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BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folates role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Abstract Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOS SMARCB1- , which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOS SMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOS Smarcb1- . In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOS SMARCB1- within the TME.

Abstract The government of Serdang Bedagai Regency initiated a supplementation program to reduce the high prevalence of stunting in the area by delivering extra supplementation, which were nutritious biscuits from national government and fish-based supplement produced from local resources. A 6-month study from April 2022 to September 2022 was conducted to monitor and evaluate the government program that involved 219 under-5-year-old children with height-for-age Z-score (HAZ-score) below − 2. We observed the stunting prevalence reduction by 37.00%, where 81 children recovered from stunting (HAZ-score ≥ − 2). Furthermore, the mean HAZ-score and WHZ-score (Weight-for-Height Z-score) were monitored to significantly improve by 0.97 ± 1.45 (P-value = 1.74e−14) and 1.00 ± 2.18 (P-value = and 2.40e−8), subsequently. The most significant improvement in HAZ-score was monitored among children receiving fish-based supplements with 1.04 ± 1.44 improvement (P-value = 6.59e−17). Then, a significant WHZ-score improvement was reported from children consuming fish-based supplements and a combination of fish-based supplements with nutritious biscuits (P-value = 2.32e−8 and 5.48e−5) by 1.04 ± 2.29 and 0.83 ± 1.84, respectively. The results of the observation become evidence that the program could effectively reduce the prevalence of stunting in children below five years old, especially among children who received locally produced fish-based supplements.

Postsecondary institutions across Canada have implemented various Indigenization strategies. Critical reflection is needed about the development, implementation, and impact of these strategies to ensure they serve more than checked boxes, and that they strive towards institutional decolonization. The purpose of this article is to present the development of an undergraduate course on Indigenous wellness at a Canadian postsecondary institution. Applying a reflective case narrative scholarly approach, we self-situate to present contextual information about ourselves and the course, as well as our motivation for course development and the scope of curriculum design. We consider five indicators of course design success within Dimitrov and Haque's (2016) intercultural curriculum design competencies, and we recommend changes to the course design process for Indigenization sake. Reflecting on and interpreting our approach, we propose a three-party relational model to Indigenous course development consisting of the course instructor, a keeper of traditional knowledges, and a teaching and learning expert. In doing so we attempt to inform and prompt the thinking of others with similar or related course design goals.

Background: Early restoration of normal physiology when return of spontaneous circulation (ROSC) is obtained after an out-of-hospital cardiac arrest (OHCA) reduces the risk of developing post-cardiac arrest syndrome (PCAS). This study aims to investigate if (and to which extent) this can be achieved within the scope of practice of standard emergency medical services (EMS) crews. Methods: A prospective mixed-methods quantitative and qualitative cohort study was performed including adult patients with a non-traumatic OHCA presented to a university hospital emergency department (ED) in the Netherlands after pre-hospital ROSC was obtained. Primary endpoint was the percentage of patients with deranged physiology post-ROSC in whom EMS crews were able to reach recommended treatment targets. Results: During a 32-month period, 160 patients presenting with ROSC after OHCA were included. Median (IQR) pre-hospital treatment duration was 40 (34–51) minutes. When deranged physiology was present (n = 133), it could be restored by EMS crews in 29% of the patients. Although average etCO2 and SpO2 improved gradually over time during pre-hospital treatment, recommended treatment targets could not be achieved in respectively 55% (30/55) and 43% (20/46) of the patients. Similarly, airway problems (24/46, 52%), hypotension (20/23, 87%) and post-anoxic agitation (16/43, 37%) could often not be resolved by EMS crews. The ability to restore normal physiology by EMS could not be predicted based on patient characteristics or in-arrest variables. Conclusion: Deranged physiology after an OHCA is commonly encountered, and often difficult to treat within the scope of practice of regular EMS crews. Involvement of advanced critical care teams with a wider scope of practice at an early stage may contribute to a better outcome for these patients.

