bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategi Penerapan Produksi Bersih (Clean Production) Di Pabrik Kelapa Sawit PT. SPA
Authors: Widodo Teguh Sugeng Rahayu , Suwondo  , Zulkifli
Published: July 2024

Industri kelapa sawit diproyeksikan akan mencapai 240 juta ton permintaan produksi pada tahun 2050, yang membutuhkan pabrik pengolahan efisien dengan penanganan limbah sesuai standar. Pabrik Kelapa Sawit PT. SPA, berfokus pada pengolahan kelapa sawit dan memproduksi minyak sawit (CPO) dan inti sawit. Limbah padat, cair, dan gas merupakan hasil samping dari pengolahan. Konsep produksi bersih diajukan sebagai solusi holistik dengan dampak ekologis, ekonomis, sosial, dan teknis positif. pemborosan dan kerugian di berbagai stasiun produksi, menekankan perlunya pengurangan kuantitas dan peningkatan kualitas. Limbah buah kelapa sawit berserakan dan kebocoran minyak menciptakan lingkungan risiko tinggi dan kurang nyaman bagi pekerja. Penelitian ini bertujuan menganalisis strategi produksi bersih di Pabrik PT. Kelapa Sawit SPA, mengevaluasi implementasi, mengidentifikasi faktor dominan, dan menetapkan prioritas strategis. Survei lapangan, observasi, dan wawancara digunakan dengan metode Analytical Hierarchy Process (AHP) untuk analisis deskriptif kuantitatif. Hasil menunjukkan program housekeeping efektif sebagai strategi utama, dengan pemahaman, kesadaran, dan partisipasi karyawan sebagai faktor utama. Perbaikan perlu diterapkan, menggarisbawahi pentingnya produksi bersih dalam pabrik kelapa sawit.
WITHDRAWN: Chemerin and Sfrp5 levels in Subclinical Hypothyroid
Authors: Şerefli Köksal , Bilgici Birşen , Akcan Songül , Tomak Leman , Atmaca Ayşegül Akın
Published: July 2024

The full text of this preprint has been withdrawn, as it was submitted in error. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.
Oxysterol binding protein (OSBP) is needed for hepatitis E virus replication
Authors: Zhang Yanjin
Published: July 2024

Hepatitis E virus (HEV) is a positive-sense, single-stranded RNA virus and causes primarily acute self-limiting infections. The ORF1 of the HEV genome encodes a polyprotein around 190 kDa, which contains several putative domains, including helicase and RNA-dependent RNA polymerase. The HEV-encoded helicase is a member of the superfamily 1 helicase family and possesses multiple enzymatic functions, such as RNA 5’-triphosphatase, RNA unwinding, and NTPase, which are thought to contribute to viral RNA synthesis. However, the helicase interaction with cellular proteins remains less known. Oxysterol binding protein (OSBP) is a lipid regulator that shuffles between the Golgi apparatus and the endoplasmic reticulum (ER) for cholesterol and phosphatidylinositol-4-phosphate (PI4P) exchange and controls the efflux of cholesterol from cells. In this study, the deficiency of OSBP significantly reduced HEV replication. Further studies indicate that the HEV helicase interacted with OSBP, shown by co-immunoprecipitation and co-localization in co-transfected cells. The presence of helicase blocked OSBP preferential translocation to the Golgi apparatus. These results demonstrate that OSBP contributes to HEV replication and enrich our understanding of the HEV-cell interactions.
Emotional responses to climate change, mental health, and climate action: How are they related?
Authors: Mintz Keren Kaplan
Published: July 2024

As climate change becomes a reality, people are becoming increasingly aware of the threats associated with global warming. Many people may experience climate change as an unremitting psychological stressor associated with high levels of concern, worry and anxiety, that can emerge even in the absence of short-term or direct effects. Because emotions are related both to mitigation behavior and to promoting resilience and well-being, studying people’s emotional responses to climate change is important. This study explores the links of different emotional responses to climate change with mental health and pro-environmental behavior, using an online survey of a nationwide representative sample in Israel. An online survey of a nationwide representative sample of Hebrew speakers (N=302) revealed high levels of negative emotions, along with low levels of climate anxiety and moderate levels of positive emotions and indifference. Both climate change anxiety and negative emotions were associated with impairment in mental health. Positive emotions predicted an increase in both private-sphere and collective pro-environmental behavior, whereas indifference predicted a decrease in both types of behavior. Climate change anxiety predicted an increase in collective but not in private-sphere pro-environmental behavior. The research findings extend our understanding of the role played by different emotional responses to climate change in explaining impairment in mental health and adaptive pro-environmental behavior.
The Genomic Architecture of Circulating Cytokine Levels Points to Drug Targets for Immune-Related Diseases
Authors: Konieczny Marek J. , Omarov Murad , Malik Rainer , Richardson Tom G. , Baumeister Sebastian-Edgar , Bernhagen Jürgen , Dichgans Martin , Georgakis Marios K.
Published: July 2024

