bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence: the key role of dopamine neurotransmission gene polymorphisms
Authors: Kibitov A. O. , Rybakova K. V. , Brodyansky V. M. , Berntsev V. A. , Skurat E. P. , Krupitsky E. M. 
Published: February 2024

The actual direction of increasing the efficacy of alcohol dependence (AD) treatment is the search for opportunities for individualization of therapy using pharmacogenetic markers to stratify patients in order to select the most optimal therapeutic tactics.Aims. To test an associations of possible pharmacogenetic markers with indicators of the efficacy of disulfiram and cyanamide to stabilize remission in patients with AD.Materials and methods. A pharmacogenetic study was conducted on the basis of a double-blind, randomized, comparative, placebo-controlled clinical study of the efficacy and tolerability of disulfiram and cyanamide in the treatment of alcohol dependence syndrome. The main outcome: the duration of retention of patients in the treatment program (in remission), and withdrawal from the treatment program for any reason was considered a negative outcome. Secondary outcomes: time to relapse to alcohol use and time to recurrence to AD. 150 patients with AD (ICD-10 criteria) (av. age - 40.65±1.09 y.o., 19.3% females) were randomly assigned to one of three treatment groups (50 subjects in each): Disulfiram, Cyanamid and Placebo. All patients had weekly (12 weeks) visits to research clinic for brief counselling session. The genetic panel of the study consisted of 15 polymorphic loci in 9 genes: dopamine receptors 2 (DRD2) and 4 (DRD4) types, transmembrane dopamine transporter (DAT), enzymes dopamine-beta-hydroxylase (DBH) and catechol-ortho-methyl-transferase, as well as a two polymorphisms in the genes of the endogenous opioid system and the aldehyde dehydrogenase enzyme gene cluster.Results. For disulfiram, the DBH rs1108580 is associated with a longer remission (p=0.053, trend), and DRD4 VNTR 48 bp is associated with a shorter remission (p=0.006). For cyanamide, DAT VNTR 40 bp was associated with shorter remission (p=0.006) and rapid recurrence to AD (p=0.045). DAT rs27072 has an effect simultaneously in two treatment groups, while the direction of the effect is opposite. For cyanamide, the marker is slightly associated with a longer remission (p = 0.082, trend), a longer time to relapse (p = 0.063, trend) and a longer time to recurrence to AD (p = 0.083, trend). For placebo, DAT rs27072, on the contrary, is associated with a shorter time to to recurrence to AD (p = 0.066, trend). For placebo, DRD2 rs1799732 was associated with a shorter remission (p = 0.001), a shorter time to relapse (p = 0.018), and a shorter time to recurrence to AD (p = 0.001).Conclusion. Preliminary pharmacogenetic markers of the efficacy of alcohol dependence treatment have been identified in genes that control dopaminergic neurotransmission. After independent validation, the obtained genetic markers may be used for pharmacogenetic stratification of patients in order to select the optimal treatment options for alcohol dependence.
Prediksi Nilai Akhir Mahasiswa Dengan Metode Naïve Bayes
Authors: Brama Rizky Setia Dwinanda  , Azriel Noer Ilhami  , Hana Choerunisya  , Indra Jiwana Thira  
Published: February 2024

Memprediksi prestasi belajar atau nilai akhir mahasiswa menjadi suatu hal yang sangat berguna karena dapat mencegah mahasiswa yang beresiko gagal dalam perkuliahan. Prediksi merupakan upaya untuk memperkirakan kemungkinan suatu kejadian, dan hasil dari prediksi tidak dapat dijamin akan terjadi secara pasti. Meskipun begitu kita bisa mengusahakan untuk mencari jawaban sedekat mungkin dengan apa yang akan terjadi. Penelitian ini bertujuan untuk memprediksi nilai akhir mahasiswa berdasarkan IPK yang didapat pada semester 2, karena nilai tersebut bisa digunakan sebagai penilaian awal untuk memperkirakan adanya peningkatan atau penurunan nilai yang akan didapat pada semester berikutnya. Output dari penelitian ini adalah rentang nilai yang disesuaikan dengan predikat kelulusan. Data yang digunakan dalam penelitian ini berjumlah 379 yang kemudian dibagi menjadi dua bagian, yaitu data training dengan jumlah 303 data dan data testing dengan jumlah 76 data. Penelitian ini menggunakan metode naïve bayes untuk menghitung probabilitas berdasarkan peristiwa yang telah terjadi sebelumnya. Keterbatasan dataset yang dimiliki, menyebabkan penyebaran data dalam penelitian ini tidaklah merata, sehingga memengaruhi hasil dari penelitian. Hasil penelitian menunjukkan tingkat akurasi dari model algoritma naïve bayes yang digunakan sebesar 78.95%.
News Recommender System Considering Temporal Dynamics and Accuracy-Diversity Tradeoff
Authors: Raza Shaina 
Published: February 2024