BackgroundThe use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk.MethodsWe conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants.ResultsThe use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P

IntroductionThe human leukocyte antigen complex (HLA) is essential for inducing specific immune responses to cancer by presenting tumor-associated peptides (TAP) to T cells. Overexpressed tumor associated antigens, mainly cancer-testis antigens (CTA), are outlined as essential targets for immunotherapy in oropharyngeal squamous cell carcinoma (OPSCC). This study assessed the degree to which presentation, gene expression, and antibody response (AR) of TAP, mainly CTA, are correlated in OPSCC patients to evaluate their potential as immunotherapy targets.Materials and methodsSnap-frozen tumor (NLigand/RNA=40), healthy mucosa (NRNA=6), and healthy tonsils (NLigand=5) samples were obtained. RNA-Seq was performed using Illumina HiSeq 2500/NovaSeq 6000 and whole exome sequencing (WES) utilizing NextSeq500. HLA ligands were isolated from tumor tissue using immunoaffinity purification, UHPLC, and analyzed by tandem MS. Antibodies were measured in serum (NAb=27) utilizing the KREX™ CT262 protein array. Data analysis focused on 312 proteins (KREX™ CT262 panel + overexpressed self-proteins).Results183 and 94 of HLA class I and II TAP were identified by comparative profiling with healthy tonsils. Genes from 26 TAP were overexpressed in tumors compared to healthy mucosa (LFC>1; FDR

Summary: Background: Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Methods: Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Findings: Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61–79): 33 pre-Sézary (9.7% of 339), 296 Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53–68). OS was 46.5% (95% CI, 40.6%–53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus

This research endeavors to conduct a thorough investigation into pediatric health in the Papua and West Papua regions of Indonesia, employing a multifaceted approach that integrates data from various sources including RISKESDAS, SUSENAS, and remote sensing indicators such as NDVI (Normalized Difference Vegetation Index) and PDSI (Palmer Drought Severity Index). By amalgamating socio-economic data, health metrics, and environmental variables, the study seeks to achieve a comprehensive understanding of the factors influencing child health. Advanced analytical tools, notably the Generalized Linear Latent Variable Model (GLLVM), are utilized to conduct a dual-analysis of the intricate interplay between health indicators and environmental variables. The incorporation of NDVI and PDSI, derived from remote sensing data, introduces an ecological dimension to the investigation, facilitating a nuanced exploration of the impact of vegetation health and drought severity on pediatric health outcomes. This interdisciplinary research endeavors to unveil correlations, patterns, and potential causal relationships between environmental factors and the prevalence of various health issues among children, including pneumonia, acute respiratory infections, diarrhea, underweight, and stunting. The anticipated results aim to not only enrich our understanding of pediatric health in Papua and West Papua but also to contribute to broader discussions concerning the complex connections between health, socio-economic conditions, and environmental variables. By integrating remote sensing data with health and socio-economic datasets, this study provides a comprehensive perspective, enabling a more robust assessment of the determinants of child well-being. The insights gleaned from this research are poised to have significant implications for policymakers, environmental scientists, and public health professionals, informing the development of strategies aimed at enhancing child health outcomes in these regions. Furthermore, this study underscores the importance of initiatives like the Free Lunch and Milk Program proposed by Prabowo and Gibran in the 2024 Indonesian Presidential Election, emphasizing the critical role of holistic approaches in addressing the multifaceted challenges surrounding child health and well-being.

Particulate matter forecasting is fundamental for early warning and controlling air pollution, especially PM2.5. The increase in this level of concentration will lead to a negative impact on public health. This study develops a hybrid model of CNN-LSTM and CONV-LSTM by combining a convolutional neural network (CNN) with an LSTM network to forecast PM2.5 concentration for the next few hours in Kemayoran DKI Jakarta, which is known as a busy area. We discovered the advantages of CNN in effectively extracting features and LSTM in learning long-term historical data from PM2.5 concentration time series data. The predictive model of CNN-LSTM is carried out in a different architecture where the CNN process is carried out first to become the input of LSTM. For CONV-LSTM, it is carried out in one architecture where the multiplication in the LSTM architecture is coupled with the convolution process. This research will explain how the method of developing hybrid CNN-LSTM and CONV-LSTM in predicting PM2.5 concentrations. Based on metric evaluation, the two models are compared to find the best model. Both predictive models produce MAPE values that fall into the good enough category with values < 20%. Results were obtained for CONV-LSTM with MAE worth 6.52, RMSE 8.55, and MAPE 16.39%. As a result, the CONV-LSTM model performs better than CNN-LSTM in nowcasting PM2.5.