Circulating cytokines orchestrate immune reactions and are promising drug targets for immune-mediated and inflammatory diseases. Exploring the genetic architecture of circulating cytokine levels could yield key insights into causal mediators of human disease. Here, we performed genome-wide association studies (GWAS) for 40 circulating cytokines in meta-analyses of 74,783 individuals. We detected 359 significant associations between cytokine levels and variants in 169 independent loci, including 150 trans- and 19 cis-acting loci. Integration with transcriptomic data point to key regulatory mechanisms, such as the buffering function of ACKR1 acting as scavenger for multiple chemokines and the role of TRAFD1 in modulating the cytokine storm triggered by TNF signaling. Applying Mendelian randomization (MR), we detected a network of complex cytokine interconnections with TNF-b, VEGF, and IL-1ra exhibiting pleiotropic downstream effects on multiple cytokines. Drug target cis-MR paired with colocalization revealed G-CSF/CSF-3 and CXCL9/MIG as potential causal mediators of asthma and Crohn’s disease, respectively, but also a potentially protective role of TNF-b in multiple sclerosis. Our results provide an overview of the genetic architecture of circulating cytokines and could guide the development of targeted immunotherapies.
Generative-discriminative machine learning models for high-frequency financial regime classification
Authors: KOUKORINIS Andreas , PETERS Gareth W. , GERMANO Guido
Published: July 2024

We combine a hidden Markov model (HMM) and a kernel machine (SVM/MKL) into a hybrid HMM-SVM/MKL generative-discriminative machine learning approach to accurately classify high-frequency financial regimes and predict the direction of trades. The model captures temporal dependencies and key stylized facts in high-frequency financial time series by integrating the HMM to produce model-based generative feature embeddings from microstructure time series data. These generative embeddings then serve as inputs to a SVM with single-and multi-kernel (MKL) formulations for predictive discrimination. Our methodology, which does not require manual feature engineering, improves classification accuracy consistently over six trading regimes, outperforming a logistic classifier, single-kernel SVMs, a feed forward network and kernel target alignment methods. This hybrid HMM-SVM-MKL approach shows high-frequency time-series classification improvements that can significantly benefit applications in finance.
Deep Convolutional Networks for Affective Content Extraction from Textual Sources
Authors: Manda Asha Priyadarshini , Mohan A. Krishna
Published: July 2024

This paper proposes a Convolutional Neural Network (CNN) based system for classifying emotions in text data. The system tackles the challenge of automatically recognizing emotions expressed within textual content. The paper presents a comprehensive approach encompassing data preparation, model building, training, evaluation, saving, and prediction. The data preparation stage involves cleaning, balancing for imbalanced datasets, and pre-processing techniques such as tokenization and padding. The CNN model employs two branches with similar CNN layers for feature extraction. These features are then concatenated to create a richer representation. Dropout techniques are utilized during training to prevent over fitting. The system's performance is evaluated using various metrics like accuracy, precision, and recall. We visualize the learning process through training and validation curves. Additionally, confusion matrix and classification reports are employed to analyze the model's performance. Finally, the trained model and tokenizer are saved for future prediction tasks. This work offers a comprehensive framework for text emotion classification using CNNs, demonstrating its effectiveness in identifying emotions from textual data.
Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study
Authors: Ye Zhi-Xian , Chen Xuan-Yu , Li Meng-Cheng , Chen Xin-Yuan , Qiu Yu-Sen , Yuan Ru-Ying , Chen Zhi-Li , Lin Min-Ting , Hu Jian-Ping , Fu Ying , Chen Wan-Jin , Wang Ning , Gan Shi-Rui
Published: July 2024

Background: Spinocerebellar ataxia type 3 (SCA3) is a hereditary polyglutamine disease, caused by abnormally expanded cytosine–adenine–guanine (CAG) repeats in ATXN3 gene. It is classically characterized by cerebellar and spinal cord atrophy and presents with progressive ataxia. we here investigated the associations between expanded CAG repeat size, brain and spinal cord volume loss, and motor functions in SCA3.
Methods: In this prospective cross-observational study, we analyzed 3D T1-weighted MRIs from 92 patients with SCA3 and 42 healthy controls using voxel-based morphometry and region of interest approaches. Associations between CAG repeat size, brain and spinal cord volume loss, and International Cooperative Ataxia Rating Scale (ICARS) score were investigated using partial correlation and mediation analyses. Sample sizes of potential markers were calculated.
Results:Compared with healthy controls, SCA3 patients had lower cerebellar volume and cervical spinal cord area. SCA3 patients evolved along a stage-independent decline that began in the cerebellum, progressed to spinal cord, brainstem, thalami, and basal ganglia, and extensive subcortex. CAG repeat size was associated with right cerebellar lobule IV volume (r = -0.423, P < 0.001) and cervical spinal cord area (r = -0.405, P < 0.001), and higher ICARS (r = 0.416, P < 0.001). Mediation analysis revealed an indirect effect of CAG repeat size on ICARS through spinal cord. Sample sizes estimation revealed that a minimum sample size was achieved with spinal cordmeasures.
Conclusions: CAG repeat size influenced cerebellar lobule IV and cervical spinal cord volume loss. Our results indicated the potential of cervical spinal cord area as a marker for disease progression and sample size estimations in future SCA3 clinical studies.
The influence of ENSO-type on rainfall characteristics over Southern Africa during the austral summer
Authors: Mpheshea Lerato Elizabeth , Blamey Ross C. , Reason Chris J.C.
Published: July 2024

