bluuebunny/crossref_metadata_2025 huggingface dataset:
An Intelligent Chinese Driver Road Performance Assessment Model (RPAM) for Future Licensing Examinations
Authors: Gong Jianguo , Zhang Boao , Liu Yibing , Lu Jiayi , Ma Yuan , Cao Yaoguang
Published: December 2023

As the demand for private vehicles rises, there has been a gradual increase in the number of motor vehicles on the roads, leading to a growing concern about addressing traffic safety. Currently, China’s approach to assessing driver capabilities remains rooted in traditional, non-intelligent, and standardized evaluation methods based on examination subjects. The traditional model often falls short in providing constructive feedback on a driver’s real-world vehicle handling abilities, as many of the examination subjects can be practiced in advance to achieve a mere passing result, which, undoubtedly, increases the likelihood of underqualified drivers on the road. To address the issues of the current examination-oriented driver evaluation system in China, we propose a road performance assessment model (RPAM) that assesses drivers comprehensively by evaluating their road environment perception and vehicle operation abilities based on an in-vehicle and out-vehicle perception system. The model leverages patterns of the driver’s head posture, along with real-time information on the vehicle’s behavior and the road conditions, to quantify various performance metrics related to reasonable operation processes. These metrics are then integrated to generate a holistic assessment of the driving capabilities. This paper ultimately conducted tests of the RPAM on one actual examination route in Beijing. Two drivers were randomly selected for the examination. The model successfully computed the overall ability scores for each driver, validating the effectiveness.
Alternative Fuels for the Marine Sector and Their Applicability for Purse Seiners in a Life-Cycle Framework
Authors: Perčić Maja , Vladimir Nikola , Koričan Marija , Jovanović Ivana , Haramina Tatjana
Published: December 2023

Fossil fuel combustion is a major source of Greenhouse Gases (GHGs), which cause global warming. To prevent further increases in anthropogenic GHGs, the global community needs to take action in each segment of the economy, including the shipping sector. Among different measures for reducing shipping emissions, the most promising one is the replacement of conventional marine fuels with alternatives. According to the International Maritime Organisation’s regulations, ships engaged in international shipping need to reduce their annual emissions by at least 50% by 2050. However, this does not apply to fishing vessels, which are highly dependent on fossil fuels and greatly contribute to air pollution. This paper investigates the environmental footprint of a fishing vessel (purse seiner) through the implementation of various alternative fuels. Within the research, Life-Cycle Assessments (LCAs) and Life-Cycle Cost Assessments (LCCAs) are performed, resulting in life-cycle emissions and lifetime costs for each alternative, which are then compared to a diesel-powered ship (baseline scenario). The comparison, based on environmental and economic criteria, highlighted methanol as the most suitable alternative for the purse seiner, as its use onboard resulted in 22.4% lower GHGs and 23.3% lower costs in comparison to a diesel-powered ship.
Toward a Model to Evaluate Machine-Processing Quality in Scientific Documentation and Its Impact on Information Retrieval
Authors: Suárez López Diana , Álvarez-Rodríguez José María , Molina-Cardenas Marvin
Published: December 2023

The lack of quality in scientific documents affects how documents can be retrieved depending on a user query. Existing search tools for scientific documentation usually retrieve a vast number of documents, of which only a small fraction proves relevant to the user’s query. However, these documents do not always appear at the top of the retrieval process output. This is mainly due to the substantial volume of continuously generated information, which complicates the search and access not properly considering all metadata and content. Regarding document content, the way in which the author structures it and the way the user formulates the query can lead to linguistic differences, potentially resulting in issues of ambiguity between the vocabulary employed by authors and users. In this context, our research aims to address the challenge of evaluating the machine-processing quality of scientific documentation and measure its influence on the processes of indexing and information retrieval. To achieve this objective, we propose a set of indicators and metrics for the construction of the evaluation model. This set of quality indicators have been grouped into three main areas based on the principles of Open Science: accessibility, content, and reproducibility. In this sense, quality is defined as the value that determines whether a document meets the requirements to be retrieved successfully. To prioritize the different indicators, a hierarchical analysis process (AHP) has been carried out with the participation of three referees, obtaining as a result a set of nine weighted indicators. Furthermore, a method to implement the quality model has been designed to support the automatic evaluation of quality and perform the indexing and retrieval process. The impact of quality in the retrieval process has been validated through a case study comprising 120 scientific documents from the field of the computer science discipline and 25 queries, obtaining as a result 21% high, 39% low, and 40% moderate quality.
Gain-Scheduled Model Predictive Control for Cart–Inverted-Pendulum with Friction and Disturbances
Authors: He Jue , Li Yongbo , Wei Ziang , Huang Zixin
Published: December 2023