The rising prevalence of behavioral and mental health challenges among Indonesian adolescents, affecting nearly one in three, is a pressing concern intensified by constant internet exposure and heightened social comparisons. This study, using data from Indonesia’s National Socioeconomic Survey, examines the likelihood of mental health issues in adolescents, incorporating variables like mobile phone usage, emotional and behavioral disorder classifications, travel experiences, insurance ownership, maternal residence, house surface area, and night light remote sensing data. Our findings reveal that urban adolescents face a higher susceptibility to behavioral disorders compared to rural peers, with males being 1.18 times more likely to experience behavioral and emotional disturbances than females. This research validates the suitability of these variables for assessing vulnerability among adolescents. Leveraging big data analytics, it highlights the multifaceted determinants of adolescent vulnerability in Indonesia, stressing the need for targeted interventions and policies to enhance their well-being.

Abstract Background Activation of dominant oncogenes by small or structural genomic alterations is a common driver mechanism in many cancers. Silencing of such dominantly activated oncogenic alleles, thus, is a promising strategy to treat cancer. Recently, allele-specific epigenome editing (ASEE) has been described as a means to reduce transcription of genes in an allele-specific manner. In cancer, specificity to an oncogenic allele can be reached by either targeting directly a pathogenic single-nucleotide variant or a polymorphic single-nucleotide variant linked to the oncogenic allele. To investigate the potential of ASEE in cancer, we here explored this approach by targeting variants at the TERT promoter region. The TERT promoter region has been described as one of the most frequently mutated non-coding cancer drivers. Results Sequencing of the TERT promoter in cancer cell lines showed 53% (41/77) to contain at least one heterozygous sequence variant allowing allele distinction. We chose the hepatoblastoma cell line Hep-G2 and the lung cancer cell line A-549 for this proof-of-principle study, as they contained two different kinds of variants, namely the activating mutation C228T in the TERT core promoter and the common SNP rs2853669 in the THOR region, respectively. These variants were targeted in an allele-specific manner using sgRNA-guided dCas9-DNMT3A-3L complexes. In both cell lines, we successfully introduced DNA methylation specifically to the on-target allele of the TERT promoter with limited background methylation on the off-target allele or an off-target locus (VEGFA), respectively. We observed a maximum CpG methylation gain of 39% and 76% on the target allele when targeting the activating mutation and the common SNP, respectively. The epigenome editing translated into reduced TERT RNA expression in Hep-G2. Conclusions We applied an ASEE-mediated approach to silence TERT allele specifically. Our results show that the concept of dominant oncogene inactivation by allele-specific epigenome editing can be successfully translated into cancer models. This new strategy may have important advantages in comparison with existing therapeutic approaches, e.g., targeting telomerase, especially with regard to reducing adverse side effects.