Although the El Niño-Southern Oscillation (ENSO) is the leading mode of climate variability in southern Africa during the austral summer season, the impacts are nonlinear and not all events result in the expected impact. Limited work has been carried out to explore the role ENSO diversity plays in southern African climate, which this study aims to address. Here, the influence of El Niño diversity on rainfall characteristics and whether the impact evolves on sub-seasonal scales are examined. Two broad types of El Niño events, namely Eastern Pacific (EP) and Central Pacific (EP) events, are first determined by the location of the positive SST anomaly in the equatorial Pacific. For the 1950-2022 period, 9 EP El Niño events and 10 CP El Niño events are identified. Results show significant variability in ENSO impacts on a sub-seasonal scale across southern Africa during the summer half of the year (October-March). EP events affect rainfall throughout the summer, with the strongest impacts in the core months (Dec-Jan), characterized by less rainfall, more frequent dry spells and extended dry periods. EP events have a stronger relationship with various rainfall characteristics across most of southern Africa compared to CP events. Consequently, the likelihood of experiencing a significant summer rainfall deficit is higher during EP events. These findings indicate that traditional seasonal definitions, like JFM, or generalizing ENSO as a single type of event, may be inadequate in assessing ENSO-induced rainfall impacts from a seasonal forecasting perspective.
Predictors of massive transfusion in patients with hollow organ injury after blunt abdominal trauma: a cohort of blunt bowel mesenteric injury
Authors: Hsieh Ting-Min , Chuang Po-Chun , Liu Chun-Ting , Wu Bei-Yu , Hsieh Ching-Hua , Cheng Fu-Jen
Published: July 2024

Background
Massive transfusion (MT) is life-saving for patients with exsanguination, especially after blunt abdominopelvic trauma, due to subtle manifestations. Blunt bowel mesenteric injuries (BBMI), besides their potential risk of peritonitis, are still one of the few indications for emergency laparotomy for hemorrhagic shock in the era of non-operative management. Early prediction of the necessity for MT is a critical point in resuscitation.
Methods
This retrospective study reviewed the data of hospitalized patients with trauma between 2009 and 2022, and included 163 adult patients with surgically proven BBMI. The patients were divided based on the presence or absence of MT before emergency laparotomy. Associated injury parameters and bowel mesenteric injury characteristics were used in multivariate regression analysis to identify independent predictors of MT.
Results
The MT (+) group included 30.6% of patients (n = 50). Compared to the MT (-) group, BBMI patients receiving MT had worse clinical injury severity, vital signs, and prognosis; received more units of blood products and more invasive treatments; had more isolated mesenteric injury or combined injury; and had both higher morbidity and mortality rates (94% vs. 55.8%, p < 0.001 and 32% vs. 4.4%, p < 0.001). In multivariate analysis, the presence of traumatic brain injury (TBI) (odds ratio [OR] = 6.7, 95% confidence intervals [CIs]: 1.66–27.02) and pelvic fracture (OR = 6.01, 95% CIs = 1.45–24.89) was identified as an independent predictor of MT after adjusting for confounding factors.
Conclusions
Almost half the patients with BBMI present with shock episodes, and one-third of them require MT before laparotomy, reflecting the critical status for their exsanguination. Patients with associated TBI and pelvic fracture injuries are at increased risk of MT and need to be prioritized for resuscitation.
Development of a Pellet Extruder for Blending Different Materials and Study on the Properties of Eco-friendly Flame Retardant Materials Printed Using a Large-scale 3D Printer
Authors: Jung minsu , Ha Jeong-Ung , Park Jong-kyu
Published: July 2024

This study aims to design and fabricate a pellet extruder capable of blending different materials for the application of flame-retardant building materials in 3D printing and to evaluate the properties of eco-friendly flame-retardant materials printed using a large-scale 3D printer. The main content of the research is as follows: To ensure the printing stability of the large 3D printer, the deflection amount of the axis due to the weight of the pellet extruder was verified through structural analysis. This made it possible to achieve stable printing even on a large bed (1000mm x 1000mm). Next, a pellet extruder capable of blending different materials was developed to quickly collect initial mixing ratios and temperature data, and specimen printing was conducted using this extruder. The flame-retardant performance and mechanical properties of the printed flame-retardant material were evaluated, and PLA specimens mixed with calcium carbonate at various ratios from 5% to 20% were produced to conduct flame-retardant performance tests and tensile tests according to UL-94 standards. As a result, it was found that the flame-retardant performance improved as the calcium carbonate content increased, and the optimal mixing ratio was derived. Finally, to verify the printing stability of the extruder and large 3D printer, a honeycomb composite structure was printed continuously for 1 hour and 30 minutes, and it was confirmed that continuous printing was possible with a maximum error of 1mm. The proposed development systems satisfy both stable printing of large composite structures and excellent flame-retardant performance, confirming the potential for use as eco-friendly building material prints.
The foresight methodology for transitional shale gas reservoirs prediction based on a knowledge graph
Authors: Li Wenyu , Zhao Jingtao , Qiu Zhen , Gao Wanli , Peng Hongjie , Zhang Qin
Published: July 2024