<p>News recommender systems aim to personalize users experience for online news readers and help them discover relevant and interesting news items from a broad and diverse search space. However, recommending news is a challenging task. There are hundreds of news articles published every day, many of which quickly become obsolete and irrelevant to the readers. Readers’ preferences (interests) also exhibit dynamic behavior and the relevance of readers’ preferences strongly depend on the context. Some of the readers’ preferences are long-term, reflecting the personality or behavior, whereas others are short-term, showing their current interests. External events, such as breaking news and trends, also influence readers’ interests. Although the high recommendation accuracy is appreciated, focusing on it too much sacrifices diversity and limits readers’ options. </p>
<p>The main contribution of this research is to design a recommender system to tackle the specific challenges of news recommendations. To address these challenges, we propose a recommendation strategy that seamlessly integrates readers’ long-term and short-term preferences when recommending news items. In addition to high accuracy, we focus on promoting reasonable diversity in news recommendations. To achieve a balanced objective (high accuracy and reasonable diversity), we formulate a combined optimization strategy that includes both of these aspects in the recommendation process. </p>
<p>More specifically, to achieve high accuracy, we propose novel latent factor models such as matrix factorization and a generalized linear model. In addition, we propose a regularized latent factor model to achieve reasonable diversity while maintaining high accuracy. Then, for the same purpose, we propose a deep learning-based framework composed of network components of news modelling and reader modelling. We use different regularization terms in the latent factor model to achieve accuracy-diversity balance, and the neural attention mechanism in deep neural networks for the same purpose. </p>
<p>We also introduce a new evaluation metric to measure the tradeoff performance with respect to accuracy and diversity. Experiments on real-world data have demonstrated the effectiveness of our proposed approach on quality factors such as accuracy, diversity as well as this tradeoff metric. Our model has achieved an improvement on this new tradeoff metric by 10-30% when compared to traditional and state-of-the-art recommendation algorithms.</p>
REEP4 variant analysis in blepharospasm and other neurological disorders
Authors: Saeirad Samira , LeDoux Mark S. 
Published: February 2024

Introduction: In preceding work, a deleterious REEP4 variant [GRCh38/hg38, NC_000008.11:g.22140245G&gt;A, NM_025232.4:c.109C&gt;T, p.Arg37Trp] was found to co-segregate with blepharospasm (BSP) in a large African-American pedigree. Other REEP4 variants have been reported in genetic screening studies of dystonia. The REEP4 paralogs, REEP1 and REEP2, are associated with spastic paraplegia. The causal contributions of REEP4 variants to dystonia and other neurological disorders remains indecisive.Methods: Sanger sequencing was used to screen subjects (N = 307) with BSP and BSP-plus dystonia affecting additional anatomical segments (BSP+) phenotypes for variants in REEP4. In silico tools were used to examine the deleteriousness of reported (ClinVar) and previously published REEP4 variants.Results: No highly deleterious variant was identified in coding or contiguous splice site regions of REEP4 in our cohort of 307 subjects. In silico analysis identified numerous deleterious REEP4 variants in published screening studies of dystonia and several highly deleterious single nucleotide REEP4 variants in ClinVar.Conclusion: Highly deleterious REEP4 variants are rare in BSP and BSP+ phenotypes.
Exploration of commercial cyclen-based chelators for mercury-197 m/g incorporation into theranostic radiopharmaceuticals
Authors: Randhawa Parmissa , Carbo-Bague Imma , Davey Patrick R. W. J. , Chen Shaohuang , Merkens Helen , Uribe Carlos F. , Zhang Chengcheng , Tosato Marianna , Bénard François , Radchenko Valery , Ramogida Caterina F. 
Published: February 2024