Abstract Background Epigenome editing refers to the targeted reprogramming of genomic loci using an EpiEditor which may consist of an sgRNA/dCas9 complex that recruits DNMT3A/3L to the target locus. Methylation of the locus can lead to a modulation of gene expression. Allele-specific DNA methylation (ASM) refers to the targeted methylation delivery only to one allele of a locus. In the context of diseases caused by a dominant mutation, the selective DNA methylation of the mutant allele could be used to repress its expression but retain the functionality of the normal gene. Results To set up allele-specific targeted DNA methylation, target regions were selected from hypomethylated CGIs bearing a heterozygous SNP in their promoters in the HEK293 cell line. We aimed at delivering maximum DNA methylation with highest allelic specificity in the targeted regions. Placing SNPs in the PAM or seed regions of the sgRNA, we designed 24 different sgRNAs targeting single alleles in 14 different gene loci. We achieved efficient ASM in multiple cases, such as ISG15, MSH6, GPD1L, MRPL52, PDE8A, NARF, DAP3, and GSPT1, which in best cases led to five to tenfold stronger average DNA methylation at the on-target allele and absolute differences in the DNA methylation gain at on- and off-target alleles of > 50%. In general, loci with the allele discriminatory SNP positioned in the PAM region showed higher success rate of ASM and better specificity. Highest DNA methylation was observed on day 3 after transfection followed by a gradual decline. In selected cases, ASM was stable up to 11 days in HEK293 cells and it led up to a 3.6-fold change in allelic expression ratios. Conclusions We successfully delivered ASM at multiple genomic loci with high specificity, efficiency and stability. This form of super-specific epigenome editing could find applications in the treatment of diseases caused by dominant mutations, because it allows silencing of the mutant allele without repression of the expression of the normal allele thereby minimizing potential side-effects of the treatment.

Pleuronectiformes are flatfishes with high commercial value and a prominent example of successful marine adaptation through chromosomal evolution. Hence, the aim of this study was to analyze the 14 relative abundance of repetitive elements (satellite DNA and transposable elements (TE)) in the 15 genome of 10 fish species (8 flatfish) delving into the study of the species of special relevance, 16 Senegalese sole, Solea senegalensis. The results showed differences in the abundance of repetitive elements, with S. senegalensis exhibiting the highest frequency and coverage of these elements reaching the 40% of the genome and not at random distribution. It is noteworthy the presence of relevant peaks of Helitrons in centromeric/pericentromeric positions mainly in the bi-armed chromosomes 1, 2, 4, 6, 7, and 9. The position of the centromeres of this species determined through the genomic localization of the family of satellite DNA PvuII, and other repetitive sequences was obtained de novo. This allowed us to know the genomic position of the centromeres in 19 out of the 21 chromosomes of S. senegalensis. Helitrons showed an accumulation of tandem copies mainly in the pericentromeric positions of chromosomes 1 and 2, occupying a region, in the first case, of 600Kb of tandem repeats. That has only been previously described in mammals and plants. Divergence and copy number studies indicated the presence of active families in the species’ genome and the existence of two important events of transposon activity (burst) in the genome of S. senegalensis, mainly accentuated in Helitrons. The results showed that only the families of DNA transposons exhibited a landscape with symmetrical bell-shaped distribution. The phylogenetic analysis of Helitron families revealed the presence of two large groups of families and the presence of four groups of sequences with heterogeneous distribution among chromosomes. Finally, the phylogenomic analysis of 8615 sequences belonging to Helitron insertions from 5 families of flatfish and two external species, allowed to classify the copies into nine groups of sequences with different levels of divergence and clusters, including some branches with distant phylogenetically species. The implications of this study will help to expand the knowledge of chromosome structure and evolution of these species.

Summary: Glucocorticoid (GC) signaling is essential for mounting a stress response, however, chronic stress or prolonged GC therapy downregulates the GC receptor (GR), leading to GC resistance. Regulatory mechanisms that refine this equilibrium are not well understood. Here, we identify seven lysine acetylation sites in the amino terminal domain of GR, with lysine 154 (Lys154) in the AF-1 region being the dominant acetyl-acceptor. GR-Lys154 acetylation is mediated by p300/CBP in the nucleus in an agonist-dependent manner and correlates with transcriptional activity. Deacetylation by NAD+-dependent SIRT1 facilitates dynamic regulation of this mark. Notably, agonist-binding to both wild-type GR and an acetylation-deficient mutant elicits similar short-term target gene expression. In contrast, upon extended treatment, the polyubiquitination of the acetylation-deficient GR mutant is impaired resulting in higher protein stability, increased chromatin association and prolonged transactivation. Taken together, reversible acetylation fine-tunes duration of the GC response by regulating proteasomal degradation of activated GR.