The sedimentary environment in the eastern Ordos area of China is complex and contains a large number of transitional facies environments. Yet, there are many characteristics such as large vertical lithology changes, complex lateral sedimentary environment changes, small monolith thickness and large organic matter content changes, which lead to large uncertainty in the prediction of favorable areas for transitional shale gas. As the intricate reservoirs continue to unfold, the conventional linear prediction methods find themselves facing an arduous path to meet the demands of development. The ever-evolving complexity of these reservoirs has outpaced the capabilities of these traditional approaches. It becomes apparent that a more comprehensive and adaptable approach is necessary to navigate the intricacies of these reservoirs and unlock their hidden potential. Therefore, we put forward a method of introducing knowledge graph into shale gas reservoir prediction by using big data technology. Because artificial intelligence big data relies heavily on data tags, it is particularly important for the construction of tags. Firstly, a top-down knowledge graph in the field of reservoir prediction is constructed to determine the key parameters used in prediction, namely porosity, total organic carbon (TOC) and brittleness index. Secondly, the decision tree knowledge graph optimization label is constructed in a bottom-up way. The key parameter of this prediction is the knowledge graph obtained according to the professional knowledge of reservoir prediction, so as to optimize the school label of U-net and reduce the workload of artificial judgment. The results of the combination of the two methods are applied to 11 wells in Daji area of Ordos, and the experimental results are consistent with the actual situation of the reservoir. Based on the foundation of theoretical knowledge, this method enhances the efficiency and accuracy of interpretation and evaluation. It provides fundamental and technical support for the selection of favorable areas in shale gas exploration and the evaluation of exploration and development prospects, particularly in transitional shale gas areas, which is innovative and advanced in the field.
Three-dimensional stability calculation method and application of intermediate bridge supporting consequent bedding slope in open-pit mine
Authors: Wang Dong , Liang Zuchao , Li guanghe , Xv Yongchao , Zhao lichun , Zhang Jie
Published: July 2024

Solving the dynamic synergistic design challenge of slope and intermediate bridge during parallel stripping of multi-pits is crucial to realizing both safe production and economic benefits of mines. Based on the analysis of the failure mode of the intermediate bridge supporting consequent bedding slope, constructed a 3D mechanical model of the intermediate bridge, and analyzed the 3D supporting effect quantitatively. Combined with Mohr-Coulomb shear strength theory, a 2D equivalent method considering the 3D supporting effect of intermediate bridge under different failure modes is proposed, and a 3D stability calculation method of slope under this effect is established. In addition, the main influencing factors of the intermediate bridge supporting effect are analyzed. The 3D stability coefficient regression model is constructed by using the response surface method, and the validity of the model for solving practical engineering problems is verified by engineering application. The results show that when considering the combined sliding failure mode, the design bottom width d should be given priority in the establishment of supporting structures such as dump bridges, for the intermediate bridge demolition design project, the design bridge length should be given priority b. The interaction between the bottom width d and the bridge height h has a significant effect on the 3D stability of the slope; For the shear dilatancy failure mode, the supporting and demolition engineering should give priority to the design of bridge height h and bottom width d respectively. The interaction between bridge height h and bridge length b has the most significant effect on the 3D stability of the slope. The error rate between the 3D stability calculation results and the predicted value of the regression model is 1.9–3.3%, and the regression model can fully meet the actual needs of the project. This study lays a theoretical and application foundation for the dynamic collaborative design, stability control and engineering implementation of slope and intermediate bridge in multi-pit parallel stripping open-pit coal mine.
Investigation of the Applicability of the Boer Formula for Estimating the Angular Velocity of Rotation of a Small Spacecraft by Measuring the Components of the Induction Vector of the Earth's Magnetic Field in Evaluating Micro-Accelerations and Forming Control Laws
Authors: Sedelnikov Andry , Skidanov Roman , Taneeva Anastasia , Manukyan Luisa , Ivanushkin Maksim , Mordanov Marsel
Published: July 2024

The paper presents studies on the correctness of the application of the simplified Boer formula for estimating the components of the angular velocity vector of the spacecraft using the example of the small ISOI spacecraft (SXC3-219). The simplification consists in neglecting the total derivative of the induction vector of the Earth's magnetic field in time compared to the local derivative. This is due to the fact that measurements are carried out quite often. Therefore, the magnetic induction vector in two adjacent dimensions can be considered unchanged. The aim of the work is to estimate the error in determining the angular velocity due to this simplification. The presented results show the admissibility of neglecting the full derivative, provided that the measurement frequency is sufficient. Reference metrological tests were carried out, in which a gyroscopic angular velocity vector meter was selected as the reference measuring instrument. The errors in the estimates of micro-accelerations and the control moment, which are a consequence of the error in determining the angular velocity, are calculated.
Reliability Research of Thyristors for HVDC Transmission System
Authors: XU Yang , Pang Lei , Xie Tianxi , Chen Zhengguang , Guo Jun
Published: July 2024

The long-term operation performance of HVDC transmission systems is significantly influenced by the reliability of thyristors. However, the current reliability research of thyristors is mainly based on the leakage current and there is no comprehensive degradation characteristics of thyristors. In this article, the degradation characteristics of thyristors under voltage and temperature accelerated ageing tests are obtained, including the reverse recovery characteristic, on-state characteristic, blocking characteristic and gate characteristic. The reverse recovery characteristic obviously degrades under the voltage accelerated ageing tests. The reverse recovery charge and reverse recovery time decrease by over 10% after the tests. Seven thyristors operating for a certain number of years from two HVDC stations are tested, and the results verify the thyristor degradation characteristics obtained from the ageing tests. Moreover, the mechanisms of the leakage current and reverse recovery characteristic are analyzed in detail.
Functional and Symbolic Aspects of App Use for Improving Physical Activity: A Six-month Prospective Analysis
Authors: Takano Keisuke , Oba Takeyuki , Katahira Kentaro , Kimura Kenta
Published: July 2024

