Modification of Mangostins: A Comprehensive Review on Structural Modifications for Drug Discover.

Mangosteens, a prominent component of Garcinia mangostana, have been ex-tensively studied for their biological activities and structural modifications. Chemical methods, including cyclization reactions under acidic conditions, have yielded many de-rivatives, which often exhibit enhanced pharmacological properties compared to itself. Enzymatic biotransformation, such as glycosylation and oxidation mediated by fungal species and enzymes like horseradish peroxidase, have provided regioselective pathways to functionalized mangostin derivatives. These studies highlight the versatility of mangos-tin as a scaffold for designing compounds with tailored biological functions. Overall, mangosteen represents a promising platform for developing compounds with enhanced pharmacological activities, paving the way for innovative approaches in biomedicine and pharmaceutical sciences. This review provides a comprehensive examination of the chem-istry of mangosteens, detailing their total synthesis and the derivatives obtained through both chemical and enzymatic methodologies.

C3 glomerulonephritis with genetically confirmed C3 deficiency in a pediatric patient: a case report

Complement component 3 glomerulonephritis (C3GN) is a rare kidney disease characterized by complement dysregulation that results in prominent complement component 3 (C3) deposition in the kidneys. The clinical course of C3GN varies from mild hematuria to progressive chronic kidney disease. In most patients, C3GN is driven by acquired factors, namely, autoantibodies that target C3 or C5 convertases. Genetic variations in complement-related genes are less frequent. We report the case of a 9-yearold Korean boy who presented with microscopic hematuria and a persistently low C3 level and had biopsy findings of C3GN, with the presence of a C3 gene mutation: a frameshift mutation associated with C3 deficiency. However, the patient did not exhibit any other symptoms of complement deficiency. Direct DNA sequencing of his family members revealed the same genetic mutation in his father and older brother. This case report is significant because there are very few such reports worldwide concerning gene mutations related to C3 deficiency to be discovered in patients with C3GN. Explaining C3GN pathogenesis is challenging; therefore, additional research is required in the future.

Discovery of Lacto-N-Biosidases and a Novel N-Acetyllactosaminidase Activity in the CAZy Family GH20: Functional Diversity and Structural Insights.

The glycoside hydrolase family 20 (GH20) predominantly features N-acetylhexosaminidases (EC 3.2.1.52), with only few known lacto-N-biosidases (EC 3.2.1.140; LNBases). LNBases catalyze the degradation of lacto-N-tetraose (LNT), a prominent component of human milk oligosaccharides, thereby supporting a healthy infant gut microbiome development. We investigated GH20 diversity to discover novel enzymes that release disaccharides such as lacto-N-biose (LNB). Our approach combined peptide clustering, sequence analysis, and 3D structure model evaluation to assess active site topologies, focusing on the presence of a subsite -2. Five LNBases were active on pNP-LNB and four showed activity on LNT. One enzyme displayed activity on both pNP-LacNAc and pNP-LNB, establishing the first report of N-acetyllactosaminidase (LacNAcase) activity. Exploration of this enzyme cluster led to the identification of four additional enzymes sharing this dual substrate specificity. Comparing the determined crystal structure of a specific LNBase (TrpyGH20) and the first crystal structure of an enzyme with dual LacNAcase/LNBase activity (TrdeGH20) revealed a highly conserved subsite -1, common to GH20 enzymes, while the -2 subsites varied significantly. TrdeGH20 had a wider subsite -2, accommodating Gal with both β1,4- and β1,3-linkages to the GlcNAc in subsite -1. Biotechnological applications of these enzymes may include structural elucidation of complex carbohydrates and glycoengineering.

Visuality of M. Elizarov’s Novels “Librarian” and “Cartoons” as a Means of Transforming Socialist Realist Canon

This article examines the role of the visual aspect of the text in the recontextualization of elements from the socialist realist canon. The study focuses on Mikhail Elizarov’s novels “Librarian” and “Cartoons.” It is established that, firstly, Elizarov consciously constructs his works according to the principles of literary cinematicity, with visuality serving as a prominent component. Secondly, visuality facilitates the integration of elements from the Soviet project into the narrative, expressed through spaces and objects. Furthermore, it allows for their recontextualization by embedding them within new contexts. Thirdly, the reactivation of spaces and objects is aided by the figure of the protagonist, who is presented through the technique of traveling. Fourthly, the narrative development of the novels bears similarities to socialist realist plots concerning re-education. Additionally, through the image of the protagonist, the relevance of the opposition between “eye” and “gaze” is emphasized, which in turn contributes to the actualization of ideas related to control and behavior modeling. The gaze of the Other, experienced by the characters, draws them into narrative structures akin to those found in socialist realism, compelling them to adopt specific roles — the role of a character burdened with socialist realist motives. Finally, it is noted that the protagonist’s distinctive position enhances reader identification and alters the very status of the Book.