A comprehensive investigation of the Hg2+ coordination chemistry and 197m/gHg radiolabeling capabilities of cyclen-based commercial chelators, namely, DOTA and DOTAM (aka TCMC), along with their bifunctional counterparts, p-SCN-Bn-DOTA and p-SCN-Bn-TCMC, was conducted to assess the suitability of these frameworks as bifunctional chelators for the 197m/gHg2+ theranostic pair. Radiolabeling studies revealed that TCMC and DOTA exhibited low radiochemical yields (0%–6%), even when subjected to harsh conditions (80°C) and high ligand concentrations (10–4 M). In contrast, p-SCN-Bn-TCMC and p-SCN-Bn-DOTA demonstrated significantly higher 197m/gHg radiochemical yields (100% ± 0.0% and 70.9% ± 1.1%, respectively) under the same conditions. The [197 m/gHg]Hg-p-SCN-Bn-TCMC complex was kinetically inert when challenged against human serum and glutathione. To understand the differences in labeling between the commercial chelators and their bifunctional counterparts, non-radioactive natHg2+ complexes were assessed using NMR spectroscopy and DFT calculations. The NMR spectra of Hg-TCMC and Hg-p-SCN-Bn-TCMC suggested binding of the Hg2+ ion through the cyclen backbone framework. DFT studies indicated that binding of the Hg2+ ion within the backbone forms a thermodynamically stable product. However, competition can form between isothiocyanate binding and binding through the macrocycle, which was experimentally observed. The isothiocyanate bound coordination product was dominant at the radiochemical scale as, in comparison, the macrocycle bound product was seen at the NMR scale, agreeing with the DFT result. Furthermore, a bioconjugate of TCMC (TCMC-PSMA) targeting prostate-specific membrane antigen was synthesized and radiolabeled, resulting in an apparent molar activity of 0.089 MBq/nmol. However, the complex demonstrated significant degradation over 24 h when exposed to human serum and glutathione. Subsequently, cell binding assays were conducted, revealing a Ki value ranging from 19.0 to 19.6 nM. This research provides crucial insight into the effectiveness of current commercial chelators in the context of 197m/gHg2+ radiolabeling. It underscores the necessity for the development of specific and customized chelators to these unique “soft” radiometals to advance 197m/gHg2+ radiopharmaceuticals.
Elevated hyaluronic acid levels in severe SARS-CoV-2 infection in the post-COVID-19 era
Authors: Li Yanyan , Cui Xinyu , Zhu Na , Lin Yingying , Li Xin 
Published: February 2024

ObjectiveHuman identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promoted the coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA) via NamiRNA-enhancer network, based on previous experimental research. This study aimed to investigate the predictive value of HA for the severity of SARS-CoV-2 infection in the post-COVID-19 era.MethodsA total of 217 consecutive patients with COVID-19 were enrolled at Beijing Ditan Hospital between July 2023 and October 2023. HA levels were analyzed using biochemical detector. Logistic regression analysis was used to screen independent factors for severe COVID-19. The predictive performance of HA for severe infection was assessed by ROC curve. Furthermore, the relationship between HA levels and COVID-19 severity was investigated using multivariate logistic regression models after adjustment for potential confounders.ResultsAccording to the cut-off value of HA, COVID-19 patients were divided into HA &lt; 90 ng/mL group (80 cases) and HA ≥ 90 ng/mL group (137 cases). High HA levels were positively associated with the severe SARS-CoV-2 infection, including elevated inflammatory indicators, severe lung involvement, prolonged clinical course, and higher incidence of respiratory failure and death (P &lt; 0.05). Logistic regression analysis suggested that HA was an independent predictor of severe COVID-19 (OR = 4.540, 95% CI = 2.105-9.790, P &lt; 0.001). ROC curve analysis showed that the AUC of HA for severe infection was 0.724. HA levels were significantly higher in COVID-19 cases compared to the healthy population (123.9 (82.6, 174.1) vs. 50.5 (37.8, 66.8), P &lt; 0.001), but similar to those with non-SARS-CoV-2 lung infection (121.6 (78.5, 175.6) vs. 106.0 (66.5, 149.7), P = 0.244). We also found that the first COVID-19 infections had higher HA levels (118.8 (79.5, 174.3) vs. 85.0 (61.1, 128.8), P &lt; 0.001) and a higher proportion of severe infection (37.1% vs. 21.3%, P = 0.043) than re-infections. However, HA expression failed to fully return to normal levels with infection recovery (204.7 (152.9, 242.2) vs. 97.0 (69.3, 137.3), P &lt; 0.001).ConclusionHA was associated with severe SARS-CoV-2 infection and could be used as a novel serum biomarker to predict the risk of COVID-19 progression in the post-COVID-19 era.
Smoking and BMI mediate the causal effect of education on lower back pain: observational and Mendelian randomization analyses
Authors: Xu Zhangmeng , Qi Luming , Zhang Huiwu , Yu Duoduo , Shi Yushan , Yu Yaming , Zhu Tianmin 
Published: February 2024