Background:
Mobile health technology plays an important role in improving physical activity (PA). However, commercial healthcare applications for smartphones (apps) have poor retention, and understanding how people adopt and integrate app use in daily life is critical. We investigated the use patterns of PA apps and explored the use styles that are predictive of (dis)continuation of use and changes in PA levels over time.
Methods:
We analyzed two-wave longitudinal survey data concerning commercial PA-app use, which included 4465 respondents (mean age = 50.7; 1932 women) identified as PA-app users at baseline. The participants completed a questionnaire regarding how and for what purpose they used the apps. A six-month follow-up survey was administered that asked participants about their current app use and PA levels.
Results:
At baseline, 2737 were identified as long-term users of a PA app (i.e., use for more than six months). Long-term users reported appreciating the lifestyle management aspects (e.g., constant accessibility to health information, tracking, and monitoring PA), whereas short-term users indicated that they appreciated their app’s distraction and building relationships (e.g., finding like-minded peers) aspects. Prospective analyses demonstrated that lifestyle management was associated with continuing to use the app and increased PA levels at the 6-month follow-up, whereas distraction predicted discontinuing the use of the app and decreased PA levels.
Conclusions:
These findings suggest that on-purpose use (i.e., using a PA app to improve one’s PA) is the key feature of being in an appropriation state, whereas off-purpose use may hinder app use, leading to less active lifestyles. The implications of appropriation theory and practice are also discussed.
School-based immunization policy compliance in preschools of Karachi, Pakistan: An explanatory sequential mixed-method study
Authors: Samnani Saira , Azam Syed Iqbal , Rizvi Narjis
Published: July 2024

Background
Healthcare providers in schools play a crucial role in ensuring student wellness and maintaining effective communication with parents regarding their children's health. In 2022, the Government of Pakistan introduced the national school-based immunization policy, but the factors affecting policy compliance and the role of preschool healthcare providers in it are still unexplored. Thus, the study aims to assess the implementation of the school-based immunization policy in preschools, considering the presence of preschool healthcare providers and other factors that may influence policy compliance.
Methods
The study used an explanatory sequential mixed-method design. It included all preschools in Karachi that met the defined eligibility criteria. Preschools were surveyed using systematic sampling, with data obtained from preschool administrators through structured questionnaires. Subsequently, administrators were approached for in-depth interviews. Descriptive statistics and multiple linear regression along with thematic framework analysis were used to analyze quantitative and qualitative data respectively. The findings from both datasets were triangulated.
Results
A total of 223 preschools were surveyed and 9 in-depth interviews were conducted with preschool administrators. The survey revealed that 97 (43.5%) of the preschools relied on manual vaccination record-keeping methods, consistent with 3 out of 9 preschools found in in-depth interviews. 179 (80.3%) administrators reported that parents cooperate with school management in vaccinating their child(ren) at preschool, consistent with qualitative findings. 200 (89.7%) administrators were unaware of EPI, consistent with 7 out of 9 in-depth interviews. A significant mean difference (3.91; 95% CI 2.15–5.66) in compliance scores was observed between preschools with and without healthcare providers. The final model included the vaccination records storage method (β 5.05; 95% CI 3.47–6.63), parents’ cooperation (β 1.32; 95% CI 0.16–2.49), and a statistically significant interaction between the presence of preschool healthcare providers and awareness of EPI among preschool administrators at a p-value < 0.1.
Conclusion
The healthcare providers in preschools facilitate school-based immunization policy compliance, while the absence of staff training for vaccination record-keeping and supporting vaccination drives impedes compliance. Understanding and addressing these factors can optimize policy compliance.
Pharmaceutical quality of dispersible diclofenac tablets in the Saudi market
Authors: Alhabardi¹ Samiah , Mahrous¹ Gamal , Alshahrani¹ Asma , Taha Ehab
Published: July 2024

The fundamental objective in developing any drug delivery approach is to achieve effective and safe therapy. Medications classified as generics are those that contain the same active ingredients and have the same quality as the reference medications. Several generic drugs are available on the market, all at a reasonable cost. In this study, the quality of Three generic brands of diclofenac dispersible tablets (DT) available in the Saudi market was assessed, namely: G1 and G2, and G3.
Except for the borderline performance of one generic formulation (G3), all formulations passed in vitro quality tests according to the United States Pharmacopoeia. According to the US Pharmacopoeia, every generic formulation passed in vitro quality tests, except for one generic formulation (G3) that performed inconclusively. All brands demonstrated minimal weight variation, with average weights falling within the acceptable range of ±5% from the mean and a rapid dispersion time of around 5 sec. All the brands displayed acceptable friability and minimal weight loss. The potency results demonstrated that all of the three brands complied with United States Pharmacopeia (USP) specifications, which typically fall between 90% and 110% of the labeled amount. G1 and G2 passed the content uniformity test in their first attempt. G3 initially failed the content uniformity test but passed upon retesting with additional samples. G1 and G2 tablets passed the USP Acceptance criteria in stage one, and G3 tablets met the requirements in stage two. G1 showed the highest DE (%78.83), followed by G2 (%72.23), and G3 (%67.50). The G1 dissolution data, which showed the highest dissolution efficiency, were used as the reference product to calculate the similarity factor (f2 (ratio. G1 (Reference) and G2 with an f2 of (58.3) have similar dissolution profiles. G3, with an f2 of (47.5) showed borderline performance. This study highlights the importance of post-marketing evaluations of generic drugperformance.
Textual emotion detection – A systematic literature review
Authors: Truong Vinh
Published: July 2024