The cart–inverted pendulum system (CIPS) is a typical example of underactuated mechanical systems. For the CIPS with friction and disturbances, a gain-scheduled model predictive control method is proposed to achieve the upright stabilization objective of the single inverted pendulum (SIP) while controlling the cart to reach a desired new position. To this end, first, a dynamic equation of the CIPS with friction and disturbances is formulated based on the Newton–Euler equation. On the basis of the dynamic equation of the CIPS, its motion characteristics and control process are analyzed. Next, the given dynamic equation of the CIPS is linearized to obtain a series of linearized models at seven different pendulum angles. Then, seven model predictive controllers (MPCs) are designed based on the above-linearized models, respectively. Introducing the idea of the gain-schedule, a gain-scheduled MPC (GSMPC) is designed to switch one of these seven MPCs to realize the control objective of the CIPS, according to the actual pendulum angle of the SIP during the control process. Finally, multi-group simulations that consider the friction and disturbances of the CIPS are implemented to demonstrate the effectiveness of the proposed gain-scheduled model predictive control method.
The Influence of Mountain Height and Distance on Shape Factor of Wind Load of Plastic Tunnel
Authors: Xu Jing , Ren Xiaoying , He Guifeng , Di Shaohan , Shi Zhiqing , Liang Zongmin
Published: December 2023

Due to their soft structure and covering material, plastic greenhouses are vulnerable to wind disasters, causing large-scale damage and huge economic losses. The wind load of greenhouses depends on the surface wind pressure distribution, which is different for greenhouses located in valleys from those in plain areas. To study the wind pressure distribution law for various regions of greenhouses built in valleys, mountain and greenhouse models have been built by Computational Fluid Dynamics, in which the length direction of the greenhouse is perpendicular to the valley and the wind direction is parallel to the valley. In the analysis, the verified turbulence model and grid division method are both introduced, and the effect of the height and distance of mountains is considered. According to the distribution law of wind pressure, the greenhouse’s surface is partitioned, and the variation law of the shape factor of wind load on a plastic tunnel is analyzed. Then, the calculation model for the shape factor of the wind load on the greenhouse located in a valley is proposed. The conclusions show that: (a) When the wind inflow direction angle is parallel to the valley, the distribution pattern of wind pressure on the surface of the greenhouse is similar to that on the plain regardless of the distance and height of the mountains, while the values of the wind pressure are greatly affected by the mountain height and distance. The distance between mountains has greater influence than the effect of mountain height. (b) The shape factor of wind load on the suction area of the greenhouse decreases as the distance of mountains increases, while the shape factor on the pressure area of the greenhouse increases with the increase in the distance. It can be seen that the valley effect is non-negligible. The narrower and deeper the valley, the greater the wind pressure effect. (c) When the ratio of the distance between the foot of the mountain and the greenhouse d to the height of the mountain H is less than 5, i.e., d/H < 5, the ratio of the distance to the height has a significant impact on the shape factor of wind load on the greenhouse. When d/H is close to 10, the shape factor of the wind load in the valley area is close to that in the plain area, and the effect of the ratio between the height and the distance is negligible. (d) The proposed calculation model can be used to calculate the effect of mountain height and distance on the shape factor of wind load. The research results can be used in the wind resistance design of plastic greenhouses in valley areas, and can also provide some data support for the revision of the greenhouse structural load code.
Vehicle Routing Problem with Drones Considering Time Windows and Dynamic Demand
Authors: Han Jing , Liu Yanqiu , Li Yan
Published: December 2023

As a new delivery mode, the collaborative delivery of packages using trucks and drones has been proven to reduce delivery costs and delivery time. To cope with the huge cost challenges brought by strict time constraints and ever-changing customer orders in the actual delivery process, we established a two-stage optimization model based on different demand response strategies with the goal of minimizing delivery costs. To solve this problem, we designed a simulated annealing chimp optimization algorithm with a sine–cosine operator. The performance of this algorithm is improved by designing a variable-dimensional matrix encode to generate an initial solution, incorporating a sine–cosine operator and a simulated annealing mechanism to avoid falling into a local optimum. Numerical experiments verify the effectiveness of the proposed algorithm and strategy. Finally, we analyze the impact of dynamic degree on delivery cost. The proposed model and algorithm extend the theory of the vehicle routing problem with drones and also provide a feasible solution for route planning, taking into account dynamic demands and time windows.
Analysis of Inverted Charge Structure and Lightning Activity during the 8.14 Local Hailstorm on the Qinghai–Tibet Plateau
Authors: Li Yajun , Zhang Guangshu , Lyu Weitao , Zhao Yuxiang
Published: December 2023

In this paper, the charge structure and lightning activity characteristics of the thunderstorm that occurred on the Qinghai–Tibet Plateau on 14 August 2014 were analyzed using data collected from a three-dimensional (3D) lightning very-high-frequency (VHF) radiation source location system and Doppler weather radar. The analysis results showed that the charge structure of the hailstorm was maintained as an inverted dipole throughout the thunderstorm’s development process. The negatively charged region height was distributed in the 5–7 km range (above ground level (AGL)), and the positively charged region was distributed from 2 to 5 km (AGL). The lightning flash types included only cloud flashes and negative cloud–to–ground (CG) flashes in the hailstorm, and cloud flashes accounted for 93% of the total lightning flashes. Cloud flashes accounted for a high proportion of the total flashes, which may have been related to the deep lower positively charged region observed throughout the thunderstorm process. In the hailstorm development stage, the electric field was dominated by positive polarity. When the hail fell, the electric field changed negatively. When the hail ended, the electric field was dominated by negative polarity. A hail event occurred only once and lasted for a long time in the development stage, but in the mature stage, hail fell many times and every time for only a short time, and in the dissipating stage, hail events also occurred many times and each time for a long time. By comparing the radar echoes of the hailstorm cells and normal thunderstorm cells, we found that the area of the 50 dBZ echo in the hailstorm was small, the occurrence time was late, and the duration was short.
Challenges and Approaches of Culturing the Unculturable Archaea
Authors: Rafiq Muhammad , Hassan Noor , Rehman Maliha , Hayat Muhammad , Nadeem Gullasht , Hassan Farwa , Iqbal Naveed , Ali Hazrat , Zada Sahib , Kang Yingqian , Sajjad Wasim , Jamal Muhsin
Published: December 2023