The Solar Dryer Dome (SDD), an independent energy system equipped with Artificial Intelligence to support the drying process, has been developed. However, inaccurate state-of-charge (SOC) predictions in each battery cell resulted in the vulnerability of the battery to over-charging and over-discharging, which accelerated the battery performance degradation. This research aims to develop an accurate neural network model for predicting the SOC of battery-cell level. The model aims to maintain the battery cell balance under dynamic load applications. It is accompanied by a developed dashboard to monitor and provide crucial information for early maintenance of the battery in the SDD. The results show that the neural network estimates the SOC with the lowest MAE of 0.175, followed by the Random Forest and support vector machine methods with MAE of 0.223 and 0.259, respectively. A dashboard was developed to help farmers monitor batteries efficiently. This research contributes to battery-cell level SOC prediction and the dashboard for battery status monitoring. Doi: 10.28991/ESJ-2023-07-03-02 Full Text: PDF

AbstractThis study examines the interplay of air connectivity, sports events, infrastructures, and fiscal support during the period 2017 and 2022 in a designated area called Special Economic Zone in Mandalika, Lombok Island, West Nusa Tenggara to boost tourism development in Indonesia by utilizing big data cognitive analytics. We examine the tourism development impacted by the MotoGP event in 2022 and air connectivity. Further, this paper discusses the network connectivity of flights at Zainuddin Abdul Madjid International Airport during the COVID-19 Pandemic and the new normal. We found that the combination of an international airport, globally recognized sports events, and government support has directly and positively improved the tourism industry’s performance in the country and especially within Lombok Island. We suggest policy recommendations to support economic activities in Mandalika’s Special Economic Zone and its hinterland to maintain business sustainability and utilize the existing infrastructures at the optimum level. Lessons learned from the Indonesian experience could help other developing countries that are devising policies and strategies to develop the tourism industry by employing proper instruments such as infrastructure, events, and fiscal policies.

Abstract This article examines the engagement of domestic actors in public conversation surrounding free trade negotiations with a focus on the framing of these negotiations as economic, strategic or domestic issues. To analyse this topic, this article utilises the use of Twitter as a barometer of public sentiment toward the Regional Comprehensive Economic Partnership (RCEP). We employ topic classification and sentiment analysis to understand how RCEP is discussed in 345,015 tweets. Our findings show that the overall sentiment score towards RCEP is neutral. However, we find that when RCEP is discussed as a strategic issue, the sentiment is slightly more negative than when discussed as a domestic or economic issue. This article further suggests that discussion of RCEP is driven by the fear of China’s geopolitical ambitions, domestic protectionist agendas, and impact of RCEP on the domestic economy. This article contributes to the growing use of big data in understanding trade negotiations. Furthermore, it contributes to the study of free trade negotiation by examining how domestic political actors frame free trade negotiations.

Abstract Brain injury and cerebral vasospasm during the 14 days after the subarachnoid hemorrhage (SAH) are considered the leading causes of poor outcomes. The primary injury induces a cascade of events, including increased intracranial pressure, cerebral vasospasm and ischemia, glutamate excitotoxicity, and neuronal cell death. The objective of this study was to monitor the time course of glutamate, and associated enzymes, such as glutamate–oxaloacetate transaminase (GOT1), glutamate-pyruvate transaminase (GPT) in cerebrospinal fluid (CSF) and serum, shortly after SAH, and to assess their prognostic value. A total of 74 participants participated in this study: 45 participants with SAH and 29 controls. Serum and CSF were sampled up to 14 days after SAH. SAH participants' clinical and neurological status were assessed at hospitalization, at discharge from the hospital, and 3 months after SAH. Furthermore, a logistic regression analysis was carried out to evaluate the ability of GOT1 and glutamate levels to predict neurological outcomes. Our results demonstrated consistently elevated serum and CSF glutamate levels after SAH. Furthermore, serum glutamate level was significantly higher in patients with cerebral ischemia and poor neurological outcome. CSF GOT1 was significantly higher in patients with uncontrolled intracranial hypertension and cerebral ischemia post-SAH, and independently predicted poor neurological outcomes.