Textual emotion detection is a critical area of study with significant applications in business, education, and healthcare. Despite substantial theoretical advancements over the years, there is a notable gap in the practical implementation of these methods in the aforementioned fields. The techniques currently available do not yet seem ready for real-world application. This study offers a comprehensive review of existing approaches, datasets, and models used in textual emotion detection. Its primary objective is to identify the challenges faced in both current literature and practical applications. The findings reveal that textual datasets annotated with emotional markers are scarce, making it difficult to develop robust supervised classification models for this task. There is also a pressing need for improved models that can accurately categorize a wider range of emotional states distinctly. Finally, there is a demand for techniques capable of dimensionally detecting valence, arousal, and dominance scores from emotional experiences. These challenges stem not only from the models and applications themselves but also from the readiness of current approaches and datasets in the rapidly evolving fields of machine learning and affective computing.
High expression of LncRNA HOTAIR is a risk factor for temozolomide resistance in glioblastoma via activation of the miR-214/β-catenin/MGMT pathway
Authors: Lan Tian , Quan Wei , Yu Dong-Hu , Chen Xi , Wang Ze-Fen , Li Zhi-Qiang
Published: July 2024

Backgroud:
HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. However, the mechanisms underlying HOTAIR-mediated TMZ resistance remains poorly understood.
Methods
HOTAIR expression in glioma-related public datasets and drug response estimation were analyzed using bioinformatics. These findings were verified by overexpressing HOTAIR in TMZ-sensitive U251 cells and/or silencing HOTAIR in resistant U251 cells (U251R). The cytotoxic effects were evaluated using cell viability assay and flow cytometry analysis of cell clycle and apoptosis.
Results
HOTAIR was upregulated in TMZ-resistant GBM cell lines and patients with high HOTAIR expression responded poorly to TMZ therapy. HOTAIR knockdown restored TMZ sensitivity in U251R cells, while HOTAIR overexpression conferred TMZ resistance in U251 cells. Wnt/β-catenin signaling was enriched in patients with high HOTAIR expression; consistently, HOTAIR positively regulated β-catenin expression in U251 cells. Moreover, HOTAIR-mediated TMZ resistance was associated with increased MGMT protein level, which resulted from the HOTAIR/miR-214-3p/β-catenin network. GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and β-catenin.
Conclusions
HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.
Nomograms for Predicting Overall and Cancer-Specific Survival Among Second Primary Endometrial Cancer in Primary Colorectal Carcinoma Patients
Authors: LIU linli , JIN Qiong
Published: July 2024

Endometrial cancer (EC) is one of the most frequent gynecologic cancers, approximately 20% of patients are regarded as high-risk with poor prognosis. However, more details of patients with second primary endometrial cancer (SPEC) after colorectal cancer (CRC) remain poorly understood.We therefore purposed to construct two nomograms to predict 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates to facilitate clinical application. Nomograms for predicting OS and CSS were constructed and validated. The receiver operating characteristic curves, calibration plot, decision curve analysis, C-index, net reclassification improvement, and integrated discrimination improvement were applied to evaluate the predictive performance. Finally, the Prognostic index was calculated and used for risk stratification of Kaplan-Meier survival analysis based on different treatment options. Nomograms of OS and CSS were formulated based on the independent prognostic factors utilizing the training set. The 3- and 5- years of OS nomogram demonstrated good discrimination (AUC = 0.840 and 0.829, respectively), well-calibrated power, and excellent clinical effectiveness. Our nomograms of predicting OS and CSS had a concordance index of 0.801 and 0.866 compared with 0.676 and 0.746 for the AJCC staging system, and more importantly, demonstrated a better forecast accuracy. Chemoradiotherapy displayed a significant survival benefit in the high-risk groups, but proceeding to surgery plus chemotherapy showed a favorable survival for the low groups based on all patients. We developed and internally validated multivariable models that predict OS and CSS risk of SPEC in patients with a CRC to help clinicians make applicable clinical decisions for patients.
Magnetic nanoparticle-decorated metal organic frameworks for chemiluminescence detection of glutathione
Authors: Ma Xiaohu , Jiang Peiyu , Geng Jingbo , Li Xinyi , Jin Yan , Li Baoxin , Liu Wei
Published: July 2024