Since Carl Woese’s discovery of archaea as a third domain of life, numerous archaeal species have been discovered, yet archaeal diversity is poorly characterized. Culturing archaea is complicated, but several queries about archaeal cell biology, evolution, physiology, and diversity need to be solved by culturing and culture-dependent techniques. Increasing interest in demand for innovative culturing methods has led to various technological and methodological advances. The current review explains frequent hurdles hindering uncultured archaea isolation and discusses features for more archaeal cultivation. This review also discusses successful strategies and available media for archaeal culturing, which might be helpful for future culturing practices.
The B Cell Response and Formation of Allergenic and Anti-Allergenic Antibodies in Food Allergy
Authors: Udoye Christopher C. , Ehlers Marc , Manz Rudolf A.
Published: December 2023

Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc N-glycosylation patterns that can affect the allergic reaction to food in multiple ways. High-affinity IgE is required to induce strong mast cell activation eventually leading to allergic anaphylaxis, while low-affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgA and IgG antibodies can inhibit IgE-mediated mast cell activation through various mechanisms, thereby protecting IgE-positive individuals from allergy development. The production of IgE and IgG with differential allergenic potential seems to be affected by the signaling strength of individual B cell receptors, and by cytokines from T cells. This review provides an overview of the diversity of the B cell response and the diverse roles of antibodies in food allergy.
A Novel Form of Neuregulin 1 Type III Caused by N-Terminal Processing
Authors: Wang Yukai , Zhang Yu , Wang Yingxing , Chen Hong , Pan Liangjing , Liao Xufeng , Wang Shunqi
Published: December 2023

Nrg1 (Neuregulin 1) type III, a susceptible gene of schizophrenia, exhibits a critical role in the central nervous system and is essential at each stage of Schwann’s cell development. Nrg1 type III comprises double-pass transmembrane domains, with the N-terminal and C-terminal localizing inside the cells. The N-terminal transmembrane helix partially overlaps with the cysteine-rich domain (CRD). In this study, Nrg1 type III constructs with different tags were transformed into cultured cells to verify whether CRD destroyed the transmembrane helix formation. We took advantage of immunofluorescent and immunoprecipitation assays on whole cells and analyzed the N-terminal distribution. Astonishingly, we found that a novel form of Nrg1 type III, about 10% of Nrg1 type III, omitted the N-terminal transmembrane helix, with the N-terminal positioning outside the membrane. The results indicated that the novel single-pass transmembrane status was a minor form of Nrg1 type III caused by N-terminal processing, while the major form was a double-pass transmembrane status.
Blast-Derived Small Extracellular Vesicles in the Plasma of Patients with Acute Myeloid Leukemia Predict Responses to Chemotherapy
Authors: Boyiadzis Michael , Hong Chang-Sook , Yerneni Saigopalakrishna , Im Annie , Diergaarde Brenda , Whiteside Theresa L.
Published: December 2023

The small extracellular vesicles (sEV) accumulating in acute myeloid leukemia (AML) patients’ plasma are mixtures of vesicles produced by leukemic and non-malignant cells. sEV originating from leukemia blasts could serve as potential non-invasive biomarkers of AML response to therapy. To isolate blast-derived sEV from patients’ plasma, we developed a bioprinted microarray-based immunoassay using monoclonal antibodies (mAbs) specific for leukemia-associated antigens (LAAs) and mAbs specific for a mix of tetraspanins (CD9, CD63, and CD81). We determined the proportion of LAA+ sEV relative to total plasma sEV (the LAA+/total sEV ratio) in serially collected samples of newly diagnosed AML patients prior to, during, and after chemotherapy. At AML diagnosis, the LAA+/total sEV ratio was significantly higher in patients than in healthy donors (HDs). In patients who achieved complete remission (CR) after induction chemotherapy, the LAA+/total sEV ratios significantly decreased after each chemotherapy cycle to levels seen in HDs. In contrast, the LAA+/total sEV ratios in AML patients with persistent leukemia after therapy remained elevated during and after therapy, as did the percentage of leukemic blasts in these patients’ bone marrows. The LAA+/total sEV ratio emerges as a promising non-invasive biomarker of leukemia response to therapy.
Cannabidiol Modifies the Glutamate Over-Release in Brain Tissue of Patients and Rats with Epilepsy: A Pilot Study
Authors: Martínez-Aguirre Christopher , Márquez Luis Alfredo , Santiago-Castañeda Cindy Lizbeth , Carmona-Cruz Francia , Nuñez-Lumbreras Maria de los Angeles , Martínez-Rojas Vladimir A. , Alonso-Vanegas Mario , Aguado-Carrillo Gustavo , Gómez-Víquez Norma L. , Galván Emilio J. , Cuéllar-Herrera Manola , Rocha Luisa
Published: December 2023