ObjectiveLow back pain (LBP) has been associated with education in previous observational studies, but the causality remains unclear. This study aims to assess the impact of education on LBP and to explore mediation by multiple lifestyle factors.DesignUnivariable Mendelian randomization (MR) was performed to examine the overall effect of education on LBP. Subsequently, multivariable MR was conducted to assess both the direct effect of education on LBP and the influence of potential mediators. Indirect effects were estimated using either the coefficient product method or the difference method, and the proportion of mediation was calculated by dividing the indirect effect by the total effect. The observational study utilized data from the NHANES database collected between 1999 and 2004, and included 15,580 participants aged 20 years and above.ResultsIncreasing education by 4.2 years leads to a 48% reduction in the risk of LBP (OR=0.52; 95% CI: 0.46 to 0.59). Compared to individuals with less than a high school education, those with education beyond high school have a 28% lower risk of LBP (OR=0.72; 95% CI: 0.63 to 0.83). In the MR study, smoking accounts for 12.8% (95% CI: 1.04% to 20.8%) of the total effect, while BMI accounts for 5.9% (95% CI: 2.99% to 8.55%). The combined mediation effect of smoking and BMI is 27.6% (95% CI: 23.99% to 32.7%). In the NHANES study, only smoking exhibits a mediating effect, accounting for 34.3% (95% CI: 21.07% to 41.65%) of the effect, while BMI does not demonstrate a mediating role.ConclusionsHigher levels of education provide a protective effect against the risk of LBP. Additionally, implementing interventions to reduce smoking and promote weight loss among individuals with lower levels of education can also decrease this risk.
Psychiatric adverse events associated with GLP-1 receptor agonists: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database
Authors: Chen Wei , Cai Peishan , Zou Wenbin , Fu Zhiwen 
Published: February 2024

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used due to their profound efficacy in glycemic control and weight management. Within real-world contexts, the manifestation of certain psychiatric adverse events (AEs) has been observed, which is potentially linked to the administration of GLP-1 RAs. The objective of this study was to undertake a comprehensive investigation and characterization of the psychiatric AEs associated with GLP-1 RAs.MethodsWe retrieved reports of AEs associated with treatment with GLP-1 RAs during the period from the first quarter (Q1) of 2004 to Q1 2023 from the FDA Adverse Event Reporting System (FAERS) database. Descriptive analysis was performed to examine the clinical characteristics and time to onset of the psychiatric AEs caused by GLP-1 RAs. Moreover, disproportionality analyses were performed using the reporting odds ratio (ROR) to identify GLP-1 RA-related psychiatric AEs.ResultsA total of 8,240 reports of psychiatric AEs were analyzed out of 181,238 AE reports with treatment with GLP-1 RAs. Among these cases, a higher percentage was represented by women compared to men (65.89% vs. 30.96%). The median age of these patients was 56 years, with an interquartile range (IQR) of 48–67 years, based on data available in 286 case reports. This study showed that the median time to onset of the overall GLP-1 RA-related AEs was 31 days (IQR = 7–145.4 days), which varied among GLP-1 RA regimens. Specifically, exenatide had a significantly longer onset time at 45 days (IQR = 11–213 days), with statistically significant differences from the onset times of the other five GLP-1 RAs (p&lt; 0.0001). Moreover, eight categories of psychiatric AEs, namely, nervousness (ROR = 1.97, 95% CI = 1.85–2.11), stress (ROR = 1.28, 95% CI = 1.19–1.38), eating disorder (ROR = 1.57, 95% CI = 1.40–1.77), fear of injection (ROR = 1.96, 95% CI = 1.60–2.40), sleep disorder due to general medical condition—insomnia type (ROR = 2.01, 95% CI = 1.60–2.52), binge eating (ROR = 2.70, 95% CI = 1.75–4.16), fear of eating (ROR 3.35, 95% CI = 1.65–6.78), and self-induced vomiting (ROR = 3.77, 95% CI = 1.77–8.03), were defined as GLP-1 RA-related psychiatric AEs through disproportionality analysis.ConclusionOur findings demonstrate a significant association between GLP-1 RAs and the development of specific psychiatric AEs. Despite the observational nature of this pharmacovigilance study and the inherent limitations of the FAERS database, our preliminary findings in this work could provide a better basis for understanding the potential psychiatric AEs that may occur with GLP-1 RA treatment, assisting clinicians to focus on these AEs and provide early intervention for optimal risk management.
Causal association of gut microbiota on spondyloarthritis and its subtypes: a Mendelian randomization analysis
Authors: Tang Jun , Mo Shiyan , Fan Lina , Fu Shihui , Liu Xiaofei 
Published: February 2024