In this study, a chemiluminescence (CL) method for determination of glutathione (GSH) was developed with magnetic nanoparticle-decorated metal organic frameworks (Fe3O4 NPs@Cu-TATB). The composite material was synthesized via a hydrothermal method and glutathione (GSH) can be tested by both visual and chemiluminescence (CL) methods. The synthesized Fe3O4 NPs@Cu-TATB exhibited excellent catalytic activity in the luminol-H2O2 CL system. The mechanism revealed that three types of oxygen-containing radicals (ROS) was generated in this system. As GSH can reduce the catalytic effect of generated ROS radicals, the inhibiting CL signal was produced in the Fe3O4 NPs@Cu-TATB-luminol-H2O2 system. Based on the established CL system, the detection limits for GSH using CL and visual methods were found to be 0.3 µM and 0.7 µM, respectively. This low-cost and convenient detection method can be applied to the analysis of GSH content in human blood.
Genome-wide functional CRISPR screen reveals CDK7 as a targetable therapeutic vulnerability for head and neck cancer
Authors: Otero-Rosales María , Álvarez-González Miguel , de Luxán-Delgado Beatriz , Marro Sonia Del , Pozo-Agundo Esperanza , Rodríguez-Santamaría Mar , López-Fernández Ana , Corte-Torres Daniela , Granda-Díaz Rocío , Álvarez-Teijeiro Saúl , Lorz Corina , García-Escudero Ramón , Rodrigo Juan Pablo , Tzelepis Konstantinos , Vassiliou George , Álvarez-Fernández Mónica , García-Pedrero Juana María , Hermida-Prado Francisco
Published: July 2024

Background: Head and neck squamous cell carcinoma (HNSCC) remains a challenging prevalent lethal malignancy, with still scarce targeted therapies and rather limited clinical benefit. We conducted an optimized genome-wide functional CRISPR screen aimed at identifying actionable genetic vulnerabilities for rapid preclinical evaluation as novel targeted therapies. Cyclin-dependent kinases (CDKs) were prioritized as pivotal in cancer therapy.
Methods: Whole-genome CRISPR KO screen was performed in a panel of five HNSCC cell lines. CDK7 was selected for further functional and molecular characterization. The effects of CRISPR CDK7 knockout (KO) and CDK7-selective inhibitors were thoroughly investigated in cellular models using viability, colony formation and apoptosis assays, cell cycle analysis, and global transcriptomics by RNAseq. CDK7 inhibition was also therapeutically evaluated in mouse xenografts and patient-derived organoids (PDOs).
Results: CDK7 was identified as an essential gene across all five HNSCC cell lines screened. Genetic and pharmacological CDK7 inhibition significantly and consistently reduced tumor cell proliferation due to generalized cell cycle arrest and apoptosis induction. CDK7 KO, YKL-5-124 and samuraciclib also showed a potent antitumor activity effectively abrogating tumor growth in HNSCC PDOs and also in mouse xenograft models without significant toxicity. Mechanistically, CDK7 inhibition led to a broad downregulation of gene sets for cell cycle progression, DNA repair, and massively reduced the transcription of several essential genes and untargetable vulnerabilities identified by our CRISPR screen.
Conclusions: CDK7 emerges as a promising targetable therapeutic vulnerability for HNSCC. Our study provides broad-based evidence for the robust antitumor activity of CDK7-selective inhibitors in disease-relevant preclinical models, strongly supporting patient testing.
Superconductivity in bcc-selenium under megabar pressure
Authors: Wu Zhongyan , Fedotenko Timofey , Giordano Nico , Kim Jaeyong
Published: July 2024

We report enhanced superconductivity in the selenium on the verge of the β-Po–bcc phase transition, achieving up to 9.4 K at 140 GPa. The onset of superconductivity is confirmed by a direct zero-resistance drop R(T), and its nature was further validated by its suppression under an external magnetic field, µ0Hc(0) = 0.26 T at 140 GPa. An anomalously high R(T) peak preceding the zero resistance state suggests granular superconductivity. Our studies indicate that selenium does not react with hydrogen at 182 GPa at room temperature nor 102 GPa with laser heating to 3000 K, implying that the synthesis of selenium hydride requires higher energy conditions than the ones predicted theoretically. Our findings offer insights into the mechanism of phase-transition-related enhanced superconductivity and motivate further study into the search for high Tc superconductors in elements at extremely high pressure.
The negative chronotropic effects of (±)-propranolol and (±)- 4-NO 2 -propranolol in the rat isolated right atrium are due to blockade of the 6-nitrodopamine receptor
Authors: Oliveira Denis Lima , Cardoso Vinicius Francisco , Britto-Júnior Jose , Fuguhara Vivian , Frecentese Francesco , Sparaco Rosa , Santagada Vincenzo , Caliendo Giuseppe , Pupo André Sampaio , Antunes Edson , Nucci Gilberto
Published: July 2024

The positive chronotropic action induced by 6-mitrodopamine (6-ND) is selectively blocked by β1-adrenoceptor antagonists at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline. Here the effects of (±)-propranolol, (±)-4-NO2-propranolol, and (±)-7-NO2-propranolol, were investigated in the rat isolated right atrium. The atrium was mounted in glass chambers containing gassed (95%O2:5%CO2) and warmed (37°C) Krebs-Henseleit’s solution, and the isometric tension registered (PowerLab system). (±)-propranolol, (±)-4-NO2-propranolol and (±)-7-NO2-propranolol, caused concentration-dependent falls in the spontaneous atrial frequency (pIC50 were 4.80±0.10, 4.64±0.10, and 4.95±0.10, respectively). The calculated pA2 values for (±)-propranolol, (±)-4-NO2-propranolol, and (±)-7-NO2-propranol obtained for noradrenaline-induced positive chronotropic effects were 8.44±0.08, 6.41±0.07, and 9.21±0.29, respectively. The positive chronotropism induced by 6-ND (10pM) was blocked by (±)-propranolol (1mM), and (±)-4-NO2-propranolol (30nM). (±)-7-NO2-propranol (1mM) had no effect on 6-ND (10pM)-induced increases in atrial rate. The pIC50 of (±)-propranolol, (±)-4-NO2-propranolol and (±)-7-NO2-propranolol were significantly shifted to the right in L-NAME treated atria. The discrepancy between pA2 values of (±)-propranolol and its respective pIC50 indicates that the falls in atrial rate induced by (±)-propranolol should not be attributed to b-adrenergic antagonism. The reduced chronotropism by (±)-propranolol (10µM) was unaffected by the sodium channel inhibitors tetrodotoxin (1µM) and lidocaine (10µM) but abolished in atria pre-treated with (±)-4-NO2-propranolol (10µM). The finding that (±)-propranolol causes falls in spontaneous atrial rate only in concentrations that affect 6-ND positive chronotropic effect, confirms the role of this catecholamine as endogenous modulator of heart chronotropism. (±)-4-NO2-propranolol behaves as a selective antagonist of 6-ND in the rat isolated atrium.
Enhancing Machine Learning Models and Classification Accuracy with Advanced Attention Mechanisms
Authors: Donthu Somasekhar , Nassa Vinay Kumar , Mohan Chinnem Rama , Keerthika T. , Krishnam Nagendra Prasad , Prasad Ch Raghava , Kapila Dhiraj
Published: July 2024