Drug-resistant epilepsy (DRE) is associated with high extracellular levels of glutamate. Studies support the idea that cannabidiol (CBD) decreases glutamate over-release. This study focused on investigating whether CBD reduces the evoked glutamate release in cortical synaptic terminals obtained from patients with DRE as well as in a preclinical model of epilepsy. Synaptic terminals (synaptosomes) were obtained from the epileptic neocortex of patients with drug-resistant temporal lobe epilepsy (DR-TLE, n = 10) or drug-resistant extratemporal lobe epilepsy (DR-ETLE, n = 10) submitted to epilepsy surgery. Synaptosomes highly purified by Percoll-sucrose density gradient were characterized by confocal microscopy and Western blot. Synaptosomes were used to estimate the high KCl (33 mM)-evoked glutamate release in the presence of CBD at different concentrations. Our results revealed responsive tissue obtained from seven patients with DR-TLE and seven patients with DR-ETLE. Responsive tissue showed lower glutamate release (p < 0.05) when incubated with CBD at low concentrations (less than 100 µM) but not at higher concentrations. Tissue that was non-responsive to CBD (DR-TLE, n = 3 and DR-ELTE, n = 3) showed high glutamate release despite CBD exposure at different concentrations. Simultaneously, a block of the human epileptic neocortex was used to determine its viability through whole-cell and extracellular electrophysiological recordings. The electrophysiological evaluations supported that the responsive and non-responsive human epileptic neocortices used in the present study exhibited proper neuronal viability and stability to acquire electrophysiological responses. We also investigated whether the subchronic administration of CBD could reduce glutamate over-release in a preclinical model of temporal lobe epilepsy. Administration of CBD (200 mg/kg, p.o. every 24 h for 7 days) to rats with lithium-pilocarpine-evoked spontaneous recurrent seizures reduced glutamate over-release in the hippocampus. The present study revealed that acute exposure to low concentrations of CBD can reduce the glutamate over-release in synaptic terminals obtained from some patients with DRE. This effect is also evident when applied subchronically in rats with spontaneous recurrent seizures. An important finding was the identification of a group of patients that were non-responsive to CBD effects. Future studies are essential to identify biomarkers of responsiveness to CBD to control DRE.
Characterization of the circRNA Landscape in Interleukin-4 Induced Anti-Inflammatory Microglia
Authors: Li Chaoyi , Wang Huakun , Tang Yu , Wu Junjiao
Published: December 2023

Microglia are resident innate immune cells that play an essential role in the development and surveillance of the central nervous system as well as the shared pathogenesis of neurodegenerative diseases. Microglia rapidly respond to multiple inflammatory stimuli and activate towards different phenotypes, such as pro-inflammatory and anti-inflammatory phenotypes. Cytokines, epigenetic and long non-coding RNA modulations have been shown to regulate microglial activation; however, the role of circRNAs in microglia-mediated neuroinflammation remains elusive. Here, we performed circRNA sequencing in IL-4-treated anti-inflammatory microglia and discovered 120 differentially expressed circRNAs. We systemically verified the identities of circRNAs by assays of PCR, RNase R treatment and fluorescent in situ hybridization (FISH), among others. We found that circAdgre1 promoted IL-4-induced anti-inflammatory responses and further conferred neuroprotective effects upon lipopolysaccharide (LPS) stimuli. Taken together, our results show that circRNAs might be possible therapeutic targets for microglia-mediated neuroinflammation and neurodegenerative diseases.
The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity
Authors: Zhang Mengyun , Shao Yingjie , Gu Wendong
Published: December 2023

Radiotherapy, a treatment method employing radiation to eradicate tumor cells and subsequently reduce or eliminate tumor masses, is widely applied in the management of numerous patients with tumors. However, its therapeutic effectiveness is somewhat constrained by various drug-resistant factors. Recent studies have highlighted the ubiquitination/deubiquitination system, a reversible molecular modification pathway, for its dual role in influencing tumor behaviors. It can either promote or inhibit tumor progression, impacting tumor proliferation, migration, invasion, and associated therapeutic resistance. Consequently, delving into the potential mechanisms through which ubiquitination and deubiquitination systems modulate the response to radiotherapy in malignant tumors holds paramount significance in augmenting its efficacy. In this paper, we comprehensively examine the strides made in research and the pertinent mechanisms of ubiquitination and deubiquitination systems in governing radiotherapy resistance in tumors. This underscores the potential for developing diverse radiosensitizers targeting distinct mechanisms, with the aim of enhancing the effectiveness of radiotherapy.
Networking to Optimize Dmd exon 53 Skipping in the Brain of mdx52 Mouse Model
Authors: Doisy Mathilde , Vacca Ophélie , Fergus Claire , Gileadi Talia , Verhaeg Minou , Saoudi Amel , Tensorer Thomas , Garcia Luis , Kelly Vincent P. , Montanaro Federica , Morgan Jennifer E. , van Putten Maaike , Aartsma-Rus Annemieke , Vaillend Cyrille , Muntoni Francesco , Goyenvalle Aurélie
Published: December 2023