Air quality conditions are now more severe in the Jakarta area that is among the world’s top eight worst cities according to the 2022 Air Quality Index (AQI) report. In particular, the data from the Meteorological, Climatological, and Geophysical Agency (BMKG) of the Republic of Indonesia, the latest outcomes in air quality conditions in Jakarta and surrounding areas, says that PM2.5 concentrations have increased and peaked at $148~\mu \text{g}/\text{m}^{3}$ in 2022. While a classification system for this pollution is necessary and critical, the observation of PM2.5 concentrations measured through the BMKG Kemayoran station, Jakarta, turns out to be identified as an unbalanced data class. Thus, in this work, we perform boosting algorithm supervised learning to handle such an unbalanced classification toward PM2.5 concentration levels by observing meteorological patterns in Jakarta during 1 January 2015 to 7 July 2022. The boosting algorithms considered in this research include Adaptive Boosting (AdaBoost), Extreme Gradient Boosting (XGBoost), Categorical Boosting (CatBoost), and Light Gradient Boosting Machine (LightGBM). Our simulations have proven that boosting classification can significantly reduce bias in combination with variance reduction with unbalanced within-class coefficients, with the classification of PM2.5 class values: good 62%, moderate 34%, and unhealthy 59%, respectively.

Abstract As the fourth most populous country in the world, Indonesia must increase the annual rice production rate to achieve national food security by 2050. One possible solution comes from the nanoscopic level: a genetic variant called Single Nucleotide Polymorphism (SNP), which can express significant yield-associated genes. The prior benchmark of this study utilized a statistical genetics model where no SNP position information and attention mechanism were involved. Hence, we developed a novel deep polygenic neural network, named the NucleoNet model, to address these obstacles. The NucleoNets were constructed with the combination of prominent components that include positional SNP encoding, the context vector, wide models, Elastic Net, and Shannon’s entropy loss. This polygenic modeling obtained up to 2.779 of Mean Squared Error (MSE) with 47.156% of Symmetric Mean Absolute Percentage Error (SMAPE), while revealing 15 new important SNPs. Furthermore, the NucleoNets reduced the MSE score up to 32.28% compared to the Ordinary Least Squares (OLS) model. Through the ablation study, we learned that the combination of Xavier distribution for weights initialization and Normal distribution for biases initialization sparked more various important SNPs throughout 12 chromosomes. Our findings confirmed that the NucleoNet model was successfully outperformed the OLS model and identified important SNPs to Indonesian rice yields.

Summary: Cell surface receptor internalization can either terminate signaling or activate alternative endosomal signaling pathways. We investigated here whether endosomal signaling is involved in the function of the human receptors for Fc immunoglobulin fragments (FcRs): FcαRI, FcγRIIA, and FcγRI. All these receptors were internalized after their cross-linking with receptor-specific antibodies, but their intracellular trafficking was different. FcαRI was targeted directly to lysosomes, while FcγRIIA and FcγRI were internalized in particular endosomal compartments described by the insulin responsive aminopeptidase (IRAP), where they recruited signaling molecules, such as the active form of the kinase Syk, PLCγ and the adaptor LAT. Destabilization of FcγR endosomal signaling in the absence of IRAP compromised cytokine secretion downstream FcγR activation and macrophage ability to kill tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Our results indicate that FcγR endosomal signaling is required for the FcγR-driven inflammatory reaction and possibly for the therapeutic action of monoclonal antibodies.