This paper provides a detailed discussion of multiple machine learning algorithms and pays close attention to their use, advantages, and disadvantages. Specifically, the Random Forest classifier is highlighted for being more effective with a classification accuracy of 93% being achieved in a binary classification problem. The current method proves superior to known methods and preserves the spatial relationships, thus solving the vanishing gradient problem with the help of two kinds of attention mechanisms. This paper also examines various techniques, such as convolutional neural networks, k-means clustering, and collaborative filtering, explaining how these methods can be applied and optimized. Thus, the rationale of the paper lies in comparison of the above-mentioned methods, emphasizing the significance of modern approaches to ensemble learning for the improvement of model accuracy and stability. Moreover, the paper highlights areas for future research to explore, such as hyper parameters tuning, integration with deep learning frameworks, and use cases in practice. As a result, the presented results can be useful for more advanced studies in the field of machine learning as well as for practical applications for various domains when it is necessary to develop more effective approaches to the use of big data.
Passive and Discrete Sampling of Neonicotinoid Pesticides in Saginaw, Michigan (United States) and Implications for the Protection of Aquatic Life
Authors: Nedrich Sara , Bowman Sarah , Stieber Elizabeth , Rhodes Geoff , Armstrong Brandon
Published: July 2024

Neonicotinoid pesticides are widely applied in urban and agricultural settings despite their toxicity to aquatic organisms at low concentrations. Monitoring for six neonicotinoids (acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, thiamethoxam) in the Saginaw River watershed of Michigan shows detections of imidacloprid exceeding final chronic values (FCVs) developed to protect aquatic life. The study design implemented both discrete and passive surface water sampling to capture the episodic nature of pesticide release. Fourteen sites were sampled monthly from August-October 2021 and April-July 2022. One or more neonicotinoids were detected in 86% of discrete and 100% of passive samples. Imidacloprid was detected at the highest maximum concentration (220 ng L-1), followed by clothianidin (98 ng L-1), and thiamethoxam (32 ng L-1). Development of aquatic life values for imidacloprid, clothianidin, and thiamethoxam, pursuant to Michigan statute and Rule 57 (Water Quality Standards), resulted in FCVs of 29 ng L-1, 81 ng L-1, and 280 ng L-1, respectively. Seven out of 14 sample locations exceeded the FCV for imidacloprid. The most sensitive species included in derivation of neonicotinoid aquatic life values included mayflies (Neocloeon triangulifer, Cloeon sp., and McCaffertium sp.) and a midge (Chironomus dilutus). This study provides new insight on monitoring for neonicotinoid pesticides and weighs the costs and benefits of passive and discrete sampling methodologies.
Regulation Mechanism of Nitrite Degradation in Lactobacillus plantarum WU14 Mediated by Fnr
Authors: Chen Shaoxian , Zeng Hao , Qiu Hulin , Yin Aiguo , Shen Fengfei , Li Ying , Xiao Yunyi , Hai Jinping , Xu Bo
Published: July 2024

Fumarate and nitrate reduction regulatory protein (Fnr), as a global transcriptional regulator, could directly or indirectly regulate many genes in different metabolic pathways at the top of the bacterial transcription regulation network. The present study aimed to explore the regulatory mechanism of Fnr-mediated nitrite degradation in Lactobacillus plantarum WU14 through gene transcription and expression analysis of oxygen sensing and nir operon expression regulation by Fnr, and the interaction and the mechanism of transcriptional regulation between Fnr and GlnR under nitrite stress. After the purification of Fnr and GlnR by GST tags, they were successfully expressed in Escherichia coli by constructing an expression vector. The electrophoresis mobility shift assay and qRT-PCR results indicated that Fnr could specifically bind to the PglnR and Pnir promoters and regulate the expression of nitrite reductase (Nir) and GlnR. After 6-12 h of culture, the expression of fnr and nir under anaerobic condition (A) were higher than that under aerobic condition (O), and the expression of these two genes increased with the addition of NaNO2 during aerobic culture. Overall, the present study results indicated that Fnr could not only directly participate in the expression of Nir and GlnR but also indirectly regulate the expression of Nir through GlnR regulation.