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene that disrupt the open reading frame and thus prevent production of functional dystrophin proteins. Recent advances in DMD treatment, notably exon skipping and AAV gene therapy, have achieved some success aimed at alleviating the symptoms related to progressive muscle damage. However, they do not address the brain comorbidities associated with DMD, which remains a critical aspect of the disease. The mdx52 mouse model recapitulates one of the most frequent genetic pathogenic variants associated with brain involvement in DMD. Deletion of exon 52 impedes expression of two brain dystrophins, Dp427 and Dp140, expressed from distinct promoters. Interestingly, this mutation is eligible for exon skipping strategies aimed at excluding exon 51 or 53 from dystrophin mRNA. We previously showed that exon 51 skipping can restore partial expression of internally deleted yet functional Dp427 in the brain following intracerebroventricular (ICV) injection of antisense oligonucleotides (ASO). This was associated with a partial improvement of anxiety traits, unconditioned fear response, and Pavlovian fear learning and memory in the mdx52 mouse model. In the present study, we investigated in the same mouse model the skipping of exon 53 in order to restore expression of both Dp427 and Dp140. However, in contrast to exon 51, we found that exon 53 skipping was particularly difficult in mdx52 mice and a combination of multiple ASOs had to be used simultaneously to reach substantial levels of exon 53 skipping, regardless of their chemistry (tcDNA, PMO, or 2′MOE). Following ICV injection of a combination of ASO sequences, we measured up to 25% of exon 53 skipping in the hippocampus of treated mdx52 mice, but this did not elicit significant protein restoration. These findings indicate that skipping mouse dystrophin exon 53 is challenging. As such, it has not yet been possible to answer the pertinent question whether rescuing both Dp427 and Dp140 in the brain is imperative to more optimal treatment of neurological aspects of dystrophinopathy.
Urinary Collectrin as Promising Biomarker for Acute Kidney Injury in Patients Undergoing Cardiac Surgery
Authors: Tichy Johanna , Pajenda Sahra , Bernardi Martin H. , Wagner Ludwig , Ryz Sylvia , Aiad Monika , Gerges Daniela , Schmidt Alice , Lassnigg Andrea , Herkner Harald , Winnicki Wolfgang
Published: December 2023

Background: Early detection of acute kidney injury (AKI) is crucial for timely intervention and improved patient outcomes after cardiac surgery. This study aimed to evaluate the potential of urinary collectrin as a novel biomarker for AKI in this patient population. Methods: In this prospective, observational cohort study, 63 patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) were studied at the Medical University of Vienna between 2016 and 2018. We collected urine samples prospectively at four perioperative time points, and urinary collectrin was measured using an enzyme-linked immunosorbent assay. Patients were divided into two groups, AKI and non-AKI, defined by Kidney Disease: Improving Global Outcomes Guidelines, and differences between groups were analyzed. Results: Postoperative AKI was found in 19 (30%) patients. Urine sample analysis revealed an inverse correlation between urinary collectrin and creatinine and AKI stages, as well as significant changes in collectrin levels during the perioperative course. Baseline collectrin levels were 5050 ± 3294 pg/mL, decreased after the start of CPB, reached their nadir at the end of surgery, and began to recover slightly on postoperative day (POD) 1. The most effective timepoint for distinguishing between AKI and non-AKI patients based on collectrin levels was POD 1, with collectrin levels of 2190 ± 3728 pg/mL in AKI patients and 3768 ± 3435 pg/mL in non-AKI patients (p = 0.01). Conclusions: Urinary collectrin shows promise as a novel biomarker for the early detection of AKI in patients undergoing cardiac surgery on CPB. Its dynamic changes throughout the perioperative period, especially on POD 1, provide valuable insights for timely diagnosis and intervention. Further research and validation studies are needed to confirm its clinical usefulness and potential impact on patient outcomes.
Effect of CYP2C19 Pharmacogenetic Testing on Predicting Citalopram and Escitalopram Tolerability and Efficacy: A Retrospective, Longitudinal Cohort Study
Authors: Mahajna Mahmood , Abu Fanne Rami , Berkovitch Matitiahu , Tannous Elias , Vinker Shlomo , Green Ilan , Matok Ilan
Published: December 2023

Background—Various antidepressant agents are metabolized by the CYP2C19 enzyme, including Citalopram and Escitalopram. Variation in CYP2C19 expression might give rise to different plasma concentrations of the active metabolites, potentially affecting both drugs’ efficacy and tolerability. Aim—The aim of this study was to evaluate differences in the Escitalopram and Citalopram efficacy and tolerability between different CYP2C19 genotype-based metabolizing categories in outpatients suffering from major depressive disorder (MDD). Methods—In a retrospective, longitudinal cohort study of electronic medical-record data, 283 patients with MDD who were prescribed Escitalopram or Citalopram with the available CYP2C19-genotyping test were enrolled. The primary efficacy end point was adverse drug reactions recorded in the medical files. A proportional-odds, multilevel-regression model for longitudinal ordinal data was used to estimate the relation between the CYP2C19 genotype and adverse drug reactions, adjusting for potential confounding variables and other explanatory variables. Latent-class analysis (LCA) was utilized to detect the presence of clinically significant subgroups and their relation to an individual’s metabolizing status for CYP2D6/CYP2C19. Results—With poor CYP2C19 metabolizers as a reference, for each unit difference in the activity score of the CYP2C19 phenotype, the odds ratio for drug intolerability was lowered by 0.73 (95% credible intervals: 0.56–0.89), adjusting for significant covariates. In addition, applying LCA, we identified two qualitatively different subgroups: the first group (61.85%) exhibited multiple side effects, low compliance, and frequent treatment changes, whereas the second group (38.15%) demonstrated fewer side effects, good adherence, and fewer treatment changes. The CYP2C19 phenotype was substantially associated with the group membership. Conclusions—We found a positive association between the CYP2C19 activity scores, as inferred from the genotype, and both the efficacy of and tolerability to both Es/Citalopram. LCA enabled valuable insights into the underlying structure of the population; the CYP2C19 phenotype has a predictive value that discriminates between low-adherence, low-drug-tolerance, and low-response patients and high-adherence, high-drug-tolerance, and high-response patients. Personalized medicine based on CYP2C19 genotyping could evolve as a promising new avenue towards mitigating Escitalopram and Citalopram therapy and the associated side effects and enhancing treatment success.
Emerging and Future Targeted Therapies for Pediatric Acute Myeloid Leukemia: Targeting the Leukemia Stem Cells
Authors: Murphy Lindsey A. , Winters Amanda C.
Published: December 2023