Once an infrequent disease in parts of Asia, the rate of colorectal cancer in recent decades appears to be steadily increasing. Colorectal cancer represents one of the most important causes of cancer mortality worldwide, including in many regions in Asia. Rapid changes in socioeconomic and lifestyle habits have been attributed to the notable increase in the incidence of colorectal cancers in many Asian countries. Through published data from the International Agency for Cancer Research (IARC), we utilized available continuous data to determine which Asian nations had a rise in colorectal cancer rates. We found that East and South East Asian countries had a significant rise in colorectal cancer rates. Subsequently, we summarized here the known genetics and environmental risk factors for colorectal cancer among populations in this region as well as approaches to screening and early detection that have been considered across various countries in the region.

In comparison to bulk sequencing or single cell sequencing, spatial transcriptomics preserves the spatial information in tissue slices and can even be mapped to immunofluorescent stainings, allowing translation of gene expression information into their spatial context. This enables to unravel complex interactions of neighboring cells or to link cell morphology to transcriptome data. The 10× Genomics Visium platform offers to combine spatial transcriptomics with immunofluorescent staining of cryo-sectioned tissue slices. We applied this technique to fresh frozen mouse brain slices and developed a protocol that still protects RNA quality while improving buffers for immunofluorescent staining. We investigated the impact of various parameters, including fixation time and buffer composition, on RNA quality and antibody binding. Here, we propose an improved version of the manufacturer protocol, which does not alter RNA quality and facilitates the use of multiple additional antibodies that were not compatible with the manufacturer protocol before. Finally, we discuss the influence of various staining parameters, which contribute to the development of application specific staining protocols.

Objectives Genome-wide association studies (GWAS) are performed to study the associations between genetic variants with respect to certain phenotypic traits such as cancer. However, the method that is commonly used in GWAS assumes that certain traits are solely affected by a single mutation. We propose a network analysis method, in which we generate association networks of single-nucleotide polymorphisms (SNPs) that can differentiate case and control groups. We hypothesize that certain phenotypic traits are attributable to mutations in groups of associated SNPs. Methods We propose a method based on a network analysis framework to study SNP-SNP interactions related to cancer incidence. We employed logistic regression to measure the significance of all SNP pairs from GWAS for the incidence of colorectal cancer and computed a cancer risk score based on the generated SNP networks. Results We demonstrated our method in a dataset from a case-control study of colorectal cancer in the South Sulawesi population. From the GWAS results, 20,094 pairs of 200 SNPs were created. We obtained one cluster containing four pairs of five SNPs that passed the filtering threshold based on their p-values. A locus on chromosome 12 (12:54410007) was found to be strongly connected to the four variants on chromosome 1. A polygenic risk score was computed from the five SNPs, and a significant difference in colorectal cancer risk was obtained between the case and control groups. Conclusions Our results demonstrate the applicability of our method to understand SNP-SNP interactions and compute risk scores for various types of cancer.

Abstract Albatross Analytics is a statistical and data science data processing platform that researchers can use in disciplines of various fields. Albatross Analytics makes it easy to implement fundamental analysis for various regressions with random model effects, including Hierarchical Generalized Linear Models (HGLMs), Double Hierarchical Generalized Linear Models (DHGLMs), Multivariate Double Hierarchical Generalized Linear Models (MDHGLMs), Survival Analysis, Frailty Models, Support Vector Machines (SVMs), and Hierarchical Likelihood Structural Equation Models (HSEMs). We provide 94 types of dataset examples.

People live their lives and experience the conflicts in which they are involved in the context of competing normative orders. But how do people navigate this normative pluralism? To understand this, Keebet von Benda-Beckmann's model of 'forum shopping' and 'shopping forums', derived from an ethnographic analysis of conflict resolution, remains an indispensable starting point. Building on this approach, I argue that in order to understand the navigation of normative orders more broadly, it is important to bring the analysis of sentiments to the study of normative pluralism. Drawing on ethnographic fieldwork on the International Criminal Court's transitional justice interventions in northern Uganda, I argue that when confronted with different international, national, religious, and indigenous normative options for dealing with mass violence, people navigate normative pluralism by creating, mobilising, maintaining, and transforming sentiments. [ABSTRACT FROM AUTHOR]