BackgroundDespite establishing an association between gut microbiota and spondyloarthritis (SpA) subtypes, the causal relationship between them remains unclear.MethodsGut microbiota data were obtained from the MiBioGen collaboration, and SpA genome-wide association study (GWAS) summary data were obtained from the FinnGen collaboration. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance-weighted method supplemented with four additional MR methods (MR-Egger, weighted median, simple mode, and weighted mode). Pleiotropy and heterogeneity were also assessed. Reverse MR analysis was used to detect reverse causal relationships.ResultsWe identified 23 causal links between specific gut microbiota taxa and SpA levels. Of these, 22 displayed nominal causal associations, and only one demonstrated a robust causal connection. Actinobacteria id.419 increased the risk of ankylosing spondylitis (AS) (odds ratio (OR) = 1.86 (95% confidence interval (CI): 1.29–2.69); p = 8.63E−04). The family Rikenellaceae id.967 was associated with a reduced risk of both AS (OR = 0.66 (95% CI: 0.47–0.93); p = 1.81E−02) and psoriatic arthritis (OR = 0.70 (95% CI: 0.50–0.97); p = 3.00E−02). Bacillales id.1674 increased the risk of AS (OR = 1.23 (95% CI: 1.00–1.51); p = 4.94E−02) and decreased the risk of enteropathic arthritis (OR = 0.56 (95% CI: 0.35–0.88); p = 1.14E−02). Directional pleiotropy, or heterogeneity, was not observed. No reverse causal associations were observed between the diseases and the gut microbiota.ConclusionOur MR analysis suggested a genetic-level causal relationship between specific gut microbiota and SpA, providing insights into the underlying mechanisms behind SpA development mediated by gut microbiota.
Bibliometric analysis of evolutionary trajectory and prospective directions of LAG-3 in cancer
Authors: Wang Jin , Wang Siying , Zhang Yuting , Zhang Wei 
Published: February 2024

ObjectivesPerform a bibliometric analysis on the role of LAG-3 in the domain of cancer, elucidate the prevailing areas of research, and visually depict the evolutionary trajectory and prospective directions of LAG-3 research over the past twenty-three decades.Materials and methodsBetween 2000 and 2023, a comprehensive review of scholarly articles pertaining to LAG-3 research in the context of cancer was carried out using the Web of Science Core Collection (WoSCC) database. Bibliometric analysis can be conducted by taking advantage of VOSviewer (version 1.6.16) and CiteSpace (version 6.2.R4). Create a network diagram to visually represent various authors, countries, and organizations while assessing the publishing years, journals, references, and keywords.ResultsIn conclusion, 1841 records were identified and published in 587 publications. These records were authored by 12,849 individuals affiliated with 2491 institutes across 74 countries. There has been a substantial surge in publications subsequent to 2013. The USA, China, and Germany gave the majority of records, amounting to 69.69%. American institutions actively engage in collaboration with institutions located in other countries. Triebel, F., Vignali, Dario A. A., Workman, Creg J. Drake, Charles G., and Elkord, Eyad are highly regarded authors in their respective fields. However, it is worth noting that Triebel exhibits limited collaboration with other writers. The examination of the role of LAG-3 in cancer and its potential for use in clinical settings is a discernible trend, as seen by keyword analysis.ConclusionThe scientific interest in and attention towards LAG-3 has experienced a significant rise since 2013. The United States is leading the way, with China following closely behind. Promoting collaboration among writers, nations, and institutions with varied backgrounds is imperative. The discipline of immunotherapy is currently seeing ongoing progress. A thorough investigation of the distinctive cis ligand TCR-CD3 complex of LAG-3 and its signal transduction mechanism is necessary. Additionally, it is worthwhile to explore novel combinations of LAG-3 therapy.