Acute myeloid leukemia (AML) is a rare subtype of acute leukemia in the pediatric and adolescent population but causes disproportionate morbidity and mortality in this age group. Standard chemotherapeutic regimens for AML have changed very little in the past 3–4 decades, but the addition of targeted agents in recent years has led to improved survival in select subsets of patients as well as a better biological understanding of the disease. Currently, one key paradigm of bench-to-bedside practice in the context of adult AML is the focus on leukemia stem cell (LSC)-targeted therapies. Here, we review current and emerging immunotherapies and other targeted agents that are in clinical use for pediatric AML through the lens of what is known (and not known) about their LSC-targeting capability. Based on a growing understanding of pediatric LSC biology, we also briefly discuss potential future agents on the horizon.
Bitcoin and Renewable Energy Mining: A Survey
Authors: Tomatsu Yusuke , Han Wenlin
Published: December 2023

Bitcoin, the most valuable and energy-consuming cryptocurrency, has recently been at the center of a heated debate over its environmental impact. This controversy has caught the public’s attention, prompting us to investigate the energy consumption of Bitcoin. In this paper, we have conducted a review of the literature on various aspects of Bitcoin mining, including its mechanisms, energy consumption, mining sites, and the potential for renewable energy use. Our findings reveal that the power consumption of Bitcoin is bound to increase with the continued adoption of the proof-of-work (PoW) consensus algorithm. Nonetheless, the growing availability of affordable renewable energy sources worldwide brings hope that Bitcoin mining will shift towards cleaner energy in the near future.
Acid-Sensing Ion Channel 1a Contributes to the Prefrontal Cortex Ischemia-Enhanced Neuronal Activities in the Amygdala
Authors: Park Gyeongah , Ge Qian , Jin Zhen , Du Jianyang
Published: December 2023

Following a stroke, the emergence of amygdala-related disorders poses a significant challenge, with severe implications for post-stroke mental health, including conditions such as anxiety and depression. These disorders not only hinder post-stroke recovery but also elevate mortality rates. Despite their profound impact, the precise origins of aberrant amygdala function after a stroke remain elusive. As a target of reduced brain pH in ischemia, acid-sensing ion channels (ASICs) have been implicated in synaptic transmission after ischemia, hinting at their potential role in reshaping neural circuits following a stroke. This study delves into the intriguing relationship between post-stroke alterations and ASICs, specifically focusing on postsynaptic ASIC1a enhancement in the amygdala following prefrontal cortex (PFC) ischemia induced by endothelin-1 (ET-1) injection. Our findings intriguingly illustrate that mPFC ischemia not only accentuates the PFC to the amygdala circuit but also implicates ASIC1a in fostering augmented synaptic plasticity after ischemia. In contrast, the absence of ASIC1a impairs the heightened induction of long-term potentiation (LTP) in the amygdala induced by ischemia. This pivotal research introduces a novel concept with the potential to inaugurate an entirely new avenue of inquiry, thereby significantly enhancing our comprehension of the intricate mechanisms underlying post-stroke neural circuit reconfiguration. Importantly, these revelations hold the promise of paving the way for groundbreaking therapeutic interventions.
Three-Dimensional Magnetic Rehabilitation, Robot-Enhanced Hand-Motor Recovery after Subacute Stroke: A Randomized Controlled Trial
Authors: Kim Sung-Hoon , Ji Dong-Min , Hwang In-Su , Ryu Jinwhan , Jin Sol , Kim Soo-A , Kim Min-Su
Published: December 2023