Evaluating the significance of latent tuberculosis infection treatment in high‐incidence countries

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a devastating and rapidly spreading disease. Despite years of scientific research and numerous efforts, it is still a major and resurgent health problem worldwide, with high mortality rates. Added to the concern is that TB persists as a latent infection, an occult face of TB, that becomes a potential reservoir for active tuberculosis. Since latent TB‐infected patients may eventually advance to the active form of TB, an accurate diagnosis and effective treatment of latent tuberculosis are essential for TB control. Latent tuberculosis infection (LTBI) treatment is a prominent component of TB control in low‐prevalence countries like the United States; however, its implication in high‐incidence countries like India is still challenging. Therefore, the present study aimed to evaluate the impact of implementing diagnosis and treatment of LTBI in high‐incidence countries using a mathematical model‐based approach. Through our model, we predicted the incidence rate based on the current treatment regimen in India for the year 2035, which is one of the milestones of WHO for a substantial reduction in TB incidence. We observed demographic variability in the effects of various parameters on the TB incidence rate. Finally, we formulated the putative treatment strategies to reduce the TB burden in high‐incidence scenarios. Further, we estimated the impact of these proposed treatment strategies on the drug‐resistant population in high‐incidence scenarios. The model predictions suggested molding the current treatment strategies and focused implementation of LTBI diagnosis and treatment in high‐incidence scenarios.

Family‐centered creative arts therapies for children with autism: A configurative systematic review

AbstractObjectiveThis configurative systematic review analyzed family‐centered creative arts therapies for children with autism to understand why and how they are done.BackgroundCreative arts therapies and family‐centered practice are both beneficial for children with autism. Research combining both approaches—that is, family‐centered creative arts therapies—is emerging, and reported findings are promising. A deeper understanding of the theoretical influences and mechanisms of these therapies may generate new ways of thinking and working with families with children with autism.MethodsFollowing registration with PROSPERO and in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines, a literature search was performed, resulting in 17 studies. Thematic analysis considered the studies in terms of theoretical influences, creative arts therapy components, and family‐centered components.ResultsThe development‐in‐context perspective was a key theoretical influence. In addition to music and singing, body movement/physical activity was a prominent component of creative arts therapies. Verbal support as well as modeling behaviors and strategies to parents were salient family‐centered components.ConclusionThis systematic review reveals common principles, practices, and gaps in the existing literature and their relevance for families with children with autism.ImplicationsThese findings bear implications for families, therapists, Certified Family Life Educators, and other professionals working with families with children with autism.

Phytochemical Analysis and Anti‐inflammatory Potential of Floscopa Scandens Lour. and Exploring Ecdysterone as Promising Therapeutic Agent: An HR‐LCMS Screening and Molecular Docking Analysis

AbstractThis study delved into the exploration of bioactive constituent profiling of Floscopa scandens Lour. by using HRLC‐MS. The plant is well‐known as a folklore herb. It is extensively utilized in traditional medicine to address various ailments such as fractures, sore eyes, fevers, abscesses, pyoderma, and acute nephritis. This study aimed to explore the phytochemical composition of F. scandens and assess the anti‐inflammatory activity of the ecdysterone marker compound by molecular docking studies followed by MD simulations. Extracts were prepared using hexane, chloroform, and methanol solvents. Chromatographic techniques were applied to isolate compounds from the methanol extract, which underwent phytochemical screening via HR‐LCMS. Functional groups were assessed using NMR and Fourier transform infrared (FTIR), confirming the presence of bioactive compounds. HR‐LCMS analysis identified 21 phytoconstituents in the methanolic fraction, with ecdysterone being a prominent component characterized through spectroscopic techniques. Our findings confirm known molecules while unveiling new bioactive constituents, particularly highlighting the potential of ecdysterone as a novel chemical entity. Molecular docking and molecular dynamic simulation analysis further show the anti‐inflammatory properties of ecdysterone with various enzymes in the body.

Protective Effects of Anethole in Foeniculum vulgare Mill. Seed Ethanol Extract on Hypoxia/Reoxygenation Injury in H9C2 Heart Myoblast Cells.

Active compounds from plants and herbs are increasingly incorporated into modern medical systems to address cardiovascular diseases (CVDs). Foeniculum vulgare Mill., commonly known as fennel, is an aromatic medicinal plant and culinary herb that is popular worldwide. Protective effects against cellular damage were assessed in the H9C2 cardiomyocyte hypoxia/reoxygenation (H/R) experimental model. The identities of phytochemicals in FVSE were determined by GC-MS analysis. The phytochemical's potential for nutrients and pharmacokinetic properties was assessed by ADMET analysis. GC-MS analysis of the ethanol extracts of F. vulgare identified 41 bioactive compounds, with four prominent ones: anethole, 1-(4-methoxyphenyl)-2-propanone, ethoxydimethylphenylsilane, and para-anisaldehyde diethyl acetal. Among these, anethole stands out due to its potential for nutrients and pharmacokinetic properties assessed by ADMET analysis, such as bioavailability, lipophilicity, flexibility, and compliance with Lipinski's Rule of Five. In the H/R injury model of H9C2 heart myoblast cells, FVSE and anethole suppressed H/R-induced reactive oxygen species (ROS) generation, DNA double-strand break damage, nuclear condensation, and the dissipation of mitochondrial membrane potential (ΔΨm). These findings highlight the therapeutic potential of FVSE and its prominent component, anethole, in the treatment of CVDs, particularly those associated with hypoxia-induced damage.

Psychiatric neuroimaging at a crossroads: Insights from psychiatric genetics

Thanks to methodological advances, large-scale data collections, and longitudinal designs, psychiatric neuroimaging is better equipped than ever to identify the neurobiological underpinnings of youth mental health problems. However, the complexity of such endeavors has become increasingly evident, as the field has been confronted by limited clinical relevance, inconsistent results, and small effect sizes. Some of these challenges parallel those historically encountered by psychiatric genetics. In past genetic research, robust findings were historically undermined by oversimplified biological hypotheses, mistaken assumptions about expectable effect sizes, replication problems, confounding by population structure, and shared biological patterns across disorders. Overcoming these challenges has contributed to current successes in the field. Drawing parallels across psychiatric genetics and neuroimaging, we identify key shared challenges as well as pinpoint relevant insights that could be gained in psychiatric neuroimaging from the transition that occurred from the candidate gene to (post) genome-wide “eras” of psychiatric genetics. Finally, we discuss the prominent developmental component of psychiatric neuroimaging and how that might be informed by epidemiological and omics approaches. The evolution of psychiatric genetic research offers valuable insights that may expedite the resolution of key challenges in psychiatric neuroimaging, thus potentially moving our understanding of psychiatric pathophysiology forward.

Evaluating the climatic suitability for camping in South Africa: an application of the Camping Climate Index (CCI)

ABSTRACT Nature-based tourism is a prominent component of the tourism sector in South Africa, attracting both domestic and international travellers. Camping plays a crucial role, providing both affordable lodging and an opportunity to engage more directly and continuously with the natural environment. Climate is a key determinant of the feasibility of camping activities and has been empirically established as a significant influence in tourists’ decision-making process when selecting a destination. The climate in South Africa, while highly heterogenous, has been generally classified as ‘ideal’ for tourism. The Camping Climate Index (CCI) has recently been developed to quantify the climatic suitability of diverse camping locations, and the suitability of the index confirmed for South Africa. This study applies the CCI to 33 stations across South Africa for the period 1990–2022 or for the longest time period for which data are available. The average annual CCI scores range from 3.5 (‘unfavourable’) for Sutherland to 5.3 (‘acceptable’) for King Shaka International Airport. Mean monthly scores for the common period 2017–2021 range from 2.7 (‘unfavourable’) for Sutherland in August to 6.2 (‘good’) for Springbok in January and December. This facilitates the advancement of the tourism sector in South Africa by providing a quantitative assessment of the climatic conditions suitable for camping activities.