We developed an end-effector-type rehabilitation robot that can uses electro- and permanent magnets to generate a three-way magnetic field to assist hand movements and perform rehabilitation therapy. This study aimed to investigate the therapeutic effect of a rehabilitation program using a three-dimensional (3D) magnetic force-based hand rehabilitation robot on the motor function recovery of the paralyzed hands of patients with stroke. This was a double-blind randomized controlled trial in which 36 patients with subacute stroke were assigned to intervention and control groups of 18 patients each. The intervention group received 30 min of rehabilitation therapy per day for a month using a 3D magnetic force-driven hand rehabilitation robot, whereas the control group received 30 min of conventional occupational therapy to restore upper-limb function. The patients underwent three behavioral assessments at three time points: before starting treatment (T0), after 1 month of treatment (T1), and at the follow-up 1-month after treatment completion (T2). The primary outcome measure was the Wolf Motor Function Test (WMFT), and secondary outcome measures included the Fugl–Meyer Assessment of the Upper Limb (FMA_U), Modified Barthel Index (MBI), and European Quality of Life Five Dimensions (EQ-5D) questionnaire. No participant safety issues were reported during the intervention. Analysis using repeated measures analysis of variance showed significant interaction effects between time and group for both the WMFT score (p = 0.012) and time (p = 0.010). In post hoc analysis, the WMFT scores and time improved significantly more in the patients who received robotic rehabilitation at T1 than in the controls (p = 0.018 and p = 0.012). At T2, we also consistently found improvements in both the WMFT scores and times for the intervention group that were superior to those in the control group (p = 0.024 and p = 0.018, respectively). Similar results were observed for FMA_U, MBI, and EQ-5D. Rehabilitation using the 3D hand-rehabilitation robot effectively restored hand function in the patients with subacute stroke, contributing to improvement in daily independence and quality of life.
Potential Application of Marine Algae and Their Bioactive Metabolites in Brain Disease Treatment: Pharmacognosy and Pharmacology Insights for Therapeutic Advances
Authors: Khairinisa Miski Aghnia , Latarissa Irma Rahayu , Athaya Nadiyah Salma , Charlie Vandie , Musyaffa Hanif Azhar , Prasedya Eka Sunarwidhi , Puspitasari Irma Melyani
Published: December 2023

Seaweeds, also known as edible marine algae, are an abundant source of phytosterols, carotenoids, and polysaccharides, among other bioactive substances. Studies conducted in the past few decades have demonstrated that substances derived from seaweed may be able to pass through the blood–brain barrier and act as neuroprotectants. According to preliminary clinical research, seaweed may also help prevent or lessen the symptoms of cerebrovascular illnesses by reducing mental fatigue, preventing endothelial damage to the vascular wall of brain vessels, and regulating internal pressure. They have the ability to control neurotransmitter levels, lessen neuroinflammation, lessen oxidative stress, and prevent the development of amyloid plaques. This review aims to understand the application potential of marine algae and their influence on brain development, highlighting the nutritional value of this “superfood” and providing current knowledge on the molecular mechanisms in the brain associated with their dietary introduction.
Experimental Study on Flexural Performance of Recycled Steel Fiber Concrete Beams
Authors: Yan Jinqiu , Gao Yongtao , Fan Tao , Xu Qiang , Yuan Weiguang , Zhao Xiao
Published: December 2023

We sorted the waste from mechanical processing to form recycled steel fibers. In order to study the flexural mechanical properties of reinforced concrete beams after the addition of recycled steel fibers, four recycled steel fiber concrete beams (RSFCBs) and one normal concrete beam (NCB) were designed and poured using the volume fraction of steel fibers (0%, 0.5%, 1%, 1.5%, 2%) as the variables. Normal section bending tests were conducted on them under a concentrated load. We obtained experimental data such as the cracking load, ultimate load, mid-span deflection, and steel and concrete strain of the beam by gradually loading the test beam, and we observed and recorded the development of cracks. The results indicate that the NCB exhibits crushing failure, while the RSFCBs exhibit equilibrium failure. The addition of recycled steel fibers effectively controls the extension of cracks, resulting in a better bending toughness of the beam. The bending performance of RSFCBs with different volume additions shows a trend of first increasing and then decreasing with the increase in steel fiber content. The peak value was reached when the steel fiber content was 1.5%, which increased the bending bearing capacity by 54.72% compared with the NCB. With the increase in steel fiber content, the required load value for tensile steel bars to yield also increases, reaching a peak at a content of 1.5%, which increases the bending bearing capacity by 44.64% compared with the NCB. The addition of recycled steel fibers enables the beam to improve its bearing capacity while limiting the development of longitudinal reinforcement strain, allowing the longitudinal reinforcement to yield under higher loads and improving the overall bending performance of the beam.
Fabrication of Gold Nanoparticles Embedded Laser-Induced Graphene (LIG) Electrode for Hydrogen Evolution Reaction
Authors: Deepak Deepak , Vuruputuri Vennela , Bhattacharya Gourav , McLaughlin James A. , Roy Susanta Sinha
Published: December 2023

The advancement of renewable energy technologies like water electrolysis and hydrogen fuel cells relies on the fabrication of effective and reliable catalysts for the hydrogen evolution process (HER). In this regard, we report gold nanoparticles embedded in laser-induced graphene electrodes for regulation of overpotential and electrocatalytic performance of hydrogen evolution reaction. Gold nanoparticles were deposited onto the LIG surface using electrode deposition via cyclic voltammetry (CV) at different cycle lengths. The catalyst fabrication technique enables the manipulation of many electrochemical parameters, such as overpotential value, charge transfer resistance, electrochemical active surface area, and tafel slope, through the adjustment of cyclic voltammetry (CV) cycles. The LIG-Au@50 sample demonstrates remarkable electrocatalytic characteristics, as evidenced by its low overpotential of 141 mV at a current density of 10 mA/cm2 and reduced tafel slope of 131 mV/decade in an acidic environment. Furthermore, the presence of an augmented electrochemical active surface area, a mass activity of 8.80 A/g, and a high turnover frequency of 0.0091 s−1 suggest elevated and significant accessibility to plentiful active sites. A significant decrease in charge transfer resistance resulted in an enhanced rate of the water-splitting reaction.
Urinary, Gastrointestinal, and Sexual Dysfunctions after Chemotherapy, Radiotherapy, Radical Surgery or Multimodal Treatment in Women with Locally Advanced Cervical Cancer: A Multicenter Retrospective Study
Authors: Di Donna Mariano Catello , Cucinella Giuseppe , Giallombardo Vincenzo , Sozzi Giulio , Bizzarri Nicolò , Scambia Giovanni , Pecorino Basilio , Scollo Paolo , Berretta Roberto , Capozzi Vito Andrea , Laganà Antonio Simone , Chiantera Vito
Published: December 2023