Lennox- Gastaut Syndrome (Childhood Epileptic Encephalopathy) – A Rare Case Report

Lennox-Gastaut syndrome (LGS) is a severe form of childhood epilepsy that is defined by generalized multiple type seizures, slowness of intellectual growth, and a specific EEG disturbance. Children affected may previously had infantile spasms or underlying brain disorder, but the aetiology can be idiopathic or symptomatic. The incidence of secondary epilepsy is higher in developed countries resulting in higher the incidence of disease. Lennox-Gastaut syndrome (LGS) 18 is characterized by multiple seizure types. An axial tonic seizure is the hallmark of LGS. Later on, atypical absence, atonic and myoclonic falls and recurrent status observed. Cognitive and behavioural abnormalities are common. Gastaut syndrome is usually between 2-7 years with a peak onset between 3 to 5 years. The awake EEG record shows 2-to2.5-Hz spike-and-wave and polyspike and wave discharges, which are usually diffuse and maximal bifrontal. The prognosis is unfavourable and only a minority of patients achieves seizure control. Newer antiepileptic drugs (AEDs) like felbamate lamotrigine and topiramate have been found to be useful. Anterior corpus callostomy may reduce seizure frequency in some patients. Astatic seizures preceded by a prominent tonic component are most improved by these procedures in some cases. LGS seizures are often treatment resistant and the long-term prognosis is poor.

A comparative analysis of the characterization, antibacterial and antioxidant properties of oak tasar (Antheraea proylei) and mulberry (Bombyx mori) pupae oils

Silkworm pupae oils have emerged as a great source of functional fatty acids in recent days. However, certain wild races of silkworm pupae are yet to be explored to know their potentiality in human health. Therefore, the current study aims to validate their efficacy towards therapeutic values through a comparative analysis between two races of silkworm pupae oil, namely, oak tasar pupae oil (OTPO) and mulberry silkworm pupae oil (MSPO). The pupae oils were extracted using the Soxhlet method followed by the fatty acids profile and functional group analysis using Gas Chromatography Mass Spectrometry (GC-MS) and Fourier Transform Infrared (FTIR) respectively. The radical scavenging activities of both oils were determined by 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH). Further, both the oils were tested for their antibacterial activity using the agar well diffusion method. The oil yield was recorded as 24.62 ± 0.341 % and 24.16 ± 0.764 % for OTPO and MSPO respectively. GC-MS analysis revealed the presence of conjugated linoleic acid (ω-6 fatty acids) as a prominent component in both OTPO (23.49 %) and MSPO (37.99 %), followed by other bioactive constituents in minor amounts. The FTIR analysis and chemical properties correlated to the peaks of common edible oils. Meanwhile, MSPO (150.50±0.45 μg/mL) had a higher TPC when compared to OTPO (44.599±0.514 μg/mL). Moreover, OTPO showed better radical scavenging properties than MSPO. Further, OTPO exhibited antibacterial activity against E. coli, E. cloacae, and S. typhi at different dilutions. However, MSPO was found to be ineffective against the tested bacterial strains. In conclusion, the present study indicates that both oils could be used as an alternative edible oil source as well as a therapeutic agent in the near future.

Concurrent ependymal and ganglionic differentiation in a subset of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement

Neuroepithelial tumors with fusion of PLAGL1 or amplification of PLAGL1/PLAGL2 have recently been described often with ependymoma-like or embryonal histology respectively. To further evaluate emerging entities with PLAG-family genetic alterations, the histologic, molecular, clinical, and imaging features are described for 8 clinical cases encountered at St. Jude (EWSR1-PLAGL1 fusion n = 6; PLAGL1 amplification n = 1; PLAGL2 amplification n = 1). A histologic feature observed on initial resection in a subset (4/6) of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement was the presence of concurrent ependymal and ganglionic differentiation. This ranged from prominent clusters of ganglion cells within ependymoma/subependymoma-like areas, to interspersed ganglion cells of low to moderate frequency among otherwise ependymal-like histology, or focal areas with a ganglion cell component. When present, the combination of ependymal-like and ganglionic features within a supratentorial neuroepithelial tumor may raise consideration for an EWSR1-PLAGL1 fusion, and prompt initiation of appropriate molecular testing such as RNA sequencing and methylation profiling. One of the EWSR1-PLAGL1 fusion cases showed subclonal INI1 loss in a region containing small clusters of rhabdoid/embryonal cells, and developed a prominent ganglion cell component on recurrence. As such, EWSR1-PLAGL1 neuroepithelial tumors are a tumor type in which acquired inactivation of SMARCB1 and development of AT/RT features may occur and lead to clinical progression. In contrast, the PLAGL2 and PLAGL1 amplified cases showed either embryonal histology or contained an embryonal component with a significant degree of desmin staining, which could also serve to raise consideration for a PLAG entity when present. Continued compilation of associated clinical data and histopathologic findings will be critical for understanding emerging entities with PLAG-family genetic alterations.