Background: Different strategies have been proposed for the treatment of locally advanced cervical cancer (LACC), with different impacts on patient’s quality of life (QoL). This study aimed to analyze urinary, bowel, and sexual dysfunctions in a series of LACC patients who underwent chemotherapy, radiotherapy, radical surgery, or a combination of these treatments. Methods: Patients with LACC who underwent neoadjuvant radio–chemotherapy (NART/CT; n = 35), neoadjuvant chemotherapy (NACT; n = 17), exclusive radio–chemotherapy (ERT/CT; n = 28), or upfront surgery (UPS; n = 10) from November 2010 to September 2019 were identified from five oncological referral centers. A customized questionnaire was used for the valuation of urinary, gastrointestinal, and sexual dysfunctions. Results: A total of 90 patients were included. Increased urinary frequency (>8 times/day) was higher in ERT/CT compared with NACT/RT (57.1% vs. 28.6%; p = 0.02) and NACT (57.1% vs. 17.6%; p = 0.01). The use of sanitary pads for urinary leakage was higher in ERT/CT compared with NACT/RT (42.9% vs. 14.3%; p = 0.01) and NACT (42.9% vs. 11.8%; p = 0.03). The rate of reduced evacuations (<3 times a week) was less in UPS compared with NACT/RT (50% vs. 97.1%; p < 0.01), NACT (50% vs. 88.2, p < 0.01), and ERT/CT (50% vs. 96.4%; p < 0.01). A total of 52 women were not sexually active after therapy, and pain was the principal reason for the avoidance of sexual activity. Conclusions: The rate and severity of urinary, gastrointestinal, and sexual dysfunction were similar in the four groups of treatment. Nevertheless, ERT/CT was associated with worse sexual and urinary outcomes.
The Impact of Outpatient versus Inpatient Administration of CAR-T Therapies on Clinical, Economic, and Humanistic Outcomes in Patients with Hematological Cancer: A Systematic Literature Review
Authors: Hansen Doris K. , Liu Yi-Hsuan , Ranjan Sandip , Bhandari Hitesh , Potluri Ravi , McFarland Lindsay , De Braganca Kevin C. , Huo Stephen
Published: December 2023

Although chimeric antigen receptor (CAR)-T cell therapies are typically administered in the inpatient setting, outpatient administration is rapidly expanding. However, there is limited summarized evidence comparing outcomes between outpatient and inpatient administration. This systematic literature review aims to compare the safety, efficacy, quality of life (QoL), costs, and healthcare resource utilization (HCRU) outcomes in patients with hematological cancer who are administered CAR-T therapy in an outpatient versus an inpatient setting. Publications (2016 or later) that reported the outcomes of interest in patients treated with a CAR-T therapy in both outpatient and inpatient settings, or only the outpatient setting, were reviewed. In total, 38 publications based on 21 studies were included. Safety findings suggested the comparable frequency of adverse events in the two settings. Eleven studies that reported data in both settings showed comparable response rates (80–82% in outpatient and 72–80% in inpatient). Improvements in the QoL were observed in both settings while costs associated with CAR-T therapy were lower in the outpatient setting. Although unplanned hospitalizations were higher in the outpatient cohort, overall HCRU was lower. Outpatient administration of CAR-T therapy appears to have comparable outcomes in safety, efficacy, and QoL to inpatient administration while reducing the economic burden.
Bioengineered Flagellin–TiO2 Nanoparticle-Based Modified Glassy Carbon Electrodes as a Highly Selective Platform for the Determination of Diclofenac Sodium
Authors: Hidalgo Juan Santiago , Tóth Éva , Jankovics Hajnalka , Fort Carmen Ioana , Turdean Graziella Liana , Tombacz Etelka , Galambos Ildiko
Published: December 2023

This study describes the incorporation of bioengineered flagellin (4HIS) protein in conjunction with TiO2 anatase nanoparticles into a chitosan (Chit) polymeric matrix as a highly sensitive electrode modifier for the determination of diclofenac sodium (DS) in wastewater. Two types of electrodes were prepared using a simple drop-casting method. The inner structure of the obtained modified electrode was characterized by scanning electron microscopy (SEM) in combination with energy-dispersive X-ray spectroscopy and isothermal titration calorimetry (ITC). The electrochemical and electroanalytical parameters of DS oxidation at the nanostructured interface of the modified electrode were obtained via cyclic voltammetry and square-wave voltammetry. The analytical parameters for diclofenac electro-detection showed a 50% decrease in LOD and LOQ at Chit + TiO2 + 4HIS/GCE-modified electrode compared with the Chit + 4HIS/GCE-modified electrode. The obtained tools were successfully used for DS detection in drug tablets and wastewater samples. Thus, it was demonstrated that in the presence of a histidine-containing flagellin variant, the electrode has DS recognition capacity which increases in the presence of TiO2 nanoparticles, and both induce excellent performances of the prepared tools, either in synthetic solution or in real samples.